Mutation of pescadillo Disrupts Oligodendrocyte Formation in Zebrafish

Background: In vertebrates, the myelin sheath is essential for efficient propagation of action potentials along the axon shaft. Oligodendrocytes are the cells of the central nervous system that create myelin sheaths. During embryogenesis, ventral neural tube precursors give rise to oligodendrocyte progenitor cells, which divide and migrate throughout the central nervous system. This study aimed to investigate mechanisms that regulate oligodendrocyte progenitor cell formation. Methodology/Principal Findings: By conducting a mutagenesis screen in transgenic zebrafish, we identified a mutation, designated vu166, by an apparent reduction in the number of oligodendrocyte progenitor cells in the dorsal spinal cord. We subsequently determined that vu166 is an allele of pescadillo, a gene known to play a role in ribosome biogenesis and cell proliferation. We found that pescadillo function is required for both the proper number of oligodendrocyte progenitors to form, by regulating cell cycle progression, and for normal levels of myelin gene expression. Conclusions/Significance: Our data provide evidence that neural precursors require pes function to progress through th

Heterologous Expression of Alteromonas macleodii and Thiocapsa roseopersicina [NiFe] Hydrogenases in Synechococcus elongatus

Oxygen-tolerant [NiFe] hydrogenases may be used in future photobiological hydrogen production systems once the enzymes can be heterologously expressed in host organisms of interest. To achieve heterologous expression of [NiFe] hydrogenases in cyanobacteria, the two hydrogenase structural genes from Alteromonas macleodii Deep ecotype (AltDE), hynS and hynL, along with the surrounding genes in the gene operon of HynSL were cloned in a vector with an IPTG-inducible promoter and introduced into Synechococcus elongatus PCC7942. The hydrogenase protein was expressed at the correct size upon induction with IPTG. The heterologously-expressed HynSL hydrogenase was active when tested by in vitro H2 evolution assay, indicating the correct assembly of the catalytic center in the cyanobacterial host. Using a similar expression system, the hydrogenase structural genes from Thiocapsa roseopersicina (hynSL) and the entire set of known accessory genes were transferred to S. elongatus. A protein of the correct size was expressed but had no activity. However, when the 11 accessory genes from AltDE were co-expressed with hynSL, the T. roseopersicina hydrogenase was found to be active by in vitro assay. This is the first report of active, heterologously-expressed [NiFe] hydrogenases in cyanobacteria

Dietary Protein and Blood Pressure: A Systematic Review

Background - Elevated blood pressure (BP), which is a major risk factor for cardiovascular disease, is highly prevalent worldwide. Recently, interest has grown in the role of dietary protein in human BP. We performed a systematic review of all published scientific literature on dietary protein, including protein from various sources, in relation to human BP. Methodology/Principal Findings - We performed a MEDLINE search and a manual search to identify English language studies on the association between protein and blood pressure, published before June 2010. A total of 46 papers met the inclusion criteria. Most observational studies showed no association or an inverse association between total dietary protein and BP or incident hypertension. Results of biomarker studies and randomized controlled trials indicated a beneficial effect of protein on BP. This beneficial effect may be mainly driven by plant protein, according to results in observational studies. Data on protein from specific sources (e.g. from fish, dairy, grain, soy, and nut) were scarce. There was some evidence that BP in people with elevated BP and/or older age could be more sensitive to dietary protein. Conclusions/Significance - In conclusion, evidence suggests a small beneficial effect of protein on BP, especially for plant protein. A blood pressure lowering effect of protein may have important public health implications. However, this warrants further investigation in randomized controlled trials. Furthermore, more data are needed on protein from specific sources in relation to BP, and on the protein-BP relation in population subgroup

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition

Mannose-Binding Lectin 2 Polymorphisms Do Not Influence Frequency or Type of Infection in Adults with Chemotherapy Induced Neutropaenia

