A DUF-246 family glycosyltransferase-like gene affects male fertility and the biosynthesis of pectic arabinogalactans.
Pectins are a group of structurally complex plant cell wall polysaccharides whose biosynthesis and function remain poorly understood. The pectic polysaccharide rhamnogalacturonan-I (RG-I) has two types of arabinogalactan side chains, type-I and type-II arabinogalactans. To date few enzymes involved in the biosynthesis of pectin have been described. Here we report the identification of a highly conserved putative glycosyltransferase encoding gene, Pectic ArabinoGalactan synthesis-Related (PAGR), affecting the biosynthesis of RG-I arabinogalactans and critical for pollen tube growth. T-DNA insertions in PAGR were identified in Arabidopsis thaliana and were found to segregate at a 1:1 ratio of heterozygotes to wild type. We were unable to isolate homozygous pagr mutants as pagr mutant alleles were not transmitted via pollen. In vitro pollen germination assays revealed reduced rates of pollen tube formation in pollen from pagr heterozygotes. To characterize a loss-of-function phenotype for PAGR, the Nicotiana benthamiana orthologs, NbPAGR-A and B, were transiently silenced using Virus Induced Gene Silencing. NbPAGR-silenced plants exhibited reduced internode and petiole expansion. Cell wall materials from NbPAGR-silenced plants had reduced galactose content compared to the control. Immunological and linkage analyses support that RG-I has reduced type-I arabinogalactan content and reduced branching of the RG-I backbone in NbPAGR-silenced plants. Arabidopsis lines overexpressing PAGR exhibit pleiotropic developmental phenotypes and the loss of apical dominance as well as an increase in RG-I type-II arabinogalactan content. Together, results support a function for PAGR in the biosynthesis of RG-I arabinogalactans and illustrate the essential roles of these polysaccharides in vegetative and reproductive plant growth.


Mortality and causes of death among homeless in Finland: a 10-year follow-up study.
Homelessness is associated with increased mortality, and some predictors of mortality have been previously identified. We examined the overall and cause-specific mortality among homeless men in Helsinki and the associations of social background and health service use with mortality. To assess cause-specific mortality in a competing risks framework, we performed a register-based, case-control study of 617 homeless men and an age-matched control group of 1240 men from the general population that were followed for 10 years between 2004 and 2014. Cox proportional hazards model was used to calculate HR for death and a competing risks model to calculate sub-HRs (sHR) for cause-specific death. During the follow-up, 45.0% of the homeless died compared with 10.5% of controls (HR 5.38, 95% CI 4.39 to 6.59). The risk of death was particularly elevated for the homeless aged≤50 years (HR 10.3, 95% CI 7.0 to 15.2). External causes caused 34% of the deaths (sHR 11.2, 95% CI 6.8 to 18.2), but also deaths from medical causes were common (sHR 3.6, 95% CI 2.9 to 4.6). Age and somatic hospitalisation were significant predictors of death both among homeless and controls. Educational attainment, marital status, employment and psychiatric hospitalisation were significant predictors of mortality among the controls, but not among the homeless. Homelessness is associated with a fivefold mortality compared with the controls, and especially homeless aged ≤50 years have an increased risk of death. Being homeless eliminates the protective effects of marriage, employment and education on mortality risk.


Melanin is not required for turgor generation but enhances cell-wall rigidity in appressoria of the corn pathogen Colletotrichum graminicola.
The ascomycete and causative agent of maize anthracnose and stem rot, Colletotrichum graminicola, differentiates melanized infection cells called appressoria that are indispensable for breaching the plant cell wall. High concentrations of osmolytes accumulate within the appressorium, and the internal turgor pressure of up to 5.4 MPa provides sufficient force to penetrate the leaf epidermis directly. In order to assess the function of melanin in C. graminicola appressoria, we identified and characterized the polyketide synthase 1 (CgPKS1) gene which displayed high similarity to fungal polyketide synthases (PKS) involved in synthesis of 1,3,6,8-tetrahydronaphthalene, the first intermediate in melanin biosynthesis. Cgpks1 albino mutants created by targeted gene disruption were unable to penetrate intact leaves and ruptured frequently but, surprisingly, were able to penetrate ultrathin polytetrafluoroethylene membranes mimicking the plant surface. Nonmelanized Cgpks1 appressoria were sensitive to externally applied cell-wall-degrading enzymes whereas melanized appressoria were not affected. Expression studies using a truncated CgPKS1 fused to green fluorescent protein revealed fluorescence in immature appressoria and in setae, which is in agreement with transcript data obtained by RNA-Seq and quantitative polymerase chain reaction. Unexpectedly, surface scans of mutant and wild-type appressoria revealed considerable differences in cell-wall morphology. Melanization of appressoria is indispensable for successful infection of intact leaves. However, cell collapse experiments and analysis of the appressorial osmolyte content by Mach-Zehnder interferometry convincingly showed that melanin is not required for solute accumulation and turgor generation, thus questioning the role of melanin as a barrier for osmolytes in appressoria of C. graminicola.


Participation of the immune system in regression of a rat Mc7 sarcoma by hyperthermia.
Participation of the host immune response in eradication of tumor by hyperthermia has been suspected for a long time. The effect of local tumor heating on the immunocompetence of rats bearing Mc7 sarcoma was studied. Following heat treatment of 1- to 1.5-ml foot tumors at 43 degrees for 2 hr, regression of primary tumors resulted in host cure (15 of 21; 71%), and this was accompanied by an increased skin response to both 3 M KCl extract of Mc7 and dinitrochlorobenzene as well as in elevation of antibody to bovine serum albumin. Animals that were cured by hyperthermia showed no sign of metastatic tumor in lymph nodes and lungs; most control animals at the time of heat treatment had secondary tumor deposits in lymph nodes and lungs. Tumor regression after curative heating did not occur in rats (0 to 10) treated by whole-body X-rays (150 R; 3 times) plus cortisone acetate (60 mg/kg; 4 times; s.c.), and the tumor cure rate was reduced (9 of 21; 43%) by blocking macrophage activity with silica (1 g/kg; i.v. and i.p.). Also, these rats (43%) succumbed to tumor challenge with 2.5 x 10(6) Mc7 cells; 50% of the heat-cured animals not given silica consistently rejected this challenge dose. The results imply that immunostimulation comprising mainly T-cells and macrophages plays a major part in tumor regression by hyperthermia.


Tuning the Doping of Epitaxial Graphene on a Conventional Semiconductor via Substrate Surface Reconstruction.
Combining scanning tunneling microscopy and angle-resolved photoemission spectroscopy, we demonstrate how to tune the doping of epitaxial graphene from p to n by exploiting the structural changes that occur spontaneously on the Ge surface upon thermal annealing. Furthermore, using first-principle calculations, we build a model that successfully reproduces the experimental observations. Since the ability to modify graphene electronic properties is of fundamental importance when it comes to applications, our results provide an important contribution toward the integration of graphene with conventional semiconductors.


Biotechnological applications of acetic acid bacteria.
The acetic acid bacteria (AAB) have important roles in food and beverage production, as well as in the bioproduction of industrial chemicals. In recent years, there have been major advances in understanding their taxonomy, molecular biology, and physiology, and in methods for their isolation and identification. AAB are obligate aerobes that oxidize sugars, sugar alcohols, and ethanol with the production of acetic acid as the major end product. This special type of metabolism differentiates them from all other bacteria. Recently, the AAB taxonomy has been strongly rearranged as new techniques using 16S rRNA sequence analysis have been introduced. Currently, the AAB are classified in ten genera in the family Acetobacteriaceae. AAB can not only play a positive role in the production of selected foods and beverages, but they can also spoil other foods and beverages. AAB occur in sugar- and alcohol-enriched environments. The difficulty of cultivation of AAB on semisolid media in the past resulted in poor knowledge of the species present in industrial processes. The first step of acetic acid production is the conversion of ethanol from a carbohydrate carried out by yeasts, and the second step is the oxidation of ethanol to acetic acid carried out by AAB. Vinegar is traditionally the product of acetous fermentation of natural alcoholic substrates. Depending on the substrate, vinegars can be classified as fruit, starch, or spirit substrate vinegars. Although a variety of bacteria can produce acetic acid, mostly members of Acetobacter, Gluconacetobacter, and Gluconobacter are used commercially. Industrial vinegar manufacturing processes fall into three main categories: slow processes, quick processes, and submerged processes. AAB also play an important role in cocoa production, which represents a significant means of income for some countries. Microbial cellulose, produced by AAB, possesses some excellent physical properties and has potential for many applications. Other products of biotransformations by AAB or their enzymes include 2-keto-L-gulonic acid, which is used for the production of vitamin C; D-tagatose, which is used as a bulking agent in food and a noncalorific sweetener; and shikimate, which is a key intermediate for a large number of antibiotics. Recently, for the first time, a pathogenic acetic acid bacterium was described, representing the newest and tenth genus of AAB.


[Retracted] Combined treatment with extracorporeal shock‑wave therapy and bone marrow mesenchymal stem cell transplantation improves bone repair in a rabbit model of bone nonunion.
The authors of the above article wish to retract it on account of two reasons: First, the authors have experienced irreconcilable difficulties in deciding upon the suitable order of the authors in the author list. Secondly, due to the authors' negligence, the graph featured in Fig. 1 on p. 1328 does not match with the textual description, and the authors intend to rectify this discrepancy by performing further experiments. The authors regret any inconvenience that this retraction has caused. [the original article was published in Molecular Medicine Reports 17: 1326‑1332, 2018; DOI: 10.3892/mmr.2017.7984].


An Investigation into Three Visual Characteristics of Complex Scenes that Evoke Human Emotion.
Prior computational studies have examined hundreds of visual characteristics related to color, texture, and composition in an attempt to predict human emotional responses. Beyond those myriad features examined in computer science, roundness, angularity, and visual complexity have also been found to evoke emotions in human perceivers, as demonstrated in psychological studies of facial expressions, dance poses, and even simple synthetic visual patterns. Capturing these characteristics algorithmically to incorporate in computational studies, however, has proven difficult. Here we expand the scope of previous computer vision work by examining these three visual characteristics in computer analysis of complex scenes, and compare the results to the hundreds of visual qualities previously examined. A large collection of ecologically valid stimuli (i.e., photos that humans regularly encounter on the web), named the EmoSet and containing more than 40,000 images crawled from web albums, was generated using crowd-sourcing and subjected to human subject emotion ratings. We developed computational methods to the separate indices of roundness, angularity, and complexity, thereby establishing three new computational constructs. Critically, these three new physically interpretable visual constructs achieve comparable classification accuracy to the hundreds of shape, texture, composition, and facial feature characteristics previously examined. In addition, our experimental results show that color features related most strongly with the positivity of perceived emotions, the texture features related more to calmness or excitement, and roundness, angularity, and simplicity related similarly with both of these emotions dimensions.


