Using paired-end sequences to optimise parameters for alignment of sequence reads against related genomes.
The advent of cheap high through-put sequencing methods has facilitated low coverage skims of a large number of organisms. To maximise the utility of the sequences, assembly into contigs and then ordering of those contigs is required. Whilst sequences can be assembled into contigs de novo, using assembled genomes of closely related organisms as a framework can considerably aid the process. However, the preferred search programs and parameters that will optimise the sensitivity and specificity of the alignments between the sequence reads and the framework genome(s) are not necessarily obvious. Here we demonstrate a process that uses paired-end sequence reads to choose an optimal program and alignment parameters. Unlike two single fragment reads, in paired-end sequence reads, such as BAC-end sequences, the two sequences in the pair have a known positional relationship in the original genome. This provides an additional level of confidence over match scores and e-values in the accuracy of the positional assignment of the reads in the comparative genome. Three commonly used sequence alignment programs: MegaBLAST, Blastz and PatternHunter were used to align a set of ovine BAC-end sequences against the equine genome assembly. A range of different search parameters, with a particular focus on contiguous and discontiguous seeds, were used for each program. The number of reads with a hit and the number of read pairs with hits for the two end sequences in the tail-to-tail paired-end configuration were plotted relative to the theoretical maximum expected curve. Of the programs tested, MegaBLAST with short contiguous seed lengths (word size 8-11) performed best in this particular task. In addition the data also provides estimates of the false positive and false negative rates, which can be used to determine the appropriate values of additional parameters, such as score cut-off, to balance sensitivity and specificity. To determine whether the approach also worked for the alignment of shorter reads, the first 240 bases of each BAC end sequence were also aligned to the equine genome. Again, contiguous MegaBLAST performed the best in optimising the sensitivity and specificity with which sheep BAC end reads map to the equine and bovine genomes. Paired-end reads, such as BAC-end sequences, provide an efficient mechanism to optimise sequence alignment parameters, for example for comparative genome assemblies, by providing an objective standard to evaluate performance.


The SARS-CoV-2 pandemic and asthma: What we have learned and what is still unknown.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has brought new insights into the immunologic intricacies of asthma. In this review, we discuss the epidemiology of asthma in patients infected with SARS-CoV-2 and the risk of severe infection. Type 2 inflammation had an overall protective effect against SARS-CoV-2 infection by various mechanisms summarized in this review. Asthma, intranasal, and inhaled corticosteroids decreased the angiotensin-converting enzyme 2 receptor, an important receptor for SARS-CoV-2 entry into host cells. We summarize the nuances of the treatment of type 2 inflammation despite its underlying protective effects. Research to date has shown that patients on various allergen immunotherapies and biologics do benefit from being vaccinated.


[Chaos, complexity and cardiology].
Science is an ever-changing discipline. Modern medical knowledge is based on science. Current medical paradigm is both linear and reductionist. There is a new general theory validated by computer's calculations named chaos and complexity theory. This new paradigm will probably have an impact on medical practice. Cardiovascular physiology may display fractal and/ or chaotic behavior. Computerized heart rhythm analyses enhanced our understanding of complex diseases otherwise not explainable by current linear-reductionist paradigms. Cases in point are diverse dysautonomia including orthostatic intolerance, cardiac X syndrome and fibromyalgia. Derived from this, new knowledge is a different diagnostic and therapeutic stance: scientific holism.


Coronary spastic angina in patients with connective tissue disease.
Connective tissue disease, which is an inflammatory condition represented by C-reactive protein (CRP), is a risk factor for ischemic heart disease. The aim of the present study was to examine if there is a relationship between connective tissue disease and coronary spastic angina, and whether the inflammatory condition was associated with ischemic heart disease, even in patients with connective tissue disease. The study group comprised 73 consecutive patients with connective tissue disease who were admitted to the Department of Cardiovascular Medicine between April 2000 and March 2003. Of the 73 patients, 38 (19 men, 19 women) were diagnosed as having an ischemic heart disease (7 patients acute coronary syndrome, 19 patients coronary spastic angina, 12 patients stable exertional angina). In the present study, 19 (50.0%) of the 38 patients of ischemic heart disease were diagnosed as having coronary spastic angina. In the same study period, 151 (38.7%) of 390 patients with ischemic heart disease (without connective tissue disease) were diagnosed as having coronary spastic angina. The frequency of the patients with coronary spastic angina tended to be higher in patients with connective tissue disease than in patients without connective tissue disease. Among the study patients, serum CRP concentrations (mg/dl) were higher in patients with acute coronary syndrome (1.50 +/- 1.19, n=7) and those with coronary spastic angina (1.06 +/- 1.78, n=19) than in those with non-ischemia (0.35 +/- 0.40, n=35, p<0.05). Coronary spastic angina is a frequent complication in patients with connective tissue disease and the inflammatory condition is associated with coronary spastic angina and unstable angina in patients with connective tissue disease.


Absorption, disposition kinetics, and metabolic pathways of cyclohexene oxide in the male Fischer 344 rat and female B6C3F1 mouse.
Cyclohexene oxide (CHO) is a monomer intermediate used in the synthesis of pesticides, pharmaceuticals, and perfumes. Although CHO has a variety of industrial uses where direct human exposure is possible, very little is known about its fate in the body. Therefore, the objectives of this study were to determine the absorption, distribution, metabolism, and excretion of cyclohexene oxide after oral, intravenous, and dermal exposure in male Fischer 344 rats and female B6C3F, mice. After intravenous administration of [14C]CHO (50 mg/kg), CHO was rapidly distributed, metabolized, and excreted into the urine. Plasma concentrations of CHO rapidly declined and were below the limit of detection within 60 min. Average (+/- SD) values for terminal disposition half-life, apparent volume of distribution at steady-state, and systemic body clearance were: 19.3 +/- 1.6 min; 0.44 +/- 0.08 liter/kg; and 31.3 +/- 0.5 ml/kg * min, respectively. After oral administration of [14C]CHO (10 and 100 mg/kg), it was found that 14C-equivalents were rapidly excreted in the urine of both species. At 48 hr, the majority of the dose (73-93%) was recovered in urine, whereas fecal elimination accounted for only 2-5% of the dose. At no time after oral administration was parent CHO detected in the blood. However, its primary metabolite cyclohexane-1,2-diol was present for different lengths of time depending on the dose. Four metabolites were detected and identified in mouse urine by MS: cyclohexane-1,2-diol; cyclohexane-1,2-diol-O-glucuronide; N-acetyl-S-(2-hydroxycyclohexyl)-L-cysteine; and cyclohexane-1,2-diol-O-sulfate. The sulfate conjugate was not present in rat urine. Topical application of [14C]CHO (60 mg/kg) provided poor absorption in both species. The majority of 14C-equivalents applied dermally were recovered from the charcoal skin trap (approximately 90% of the dose). Only 4% of the dose was absorbed, and the major route of elimination was via the urine. To evaluate the toxicity of CHO, animals were given daily doses of CHO orally and topically for 28 days. No statistically significant changes in final body weights or relative organ weights were noted in rats or mice treated orally with CHO up to 100 mg/kg or up to 60 mg/kg when given topically. Very few lesions were found at necropsy, and none were considered compound related. In conclusion, regardless of route, CHO is rapidly eliminated and excreted into the urine. Furthermore, after either oral or dermal administration, it is unlikely that CHO reaches the systemic circulation intact due to its rapid metabolism, and is therefore unable to cause toxicity in the whole animal under the test conditions used in this study.


Chain transplantation: initial experience of a large multicenter program.
We report the results of a large series of chain transplantations that were facilitated by a multicenter US database in which 57 centers pooled incompatible donor/recipient pairs. Chains, initiated by nondirected donors, were identified using a computer algorithm incorporating virtual cross-matches and potential to extend chains. The first 54 chains facilitated 272 kidney transplants (mean chain length = 5.0). Seven chains ended because potential donors became unavailable to donate after their recipient received a kidney; however, every recipient whose intended donor donated was transplanted. The remaining 47 chains were eventually closed by having the last donor donate to the waiting list. Of the 272 chain recipients 46% were ethnic minorities and 63% of grafts were shipped from other centers. The number of blood type O-patients receiving a transplant (n = 90) was greater than the number of blood type O-non-directed donors (n = 32) initiating chains. We have 1-year follow up on the first 100 transplants. The mean 1-year creatinine of the first 100 transplants from this series was 1.3 mg/dL. Chain transplantation enables many recipients with immunologically incompatible donors to be transplanted with high quality grafts.


Single-Subject Research in Psychiatry: Facts and Fictions.
Scientific evidence in the field of psychiatry is mainly derived from group-based ("nomothetic") studies that yield group-aggregated results, while often the need is to answer questions that apply to individuals. Particularly in the presence of great inter-individual differences and temporal complexities, information at the individual-person level may be valuable for personalized treatment decisions, individual predictions and diagnostics. The single-subject study design can be used to make inferences about individual persons. Yet, the single-subject study is not often used in the field of psychiatry. We believe that this is because of a lack of awareness of its value rather than a lack of usefulness or feasibility. In the present paper, we aimed to resolve some common misconceptions and beliefs about single-subject studies by discussing some commonly heard "facts and fictions." We also discuss some situations in which the single-subject study is more or less appropriate, and the potential of combining single-subject and group-based study designs into one study. While not intending to plea for single-subject studies at the expense of group-based studies, we hope to increase awareness of the value of single-subject research by informing the reader about several aspects of this design, resolving misunderstanding, and providing references for further reading.


