Virgin Birth in a Hammerhead Shark

Parthenogenesis has been documented in all major jawed vertebrate lineages except mammals and cartilaginous fishes (class Chondrichthyes: sharks, batoids and chimeras). Reports of captive female sharks giving birth despite being held in the extended absence of males have generally been ascribed to prior matings coupled with long-term sperm storage by the females. Here, we provide the first genetic evidence for chondrichthyan parthenogenesis, involving a hammerhead shark (Sphyrna tiburo). This finding also broadens the known occurrence of a specific type of asexual development (automictic parthenogenesis) among vertebrates, extending recently raised concerns about the potential negative effect of this type of facultative parthenogenesis on the genetic diversity of threatened vertebrate species

Neurotransmitter signaling regulates distinct phases of multimodal human interneuron migration

Inhibitory GABAergic interneurons migrate over long distances from their extracortical origin into the developing cortex. In humans, this process is uniquely slow and prolonged, and it is unclear whether guidance cues unique to humans govern the various phases of this complex developmental process. Here, we use fused cerebral organoids to identify key roles of neurotransmitter signaling pathways in guiding the migratory behavior of human cortical interneurons. We use scRNAseq to reveal expression of GABA, glutamate, glycine, and serotonin receptors along distinct maturation trajectories across interneuron migration. We develop an image analysis software package, TrackPal, to simultaneously assess 48 parameters for entire migration tracks of individual cells. By chemical screening, we show that different modes of interneuron migration depend on distinct neurotransmitter signaling pathways, linking transcriptional maturation of interneurons with their migratory behavior. Altogether, our study provides a comprehensive quantitative analysis of human interneuron migration and its functional modulation by neurotransmitter signaling

Oral supplementation of healthy adults with 2'-O-fucosyllactose and lacto-N-neotetraose is well tolerated and shifts the intestinal microbiota

The gut microbiota has been established as an important player influencing many aspects of human physiology. Breast milk, the first diet for an infant, contains human milk oligosaccharides (HMO) that shape the infant's gut microbiota by selectively stimulating the growth of specific bacteria, especially bifidobacteria. In addition to their bifidogenic activity, the ability of HMO to modulate immune function and the gut barrier makes them prime candidates to restore a beneficial microbiota in dysbiotic adults and provide health benefits. We conducted a parallel, double-blind, randomised, placebo-controlled, HMO-supplementation study in 100 healthy, adult volunteers, consuming chemically produced 2'-O-fucosyllactose (2'FL) and/or lacto-N-neotetraose (LNnT) at various daily doses and mixes or placebo for 2 weeks. All participants completed the study without premature discontinuation. Supplementation of 2'FL and LNnT at daily doses up to 20 g was shown to be safe and well tolerated, as assessed using the gastrointestinal symptoms rating scale. 16S rRNA sequencing analysis showed that HMO supplementation specifically modified the adult gut microbiota with the primary impact being substantial increases in relative abundance of Actinobacteria and Bifidobacterium in particular and a reduction in relative abundance of Firmicutes and Proteobacteria. This study provides the first set of data on safety, tolerance and impact of HMO on the adult gut microbiota. Collectively, the results from this study show that supplementing the diet with HMO is a valuable strategy to shape the human gut microbiota and specifically promote the growth of beneficial bifidobacteria

Tet1 and Tet2 Regulate 5-Hydroxymethylcytosine Production and Cell Lineage Specification in Mouse Embryonic Stem Cells

SummaryTET family enzymes convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) in DNA. Here, we show that Tet1 and Tet2 are Oct4-regulated enzymes that together sustain 5hmC in mouse embryonic stem cells (ESCs) and are induced concomitantly with 5hmC during reprogramming of fibroblasts to induced pluripotent stem cells. ESCs depleted of Tet1 by RNAi show diminished expression of the Nodal antagonist Lefty1 and display hyperactive Nodal signaling and skewed differentiation into the endoderm-mesoderm lineage in embryoid bodies in vitro. In Fgf4- and heparin-supplemented culture conditions, Tet1-depleted ESCs activate the trophoblast stem cell lineage determinant Elf5 and can colonize the placenta in midgestation embryo chimeras. Consistent with these findings, Tet1-depleted ESCs form aggressive hemorrhagic teratomas with increased endoderm, reduced neuroectoderm, and ectopic appearance of trophoblastic giant cells. Thus, 5hmC is an epigenetic modification associated with the pluripotent state, and Tet1 functions to regulate the lineage differentiation potential of ESCs