Microscopical recognition and characterization of solution dyed fibers.
Solution dyed fibers are synthetic fibers colored through the addition of insoluble pigmentation to the polymer prior to extrusion. This is in contrast to most textile fibers, which are traditionally colored via immersion in liquid dyebaths following extrusion. Solution dyed fibers are increasing in market share in numerous applications (e.g., apparel, carpet, upholstery), and thus, the microscopic characteristics and variety of pigments used to color them represent unexploited properties in forensic fiber comparisons. This paper presents the development of a microscopical process to first recognize a fiber as solution dyed and subsequently characterize the color and optical properties of each type of pigment found in a given fiber. To this end, a set of 76 fibers, representing polypropylene, nylon, polyester, and rayon, spanning all nominal colors and several consumer applications were analyzed longitudinally and in cross section using a combination of polarized light, fluorescence, and oil immersion microscopy. A given fiber contained between one and six different pigments, and a total of 260 pigments (not all unique) were recognized within this set of fibers. Pigment morphologies were categorized as angular, elongated, rounded, finely divided, or streaky, and about 40% of the pigments fluoresced. Ultimately, this body of data is intended to provide trace evidence examiners with a specific approach to recognize and begin to exploit pigmented fibers encountered in casework.


Common variations in the genes encoding C-reactive protein, tumor necrosis factor-alpha, and interleukin-6, and the risk of clinical diabetes in the Women's Health Initiative Observational Study.
Circulating concentrations of high-sensitivity C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) have been associated with an increased risk of diabetes. To examine the roles of genetic variation in the genes encoding CRP, TNF- α, and IL-6 in the development of diabetes, we conducted a prospective case-control study nested within the Women's Health Initiative Observational Study. We followed 82 069 postmenopausal women (50-79 years of age) with no history of diabetes for incident diabetes for a mean follow-up of 5.5 years. We identified 1584 cases and matched them with 2198 controls with respect to age, ethnicity, clinical center, time of blood draw, and length of follow-up. We genotyped 13 haplotype-tagging single-nucleotide polymorphisms (tSNPs) across 2.3 kb of the CRP (C-reactive protein, pentraxin-related) gene, 16 tSNPs across 2.8 kb of the TNF (tumor necrosis factor) gene, and 14 tSNPs across 4.8 kb of the IL6 [interleukin 6 (interferon, beta 2)] gene. Plasma concentrations of TNF-α receptor 2 (TNF-α-R2) and IL-6 were measured. After adjusting for matching factors, confounding variables, and multiple comparisons, we found 8 variants in the TNF gene to be associated with plasma TNF-α-R2 concentrations in white women (q < 0.05). After adjusting for multiple comparisons (q > 0.05), we found no association of any IL6 gene variant with plasma IL-6 concentration, nor did we find any significant associations between any SNPs among these 3 genes and diabetes risk (q > 0.05). We found modest associations between TNF variants and circulating concentrations of TNF-α-R2. Common variants of the CRP, TNF, and IL6 genes were not significantly associated with risk of clinical diabetes in postmenopausal women.


An epidemiologically valuable typing method for Neisseria meningitidis by analysis of restriction fragment length polymorphisms.
A restriction fragment length polymorphism (RFLP) typing method was developed for Neisseria meningitidis. A cloned EcoRI fragment from a Neisseria meningitidis Group B serotype 15P1.16 sulphonamide-resistant strain was used to probe Southern blots of total chromosomal DNA restriction fragments (enzyme AvaI). A group of 75 apparently unrelated organisms gave rise to 26 different restriction fragment length patterns and two different groups of epidemiologically related strains had RFLP patterns that were distinct for each group. The technique was highly reproducible and discriminatory. The RFLP data were compared with the results of serotyping and subtyping and isoenzyme electrophoretotyping. The RFLP data were consistent with those from the alternative typing methods; clones defined by isoenzyme analysis were subdivided by this technique. The use of RFLP typing by cloned probes should be of considerable epidemiological value.


Similar specificities of symbiont uptake by adults and larvae in an anemone model system for coral biology.
Reef-building corals depend for much of their energy on photosynthesis by symbiotic dinoflagellate algae (genus Symbiodinium) that live within their gastrodermal cells. However, the cellular mechanisms underpinning this ecologically critical symbiosis, including those governing the specificity of symbiont uptake by the host, remain poorly understood, in part because of the difficulties of working with corals in the laboratory. Here, we used the small symbiotic sea anemone Aiptasia as an experimentally tractable model system to analyze the specificity and timing of symbiosis onset in larval and adult animals under controlled laboratory conditions. Using four clonal, axenic Symbiodinium strains, we found no difference in uptake specificity between larvae (even when very young) and adults. Although both compatible and incompatible algal strains were found within the larval guts, only the former appeared to be internalized by gastrodermal cells, and they (but not incompatible algae) proliferated rapidly within the larvae in the absence of detectable exchange with other larvae. Older larvae showed reduced ingestion of both compatible and incompatible algae, and the addition of food failed to promote the uptake of an incompatible algal strain. Thus, Aiptasia adults and larvae appear to have similar mechanisms for discriminating between compatible and incompatible dinoflagellate types prior to phagocytosis by host gastrodermal cells. Whether a particular algal strain is compatible or incompatible appears to be stable during years of axenic culture in the absence of a host. These studies provide a foundation for future analyses of the mechanisms of symbiont-uptake specificity in this emerging model system.


Binding to histo-blood group antigen-expressing bacteria protects human norovirus from acute heat stress.
This study aims to investigate if histo-blood group antigen (HBGA) expressing bacteria have any protective role on human norovirus (NoV) from acute heat stress. Eleven bacterial strains were included, belonging to Escherichia coli, Enterobacter cloacae, Enterobacter aerogenes, Clostridium difficile, Bifidobacterium adolescentis, and B. longum. HBGA expression of the bacteria as well as binding of human NoV virus-like particles (VLPs, GI.1, and GII.4 strains) to the bacteria were detected by flow cytometry. NoV VLPs pre-incubated with HBGA expressing or non-HBGA expressing bacteria were heated and detected by both direct ELISA and porcine gastric mucin-binding assay. The NoV-binding abilities of the bacteria correlated well with their HBGA expression profiles. Two HBGA expressing E. coli (LMG8223 and LFMFP861, both GI.1 and GII.4 binders) and one non-HBGA expressing E. coli (ATCC8739, neither GI.1 nor GII.4 binder) were selected for the heat treatment test with NoV VLPs. Compared with the same cell numbers of non-HBGA expressing E. coli, the presence of HBGA-expressing E. coli could always maintain higher antigen integrity, as well as mucin-binding ability of NoV VLPs of both GI.1 and GII.4 after heat-treatment at 90°C for 2 min. These results indicate that HBGA-expressing bacteria may protect NoVs during the food processing treatments, thereby facilitating their transmission.


The impact of disease pattern, surgical management, and individual surgeons on the risk for relaparotomy for recurrent Crohn's disease.
The authors provide a multivariate analysis of a large single-center experience with limited surgery for Crohn's disease. During the past decade, the aim of surgery for Crohn's disease has shifted from radical operation, achieving inflammation-free margins of resection, to "minimal surgery," intended to remove just grossly inflamed tissue or performing strictureplasties. Seven hundred ninety-three cases of resection and/or strictureplasty in 689 individuals with histologically verified Crohn's disease were followed for a mean period of 50 months (range, 5-166 months). Two different end points were analyzed: 1) any relaparotomy for recurrent (or persistent) Crohn's disease and 2) relaparotomy for site-specific recurrence. More than 30 variables of patient/disease characteristics and surgical management were included in a proportional hazard model. Five parameters were associated independently with the risk for relaparotomy: increased risk coincided with young age at onset of disease, involvement of jejunum, enterocutaneous fistula, or performed strictureplasty, and decreased risk followed ileocecal resection. Site-specific risks of reoperation were calculated on the basis of 1260 intestinal resections or anastomoses performed in these patients. Young age at onset, duodenal and jejunal involvement, presence of enterocutaneous or perianal fistula, and a single surgeon (of 23) were associated significantly with increased risk of regional recurrence but not strictureplasty or inflammation at margins of resection. Limited surgery for Crohn's disease is not associated with increased risk of regional recurrence requiring reoperation. However, patients with juvenile onset, proximal small bowel disease, and some types of fistulae are at a considerable risk of experiencing early surgical recurrence.


New semi-empirical formulae for (n,d) cross sections at 14-15 MeV.
The aim of this letter is to suggest new semi-empirical formulae for the prediction of (n,d) cross sections with a neutron energy of 14-15 MeV. In this context, the cross sections are calculated using systematic that is function only of the reaction Q-value and mass number A. The (n,d) reactions are analyzed by using the systematics based on the statistical theory. Thus, the present semi-empirical formulae compared with the cross section data in literature give a good fit for the prediction of the (n,d) cross sections at 14-15 MeV.


Diarrhea-associated biofilm formed by enteroaggregative Escherichia coli and aggregative Citrobacter freundii: a consortium mediated by putative F pili.
Enteroaggregative Escherichia coli (EAEC) are enteropathogenic strains identified by the aggregative adhesion (AA) pattern that share the capability to form biofilms. Citrobacter freundii is classically considered as an indigenous intestinal species that is sporadically associated with diarrhea. During an epidemiologic study focusing on infantile diarrhea, aggregative C. freundii (EACF) and EAEC strains were concomitantly recovered from a severe case of mucous diarrhea. Thereby, the occurrence of synergic events involving these strains was investigated. Coinfection of HeLa cells with EACF and EAEC strains showed an 8-fold increase in the overall bacterial adhesion compared with single infections (P < 0.001). The synergic effect was mediated by physical interactions among the bacteria and primed in the absence of chemical signaling and without the participation of host cells. Thus, significant increases (2.7-fold on average) in bacterial adhesion were also observed during the formation of mixed biofilms on abiotic surfaces. Bacterial settling assays showed that EAEC strains harboring F-pili genes (traA) were capable of forming bacterial aggregates only in the presence of EACF. Scanning electronic microscopy analyses revealed that bacterial aggregates as well as enhanced biofilms formed by EACF and traA-positive EAEC were mediated by non-bundle forming, flexible pili. Moreover, mixed biofilms formed by EACF and traA-positive EAEC strains were significantly reduced using nonlethal concentration of zinc, a specific inhibitor of F pili. In addition, EAEC strains isolated from diarrheic children frequently produced single biofilms sensitive to zinc. Putative F pili expressed by EAEC strains boosted mixed biofilm formation when in the presence of aggregative C. freundii.