Salt intake is related to soft drink consumption in children and adolescents: a link to obesity?
Dietary salt is a major determinant of fluid intake in adults; however, little is known about this relationship in children. Sugar-sweetened soft drink consumption is related to childhood obesity, but it is unclear whether there is a link between salt and sugar-sweetened soft drink consumption. We analyzed the data of a cross-sectional study, the National Diet and Nutrition Survey for young people in Great Britain. Salt intake and fluid intake were assessed in 1688 participants aged 4 to 18 years, using a 7-day dietary record. There was a significant association between salt intake and total fluid, as well as sugar-sweetened soft drink consumption (P<0.001), after adjusting for potential confounding factors. A difference of 1 g/d in salt intake was associated with a difference of 100 and 27 g/d in total fluid and sugar-sweetened soft drink consumption, respectively. These results, in conjunction with other evidence, particularly that from experimental studies where only salt intake was changed, demonstrate that salt is a major determinant of fluid and sugar-sweetened soft drink consumption during childhood. If salt intake in children in the United Kingdom was reduced by half (mean decrease: 3 g/d), there would be an average reduction of approximately 2.3 sugar-sweetened soft drinks per week per child. A reduction in salt intake could, therefore, play a role in helping to reduce childhood obesity through its effect on sugar-sweetened soft drink consumption. This would have a beneficial effect on preventing cardiovascular disease independent of and additive to the effect of salt reduction on blood pressure.


Molecular basis for sequence-dependent induced DNA bending.
With a growing understanding of the microstructural variations of DNA, it has become apparent that subtle conformational features are essential for specific DNA molecular recognition and function. DNA containing an A-tract has a narrow minor groove and a globally bent conformation but the structural features of alternating AT DNA are less well understood. Several studies indicate that alternating AT sequences are polymorphic with different global and local properties from A-tracts. The mobility of alternating AT DNA in gel electrophoresis is extensively reduced upon binding with minor-groove binding agents such as netropsin. Although this suggests that such complexes are bent, similarly to A-tract DNA, direct evidence and structural information on AT DNA and the induced conformational change is lacking. We have used NMR spectroscopy and residual dipolar coupling together with restrained molecular-dynamics simulations to determine the solution structures of an alternating AT DNA segment, with and without netropsin, in order to evaluate the molecular basis of the binding-induced effects. Complex formation causes a significant narrowing of the minor groove and a pronounced change in bending, from a slight bend towards the major groove for the free DNA to a pronounced bend towards the minor groove in the complex. This observation demonstrates that conformational features and the inherent malleability of AT sequences are essential for specific molecular recognition and function. These results take the field of DNA structures into new areas while opening up avenues to target novel DNA sequences.


Report of eight infants with acute infantile hemorrhagic edema and review of the literature.
Acute infantile hemorrhagic edema (AIHE) is a cutaneous leukocytoclastic vasculitis, clinically characterized by the symptom triad of fever, large purpuric skin lesions, and edema. The clinical picture has a violent onset, a short benign course, and spontaneous complete recovery. In this article, we present eight patients who were admitted with rashes on the skin and edema on the eyelids and extremities, and were diagnosed with AIHE according to their clinical and histopathological features (immunohistological study was also performed in three of them). Our purpose was to emphasize that, aside from Henoch-Schönlein purpura, meningococcemia, septicemia, and purpura fulminans, AIHE benign disorder should also be considered in the differential diagnosis to determine the clinical course and treatment protocol in patients with purpuric rashes.


Pharmacometabolomic mapping of early biochemical changes induced by sertraline and placebo.
In this study, we characterized early biochemical changes associated with sertraline and placebo administration and changes associated with a reduction in depressive symptoms in patients with major depressive disorder (MDD). MDD patients received sertraline or placebo in a double-blind 4-week trial; baseline, 1 week, and 4 weeks serum samples were profiled using a gas chromatography time of flight mass spectrometry metabolomics platform. Intermediates of TCA and urea cycles, fatty acids and intermediates of lipid biosynthesis, amino acids, sugars and gut-derived metabolites were changed after 1 and 4 weeks of treatment. Some of the changes were common to the sertraline- and placebo-treated groups. Changes after 4 weeks of treatment in both groups were more extensive. Pathway analysis in the sertraline group suggested an effect of drug on ABC and solute transporters, fatty acid receptors and transporters, G signaling molecules and regulation of lipid metabolism. Correlation between biochemical changes and treatment outcomes in the sertraline group suggested a strong association with changes in levels of branched chain amino acids (BCAAs), lower BCAAs levels correlated with better treatment outcomes; pathway analysis in this group revealed that methionine and tyrosine correlated with BCAAs. Lower levels of lactic acid, higher levels of TCA/urea cycle intermediates, and 3-hydroxybutanoic acid correlated with better treatment outcomes in placebo group. Results of this study indicate that biochemical changes induced by drug continue to evolve over 4 weeks of treatment and that might explain partially delayed response. Response to drug and response to placebo share common pathways but some pathways are more affected by drug treatment. BCAAs seem to be implicated in mechanisms of recovery from a depressed state following sertraline treatment.


Ang II-salt hypertension depends on neuronal activity in the hypothalamic paraventricular nucleus but not on local actions of tumor necrosis factor-α.
Development of angiotensin II (Ang II)-dependent hypertension involves microglial activation and proinflammatory cytokine actions in the hypothalamic paraventricular nucleus (PVN). Cytokines activate receptor signaling pathways that can both acutely grade neuronal discharge and trigger long-term adaptive changes that modulate neuronal excitability through gene transcription. Here, we investigated contributions of PVN cytokines to maintenance of hypertension induced by subcutaneous infusion of Ang II (150 ng/kg per min) for 14 days in rats consuming a 2% NaCl diet. Results indicate that bilateral PVN inhibition with the GABA-A receptor agonist muscimol (100 pmol/50 nL) caused significantly greater reductions of renal and splanchnic sympathetic nerve activity (SNA) and mean arterial pressure in hypertensive than in normotensive rats (P<0.01). Thus, ongoing PVN neuronal activity seems required for support of hypertension. Next, the role of the prototypical cytokine tumor necrosis factor-α was investigated. Whereas PVN injection of tumor necrosis factor-α (0.3 pmol/50 nL) acutely increased lumbar and splanchnic SNA and mean arterial pressure, interfering with endogenous tumor necrosis factor-α by injection of etanercept (10 μg/50 nL) was without effect in hypertensive and normotensive rats. Next, we determined that although microglial activation in PVN was increased in hypertensive rats, bilateral injections of minocycline (0.5 μg/50 nL), an inhibitor of microglial activation, failed to reduce lumbar or splanchnic SNA or mean arterial pressure in hypertensive or in normotensive rats. Collectively, these findings indicate that established Ang II-salt hypertension is supported by PVN neuronal activity, but short term maintenance of SNA and arterial blood pressure does not depend on ongoing local actions of tumor necrosis factor-α.


Drawing on three discursive modes in learning disability nurse education.
This article presents ideas generated by a qualitative study exploring the complexities of the social construction of learning disability/intellectual disability. The ideas are based upon a larger doctoral study which investigated the social construction of learning disability as seen through the discourses and discursive devices used by nurse teachers in classroom teaching in particular during story telling activities to students. The investigations centred upon the stories and were supported by subsequent interviews with the teachers and observations of teaching sessions. The findings highlight three discursive devices which I call discursivemodes used in the social construction of learning disability/intellectual disability by nurse educators and help to explain the personal and professional tensions experienced by nurses faced with the dominant discourses of today.


Asthma disease as cause of admission to hospitals due to exposure to ambient oxidants in Mashhad, Iran.
Nowadays, asthma is one of the most common chronic respiratory diseases, worldwide. Many reports have emphasized the correlation between the short-term exposure to the ambient air pollutants and acute respiratory diseases, especially among children with asthmatic symptoms. The aim of this study was to evaluate the relationship between the exposure to three atmospheric antioxidants (NO2, SO2, and O3) and hospital admission due to asthmatic disease (HAAD) in the city of Mashhad, Iran. The concentrations of atmospheric antioxidants were obtained from the real-time monitoring stations located in the city. The collected data were employed for developing predictive models in the AirQ software. In order to investigate the association between short-term exposure to air pollutants and HAAD, the study participants were categorized into two age groups: less than 15 and from 15 to 64 years old. The results indicated that in people less than 15 years increase in NO2 (attributable proportion (AP) = 3.775%, 95% CI 0.897-6.883%), SO2 (AP = 3.649%, 95% CI 1.295-5.937%), and O3 (AP = 0.554%,95% CI 0.00-3.321) results in increase in HAAD. While for those aged between 15 and 64 years, the AP was 4.192% (95% CI 0.450-7.662%) for NO2; 0.0% (95% CI 0.00-1.687%) for SO2; and 0.236% (95% CI 0.00-1.216%) for O3. The number of asthmatic cases who were less than 15 years admitted to the hospitals during the study period was higher than that of those within the age groups between 15 and 64 years as a consequence of exposure to NO2 (101 vs. 75), SO2 (98 vs. 0), and O3 (15 vs. 3), respectively. To the best of our knowledge, the AirQ model has not been applied before to estimate the effect of atmospheric antioxidant exposure on hospital admission because of asthma disease. Eventually, this model is proposed to be applicable for other cities around the world.


Relation between Neonatal Icter and Gilbert Syndrome in Gloucose-6-Phosphate Dehydrogenase Deficient Subjects.
The pathogenesis of neonatal hyperbilirubinemia hasn't been completely defined in Gloucose-6-Phosphate Dehydrogenase (G6PD) deficient newborns. The aim of this study was to detect the relationship between Gilbert's syndrome and hyperbilirubinemia in Gloucose-6-Phosphate Dehydrogenase (G6PD) deficient neonates. This case-control study was conducted in Amirkola pediatrics teaching hospital, Babol, Iran. A total number of one hundred four infants were included in the study (51 infants with neonatal jaundice and Gloucose-6-Phosphate Dehydrogenase (G6PD) deficiency admitted to phototherapy or transfusion were selected as the case group and 53 infants with Gloucose-6-Phosphate Dehydrogenase (G6PD) deficiency admitted for other reasons than jaundice were selected as the control group). Exclusion criteria were ABO or Rh incompatibility or other reasons that made Coombs test positive, sepsis, hepatosplenomegaly, metabolic diseases, medical treatment and phototherapy. The promoter and coding regions of Uridine diphosphate Glucuronosyl Transferase 1A1 (UGT1A1) of genomic DNA were amplified by polymerase chain reaction (PCR) isolated from leukocytes. We used chi-square test and t-test to compare cases and controls. Distribution of Gilbert genome was not significantly different between the two groups; among cases, 33.3% were homozygote, 35.3% heterozygote, and 31.4% normal. Among controls, 22.6% were homozygote, 34% heterozygote, and 43.4% normal (p-value=xxx). Hyperbilirubinemia family history didn't differ significantly between these two groups. We showed that in Gloucose-6-Phosphate Dehydrogenase (G6PD) deficient neonates, there was no significant association between Gilbert's syndrome (promoter polymorphism) and hyperbilirubinemia.


