Herpes simplex virus blocks host transcription termination via the bimodal activities of ICP27

Infection by viruses, including herpes simplex virus-1 (HSV-1), and cellular stresses cause widespread disruption of transcription termination (DoTT) of RNA polymerase II (RNAPII) in host genes. However, the underlying mechanisms remain unclear. Here, we demonstrate that the HSV-1 immediate early protein ICP27 induces DoTT by directly binding to the essential mRNA 3' processing factor CPSF. It thereby induces the assembly of a dead-end 3' processing complex, blocking mRNA 3' cleavage. Remarkably, ICP27 also acts as a sequence-dependent activator of mRNA 3' processing for viral and a subset of host transcripts. Our results unravel a bimodal activity of ICP27 that plays a key role in HSV-1-induced host shutoff and identify CPSF as an important factor that mediates regulation of transcription termination. These findings have broad implications for understanding the regulation of transcription termination by other viruses, cellular stress and cancer

Exploring Spirituality in Teaching Within a Christian School Context Through Collaborative Action Research

This article reports on a collaborative action research project conducted in New Zealand, during 2012, exploring spirituality in teaching within a Christian school context. The experienced primary school teacher participant chose to take action around the issue of personal fear and insecurity which were believed to be hindering professional growth and relationships. Through self-directed inquiry, critical reflective journaling, Bible study, fellowship and prayer with trusted friends, the teacher experienced a renewed sense of peace and freedom in Christ. This personal transformation was believed to be influential on subsequent professional practice, assisting the teacher to become more relational, responsive and compassionate. The findings provide a rich description of the participant’s spirituality, the lived reality of a person’s spiritual life. This report will be of interest to teachers, teacher-leaders and teacher-educators who desire to explore Christian spirituality through practitioner-led inquiry

Automated tracking reveals the social network of beach mice and their burrows

Evolutionary biologists have long sought to understand the selective pressures driving phenotypic evolution. While most experimental data come from the study of morphological evolution, we know much less about the ultimate drivers of behavioral variation. Among the most striking examples of behavioral evolution are the long, complex burrows constructed by oldfield mice (Peromyscus polionotus ssp.). Yet how these mice use burrows in the wild, and whether burrow length may affect fitness, remains unknown. A major barrier to studying behavior in the wild has been the lack of technologies to continuously monitor – in this case, nocturnal and underground – behavior. Here, we designed and implemented a novel radio frequency identification (RFID) system to track patterns of burrow use in a natural population of beach mice. We combine RFID monitoring with burrow measurements, genetic data, and social network analysis to uncover how these monogamous mice use burrows under fully natural ecological and social conditions. We first found that long burrows provide a more stable thermal environment and have higher juvenile activity than short burrows, underscoring the likely importance of long burrows for rearing young. We also find that adult mice consistently use multiple burrows throughout their home range and tend to use the same burrows at the same time as their genetic relatives, suggesting that inclusive fitness benefits may accrue for individuals that construct and maintain multiple burrows. Our study highlights how new automated tracking approaches can provide novel insights into animal behavior in the wild

A transmission spectrum of the sub-Earth planet L98-59~b in 1.1-1.7 μ\mum

With the increasing number of planets discovered by TESS, the atmospheric characterization of small exoplanets is accelerating. L98-59 is a M-dwarf hosting a multi-planet system, and so far, four small planets have been confirmed. The innermost planet b is $\sim15\%$ smaller and $\sim60\%$ lighter than Earth, and should thus have a predominantly rocky composition. The Hubble Space Telescope observed five primary transits of L98-59b in $1.1-1.7\ \mu$m, and here we report the data analysis and the resulting transmission spectrum of the planet. We measure the transit depths for each of the five transits and, by combination, we obtain a transmission spectrum with an overall precision of $\sim20$ ppm in for each of the 18 spectrophotometric channels. With this level of precision, the transmission spectrum does not show significant modulation, and is thus consistent with a planet without any atmosphere or a planet having an atmosphere and high-altitude clouds or haze. The scenarios involving an aerosol-free, H$_2$-dominated atmosphere with H$_2$O or CH$_4$ are inconsistent with the data. The transmission spectrum also disfavors, but does not rules out, an H$_2$O-dominated atmosphere without clouds. A spectral retrieval process suggests that an H$_2$-dominated atmosphere with HCN and clouds or haze may be the preferred solution, but this indication is non-conclusive. Future James Webb Space Telescope observations may find out the nature of the planet among the remaining viable scenarios.Comment: 17 pages, 5 figures, 7 tables, accepted for publication in A

Efficient Induction of Extrinsic Cell Death by Dandelion Root Extract in Human Chronic Myelomonocytic Leukemia (CMML) Cells

BACKGROUND: Chronic Myelomonocytic Leukemia (CMML) is a heterogeneous disease that is not only hard to diagnose and classify, but is also highly resistant to treatment. Available forms of therapy for this disease have not shown significant effects and patients rapidly develop resistance early on in therapy. These factors lead to the very poor prognosis observed with CMML patients, with median survival duration between 12 and 24 months after diagnosis. This study is therefore centered around evaluating the selective efficacy of a natural extract from dandelion roots, in inducing programmed cell death in aggressive and resistant CMML cell lines. METHODOLOGY/PRINCIPAL FINDINGS: To confirm the induction of programmed cell death in three human CMML cell lines, nuclear condensation and externalization of the phosphatidylserine, two main characteristics of apoptosis, were detected using Hoechst staining and annexin-V binding assay. The induction of another mode of cell death, autophagy, was determined using a monodansylcadaverine (MDC) stain, to detect the formation of autophagy vacuoles. The results from this study indicate that Dandelion Root Extract (DRE) is able to efficiently and selectively induce apoptosis and autophagy in these cell lines in a dose and time dependent manner, with no significant toxicity on non-cancerous peripheral blood mononuclear cells. More importantly, we observed early activation of initiator caspase-8, which led to mitochondrial destabilization and the induction of autophagy, suggesting that DRE acts through the extrinsic pathway of apoptosis. The inability of DRE to induce apoptosis in dominant-negative FADD cells, confirms the mechanism of action of DRE in in vitro models of CMML. CONCLUSION: The results from this study indicate that natural products, in particular Dandelion Root Extract, have great potential, as non-toxic and effective alternatives to conventional modes of chemotherapy available today

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

The effects of kisspeptin on β-cell function, serum metabolites and appetite in humans

Aims: To investigate the effect of kisspeptin on glucose-stimulated insulin secretion and appetite in humans. Materials and methods: In 15 healthy men (age: 25.2 ± 1.1 years; BMI: 22.3 ± 0.5 kg m−2), we compared the effects of 1 nmol kg−1 h−1 kisspeptin versus vehicle administration on glucose-stimulated insulin secretion, metabolites, gut hormones, appetite and food intake. In addition, we assessed the effect of kisspeptin on glucose-stimulated insulin secretion in vitro in human pancreatic islets and a human β-cell line (EndoC-βH1 cells). Results: Kisspeptin administration to healthy men enhanced insulin secretion following an intravenous glucose load, and modulated serum metabolites. In keeping with this, kisspeptin increased glucose-stimulated insulin secretion from human islets and a human pancreatic cell line in vitro. In addition, kisspeptin administration did not alter gut hormones, appetite or food intake in healthy men. Conclusions: Collectively, these data demonstrate for the first time a beneficial role for kisspeptin in insulin secretion in humans in vivo. This has important implications for our understanding of the links between reproduction and metabolism in humans, as well as for the ongoing translational development of kisspeptin-based therapies for reproductive and potentially metabolic conditions