Hybrid EEG-fNIRS Asynchronous Brain-Computer Interface for Multiple Motor Tasks.
Non-invasive Brain-Computer Interfaces (BCI) have demonstrated great promise for neuroprosthetics and assistive devices. Here we aim to investigate methods to combine Electroencephalography (EEG) and functional Near-Infrared Spectroscopy (fNIRS) in an asynchronous Sensory Motor rhythm (SMR)-based BCI. We attempted to classify 4 different executed movements, namely, Right-Arm-Left-Arm-Right-Hand-Left-Hand tasks. Previous studies demonstrated the benefit of EEG-fNIRS combination. However, since normally fNIRS hemodynamic response shows a long delay, we investigated new features, involving slope indicators, in order to immediately detect changes in the signals. Moreover, Common Spatial Patterns (CSPs) have been applied to both EEG and fNIRS signals. 15 healthy subjects took part in the experiments and since 25 trials per class were available, CSPs have been regularized with information from the entire population of participants and optimized using genetic algorithms. The different features have been compared in terms of performance and the dynamic accuracy over trials shows that the introduced methods diminish the fNIRS delay in the detection of changes.


A latent trajectory analysis of young sexual and gender minorities' adherence to three rectal microbicide placebo formulations (MTN-035; a randomized crossover trial).
Rectal microbicides (RM) are biomedical HIV prevention products that aim to prevent or reduce the transmission of HIV and other sexually transmitted infections (STIs). RM modalities may be beneficial for populations who have complex lifestyles, difficulties adhering to pre-exposure prophylaxis (PrEP) regimens, and/or have limited access to care. MTN-035 (DESIRE; Developing and Evaluating Short-Acting Innovations for Rectal Use), a randomized crossover trial, aimed to evaluate the safety and acceptability of, and adherence to, three placebo RM modalities (douche, insert, and suppository) prior to receptive anal intercourse. We conducted latent trajectory analysis to identify clusters of individuals who shared similar trajectories in acceptability and adherence for each product (douche, insert, and suppository) over time. We analyzed weekly short messaging service (SMS) use reports for each modality as reported by enrolled sexual and gender minority (SGM) participants. Two trajectories for each product were identified: a "protocol compliant" trajectory (i.e., at least one product use occasion per week) and "high use" trajectory (i.e., more than three product use occasions per week). Participants with high use were more likely to lack access to PrEP and have higher intentions to utilize RM modalities compared to those who were protocol compliant. This study highlighted high adherence to RM modalities among SGM. As research into viable HIV prevention modalities continues to evolve, tailored intervention strategies are needed to support the uptake of and adherence to alternative prevention modalities that are behaviorally congruent with targeted users. NCT03671239 (14/09/2018).


Ditopic Covalent Cage for Ion-Pair Binding: Influence of Anion Complexation on the Cation Exchange Rate.
A new hemicryptophane host with a ditopic molecular cavity combining a cyclotriveratrylene (CTV) unit with a tris-urea moiety was synthesized. The complexation of halides, tetramethylammonium (TMA+ ) cation, and ion pairs was investigated. A positive cooperativity was observed, since halides display a higher binding constant when a TMA+ cation is already present inside the cage. When TMA+ was complexed alone, a decrease of temperature from 298 K to 230 K was required to switch from a fast to a slow exchange regime on the NMR time scale. Nevertheless, the prior complexation of a halide guest in the lower part of the host resulted in significant decrease of the exchange rate of the subsequent complexation of the TMA+ cation. Under these conditions, the 1 H NMR signals characteristic of a slow exchange regime were observed at 298 K. Addition of an excess of salts, increases the ionic strength of the solution, restoring the fast exchange dynamics. This result provides insight on how the exchange rate of a cation guest can be modulated by the complexation of a co-guest anion.


Using concept mapping to inform the development of a transitional reintegration intervention program for formerly incarcerated people with HIV.
Accessing HIV-related care is challenging for formerly incarcerated people with HIV. Interventions informed by the perspectives of these individuals could facilitate engagement with care and address competing priorities that may act as barriers to this process. We used concept mapping to identify and prioritize the main obstacles to engaging with HIV-related care following prison release. In brainstorming sessions, formerly incarcerated people with HIV generated responses to a focused prompt regarding the main barriers to reengaging with care. These were consolidated in 35 statements. Next, participants sorted the consolidated list of responses into groups and rated each from lowest to highest in terms of its importance and feasibility of being addressed. We used cluster analysis to generate concept maps that were interpreted with participants. Overall, 39 participants participated in brainstorming sessions, among whom 18 returned for rating and sorting. Following analysis, a seven-cluster map was generated, with participants rating the 'Practical Considerations' (e.g. lack of transportation from prison) and 'Survival Needs' (e.g. securing housing and food) clusters as most important. Although ratings were generally similar between women and men, women assigned greater importance to barriers related to reconnecting with children. Using concept mapping, we worked with formerly incarcerated people with HIV to identify and prioritize key challenges related to accessing health and social services following prison release. Transitional intervention programs should include programs and processes that address meeting basic subsistence needs and overcoming logistical barriers related to community re-entry.


When philosophical nuance matters: safeguarding consciousness research from restrictive assumptions.
In this paper, we revisit the debate surrounding the Unfolding Argument (UA) against causal structure theories of consciousness (as well as the hard-criteria research program it prescribes), using it as a platform for discussing theoretical and methodological issues in consciousness research. Causal structure theories assert that consciousness depends on a particular causal structure of the brain. Our claim is that some of the assumptions fueling the UA are not warranted, and therefore we should reject the methodology for consciousness science that the UA prescribes. First, we briefly survey the most popular philosophical positions in consciousness science, namely physicalism and functionalism. We discuss the relations between these positions and the behaviorist methodology that the UA assumptions express, despite the contrary claim of its proponents. Second, we argue that the same reasoning that the UA applies against causal structure theories can be applied to functionalist approaches, thus proving too much and deeming as unscientific a whole range of (non-causal structure) theories. Since this is overly restrictive and fits poorly with common practice in cognitive neuroscience, we suggest that the reasoning of the UA must be flawed. Third, we assess its philosophical assumptions, which express a restrictive methodology, and conclude that there are reasons to reject them. Finally, we propose a more inclusive methodology for consciousness science, that includes neural, behavioral, and phenomenological evidence (provided by the first-person perspective) without which consciousness science could not even start. Then, we extend this discussion to the scope of consciousness science, and conclude that theories of consciousness should be tested and evaluated on humans, and not on systems considerably different from us. Rather than restricting the methodology of consciousness science, we should, at this point, restrict the range of systems upon which it is supposed to be built.


Kinetics of Drug Release from Clay Using Enhanced Sampling Methods.
A key step in the development of a new drug, is the design of drug-excipient complexes that lead to optimal drug release kinetics. Computational chemistry and specifically enhanced sampling molecular dynamics methods can play a key role in this context, by minimizing the need for expensive experiments, and reducing cost and time. Here we show that recent advances in enhanced sampling methodologies can be brought to fruition in this area. We demonstrate the potential of these methodologies by simulating the drug release kinetics of the complex praziquantel-montmorillonite in water. Praziquantel finds promising applications in the treatment of schistosomiasis, but its biopharmaceutical profile needs to be improved, and a cheap material such as the montmorillonite clay would be a very convenient excipient. We simulate the drug release both from surface and interlayer space, and find that the diffusion of the praziquantel inside the interlayer space is the process that limits the rate of drug release.


Effects of Low-Level Laser Therapy on Muscular Performance and Soreness Recovery in Athletes: A Meta-analysis of Randomized Controlled Trials.
Athletes must maintain their peak state of strength. Previous studies have investigated the effect of low-level laser therapy (LLLT) on muscular performance. A previous systematic review and meta-analysis has investigated this issue in healthy participants but not in physically active athletes. To investigate whether LLLT can improve muscular performance and soreness recovery in athletes. PubMed, EMBASE, and Cochrane Library. Published randomized controlled trials and crossover studies till December 2020. Systematic review and meta-analysis. Level 3. Assessment of study quality was rated using the risk of bias assessment method for randomized trials (Cochrane Handbook for Systematic Reviews of Interventions). A total of 24 studies were included. LLLT application before exercise significantly improved lower-limb muscle strength in 24-hour, 48-hour, 96-hour, and 8-week follow-up groups. Furthermore, decreased soreness index, serum creatine kinase concentrations, interleukin-6, and thiobarbituric acid reactive substance concentrations and a trend toward the improvement of contract repetition number and VO2 kinetic outcomes were observed. Although a definite therapeutic effect of LLLT is yet to be established, the current evidence supports that LLLT use improves muscular performance in physically active athletes. Additional trials with large sample sizes and robust design should be conducted before strong recommendations are made.


Preoperative predictors of liver decompensation after mini-invasive liver resection.
Post-hepatectomy liver failure (PHLF) represents the most frequent complication after liver surgery, and the most common cause of morbidity and mortality. Aim of the study is to identify the predictors of PHLF after mini-invasive liver surgery in cirrhosis and chronic liver disease, and to develop a model for risk prediction. The present study is a multicentric prospective cohort study on 490 consecutive patients who underwent mini-invasive liver resection from the Italian Registry of Mini-invasive Liver Surgery (I go MILS). Retrospective additional biochemical and clinical data were collected. On 490 patients (26.5% females), PHLF occurred in 89 patients (18.2%). The only independent predictors of PHLF were Albumin-Bilirubin (ALBI) score (OR 3.213; 95% CI 1.661-6.215; p < .0.0001) and presence of ascites (OR 3.320; 95% CI 1.468-7.508; p = 0.004). Classification and regression tree (CART) modeling led to the identification of three risk groups: PHLF occurred in 23/217 patients with ALBI grade 1 (10.6%, low risk group), in 54/254 patients with ALBI score 2 or 3 and absence of ascites (21.3%, intermediate risk group) and in 12/19 patients with ALBI score 2 or 3 and evidence of ascites (63.2%, high risk group), p < 0.0001. The three groups showed a corresponding increase in postoperative complications (20.0%, 27.5% and 66.7%), Comprehensive Complication Index (5.1 ± 11.1, 6.0 ± 10.9 and 18.8 ± 18.9) and hospital stay (6.0 ± 4.0, 6.0 ± 6.0 and 8.0 ± 5.0 days). The risk of PHLF can be stratified by determining two easily available preoperative factors: ALBI and ascites. This model of risk prediction offers an objective instrument for a correct clinical decision-making.