Dating the diversification of the major lineages of Ascomycota (Fungi).
Establishing the dates for the origin and main diversification events in the phylogeny of Ascomycota is among the most crucial remaining goals in understanding the evolution of Fungi. There have been several analyses of divergence times in the fungal tree of life in the last two decades, but most have yielded contrasting results for the origin of the major lineages. Moreover, very few studies have provided temporal estimates for a large set of clades within Ascomycota. We performed molecular dating to estimate the divergence times of most of the major groups of Ascomycota. To account for paleontological uncertainty, we included alternative fossil constraints as different scenarios to enable a discussion of the effect of selection of fossils. We used data from 6 molecular markers and 121 extant taxa within Ascomycota. Our various 'relaxed clock' scenarios suggest that the origin and diversification of the Pezizomycotina occurred in the Cambrian. The main lineages of lichen-forming Ascomycota originated at least as early as the Carboniferous, with successive radiations in the Jurassic and Cretaceous generating the diversity of the main modern groups. Our study provides new information about the timing of the main diversification events in Ascomycota, including estimates for classes, orders and families of both lichenized and non-lichenized Ascomycota, many of which had not been previously dated.


Assuring restorative integrity in extensive posterior resin composite restorations: pushing the envelope.
Clinicians are increasingly being called on to satisfy the restorative demands of patients who request tooth-colored restorations but are unable to afford an optimum indirect restorative option. Consequently, in clinical practice, the limits of the direct posterior resin composite technique are being stretched. There is a need for techniques that will satisfy the complex variables of clinical practice and allow for successful utilization of posterior resin composite in large cavity preparations. The objective of this article is to explain the rationale behind the materials and techniques involved in the delivery of these complicated restorations.


The BET/BRD inhibitor JQ1 improves brain plasticity in WT and APP mice.
Histone acetylation is essential for memory formation and its deregulation contributes to the pathogenesis of Alzheimer's disease. Thus, targeting histone acetylation is discussed as a novel approach to treat dementia. The histone acetylation landscape is shaped by chromatin writer and eraser proteins, while readers link chromatin state to cellular function. Chromatin readers emerged novel drug targets in cancer research but little is known about the manipulation of readers in the adult brain. Here we tested the effect of JQ1-a small-molecule inhibitor of the chromatin readers BRD2, BRD3, BRD4 and BRDT-on brain function and show that JQ1 is able to enhance cognitive performance and long-term potentiation in wild-type animals and in a mouse model for Alzheimer's disease. Systemic administration of JQ1 elicited a hippocampal gene expression program that is associated with ion channel activity, transcription and DNA repair. Our findings suggest that JQ1 could be used as a therapy against dementia and should be further tested in the context of learning and memory.


[Expectations of adolescents in relation to the changes of nutritional profile].
This article presents results of a research of nature quanti-qualitative on nutrition and adolescents of Centro Salesiano do Menor, located in Vitória (ES). The aim of this study was to know the nutritional profile and expectations of the adolescents in relation the changes in the nutritional profile. Structured interview with subjective and objective questions was realized with 43 adolescents 14 to 17 years old and collected anthropometric date to valuation of the state nutritional according to the body mass index (BMI). Fragments of the speeches were selected and transcripts in the text as form of briefing of the open answers. The majority (86%) was classified as eutrófica and had disclosed to dissatisfaction with the body and a great concern with the beauty. The results had evidenced the importance given to the aesthetic one, as the main reason to desire a corporal change. Difficulties had been told in what it says respect to the alimentary control and the accomplishment of physical activity. Feeling of discrimination of the society to that they do not correspond to the beauty standard appeared in the answers of the adolescents. One concludes that the adolescents present perception of its weight not have correspondence with the found results of BMI and low self-esteem, desiring changes.


Evaluation of a new CPC-to-gauge bonding technique with the use of in vitro fluid flow.
Strain gauging enables the measurement of bone deformation during physical activity, leading to a better understanding of the physiological effects of loading on bone growth and remodeling. Development of a technology that will withstand long-term in vivo exposure and bond securely to bone is imperative for accurate, consistent measurement collection. Polysulfone is currently used to attach calcium-phosphate ceramic (CPC) particles, which promote bone-to-gauge bonding, to polyimide-backed strain gauges. This study evaluated the use of an implant-grade epoxy as an alternative CPC-polyimide adhesive. Polyimide-epoxy-CPC interfaces were loaded to failure and shear strengths calculated. In vitro studies providing a constant flow of medium over test specimens were designed, and long-term in vitro fluid exposure studies of the epoxy's shear strength were conducted. Average shear strength of polysulfone-polyimide interfaces were reported to be 7 MPa. The average shear strength of the epoxy-polyimide interface before long-term in vitro exposure was 17 MPa, which is stronger than the shear strength of the bone-CPC interface. The strength of the epoxy-polyimide interface decreased to 6.8 MPa after 24 weeks in vitro and 3 MPa after 24 weeks in vivo.


Exploiting the functional and taxonomic structure of genomic data by probabilistic topic modeling.
In this paper, we present a method that enable both homology-based approach and composition-based approach to further study the functional core (i.e., microbial core and gene core, correspondingly). In the proposed method, the identification of major functionality groups is achieved by generative topic modeling, which is able to extract useful information from unlabeled data. We first show that generative topic model can be used to model the taxon abundance information obtained by homology-based approach and study the microbial core. The model considers each sample as a "document," which has a mixture of functional groups, while each functional group (also known as a "latent topic") is a weight mixture of species. Therefore, estimating the generative topic model for taxon abundance data will uncover the distribution over latent functions (latent topic) in each sample. Second, we show that, generative topic model can also be used to study the genome-level composition of "N-mer" features (DNA subreads obtained by composition-based approaches). The model consider each genome as a mixture of latten genetic patterns (latent topics), while each functional pattern is a weighted mixture of the "N-mer" features, thus the existence of core genomes can be indicated by a set of common N-mer features. After studying the mutual information between latent topics and gene regions, we provide an explanation of the functional roles of uncovered latten genetic patterns. The experimental results demonstrate the effectiveness of proposed method.


Poxvirus Host Range Genes and Virus-Host Spectrum: A Critical Review.
The Poxviridae family is comprised of double-stranded DNA viruses belonging to nucleocytoplasmic large DNA viruses (NCLDV). Among the NCLDV, poxviruses exhibit the widest known host range, which is likely observed because this viral family has been more heavily investigated. However, relative to each member of the Poxviridae family, the spectrum of the host is variable, where certain viruses can infect a large range of hosts, while others are restricted to only one host species. It has been suggested that the variability in host spectrum among poxviruses is linked with the presence or absence of some host range genes. Would it be possible to extrapolate the restriction of viral replication in a specific cell lineage to an animal, a far more complex organism? In this study, we compare and discuss the relationship between the host range of poxvirus species and the abundance/diversity of host range genes. We analyzed the sequences of 38 previously identified and putative homologs of poxvirus host range genes, and updated these data with deposited sequences of new poxvirus genomes. Overall, the term host range genes might not be the most appropriate for these genes, since no correlation between them and the viruses' host spectrum was observed, and a change in nomenclature should be considered. Finally, we analyzed the evolutionary history of these genes, and reaffirmed the occurrence of horizontal gene transfer (HGT) for certain elements, as previously suggested. Considering the data presented in this study, it is not possible to associate the diversity of host range factors with the amount of hosts of known poxviruses, and this traditional nomenclature creates misunderstandings.


Behavioral manipulation-key to the successful global spread of the new coronavirus SARS-CoV-2?
Human-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) interaction can have an array of various outcomes-it could be mortal, morbid or merely carrying minor health consequences. The very rapid global spread has raised the issue whether there are further multi-dimensional consequences of SARS-CoV-2 infection on human behavior, the key of its transmission. During the coronavirus crisis, odd, abnormal, and irresponsible behavior has been reported in coronavirus disease 2019 (COVID-19) individuals, particularly in super-spreaders, that is, persons with a high viral load, thus constituting also super-emitters. Indeed, cases of infected persons ignoring self-confinement orders, intentionally disregarding physical distancing and multiplying social interactions, or even deliberately sneezing, spitting or coughing were reported. While it is known that some other viruses, such as rabies and even influenza do change human behavior, this remains unclear for SARS-CoV-2. In this perspective, we highlight the possibility that COVID-19 is facilitated by altered human social behavior that benefits SARS-CoV-2 transmission, through showcasing similar virus-induced changed behavior by other pathogens and relating this to reports from the gray literature.


Aging, infections, and the immune system.
There is increasing clinical and laboratory evidence of decline in the immune system in the elderly patient with a simultaneous rise in the incidence of certain infections. Along with the involution of the thymus gland with age, there is evidence of decline in both T- and B-lymphocyte function and also in delayed hypersensitivity. In addition, there is evidence of an increase in various autoantibodies as a person ages. In recent years evidence has been presented of a genetic basis to this declining system. Because of these changes and because severe infections present more subtly in the elderly patient than in the young, the physician's suspicion for serious infections in the elderly should be heightened and immunization programs in the elderly adhered to.


β-adrenergic receptor responsiveness in aging heart and clinical implications.
Elderly healthy individuals have a reduced exercise tolerance and a decreased left ventricle inotropic reserve related to increased vascular afterload, arterial-ventricular load mismatching, physical deconditioning and impaired autonomic regulation (the so called "β-adrenergic desensitization"). Adrenergic responsiveness is altered with aging and the age-related changes are limited to the β-adrenergic receptor density reduction and to the β-adrenoceptor-G-protein(s)-adenylyl cyclase system abnormalities, while the type and level of abnormalities change with species and tissues. Epidemiological studies have shown an high incidence and prevalence of heart failure in the elderly and a great body of evidence correlate the changes of β-adrenergic system with heart failure pathogenesis. In particular it is well known that: (a) levels of cathecolamines are directly correlated with mortality and functional status in heart failure, (b) β1-adrenergic receptor subtype is down-regulated in heart failure, (c) heart failure-dependent cardiac adrenergic responsiveness reduction is related to changes in G proteins activity. In this review we focus on the cardiovascular β-adrenergic changes involvement in the aging process and on similarities and differences between aging heart and heart failure.


