Activity and stability of a recombinant plasmid-borne TCE degradative pathway in biofilm cultures
The activity and stability of the TCE degradative plasmid TOM31c in the transconjugant host Burkholderia cepacia 17616 was studied in selective and non-selective biofilm cultures. The activity of plasmid TOM31c in biofilm cultures was measured by both TCE degradative studies and the expression of the Tom pathway. Plasmid loss was measured using continuous flow, rotating annular biofilm reactors, and various analytical and microbiological techniques. The probability of plasmid loss in the biofilm cultures was determined using a non-steady-state biofilm plasmid loss model that was derived from a simple mass balance, incorporating results from biofilm growth and plasmid loss studies. The plasmid loss model also utilized Andrew's inhibition growth kinetics and a biofilm detachment term. Results from these biofilm studies were compared to similar studies performed on suspended cultures of Burkholderia cepacia 17616-TOM31c to determine if biofilm growth has a significant effect on either plasmid retention or Tom pathway expression (i.e., TCE degradation rates). Results show that the activity and expression of the Tom pathway measured in biofilm cultures was significantly less than that found in suspended cultures at comparable growth rates. The data obtained from these studies fit the plasmid loss model well, providing plasmid loss probability factors for biofilm cultures that were equivalent to those previously found for suspended cultures. The probability of plasmid loss in the B. cepacia 17616-TOM31c biofilm cultures was equivalent to those found in the suspended cultures. The results indicate that biofilm growth neither helps nor hinders plasmid stability. In both the suspended and the biofilm cultures, plasmid retention and expression could be maintained using selective growth substrates and/or an appropriate plasmid-selective antibiotic. Copyright 1998 John Wiley & Sons, Inc.


Investigation of environmental and host-related risk factors for tuberculosis in Africa. I. Methodological aspects of a combined design.
Host-related and environmental factors for tuberculosis have usually been investigated separately using different study designs. Joint investigation of the genetic, immunologic, and environmental factors at play in susceptibility to tuberculosis represents an innovative goal for obtaining a better understanding of the pathogenesis of the disease. In this paper, the authors describe methods being used to investigate these points in a West African study combining several designs. Patients with newly diagnosed smear-positive cases of tuberculosis are recruited. The effect of host-related factors is assessed by comparing each case with a healthy control from the case's household. The role of environmental factors is estimated by comparing cases with randomly selected community controls. The frequencies of candidate gene variants are compared between cases and community controls, and results are validated through family-based association studies. Members of the households of cases and community controls are being followed prospectively to determine the incidence of "secondary" tuberculosis and to evaluate the influence of geographic and genetic proximity to the index case. This type of design raises important methodological issues that may be useful to consider in studies investigating the natural history of infectious diseases and in attempts to disentangle the effects of environmental and genetic factors in response to infection.


The bimodal quasi-static and dynamic elastance of the murine lung.
The double sigmoidal nature of the mouse pressure-volume (PV) curve is well recognized but largely ignored. This study systematically examined the effect of inflating the mouse lung to 40 cm H2O transrespiratory pressure (Prs) in vivo. Adult BALB/c mice were anesthetized, tracheostomized, and mechanically ventilated. Thoracic gas volume was calculated using plethysmography and electrical stimulation of the intercostal muscles. Lung mechanics were tracked during inflation-deflation maneuvers using a modification of the forced oscillation technique. Inflation beyond 20 cm H2O caused a shift in subsequent PV curves with an increase in slope of the inflation limb and an increase in lung volume at 20 cm H2O. There was an overall decrease in tissue elastance and a fundamental change in its volume dependence. This apparent "softening" of the lung could be recovered by partial degassing of the lung or applying a negative transrespiratory pressure such that lung volume decreased below functional residual capacity. Allowing the lung to spontaneously recover revealed that the lung required approximately 1 h of mechanical ventilation to return to the original state. We propose a number of possible mechanisms for these observations and suggest that they are most likely explained by the unfolding of alveolar septa and the subsequent redistribution of the fluid lining the alveoli at high transrespiratory pressure.


Wafer-scale highly-transparent and superhydrophilic sapphires for high-performance optics.
We reported the wafer-scale highly-transparent and superhydrophilic sapphires with antireflective subwavelength structures (SWSs) which were fabricated by dry etching using thermally dewetted gold (Au) nanomasks. Their optical transmittance properties were experimentally and theoretically investigated. The density, size, and period of the thermally dewetted Au nanopatterns can be controlled by the Au film thickness. For the sapphire with both-side SWSs at 5 nm of Au film, the average total transmittance (T(avg)) of ~96.5% at 350-800 nm was obtained, indicating a higher value than those of the flat sapphire (T(avg)~85.6%) and the sapphire with one-side SWSs (T(avg)~91%), and the less angle-dependent transmittance property was observed. The calculated transmittance results also showed a similar tendency to the measured data. The SWSs enhanced significantly the surface hydrophilicity of sapphires, exhibiting a water contact angle (θ(c)) of < 5° for Au film of 5 nm compared to θ(c)~37° of the flat sapphire.


Urine collection in the emergency department: what really happens in there?
In women with suspected urinary tract infection (UTI), a non-contaminated voided specimen is considered important for valid urinalysis and culture results. We assess whether midstream parted-labia catch (MSPC) instructions were provided by nurses, understood, and performed correctly, according to the patient. We conducted a cross-sectional survey of English- and Spanish-speaking female patients submitting voided urine samples for urinalysis for suspected UTI. The survey was conducted in a public teaching hospital emergency department (ED) from June to December 2010, beginning 2 months after development and dissemination of a nursing MSPC instructions protocol. Research assistants administered the survey within 2 hours of urine collection. Nurses were unaware of the study purpose. Of 129 patients approached, 74 (57%) consented and were included in the analysis. Median age was 35; 44% were Latino. Regarding instructions from nurses, patients reported the following: 45 (61%; 95% CI 50-72%) received any instructions; of whom 37 (82%; 95% CI 71-93%) understood them completely. Sixteen (36%; 95% CI 22-51%) were instructed to collect midstream; and 7 (16%; 95% CI 6-29%) to part the labia. Regardless of receiving or understanding instructions, 33 (45%; 95% CI 33-57%) reported actually collecting midstream, and 11 (15%, 95% CI 8-25%) parting the labia. In this ED, instructions for MSPC urine collection frequently were not given, despite a nursing protocol, and patients rarely performed the essential steps. An evidence-based approach to urine testing in the ED that considers urine collection technique, is needed.


When bias binds: Effect of implicit outgroup bias on ingroup affiliation.
We tested a novel process we term implicit homophily in which perceivers' implicit outgroup bias shapes their affiliative responses toward ingroup targets with outgroup friends as a function of perceived similarity. Across 4 studies, we tested implicit homophily in the context of racial groups. We found that White participants with higher implicit anti-Black bias reported less affiliative responses toward White targets with Black friends compared with White targets with White friends, and this effect persisted above and beyond the effects of implicit pro-White bias and explicit racial bias (Studies 1-3). We further found evidence that this relationship between implicit anti-Black bias and affiliation exists because participants infer how comfortable targets are around outgroup members (Preliminary Study) and use this information to infer similarity on this dimension (Studies 1-3). Our findings also suggested that stigma transference and expectancy violation were not viable alternative mediators (Preliminary Study and Study 1). Finally, women's implicit anti-Black bias predicted their likelihood of having Facebook friends with Black friends, providing ecological and behavioral evidence of implicit homophily (Study 4). Implications for research on stigma by association, extended contact, affiliation, and network formation are discussed.


Head-to-head comparison of second-generation nucleic acid amplification tests for detection of Chlamydia trachomatis and Neisseria gonorrhoeae on urine samples from female subjects and self-collected vaginal swabs.
In a comparison of 4 second-generation nucleic acid amplification tests performed with self-collected vaginal swab (SCVS) and first-void urine (FVU) specimens from 575 women, SCVS specimens indicated more infections than did FVU specimens in all assays. The prevalence rates were 9% (53/575 patients) for Chlamydia trachomatis and 2% (11/575 patients) for Neisseria gonorrhoeae. The clinical sensitivities for testing SCVS specimens for C. trachomatis were 98.1% on a Tigris system and 96.2% on a Panther system for the Aptima Combo 2 assay (Hologic Gen-Probe), 98.0% for the RealTime CT/NG assay on an m2000 instrument (Abbott), 90.6% for the ProbeTec CT/GC Q(x) assay on the Viper system (Becton Dickinson), and 84.6% for the cobas CT/NG assay on the cobas 4800 platform (Roche). Clinical sensitivities for C. trachomatis in FVU specimens were 88.7% (Tigris) and 88.0% (Panther) for the Aptima Combo 2 assay, 76.9% for the RealTime CT/NG assay, 75.5% for the ProbeTec CT/GC Q(x) assay, and 81.1% for the cobas CT/NG assay. Clinical sensitivities of the assays for N. gonorrhoeae, with limited positive results, ranged from 63.6% to 100%. Specificities for both infections ranged from 98.4 to 100%. Differences in analytical sensitivities and levels of molecular targets in clinical samples but not inhibitors of amplification may explain the differences in clinical sensitivities.


Achromatic diffractive lens written onto a liquid crystal display.
We propose a programmable diffractive lens written onto a liquid crystal display (LCD) that is able to provide equal focal lengths for several wavelengths simultaneously. To achieve this goal it is necessary that the LCD operate in the phase-only regime simultaneously for the different wavelengths. We design the appropriate lens for each wavelength, and then the lenses are spatially multiplexed onto the LCD. Various multiplexing schemes have been analyzed, and the random scheme shows the best performance. We further show the possibility of finely tuning the chromaticity of the focal spot by changing the relative weights of the multiplexing among the various wavelengths.


Efficacy of cetuximab in the treatment of Menetrier's disease.
Ménétrier's disease is a rare premalignant disorder of the stomach with no proven effective medical therapy. Increased epidermal growth factor receptor signaling has been implicated in the pathogenesis of Ménétrier's disease. We conducted a single-arm clinical trial with cetuximab, a monoclonal antibody that blocks epidermal growth factor receptor signaling, in nine individuals with clinically and histologically documented severe Ménétrier's disease that impaired quality of life to the extent that gastrectomy was being considered. Of the seven patients who completed the 1-month course of treatment, all showed statistically significant improvement both clinically (quality-of-life indices) and biochemically (increased parietal cell mass and gastric acidity). Furthermore, all seven patients who completed the 1-month trial elected to continue treatment, and four subsequently showed near-complete histological remission. Cetuximab should be considered as first-line therapy for Ménétrier's disease.