Vascular remodeling of the vitelline artery initiates extravascular emergence of hematopoietic clusters.
The vitelline artery is a temporary structure that undergoes extensive remodeling during midgestation to eventually become the superior mesenteric artery (also called the cranial mesenteric artery, in the mouse). Here we show that, during this remodeling process, large clusters of hematopoietic progenitors emerge via extravascular budding and form structures that resemble previously described mesenteric blood islands. We demonstrate through fate mapping of vascular endothelium that these mesenteric blood islands are derived from the endothelium of the vitelline artery. We further show that the vitelline arterial endothelium and subsequent blood island structures originate from a lateral plate mesodermal population. Lineage tracing of the lateral plate mesoderm demonstrates contribution to all hemogenic vascular beds in the embryo, and eventually, all hematopoietic cells in the adult. The intraembryonic hematopoietic cell clusters contain viable, proliferative cells that exhibit hematopoietic stem cell markers and are able to further differentiate into myeloid and erythroid lineages. Vitelline artery-derived hematopoietic progenitor clusters appear between embryonic day 10 and embryonic day 10.75 in the caudal half of the midgut mesentery, but by embryonic day 11.0 are sporadically found on the cranial side of the midgut, thus suggesting possible extravascular migration aided by midgut rotation.


A Chiral Nanocomplex for Multitarget Therapy to Alleviate Neuropathology and Rescue Alzheimer's Cognitive Deficits.
Alzheimer's disease (AD) is a severe neurodegenerative condition characterized by inflammation, beta-amyloid (Aβ) plaques, and neurodegeneration, which currently lack effective treatments. Chiral nanomaterials have emerged as a promising option for treating neurodegenerative disorders due to their high biocompatibility, strong sustained release ability, and specific enantiomer selectivity. The development of a stimulus-responsive chiral nanomaterial, UiO-66-NH2 @l-MoS2 QDs@PA-Ni (MSP-U), for the treatment of AD is reported. MSP-U is found to stimulate neural stem cell (NSCs) differentiation, promote in situ hydrogen (H2 ) production, and clear Aβ plaques. l-MoS2 QDs modified with l-Cysteine (l-Cys) effectively enhance the differentiation of NSCs into neurons through circularly polarized near-infrared radiation. Doped-phytic acid nickel (PA-Ni) improves the activity of l-MoS2 QDs in scavenging reactive oxygen species at the lesion site via photocatalytic H2 production. Loading l-MoS2 QDs with UiO-66 type metal oxide suppresses electron-hole recombination effect, thereby achieving rapid charge separation and improving transport of photogenerated electrons, leading to significantly improved H2 production efficiency. The photothermal effect of MSP-U also clears the generated Aβ plaques. In vivo evaluations show that MSP-U improves spatial cognition and memory, suggesting a promising potential candidate for the treatment of AD using chiral nanomaterials.


[The changes of oxidative-reductive processes and fatty acid composition of liver lipids in rats with streptozotocin-induced diabetes].
The processes of lipid peroxidation, oxidative modification of proteins, the state of antioxidant protection system enzymes and fatty acid composition of liver lipids were investigated in rats with streptosotocin-induced diabetes. The development of diabetes is accompanied by oxidative stress, which results in the activation of lipid peroxidation processes and the increase in the amount of nitrogen oxide and the activity of antioxidant protection system enzymes. The increase of the amount of saturated fatty acid and fall in the amount of unsaturated fatty acid has been detected. The rise of the processes of protein oxidation was established, which can lead to loss of their biological activity.


Deep learning applied to hyperspectral endoscopy for online spectral classification.
Hyperspectral imaging (HSI) is being explored in endoscopy as a tool to extract biochemical information that may improve contrast for early cancer detection in the gastrointestinal tract. Motion artefacts during medical endoscopy have traditionally limited HSI application, however, recent developments in the field have led to real-time HSI deployments. Unfortunately, traditional HSI analysis methods remain unable to rapidly process the volume of hyperspectral data in order to provide real-time feedback to the operator. Here, a convolutional neural network (CNN) is proposed to enable online classification of data obtained during HSI endoscopy. A five-layered CNN was trained and fine-tuned on a dataset of 300 hyperspectral endoscopy images acquired from a planar Macbeth ColorChecker chart and was able to distinguish between its 18 constituent colors with an average accuracy of 94.3% achieved at 8.8 fps. Performance was then tested on a set of images simulating an endoscopy environment, consisting of color charts warped inside a rigid tube mimicking a lumen. The algorithm proved robust to such variations, with classification accuracies over 90% being obtained despite the variations, with an average drop in accuracy of 2.4% being registered at the points of longest working distance and most inclination. For further validation of the color-based classification system, ex vivo videos of a methylene blue dyed pig esophagus and images of different disease stages in the human esophagus were analyzed, showing spatially distinct color classifications. These results suggest that the CNN has potential to provide color-based classification during real-time HSI in endoscopy.


Regulation of membrane phospholipids during the adult life of worker honey bee.
Two female castes that are genetically identical are found in honey bees: workers and queens. Adult female honey bees differ in their morphology and behaviors, but the most intriguing difference between the castes is the difference in their longevity. Queens live for years while workers live generally for weeks. The mechanisms that mediate this extraordinary difference in lifespan remain mostly unknown. Both castes share similar developmental stages and are fed liquid food (i.e. a jelly) during development. However, after emergence, workers begin to feed on pollen while queens are fed the same larval food for their entire life. Pollen has a high content of polyunsaturated fatty acids (PUFA) while royal jelly has negligible amounts. The difference in food during adult life leads to drastic changes in membrane phospholipids of female honey bees, and those changes have been proposed as mechanisms that could explain the difference in lifespan. To provide further details on those mechanisms, we characterized the membrane phospholipids of adult workers at seven different ages covering all life-history stages. Our results suggest that the majority of changes in worker membranes occur in the first four days of adult life. Shortly after emergence, workers increase their level of total phospholipids by producing phospholipids that contained saturated (SFA) and monounsaturated fatty acids (MUFA). From the second day, workers start replacing fatty acid chains from those pre-synthesized molecules with PUFA acquired from pollen. After four days, worker membranes are set and appear to be maintained for the rest of adult life, suggesting that damaged PUFA are replaced effectively. Plasmalogen phospholipids increase continuously throughout worker adult life, suggesting that plasmalogen might help to reduce lipid peroxidation in worker membranes. We postulate that the diet-induced increase in PUFA in worker membranes makes them far more prone to lipid-based oxidative damage compared to queens.


Brain-derived neurotrophic factor ameliorates brain stem cardiovascular dysregulation during experimental temporal lobe status epilepticus.
Status epilepticus (SE) is an acute, prolonged epileptic crisis with a mortality rate of 20-30%; the underlying mechanism is not completely understood. We assessed the hypothesis that brain stem cardiovascular dysregulation occurs during SE because of oxidative stress in rostral ventrolateral medulla (RVLM), a key nucleus of the baroreflex loop; to be ameliorated by brain-derived neurotrophic factor (BDNF) via an antioxidant action. In a clinically relevant experimental model of temporal lobe SE (TLSE) using Sprague-Dawley rats, sustained hippocampal seizure activity was accompanied by progressive hypotension that was preceded by a reduction in baroreflex-mediated sympathetic vasomotor tone; heart rate and baroreflex-mediated cardiac responses remained unaltered. Biochemical experiments further showed concurrent augmentation of superoxide anion, phosphorylated p47(phox) subunit of NADPH oxidase and mRNA or protein levels of BDNF, tropomyosin receptor kinase B (TrkB), angiotensin AT1 receptor subtype (AT1R), nitric oxide synthase II (NOS II) or peroxynitrite in RVLM. Whereas pretreatment by microinjection bilaterally into RVLM of a superoxide dismutase mimetic (tempol), a specific antagonist of NADPH oxidase (apocynin) or an AT1R antagonist (losartan) blunted significantly the augmented superoxide anion or phosphorylated p47(phox) subunit in RVLM, hypotension and the reduced baroreflex-mediated sympathetic vasomotor tone during experimental TLSE, pretreatment with a recombinant human TrkB-Fc fusion protein or an antisense bdnf oligonucleotide significantly potentiated all those events, alongside peroxynitrite. However, none of the pretreatments affected the insignificant changes in heart rate and baroreflex-mediated cardiac responses. We conclude that formation of peroxynitrite by a reaction between superoxide anion generated by NADPH oxidase in RVLM on activation by AT1R and NOS II-derived NO leads to a reduction in baroreflex-mediated sympathetic vasomotor tone during experimental TLSE; to be ameliorated by the upregulated BDNF/TrkB signaling via inhibition of p47(phox) phosphorylation. This information offers a new vista in devising therapeutic strategy towards minimizing mortality associated with TLSE.


An intestinal galactose-specific lectin mediates the binding of murine IgE to mouse intestinal epithelial cells.
A number of lactose-binding lectins have recently been identified in the rat and mouse intestine, one of which corresponds to the C-terminal domain of IgE-binding proteins, originally identified in rat basophilic leukemia (RBL) cells and mouse 3T3 fibroblasts. In the present report, we describe the affinity purification of a rat intestinal lactose-specific lectin which binds murine IgE antibodies. This binding most likely occurs via the immunoglobulin carbohydrate chains, as it is inhibited by lactose. This intestinal lectin molecule is also immunologically related to the previously described IgE-binding protein (epsilon BP) isolated from RBL cells, since it is recognized by antibodies raised against recombinant epsilon BP. This intestinal form of epsilon BP has a molecular mass of 17.5 kDa, which is much lower than that of its RBL cell analogue (31 kDa). The attachment of IgE to the mouse intestinal epithelium was demonstrated by immunohistochemistry, along with the presence of a corresponding mouse intestinal epsilon BP. The carbohydrate-dependent nature of this attachment was established by demonstrating that IgE binding to mouse epithelium was specifically abolished by lactose (4 mM) and by a blood-group-A-active tetrasaccharide (0.2 mM), but not by mannose (10 mM). Finally, the association of IgE with the mouse intestinal epithelium was prevented by competition with the purified IgE-binding lectin isolated from rat intestine. Although the physiological function of this intestinal protein is still unknown, the finding that IgE binds to a lectin in the intestinal epithelium pinpoints a possible novel mechanism for the regulation of IgE-mediated disorders, such as food allergy.


