AEBP2 as a potential targeting protein for Polycomb Repression Complex PRC2

AEBP2 is a zinc finger protein that has been shown to interact with the mammalian Polycomb Repression Complex 2 (PRC2). In the current study, we characterized this unknown protein and tested its potential targeting roles for the PRC2. AEBP2 is an evolutionarily well-conserved gene that is found in the animals ranging from flying insects to mammals. The transcription of mammalian AEBP2 is driven by two alternative promoters and produces at least two isoforms of the protein. These isoforms show developmental stage-specific expression patterns: the adult-specific larger form (51 kDa) and the embryo-specific smaller form (32 kDa). The AEBP2 protein binds to a DNA-binding motif with an unusual bipartite structure, CTT(N)15-23cagGCC with lower-case being less critical. A large fraction of AEBP2's target loci also map closely to the known target loci of the PRC2. In fact, many of these loci are co-occupied by the two proteins, AEBP2 and SUZ12. This suggests that AEBP2 is most likely a targeting protein for the mammalian PRC2 complex

Strain- and Adsorption-Dependent Electronic States and Transport or Localization in Graphene

The chapter generalizes results on influence of uniaxial strain and adsorption on the electron states and charge transport or localization in graphene with different configurations of imperfections (point defects): resonant (neutral) adsorbed atoms either oxygen- or hydrogen-containing molecules or functional groups, vacancies or substitutional atoms, charged impurity atoms or molecules, and distortions. To observe electronic properties of graphene-admolecules system, we applied electron paramagnetic resonance technique in a broad temperature range for graphene oxides as a good basis for understanding the electrotransport properties of other active carbons. Applied technique allowed observation of possible metal-insulator transition and sorption pumping effect as well as discussion of results in relation to the granular metal model. The electronic and transport properties are calculated within the framework of the tight-binding model along with the Kubo-Greenwood quantum-mechanical formalism. Depending on electron density and type of the sites, the conductivity for correlated and ordered adsorbates is found to be enhanced in dozens of times as compared to the cases of their random distribution. In case of the uniaxially strained graphene, the presence of point defects counteracts against or contributes to the band-gap opening according to their configurations. The band-gap behaviour is found to be nonmonotonic with strain in case of a simultaneous action of defect ordering and zigzag deformation. The amount of localized charge carriers (spins) is found to be correlated with the content of adsorbed centres responsible for the formation of potential barriers and, in turn, for the localization effects. Physical and chemical states of graphene edges, especially at a uniaxial strain along one of them, play a crucial role in electrical transport phenomena in graphene-based materials.Comment: 16 pages, 10 figure

Rapid Assessment of Mineral Concentration in Meadow Grasses by Near Infrared Reflectance Spectroscopy

A near infrared reflectance spectroscopy (NIRS) method for rapid determination of nitrogen, phosphorous and potassium in diverse meadow grasses was developed with a view towards utilizing this material for biogas production and organic fertilizer. NIRS spectra between 12,000 cm−1 and 4,000 cm−1 were used. When validated on samples from different years to those used for the calibration set, the NIRS prediction of nitrogen was considered moderately useful with R2 = 0.77, ratio of standard error of prediction to reference data range (RER) of 9.32 and ratio of standard error of prediction to standard deviation of reference data (RPD) of 2.33. Prediction of potassium was less accurate, with R2 = 0.77, RER of 6.56 and RPD of 1.45, whilst prediction of phosphorous was not considered accurate enough to be of any practical use. This work is of interest from the point of view of both the removal of excess nutrients from formerly intensively farmed areas and also for assessing the plant biomass suitability for conversion into carbon neutral energy through biogas production

Effects of High-Frequency Transcranial Magnetic Stimulation for Cognitive Deficit in Schizophrenia: A Meta-Analysis

Objective: Repetitive transcranial magnetic stimulation (rTMS) has been applied to dorsolateral prefrontal cortex (DLPFC) to improve cognitive function of patients with schizophrenia (SZs). The aim of this meta-analysis was to evaluate whether a high-frequency rTMS course could enhance cognitive function in SZs.Methods: Studies published in PubMed, Cochrane Library, Embase, ScienceDirect, and Web of science were searched until April 2018. The search terms included: “repetitive transcranial magnetic stimulation” or “Rtms,” “SZ,” or “schizophrenia,” and “neuro-cognition” or “neurocognitive performance” or “cognitive effects” or “cognitive” or “cognition” or “working memory” or “executive function” or “language function” or “processing speed,” After screening the literatures according to inclusion and exclusion criteria, extracting data, and evaluating the methodological quality of the included studies, a meta-analysis was performed using RevMan 5.3 software (The Cochrane Collaboration, USA).Results: A total of 9 studies on cognitive dysfunction of SZs were included and involved 351 patients. A significant efficacy of high-frequency rTMS on working memory in SZs was found compared to sham stimulation [p = 0.009, standardized mean difference (SMD) = 0.34]. Specifically, rTMS treatment positioned on the left DLPFC, with a total pluses <30,000 was more significantly more effective in improving the working memory (SMD = 0.33, p = 0.03). No improvement was found in other cognitive domains such as executive function, attention, processing speed, and language function. For the follow-up observations, high-frequency rTMS had long-lasting sustained effects on working memory (SMD = 0.45, p = 0.01) and language function (SMD = 0.77, p = 0.02) in SZs.Conclusions: High-frequency rTMS over the left DLPFC with a total pulses <30,000 stimulation could significantly improve working memory in SZs for an extended period of time