Capturing the Freeze-Drying Dynamics of NaCl Nanoparticles Using THz Spectroscopy.
Sodium chloride (NaCl) aqueous solution becomes NaCl hydrate, NaCl·2H2O, at low temperature, which is different from potassium chloride and is a typical complex model for studying the freeze-drying process in foods and pharmaceuticals. Here, we detected unit-cell-sized NaCl particles in ice as precursor substances of NaCl·2H2O during freezing of NaCl solution by using terahertz (THz) spectroscopy. In the freezing process, Na+ and Cl- ions form two types of metastable unit-cell-sized NaCl particles on the pathway to the well-known NaCl·2H2O crystal production, which are not listed in the phase diagram of freezing of NaCl solution but have absorption peaks in THz spectra. This finding of single unit-cell-sized particles signifies the importance of studying the freeze-drying process in-depth and offers a new possibility for the development of freeze-drying technology for the manufacture of nanometer-sized particles such as ultrafine pharmaceutical powders, which more readily dissolve in water.


Glycan microarray reveal induced IgGs repertoire shift against a dietary carbohydrate in response to rabbit anti-human thymocyte therapy.
Humans have circulating antibodies against diverse glycans containing N-glycolylneuraminic acid (Neu5Gc) due to function-loss mutation of the CMAH gene. This xenogenic non-human carbohydrate is abundant in red meat, xenografts and biotherapeutics. Low levels of diet-derived Neu5Gc is also present on normal human endothelial cells, and together with anti-Neu5Gc antibodies could potentially mediate "xenosialitis" chronic-inflammation. Rabbit anti-human thymocyte globulin (ATG) is a drug containing polyclonal IgG glycoproteins commonly used as an immunosuppressant in human transplantation and autoimmune diseases. In type-1 diabetes patients, infusion of Neu5Gc-glycosylated ATG caused increased global anti-Neu5Gc response. Here, for the first time we explore changes in anti-Neu5Gc IgG repertoire following the immunization elicited by ATG, compared with the basal antibodies repertoire that reflect exposure to dietary-Neu5Gc. We used glycan microarrays with multiple Neu5Gc-glycans and controls to elucidate eventual differences in ATG-elicited repertoire, before/after ATG administration and track their kinetics (0, 1, 18 and 24 months). Response of all basal-pre-existing Neu5Gc-specific antibodies rapidly increased. This response peaked at one month post-ATG, with enhanced affinity, then resolved at 18-24 months. Induced-antibodies showed expanded diversity and de-novo recognition of different Neu5Gc-glycans, including endogenous glycolipids, that was further validated by affinity-purified anti-Neu5Gc antibodies from patients' sera. These findings strongly suggest that ATG-induced anti-Neu5Gc IgGs represent a secondary exposure to this dietary carbohydrate-antigen in humans, with immune memory. Given their modified recognition patterns, ATG-evoked anti-Neu5Gc antibodies could potentially mediate biological effects different from pre-existing antibodies.


Perforated peptic ulcer in children: a 20-year experience.
Although the detection of pediatric peptic ulcer disease (PUD) has recently been increasing, perforated peptic ulcer (PPU) in children is rare. We report our experience with PPU in children. The charts of children diagnosed with PPU at our hospital from January 1986 to June 2005 were reviewed. Data were obtained on demographics, coexisting clinical events, perforation sites, delay in surgery, operative findings and methods, and outcomes. The data were analyzed using the chi2, Student t test, and multivariate logistic regression for possible risk factors. There were 42 male and 10 female patients aged 2 to 18 years (mean, 14.2 years) included in the study. Forty-seven patients were adolescents (90%). Eight patients had coexisting clinical events before PPU. All of the patients manifested acute abdominal pain. Forty-nine patients (94.2%) had peritoneal signs. Radiography showed subdiaphragmatic free air in 43 patients (82.7%); this was the most important tool for establishing diagnosis. Nine patients (17.3%) had postoperative complications. Two patients died (3.8%). Univariate analysis showed that poor outcome was significantly associated with female sex, more coexisting clinical events, no evidence of chronic ulcer, and treatment by simple suture (P < 0.05). Only female sex and simple suture remained statistically significant in multivariate analysis. Although delay in surgery (>12 hours) was not significantly related to complications, there was a greater tendency toward the development of complications. PPU should be suspected in adolescents who manifest acute abdominal pain and have peritoneal signs. Children with PPU have a more favorable outcome than adults.


Enhanced electromechanical response of ferroelectrics due to charged domain walls.
While commonly used piezoelectric materials contain lead, non-hazardous, high-performance piezoelectrics are yet to be discovered. Charged domain walls in ferroelectrics are considered inactive with regards to the piezoelectric response and, therefore, are largely ignored in this search. Here we demonstrate a mechanism that leads to a strong enhancement of the dielectric and piezoelectric properties in ferroelectrics with increasing density of charged domain walls. We show that an incomplete compensation of bound polarization charge at these walls creates a stable built-in depolarizing field across each domain leading to increased electromechanical response. Our model clarifies a long-standing unexplained effect of domain wall density on macroscopic properties of domain-engineered ferroelectrics. We show that non-toxic ferroelectrics like BaTiO(3) with dense patterns of charged domain walls are expected to have strongly enhanced piezoelectric properties, thus suggesting a new route to high-performance, lead-free ferroelectrics.


Lycopene and Risk of Prostate Cancer: A Systematic Review and Meta-Analysis.
Prostate cancer (PCa) is a common illness for aging males. Lycopene has been identified as an antioxidant agent with potential anticancer properties. Studies investigating the relation between lycopene and PCa risk have produced inconsistent results. This study aims to determine dietary lycopene consumption/circulating concentration and any potential dose-response associations with the risk of PCa. Eligible studies published in English up to April 10, 2014, were searched and identified from Pubmed, Sciencedirect Online, Wiley online library databases and hand searching. The STATA (version 12.0) was applied to process the dose-response meta-analysis. Random effects models were used to calculate pooled relative risks (RRs) and 95% confidence intervals (CIs) and to incorporate variation between studies. The linear and nonlinear dose-response relations were evaluated with data from categories of lycopene consumption/circulating concentrations. Twenty-six studies were included with 17,517 cases of PCa reported from 563,299 participants. Although inverse association between lycopene consumption and PCa risk was not found in all studies, there was a trend that with higher lycopene intake, there was reduced incidence of PCa (P = 0.078). Removal of one Chinese study in sensitivity analysis, or recalculation using data from only high-quality studies for subgroup analysis, indicated that higher lycopene consumption significantly lowered PCa risk. Furthermore, our dose-response meta-analysis demonstrated that higher lycopene consumption was linearly associated with a reduced risk of PCa with a threshold between 9 and 21 mg/day. Consistently, higher circulating lycopene levels significantly reduced the risk of PCa. Interestingly, the concentration of circulating lycopene between 2.17 and 85 μg/dL was linearly inversed with PCa risk whereas there was no linear association >85 μg/dL. In addition, greater efficacy for the circulating lycopene concentration on preventing PCa was found for studies with high quality, follow-up >10 years and where results were adjusted by the age or the body mass index. In conclusion, our novel data demonstrates that higher lycopene consumption/circulating concentration is associated with a lower risk of PCa. However, further studies are required to determine the mechanism by which lycopene reduces the risk of PCa and if there are other factors in tomato products that might potentially decrease PCa risk and progression.


Association of the TNF-alpha-308 (G-->A) polymorphism with self-reported history of childhood asthma.
Asthma is a complex disease involving genetic and environmental aetiology. The tumour necrosis factor-alpha (TNF-alpha) and angiotensin-converting enzyme (ACE) genes have been implicated in asthma pathogenesis. This study investigated the association of a G-308A variant of TNF-alpha and an insertion/deletion (I/D) variant of ACE with a self-reported history of childhood asthma, in two population groups. At Northwick Park Hospital, London, 1,811 pregnant women attending for antenatal care were recruited. Participants with a self-reported history of childhood asthma, determined by a researcher-administered questionnaire, and controls with no personal or family history of asthma, of UK/Irish (cases n=20; controls n=416) and South Asian (cases n=6; controls n=275) origin were used in this study. Participants were genotyped for the TNF-alpha-308 and ACE I/D variants by a PCR-RFLP and PCR approach. The TNF-alpha-308 allele 2 (-308A) was significantly associated with self-reported childhood asthma in the UK/Irish (Odds ratios (OR): 2.6; 95% confidence intervals (CI): 1.1-6.2; P=0.03) but not in the South Asian population. The ACE DD genotype was not associated with childhood asthma in either population group. Gametic phase disequilibrium between the TNF-alpha-308 and ACE I/D variants was significantly different from zero in UK/Irish cases (delta=0.09; P=0.034). The TNF-alpha308 allele 2 or a linked major histocompatibility complex (MHC) variant may be a genetic risk factor for childhood asthma in the UK/Irish sample.


Novel three-color FRET tool box for advanced protein and DNA analysis.
We report on a new three-color FRET system which we were able to verify in peptides as well as in synthetic DNA. All three chromophores could be introduced by a building block approach avoiding postsynthetic labeling. Additional features are robustness, matching spectroscopic properties, high-energy transfer, and sensitivity. The system was investigated in detail on a set of peptides as well as an array of tailored oligonucleotides. The detailed analysis of the experimental data and comparison with theoretical considerations were in excellent agreement. It is shown that in the case of polypeptides specific interaction with the fluorescence probes has to be considered. In contrast with DNA, the fluorescence probes did not show any indications of such interactions. The novel three-color FRET toolbox revealed the potential for applications studying fundamental processes of three interacting molecules in life science applications.