Closure of nasal septal perforations.
Twenty patients with nasal septal perforations were treated in a seven-year period by closure with a combined flap and graft technique. Nineteen patients (95%) reported relief of symptoms and showed complete closure of their perforations on follow-up examinations one to seven years later. The technique employs bipedicled mucosal advancement flaps, designed to maximize blood supply for flap viability, and an underlying connective tissue autograft (fascia or pericranium) for structural reinforcement.


[The state of sympathetic-adrenal system in patients with chronic cardiac insufficiency].
Activation of sympato-adrenal system plays an important role in the development of chronic cardiac failure (CCF). However, its relation to morpho-functional state of myocardium in CCF patients is virtually unknown. HPLC with electrochemical detection was used to determine plasma noradrenalin, adrenalin, and their precursors, 3,4-dioxyphenylalanine (DOPA) and dopamine, in patients with different morpho-functional changes in myocardium. The study demonstrated enhanced activity of sympato-adrenal system in patients with CCF. It showed for the first time that activity of sympato-adrenal system in CCF patients depends on the morpho-functional status of myocardium.


Mucocutaneous lymph node syndrome in Calabar--a case report.
A four and a half-year old Nigerian girl, living at home, who presented with protracted fever, multifocal lymph node enlargement, extensive scaly rash, injected conjunctivae, fissuring of the lip and other features consistent with a diagnosis of Kawasaki disease is reported. This disease, first seen in Japan and then other parts of the world including black Africa has not yet been reported in Nigeria. Child care physicians in Nigeria are hereby cautioned to look out for this unusual disease.


Otitis media in 2253 Pittsburgh-area infants: prevalence and risk factors during the first two years of life.
As part of a long-term study of possible effects of early-life otitis media on speech, language, cognitive, and psychosocial development, we set out to delineate the occurrence and course of otitis media during the first 2 years of life in a sociodemographically diverse population of infants, and to identify related risk factors. We enrolled healthy infants by age 2 months who presented for primary care at one of two urban hospitals or one of two small town/rural and four suburban private pediatric practices. We intensively monitored the infants' middle-ear status by pneumatic otoscopy, supplemented by tympanometry, throughout their first 2 years of life; we monitored the validity of the otoscopic observations on an ongoing basis; and we treated infants for otitis media according to specified guidelines. We followed 2253 infants until age 2 years. The proportions developing > or = 1 episode of middle-ear effusion (MEE) between age 61 days (the starting point for data analysis) and ages 6, 12, and 24 months, respectively, were 47.8%, 78.9%, and 91.1%. Overall, the mean cumulative proportion of days with MEE was 20.4% in the first year of life and 16.6% in the second year of life. Tympanostomy-tube placement was performed on 1.8% and 4.2% of the infants during the first and second years of life, respectively. By every measure, the occurrence of MEE was highest among urban infants and lowest among suburban infants; these differences were greatest in the earliest months of life. Overall, unadjusted mean cumulative proportions of days with MEE were higher among boys than girls, higher among black than white infants, and higher among Medicaid than private health insurance enrollees. Cumulative proportions of days with MEE varied directly with the number of smokers in the household and with the number of other children to whom infants were exposed, whether at home or in day care, and varied inversely with birth weight, maternal age, level of maternal education, a socioeconomic index, and duration of breastfeeding. After adjustment, using multivariate analysis, the only variables that each remained independently and significantly related to the cumulative proportion of days with MEE were: during the first year of life, study site grouping, sex, the socioeconomic index, breastfeeding for > or = 4 months, the number of smokers in the household, and an index rating the degree of exposure to other children at home or in day care; and during the second year of life, sex, the socioeconomic index, and the child exposure index. The duration of breastfeeding and the degree of exposure to tobacco smoke contributed little to the explained variance; most was attributable to differences in the socioeconomic index and the child exposure index. Contrary to findings in many previous reports, the prevalence of otitis media during the first 2 years of life among lower-socioeconomic-status black infants appears to be as high as, if not higher than among lower-socioeconomic-status white infants, and certainly higher than among middle-class white infants. Among middle-class white infants the prevalence may also be higher than commonly assumed. The most important sociodemographic risk factors for otitis media appear to be low socioeconomic status and repeated exposure to large numbers of other children, whether at home or in day care.


Medroxyprogesterone acetate drives M2 macrophage differentiation toward a phenotype of decidual macrophage.
M1 macrophage differentiation plays a crucial role in enhanced inflammation during pregnancy, which may lead to pregnancy complications. Therefore, modulation of macrophage differentiation toward the M2 phenotype is desirable to ensure a successful pregnancy. Medroxyprogesterone acetate (MPA) is a potent progestin with an anti-inflammatory property, but its effect on macrophage differentiation is unknown. This study aimed to examine whether MPA can induce an M2 macrophage differentiation by using the human monocytes cell line THP-1 or primary monocytes. THP-1 cells were primed with phorbol-12-myristate-13 acetate (PMA) to initiate macrophage differentiation. By incubating with MPA, the cells (denoted as MPA-pTHP-1) underwent M2 macrophage differentiation with downregulations of CD11c, IL-1β and TNF-α, and upregulations of CD163 and IL-10; while cells incubated with progesterone (P4) did not show the M2 phenotype. Primary monocytes treated with MPA also had the same M2 phenotype. Moreover, M1 macrophages derived from IFN-γ/LPS-treated THP-1 cells, which had high levels of IL-1b and iNOS, and low levels of IL-10 and IDO, were reversed to the M2 phenotype by the MPA treatment. We also found that the MPA-pTHP-1 promoted the decidualization of endometrial stromal cells and the invasion of trophoblast cells. To mimic conditions of exposure to various pathogens, MPA-pTHP-1 cells were stimulated by different types of TLR ligands. We found they produced lower levels of IL-1β and TNF-α, as well as a higher level of IL-10, compared to untreated cells. Finally, we found the level of phosphorylated ERK in the MPA-pTHP-1 cells was increased, but its IL-10 production was suppressed by either the progesterone/glucocorticoid antagonist (Mifepristone) or MEK inhibitor (U0126). Taken together, MPA could drive monocyte differentiation toward an M2 phenotype that mimics decidual macrophages. This finding holds great potential to combat chronic endometrial inflammation.


Pharmacokinetics and metabolism of zopiclone.
Pharmacokinetics and metabolism of a new hypnotic, zopiclone (ZD), were studied under the following conditions: (1) rats and dogs were given oral doses of the molecule, 14C-labeled either on the side chain or on the pyrrolopyrazine nucleus; (2) rats, rabbits and dogs were given increasing oral doses of the cold compound; (3) human subjects in various physiopathological situations - young and elderly healthy volunteers, patients with liver or renal impairments, nursing mothers - were given single or repeated doses, p.o. or i.v. (range 3.5-15 mg). ZD is rapidly and efficiently absorbed: its oral bioavailability was greater than 75% in all species except rats, where a first-pass effect of about 65% was recorded. Plasma protein binding is about 45%. The radioactive material rapidly diffuses from the vascular compartment, with a marked affinity for the brain. Plasma kinetics of ZD are generally well described by a two-compartment open model; in man, terminal half-life is 4-5 h; total body clearance is large (300 ml/mn), renal clearance very low (10 ml/min). The relationship between doses and concentrations, doses and urinary excretion of unchanged compound and major metabolites was linear in all species, except rabbits. The major metabolic routes involve decarboxylation affecting more than 50% of dose (rats and dogs), N-demethylation and N-oxidation - more than 30% as N-desmethyl and N-oxide derivatives in urine (humans). Due to intensive metabolism, only 7-10% of the dose is recovered in urine and feces as unchanged compounds (all species). In nursing mothers, milk and plasma kinetics of ZD are similar with a milk/plasma ratio around 0.80. In human volunteers, plasma half-life of ZD increases with age, while patients with liver or renal impairments show little or no modification of pharmacokinetic parameters.


Association of maxillary and mandibular base lengths with dental crowding in different skeletal malocclusions.
Dental crowding is the one of the most frequently encountered problem for an orthodontist. The relationship between crowding and various skeletal, dental and soft tissue parameters is important to establish and consider during the overall orthodontic treatment planning. This study aimed to determine the correlation of maxillary and mandibular base lengths with dental arch crowding in different malocclusions and to evaluate the gender dimorphism for these variables. A sample of 120 subjects divided into three skeletal malocclusions was further subdivided based on amount of mandibular arch crowding. Maxillary and mandibular base lengths and dental arch crowding were measured on pre-treatment lateral cephalograms and initial casts using vernier calliper respectively. Inter-group comparisons were assessed by univariate analysis of variance. Correlation between base lengths and dental crowding was assessed by Pearson's correlation (p≤0.05). Statistically significant differences were found for maxillary (p=0.008) and mandibular base lengths (p=0.000) between different skeletal malocclusions. Mandibular base length was significantly larger in males (p=0.000). Mandibular crowding was highest in class-II and lowest in class-I (p=0.01). A significant but weak negative correlation was found between dental crowding and maxillary (r=-0.28, p=0.02) and mandibular (r=-0.20, p=0.02) base lengths, significant but moderate positive correlation between maxillary and mandibular base lengths (r=0L566, -0.000) and between maxillary and mandibular crowding (r=-0.408, p-0.000). Maxillary and mandibular base lengths are largest in skeletal class-II and class-III malocclusions respectively. Mandibular base length is larger in males as compared to females. An increase in amount of dental crowding is weakly associated with smaller skeletal base lengths.