Extracellular sodium regulates fibroblast growth factor 23 (FGF23) formation

The bone-derived hormone fibroblast growth factor-23 (FGF23) has recently received much attention due to its association with chronic kidney disease and cardiovascular disease progression. Extracellular sodium concentration ([Na$^{+}$]) plays a significant role in bone metabolism. Hyponatremia (lower serum [Na$^{+}$]) has recently been shown to be independently associated with FGF23 levels in patients with chronic systolic heart failure. However, nothing is known about the direct impact of [Na$^{+}$] on FGF23 production. Here, we show that an elevated [Na$^{+}$] (+20 mM) suppressed FGF23 formation, whereas low [Na$^{+}$] (-20 mM) increased FGF23 synthesis in the osteoblast-like cell lines UMR-106 and MC3T3-E1. Similar bidirectional changes in FGF23 abundance were observed when osmolality was altered by mannitol but not by urea, suggesting a role of tonicity in FGF23 formation. Moreover, these changes in FGF23 were inversely proportional to the expression of NFAT5 (nuclear factor of activated T cells-5), a transcription factor responsible for tonicity-mediated cellular adaptations. Furthermore arginine vasopressin (AVP), which is often responsible for hyponatremia, did not affect FGF23 production. Next, we performed a comprehensive and unbiased RNA-seq analysis of UMR-106 cells exposed to low vs. high [Na$^{+}$], which revealed several novel genes involved in cellular adaptation to altered tonicity. Additional analysis of cells with Crisp-Cas9 mediated NFAT5 deletion indicated that NFAT5 controls numerous genes associated with FGF23 synthesis, thereby confirming its role in [Na$^{+}$]-mediated FGF23 regulation. In line with these in vitro observations, we found that hyponatremia patients have higher FGF23 levels. Our results suggest that [Na$^{+}$] is a critical regulator of FGF23 synthesis

Extracellular sodium regulates fibroblast growth factor 23 (FGF23) formation.

The bone-derived hormone fibroblast growth factor-23 (FGF23) has recently received much attention due to its association with chronic kidney disease and cardiovascular disease progression. Extracellular sodium concentration ([Na+]) plays a significant role in bone metabolism. Hyponatremia (lower serum [Na+]) has recently been shown to be independently associated with FGF23 levels in patients with chronic systolic heart failure. However, nothing is known about the direct impact of [Na+] on FGF23 production. Here, we show that an elevated [Na+] (+20 mM) suppressed FGF23 formation, whereas low [Na+] (-20 mM) increased FGF23 synthesis in the osteoblast-like cell lines UMR-106 and MC3T3-E1. Similar bidirectional changes in FGF23 abundance were observed when osmolality was altered by mannitol but not by urea, suggesting a role of tonicity in FGF23 formation. Moreover, these changes in FGF23 were inversely proportional to the expression of NFAT5 (nuclear factor of activated T cells-5), a transcription factor responsible for tonicity-mediated cellular adaptations. Furthermore arginine vasopressin (AVP), which is often responsible for hyponatremia, did not affect FGF23 production. Next, we performed a comprehensive and unbiased RNA-seq analysis of UMR-106 cells exposed to low vs. high [Na+], which revealed several novel genes involved in cellular adaptation to altered tonicity. Additional analysis of cells with Crisp-Cas9 mediated NFAT5 deletion indicated that NFAT5 controls numerous genes associated with FGF23 synthesis, thereby confirming its role in [Na+]-mediated FGF23 regulation. In line with these in vitro observations, we found that hyponatremia patients have higher FGF23 levels. Our results suggest that [Na+] is a critical regulator of FGF23 synthesis

A qualitative understanding of the effects of reusable sanitary pads and puberty education: Implications for future research and practice