Activation of a 66-kilodalton human endothelial cell matrix metalloprotease by Streptococcus pyogenes extracellular cysteine protease.
Human umbilical vein endothelial cells (HUVECs) were used to gain insight into the molecular mechanism whereby the major extracellular protease from group A streptococci damages host tissue. HUVECs exposed to streptococcal cysteine protease (SCP) for various times exhibited cytopathic effect and cell detachment from the culture vessel. Gelatin substrate zymography showed that a time- and concentration-dependent increase in the level of activity of an approximately 66-kDa gelatinase occurred in culture medium taken from cells exposed to enzymatically active SCP. This gelatinase comigrated in gelatin zymograms with the activated form of purified recombinant matrix metalloprotease 2 (MMP-2) and had type IV collagenase activity. In contrast, medium taken from cells exposed to inactivated (boiled) SCP and cells exposed to SCP inhibited by treatment with N-benzyloxycarbonyl-leucyl-valyl-glycine diazomethyl ketone lacked the 66-kDa gelatinase. Appearance of the 66-kDa gelatinase activity was also prevented by 1,10-phenanthroline, a zinc chelator and MMP inhibitor. Inasmuch as proteolytically active SCP is required for the emergence of this gelatinase and MMP activation occurs by proteolytic processing, the 66-kDa gelatinase may be a proteolytic cleavage product of a latent MMP expressed extracellularly by HUVECs. Direct SCP treatment of culture supernatant taken from HUVECs not exposed to SCP also produced the 66-kDa gelatinase. The data show that SCP activates an MMP produced by human endothelial cells, a process that may contribute to endothelial cell damage, tissue destruction, and hemodynamic derangement observed in some patients with severe, invasive group A streptococcal infection.


Promotion of natural tooth repair by small molecule GSK3 antagonists.
The restoration of dentine lost in deep caries lesions in teeth is a routine and common treatment that involves the use of inorganic cements based on calcium or silicon-based mineral aggregates. Such cements remain in the tooth and fail to degrade and thus normal mineral volume is never completely restored. Here we describe a novel, biological approach to dentine restoration that stimulates the natural formation of reparative dentine via the mobilisation of resident stem cells in the tooth pulp. Biodegradable, clinically-approved collagen sponges are used to deliver low doses of small molecule glycogen synthase kinase (GSK-3) antagonists that promote the natural processes of reparative dentine formation to completely restore dentine. Since the carrier sponge is degraded over time, dentine replaces the degraded sponge leading to a complete, effective natural repair. This simple, rapid natural tooth repair process could thus potentially provide a new approach to clinical tooth restoration.


Developing the science and methods of community engagement for genomic research and biobanking in Africa.
Historically, community engagement (CE) in research has been implemented in the fields of public health, education and agricultural development. In recent years, international discussions on the ethical and practical goals of CE have been extended to human genomic research and biobanking, particularly in the African context. While there is some consensus on the goals and value of CE generally, questions remain about the effectiveness of CE practices and how to evaluate this. Under the auspices of the Human Heredity and Health in Africa Initiative (H3Africa), the H3Africa CE working group organized a workshop in Stellenbosch, South Africa in March 2016 to explore the extent to which communities should be involved in genomic research and biobanking and to examine various methods of evaluating the effectiveness of CE. In this paper, we present the key themes that emerged from the workshop and make a case for the development of a rigorous application, evaluation and learning around approaches for CE that promote a more systematic process of engaging relevant communities. We highlight the key ways in which CE should be embedded into genomic research and biobanking projects.


Postnatal deletion of Numb/Numblike reveals repair and remodeling capacity in the subventricular neurogenic niche.
Neural stem cells are retained in the postnatal subventricular zone (SVZ), a specialized neurogenic niche with unique cytoarchitecture and cell-cell contacts. Although the SVZ stem cells continuously regenerate, how they and the niche respond to local changes is unclear. Here we generated nestin-creER(tm) transgenic mice with inducible Cre recombinase in the SVZ and removed Numb/Numblike, key regulators of embryonic neurogenesis from postnatal SVZ progenitors and ependymal cells. This resulted in severe damage to brain lateral ventricle integrity and identified roles for Numb/Numblike in regulating ependymal wall integrity and SVZ neuroblast survival. Surprisingly, the ventricular damage was eventually repaired: SVZ reconstitution and ventricular wall remodeling were mediated by progenitors that escaped Numb deletion. Our results show a self-repair mechanism in the mammalian brain and may have implications for both niche plasticity in other areas of stem cell biology and the therapeutic use of neural stem cells in neurodegenerative diseases.


Dilated cardiomyopathy and impaired cardiac hypertrophic response to angiotensin II in mice lacking FGF-2.
FGF-2 has been implicated in the cardiac response to hypertrophic stimuli. Angiotensin II (Ang II) contributes to maintain elevated blood pressure in hypertensive individuals and exerts direct trophic effects on cardiac cells. However, the role of FGF-2 in Ang II-induced cardiac hypertrophy has not been established. Therefore, mice deficient in FGF-2 expression were studied using a model of Ang II-dependent hypertension and cardiac hypertrophy. Echocardiographic measurements show the presence of dilated cardiomyopathy in normotensive mice lacking FGF-2. Moreover, hypertensive mice without FGF-2 developed no compensatory cardiac hypertrophy. In wild-type mice, hypertrophy was associated with a stimulation of the c-Jun N-terminal kinase, the extracellular signal regulated kinase, and the p38 kinase pathways. In contrast, mitogen-activated protein kinase (MAPK) activation was markedly attenuated in FGF-2-deficient mice. In vitro, FGF-2 of fibroblast origin was demonstrated to be essential in the paracrine stimulation of MAPK activation in cardiomyocytes. Indeed, fibroblasts lacking FGF-2 expression have a defective capacity for releasing growth factors to induce hypertrophic responses in cardiomyocytes. Therefore, these results identify the cardiac fibroblast population as a primary integrator of hypertrophic stimuli in the heart, and suggest that FGF-2 is a crucial mediator of cardiac hypertrophy via autocrine/paracrine actions on cardiac cells.


Homeotic genes have specific functional roles in the establishment of the Drosophila embryonic peripheral nervous system.
The Drosophila embryonic peripheral nervous system (PNS) contains segment-specific spatial patterns of sensory organs which derive from the ectoderm. Many studies have established that the homeotic genes of Drosophila control segment specific characteristics of the epidermis, and more recently these genes have also been shown to control gut morphogenesis through their expression in the visceral mesoderm (Tremml, G. and Bienz, M. (1989), EMBO J. 8, 2677-2685). We report here the roles of homeotic genes in establishing the spatial patterns of sensory organs in the embryonic PNS. The PNS was examined in embryos homozygous for mutations in the homeotic genes Sex combs reduced (Scr), Antennapedia (Antp), Ultrabithorax (Ubx), abdominal-A (abd-A) and Abdominal-B (Abd-B) with antibodies that label specific subsets of sensory organs. Our results suggest that the homeotic genes have specific roles in establishing the correct spatial patterns of sensory organs in their normal domains of expression. In addition, we also report the effects of ectopic expression of the homeotic genes labial (lab), Deformed (Dfd), Scr, Antp or Ubx on the normal development of sensory organs in the embryonic PNS. Interestingly, while previous studies have concluded that ectopic expression of the homeotic genes Dfd, Scr and Antp has no effect on the segmental identity of the abdominal segments, our results demonstrate that this is not true. We show that ectopic expression of these genes does result in the disruption of the developing PNS in the abdomen. Our results are suggestive of a role for the homeotic gene products in regulating genes which are necessary for generating sensory progenitor cells in the developing PNS.


Cellular and molecular effects of metronomic vinorelbine and 4-O-deacetylvinorelbine on human umbilical vein endothelial cells.
Metronomic oral vinorelbine (VRL; Navelbine) was shown in clinical trials to yield sustainable antitumor activity possibly through antiangiogenic mechanisms. We investigated the effects of protracted low-dose VRL on human umbilical vein endothelial cells, compared with a conventional chemotherapy model. Human umbilical vein endothelial cell cultures were treated with different concentrations of VRL (0.001 nmol/l to 1 mmol/l) for 4, 24 and 96 h. The effects of different drug concentrations on cell growth, cell cycle, apoptosis and expression of the angiogenesis-modulating genes interleukin-8, cyclooxygenase-2, CD36 and peroxisome proliferator-activated receptor γ were assessed using the metronomic or conventional chemotherapy model. Apoptosis and cell-cycle effects were assessed by flow cytometry. Gene expression was measured at the transcript level by quantitative reverse transcriptase-PCR, protein expression by immunoblotting and levels of proteins secreted in the cell medium by enzyme-linked immunosorbent assay. Activation of the nuclear factor-κB pathway was investigated by immunoblot analysis of cytosolic and nuclear protein extracts. The half-maximal inhibitory concentrations (IC50) of VRL at 96 h were four orders lower compared with those after a 24-h exposure (1.23 nmol/l vs. 32 mmol/l for VRL). Drug concentrations at high nanomolar levels and above, which are relevant to conventional pulsatile dosing of VRL, induced a dose-dependent and nuclear factor-κB-related increase in proangiogenic interleukin-8 and cyclooxygenase-2 and a decrease in the thrombospondin-1 receptor CD36 and peroxisome proliferator-activated receptor γ at mRNA and protein levels. In contrast, the opposite was evident with protracted picomolar to low nanomolar concentrations (metronomic dosing). Our data provide experimental support for metronomic VRL by showing that a protracted low dose outperforms pulsed high-dose administration in inducing antiangiogenic effects in proliferating human endothelial cells.


Distance distributions in proteins recovered by using frequency-domain fluorometry. Applications to troponin I and its complex with troponin C.
We used resonance energy transfer to examine the distribution of distances between two sites on troponin I (TnI). The donor (D) was the single tryptophan residue at site 158 (Trp 158), and the acceptor (A) was cysteine 133 (Cys 133) which was labeled with N-(iodoacetyl)-N'-(1-sulfo-5-naphthyl)ethylenediamine (IE). A distribution of D-A distances results in a distribution of donor decay times, which were resolved by using frequency-domain fluorometry. In the native state we recovered a relatively narrow distribution of D-A distances. The widths of the distance distributions were found to increase progressively and dramatically with increasing concentrations of guanidine hydrochloride. Binding of calcium-free troponin C (TnC) to troponin I did not alter the distance distribution. Addition of Ca2+ to the TnI.TnC complex resulted in a sharper distance distribution and protected against the guanidine hydrochloride induced increase in the width of the distance distribution. Additionally, the same distance distributions were recovered for native and denatured TnI when the Forster distance for energy transfer was decreased by acrylamide quenching. These results demonstrate that distance distributions can be recovered with good accuracy, to the extent of revealing modest changes due to binding of other components. This technique should have widespread applications in studies of protein folding.