A Chronic Disease Prevention and Management Corridor© to Supporting System-Level Transformations for Chronic Conditions.
Improving care for chronic conditions requires system-level transformations to ensure multiple levels of adoption and sustainability of the implemented improvements. These comprehensive solutions require transformations and supports at various levels, leadership and process changes at service/program level. Recognizing the importance of an organization-wide strategy to mitigate the growing issue of chronic disease prevention and management, a novel system-level approach has been developed in a district health authority in Nova Scotia, Canada. In this paper, the contextual factors and efforts that led to the conceptual framework of the Chronic Disease Prevention and Management (CDPM) "Corridor©" to management of chronic conditions are discussed. The CDPM Corridor© essentially constitutes a system-level redesign process; common elements, tools and resources; and a hub of supports for chronic disease prevention and management. The CDPM Corridor


Thermosipho globiformans sp. nov., an anaerobic thermophilic bacterium that transforms into multicellular spheroids with a defect in peptidoglycan formation.
An anaerobic rod-shaped thermophile was isolated from a hydrothermal vent at Suiyo Seamount, Izu-Bonin Arc, western Pacific Ocean, and was named strain MN14(T). The rods were gram-negative-staining, non-motile without flagella, 2-4 µm long and 0.5 µm wide, and divided by binary fission in the mid-exponential phase. The cells were surrounded by a sheath-like structure (toga) and occurred singly or in chains. Spheroids containing multiple cells were observed not only in the stationary phase, as previously observed for species of the order Thermotogales, but also from the early exponential phase. Transmission electron microscopy revealed that the peptidoglycan in rods partly disintegrated in the early growth phases and that the outer membrane of the spheroids was not completely lined with peptidoglycan. These findings suggested that the spheroids were formed from rods by the disintegration of peptidoglycan and subsequent inflation of the outer membrane. The spheroids eventually generated tiny cells in the periplasmic space, indicating a viviparous mode of proliferation in addition to binary fission. Strain MN14(T) grew at 40-75 °C, pH 5.0-8.2 and with 0.25-5.20 % (w/v) NaCl, with optimal growth occurring at 68 °C, pH 6.8 and with 2.5 % NaCl. The shortest doubling time was 24 min, assuming that the strain propagated only by binary fission. Elemental sulfur enhanced growth, but was not essential. Thiosulfate was not an electron acceptor for growth. The strain was a chemo-organotroph that grew on yeast extract as the sole growth substrate. Tryptone and starch supported its growth in the presence of yeast extract. The G+C content of the genomic DNA was 31.7 mol%. Phylogenetic analysis based on the 16S rRNA gene sequence indicated that this strain belonged to the genus Thermosipho. No significant DNA-DNA hybridization was observed between the genomic DNA of strain MN14(T) and phylogenetically related species of the genus Thermosipho. Based on this evidence, strain MN14(T) is proposed to represent a novel species, named Thermosipho globiformans sp. nov. The species epithet globiformans reflects the formation of multicellular and reproductive spheroids by the novel strain. The type strain of this species is MN14(T) ( = JCM 15059(T) = DSM 19918(T)).


Understanding the development of human bladder cancer by using a whole-organ genomic mapping strategy.
The search for the genomic sequences involved in human cancers can be greatly facilitated by maps of genomic imbalances identifying the involved chromosomal regions, particularly those that participate in the development of occult preneoplastic conditions that progress to clinically aggressive invasive cancer. The integration of such regions with human genome sequence variation may provide valuable clues about their overall structure and gene content. By extension, such knowledge may help us understand the underlying genetic components involved in the initiation and progression of these cancers. We describe the development of a genome-wide map of human bladder cancer that tracks its progression from in situ precursor conditions to invasive disease. Testing for allelic losses using a genome-wide panel of 787 microsatellite markers was performed on multiple DNA samples, extracted from the entire mucosal surface of the bladder and corresponding to normal urothelium, in situ preneoplastic lesions, and invasive carcinoma. Using this approach, we matched the clonal allelic losses in distinct chromosomal regions to specific phases of bladder neoplasia and produced a detailed genetic map of bladder cancer development. These analyses revealed three major waves of genetic changes associated with growth advantages of successive clones and reflecting a stepwise conversion of normal urothelial cells into cancer cells. The genetic changes map to six regions at 3q22-q24, 5q22-q31, 9q21-q22, 10q26, 13q14, and 17p13, which may represent critical hits driving the development of bladder cancer. Finally, we performed high-resolution mapping using single nucleotide polymorphism markers within one region on chromosome 13q14, containing the model tumor suppressor gene RB1, and defined a minimal deleted region associated with clonal expansion of in situ neoplasia. These analyses provided new insights on the involvement of several non-coding sequences mapping to the region and identified novel target genes, termed forerunner (FR) genes, involved in early phases of cancer development.


Nanoconfinement Controls Mechanical Properties of Elastomeric Thin Films.
Mastering mechanical properties of polymers at nanometer scale is highly demanded yet remains challenging. Pioneering advances determined Young's modulus in ultrathin polymer films and attained unprecedented results including rubbery stiffening. However, many viscoelastic properties such as dynamic mechanical behavior of freestanding nanoconfined polymer films are still unknown. Here we demonstrate striking changes of stiffness and the ratio between elastic and viscous responses in thin PDMS films, using a microvibrational system which enables direct measurements of dynamic stress-strain relation of freestanding films. The results show that elastic modulus is enhanced by a factor of 135 in 50 nm films than the bulk, while the viscous response substantially increases at strains >0.05 in 125 nm films. These observations exhibit significant alterations of viscoelasticity under nanoconfinement. With insights on the underlying mechanism of these results, this study is expected to provide new evidence toward gaining a comprehensive understanding of nanoconfinement effect of soft matter.


Deletions of specific regions of the simian sarcoma-associated virus genome are found in defective viruses and in the simian sarcoma virus.
Extrachromosomal DNA was isolated from tissue culture cells that were acutely infected with simian sarcoma virus (SSV) and its associated helper (simian sarcoma-associated virus [SSAV]). Two sizes of closed circular viral genomic DNA intermediates were isolated, cleaved at the single EcoRI site, and ligated to the Charon 21A phage lambda vector. Cloned molecules of the larger size all represented the full-length (9.0-kilobase [kb]) SSAV molecule. A heterogeneous group of clones was derived from the smaller DNA circles. These included the SSV genome and SSAV deletion mutants. When two SSV clones were compared with the helper, they contained the following three characteristic deletions: (i) a 250-base pair deletion in the gag gene about 1.0 kb from the 5' end of the genome; (ii) a 1.85-kb deletion in the pol gene; and (iii) a 1.9-kb deletion at the 3' end, which included part of the env gene. This latter deletion was the site of the onc gene substitution. Six other clones of the smaller molecules represented the following variants of the SSAV genome: (i) two clones of the entire genome containing only one long terminal repeat unit; (ii) one clone with the 1.85-kb deletion of the pol gene observed in SSSV; and (iii) three clones having a deletion of the 3' end of the SSAV genome. In each of the latter clones, the 5' border of the deletion was indistinguishable from the 5' border of the onc substitution in SSV. The fidelity of genetic deletions observed suggested that certain regions of the SSAV genome were deleted at a high frequency. In certain cases, these deletions may have been accompanied by a substitution of cellular sequences to generate SSV.


Development of an automatic cow body condition scoring using body shape signature and Fourier descriptors.
Body condition evaluation is a common tool to assess energy reserves of dairy cows and to estimate their fatness or thinness. This study presents a computer-vision tool that automatically estimates cow's body condition score. Top-view images of 151 cows were collected on an Israeli research dairy farm using a digital still camera located at the entrance to the milking parlor. The cow's tailhead area and its contour were segmented and extracted automatically. Two types of features of the tailhead contour were extracted: (1) the angles and distances between 5 anatomical points; and (2) the cow signature, which is a 1-dimensional vector of the Euclidean distances from each point in the normalized tailhead contour to the shape center. Two methods were applied to describe the cow's signature and to reduce its dimension: (1) partial least squares regression, and (2) Fourier descriptors of the cow signature. Three prediction models were compared with manual scores of an expert. Results indicate that (1) it is possible to automatically extract and predict body condition from color images without any manual interference; and (2) Fourier descriptors of the cow's signature result in improved performance (R(2)=0.77).


Epithelial-mesenchymal transition (EMT) in kidney fibrosis: fact or fantasy?
Epithelial-mesenchymal transition (EMT) has become widely accepted as a mechanism by which injured renal tubular cells transform into mesenchymal cells that contribute to the development of fibrosis in chronic renal failure. However, an increasing number of studies raise doubts about the existence of this process in vivo. Herein, we review and summarize both sides of this debate, but it is our view that unequivocal evidence supporting EMT as an in vivo process in kidney fibrosis is lacking.


A Rare Presentation of Aggressive Renal Cell Carcinoma and the Utility of Early Molecular Testing in Rapidly Progressing Malignancies: A Case Report.
In rapidly progressing cancers, appropriate selection of first-line therapy is essential in prolonging survival. Alongside immunohistochemistry (IHC), comprehensive genomics, including whole exome and transcriptome sequencing (WES/WTS), can improve diagnostic accuracy and guide therapeutic management. Here, we report a young patient with rapidly progressing malignancy and unexpected post-mortem results, a scenario that may have been altered by early, comprehensive genomic sequencing. A 43-year-old man with no relevant medical history presented to the emergency department with progressive cough and dyspnea despite treatment for pneumonia. Radiology revealed enlarged subcarinal, hilar, retroperitoneal, and mesenteric lymph nodes, suspicious for metastasis, and a right kidney mass. Pathologic analysis of a retroperitoneal lymph node was felt to be most consistent with metastatic epithelioid angiomyolipoma (mEAML). Three weeks later, he was urgently treated with an mTOR inhibitor for presumed mEAML due to rapid clinical decline, and a subsequent 4R lymph node biopsy was performed to confirm the diagnosis and identify genomic targets via IHC and WES/WTS. Unfortunately, he developed hypoxic respiratory failure, and only posthumously did WES/WTS reveal pathogenic variants in BAP1 and VHL, consistent with clear cell renal cell carcinoma (ccRCC). With an earlier ccRCC diagnosis, he would have received combination immunotherapy/tyrosine kinase inhibition, which has significantly greater activity than mTOR inhibition in ccRCC. He could have received systemic treatment earlier, with optimal therapy, while potentially carrying lower tumor burden and greater clinical stability. In cases of rapidly progressing malignancies with complex histopathological presentations, early comprehensive molecular-based testing can aid in diagnosis and critical therapeutic decision-making.


Changes in lesion size after submacular surgery for subfoveal choroidal neovascularization in the submacular surgery trials pilot study.
To compare the size of subfoveal lesions based on photographic documentation before and after submacular surgery of choroidal neovascularization (CNV) lesions. Subfoveal lesion sizes at baseline and month 3 follow-up visits for patients assigned to surgery in the Submacular Surgery Trials (SST) Pilot Study were assessed categorically using Macular Photocoagulation Study (MPS) disc area (DA) circles. The Submacular Surgery Trials Pilot Study groups reviewed were as follows: Group N (age-related macular degeneration [AMD]; lesion <50% blood; classic CNV present; size < or =9 MPS DAs); Group R (AMD; prior nonfoveal laser; classic CNV present; size < or =9 MPS DAs); Group B (AMD; lesion > or =50% blood); and Group H (ocular histoplasmosis syndrome or idiopathic; classic CNV present; size < or =9 MPS DAs). Postoperative month 3 lesion size was at least 1 size category smaller than the preoperative lesion size in 6% (4/66) of Group N, 0 (0/31) of Group R, 6% (2/34) of Group H, and 45% (18/40) of Group B eyes. In Group H eyes, there was no size change in 50% (17/34), and enlargement was found in 44% (15/34). For eyes in Groups N and R, approximately one third remained stable (20/66, 30% and 12/31, 39%, respectively), whereas two thirds enlarged by at least 1 category (42/66, 64% and 19/31, 61%, respectively). The change in lesion size after submacular surgery was variable, with a tendency for Group H lesions to remain the same size or larger, Group B lesions to measure smaller, and Group N and Group R lesions to be larger.


