Molecular basis of gap junctional communication in the CNS of the leech Hirudo medicinalis

Gap junctions are intercellular channels that allow the passage of ions and small molecules between cells. In the nervous system, gap junctions mediate electrical coupling between neurons. Despite sharing a common topology and similar physiology, two unrelated gap junction protein families exist in the animal kingdom. Vertebrate gap junctions are formed by members of the connexin family, whereas invertebrate gap junctions are composed of innexin proteins. Here we report the cloning of two innexins from the leech Hirudo medicinalis. These innexins show a differential expression in the leech CNS: Hm-inx1 is expressed by every neuron in the CNS but not in glia, whereas Hm-inx2 is expressed in glia but not neurons. Heterologous expression in the paired Xenopus oocyte system demonstrated that both innexins are able to form functional homotypic gap junctions. Hm-inx1 forms channels that are not strongly gated. In contrast, Hm-inx2 forms channels that are highly voltage-dependent; these channels demonstrate properties resembling those of a double rectifier. In addition, Hm-inx1 and Hm-inx2 are able to cooperate to form heterotypic gap junctions in Xenopus oocytes. The behavior of these channels is primarily that predicted from the properties of the constituent hemichannels but also demonstrates evidence of an interaction between the two. This work represents the first demonstration of a functional gap junction protein from a Lophotrochozoan animal and supports the hypothesis that connexin-based communication is restricted to the deuterostome clade

Maternal plasma DHA levels increase prior to 29 days post-LH surge in women undergoing frozen embryo transfer: a prospective, observational study of human pregnancy

Context: Docosahexaenoic acid (DHA) is an important fatty acid required for neurological development but its importance during early fetal neurological organogenesis is unknown. Objective: To assess plasma fatty acid changes in early pregnancy in women undergoing natural cycle-frozen embryo transfer as a means of achieving accurately-timed periconceptual sampling. Design: Women undergoing frozen embryo transfer were recruited and serial fasting blood samples were taken pre-luteinising hormone (LH) surge, and at days 18, 29 and 45 post-LH surge and fatty acids were analysed using gas chromatography. Setting: Assisted Conception Unit, Glasgow Royal Infirmary, Scotland Main outcome measures: Plasma fatty acid concentrations, influence of twin pregnancies on DHA plasma concentration. Results: In pregnant women, there was a rapid, early increase in the maternal rate of change of plasma DHA concentration observed by 29 days post-LH surge (mean±SD, from 0.1±1.3 to 1.6±2.9 nmol DHA per mL plasma per day). This early pressure to increase plasma DHA concentration was further emphasised in twin pregnancies where the increase in DHA concentration over 45 days was two-fold higher than in singleton pregnancies (mean±SD increase, 74±39 nmol/mL versus 36±40 nmol/mL). An index of delta-6 desaturase activity increased 30% and positively correlated with the rate of change of DHA concentration between day 18 and 29-post LH surge (R-squared adjusted = 41%, P=0.0002). DHA was the only fatty acid with a continual accelerated increase in plasma concentration and a positive incremental area under the curve (mean±SD, 632±911 nmol/mL x day) over the first 45 days of gestation. Conclusions: An increase in maternal plasma DHA concentration is initiated in human pregnancy prior to neural tube closure which occurs at 28 days' gestation

Pre-conception maternal erythrocyte saturated to unsaturated fatty acid ratio predicts pregnancy after natural cycle frozen embryo transfer

The environment for embryo implantation and fetal growth and development is affected by maternal nutritional, metabolic and health status. The aim of this prospective, cohort study was to test whether plasma metabolic and inflammatory biomarkers can predict pregnancy resulting from in vitro fertilisation (IVF). Women with a natural menstrual cycle undergoing frozen embryo transfer (FET) were recruited and fasting baseline blood samples were collected a mean of 3.4 days prior to the luteinising hormone (LH) surge and a non-fasting blood sample was taken on the day of FET. Ongoing pregnancy was defined by positive fetal heartbeat on ultrasound scan at day 45 post LH surge. Thirty-six pregnancies resulted from FET in 143 women. In an overall stepwise multivariable analysis, erythrocyte saturated to unsaturated fatty acid ratio was positively associated with ongoing pregnancy. A similar model incorporating day of FET covariates found that erythrocyte saturated to unsaturated fatty acid ratio, erythrocyte fatty acid average chain length and plasma log-triglycerides predicted ongoing pregnancy. In conclusion, a higher peri-conceptional saturated to unsaturated fatty acid ratio predicted ongoing pregnancy after natural cycle frozen embryo transfer and may reflect a maternal nutritional status that facilitates pregnancy success in this assisted conception scenario

The ANU WiFeS SuperNovA Program (AWSNAP)