Lumiracoxib for acute postoperative dental pain: a systematic review of randomized clinical trials.
Lumiracoxib is an anti-inflammatory drug that has been used to treat acute dental pain, mainly in postsurgical settings, in which the greatest levels of pain and discomfort are experienced during the first 24 hours. This study aimed to assess the efficacy and safety of lumiracoxib for treating acute postsurgical dental pain. Systematic review developed at the Brazilian Cochrane Centre, Universidade Federal de São Paulo. An electronic search was conducted in the PubMed, Cochrane Library, Lilacs (Literatura Latino-Americana e do Caribe em Ciências da Saúde), SciELO (Scientific Electronic Library Online) and Embase databases. A manual search was also performed. Only randomized controlled trials were included, and these were selected and assessed by two researchers with regard to the risk of bias. Three clinical trials with 921 participants were included. Lumiracoxib 400 mg produced onset of analgesia in a shorter time than shown by lumiracoxib 100 mg, celecoxib 200 mg and ibuprofen 400 mg. There was no difference between lumiracoxib 400 mg and rofecoxib 50 mg. In two studies, the mean time taken to attain onset of analgesia for the placebo was not estimated because the number of participants who reached onset was too small. There is evidence with a moderate risk of bias that recommends the use of lumiracoxib for acute postoperative dental pain. However, the adverse effects are not completely known. Given that lumiracoxib is currently available in only three countries, further studies are likely to be rare and discouraged.


Symbiotic specificity, association patterns, and function determine community responses to global changes: defining critical research areas for coral-Symbiodinium symbioses.
Climate change-driven stressors threaten the persistence of coral reefs worldwide. Symbiotic relationships between scleractinian corals and photosynthetic endosymbionts (genus Symbiodinium) are the foundation of reef ecosystems, and these associations are differentially impacted by stress. Here, we couple empirical data from the coral reefs of Moorea, French Polynesia, and a network theoretic modeling approach to evaluate how patterns in coral-Symbiodinium associations influence community stability under climate change. To introduce the effect of climate perturbations, we simulate local 'extinctions' that represent either the loss of coral species or the ability to engage in symbiotic interactions. Community stability is measured by determining the duration and number of species that persist through the simulated extinctions. Our results suggest that four factors greatly increase coral-Symbiodinium community stability in response to global changes: (i) the survival of generalist hosts and symbionts maximizes potential symbiotic unions; (ii) elevated symbiont diversity provides redundant or complementary symbiotic functions; (iii) compatible symbiotic assemblages create the potential for local recolonization; and (iv) the persistence of certain traits associate with symbiotic diversity and redundancy. Symbiodinium may facilitate coral persistence through novel environmental regimes, but this capacity is mediated by symbiotic specificity, association patterns, and the functional performance of the symbionts. Our model-based approach identifies general trends and testable hypotheses in coral-Symbiodinium community responses. Future studies should consider similar methods when community size and/or environmental complexity preclude experimental approaches.


Sexuality and gender role in autism spectrum disorder: a case control study.
The 'extreme male brain theory of autism' describes an extreme male pattern of cognitive traits defined as strong systemising abilities paired with empathising weaknesses in autism spectrum disorder. However, beyond these cognitive traits, clinical observations have suggested an ambiguous gender-typed pattern regarding several sexually dimorphic traits. The aim of the present study was to investigate if patterns of non-cognitive sexually dimorphic traits differed between the autism spectrum disorder and control groups. Fifty adults with autism spectrum disorder and intelligence within the normal range, and 53 neurotypical controls responded to questions on gender role, self-perceived gender typicality and gender identity, as well as sexuality. Measures used were a Swedish modification of the Bem Sex Role Inventory and questions on sexuality and gender designed for the purpose of this study. Our results showed that one common gender role emerged in the autism spectrum disorder group. Masculinity (e.g. assertiveness, leadership and competitiveness) was weaker in the autism spectrum disorder group than in the controls, across men and women. Self-perceived gender typicality did not differ between the groups but tomboyism and bisexuality were overrepresented amongst women with autism spectrum disorder. Lower libido was reported amongst both male and female participants with autism spectrum disorder compared with controls. We conclude that the extreme male patterns of cognitive functions in the autistic brain do not seem to extend to gender role and sexuality. A gender-atypical pattern for these types of characteristics is suggested in autism spectrum disorder.


Morphogen Signals Shaping the Gastric Glands in Health and Disease.
The adult gastric mucosa is characterised by deep invaginations of the epithelium called glands. These tissue architectural elements are maintained with the contribution of morphogen signals. Morphogens are expressed in specific areas of the tissue, and their diffusion generates gradients in the microenvironment. Cells at different positions in the gland sense a specific combination of signals that instruct them to differentiate, proliferate, regenerate, or migrate. Differentiated cells perform specific functions involved in digestion, such as the production of protective mucus and the secretion of digestive enzymes or gastric acid. Biopsies from gastric precancerous conditions usually display tissue aberrations and change the shape of the glands. Alteration of the morphogen signalling microenvironment is likely to underlie those conditions. Furthermore, genes involved in morphogen signalling pathways are found to be frequently mutated in gastric cancer. We summarise the most recent findings regarding alterations of morphogen signalling during gastric carcinogenesis, and we highlight the new stem cell technologies that are improving our understanding of the regulation of human tissue shape.


Presence of growth/differentiation factor-15 cytokine in human follicular fluid, granulosa cells, and oocytes.
The purpose of the study was to determine whether the GDF-15 is present in follicular fluid; to evaluate if there is a relation between follicular and serum levels of GDF-15 and fertility status of study subjects; and to test whether granulosa cells, oocytes, or both produce GDF-15. This study used follicular fluid (FF, serum, and oocytes obtained under informed consent from women undergoing oocyte retrieval for in vitro fertilization. It also used ovaries from deceased preterm newborns. Collection of FF and blood at the time of oocyte retrieval, ELISA and western blot were performed to determine levels and forms of GDF-15. Concentrations of GDF-15 in FF and serum, its expression in ovarian tissue, and secretion from granulosa cells were analyzed. GDF-15 concentration in FF ranged from 35 to 572 ng/ml, as determined by ELISA. Western blot analysis revealed the GDF-15 pro-dimer only in FF. Both normal healthy and cancerous granulosa cells secreted GDF-15 into culture media. Primary oocytes displayed cytoplasmic GDF-15 positivity in immunostained newborn ovaries, and its expression was also observed in fully grown human oocytes. To the best of our knowledge, this is the first documentation of cytokine GDF-15 presence in follicular fluid. Its concentration was not associated with donor/patient fertility status. Our data also show that GDF-15 is expressed and inducible in both normal healthy and cancerous granulosa cells, as well as in oocytes.


Evaluation of PAPNET testing as an ancillary tool to clarify the status of the "atypical" cervical smear.
To assess the utility of the PAPNET system (Neuromedical Systems Inc., Suffern, NY) in clarifying the status of cervical smears showing borderline abnormalities, we analyzed the results of five cytotechnologists who reclassified 200 "atypical" smears by evaluating PAPNET images only. The interobserver agreement (reliability) of the PAPNET reviewers was computed, and their readings were compared with three standards: the consensus diagnosis of five pathologists who used light microscopy, the detection of cancer-associated human papillomavirus DNA by Southern analysis, and the correlation with diagnoses of biopsy specimens obtained during passive follow-up. The PAPNET reviewers classified 18 to 65% of cases as normal, 25 to 42% as equivocal, and 10 to 55% as abnormal. Unanimous interobserver agreement was achieved in only 24 (13%) cases. Four of the five PAPNET reviewers agreed moderately well with the results of the pathology reference panel. In four of the five PAPNET reviews, classification of cases as abnormal was strongly correlated with the detection of cancer-associated types of human papillomavirus. Consensus PAPNET results of abnormal were predictive of abnormal histologic findings at follow-up. Theoretically, if colposcopy had been performed on all of the women with equivocal or abnormal PAPNET results (based on the consensus of the panel), as much as 95% of biopsy-confirmed lesions could have been detected, but 79% of women would have been referred. Restriction of colposcopy referral to women with definitely abnormal PAPNET readings would have reduced referrals to 31%, but the sensitivity of the triage would have dropped to 51% of biopsy-confirmed lesions.


Antisocial burnout: an exploratory study.
The more flagrant aspects of Antisocial Personality Disorder (APD), particularly criminality, are thought to diminish or "burnout" after age 30. However, empirical evidence of burnout in clinically defined groups is lacking. This study explores burnout in a cohort of forensic psychiatric patients, aged 41 to 67, with clinically diagnosed DSM-III APD (N = 39). Conviction data revealed that criminality did appear to decline from age 27 onward, but not in a straightforward manner. Further, a significant portion of the cohort remained criminally active throughout most of their adult lives. Age did not appear to interact with crime class.


Are the neuroprotective effects of exercise training systemically mediated?
To date there is no cure available for dementia, and the field calls for novel therapeutic targets. A rapidly growing body of literature suggests that regular endurance training and high cardiorespiratory fitness attenuate cognitive impairment and reduce dementia risk. Such benefits have recently been linked to systemic neurotrophic factors induced by exercise. These circulating biomolecules may cross the blood-brain barrier and potentially protect against neurodegenerative disorders such as Alzheimer's disease. Identifying exercise-induced systemic neurotrophic factors with beneficial effects on the brain may lead to novel molecular targets for maintaining cognitive function and preventing neurodegeneration. Here we review the recent literature on potential systemic mediators of neuroprotection induced by exercise. We focus on the body of translational research in the field, integrating knowledge from the molecular level, animal models, clinical and epidemiological studies. Taken together, the current literature provides initial evidence that exercise-induced, blood-borne biomolecules, such as BDNF and FNDC5/irisin, may be powerful agents mediating the benefits of exercise on cognitive function and may form the basis for new therapeutic strategies to better prevent and treat dementia.


Ecophysiology of photosynthesis in macroalgae.
Macroalgae occur in the marine benthos from the upper intertidal to depths of more than 200 m, contributing up to 1 Pg C per year to global primary productivity. Freshwater macroalgae are mainly green (Chlorophyta) with some red (Rhodophyta) and a small contribution of brown (Phaeophyceae) algae, while in the ocean all three higher taxa are important. Attempts to relate the depth distribution of three higher taxa of marine macroalgae to their photosynthetic light use through their pigmentation in relation to variations in spectral quality of photosynthetically active radiation (PAR) with depth (complementary chromatic adaptation) and optical thickness (package effect) have been relatively unsuccessful. The presence (Chlorophyta, Phaeophyceae) or absence (Rhodophyta) of a xanthophyll cycle is also not well correlated with depth distribution of marine algae. The relative absence of freshwater brown algae does not seem to be related to their photosynthetic light use. Photosynthetic inorganic carbon acquisition in some red and a few green macroalgae involves entry of CO(2) by diffusion. Other red and green macroalgae, and brown macroalgae, have CO(2) concentrating mechanisms; these frequently involve acid and alkaline zones on the surface of the alga with CO(2) (produced from HCO(3) (-)) entering in the acid zones, while some macroalgae have CCMs based on active influx of HCO(3) (-). These various mechanisms of carbon acquisition have different responses to the thickness of the diffusion boundary layer, which is determined by macroalgal morphology and water velocity. Energetic predictions that macroalgae growing at or near the lower limit of PAR for growth should rely on diffusive CO(2) entry without acid and alkaline zones, and on NH(4) (+) rather than NO(3) (-) as nitrogen source, are only partially borne out by observation. The impact of global environmental change on marine macroalgae mainly relates to ocean acidification and warming with shoaling of the thermocline and decreased nutrient flux to the upper mixed layer. Predictions of the impact on macroalgae requires further experiments on interactions among increased inorganic carbon, increased temperature and decreased nitrogen and phosphorus supply, and, when possible, studies of genetic adaptation to environmental change.