Myostatin induces DNA damage in skeletal muscle of streptozotocin-induced type 1 diabetic mice.
One of the features of uncontrolled type 1 diabetes is oxidative stress that induces DNA damage and cell death. Skeletal muscle atrophy is also considerable in type 1 diabetes, however, the signaling mechanisms that induce oxidative stress culminating in muscle atrophy are not fully known. Here, we show that in Streptozotocin-induced diabetic wild type mice, hypo-phosphorylation of Akt, resulted in activation of Foxa2 transcription factor in the muscle. Foxa2 transcriptionally up-regulated Myostatin, contributing to exaggerated oxidative stress leading to DNA damage via p63/REDD1 pathway in skeletal muscle of Streptozotocin-treated wild type mice. In Myostatin(-/-) mice however, Streptozotocin treatment did not reduce Akt phosphorylation despite reduced IRS-1 signaling. Moreover, Foxa2 levels remained unaltered in Myostatin(-/-) mice, while levels of p63/REDD1 were higher compared with wild type mice. Consistent with these results, relatively less DNA damage and muscle atrophy was observed in Myostatin(-/-) muscle in response to Streptozotocin treatment. Taken together, our results for the first time show the role of Foxa2 in Myostatin regulation in skeletal muscle in diabetic mice. Altogether, these results demonstrate the mechanism by which Myostatin contributes to DNA damage in skeletal muscle of the diabetic mice that would lead to myofiber degeneration.


Genetic relatedness of Brazilian Colletotrichum truncatum isolates assessed by vegetative compatibility groups and RAPD analysis.
The genetic variation among nine soybean-originating isolates of Colletotrichum truncatum from different Brazilian states was studied. Nitrate non-utilizing (nit) mutants were obtained with potassium chlorate and used to characterize vegetative compatibility reactions, heterokaryosis and RAPD profile. Based on pairings of nit mutants from the different isolates, five vegetative complementation groups (VCG) were identified, and barriers to the formation of heterokaryons were observed among isolates derived from the same geographic area. No complementation was observed among any of the nit mutants recovered from the isolate A, which was designed heterokaryon-self-incompatible. Based on RAPD analysis, a polymorphism was detected among the wild isolate C and their nit1 and NitM mutants. RAPD amplification, with five different primers, also showed polymorphic profiles among Brazilian C. truncatum isolates. Dendrogram analysis resulted in a similarity degree ranging between 0.331 and 0.882 among isolates and identified three RAPD groups. Despite the lack of a correlation between the RAPD analysis and the vegetative compatibility grouping, results demonstrated the potential of VCG analysis to differentiate C. truncatum isolates genotypically similar when compared by RAPD.


Global Representations of Goal-Directed Behavior in Distinct Cell Types of Mouse Neocortex.
The successful planning and execution of adaptive behaviors in mammals may require long-range coordination of neural networks throughout cerebral cortex. The neuronal implementation of signals that could orchestrate cortex-wide activity remains unclear. Here, we develop and apply methods for cortex-wide Ca2+ imaging in mice performing decision-making behavior and identify a global cortical representation of task engagement encoded in the activity dynamics of both single cells and superficial neuropil distributed across the majority of dorsal cortex. The activity of multiple molecularly defined cell types was found to reflect this representation with type-specific dynamics. Focal optogenetic inhibition tiled across cortex revealed a crucial role for frontal cortex in triggering this cortex-wide phenomenon; local inhibition of this region blocked both the cortex-wide response to task-initiating cues and the voluntary behavior. These findings reveal cell-type-specific processes in cortex for globally representing goal-directed behavior and identify a major cortical node that gates the global broadcast of task-related information.


Sensitivity of cerebellar Purkinje neurons to neurotransmitters in genetically epileptic rats.
Epilepsy is a state of neuronal hyperactivity which may be caused by an altered relationship between inhibitory and excitatory influences on neurons. We have conducted experiments using microiontophoresis with in situ extracellular recording of anesthetized rat cerebellar Purkinje neuron activity to determine the sensitivity of these neurons to neurotransmitters in a genetic model of epilepsy. Quantitative evaluations of agonist-induced changes in activity were carried out by using poststimulus time histograms. Current-response curves were generated and linear regression analysis was performed to evaluate changes in responsiveness and sensitivity between control and genetically epilepsy-prone-9 rats. The current required to produce 50% inhibition of activity by GABA was 2.6-fold higher in the genetically epilepsy-prone-9 rats compared to control. In contrast, the amount of current required to produce 50% inhibition by norepinephrine was not significantly different between groups. There also was no significant change in cerebellar neuron sensitivity to the excitatory transmitter, glutamate. The lack of an alteration in sensitivity and responsiveness to norepinephrine or glutamate suggests that the hyperexcitability of neurons may be associated with a specific subsensitivity of the GABAergic system. Such a specific subsensitivity to gamma-aminobutyric acid would, therefore, yield a more excitable state of the neuron and may contribute to the development of the hyperactivity observed in epilepsy.


Nonadiabatic dynamics with quantum nuclei: simulating charge transfer with ring polymer surface hopping.
Investigation of many electronic processes in molecules and materials, such as charge and exciton transport, requires a computational framework that incorporates both non-adiabatic electronic effects and nuclear quantum effects, in particular at low temperatures. We have recently developed an efficient semi-empirical fewest switches surface hopping method, denoted fragment orbital-based surface hopping (FOB-SH), that was tailored towards highly efficient simulation of charge transport in molecular materials, yet with nuclei treated classically. In this work, we extend FOB-SH and include nuclear quantum effects by combining it with ring-polymer molecular dynamics (RPMD) in three different flavours: (i) RPSH with bead approximation (RPSH-BA) as suggested in Shushkov et al., J. Chem. Phys., 2012, 137, 22A549, (ii) a modification of (i) denoted RPSH with weighted bead approximation (RPSH-wBA) and (iii) the isomorphic Hamiltonian method of Tao et al., J. Chem. Phys., 2018, 148, 10237 (SH-RP-iso). We present here applications to hole transfer in a molecular dimer model and analyze detailed balance and internal consistency of all three methods and investigate the temperature and driving force dependence of the hole transfer rate. We find that RPSH-BA strongly underestimates and RPSH-wBA overestimates the exact excited state population, while SH-RP-iso gives satisfactory results. We also find that the latter predicts a flattening of the rate vs. driving force dependence in the Marcus inverted regime at low temperature, as often observed experimentally. Overall, our results suggest that FOB-SH combined with SH-RP-iso is a promising method for including zero point motion and tunneling in charge transport simulations in molecular materials and biological systems.


Tranexamic Acid Was Not Associated with Increased Complications in High-Risk Patients with Hip Fracture Undergoing Arthroplasty.
Tranexamic acid (TXA) is considered safe and efficacious for elective total joint arthroplasty. However, evidence of TXA's safety in high-risk patients with hip fracture requiring nonelective arthroplasty has been lacking. This study aimed to assess whether TXA administration to high-risk patients with a hip fracture requiring arthroplasty increased the risk of thrombotic complications or mortality. All patients who underwent hip hemiarthroplasty (HHA) or total hip arthroplasty (THA) for displaced femoral neck fractures between 2011 and 2019 at 4 sites within 1 hospital system were retrospectively identified. Patients were grouped by risk (high-risk or low-risk) and TXA treatment (with or without TXA). Propensity scores were used for risk adjustment in comparisons between surgery with and without TXA for only the high-risk group (n = 1,066) and the entire population (n = 2,166). Differences in the occurrence of postoperative mortality, deep venous thrombosis, pulmonary embolism, myocardial infarction, and stroke within 90 days of hip arthroplasty were evaluated. TXA administration was not associated with an increased risk of thrombotic complications or mortality within 90 days in either high-risk or all-patient groups. Specifically, among 1,066 matched high-risk patients who did not or did receive TXA, there were no significant differences in mortality (14.82% and 10.00%; p = 0.295), deep venous thrombosis (3.56% and 3.04%; p = 0.440), pulmonary embolism (2.44% and 1.96%; p = 0.374), myocardial infarction (3.38% and 2.14%; p = 0.704), or stroke (4.32% and 5.71%; p = 0.225). In our review of 1,066 propensity-matched high-risk patients undergoing hip arthroplasty for displaced femoral neck fractures, we found that TXA administration (compared with no TXA administration) was not associated with an increased risk of mortality, deep venous thrombosis, pulmonary embolism, myocardial infarction, or stroke. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.


The effect of the NMDA channel blocker memantine on salicylate-induced tinnitus in rats.
Short-term tinnitus develops shortly after the administration of a high dose of salicylate. Since salicylate selectively potentiates N-methyl- D-aspartate (NMDA) currents in spiral ganglion neurons, it may play a vital role in tinnitus by amplifying NMDA-mediated neurotransmission. The aim of this study was to determine whether systemic treatment with a NMDA channel blocker, memantine, could prevent salicylate-induced tinnitus in animals. Additional experiments were performed to evaluate the effect of memantine on the auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE) to test for changes in hearing function. Thirty-six rats were divided into 3 groups and treated daily for four consecutive days. One group (n = 12) was injected with salicylate (300 mg/kg/d, IP), the second (n = 12) was treated with memantine (5 mg/kg/d, IP) and the third group (n = 12) was injected with salicylate and memantine. All rats were tested for tinnitus and hearing loss at 2, 24, 48 and 72 h after the first drug administration and 24 h post treatment; tinnituslike behaviour was assessed with gap prepulse inhibition of acoustic startle (GPIAS), and hearing function was measured with DPOAE, ABR and noise burst prepulse inhibition of acoustic startle (NBPIAS). Rats in the salicylate group showed impaired GPIAS indicative of transient tinnitus-like behaviour near 16 kHz that recovered 24 h after the last salicylate treatment. Memantine did not cause a significant change in GPIAS. Combined injection of salicylate and memantine significantly attenuated GPIAS tinnitus-like behaviour at 48 hours after the first injection. None of the treatments induced permanent threshold shifts in the ABR and DPOAE, which recovered completely within one day post treatment. Animals treated with salicylate plus memantine showed results comparable to animals treated with salicylate alone, confirming that there is no effect of memantine on DPOAE which reflects OHC function. The present study confirms the role of cochlear NMDA receptors in the induction of salicylate-induced tinnitus.