This paper presents the first major data release and survey description for the ANU WiFeS SuperNovA Program (AWSNAP). AWSNAP is an ongoing supernova spectroscopy campaign utilising the Wide Field Spectrograph (WiFeS) on the Australian National University (ANU) 2.3m telescope. The first and primary data release of this program (AWSNAP-DR1) releases 357 spectra of 175 unique objects collected over 82 equivalent full nights of observing from July 2012 to August 2015. These spectra have been made publicly available via the WISeREP supernova spectroscopy repository. We analyse the AWSNAP sample of Type Ia supernova spectra, including measurements of narrow sodium absorption features afforded by the high spectral resolution of the WiFeS instrument. In some cases we were able to use the integral-field nature of the WiFeS instrument to measure the rotation velocity of the SN host galaxy near the SN location in order to obtain precision sodium absorption velocities. We also present an extensive time series of SN 2012dn, including a near-nebular spectrum which both confirms its "super-Chandrasekhar" status and enables measurement of the sub-solar host metallicity at the SN site.Comment: Submitted to Publications of the Astronomical Society of Australia (PASA). Spectra publicly released via WISeREP at http://wiserep.weizmann.ac.il

A novel SNP-based tool for estimating C-lineage introgression in the dark honey bee (Apis mellifera mellifera)

The natural distribution ofthe honeybee (Apis mellifera L.) hás been changed by humans in recent decades to such an extent that the formerly widest-spread European subspecies, Apís mellifera mellifera, is threatened by extinction through introgression from highly divergent commercial strains in large tracts of its range. Conservation efforts for A. m. mellifera are underway in multiple European countries requiring reliable and cost-efficient molecular tools to identify purebred colonies. Here, we developed four ancestry-informative SNP assays for high sample throughput genotyping using the iPLEX Mass Array system. Our customized assays were tested on DNA from individual and pooled, haploid and diploid honeybee samples extracted from different tissues using a diverse range of protocols. The assays had a high genotyping success rate and yielded accurate genotypes. Performance assessed against whole-genome data showed that individual assays behaved well, although the most accurate introgression estimates were obtained forthe fourassays combined (117 SNPs). The best compromise between accuracy ana genotyping costs was achieved when combining two assays (62 SNPs). We provide a ready-to-use cost-effective tool for accurate molecular identification and estimation of introgression leveis to more effectively monitor and manage A. m. mellífera conservatories.info:eu-repo/semantics/publishedVersio

Networks in Archaeology: Phenomena, Abstraction, Representation

The application of method and theory from network science to archaeology has dramatically increased over the last decade. In this article, we document this growth over time, discuss several of the important concepts that are used in the application of network approaches to archaeology, and introduce the other articles in this special issue on networks in archaeology. We argue that the suitability and contribution of network science techniques within particular archaeological research contexts can be usefully explored by scrutinizing the past phenomena under study, how these are abstracted into concepts, and how these in turn are represented as network data. For this reason, each of the articles in this special issue is discussed in terms of the phenomena that they seek to address, the abstraction in terms of concepts that they use to study connectivity, and the representations of network data that they employ in their analyses. The approaches currently being used are diverse and interdisciplinary, which we think are evidence of a healthy exploratory stage in the application of network science in archaeology. To facilitate further innovation, application, and collaboration, we also provide a glossary of terms that are currently being used in network science and especially those in the applications to archaeological case studies

The polygenic nature of telomere length and the anti-ageing properties of lithium

Telomere length is a promising biomarker for age-related disease and a potential anti-ageing drug target. Here, we study the genetic architecture of telomere length and the repositioning potential of lithium as an anti-ageing medication. LD score regression applied to the largest telomere length genome-wide association study to-date, revealed SNP-chip heritability estimates of 7.29%, with polygenic risk scoring capturing 4.4% of the variance in telomere length in an independent cohort (p = 6.17 × 10-5). Gene-enrichment analysis identified 13 genes associated with telomere length, with the most significant being the leucine rich repeat gene, LRRC34 (p = 3.69 × 10-18). In the context of lithium, we confirm that chronic use in a sample of 384 bipolar disorder patients is associated with longer telomeres (p = 0.03). As complementary evidence, we studied three orthologs of telomere length regulators in a Caenorhabditis elegans model of lithium-induced extended longevity and found all transcripts to be affected post-treatment (p  0.05). Consequently, this suggests that lithium may be catalysing the activity of endogenous mechanisms that promote telomere lengthening, whereby its efficacy eventually becomes limited by each individual's inherent telomere maintenance capabilities. Our work indicates a potential use of polygenic risk scoring for the prediction of adult telomere length and consequently lithium's anti-ageing efficacy

Prevalence of MRI lesions in men responding to a GP-led invitation for a prostate health check: a prospective cohort study