Men's experiences of having osteoporosis vertebral fractures: a qualitative study using interpretative phenomenological analyses.
Men and women with vertebral fractures due to osteoporosis are treated differently by society and health care professionals. This can lead to inequalities in health care and affects how men with fractures view themselves as people. We need to raise awareness that men get these fractures as well as women. There is a lack of research exploring the experience of osteoporosis from the male perspective. This study was undertaken to explore and describe the experiences of men with vertebral fractures due to osteoporosis, including their perceptions of diagnosis, treatment and changes in their sense of self. The study consists of in-depth semi-structured interviews with nine male participants of the PROVE (Physiotherapy Rehabilitation for Osteoporotic Vertebral Fracture) study. Interviews were digitally audio recorded and fully transcribed. Data were coded in accordance with an interpretative phenomenological analysis approach to analyses. Three main themes are presented. (i) Osteoporosis is considered an old women's disease. (ii) Men are diagnosed and treated differently than women in the NHS. Health care inequalities exist. (iii) Changes in self can occur in men after vertebral fracture/s due to osteoporosis. Greater awareness that men get this condition is needed in both society in general and also by health care professionals who often do not expect osteoporosis to affect men. Approaches to diagnosis and treatment need to be considered and improved to ensure that they become appropriate and effective for men as well as women.


Development of New Experimental Dentifrice of Peruvian Solanum tuberosum (Tocosh) Fermented by Water Stress: Antibacterial and Cytotoxic Activity.
"Tocosh" is a potato that has undergone a process of hydraulic oxidation that enhances its antimicrobial properties so that this natural resource can be used in medical sciences. The aim of this study was to develop and evaluate the antibacterial and cytotoxic activity of a new experimental tooth based on Solanum tuberosum "Tocosh" on the cell lines 3T3 and DU145. To evaluate the cytotoxicity, cell cultures 3T3 and DU145 were used. Cell viability was determined by the MTT assay (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) in a medium containing 10% calf serum where the cells were preincubated at a concentration of 1 × 106 cells/mL in culture medium for 3 hours at 37°C and 6.5% CO2. Then, the absorbance was measured using a microplate reader where the formazan crystals were diluted with acidic and cold isopropanol, and quantified in an ELISA reader. To evaluate the antibacterial effect, the Kirby Bauer inhibition halos method was used on strains of S. aureus (ATCC 25923), S. mutans (ATCC 25175), and S. mitis (ATCC 49456). Solanum tuberosum (tocosh) was not cytotoxic because it only had one CC50 at the concentration of 0.26927 mg/mL and 0.26845 mg/mL for the cell lines 3T3 and DU145, respectively. Tocosh toothpaste (TD) has an antibacterial effect against S. aureus and S. mutans. The new ecological dentifrice was not cytotoxic since it did not alter cell viability because its CC50 was only 0.268 and 0.269 μg/mL for the 3T3 and DU145 cell lines, respectively; however, it presented an optimal antimicrobial activity against the oral strains evaluated. This research has great potential for clinical use because this new dentifrice has antimicrobial activity against different oral germs. How to cite this article: Mayta-Tovalino F, Sedano-Balbin G, Romero-Tapia P, et al. Development of New Experimental Dentifrice of Peruvian Solanum tuberosum (Tocosh) Fermented by Water Stress: Antibacterial and Cytotoxic Activity. J Contemp Dent Pract 2019;20(10):1206-1211.


TDP-43 is directed to stress granules by sorbitol, a novel physiological osmotic and oxidative stressor.
TDP-43, or TAR DNA-binding protein 43, is a pathological marker of a spectrum of neurodegenerative disorders, including amyotrophic lateral sclerosis and frontotemporal lobar degeneration with ubiquitin-positive inclusions. TDP-43 is an RNA/DNA-binding protein implicated in transcriptional and posttranscriptional regulation. Recent work also suggests that TDP-43 associates with cytoplasmic stress granules, which are transient structures that form in response to stress. In this study, we establish sorbitol as a novel physiological stressor that directs TDP-43 to stress granules in Hek293T cells and primary cultured glia. We quantify the association of TDP-43 with stress granules over time and show that stress granule association and size are dependent on the glycine-rich region of TDP-43, which harbors the majority of pathogenic mutations. Moreover, we establish that cells harboring wild-type and mutant TDP-43 have distinct stress responses: mutant TDP-43 forms significantly larger stress granules, and is incorporated into stress granules earlier, than wild-type TDP-43; in striking contrast, wild-type TDP-43 forms more stress granules over time, but the granule size remains relatively unchanged. We propose that mutant TDP-43 alters stress granule dynamics, which may contribute to the progression of TDP-43 proteinopathies.


Surface plasmon coupled metal enhanced spectral and charge transport properties of poly(3,3'''-dialkylquarterthiophene) Langmuir Schaefer films.
The coupling of organic molecule excitons with metal nano-structure surface plasmons can improve the performance of optoelectronic devices. This paper presents the effect of localized silver metal surface plasmons on spectral as well as charge transport properties of ordered molecular Langmuir Schaefer (LS) films of a fluorescent conducting multifunctional organic polymer: poly (3,3'''-dialkylquarterthiophene) [PQT-12]. The stability and thickness of the PQT-12 LS film were studied by the pressure vs. area isotherm curve. Atomic force microscopy images indicate the formation of a smooth ordered polymer thin LS film of PQT-12 over silver nanostructure island films [SNIF] (∼40 to 50 nm in size). Raman, electronic absorption and fluorescence spectral measurements of the PQT-12 LS film, near SNIF i.e. the near field, show a plasmon coupled enhancement of ∼13 fold in the intensity of Raman bands along with a two-fold enhancement in the absorption band (531 nm) and a six-fold enhancement in the fluorescence band (665 nm) coupled with a decrease in fluorescence decay time with improved photostability as compared to an identical control sample containing no SNIF i.e. the far field condition. These results indicate the formation of a plasmon coupled unified fluorophore system due to adsorption of the PQT-12 LS film over SNIF. The effect of plasmonic coupling is also studied by applying an electric field in sandwiched structures of Al/PQT-12 LS/SNIF/ITO with respect to Al/PQT-12 LS/ITO. Nearly three orders of magnitude enhancement in the current density (J-V plot) of the PQT-12 LS film is observed in the presence of SNIF, which further increases, on illuminating the film by green laser light [532 nm], while the fluorescence intensity and decay time decrease. X-ray photoelectron spectroscopic measurements of SNIF also show a red shift in 3d3/2 and 3d5/2 transitions of silver in the PQT-12 coated LS film, which indicates partial charge transfer from the PQT-12 polymer backbone to SNIF and causes an enhancement in conductivity. This again supports the formation of a field controlled radiating plasmon coupled fluorophore unified system. These findings show greater potential in developing a voltage controlled high photon flux electroluminescent material for multifarious applications.


Effect of supranutritional organic selenium supplementation on postpartum blood micronutrients, antioxidants, metabolites, and inflammation biomarkers in selenium-replete dairy cows.
Dairy cows have increased nutritional requirements for antioxidants postpartum. Supranutritional organic Se supplementation may be beneficial because selenoproteins are involved in regulating oxidative stress and inflammation. Our objective was to determine whether feeding Se-yeast above requirements to Se-replete dairy cows during late gestation affects blood micronutrients, antioxidants, metabolites, and inflammation biomarkers postpartum. During the last 8-weeks before calving, dairy cows at a commercial farm were fed either 0 (control) or 105 mg Se-yeast once weekly (supranutritional Se-yeast), in addition to Na selenite at 0.3 mg Se/kg dry matter in their rations. Concentrations of whole-blood (WB) Se and serum Se, erythrocyte glutathione (GSH), and serum albumin, cholesterol, α-tocopherol, haptoglobin, serum amyloid A (SAA), calcium, magnesium, phosphorus, non-esterified fatty acids, and β-hydroxybutyrate were measured directly after calving, at 48 h, and 14 days of lactation in 10 cows of each group. Supranutritional Se-yeast supplementation affected indicators of antioxidant status and inflammation. Cows fed a supranutritional Se-yeast supplement during the last 8-weeks of gestation had higher Se concentrations in WB (overall 52 % higher) and serum (overall 36 % higher) at all-time points, had higher SAA concentrations at 48 h (98 % higher), had higher erythrocyte GSH (38 % higher) and serum albumin concentrations (6.6 % higher) at 14 days, and had lower serum cholesterol concentrations and higher α-tocopherol/cholesterol ratios at calving and at 48 h compared with control cows. In conclusion, feeding Se-replete cows during late gestation a supranutritional Se-yeast supplement improves antioxidant status and immune responses after calving without negatively impacting other micronutrients and energy status.


