Transcription-coupled eviction of histones H2A/H2B governs V(D)J recombination.

Initiation of V(D)J recombination critically relies on the formation of an accessible chromatin structure at recombination signal sequences (RSSs) but how this accessibility is generated is poorly understood. Immunoglobulin light-chain loci normally undergo recombination in pre-B cells. We show here that equipping (earlier) pro-B cells with the increased pre-B-cell levels of just one transcription factor, IRF4, triggers the entire cascade of events leading to premature light-chain recombination. We then used this finding to dissect the critical events that generate RSS accessibility and show that the chromatin modifications previously associated with recombination are insufficient. Instead, we establish that non-coding transcription triggers IgL RSS accessibility and find that the accessibility is transient. Transcription transiently evicts H2A/H2B dimers, releasing 35-40 bp of nucleosomal DNA, and we demonstrate that H2A/H2B loss can explain the RSS accessibility observed in vivo. We therefore propose that the transcription-mediated eviction of H2A/H2B dimers is an important mechanism that makes RSSs accessible for the initiation of recombination

Western Indian Ocean marine and terrestrial records of climate variability: a review and new concepts on land-ocean interactions since AD 1660

We examine the relationship between three tropical and two subtropical western Indian Ocean coral oxygen isotope time series to surface air temperatures (SAT) and rainfall over India, tropical East Africa and southeast Africa. We review established relationships, provide new concepts with regard to distinct rainfall seasons, and mean annual temperatures. Tropical corals are coherent with SAT over western India and East Africa at interannual and multidecadal periodicities. The subtropical corals correlate with Southeast African SAT at periodicities of 16–30 years. The relationship between the coral records and land rainfall is more complex. Running correlations suggest varying strength of interannual teleconnections between the tropical coral oxygen isotope records and rainfall over equatorial East Africa. The relationship with rainfall over India changed in the 1970s. The subtropical oxygen isotope records are coherent with South African rainfall at interdecadal periodicities. Paleoclimatological reconstructions of land rainfall and SAT reveal that the inferred relationships generally hold during the last 350 years. Thus, the Indian Ocean corals prove invaluable for investigating land–ocean interactions during past centuries

Research frontiers for improving our understanding of drought-induced tree and forest mortality

Accumulating evidence highlights increased mortality risks for trees during severe drought, particularly under warmer temperatures and increasing vapour pressure deficit (VPD). Resulting forest die-off events have severe consequences for ecosystem services, biophysical and biogeochemical land–atmosphere processes. Despite advances in monitoring, modelling and experimental studies of the causes and consequences of tree death from individual tree to ecosystem and global scale, a general mechanistic understanding and realistic predictions of drought mortality under future climate conditions are still lacking. We update a global tree mortality map and present a roadmap to a more holistic understanding of forest mortality across scales. We highlight priority research frontiers that promote: (1) new avenues for research on key tree ecophysiological responses to drought; (2) scaling from the tree/plot level to the ecosystem and region; (3) improvements of mortality risk predictions based on both empirical and mechanistic insights; and (4) a global monitoring network of forest mortality. In light of recent and anticipated large forest die-off events such a research agenda is timely and needed to achieve scientific understanding for realistic predictions of drought-induced tree mortality. The implementation of a sustainable network will require support by stakeholders and political authorities at the international level

El Niño Modulations Over The Past Seven Centuries (Letter to the editor)

postprin

Introduction to “Binary Binds”: Deconstructing Sex and Gender Dichotomies in Archaeological Practice

YesGender archaeology has made significant strides toward deconstructing the hegemony of binary categorizations. Challenging dichotomies such as man/woman, sex/gender, and biology/culture, approaches informed by poststructuralist, feminist, and queer theories have moved beyond essentialist and universalist identity constructs to more nuanced configurations. Despite the theoretical emphasis on context, multiplicity, and fluidity, binary starting points continue to streamline the spectrum of variability that is recognized, often reproducing normative assumptions in the evidence. The contributors to this special issue confront how sex, gender, and sexuality categories condition analytical visibility, aiming to develop approaches that respond to the complexity of theory in archaeological practice. The papers push the ontological and epistemological boundaries of bodies, personhood, and archaeological possibility, challenging a priori assumptions that contain how sex, gender, and sexuality categories are constituted and related to each other. Foregrounding intersectional approaches that engage with ambiguity, variability, and difference, this special issue seeks to “de-contain” categories, assumptions, and practices from “binding” our analytical gaze toward only certain kinds of persons and knowledges, in interpretations of the past and practices in the present