BACKGROUND: Mannose-binding Lectin protein (MBL) has been suggested to be relevant in the defence against infections in immunosuppressed individuals. In a Swedish adult cohort immunosuppressed from both the underlying disease and from iatrogenic treatments for their underlying disease we investigated the role of MBL in susceptibility to infection. METHODS: In this cross sectional, prospective study, blood samples obtained from 96 neutropaenic febrile episodes, representing 82 individuals were analysed for single nucleotide polymorphism (SNP) in the MBL2 gene. Concurrent measurement of plasma MBL protein concentrations was also performed for observation of acute response during febrile episodes. FINDINGS: No association was observed between MBL2 genotype or plasma MBL concentrations, and the type or frequency of infection. Adding to the literature, we found no evidence that viral infections or co-infections with virus and bacteria would be predisposed by MBL deficiency. We further saw no correlation between MBL2 genotype and the risk of fever. However, fever duration in febrile neutropaenic episodes was negatively associated with MBL2 SNP mutations (p<0.05). Patients with MBL2 SNP mutations presented a median febrile duration of 1.8 days compared with 3 days amongst patients with wildtype MBL2 genotype. INTERPRETATION: We found no clear association between infection, or infection type to MBL2 genotypes or plasma MBL concentration, and add to the reports casting doubts on the benefit of recombinant MBL replacement therapy use during iatrogenic neutropaenia

Measurement of CP-violation asymmetries in D0 to Ks pi+ pi-

We report a measurement of time-integrated CP-violation asymmetries in the resonant substructure of the three-body decay D0 to Ks pi+ pi- using CDF II data corresponding to 6.0 invfb of integrated luminosity from Tevatron ppbar collisions at sqrt(s) = 1.96 TeV. The charm mesons used in this analysis come from D*+(2010) to D0 pi+ and D*-(2010) to D0bar pi-, where the production flavor of the charm meson is determined by the charge of the accompanying pion. We apply a Dalitz-amplitude analysis for the description of the dynamic decay structure and use two complementary approaches, namely a full Dalitz-plot fit employing the isobar model for the contributing resonances and a model-independent bin-by-bin comparison of the D0 and D0bar Dalitz plots. We find no CP-violation effects and measure an asymmetry of ACP = (-0.05 +- 0.57 (stat) +- 0.54 (syst))% for the overall integrated CP-violation asymmetry, consistent with the standard model prediction.Comment: 15 page

Randomized trial of achieving healthy lifestyles in psychiatric rehabilitation: the ACHIEVE trial

<p>Abstract</p> <p>Background</p> <p>Overweight and obesity are highly prevalent among persons with serious mental illness. These conditions likely contribute to premature cardiovascular disease and a 20 to 30 percent shortened life expectancy in this vulnerable population. Persons with serious mental illness need effective, appropriately tailored behavioral interventions to achieve and maintain weight loss. Psychiatric rehabilitation day programs provide logical intervention settings because mental health consumers often attend regularly and exercise can take place on-site. This paper describes the Randomized Trial of Achieving Healthy Lifestyles in Psychiatric Rehabilitation (ACHIEVE). The goal of the study is to determine the effectiveness of a behavioral weight loss intervention among persons with serious mental illness that attend psychiatric rehabilitation programs. Participants randomized to the intervention arm of the study are hypothesized to have greater weight loss than the control group.</p> <p>Methods/Design</p> <p>A targeted 320 men and women with serious mental illness and overweight or obesity (body mass index ≥ 25.0 kg/m²) will be recruited from 10 psychiatric rehabilitation programs across Maryland. The core design is a randomized, two-arm, parallel, multi-site clinical trial to compare the effectiveness of an 18-month behavioral weight loss intervention to usual care. Active intervention participants receive weight management sessions and physical activity classes on-site led by study interventionists. The intervention incorporates cognitive adaptations for persons with serious mental illness attending psychiatric rehabilitation programs. The initial intensive intervention period is six months, followed by a twelve-month maintenance period in which trained rehabilitation program staff assume responsibility for delivering parts of the intervention. Primary outcomes are weight loss at six and 18 months.</p> <p>Discussion</p> <p>Evidence-based approaches to the high burden of obesity and cardiovascular disease risk in person with serious mental illness are urgently needed. The ACHIEVE Trial is tailored to persons with serious mental illness in community settings. This multi-site randomized clinical trial will provide a rigorous evaluation of a practical behavioral intervention designed to accomplish and sustain weight loss in persons with serious mental illness.</p> <p>Trial Registration</p> <p>Clinical Trials.gov NCT00902694</p