Plain language summary of RACE study results: addition of eltrombopag to standard treatment of severe aplastic anemia.
Severe aplastic anemia (SAA) and very severe aplastic anemia (vSAA) are blood diseases of the bone marrow. If a suitable donor for bone marrow transplant as initial treatment is unavailable, standard immunosuppression is used. Standard immunosuppression treatment includes horse antithymocyte globulin (hATG) and cyclosporin A (CsA). This summary investigated the results of standard immunosuppression treatment (Group A) versus standard immunosuppression treatment with a medication called eltrombopag (Group B) in participants with SAA and vSAA. Eltrombopag is a medicine that improves the blood platelet level and is taken by mouth (orally). Compared to Group A, more participants in Group B showed increased blood cell level to a normal range without SAA or vSAA and faster treatment response. Side effects were similar in both groups even with the addition of eltrombopag for Group B. Participants in both groups reported feeling well after 6, 12 and 24 months. Differences in the participant-reported scores (overall health, physical, emotional, and social) between Group A and Group B were minimal. Immunosuppression treatment (hATG plus CsA) with eltrombopag benefited participants with SAA and vSAA and could be the new standard for SAA in persons who cannot undergo bone marrow transplant. At this time, eltrombopag is only approved in specific countries to treat the condition under study that is discussed in this summary. Clinical Trial Registration: NCT02099747 (RACE study).


Facial Nerve Sacrifice During Parotidectomy for Metastatic Cutaneous Squamous Cell Carcinoma.
We analyzed the incidence of facial nerve sacrifice during parotidectomy for metastatic cutaneous squamous cell carcinoma (CSCC). We retrospectively reviewed the charts of patients with cutaneous squamous cell carcinoma. We used our CSCC institutional database, which includes patients treated at the University of California-Davis from 2001 to 2018. We evaluated patients who presented with biopsy-proven head and neck CSCC who underwent parotidectomy as a part of surgical treatment. We assessed the frequency of facial nerve sacrifice required in patients with normal preoperative facial nerve function with metastatic disease to the parotid. We evaluated the association between sacrifice and high-risk tumor variables using multivariate analysis. We identified 53 patients with parotid metastasis and normal preoperative facial nerve function. Thirteen percent of patients required sacrifice of the main trunk of the facial nerve and 27% required sacrifice of a branch of the facial nerve. All patients who underwent facial nerve sacrifice had extracapsular spread (ECS). Perineural invasion (PNI) in the primary tumor (odds ratio [OR], 9.11; P = .041) and location of metastasis within the parotid body (OR, 6.6; P = .044) were independently associated with facial nerve sacrifice. Patients with regionally metastatic CSCC to the parotid gland frequently require sacrifice of all or a component of the facial nerve despite normal preoperative function. The likelihood of nerve sacrifice is highest for tumors with PNI and metastatic disease within the body of the parotid.


Radical Trachelectomy for Early-Stage Cervical Cancer: A Survey of the Society of Gynecologic Oncology and Gynecologic Oncology Fellows-in-Training.
The aim of this study was to survey gynecologic oncologists and fellows-in-training regarding the role of radical trachelectomy (RT) and conservative surgery in patients with early-stage cervical cancer. From June 2012 to September 2012, the Society of Gynecologic Oncology member practitioners (n = 1353) and gynecologic oncology fellows (n = 156) were sent group-specific surveys investigating current practice, training, and the future of RT for early-stage cervical cancer management. Twenty-two percent of practitioners (n = 303) and 24.4% of fellows (n = 38) completed the surveys. Of the practitioners, 50% (n = 148) report performing RT, 98% (n = 269) support RT as treatment for squamous carcinoma, and 71% (n = 195) confirm the use of RT for adenocarcinoma. Most practitioners offer RT treatment for stages IA2 to IB1 smaller than 2 cm (n = 209, 76.8%) regardless of grade (77.7%) or lymph vascular space invasion (n = 211, 79.3%). Only 8% (n = 23) of practitioners feel that RT is appropriate for stage IBI larger than 2 cm. Respectively, both practitioners and fellows most frequently perform robotic-assisted (47.0%, n = 101 and 59.1%, n = 13) and abdominal (40.5%, n = 87 and 68.2%, n = 15) RT approaches. After training, fellows project the use of robotic-assisted (71%, n = 22) or abdominal methods (58.1%, n = 18). Overall, 75% (n = 227) of practitioners and 60% (n = 23) of fellows speculate that over the next 5 years, less radical procedures will be used to manage early-stage cervical cancer. Our findings suggest that practitioners and fellows believe RT remains an option for early-stage cervical cancer patients. However, a significant proportion of all respondents believe that less radical surgery may be a future consideration for patients with low-risk early-stage cervical cancer.


Importance of EGFR/ERCC1 interaction following radiation-induced DNA damage.
The epidermal growth factor receptor (EGFR) plays an important role in cellular response to chemotherapy and radiotherapy through modulation of DNA repair. EGFR activates DNA-dependent protein kinase (DNA-PK) stimulating repair of DNA strand breaks (SB) and interstrand crosslinks (ICL). We investigated the role of EGFR in repair of ionizing radiation (IR)-induced SB independently of DNA-PK. The EGFR interactome was investigated via mass spectrometry. IR-induced EGFR-ERCC1 binding was validated biochemically and via proximity ligation assay in different cell lines including the M059K and M059J glioma cell lines, proficient and deficient for the expression of DNAPKcs, respectively. EGFR-ERCC1 functional significance following IR-induced SB was investigated in knockdown experiments with the Comet and γH2AX foci assays. The effect of this interaction was tested with EGFR-ERCC1 knockdown in combination with gefitinib and NU7026 using the MTT and apoptosis assays. This study demonstrates that EGFR inhibition further impairs IR-induced DNA repair in cells lacking expression of DNAPKcs or in combination with the DNAPK inhibitor NU7026. Our data suggest a role for EGFR in DNA repair independent of DNAPKcs but dependent on ERCC1. Alkaline comet and γH2AX foci assays in cells depleted of EGFR, ERCC1, or EGFR-ERCC1 expression demonstrated involvement of this interaction in DNA repair. Cellular survival and apoptosis data correlate with levels of residual DNA damage underlying the importance of this complex following SB. These data emphasize the importance of understanding the various mechanisms by which EGFR modulates DNA repair to optimize targeted therapy for patients with cancer.


Hydrogen bonding changes of internal water molecules in rhodopsin during metarhodopsin I and metarhodopsin II formation.
Rhodopsin is a 7-helix, integral membrane protein found in the rod outer segments, which serves as the light receptor in vision. Light absorption by the retinylidene chromophore of rhodopsin triggers an 11-cis-->all-trans isomerization, followed by a series of protein conformational changes, which culminate in the binding and activation of the G-protein transducin by the metarhodopsin II (Meta II) intermediate. Fourier transform IR difference spectroscopy has been used to investigate the structural changes that water, as well as other OH- and NH-containing groups, undergo during the formation of the metarhodopsin I (Meta I) and Meta II intermediates. Bands associated with the OH stretch modes of water are identified by characteristic downshifts upon substitution of H2(18)O for H2O. Compared with earlier work, several negative bands associated with water molecules in unphotolysed rhodopsin were detected, which shift to lower frequencies upon formation of the Meta I and Meta II intermediates. These data indicate that at least one water molecule undergoes an increase in hydrogen bonding upon formation of the Meta I intermediate, while at least one other increases its hydrogen bonding during Meta II formation. Amino acid residue Asp-83, which undergoes a change in its hydrogen bonding during Meta II formation, does not appear to interact with any of the structurally active water molecules. Several NH and/or OH groups, which are inaccessible to hydrogen/deuterium exchange, also undergo alterations during Meta I and Meta II formation.


Inhibition of cell proliferation and in vitro markers of angiogenesis by indole-3-carbinol, a major indole metabolite present in cruciferous vegetables.
A variety of studies have suggested a cancer protective role of cruciferous vegetables. In the present study, we investigated the effect of indole-3-carbinol (I3C), a major indole metabolite in cruciferous vegetables, on cell proliferation and in vitro markers of angiogenesis in phorbol myristate acetate (PMA)-stimulated endothelial EA hy926 cells. The results showed that I3C inhibited the growth of EA hy926 cells in a concentration-dependent manner. The capillary-like tube formation by PMA-activated endothelial cells was significantly suppressed by I3C, and such inhibition was associated with decreased vascular endothelial growth factor (VEGF) and increased interleukin-8 (IL-8) secretion, but not with the expression of VEGF receptor-2 protein. Additionally, gelatin zymography analysis indicated that I3C suppressed activities of matrix metalloproteinases-2 (MMP-2) and MMP-9 stimulated by PMA. These results suggest that the dietary I3C may be useful in the treatment of human cancers and angiogenic diseases.


Proton transfer in heterocycle crystals.
We study the proton diffusion process in imidazole-based molecular crystals, which are new candidate materials for fuel cell membranes. These materials are characterized by hydrogen bonded networks of molecules, which provide viable routes for the long-range diffusion of protons. By the application of a recently developed, powerful technique to determine reaction pathways in complex systems, we are able to reproduce the diffusion process in the imidazole crystal and in the more complicated and rigid structure of imidazole 2-ethyleneoxide. Our results cast new light on the atomistic details of the molecular rearrangements sustaining the ionic diffusion.