Lack of sensitivity of staffing for 8-hour sessions to standard deviation in daily actual hours of operating room time used for surgeons with long queues.
At multiple facilities including some in the United Kingdom's National Health Service, the following are features of many surgical-anesthetic teams: i) there is sufficient workload for each operating room (OR) list to almost always be fully scheduled; ii) the workdays are organized such that a single surgeon is assigned to each block of time (usually 8 h); iii) one team is assigned per block; and iv) hardly ever would a team "split" to do cases in more than one OR simultaneously. We used Monte-Carlo simulation using normal and Weibull distributions to estimate the times to complete lists of cases scheduled into such 8 h sessions. For each combination of mean and standard deviation, inefficiencies of use of OR time were determined for 10 h versus 8 h of staffing. When the mean actual hours of OR time used averages < or = 8 h 25 min, 8 h of staffing has higher OR efficiency than 10 h for all combinations of standard deviation and relative cost of over-run to under-run. When mean > or = 8 h 50 min, 10 h staffing has higher OR efficiency. For 8 h 25 min < mean < 8 h 50 min, the economic break-even point depends on conditions. For example, break-even is: (a) 8 h 27 min for Weibull, standard deviation of 60 min and relative cost of over-run to under-run of 2.0 versus (b) 8 h 48 min for normal, standard deviation of 0 min and relative cost ratio of 1.50. Although the simplest decision rule would be to staff for 8 h if the mean workload is < or = 8 h 40 min and to staff for 10 h otherwise, performance was poor. For example, for the Weibull distribution with mean 8 h 40 min, standard deviation 60 min, and relative cost ratio of 2.00, the inefficiency of use of OR time would be 34% larger if staffing were planned for 8 h instead of 10 h. For surgical teams with 8 h sessions, use the following decision rule for anesthesiology and OR nurse staffing. If actual hours of OR time used averages < or = 8 h 25 min, plan 8 h staffing. If average > or = 8 h 50 min, plan 10 h staffing. For averages in between, perform the full analysis of McIntosh et al. (Anesth Analg 2006;103:1499-516).


Increased Consumption of Plant Foods Is Associated with Increased Bone Mineral Density.
To determine the relationship between plant food consumption and bone mineral density (BMD) in a healthy population when age, gender, BMI and physical activity are accounted for. Cross-sectional study. Participants were recruited from the Sydney Adventist hospital and the University of New South Wales, Sydney, Australia. 33 males and 40 females (total n=73) participated in this study. The mean age was 56.1 ± 8.5 years. All participants were non-diabetic and in general good health. A principle component analysis (PCA) was performed on 12 month self-report food intake data, gathered using the Cancer Council Victoria Dietary Questionnaire for Epidemiological Studies Version 2. Dual-energy X-ray absorptiometry was used to measure total BMD. Fasting plasma total protein, calcium and 25-Hydroxy Vitamin D levels were analysed by the Sydney Adventist Hospital pathology laboratory. Anthropometric measures were obtained using a standardized protocol. Self-reported physical activity levels were assessed using the International Physical Activity Questionnaire. The PCA revealed three principle components. These were termed 'Meat Based', 'Junk Food' and 'Plant Based.' After controlling for age, gender, physical activity and BMI, the Plant Based component correlated positively with BMD (p=0.054, R2=0.439) and T-score (p=0.053, R2=0.221). Using a similar model no association between the Meat Based component and BMD or T-score was found. However, when the Plant Based component was included the Meat Based component correlated positively with BMD (p=0.046, R2=0.474) and T-score (p=0.046, R2=0.279). There was no significant association between the Junk Food component and BMD or T-score. People in the third Plant (927 ± 339 vs 751 ± 255 g/day, p=0.025) and Meat Based (921 ± 270 vs 676 ± 241 g/day, p=0.002) tertile had higher calcium intakes than those in the first. People in the second Plant Based tertile had higher plasma Vitamin D levels than those in the first (63.5 ± 16.8 vs. 52.3 ± 22.1 nmol/L, p=0.053) while those in the third Junk Food tertile had lower levels than those in the first (52.4 ± 18.5 vs. 65.4 ± 19.8 nmol/L, p=0.027). No association between Plant Based tertiles and protein intake was observed, however those in the third Meat Based (99.7 ± 25.1 vs. 50.9 ± 13.8 g/day, p=0.000) and Junk Food (87.4 ± 30.7 vs. 56.6 ± 22.2 g/day, p=0.000) tertile had higher protein intake compared to those in the first tertile. In a healthy middle aged population with normal BMD, an increase in plant food consumption, either alone or in combination with a diet containing meat, is associated with improved bone mineralisation markers. This positive relationship is most likely due to the extensive range of micronutrients and phytochemicals packaged within plants.


Circadian rhythm and its association with birth and infant outcomes: research protocol of a prospective cohort study.
Circadian rhythm plays an important role as our internal body's clock that synchronizes behavior and physiology according to the external 24-h light-dark cycle. Past studies have associated disrupted circadian rhythm with higher risk of miscarriages, preterm birth and low birth weights. This paper described the protocol of a prospective cohort study which aims to determine the circadian rhythm in pregnant women, identify its association with maternal factors during pregnancy, gestational weight gain, birth and infant outcomes. Ten government maternal and child health clinics in Kuala Lumpur, Malaysia will be randomly selected. Sample size of 438 first-trimester pregnant women will be followed-up until the birth of their infant. Salivary melatonin and cortisol concentration among subsample will be determined using enzyme-linked immunosorbent assay. Data on sleep quality, psychological distress and morningness/eveningness chronotype of pregnant women will be collected using validated questionnaires. Pedometer will be used to measure 5-day physical activity data. Total gestational weight gain will be determined at the end of pregnancy. Utilization of 3-day food record is to capture meal timing and nutrient intake. All measurements will be done in 2nd and 3rd trimester. Birth outcomes will be collected through clinic records and Centers for Disease Control and Prevention (CDC) Neonatal questionnaire. Infants will be followed-up at 6 and 12 months old to obtain anthropometric measurements. There is a growing recognition of the role of maternal circadian rhythm, which entrains fetal circadian rhythms that may subsequently have long-term health consequences. The present study will identify the effect of circadian rhythm on pregnancy outcomes and infant growth in the first year of life.


Adverse outcomes in hip arthroplasty: long-term trends.
Total hip arthroplasty is a common surgical procedure, but little is known about longitudinal trends in associated adverse outcomes. Our objective was to describe long-term trends in demographics, comorbidities, and adverse outcomes for older patients who underwent primary and revision total hip arthroplasty. We identified a retrospective, observational cohort of 1,405,379 Medicare beneficiaries who underwent primary total hip arthroplasty and 337,874 who underwent revision total hip arthroplasty between 1991 and 2008. The primary outcome was a composite representing the occurrence of one or more of the following adverse outcomes during the index admission or during readmission within ninety days after discharge: death, hemorrhage, infection, pulmonary embolism, sepsis, deep venous thrombosis, and myocardial infarction. Secondary outcomes included each of these outcomes assessed individually. Between 1991 and 2008, the mean age and the mean comorbidity burden increased for all total hip arthroplasty patients. The length of hospital stay after primary and revision total hip arthroplasty declined by approximately 50% over the study period. However, the rate of readmission for any cause has recently increased and has surpassed 10% for primary total hip arthroplasty and 20% for revision total hip arthroplasty. The composite rate of adverse outcomes after primary total hip arthroplasty declined from 4% to 3.4% over the study period, whereas the composite adverse outcome rate after revision total hip arthroplasty slowly increased from 7% to 10.9%. We observed a steady decline in the rates of most individual adverse outcomes after primary total hip arthroplasty over the majority of the study period. Many of these rates stabilized or began to increase slightly near the end of the study period. In contrast, an increase in the rates of many adverse outcomes was observed in the revision total hip arthroplasty population even after accounting for changes in patient complexity. Postoperative hemorrhage has gradually increased after both primary and revision total hip arthroplasty. Patients undergoing primary and revision total hip arthroplasty are becoming more complex. Despite this increasing complexity, patient outcomes for primary total hip arthroplasty improved markedly before stabilizing in recent years. In contrast, patient outcomes after revision total hip arthroplasty have gradually worsened, likely reflecting the increase in the medical comorbidities and surgical complexity of these patients. Length of hospital stay has demonstrated a substantial decline, which has recently been coupled with an increased readmission rate. Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.


The impact of errors in infant development: Falling like a baby.
What is the role of errors in infants' acquisition of basic skills such as walking, skills that require immense amounts of practice to become flexible and generative? Do infants change their behaviors based on negative feedback from errors, as suggested by "reinforcement learning" in artificial intelligence, or do errors go largely unmarked so that learning relies on positive feedback? We used falling as a model system to examine the impact of errors in infant development. We examined fall severity based on parent reports of prior falls and videos of 563 falls incurred by 138 13- to 19-month-old infants during free play in a laboratory playroom. Parent reports of notable falls were limited to 33% of infants and medical attention was limited to 2% of infants. Video-recorded falls were typically low-impact events. After falling during free play in the laboratory, infants rarely fussed (4% of falls), caregivers rarely showed concern (8% of falls), and infants were back at play within seconds. Impact forces were mitigated by infants' effective reactive behaviors, quick arrest of the fall before torso or head impact, and small body size. Moreover, falling did not alter infants' subsequent behavior. Infants were not deterred from locomotion or from interacting with the objects and elevations implicated in their falls. We propose that a system that discounts the impact of errors in early stages of development encourages infants to practice basic skills such as walking to the point of mastery.


Effect of Plant- and Animal-Based Foods on Prostate Cancer Risk.
Many studies have explored whether plant and animal-based food consumption is associated with prostate cancer (PCa) risk, but there is much discordance. To perform an updated review of the literature that further investigates the association of plant- and animal-based food consumption with PCa risk. This review was conducted by using 3 databases and produced a total of 550 references. The search was limited to a publication date range of 2006 to February 2017, English language, and humans. After case reports, comments, letters, editorials, and duplicate references were removed, 297 citations remained for review. Articles that did not investigate the association of dietary patterns or a major component of diet with PCa were excluded. Of the 297 references found, 47 were eligible for inclusion in this review. The authors identified 2 very large cohort studies (≥100,000 participants), 6 large cohort studies (≥40,000 participants), 11 medium cohort studies (≥10,000 participants), 10 small cohort studies (<10,000 participants), 13 case-control studies, 4 meta-analyses, and 1 population study investigating diet and PCa risk. Most studies showed that plant-based foods are associated with either decreased or unchanged risk of PCa, whereas animal-based foods, particularly dairy products, are associated with either increased or unchanged risk of PCa. This review of the literature suggests that consumption of higher amounts of plant-based foods may be associated with decreased PCa risk, and consumption of higher amounts of dairy products may be associated with increased PCa risk.


New therapeutic strategies for celiac disease.
Celiac disease is an autoimmune condition affecting genetically susceptible individuals, characterized by inflammatory damage to the small intestine following ingestion of wheat gluten or barley and rye products. The only life-long treatment is strict gluten-free diet which is difficult personally and socially, affects quality of life, not widely available, more expensive, with lower palatability, resulting in low compliance. No doubt, there is therefore an urgent need for alternative therapeutic modalities. Based on the increasing knowledge on the sequential pathophysiological events driving the intestinal inflammatory cascade, new attractive and potential therapies were starting to immerge: selecting, changing, degrading, manipulating or binding the dietary toxic environmental factors, decreasing intestinal permeability toward gluten or blocking the deamination of gluten by inhibiting tissue transglutaminase or the HLA-DQ presenting groove by carefully designed false peptide, shifting the typical Th1 to Th2 inflammatory reaction or antagonizing major proinflammatory cytokines, enhancing regulatory immune function or developing preventive vaccines, blocking adhesion molecule, inducing gluten oral or intranasal tolerance or applying epithelial repairing mitogens to oppose the mucosal destruction. Safety, effectiveness, cost and affordability are prime issues to consider. Some modalities have shown promising results in vitro. Future will show who will win the race.