OBJECTIVE: In men with a raised prostate-specific antigen (PSA), MRI increases the detection of clinically significant cancer and reduces overdiagnosis, with fewer biopsies. MRI as a screening tool has not been assessed independently of PSA in a formal screening study. We report a systematic community-based assessment of the prevalence of prostate MRI lesions in an age-selected population. METHODS AND ANALYSIS: Men aged 50–75 were identified from participating general practice (GP) practices and randomly selected for invitation to a screening MRI and PSA. Men with a positive MRI or a raised PSA density (≥0.12 ng/mL2) were recommended for standard National Health Service (NHS) prostate cancer assessment. RESULTS: Eight GP practices sent invitations to 2096 men. 457 men (22%) responded and 303 completed both screening tests. Older white men were most likely to respond to the invitation, with black men having 20% of the acceptance rate of white men. One in six men (48/303 men, 16%) had a positive screening MRI, and an additional 1 in 20 men (16/303, 5%) had a raised PSA density alone. After NHS assessment, 29 men (9.6%) were diagnosed with clinically significant cancer and 3 men (1%) with clinically insignificant cancer. Two in three men with a positive MRI, and more than half of men with clinically significant disease had a PSA <3 ng/mL. CONCLUSIONS: Prostate MRI may have value in screening independently of PSA. These data will allow modelling of the use of MRI as a primary screening tool to inform larger prostate cancer screening studies. TRIAL REGISTRATION NUMBER: NCT04063566

Elimination of Schistosomiasis Transmission in Zanzibar: Baseline Findings before the Onset of a Randomized Intervention Trial.

Gaining and sustaining control of schistosomiasis and, whenever feasible, achieving local elimination are the year 2020 targets set by the World Health Organization. In Zanzibar, various institutions and stakeholders have joined forces to eliminate urogenital schistosomiasis within 5 years. We report baseline findings before the onset of a randomized intervention trial designed to assess the differential impact of community-based praziquantel administration, snail control, and behavior change interventions. In early 2012, a baseline parasitological survey was conducted in ∼20,000 people from 90 communities in Unguja and Pemba. Risk factors for schistosomiasis were assessed by administering a questionnaire to adults. In selected communities, local knowledge about schistosomiasis transmission and prevention was determined in focus group discussions and in-depths interviews. Intermediate host snails were collected and examined for shedding of cercariae. The baseline Schistosoma haematobium prevalence in school children and adults was 4.3% (range: 0-19.7%) and 2.7% (range: 0-26.5%) in Unguja, and 8.9% (range: 0-31.8%) and 5.5% (range: 0-23.4%) in Pemba, respectively. Heavy infections were detected in 15.1% and 35.6% of the positive school children in Unguja and Pemba, respectively. Males were at higher risk than females (odds ratio (OR): 1.45; 95% confidence interval (CI): 1.03-2.03). Decreasing adult age (OR: 1.04; CI: 1.02-1.06), being born in Pemba (OR: 1.48; CI: 1.02-2.13) or Tanzania (OR: 2.36; CI: 1.16-4.78), and use of freshwater (OR: 2.15; CI: 1.53-3.03) showed higher odds of infection. Community knowledge about schistosomiasis was low. Only few infected Bulinus snails were found. The relatively low S. haematobium prevalence in Zanzibar is a promising starting point for elimination. However, there is a need to improve community knowledge about disease transmission and prevention. Control measures tailored to the local context, placing particular attention to hot-spot areas, high-risk groups, and individuals, will be necessary if elimination is to be achieved

Child feces disposal practices in rural Orissa: a cross sectional study.

BACKGROUND: An estimated 2.5 billion people worldwide lack access to improved sanitation facilities. While large-scale programs in some countries have increased latrine coverage, they sometimes fail to ensure optimal latrine use, including the safe disposal of child feces, a significant source of exposure to fecal pathogens. We undertook a cross-sectional study to explore fecal disposal practices among children in rural Orissa, India in villages where the Government of India's Total Sanitation Campaign had been implemented at least three years prior to the study. METHODS AND FINDINGS: We conducted surveys with heads of 136 households with 145 children under 5 years of age in 20 villages. We describe defecation and feces disposal practices and explore associations between safe disposal and risk factors. Respondents reported that children commonly defecated on the ground, either inside the household (57.5%) for pre-ambulatory children or around the compound (55.2%) for ambulatory children. Twenty percent of pre-ambulatory children used potties and nappies; the same percentage of ambulatory children defecated in a latrine. While 78.6% of study children came from 106 households with a latrine, less than a quarter (22.8%) reported using them for disposal of child feces. Most child feces were deposited with other household waste, both for pre-ambulatory (67.5%) and ambulatory (58.1%) children. After restricting the analysis to households owning a latrine, the use of a nappy or potty was associated with safe disposal of feces (OR 6.72, 95%CI 1.02-44.38) though due to small sample size the regression could not adjust for confounders. CONCLUSIONS: In the area surveyed, the Total Sanitation Campaign has not led to high levels of safe disposal of child feces. Further research is needed to identify the actual scope of this potential gap in programming, the health risk presented and interventions to minimize any adverse effect