Antidepressant Effects of Repetitive Transcranial Magnetic Stimulation Over Prefrontal Cortex of Parkinson's Disease Patients With Depression: A Meta-Analysis

Objective: The purpose of this meta-analysis was to investigate the antidepressant effects of repetitive transcranial magnetic stimulation (rTMS) over the prefrontal cortex (PFC) of patients with Parkinson's disease (PD) and to determine the optimal rTMS parameters, such as the intensity, frequency and the delivered pattern of rTMS stimulation.Methods: EMBASE, PubMed, Web of Science, MEDLINE, and Cochrane data bases were researched for papers published before March 12, 2018. Studies investigating the anti-depression effects of rTMS over PFC in patients with PD were considered. The main outcomes of pre- and post-rTMS treatment as well as score changes were all extracted. The mean effect size was estimated by calculating the standardized mean difference (SMD) with 95% confidence interval (CI) by using fixed or random effect models as appropriate.Results: Nine studies containing 137 PD patients with depression were included. The pooled results showed significant pre-post anti-depressive effects of rTMS over PFC in PD patients with depression (SMD = −0.80, P < 0.00001). The subgroup analyses of stimulation intensity, frequencies, and models also revealed significant effects (Intensities: 90% RMT: SMD = −1.16, P = 0.0006; >100% RMT: SMD = −0.82, P < 0.0001. Frequencies: < 1.0 Hz: SMD = −0.83, P = 0.03; 5.0 Hz: SMD = −1.10, P < 0.0001; ≥10.0 Hz: SMD = −0.55, P = 0.02. Models: Continuous: SMD = −0.79, P < 0.0001; Discontinuous: SMD = −0.84, P = 0.02). But the results of the studies with place-controlled designs were not significant (Overall: SMD = −0.27, P = 0.54. Intensities: 90% RMT: SMD = 0.27, P = 0.68; 100% RMT: SMD = −0.32, P = 0.33. Frequencies: 5.0 Hz: SMD = −0.87, P = 0.10; ≥10.0 Hz: SMD = 0.27, P = 0.66. Models: Continuous: SMD = −0.28, P = 0.68; Discontinuous: SMD = −0.32, P = 0.33). The greater effect sizes of rTMS with 90% RMT, 5.0 Hz in discontinuous days can be observed rather than the other parameters in both kinds of analyses across study design.Conclusions: rTMS may have a significant positive pre-post anti-depressive effect over PFC on patients with depression, especially by using 5.0 Hz frequency with 90% RMT intensity in discontinuous days, which may produce better effects than other parameters. The real effect, though, was not different from that of the placebo. Future studies with larger sample sizes and high-quality studies are needed to further corroborate our results and to identify the optimal rTMS protocols

Bio-psychosocial determinants of time lost from work following non life threatening acute orthopaedic trauma

<p>Abstract</p> <p>Background</p> <p>To determine factors predicting the duration of time away from work following acute orthopaedic non life threatening trauma</p> <p>Methods</p> <p>Prospective cohort study conducted at four hospitals in Victoria, Australia. The cohort comprised 168 patients aged 18-64 years who were working prior to the injury and sustained a range of acute unintentional orthopaedic injuries resulting in hospitalization. Baseline data was obtained by survey and medical record review. Multivariate Cox proportional hazards regression analysis was used to examine the association between potential predictors and the duration of time away from work during the six month study. The study achieved 89% follow-up.</p> <p>Results</p> <p>Of the 168 participants recruited to the study, 68% returned to work during the six month study. Multivariate Cox proportional hazards regression analysis identified that blue collar work, negative pain attitudes with respect to work, high initial pain intensity, injury severity, older age, initial need for surgery, the presence of co-morbid health conditions at study entry and an orthopaedic injury to more than one region were associated with extended duration away from work following the injury. Participants in receipt of compensation who reported high social functioning at two weeks were 2.58 times more likely to have returned to work than similar participants reporting low social functioning. When only those who had returned to work were considered, the participant reported reason for return to work " to fill the day" was a significant predictor of earlier RTW [RR 2.41 (95% C.I 1.35-4.30)] whereas "financial security" and "because they felt able to" did not achieve significance.</p> <p>Conclusions</p> <p>Many injury-related and psycho social factors affect the duration of time away from work following orthopaedic injury. Some of these are potentially modifiable and may be amenable to intervention. Further consideration of the reasons provided by participants for returning to work may provide important opportunities for social marketing approaches designed to alleviate the financial and social burden associated with work disability.</p

Routes for breaching and protecting genetic privacy

We are entering the era of ubiquitous genetic information for research, clinical care, and personal curiosity. Sharing these datasets is vital for rapid progress in understanding the genetic basis of human diseases. However, one growing concern is the ability to protect the genetic privacy of the data originators. Here, we technically map threats to genetic privacy and discuss potential mitigation strategies for privacy-preserving dissemination of genetic data.Comment: Draft for comment