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

HOW DO BOARD-CERTIFIED HAND SURGEONS MANAGE CARPAL TUNNEL SYNDROME? A NATIONAL SURVEY

ABSTRACT Objective: To evaluate tendencies in the planning, diagnosis, and treatment of carpal tunnel syndrome (CTS) by Brazilian hand surgery specialists. Methods: This cross-sectional study was performed at the 36th Brazilian Hand Surgery Congress. We prepared a questionnaire about preferences in the management of CTS, and board-certified hand surgeons that attended the congress were asked to fill out the questionnaires. A total of 174 questionnaires were analyzed. Results: Electromyography examination is used by most surgeons. Night splinting is the most commonly used conservative treatment option. Half of the surgeons utilized prophylactic antibiotics. Most of the interviewees conduct inpatient surgery in the operating room and prefer intravenous regional anesthesia. Most of surgeons use the standard open technique associated with proximal release of the antebrachial fascia and do not perform neurolysis. Compressive dressings are most commonly used for 7 days. Conclusion: The approach to CTS among Brazilian hand surgeons with regard to pre-, intra-, and post-operatory conduct is consistent with the international literature. However, there is a need to reflect and conduct new studies on non-surgical treatment involving local corticosteroid injection, use of prophylactic antibiotics, hospital admission, and type of anesthesia in order to provide more cost-effective approach to surgical treatment for CTS. Level of Evidence V; Expert opinion.</div

Orthodontics in the era of big data analytics

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149344/1/ocr12279_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149344/2/ocr12279.pd

p38MAPK, ERK and PI3K Signaling Pathways Are Involved in C5a-Primed Neutrophils for ANCA-Mediated Activation

BACKGROUND: The complement system is one of the important contributing factors in the development of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). C5a and the neutrophil C5a receptor play a central role in antineutrophil cytoplasmic antibody (ANCA)-mediated neutrophil recruitment and activation. The current study further investigated the signaling pathways of C5a-mediated priming of human neutrophils for ANCA-induced neutrophil activation. METHODOLOGY/PRINCIPAL FINDINGS: The effects of the p38 mitogen-activated protein kinase (p38MAPK) inhibitor (SB202190), extracellular signal-regulated kinase (ERK) inhibitor (PD98059), c-Jun N-terminal kinase (JNK) inhibitor (6o) and phosphoinositol 3-kinase (PI3K) inhibitor (LY294002) were tested on respiratory burst and degranulation of C5a-primed neutrophils activated with ANCA, as well as on C5a-induced increase in expression of membrane-bound PR3 (mPR3) on neutrophils. For C5a-primed neutrophils for MPO-ANCA-induced respiratory burst, the mean fluorescence intensity (MFI) value was 254.8±67.1, which decreased to 203.6±60.3, 204.4±36.7, 202.4±49.9 and 188±47.9 upon pre-incubation with SB202190, PD98059, LY294002 and the mixture of above-mentioned three inhibitors (compared with that without inhibitors, P<0.01, P<0.05, P<0.01 and P<0.05), respectively. For PR3-ANCA-positive IgG, the MFI value increased in C5a-primed neutrophils, which decreased upon pre-incubation with above-mentioned inhibitors. The lactoferrin concentration increased in C5a-primed neutrophils induced by MPO or PR3-ANCA-positive IgG supernatant and decreased upon pre-incubation with above-mentioned three inhibitors. mPR3 expression increased from 923.3±182.4 in untreated cells to 1278.3±299.3 after C5a treatment and decreased to 1069.9±188.9, 1100±238.2, 1092.3±231.8 and 1053.9±200.3 by SB202190, PD98059, LY294002 and the mixture of above-mentioned three inhibitors (compared with that without inhibitors, P<0.01, P<0.05, P<0.01 and P<0.01), respectively. CONCLUSIONS/SIGNIFICANCE: Activation of p38MAPK, ERK and PI3K are important steps in the translocation of ANCA antigens and C5a-induced activation of neutrophils by ANCA

Of risks and regulations: how leading U.S. nanoscientists form policy stances about nanotechnology

Even though there is a high degree of scientific uncertainty about the risks of nanotechnology, many scholars have argued that policy-making cannot be placed on hold until risk assessments are complete (Faunce, Med J Aust 186(4):189–191, 2007; Kuzma, J Nanopart Res 9(1):165–182, 2007; O’Brien and Cummins, Hum Ecol Risk Assess 14(3):568–592, 2008; Powell et al., Environ Manag 42(3):426–443, 2008). In the absence of risk assessment data, decision makers often rely on scientists’ input about risks and regulation to make policy decisions. The research we present here goes beyond the earlier descriptive studies about nanotechnology regulation to explore the heuristics that the leading U.S. nanoscientists use when they make policy decisions about regulating nanotechnology. In particular, we explore the relationship between nanoscientists’ risk and benefit perceptions and their support for nanotech regulation. We conclude that nanoscientists are more supportive of regulating nanotechnology when they perceive higher levels of risks; yet, their perceived benefits about nanotechnology do not significantly impact their support for nanotech regulation. We also find some gender and disciplinary differences among the nanoscientists. Males are less supportive of nanotech regulation than their female peers and materials scientists are more supportive of nanotechnology regulation than scientists in other fields. Lastly, our findings illustrate that the leading U.S. nanoscientists see the areas of surveillance/privacy, human enhancement, medicine, and environment as the nanotech application areas that are most in need of new regulations