Leprosy as a model to understand cancer immunosurveillance and T cell anergy.
Leprosy is a disease caused by Mycobacterium leprae that presents on a spectrum of both clinical manifestations and T cell response. On one end of this spectrum, tuberculoid leprosy is a well-controlled disease, characterized by a cell-mediated immunity and immunosurveillance. On the opposite end of the spectrum, lepromatous leprosy is characterized by M. leprae proliferation and T cell anergy. Similar to progressive tumor cells, M. leprae escapes immunosurveillance in more severe forms of leprosy. The mechanisms by which M. leprae is able to evade the host immune response involve many, including the alterations of lipid droplets, microRNA, and Schwann cells, and involve the regulation of immune regulators, such as the negative checkpoint regulators CTLA-4, programmed death 1, and V-domain Ig suppressor of T cell activation-important targets in today's cancer immunotherapies. The means by which tumor cells become able to escape immunosurveillance through negative checkpoint regulators are evidenced by the successes of treatments, such as nivolumab and ipilimumab. Many parallels can be drawn between the immune responses seen in leprosy and cancer. Therefore, the understanding of how M. leprae encourages immune escape during proliferative disease states has potential to add to our understanding of cancer immunotherapy.


Purification and analysis of authentic CLIP-170 and recombinant fragments.
We have purified authentic CLIP-170 (cytoplasmic linker protein of 170 kDa) and fragments comprising functional domains of the protein to characterize the structural basis of the function of CLIP-170. Analysis of authentic CLIP-170 and the recombinant fragments by electron microscopy after glycerol spraying/low angle rotary metal shadowing reveals CLIP-170 as a thin, 135-nm-long molecule with two kinks in its central rod domain, which are approximately equally spaced from the two ends of the protein. The central domain consisting of heptad repeats, which is alpha-helical in nature and forms a 2-stranded coiled-coil, mediates dimerization of CLIP-170. The rod domain harbors two kinks, each spaced approximately 37 nm from the corresponding end of the molecule, thus providing mechanical flexibility to the highly elongated molecule. The N-terminal domain of CLIP-170 binds to microtubules in vitro with a stoichiometry of one dimeric head domain per four tubulin heterodimers. Authentic CLIP-170 binds to microtubules with lower stoichiometry, indicating that the rod and tail domains affect microtubule binding of CLIP-170. These results document that CLIP-170 is a highly elongated polar molecule with the microtubule-binding domain and the organelle-interacting domains at opposite ends of the homodimer, thus providing a structural basis for the function of CLIP-170 as a microtubule-organelle linker protein.


PET-MRI: a review of challenges and solutions in the development of integrated multimodality imaging.
The integration of positron emission tomography (PET) and magnetic resonance imaging (MRI) has been an ongoing research topic for the last 20 years. This paper gives an overview of the different developments and the technical problems associated with combining PET and MRI in one system. After explaining the different detector concepts for integrating PET-MRI and minimising interference the limitations and advantages of different solutions for the detector and system are described for preclinical and clinical imaging systems. The different integrated PET-MRI systems are described in detail. Besides detector concepts and system integration the challenges and proposed solutions for attenuation correction and the potential for motion correction and resolution recovery are also discussed in this topical review.


Community structure and functional gene profile of bacteria on healthy and diseased thalli of the red seaweed Delisea pulchra.
Disease is increasingly viewed as a major factor in the ecology of marine communities and its impact appears to be increasing with environmental change, such as global warming. The temperate macroalga Delisea pulchra bleaches in Southeast Australia during warm summer periods, a phenomenon which previous studies have indicated is caused by a temperature induced bacterial disease. In order to better understand the ecology of this disease, the bacterial communities associated with threes type of samples was investigated using 16S rRNA gene and environmental shotgun sequencing: 1) unbleached (healthy) D. pulchra 2) bleached parts of D. pulchra and 3) apparently healthy tissue adjacent to bleached regions. Phylogenetic differences between healthy and bleached communities mainly reflected relative changes in the taxa Colwelliaceae, Rhodobacteraceae, Thalassomonas and Parvularcula. Comparative metagenomics showed clear difference in the communities of healthy and diseased D. pulchra as reflected by changes in functions associated with transcriptional regulation, cation/multidrug efflux and non-ribosomal peptide synthesis. Importantly, the phylogenetic and functional composition of apparently healthy tissue adjacent to bleached sections of the thalli indicated that changes in the microbial communities already occur in the absence of visible tissue damage. This shift in unbleached sections might be due to the decrease in furanones, algal metabolites which are antagonists of bacterial quorum sensing. This study reveals the complex shift in the community composition associated with bleaching of Delisea pulchra and together with previous studies is consistent with a model in which elevated temperatures reduce levels of chemical defenses in stressed thalli, leading to colonization or proliferation by opportunistic pathogens or scavengers.


Diabetes decreases Na+-K+ pump concentration in skeletal muscles, heart ventricular muscle, and peripheral nerves of rat.
Na+-K+-ATPase or the Na+-K+ pump is essential for some specific properties of muscle and nerve tissue such as contractility and excitability. Previous studies have shown conflicting variations in Na+-K+-ATPase activity or Na+-K+ pump concentration of muscle cells in experimental diabetes. Our study demonstrates that early untreated diabetes in rats induced by injection of streptozocin is associated with decreases in [3H]ouabain binding-site concentration of 24-48% in various skeletal muscles and 16% in peripheral nerves as well as a decrease in K+-dependent 3-O-methylfluorescein phosphatase activity of 21% in the heart ventricle. These effects could be prevented by insulin treatment. They probably represent a decrease in the concentration of Na+-K+ pumps. There was no evidence for more than one population of Na+-K+ pumps in intact samples of skeletal muscle and nerves from normal, diabetic, and insulin-treated animals. The decrease in Na+-K+ pump concentration in nerve cells may be due to atrophy of the axons. In skeletal muscles, myocardium, and peripheral nerves, the observed decrease in Na+-K+ pump concentration may be important for the pathophysiology of diabetes. We emphasize that quantification of Na+-K+-ATPase or the Na+-K+ pump in muscle and nerve tissue from diabetic animals should preferably be performed with either intact samples or crude homogenates of whole tissue.


Clinical manifestations of head and neck irradiation.
Treatment of squamous cell carcinoma of the oral cavity, salivary gland tumors, and Hodgkin's disease may include radiation therapy to the head and neck region. This therapy has treatment-related sequelae to the oral cavity and can contribute to increased rates of dental caries in these patients. To prevent radiation-induced caries, patients are instructed to use a high-potency fluoride application in addition to their standard dentifrice during radiation therapy and the postradiation phases of their treatment. Traditionally, patients are prescribed a 5,000-ppm fluoride (F) gel that is applied using mouthguards. However, due to oral postoperative conditions, many patients are not complaint with this treatment. In many cases, the availability of a fluoride product that is easier to use could result in successful patient compliance.


A generic approach to simultaneous tracking and verification in video.
In this paper, a generic approach to simultaneous tracking and verification in video data is presented. The approach is based on posterior density estimation using sequential Monte Carlo methods. Visual tracking, which is in essence a temporal correspondence problem, is solved through probability density propagation, with the density being defined over a proper state space characterizing the object configuration. Verification is realized through hypothesis testing using the estimated posterior density. In its most basic form, verification can be performed as follows. Given a measurement vector Z and two hypotheses H1 and H0, we first estimate posterior probabilities P(H0/Z) and P(H1/Z), and then choose the one with the larger posterior probability as the true hypothesis. Several applications of the approach are illustrated by experiments devised to evaluate its performance. The idea is first tested on synthetic data, and then experiments with real video sequences are presented, illustrating vehicle tracking and verification, human (face) tracking and verification, facial feature tracking, and image sequence stabilization.


Benzodiazepine dependence in mice after ingestion of drug-containing food pellets.
Diazepam was administered to Swiss-Webster mice for 53 days as a mixture of drug in laboratory chow, leading to consumption as high as 1000 mg/kg/day. Low plasma concentrations of diazepam, but very high levels (generally between 5,000 and 10,000 ng/ml) of the active metabolites nordiazepam and oxazepam, were found. Animals appeared healthy throughout drug administration, but some died because of apparent drug-induced aggression. Withdrawal was precipitated by omitting drug from the food. The behavior and physiological state of each animal were observed in detail during treatment and withdrawal phases. Tests that showed stable results in control animals and changes during abstinence were used to measure the withdrawal syndrome. These changes included piloerection, tremor, pelvic elevation and tail elevation, as well as changes in body tone, abdominal tone and pupil size. A composite withdrawal score was plotted against time; this score increased significantly (P less than .01) 1 day after withdrawal and remained significantly elevated for 17 days. This technique provides a quantitative method to study the effect of withdrawal from benzodiazepines in mice.


Effects of spatial configuration and number of fixations on Kanizsa triangle detection.
Illusory figures, created by the visual system between visualizing real objects, are probably caused by processes designed to segregate objects from background. Support ratio--that is, the ratio between the physically specified and total triangle side length--has been suggested to be the main spatial determinant for suprathreshold perception of a Kanizsa-type illusion. To test this scale invariance hypothesis at threshold, illusory figure perception was studied by determining the effects of inducer size and distance at various exposure durations and fixation strategies on the frequency of seeing (FoS) an illusory Kanizsa triangle. The effect of various support ratios was studied in the first experiment by varying the intercenter distance between constant-size inducers viewed at various distances. In the second experiment, the effects of various exposure durations and fixation strategies were investigated; and the third experiment repeated the second one, with backward masking to control the processing time. In the fourth experiment, the magnification of the stimulus configuration was varied, with a support ratio that had yielded 100% FoS in the first experiment, to study the range of scale invariance in illusory figure perception. The support ratio was the main determinant for the perception of an illusory figure at various inducer sizes, exposure durations, and masking conditions when fixation was steady; FoS always increased from 0% to 100% with the support ratio of 0.30 to 0.37. However, free viewing, with and without masking, resulted in 100% illusory figure perception at all support ratios tested. Furthermore, when fixation was steady and support ratio and exposure duration were held constant, stimulus magnification reduced FoS from 100% to 0% at the smallest and largest stimulus sizes. The support ratio seems to be the main spatial determinant for illusory figure perception. However, scale invariance in Kanizsa triangle perception broke down in the smallest and largest configurations, probably because of the limitations of visual acuity and spatial integration, respectively. Integration of information from several fixations enhances FoS at small support ratios, emphasizing the importance of the binding process between separate fixations for illusory figure perception.