Arnicolide D, from the herb Centipeda minima, Is a Therapeutic Candidate against Nasopharyngeal Carcinoma.
Nasopharyngeal carcinoma (NPC) is a high morbidity and mortality cancer with an obvious racial and geographic bias, particularly endemic to Southeast China. Our previous studies demonstrated that Centipeda minima extract (CME) exhibited anti-cancer effects in human NPC cell lines. Arnicolide C and arnicolide D are sesquiterpene lactones isolated from Centipeda minima. In this study, for the first time, we investigated their anti-NPC effects and further explored the related molecular mechanisms. The effects of both arnicolide C and arnicolide D were tested in NPC cells CNE-1, CNE-2, SUNE-1, HONE1, and C666-1. The results showed that the two compounds inhibited NPC cell viability in a concentration- and time-dependent manner. As the inhibitory effect of arnicolide D was the more pronounced of the two, our following studies focused on this compound. Arnicolide D could induce cell cycle arrest at G2/M, and induce cell apoptosis. The molecular mechanism of cell cycle regulation and apoptosis induction was investigated, and the results showed that arnicolide D could downregulate cyclin D3, cdc2, p-PI3K, p-AKT, p-mTOR, and p-STAT3, and upregulate cleaved PARP, cleaved caspase 9, and Bax. Regulation of cyclin B1, cdk6, and Bcl-2 expression by arnicolide D showed dynamic changes according to dose and time. Taken together, arnicolide D modulated the cell cycle, activated the caspase signaling pathway, and inhibited the PI3K/AKT/mTOR and STAT3 signaling pathways. These findings provide a solid base of evidence for arnicolide D as a lead compound for further development, and act as proof for the viability of drug development from traditional Chinese medicines.


Repetitive cycles of high-dose cytarabine benefit patients with acute myeloid leukemia and inv(16)(p13q22) or t(16;16)(p13;q22): results from CALGB 8461.
To study the impact of repetitive (three to four courses) versus a single course of high-dose cytarabine (HDAC) consolidation therapy on outcome of patients with acute myeloid leukemia (AML) and inv(16)(p13q22) or t(16;16)(p13;q22). We examined the cumulative incidence of relapse (CIR), relapse-free survival (RFS), and overall survival (OS) for 48 adults younger than 60 years with inv(16)/t(16;16) who had attained a complete remission on one of four consecutive clinical trials and were assigned to receive HDAC consolidation therapy. Twenty-eight patients were assigned to either three or four courses of HDAC, and 20 patients were assigned to one course of HDAC followed by alternative intensive consolidation therapy. Pretreatment features were similar for the two groups. The CIR was significantly decreased in patients assigned to receive three to four cycles of HDAC compared with patients assigned to one course (P=.03; 5-year CIR, 43% v 70%, respectively). The difference in RFS also approached statistical significance (P=.06). In a multivariable analysis that adjusted for potential confounding covariates, only treatment assignment (three to four cycles of HDAC) predicted for superior RFS (P=.02). The OS of both groups was similar (P=.93; 5-year OS, 75% for the three to four cycles of HDAC group v 70% for the one cycle of HDAC group), reflecting a high success rate with stem-cell transplantation salvage treatment administered among patients in both treatment groups. We conclude that, in AML patients with inv(16)/t(16;16), repetitive HDAC therapy decreases the likelihood of relapse compared with consolidation regimens including less HDAC.


Tumor metabolism of lactate: the influence and therapeutic potential for MCT and CD147 regulation.
Tumor metabolism consists of complex interactions between oxygenation states, metabolites, ions, the vascular network and signaling cascades. Accumulation of lactate within tumors has been correlated with poor clinical outcomes. While its production has negative implications, potentially contributing to tumor progression, the implications of the ability of tumors to utilize lactate can offer new therapeutic targets for the future. Monocarboxylate transporters (MCTs) of the SLC16A gene family influence substrate availability, the metabolic path of lactate and pH balance within the tumor. CD147, a chaperone to some MCT subtypes, contributes to tumor progression and metastasis. The implications and consequences of lactate utilization by tumors are currently unknown; therefore future research is needed on the intricacies of tumor metabolism. The possibility of metabolic modification of the tumor microenvironment via regulation or manipulation of MCT1 and CD147 may prove to be promising avenues of therapeutic options.


Epithelial progenitor cell lines as models of normal breast morphogenesis and neoplasia.
The majority of human breast carcinomas exhibit luminal characteristics and as such, are most probably derived from progenitor cells within the luminal epithelial compartment. This has been subdivided recently into at least three luminal subtypes based on gene expression patterns. The value of knowing the cellular origin of individual tumours is clear and should aid in designing effective therapies. To do this, however, we need strategies aimed at defining the nature of stem and progenitor cell populations in the normal breast. In this review, we will discuss our technical approach for delineating the origin of the epithelial cell types. A major step forward was the purification of each cell type by the application of immunomagnetic cell sorting based on expression of lineage-specific surface antigens. We then developed chemically defined media that could support either the luminal epithelial or the myoepithelial cell phenotype in primary cultures. Having succeeded in continuous propagation presumably without loss of markers, we could show that a subset of the luminal epithelial cells could convert to myoepithelial cells, signifying the possible existence of a progenitor cell population. By combining the information on marker expression and in situ localization with immunomagnetic sorting and subsequent immortalization, we have identified and isolated a cytokeratin 19-positive suprabasal putative precursor cell in the luminal epithelial compartment and established representative cell lines. This suprabasal-derived epithelial cell line is able to generate both itself and differentiated luminal epithelial and myoepithelial cells, and in addition, is able to form elaborate terminal duct lobular unit (TDLU)-like structures within a reconstituted basement membrane. As more than 90% of breast cancers arise in TDLUs and more than 90% are also cytokeratin 19-positive, we suggest that this cell population contains a breast-cancer progenitor.


Receptive Field Vectors of Genetically-Identified Retinal Ganglion Cells Reveal Cell-Type-Dependent Visual Functions.
Sensory stimuli are encoded by diverse kinds of neurons but the identities of the recorded neurons that are studied are often unknown. We explored in detail the firing patterns of eight previously defined genetically-identified retinal ganglion cell (RGC) types from a single transgenic mouse line. We first introduce a new technique of deriving receptive field vectors (RFVs) which utilises a modified form of mutual information ("Quadratic Mutual Information"). We analysed the firing patterns of RGCs during presentation of short duration (~10 second) complex visual scenes (natural movies). We probed the high dimensional space formed by the visual input for a much smaller dimensional subspace of RFVs that give the most information about the response of each cell. The new technique is very efficient and fast and the derivation of novel types of RFVs formed by the natural scene visual input was possible even with limited numbers of spikes per cell. This approach enabled us to estimate the 'visual memory' of each cell type and the corresponding receptive field area by calculating Mutual Information as a function of the number of frames and radius. Finally, we made predictions of biologically relevant functions based on the RFVs of each cell type. RGC class analysis was complemented with results for the cells' response to simple visual input in the form of black and white spot stimulation, and their classification on several key physiological metrics. Thus RFVs lead to predictions of biological roles based on limited data and facilitate analysis of sensory-evoked spiking data from defined cell types.


Candida albicans Mrv8, is involved in epithelial damage and biofilm formation.
Candida albicans is the most common human fungal pathogen that can cause superficial and deep-seated infections in susceptible individuals. Despite its medical importance, the vast majority of C. albicans genes remain of unknown function. Here, we report a role for the lineage-specific gene, MRV8, in host pathogen interactions, mycelial microcolony maturation and biofilm formation. In silico analysis indicated that MRV8 encodes a four-pass transmembrane protein unique to the closely related pathogens C. albicans and Candida dubliniensis. Deletion of MRV8 did not affect C. albicans adherence to, or initial invasion into human oral epithelia, but inhibited mycelial development and strongly reduced epithelial damage. mrv8Δ/Δ cells exhibited a media-dependent defect in biofilm formation and mutant biofilm metabolic activity was enhanced by cyclosporin A. mrv8Δ/Δ biofilms were more tolerant to treatment with caspofungin, but not to fluconazole or amphotericin B. Co-stimulation with calcium chloride and calcofluor white rescued biofilm growth in the presence of caspofungin, and this rescue-effect was Mrv8-dependent. Together, our data demonstrate an important role for a lineage-specific gene (MRV8) in C. albicans biofilm formation, drug tolerance and host-pathogen interactions.


TRF2 recruits ORC through TRFH domain dimerization.
Telomeres are specialized chromatin structures that prevent the degradation and instability of the ends of linear chromosomes. While telomerase maintains long stretches of the telomeric repeat, the majority of telomeric DNA is duplicated by conventional DNA replication. A fundamental step in eukaryotic DNA replication involves chromatin binding of the origin recognition complex (ORC). In human cells, telomeric repeat binding factor 2 (TRF2) is thought to play a role in the recruitment of ORC onto telomeres. To better understand the mechanism of TRF2-mediated ORC recruitment, we utilized a lacO-LacI protein tethering system in U2OS cells and found that ectopically targeted TRF2, but not TRF1, can recruit ORC onto the lacO array. We further found that the TRF homology (TRFH) dimerization domain of TRF2, but not its mutant defective in dimerization, is sufficient for ORC and minichromosome maintenance (MCM) recruitment. Mutations impairing the dimerization also compromised ORC recruitment by full-length TRF2. Similar results were obtained using immunoprecipitation and GST pull-down assays. Together, these results suggest that dimerized TRF2 recruits ORC and stimulates pre-replication complex (pre-RC) formation at telomeres through the TRFH domain.