Osteocyte deficiency in hip fractures

Osteocytes play a central role in the regulation of bone remodeling. The aim of this study was to explore osteocyte function, and particularly the expression of SOST, a Wnt inhibitor, in patients with hip fractures. Serum sclerostin levels were measured by ELISA. The expression of several osteocytic genes was studied by quantitative PCR in trabecular samples of the femoral head of patients with hip fractures, hip osteoarthritis and control subjects. The presence of sclerostin protein and activated caspase 3 was revealed by immunostaining. There were no significant differences in serum sclerostin between the three groups. Patients with fractures have fewer lacunae occupied by osteocytes (60 ± 5% vs. 64 ± 6% in control subjects, P = 0.014) and higher numbers of osteocytes expressing activated caspase 3, a marker of apoptosis. The proportion of sclerostin-positive lacunae was lower in patients with fractures than in control subjects (34 ± 11% vs. 69 ± 10%, P = 2 × 10(-8)). The proportion of sclerostin-positive osteocytes was also lower in patients. RNA transcripts of SOST, FGF23 and PHEX were also less abundant in fractures than in control bones (P = 0.002, 5 × 10(-6), and 0.04, respectively). On the contrary, in patients with osteoarthritis, there was a decreased expression of SOST and FGF23, without differences in PHEX transcripts or osteocyte numbers. Osteocyte activity is altered in patients with hip fractures, with increased osteocyte apoptosis and reduced osteocyte numbers, as well as decreased transcription of osteocytic genes. Therefore, these results suggest that an osteocyte deficiency may play a role in the propensity to hip fractures

A pilot study comparing two weight loss maintenance interventions among low-income, mid-life women

BACKGROUND: Despite high obesity prevalence rates, few low-income midlife women participate in weight loss maintenance trials. This pilot study aims to assess the effectiveness of two weight loss maintenance interventions in this under-represented population. METHODS: Low-income midlife women who completed a 16-week weight loss intervention and lost ≥ 8 lbs (3.6 kg) were eligible to enroll in one of two 12-month maintenance programs. The programs were similar in content and had the same number of total contacts, but were different in the contact modality (Phone + Face-to-Face vs. Face-to-Face Only). Two criteria were used to assess successful weight loss maintenance at 12 months: (1) retaining a loss of ≥ 5% of body weight from the start of the weight loss phase and (2) a change in body weight of < 3%, from the start to the end of the maintenance program. Outcome measures of changes in physiologic and psychosocial factors, and evaluations of process measures and program acceptability (measured at 12 months) are also reported. For categorical variables, likelihood ratio or Fisher’s Exact (for small samples) tests were used to evaluate statistically significant relationships; for continuous variables, t-tests or their equivalents were used to assess differences between means and also to identify correlates of weight loss maintenance. RESULTS: Overall, during the 12-month maintenance period, 41% (24/58) of participants maintained a loss of ≥ 5% of initial weight and 43% (25/58) had a <3% change in weight. None of the comparisons between the two maintenance programs were statistically significant. However, improvements in blood pressure and dietary behaviors remained significant at the end of the 12-month maintenance period for participants in both programs. Participant attendance and acceptability were high for both programs. CONCLUSIONS: The effectiveness of two pilot 12-month maintenance interventions provides support for further research in weight loss maintenance among high-risk, low-income women. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT0028830

Deceleration during 'real life' motor vehicle collisions – a sensitive predictor for the risk of sustaining a cervical spine injury?

<p>Abstract</p> <p>Background</p> <p>The predictive value of trauma impact for the severity of whiplash injuries has mainly been investigated in sled- and crash-test studies. However, very little data exist for real-life accidents. Therefore, the predictive value of the trauma impact as assessed by the change in velocity of the car due to the collision (ΔV) for the resulting cervical spine injuries were investigated in 57 cases after real-life car accidents.</p> <p>Methods</p> <p>ΔV was determined for every car and clinical findings related to the cervical spine were assessed and classified according to the Quebec Task Force (QTF).</p> <p>Results</p> <p>In our study, 32 (56%) subjects did not complain about symptoms and were therefore classified as QTF grade 0; 25 (44%) patients complained of neck pain: 8 (14%) were classified as QTF grade I, 6 (10%) as QTF grade II, and 11 (19%) as QTF grade IV. Only a slight correlation (r = 0.55) was found between the reported pain and ΔV. No relevant correlation was found between ΔV and the neck disability index (r = 0.46) and between ΔV and the QTF grade (r = 0.45) for any of the collision types. There was no ΔV threshold associated with acceptable sensitivity and specificity for the prognosis of a cervical spine injury.</p> <p>Conclusion</p> <p>The results of this study indicate that ΔV is not a conclusive predictor for cervical spine injury in real-life motor vehicle accidents. This is of importance for surgeons involved in medicolegal expertise jobs as well as patients who suffer from whiplash-associated disorders (WADs) after motor vehicle accidents.</p> <p>Trial registration</p> <p>The study complied with applicable German law and with the principles of the Helsinki Declaration and was approved by the institutional ethics commission.</p