Amelioration of High Fructose-Induced Cardiac Hypertrophy by Naringin.
Heart failure is a frequent unfavorable outcome of pathological cardiac hypertrophy. Recent increase in dietary fructose consumption mirrors the rise in prevalence of cardiovascular diseases such as cardiac hypertrophy leading to concerns raised by public health experts. Mitochondria, comprising 30% of cardiomyocyte volume, play a central role in modulating redox-dependent cellular processes such as metabolism and apoptosis. Furthermore, mitochondrial dysfunction is a key cause of pathogenesis of fructose-induced cardiac hypertrophy. Naringin, a major flavanone glycoside in citrus species, has displayed strong antioxidant potential in models of oxidative stress. In this study, we evaluated protective effects of naringin against fructose-induced cardiac hypertrophy and associated mechanisms of action, using in vitro and in vivo models. We found that naringin suppressed mitochondrial ROS production and mitochondrial dysfunction in cardiomyocytes exposed to fructose and consequently reduced cardiomyocyte hypertrophy by regulating AMPK-mTOR signaling axis. Furthermore, naringin counteracted fructose-induced cardiomyocyte apoptosis, and this function of naringin was linked to its ability to inhibit ROS-dependent ATM-mediated p53 signaling. This result was supported by observations in in vivo mouse model of cardiac hypertrophy. These findings indicate a novel role for naringin in protecting against fructose-induced cardiac hypertrophy and suggest unique therapeutic strategies for prevention of cardiovascular diseases.


Young genes have distinct gene structure, epigenetic profiles, and transcriptional regulation.
Species-specific, new, or "orphan" genes account for 10%-30% of eukaryotic genomes. Although initially considered to have limited function, an increasing number of orphan genes have been shown to provide important phenotypic innovation. How new genes acquire regulatory sequences for proper temporal and spatial expression is unknown. Orphan gene regulation may rely in part on origination in open chromatin adjacent to preexisting promoters, although this has not yet been assessed by genome-wide analysis of chromatin states. Here, we combine taxon-rich nematode phylogenies with Iso-Seq, RNA-seq, ChIP-seq, and ATAC-seq to identify the gene structure and epigenetic signature of orphan genes in the satellite model nematode Pristionchus pacificus Consistent with previous findings, we find young genes are shorter, contain fewer exons, and are on average less strongly expressed than older genes. However, the subset of orphan genes that are expressed exhibit distinct chromatin states from similarly expressed conserved genes. Orphan gene transcription is determined by a lack of repressive histone modifications, confirming long-held hypotheses that open chromatin is important for new gene formation. Yet orphan gene start sites more closely resemble enhancers defined by H3K4me1, H3K27ac, and ATAC-seq peaks, in contrast to conserved genes that exhibit traditional promoters defined by H3K4me3 and H3K27ac. Although the majority of orphan genes are located on chromosome arms that contain high recombination rates and repressive histone marks, strongly expressed orphan genes are more randomly distributed. Our results support a model of new gene origination by rare integration into open chromatin near enhancers.


Natural rubber latex: a matter of concern for nurses.
During the past 20 years, the use of protective gloves in health care has increased, as have hypersensitivity reactions to the natural rubber latex (NRL) used in glove manufacture. A study was conducted to determine what nurses who work in environments in which NRL is commonly used know about NRL, including their education about and experience with NRL-related allergies. Nurses replied to a questionnaire with 20 statements pertaining to NRL and NRL-related allergies. The results showed that the nurses had inadequate knowledge about NRL, but nurses in a specialty training program scored significantly higher than professionally active nurses.


New therapeutic strategies to treat human cancers expressing mutant p53 proteins.
The tumor suppressor p53 plays a critical role to preserve DNA fidelity from diverse insults through the regulation of cell-cycle checkpoints, DNA repair, senescence and apoptosis. The TP53 is the most frequently inactivated gene in human cancers. This leads to the production of mutant p53 proteins that loose wild-type p53 tumor suppression functions and concomitantly acquire new oncogenic properties among which deregulated cell proliferation, increased chemoresistance, disruption of tissue architecture, promotion of migration, invasion and metastasis and several other pro-oncogenic activities. Mouse models show that the genetic reconstitution of the wild type p53 tumor suppression functions rescues tumor growth. This strongly supports the notion that either restoring wt-p53 activity or inhibiting mutant p53 oncogenic activity could provide an efficient strategy to treat human cancers. In this review we briefly summarize recent advances in the study of small molecules and compounds that subvert oncogenic activities of mutant p53 protein into wt-p53 tumor suppressor functions. We highlight inhibitors of signaling pathways aberrantly modulated by oncogenic mutant p53 proteins as promising therapeutic strategies. Finally, we consider the clinical applications of compounds targeting mutant p53 and the use of currently available drugs in the treatment of tumors expressing mutant p53 proteins.


The effect of age on self-rated skin pain in patients with hidradenitis suppurativa.
Hidradenitis suppurativa (HS) is a recalcitrant chronic inflammatory skin disease characterized by recurrent and painful nodules that negatively affect health-related quality of life. Pain is the most disabling symptom of HS, but data on HS pain remain limited. We previously observed a dissociation between pain and number of HS lesions with regards to increasing age. To further explore this observation, we investigated the relationship between experienced HS pain and age, adjusting for other relevant factors that might affect pain assessment. We conducted a retrospective cohort study (n = 342) using data from the Registry for Hidradenitis Suppurativa database. Multiple linear regression analysis was performed for self-evaluated pain (measured on a 0-10 numerical rating scale [NRS]) as an outcome with age and adjusted for the effects of sex, BMI, smoking status, lesion count and percentage of lifetime spent with HS symptoms. The multiple linear regression showed that age was associated with a decreased pain level of 0.31 NRS points/year (95% CI: -0.062; -0.0088; p = 0.044) and number of nodules was associated with an increased pain level of 0.081 NRS points/nodule (95% CI: 0.00077; 0.16; p = 0.048). Percentage of lifetime spent with HS symptoms was not found to significantly affect pain levels. This study supports our hypothesis that older HS patients report decreased levels of pain, independent of disease severity, which may be due to factors such as demyelination of nerve fibres, reduced painful physical activity, improved coping, or associated co-morbidities that distract from HS-related pain.


Evaluation of the walk-through inflatable colon as a colorectal cancer education tool: results from a pre and post research design.
Colorectal cancer (CRC) is a disease that can be prevented through early detection. Through the use of effective educational tools, individuals can become better informed about CRC and understand the importance of screening and early detection. The walk through Inflatable Colon is an innovative educational resource developed to engage and educate communities on CRC and the importance of receiving screening at the appropriate ages. The Inflatable Colon Assessment Survey (ICAS) assessed knowledge and behavioral intentions to obtain screening and promote CRC awareness. New Mexico State University faculty, staff, and students completed a consent form, took the pre-ICAS, toured the Inflatable Colon, and completed the post-ICAS. The majority of participants (92%) were young adults, mostly college students, under the age of 30 yrs. Overall, participants demonstrated increases in CRC knowledge and awareness after touring the inflatable colon (p-values < 0.001). Interestingly, both males and Hispanics had lower CRC awareness at pre-test, but exhibited maximum awareness gains equal to that of females and non Hispanic Whites after touring the IC. Behavioral intentions to obtain CRC screening in the future and to promote CRC awareness also increased (p-value < 0.001). Gender differences in behavioral intentions to act as advocators for CRC education were found (p < 0.05), with females being more likely to educate others about CRC than males. Educational efforts conducted in early adulthood may serve to promote healthier lifestyles (e.g., physical activity, healthy nutrition, screening). These educated young adults may also serve to disseminate CRC information to high-risk friends and relatives. The walk through Inflatable Colon can increase CRC knowledge and intentions to get screened among a young and diverse population.


Venous function after restoring valve competence of the great saphenous vein.
To measure changes in venous function after elimination of great saphenous vein reflux using endovenously-applied heat with a specially designed catheter. In a prospective clinical study, 13 patients (8 women; mean age 39 years, range 25-59) with symptomatic chronic venous insufficiency were treated for reflux at the saphenofemoral junction. A radiofrequency catheter (Restore) with expandable electrodes that shrinks the vein by controlled constriction of subendothelial collagen was used to restore valve competence. Extirpation of local varicosities was performed simultaneously. Main outcome was change in venous function as measured by plethysmography (foot volumetry) and change in diameter and reflux time at the saphenofemoral junction after 6 and 12 months. Reflux in the greater saphenous vein was eliminated or reduced to below 0.5 seconds in all patients. The venous function was significantly improved after 6 months' follow-up, with decreased refilling rate/expelled volume related to foot volume (p=0.019). The patients were clinically improved, although only 7 (54%) were entirely free from reflux. Three (21%) patients had thrombus in the vein the day after the treatment, 2 at the treatment site and 1 at the entry site of the introducer. After 1 year, the patients are still satisfied with the results, although venous function is no longer significantly improved compared to baseline. It is possible to safely restore valvular competence by means of internally shrinking the vein diameter. The venous function is improved, although the vein has a tendency to increase in width with time; limited reflux reappears, with deterioration of venous function.


When the same is different. A comparison of the information processing strategies of deaf and hearing people.
In this study, the information processing strategies of Gallaudet University students who are profoundly and prelingually deaf were evaluated. The subjects demonstrated the highest levels of recognition to the left and right of the fixation point, often referred to as a reading strategy when found in hearing people. Additionally, they demonstrated higher levels of recognition at positions in the top right quadrant of the display, a pattern not found in hearing people. A main effect was found: subjects whose primary and secondary school backgrounds were oral and manual combined had significantly higher levels of recognition overall than did subjects from oral-only educational backgrounds. Differences in background did not interact with strategy use in this study. These findings lead to the conclusion that the information processing strategies of deaf people need to be evaluated closely before general conclusions can be made. Alternative means for evaluating these types of findings are suggested.