BACKGROUND: The management of menstruation has come to the fore as a barrier to girls’ education attainment in low income contexts. Interventions have been proposed and piloted, but the emerging nature of the field means limited evidence is available to understand their pathways of effect. // METHODS: This study describes and compares schoolgirls’ experiences of menstruation in rural Uganda at the conclusion of a controlled trial of puberty education and sanitary pad provision to elucidate pathways of effect in the interventions. Semi-structured interviews were undertaken with schoolgirls who participated in the Menstruation and the Cycle of Poverty trial concurrent with the final set of quantitative surveys. A framework approach and cross-case analysis were employed to describe and compare the experiences of 27 menstruating girls across the four intervention conditions; education (n = 8), reusable sanitary pads (n = 8), education with reusable sanitary pads (n = 6), and control (n = 5). // RESULTS: Themes included: menstrual hygiene, soiling, irritation and infection, physical experience, knowledge of menstruation, psychological, social and cultural factors, and support from others. Those receiving reusable pads experienced improvements in comfort and reliability. This translated into reduced fears around garment soiling and related school absenteeism. Other menstrual hygiene challenges of washing, drying and privacy remained prominent. Puberty education improved girls’ confidence to discuss menstruation and prompted additional support from teachers and peers. // CONCLUSIONS: Findings have important implications for the development and evaluation of future interventions. Results suggest the provision of menstrual absorbents addresses one core barrier to menstrual health, but that interventions addressing broader needs such as privacy may improve effectiveness. Puberty education sessions should increase attention to body awareness and include strategies to address a wider range of practical menstrual challenges, including pain management. Interviews revealed possibilities for improving quantitative surveys in future research

Indicators for National and Global Monitoring of Girls' Menstrual Health and Hygiene: Development of a Priority Shortlist

Purpose Despite the importance of menstrual health and hygiene (MHH) for adolescent girls' health, education, and gender equality, few countries monitor MHH. MHH needs remain underprioritized, and progress achieved through policies, programs, or investments go unmeasured. This article reports the systematic development of an indicator shortlist to monitor adolescent girls' MHH at the national and global levels across low- and middle-income countries. Methods A core group of MHH researchers and practitioners collaborated with stakeholders from three countries with demonstrated commitment to monitoring MHH (Bangladesh, Kenya, and the Philippines), measures experts, and a global advisory group. The approach included the following: (1) define domains for monitoring MHH; (2) review and map existing indicators and measures; (3) iteratively shortlist indicators through appraising quality, feasibility, and stakeholder input; and (4) refine the shortlist and develop guidance for use. Results The shortlist comprises 21 indicators across seven domains covering menstrual materials, water, sanitation, and hygiene facilities, knowledge, discomforts and disorders, supportive social environments, menstrual health impacts, and policies. Indicators are accompanied by measures that have been tested or are expected to provide reliable data, alongside justification for their selection and guidance for use. Discussion The shortlisted indicators reflect the multisectoral collaboration necessary for ensuring girls' MHH. Uptake requires integration into monitoring systems at national and global levels. Future work remains to evaluate the performance of the indicators over time and to support their widespread use. Governments and stakeholders can use these indicators to track the progress of programs and policies, monitor unmet MHH needs, identify disparities, and set targets for improvement

Research priorities for improving menstrual health across the life-course in low- and middle-income countries

Background: Research on menstrual health is required to understand menstrual needs and generate solutions to improve health, wellbeing, and productivity. The identification of research priorities will help inform where to invest efforts and resources. Objectives: To identify research priorities for menstrual health across the life-course, in consultation with a range of stakeholder groups from a variety of geographic regions, and to identify if menstrual health research priorities varied by expertise. Methods: A modified version of the Child Health and Nutrition Research Initiative approach was utilized to reach consensus on a set of research priorities. Multisector stakeholders with menstrual health expertise, identified through networks and the literature, were invited to submit research questions through an online survey. Responses were consolidated and individuals were invited to rank these questions based on novelty, potential for intervention, and importance/impact. Research priority scores were calculated and evaluated by participants’ characteristics. Results: Eighty-two participants proposed 1135 research questions, which were consolidated into 94 unique research questions. Mean number of questions did not differ between low- and middle-income (LMIC, N=30) and high-income county participants (HIC, N=52), but significantly more questions were raised by participants with expertise in mental health and WASH. Sixty-six participants then ranked these questions. The top ten-ranked research questions included four on ‘understanding the problem’, four on ‘designing and implementing interventions’, one on ‘integrating and scaling up’, and one on ‘measurement’. Indicators for the measurement of adequate menstrual health over time was ranked the highest priority by all stakeholders. Top ten ranked research questions differed between academics and non-academics, and between participants from HICs and LMICs, reflecting differences in needs and knowledge gaps. Conclusions: A list of ranked research priorities was generated through a consultative process with stakeholders across LMICs and HICs which can inform where to invest efforts and resources