Characterization of a T4+/Leu-8+ T cell clone that directly helps B cell Ig production by secreting B cell differentiation factor.
A human T4+/Leu-8+ T cell clone (YA2) was established by phytohemagglutinin activation and interleukin 2 (IL 2) propagation. Functional characterization of this clone demonstrated that it provided potent help towards Ig production by pokeweed mitogen-stimulated B cells in the presence of small numbers of autologous T cells or by Staphylococcus aureus Cowan I (SAC)-activated B cells in the presence of B cell growth factor (BCGF). YA2 provided no help to resting B cells and minimal help to either unactivated B cells cultured with BCGF or SAC-activated B cells. Supernatant generated from clone YA2 by IL 2 stimulation had significant B cell differentiation activity but no BCGF or IL 2 activity. Thus, YA2 is a T4+/Leu-8+ potent direct helper only to B cells that are activated and proliferating due to its selective secretion of a differentiation factor, and not an activation and growth factor. The availability of phenotypically defined cloned populations of T cells with restricted functional helper activity related to the secretion of selected B cell tropic factors should prove useful in the dissection of the role of individual T cell subsets in the regulation of the human B cell cycle.


Saphenous Nerve Denervation for Chronic Pain After Compartment Syndrome of the Foot.
Denervation has been a recommended treatment option for a range of pathologies, including relief from chronic pain; however, literature discussing complete denervation of the distal saphenous nerve for foot pain has not been found. A case report of surgical decompression for compartment syndrome resulting in chronic, debilitating foot pain that was successfully alleviated by complete saphenous nerve denervation is presented. The predominant area of the patient's pain was on the medial aspect of the foot, where a thickened scar from a decompression fasciotomy was noted. The patient's initial pain score was reported as 10 of 10, with no relief from numerous conservative treatments attempted over an 11-year period. After a diagnostic injection of a local anesthetic to the distal saphenous nerve provided the patient with immediate, temporary relief, complete denervation of the distal saphenous nerve was performed. The patient reported significant pain reduction shortly after the procedure. This case suggests that physicians should be cognizant of the saphenous nerve and its branches, as well as its variable pathways during surgery. In addition, practitioners should be aware of its influence as a progenitor of pain in the foot that may require denervation.


Incidence of toxic Aeromonas isolated from food and human infection.
One hundred and ninety four Aeromonas isolates (99 from food and 95 from clinical sources) were analyzed as to the species involved and the toxins produced. Of the clinical isolates of Aeromonas, 29.4% were enterotoxigenic, 43.1% were hemolytic and 89% were cytotoxigenic. Among the food isolates, 18.2% were enterotoxigenic, 17.1% were hemolytic and 72.7% were cytotoxigenic. Aeromonas sobria and Aeromonas veronii produced more enterotoxin and cytotoxin than the other isolates, whereas A. veronii and Aeromonas salmonicida produced cell-free hemolysin. Most of the isolates produced cytotoxins (81%) active on Vero (green monkey kidney) and Chinese hamster ovary cells, but only the culture supernatant of A. sobria produced vacuolation in these cell lines.


The cephalic labial gland secretions of two socially parasitic bumblebees Bombus hyperboreus (Alpinobombus) and Bombus inexspectatus (Thoracobombus) question their inquiline strategy.
Social parasitic Hymenopterans have evolved morphological, chemical, and behavioral adaptations to overcome the sophisticated recognition and defense systems of their social host to invade host nests and exploit their worker force. In bumblebees, social parasitism appeared in at least 3 subgenera independently: in the subgenus Psithyrus consisting entirely of parasitic species, in the subgenus Alpinobombus with Bombus hyperboreus, and in the subgenus Thoracobombus with B. inexspectatus. Cuckoo bumblebee males utilize species-specific cephalic labial gland secretions for mating purposes that can impact their inquiline strategy. We performed cephalic labial gland secretions in B. hyperboreus, B. inexspectatus and their hosts. Males of both parasitic species exhibited high species specific levels of cephalic gland secretions, including different main compounds. Our results showed no chemical mimicry in the cephalic gland secretions between inquilines and their host and we did not identify the repellent compounds already known in other cuckoo bumblebees.


Transient ablation of alveolar macrophages leads to massive pathology of influenza infection without affecting cellular adaptive immunity.
Alveolar macrophages (AMs), localized at the pulmonary air-tissue interface, are one of the first lines of defense that interact with inhaled airborne pathogens such as influenza viruses. By using a new CD169-DTR transgenic mouse strain we demonstrate that specific and highly controlled in vivo ablation of this myeloid cell subset leads to severe impairment of the innate, but not adaptive, immune responses and critically affects the progression of the disease. In fact, AM-ablated mice, infected with a normally sublethal dose of PR8 influenza virus, showed dramatically increased virus load in the lungs, severe airway inflammation, pulmonary edema and vascular leakage, which caused the death of the infected animals. Our data highlight the possibilities for new therapeutic strategies focusing on modulation of AMs, which may efficiently boost innate responses to influenza infections.


Effects of healthy aging on hippocampal and rhinal memory functions: an event-related fMRI study.
Event-related functional magnetic resonance imaging was used to study the effects of healthy aging on hippocampal and rhinal memory functions. Memory for past events can be based on retrieval accompanied by specific contextual details (recollection) or on the feeling that an event is old or new without the recovery of contextual details (familiarity). There is evidence that recollection is more dependent on hippocampus, whereas familiarity is more dependent on the rhinal cortex, and that healthy aging has greater effects on recollection than on familiarity. However, little evidence is available about the neural correlates of these effects. Here, we isolated activity associated with recollection and familiarity by distinguishing between linear and quasi-exponential "perceived oldness" functions derived from recognition confidence levels. The main finding was a double dissociation within the medial temporal lobes between recollection-related activity in hippocampus, which was reduced by aging, and familiarity-related activity in rhinal cortex, which was increased by aging. In addition, age dissociations were found within parietal and posterior midline regions. Finally, aging reduced functional connectivity within a hippocampal-retrosplenial/parietotemporal network but increased connectivity within a rhinal-frontal network. These findings indicate that older adults compensate for hippocampal deficits by relying more on rhinal cortex, possibly through a top-down frontal modulation. This finding has important clinical implications because early Alzheimer's disease impairs both hippocampus and rhinal cortex.


A Y-Encoded Suppressor of Feminization Arose via Lineage-Specific Duplication of a Cytokinin Response Regulator in Kiwifruit.
Dioecy, the presence of male and female flowers on distinct individuals, has evolved independently in multiple plant lineages, and the genes involved in this differential development are just starting to be uncovered in a few species. Here, we used genomic approaches to investigate this pathway in kiwifruits (genus Actinidia). Genome-wide cataloging of male-specific subsequences, combined with transcriptome analysis, led to the identification of a type-C cytokinin response regulator as a potential sex determinant gene in this genus. Functional transgenic analyses in two model systems, Arabidopsis thaliana and Nicotiana tabacum, indicated that this gene acts as a dominant suppressor of carpel development, prompting us to name it Shy Girl (SyGI). Evolutionary analyses in a panel of Actinidia species revealed that SyGI is located in the Y-specific region of the genome and probably arose from a lineage-specific gene duplication. Comparisons with the duplicated autosomal counterpart, and with orthologs from other angiosperms, suggest that the SyGI-specific duplication and subsequent evolution of cis-elements may have played a key role in the acquisition of separate sexes in this species.


C. elegans: a novel pharmacogenetic model to study Parkinson's disease.
Parkinson's disease (PD) is characterized by the degeneration of dopaminergic neurons in the substantia nigra pars compacta. Although the use of vertebrate and tissue culture systems continue to provide valuable insight into the pathology of the neurodegeneration, the molecular determinants involved in the etiology of the disease remain elusive. Because of the high conservation of genes and metabolic pathways between invertebrates and humans, as well as the availability of genetic strategies to identify novel proteins, protein interactions and drug targets, genetic analysis using invertebrate model systems has enormous potential in deducing the factors involved in neuronal disease. In this article, we discuss the opportunities for the use of the nematode Caenorhabditis elegans (C. elegans) for gaining insight into the molecular mechanisms and pathways involved in PD.


Making the longest sugars: a chemical synthesis of heparin-related [4] n oligosaccharides from 16-mer to 40-mer.
The chemical synthesis of long oligosaccharides remains a major challenge. In particular, the synthesis of glycosaminoglycan (GAG) oligosaccharides belonging to the heparin and heparan sulfate (H/HS) family has been a high profile target, particularly with respect to the longer heparanome. Herein we describe a synthesis of the longest heparin-related oligosaccharide to date and concurrently provide an entry to the longest synthetic oligosaccharides of any type yet reported. Specifically, the iterative construction of a series of [4] n -mer heparin-backbone oligosaccharides ranging from 16-mer through to the 40-mer in length is described. This demonstrates for the first time the viability of generating long sequence heparanoids by chemical synthesis, via practical solution-phase synthesis. Pure-Shift HSQC NMR provides a dramatic improvement in anomeric signal resolution, allowing full resolution of all 12 anomeric protons and extrapolation to support anomeric integrity of the longer species. A chemically pure 6-O-desfulfated GlcNS-IdoAS icosasaccharide (20-mer) represents the longest pure synthetic heparin-like oligosaccharide.


Optical second harmonic generation from LaAlO3/SrTiO3 interfaces with different in-plane anisotropies.
Oxide growth with semiconductor-like accuracy allows the fabrication of atomically precise thin films and interfaces displaying a wide range of phases and functionalities that are absent in the corresponding oxide bulk materials. Among the other properties it was found that a two-dimensional electronic gas is formed under some circumstances at the LaAlO3/SrTiO3(0 0 1) interface separating two typical insulating perovskite crystals. The origin of this conducting state has been discussed at length, since different doping mechanisms can act in these material systems. Many experimental results point to the so-called polar catastrophe scenario as the principal mechanism driving the formation of the two-dimensional electronic gas. According to this mechanism, the existence of an interfacial polar discontinuity is the key ingredient to drive an electronic reconstruction at the LaAlO3/SrTiO3(0 0 1) interface and the consequent formation of a two-dimensional electron gas. This simple picture has been often questioned by the existence of material systems whose interface are predicted being non-polar according to the simplistic 'ionic' limit but that display an electrical behavior analogous to that of LaAlO3/SrTiO3(0 0 1) interfaces. This is the case of the LaAlO3/SrTiO3(1 1 0), i.e., a LaAlO3/SrTiO3 interface with a different in-plane orientation. It is evident that to solve such kind of controversies a detailed investigation of the polar or non-polar state of these interfaces is needed, although this is not simple for the lack of experimental tools that are specifically sensitive to interfacial polarity. Here we apply Optical Second Harmonic Generation to investigate LaAlO3/SrTiO3 interfaces with different in-plane orientations to bridge this gap. By comparing our results with recent theoretical findings, we will arrive to the conclusion that the real LaAlO3/SrTiO3(1 1 0) interface is strongly polar.