Designing ordered micropatterned hydroxyapatite bioceramics to promote the growth and osteogenic differentiation of bone marrow stromal cells.
Patterned structured surfaces are very useful to control a cell's microenvironment and to modulate certain cellular responses, such as cell adhesion, migration, proliferation, and differentiation. Herein, ordered micropatterns constructed by a quadrate convex with different sizes were fabricated on a hydroxyapatite [Ca10(PO4)6(OH)2, HAp] bioceramic surface using an ordered micropatterned nylon sieve as templates. The height, width and space of the convex for the patterns could be facilely regulated via simply tailoring the meshes of the template. Compared with traditional samples with flat surfaces, the fabricated HAp bioceramics with micropatterned surfaces possessed better wettability and higher surface energy, which significantly promoted the adhesion, proliferation, and osteogenic differentiation of rat bone marrow stromal cells (bMSCs). Furthermore, using a pattern size close to that of the cell size showed a better stimulation of cell response compared with larger pattern sizes. Our study suggests that the fabrication of micropatterned structured HAp bioceramics is critical for designing optimal biomaterials for bone regeneration and cell culture substrate applications.


Interventions to prevent pneumonia among older adults.
Pneumonia is a common cause of death in older people. Antimicrobial drugs do not prevent pneumonia and, because of increasingly resistant organisms, their value in curing infection will become more limited. Establishing new strategies to prevent pneumonia through consideration of the mechanisms of this devastating illness is essential. The purpose of this review is to discuss how pneumonia develops in older people and to suggest preventive strategies that may reduce the incidence of pneumonia among older adults. Aspiration of oropharyngeal bacterial pathogens to the lower respiratory tract is one of the most important risk factors for pneumonia; impairments in swallowing and cough reflexes among older adults, e.g., related to cerebrovascular disease, increase the risk for the development of pneumonia. Thus, strategies to reduce the volumes and pathogenicity of aspirated material should be pursued. For example, since both swallowing and cough reflexes are mediated by endogenous substance P, pharmacologic therapy using angiotensin-converting enzyme inhibitors, which decrease substance P catabolism, may improve both reflexes and result in the lowering of the risk of pneumonia. Similarly, since the production of substance P is regulated by dopaminergic neurons in the cerebral basal ganglia, treatment with dopamine analogs or potentiating drugs such as amantadine (and, of course, prevention of cerebral vascular disease, which can result in basal ganglia strokes) should affect the incidence of pneumonia. The purpose of this review is to consider promising pharmacologic treatments as methods of preventing pneumonia in older adults and to review other proven strategies, e.g., infection control and cerebrovascular disease prevention that will lessen the incidence of pneumonia.


N-Acetylcysteine in psychodermatological disorders.
Treatment of psychodermatological conditions, particularly body-focused repetitive behavior disorders, is often unsatisfactory. Various psychopharmacological and non-pharmacological treatments have been used to ameliorate the symptoms of these disorders. N-Acetylcysteine (NAC) is a newer modality in the treatment of these disorders. This short review focuses on pharmacology, mode of action, and use of NAC in common body-focused repetitive disorders such as trichotillomania, skin-picking disorders, and onychotillomania (nail biting). Current research and literature review have been evaluated and will be discussed.


Systematization of perioperative nursing care in robotic surgery: instrument validation.
To develop and validate an instrument to assist in the systematization of perioperative nursing care in robotic surgery. Methodological study developed in four phases: content survey; textual elaboration; content validation by the group of expert judges and target audience; and elaboration of the electronic instrument layout. Eleven expert judges and seven evaluators of the target audience participated. For validation, the Content Validity Index (CVI) was used with a 0.78 cutoff point. The instrument total CVI after evaluation was 0.90 by the expert judges and 0.88 by the target audience. The tool built was proved satisfactory for the systematization of perioperative nursing care. The instrument construction was based on the updated scientific literature and validated by the expert judges and target audience.


Relative versus absolute quantitation in disease glycomics.
The glycome of a diagnostic biological material such as blood, urine, saliva, tissue, or cell cultures comprises of a vast array of structurally distinct glycans attached to the protein complement. Aberrant glycan structures and distributions result from changes in specific glycosyltransferase activities and have different biological significance, making proper quantitation of glycans highly important. In this review, common HPLC/CE and LC-MS/MS-based methods for glycomics, their advantages and disadvantages, will be discussed with respect to the main quantitative strategies. With the increasing interest in absolute quantitation for glycomics, we discuss absolute and relative glycome quantitation and how it affects the resulting conclusions drawn from glycomics studies. We argue that while absolute quantitation of glycomes may be attractive for some areas of clinical glycomics, relative quantitation of glycans remains the most informative and time/cost-effective method to obtain biological insight into the regulation of the cellular glycosylation machinery and the synthesis of the resultant glycan structures in most research questions due to the enzymatic relatedness of the biosynthesized glycans. Recent developments in multiplexing of glycomes by the introduction of stable isotopic labeling of glycans show promise for providing another level of information to the existing benefits of relative quantitation.


Probing interfaces between pharmaceutical crystals and polymers by neutron reflectometry.
Pharmaceutical powder engineering often involves forming interfaces between the drug and a suitable polymer. The structure at the interface plays a critical role in the properties and performance of the composite. However, interface structures have not been well understood due to a lack of suitable characterization tool. In this work, we have used ellipsometry and neutron reflectometry to characterize the structure of such interfaces in detail. Ellipsometry provided a quick estimate of the number of layers and their thicknesses, whereas neutron reflectometry provided richer structural information such as density, thickness, roughness, and intermixing of different layers. The combined information allowed us to develop an accurate model about the layered structure and provided information about intermixing of different layer components. Systematic use of these characterization techniques on several model systems suggests that the nature of the polymer had a small effect on the interfacial structure, while the solvent used in polymer coating had a large effect. These results provide useful information on the efforts of engineering particle properties through the control of the interfacial chemistry.


Developmental specialization of the left intraparietal sulcus for symbolic ordinal processing.
Symbolic numbers have both cardinal (symbol-quantity) and ordinal (symbol-symbol) referents. Despite behavioural evidence suggesting distinct processing of cardinal and ordinal referents, little consensus has emerged from the neuroimaging literature on whether these processes have shared or distinct neural underpinnings. Moreover, it remains unclear how the neural correlates of cardinal and ordinal processing change with age. To address these unresolved questions, we investigated the neural correlates of cardinal (neural distance effect) and ordinal processing (neural reverse distance effect) in 50 children (ages 7-10) and 26 adults (ages 19-26). We found that adults recruited a largely left lateralized set of fronto-parietal regions for ordinal processing, whereas children showed activation in the right lateral orbital and inferior frontal gyri for both ordinal and cardinal processing. Additional analyses suggested that adults recruited the left intraparietal sulcus (IPS) more than children for ordinal processing, suggesting that the IPS may become increasingly tuned to ordinal symbolic properties over development. Together with previous literature documenting the importance of the left IPS for cardinal processing, our results suggest that cardinal and ordinal processing may share neural substrates in the left IPS and that this region may become specialized for both skills over development.


Could trained providers provide better quality of IUD services? Results of a secondary data analysis of complications as a proxy indicator.
Background: For accelerating its progress towards FP2020 goals, the Government of India has focused on improving the quality of intrauterine device (IUD) services. EngenderHealth has supported the Governments of Rajasthan and Gujarat since 2014 through its Expanding Access to IUD Services in India (EAISI) project by building the capacity of service providers, monitoring their compliance with standard practices, and strengthening health systems. This study sought to assess whether EAISI trained providers provide a better quality of IUD services as compared to non-EAISI trained providers, as indicated by a reduction in confirmed IUD complications? Methods: This study was an analytical cross-sectional study of secondary data collected from the follow-up registers of 176 intervention facilities (138 in Rajasthan and 38 in Gujarat) during Phase I of EAISI project. The analysis included clients who returned between April 2018 and March 2019 to the same facility for a follow-up visit. Multivariate logistic regression was performed to determine factors associated with IUD complications. Results: A total of 56,733 IUD insertions were conducted, and 10,747 (18.9%) client follow-ups were documented. Of these, 49.4% (N=5,305) clients received IUDs from EAISI-trained providers, while 50.6% (N=5,442) received IUDs from non-EAISI trained providers. A total of 4.0% (N=432) of clients experienced complications (Expulsion: 1.3%, Missing Strings: 1.7%, Infection: 1.1%). Clients who received IUDs from non-EAISI-trained providers were 55.5% more likely [95% CI (26.2%, 91.5%), p<0.0005] to have complications compared to clients who received insertions from EAISI-trained providers. Other significant factors include the type of IUD, timing of the follow-up visit and timing of the insertion. Conclusion: The findings demonstrate that intensive, hands-on training of providers to improve clinical skills for IUD insertions can have a positive impact on the reduction of post-insertion complications.


Large-scale first principles configuration interaction calculations of optical absorption in aluminum clusters.
We report the linear optical absorption spectra of aluminum clusters Aln (n = 2-5) involving valence transitions, computed using the large-scale all-electron configuration interaction (CI) methodology. Several low-lying isomers of each cluster were considered, and their geometries were optimized at the coupled-cluster singles-doubles (CCSD) level of theory. With these optimized ground-state geometries, excited states of different clusters were computed using the multi-reference singles-doubles configuration-interaction (MRSDCI) approach, which includes electron correlation effects at a sophisticated level. These CI wave functions were used to compute the transition dipole matrix elements connecting the ground and various excited states of different clusters, and thus their photoabsorption spectra. The convergence of our results with respect to the basis sets, and the size of the CI expansion, was carefully examined. Our results were found to be significantly different as compared to those obtained using time-dependent density functional theory (TDDFT) [Deshpande et al. Phys. Rev. B: Condens. Matter Mater. Phys., 2003, 68, 035428]. When compared to the available experimental data for the isomers of Al2 and Al3, our results are in very good agreement as far as important peak positions are concerned. The contribution of configurations to many body wave functions of various excited states suggests that in most cases optical excitations involved are collective, and plasmonic in nature.


Recent clinical trials in atrial fibrillation.
Management of atrial fibrillation can be overwhelming with the amount of information and treatment options available today. This review discusses landmark and other clinically relevant trials published in the last 18 months. There have been several recent key clinical trials and subanalyses in the field of atrial fibrillation. Early rhythm control with ablation or antiarrhythmic medications has upended the previous practice of rate control for patients with atrial fibrillation. Vein of Marshall alcohol ablation in combination with endocardial mitral annular ablation and a hybrid epicardial/endocardial approach has shown promising results in the fight against persistent atrial fibrillation. Early ablation with cryoballoon therapy vs. antiarrhythmic therapy gives further evidence for early ablation in patients with symptomatic paroxysmal atrial fibrillation. The rapid development in technology and medications to treat atrial fibrillation, prevent stroke and improve quality of life for patients has created a vast amount of information for physicians to process. The present review will focus on the recent (within 2 years) clinical trials in atrial fibrillation and the impact they may have on your practice.