Epigenetics and Cancer Stem Cells: Unleashing, Hijacking, and Restricting Cellular Plasticity.
Epigenetic mechanisms have emerged as key players in cancer development which affect cellular states at multiple stages of the disease. During carcinogenesis, alterations in chromatin and DNA methylation resulting from genetic lesions unleash cellular plasticity and favor oncogenic cellular reprogramming. At later stages, during cancer growth and progression, additional epigenetic changes triggered by interaction with the microenvironment modulate cancer cell phenotypes and properties, and shape tumor architecture. We review here recent advances highlighting the interplay between epigenetics, genetics, and cell-to-cell signaling in cancer, with particular emphasis on mechanisms relevant for cancer stem cell formation (CSC) and function.


[Convulsive syndrome in infectious-toxic lesions of the brain in children].
A clinico-electroencephalographic study covered 64 children aged 1 month to 5 years who presented the encephalitic syndrome, encephalitis and meningoencephalitis due to respiratory and enteroviral infection. Age-specific characteristics of the paroxysmal syndrome are described in detail. It has been shown that an important role in the genesis of the development of paroxysmal attacks in young children is played by a low threshold of convulsive readiness and by an unfavourable premorbid background. Children under 5 years of age presented no epileptic foci on the EEG in the course of the encephalitic syndrome, encephalitis and meningoencephalitis.


Enemy deterrence in the recruitment strategy of a termite: Soldier-organized foraging in Nasutitermes costalis.
The nasute soldiers of the neotropical termite Nasutitermes costalis function as scouts by exploring new terrain for food in advance of the worker caste and regulate foraging activity by laying trails composed of sternal gland pheromone. Additional soldiers are at first recruited in large numbers, and subsequently workers appear as the pheromone concentration increases. The role of the nasutes in the organization of foraging is extremely unusual for the soldier caste in social insects and appears to be a component of a foraging/defense system that controls the recruitment of foragers and effectively deters attacks by ants, the most fierce and important predators of termites.


Differential inhibition of six copper amine oxidases by a family of 4-(aryloxy)-2-butynamines: evidence for a new mode of inactivation.
A series of compounds derived from a previously identified substrate analogue of copper amine oxidases (CuAOs) (Shepard et al. (2002) Eur. J. Biochem. 269, 3645-3658) has been screened against six different CuAOs with a view to designing potent and selective inhibitors. The substrate analogues investigated were 4-(1-naphthyloxy)-2-butyn-1-amine, 4-(2-methylphenoxy)-2-butyn-1-amine, 4-(3-methylphenoxy)-2-butyn-1-amine, 4-(4-methylphenoxy)-2-butyn-1-amine, and 4-phenoxy-2-butyn-1-amine. These compounds were screened against equine plasma amine oxidase (EPAO), Pisum sativum amine oxidase (PSAO), Pichia pastoris lysyl oxidase (PPLO), bovine plasma amine oxidase (BPAO), human kidney diamine oxidase (KDAO), and Arthrobacter globiformis amine oxidase (AGAO) to examine the effect of different substituent groups on potency. Despite the similar structures of the 4-aryloxy analogues evaluated, striking differences in potency were observed. In addition, crystal structures of AGAO derivitized with 4-(2-naphthyloxy)-2-butyn-1-amine and 4-(4-methylphenoxy)-2-butyn-1-amine were obtained at a resolution of 1.7 A. The structures reveal a novel and unprecedented reaction mechanism involving covalent attachment of the alpha,beta-unsaturated aldehyde turnover product to the amino group of the reduced 2,4,5-trihydroxyphenylalanine quinone (TPQ) cofactor. Collectively, the structural and inhibition results support the feasibility of designing selective mechanism-based inhibitors of copper amine oxidases.


The effect of vitamin D on GATA3 gene expression in peripheral blood mononuclear cells in allergic asthma.
Asthma is becoming a major health problem in many countries. Immune responses in allergic asthma, as the most prevalent asthmatic phenotype, are mediated mostly by a subtype of T lymphocytes referred to as the effector lineage of Type 2 Th cells (Th2). The development of Th2 cells is mainly governed by a zinc finger transcription factor, i.e., GATA-binding protein 3 (GATA3). Allergic asthma is a complex disease, and vitamin D deficiency has been named as a non-genetic risk factor for its development. Vitamin D, a steroid hormone belonging to the family of nuclear receptors, has shown significant immunosuppressive effects in previous studies. In this study, given its immunomodulatory properties, we aimed to investigate the effects of different concentrations of vitamin D on GATA3 gene expression in peripheral blood mononuclear cells (PBMCs), including Th2 cells, and compare GATA3 expression levels between PBMCs taken from allergic asthmatic patients and healthy controls. The total sample size was 40 and the quantitative real-time PCR (qPCR) procedure was applied to assess the mRNA expression levels of GATA3 in different groups. Collectively, our results demonstrated that the expression of GATA3 in PBMCs taken from patients with allergic asthma is lower than in that from healthy controls. In addition, in the control group, cells co-cultured with vitamin D had a significantly increased GATA3 expression. However, in the patient group, such an increase was only observed in cells treated with 10⁻⁷M-vitamin D. By contrast, incubation with vitamin D at the concentration of 10-6 M slightly decreased the expression of GATA3 among patients. In summary, it is likely that vitamin D should regulate GATA3 gene expression in the PBMCs in a dose-dependent manner. The impacts of this steroid hormone can also differ between the status of health and allergic asthma in either extent or direction.


The Promoter of the Immune-Modulating Gene TIR-Containing Protein C of the Uropathogenic Escherichia coli Strain CFT073 Reacts to the Pathogen's Environment.
The TIR-containing protein C (TcpC) of the uropathogenic Escherichia coli strain CFT073 modulates innate immunity by interfering with the Toll-like receptor and NALP3 inflammasome signaling cascade. During a urinary tract infection the pathogen encounters epithelial and innate immune cells and replicates by several orders of magnitude. We therefore analyzed whether these cell types and also the density of the pathogen would induce the recently defined promoter of the CFT073 tcpC gene to, in time, dampen innate immune responses. Using reporter constructs we found that the uroepithelial cell line T24/83 and the monocytic cell line THP-1 induced the tcpC promoter. Differentiation of monocytic THP-1 cells to macrophages increased their potential to switch on the promoter. Cell-associated CFT073 displayed the highest promoter activity. Since potassium represents the most abundant intracellular ion and is secreted to induce the NLRP3 inflammasome, we tested its ability to activate the tcpC promoter. Potassium induced the promoter with high efficiency. Sodium, which is enriched in the renal cortex generating an antibacterial hypersalinity, also induced the tcpC promoter. Finally, the bacterial density modulated the tcpC promoter activity. In the search for promoter-regulating proteins, we found that the DNA-binding protein H-NS dampens the promoter activity. Taken together, different cell types and salts, present in the kidney, are able to induce the tcpC promoter and might explain the mechanism of TcpC induction during a kidney infection with uropathogenic E. coli strains.


Phylogenomics of fescue grass-derived fungal endophytes based on selected nuclear genes and the mitochondrial gene complement.
Tall fescue and meadow fescue are important as temperate pasture grasses, forming mutualistic associations with asexual Neotyphodium endophytes. The most frequently identified endophyte of Continental allohexaploid tall fescue is Neotyphodium coenophialum, while representatives of two other taxa (FaTG-2 and FaTG-3) have been described as colonising decaploid and Mediterranean hexaploid tall fescue, respectively. In addition, a recent study identified two other putatively novel endophyte taxa from Mediterranean hexaploid and decaploid tall fescue accessions, which were designated as uncharacterised Neotyphodium species (UNS) and FaTG-3-like respectively. In contrast, diploid meadow fescue mainly forms associations with the endophyte taxon Neotyphodium uncinatum, although a second endophyte taxon, termed N. siegelii, has also been described. Multiple copies of the translation elongation factor 1-a (tefA) and β-tubulin (tub2) 'house-keeping' genes, as well as the endophyte-specific perA gene, were identified for each fescue-derived endophyte taxon from whole genome sequence data. The assembled gene sequences were used to reconstruct evolutionary relationships between the heteroploid fescue-derived endophytes and putative ancestral sub-genomes derived from known sexual Epichloë species. In addition to the nuclear genome-derived genes, the complete mitochondrial genome (mt genome) sequence was obtained for each of the sequenced endophyte, and phylogenetic relationships between the mt genome protein coding gene complements were also reconstructed. Complex and highly reticulated evolutionary relationships between Epichloë-Neotyphodium endophytes have been predicted on the basis of multiple nuclear genes and entire mitochondrial protein-coding gene complements, derived from independent assembly of whole genome sequence reads. The results are consistent with previous studies while also providing novel phylogenetic insights, particularly through inclusion of data from the endophyte lineage-specific gene, as well as affording evidence for the origin of cytoplasmic genomes. In particular, the results obtained from the present study imply the possible occurrence of at least two distinct E. typhina progenitors for heteropoid taxa, as well the ancestral contribution of an endophyte species distinct from (although related to) contemporary E. baconii to the extant hybrid species. Furthermore, the present study confirmed the distinct taxonomic status of the newly identified fescue endophyte taxa, FaTG-3-like and UNS, which are consequently proposed to be renamed FaTG4 and FaTG5, respectively.


Fire blight protection with avirulent mutants of Erwinia amylovora.
Fire blight is a necrotic disease caused by the bacterium Erwinia amyiovora, which affects pears, apples and ornamentals including Crataegus, Pyracantha, and Cotoneaster. The disease can be only partially controlled, through the use of resistant genotypes, cultural measures and antibacterial compounds, thus other methods must be investigated. It has long been established that avirulent isolates of the pathogen can control the disease, under experimental conditions. However, field use of avirulent isolates is not acceptable because of their unknown genetic stability. The protective ability under controlled conditions of genetically characterized avirulent insertion mutants of E. amylovora was examined. A bioassay on apple seedlings was used for the determination of the protective ability of 34 insertion mutants (hrp, dsp, ams). Some protective effect could be observed with most of the mutants tested and was dependent on the avirulent/virulent inoculum ratio as well as on the level of virulence of the pathogen; a minimal concentration of the avirulent mutant was necessary to give a significant level of protection. An early competition between avirulent and virulent strains for putative infection sites might be involved. For six of the mutants tested, the protective ability was particularly high and might be related to the alteration of regulatory functions of hrp genes. Results obtained with Ams- and Ams- Hrp- mutants suggested that the bacterial exopolysaccharide might play a role in the protection.