Detecting Neuroendocrine Prostate Cancer Through Tissue-Informed Cell-Free DNA Methylation Analysis

Purpose: Neuroendocrine prostate cancer (NEPC) is a resistance phenotype that emerges in men with metastatic castration-resistant prostate adenocarcinoma (CR-PRAD) and has important clinical implications, but is challenging to detect in practice. Herein, we report a novel tissue-informed epigenetic approach to noninvasively detect NEPC. Experimental Design: We first performed methylated immunoprecipitation and high-throughput sequencing (MeDIP-seq) on a training set of tumors, identified differentially methylated regions between NEPC and CR-PRAD, and built a model to predict the presence of NEPC (termed NEPC Risk Score). We then performed MeDIP-seq on cell-free DNA (cfDNA) from two independent cohorts of men with NEPC or CR-PRAD and assessed the accuracy of the model to predict the presence NEPC. Results: The test cohort comprised cfDNA samples from 48 men, 9 with NEPC and 39 with CR-PRAD. NEPC Risk Scores were significantly higher in men with NEPC than CR-PRAD (P = 4.3 × 10-7) and discriminated between NEPC and CR-PRAD with high accuracy (AUROC 0.96). The optimal NEPC Risk Score cutoff demonstrated 100% sensitivity and 90% specificity for detecting NEPC. The independent, multi-institutional validation cohort included cfDNA from 53 men, including 12 with NEPC and 41 with CR-PRAD. NEPC Risk Scores were significantly higher in men with NEPC than CR-PRAD (P = 7.5×10-12) and perfectly discriminated NEPC from CR-PRAD (AUROC 1.0). Applying the predefined NEPC Risk Score cutoff to the validation cohort resulted in 100% sensitivity and 95% specificity for detecting NEPC. Conclusions: Tissue-informed cfDNA methylation analysis is a promising approach for noninvasive detection of NEPC in men with advanced prostate cancer

Observations of mixed-species bird flocks at Kichwa Tembo Camp, Kenya

Mixed-species foraging flocks were studied at Kichwa Tembo Camp on the edge of the Masai Mara National Reserve in Kenya between July and September 2004. Observations were made on 29 mixed-species flocks, in which 24 species participated. African Paradise-Flycatcher Terpsiphone viridis, Black-backed Puffback Dryoscopus cubla, Grey-backed Camaroptera Camaroptera brachyura, Collared Sunbird Hedydipna collars and Cabanis's Greenbul Phyllastrephus cabanisi were the most common participants in mixed-species flocks, as well as among the most frequently encountered bird species overall. The Black-backed Puffback was identified as the nuclear species in flocks due to their abundance and frequency with which they were followed by other species. Mixed-species flocks represent another niche dimension in this diverse bird community, but few of these species could be described as flock specialists; most of the birds observed in mixed-species flocks in this study were opportunistic attendant species, including the African Pygmy-Kingfisher Ispidina picta, not previously described as joining mixed-species flocks

The power of practice: simulation training improving the quality of neonatal resuscitation skills in Bihar, India.

BACKGROUND: Globally, neonatal mortality accounts for nearly half of under-five mortality, and intrapartum related events are a leading cause. Despite the rise in neonatal resuscitation (NR) training programs in low- and middle-income countries, their impact on the quality of NR skills amongst providers with limited formal medical education, particularly those working in rural primary health centers (PHCs), remains incompletely understood. METHODS: This study evaluates the impact of PRONTO International simulation training on the quality of NR skills in simulated resuscitations and live deliveries in rural PHCs throughout Bihar, India. Further, it explores barriers to performance of key NR skills. PRONTO training was conducted within CARE India's AMANAT intervention, a maternal and child health quality improvement project. Performance in simulations was evaluated using video-recorded assessment simulations at weeks 4 and 8 of training. Performance in live deliveries was evaluated in real time using a mobile-phone application. Barriers were explored through semi-structured interviews with simulation facilitators. RESULTS: In total, 1342 nurses participated in PRONTO training and 226 NR assessment simulations were matched by PHC and evaluated. From week 4 to 8 of training, proper neck extension, positive pressure ventilation (PPV) with chest rise, and assessment of heart rate increased by 14%, 19%, and 12% respectively (all p ≤ 0.01). No difference was noted in stimulation, suction, proper PPV rate, or time to completion of key steps. In 252 live deliveries, identification of non-vigorous neonates, use of suction, and use of PPV increased by 21%, 25%, and 23% respectively (all p < 0.01) between weeks 1-3 and 4-8. Eighteen interviews revealed individual, logistical, and cultural barriers to key NR skills. CONCLUSION: PRONTO simulation training had a positive impact on the quality of key skills in simulated and live resuscitations throughout Bihar. Nevertheless, there is need for ongoing improvement that will likely require both further clinical training and addressing barriers that go beyond the scope of such training. In settings where clinical outcome data is unreliable, data triangulation, the process of synthesizing multiple data sources to generate a better-informed evaluation, offers a powerful tool for guiding this process