Madelung Deformity in a Collegiate Gymnast: A Case Report.
OBJECTIVE: To present the case of a 21-year-old female collegiate gymnast with acute left wrist pain. BACKGROUND: Madelung deformity is a developmental abnormality of the wrist. It is characterized by anatomic changes in the radius, ulna, and carpal bones, leading to palmar and ulnar wrist subluxation. It is more common in female patients and is usually present bilaterally. The deformity usually becomes evident clinically between the ages of 6 and 13 years. DIFFERENTIAL DIAGNOSIS: Traumatic distal radius physeal arrest, congenital anatomic variant. TREATMENT: The athlete was treated with symptomatic therapeutic modalities and nonsteroidal anti-inflammatory medication for pain. She was able to continue to participate successfully in competitive gymnastics, minimally restricted, with the aid of palmar wrist tape and a commercially available wrist brace to prevent end-range wrist extension. UNIQUENESS: Madelung deformity can result in wrist pain and loss of forearm rotation, leading to decreased function of the wrist and hand. This patient was able to participate successfully in elite- and college-level gymnastics with no wrist pain or injury until the age of 21 years. Furthermore, she was able to continue to participate, experiencing only periodic pain, with the aid of taping and bracing support and without the need for reconstructive surgery. CONCLUSIONS: Although rare, Madelung deformity is typically corrected surgically in athletes with chronic pain and disability. This case demonstrates an example of successful conservative management in which the athlete continued to participate in sport.


Effect of Informational Support on Anxiety in Family Caregivers of Patients with Hemiplegic Stroke.
Brain stroke causes physical and mental disabilities, as well as dependence on one's family. In such cases, the families suffer from severe crisis and anxiety due to the unexpected incidence of the disease and unawareness of the associated consequences. The aim of the present study was to evaluate the effectiveness of informational support on the level of anxiety in family caregivers of hemiplegic stroke patients. This quasi-experimental study was performed on 78 family caregivers of hemiplegic stroke patients admitted to the Neurology Department of Farshchian Hospital in Hamadan, Iran, over 8 months. The subjects were selected through convenience sampling method and divided into two groups of intervention (n = 40) and control (n = 38). Intervention started from the third day of hospitalization and continued until the eleventh day. During this period, information about the ward, equipment, patient status, and care procedure at home, was provided for the intervention group individually and in groups. On the other hand, the control group only received the routine care. Anxiety level of caregivers was measured through the Spielberger scale both before and after the intervention. Data analysis was performed in SPSS software (version 16). Based on the results, both groups were similar in terms of demographic variables (P > 0.05). Moreover, there was no significant difference between the two groups regarding the mean level of state and trait anxiety before the intervention (P > 0.05). However, after intervention, the mean level of state and trait anxiety of the intervention group showed a significant reduction in comparison to that of the control group (P < 0.05). According to the findings, it can be concluded that informational support is effective in reducing the state and trait anxiety in family caregivers of stroke patients. Therefore, it is suggested that nurses consider informational support as an important nursing intervention during hospitalization.


Conformation of d(CpG) modified by the carcinogen 4-aminobiphenyl: a combined experimental and theoretical analysis.
The change in DNA conformation produced by the attachment of a reactive substance is likely to be a vital factor in determining the biological consequences of the reaction. We have prepared a deoxydinucleoside monophosphate containing the major adduct derived from the carcinogenic amine 4-aminobiphenyl and analyzed its conformation by theoretical and experimental methods. Reaction of d(CpG) with N-acetoxy-N-(trifluoroacetyl)-4-aminobiphenyl afforded the product modified at C-8 of guanine with 4-aminobiphenyl. After purification by reverse-phase high-performance liquid chromatography, milligram amounts of product were obtained. It was analyzed by circular dichroism, proton magnetic resonance, and minimized potential-energy calculations. A flexible molecule with a mixture of conformers is indicated. Both carcinogen-base-stacked states and base-base-stacked states, with guanine both syn anti, contribute to the population mixture on the dimer level. The global minimum-energy conformation has syn-guanine and carcinogen-base stacking. Forms of this type are calculated to represent roughly 58% of the conformer population. Because of the twisted nature of the biphenyl moiety, carcinogen-base stacking inherently involves less overlap than that in the planar and rigid three-ringed aminofluorene analogue. This difference might relate to the diminished effectiveness of the aminobiphenyl vs. the aminofluorene adduct as a frameshift mutagen in Salmonella typhimurium 1538.


A long-term field experiment of soil transplantation demonstrating the role of contemporary geographic separation in shaping soil microbial community structure.
The spatial patterns of microbial communities are largely determined by the combined effects of historical contingencies and contemporary environmental disturbances, but their relative importance remains poorly understood. Empirical biogeographic data currently available are mostly based on the traditional method of observational survey, which typically involves comparing indigenous microbial communities across spatial scales. Here, we report a long-term soil transplantation experiment, whereby the same two soils (red Acrisol and purple Cambisol from Yingtan) were placed into two geographic locations of ∼1000 km apart (i.e., Yingtan in the mid-subtropical region and Fengqiu in warm-temperate region; both located in China). Twenty years after the transplantation, the resulting soil microbial communities were subject to high-throughput 454 pyrosequencing analysis of 16S and 18S rRNA genes. Additionally, bacteria and archaea involved in nitrogen cycling were estimated using clone library analysis of four genes: archaeal amoA, bacterial amoA,nirK, and nifH. Data of subsequent phylogenetic analysis show that bacteria, fungi, and other microbial eukaryotes, as well as the nitrogen cycling genes, are grouped primarily by the factor of geographic location rather than soil type. Moreover, a shift of microbial communities toward those in local soil (i.e., Chao soil in Fengqiu) has been observed. The results thus suggest that the historical effects persistent in the soil microbial communities can be largely erased by contemporary disturbance within a short period of 20 years, implicating weak effects of historical contingencies on the structure and composition of microbial communities in the soil.


T cell receptor engagement of peptide-major histocompatibility complex class I does not modify CD8 binding.
Activation of cytotoxic T cells is initiated by engagement of the T-cell receptor (TCR) with peptide-major histocompatibility class I complexes (pMHCI). The CD8 co-receptor also binds to pMHCI, but at a distinct site, and allows the potential for tripartite TCR/pMHCI/CD8 interactions, which can increase T cell antigen sensitivity. There has been a substantial interest in the effect of the pMHCI/CD8 interaction upon TCR/pMHCI engagement, and several conflicting studies have examined this event, using the soluble extracellular domains of CD8 and the TCR, by surface plasmon resonance. However, the evidence to date suggests that the TCR engages cognate pMHCI before CD8 recruitment, so the question of whether TCR engagement alters CD8 binding is likely to be more relevant to the biological order of T cell antigen encounter. Here, we have examined the binding of CD8 to several variants of the HLA A2-restricted telomerase(540-548) antigen (ILAKFLHWL) and the HLA A2-restricted NY-ESO-1(157-165) antigen (SLLMWITQC) that bind to their cognate TCRs with distinct affinities and kinetics. These interactions represent a range of agonists that exhibit different CD8 dependency for activation of their respective T cells. By using engineered affinity enhanced TCRs to these ligands, which have extended off-rates of approximately 1h compared to seconds for the wildtype TCRs, we have examined pMHCI/CD8 binding before and during TCR-engagement. Here we show that the binding of the extracellular domain of the TCR to pMHCI does not transmit structural changes to the pMHCI-CD8 binding site that would alter the subsequent pMHCI/CD8 interaction.


Detection of toxigenic Vibrio cholerae O1 in freshwater lakes of the former Soviet Republic of Georgia.
Three freshwater lakes, Lisi Lake, Kumisi Lake and Tbilisi Sea, near Tbilisi, Georgia, were studied from January 2006 to December 2007 to determine the presence of Vibrio cholerae employing both bacteriological culture method and direct detection methods, namely PCR and direct fluorescent antibody (DFA). For PCR, DNA extracted from water samples was tested for presence of V. cholerae and genes coding for selected virulence factors. Vibrio cholerae non-O1/non-O139 was routinely isolated by culture from all three lakes; whereas V. cholerae O1 and O139 were not. Water samples collected during the summer months from Lisi Lake and Kumisi Lake were positive for both V. cholerae and V. cholerae ctxA, tcpA, zot, ompU and toxR by PCR. Water samples collected during the same period from both Lisi and Kumisi Lake were also positive for V. cholerae serogroup O1 by DFA. All of the samples were negative for V. cholerae serotype O139. The results of this study provide evidence for an environmental presence of toxigenic V. cholerae O1, which may represent a potential source of illness as these lakes serve as recreational water in Tbilisi, Georgia.


Decomposing of Socioeconomic Inequality in Mental Health: A Cross-Sectional Study into Female-Headed Households.
Connection between socioeconomic statuses and mental health has been reported already. Accordingly, mental health asymmetrically is distributed in society; therefore, people with disadvantaged condition suffer from inconsistent burden of mental disorders. In this study, we aimed to understand the determinants of socioeconomic inequality of mental health in the female-headed households and decomposed contributions of socioeconomic determinants in mental health. In this cross-sectional study, 787 female-headed households were enrolled using systematic random sampling in 2014. Data were taken from the household assets survey and a self-administered 28 item General Health Questionnaire (GHQ-28) as a screening tool for detection of possible cases of mental disorders. Inequality was measured by concentration index (CI) and as decomposing contribution in inequality. All analyses were performed by standard statistical software Stata 11.2. The overall CI for mental health in the female-headed households was -0.049 (95% CI: -0.072, 0.025). The highly positive contributors for inequality in mental health in the female-headed households were age (34%) and poor household economic status (22%). Socioeconomic inequalities exist in mental health into female-headed households and mental health problems more prevalent in women with lower socioeconomic status.