bluuebunny/crossref_metadata_2025_split huggingface dataset:
The zinc-finger transcription factor LSL-1 is a major regulator of the germline transcriptional program in C. elegans
Authors: Rodriguez-Crespo David , Nanchen Magali , Rajopadhye Shweta , Wicky Chantal 
Published: December 2021

ABSTRACTSpecific gene transcriptional programs are required to ensure proper proliferation and differentiation processes underlying the production of specialized cells during development. Gene activity is mainly regulated by the concerted action of transcription factors and chromatin proteins. In the nematode C. elegans, mechanisms that silence improper transcriptional programs in germline and somatic cells have been well studied, however, how are tissue specific sets of genes turned on is less known. LSL-1 is herein defined as a novel crucial transcriptional regulator of germline genes in C. elegans. LSL-1 is first detected in the P4 blastomere and remains present at all stages of germline development, from primordial germ cell proliferation to the end of meiotic prophase. lsl-1 loss-of-function mutants exhibit many defects including meiotic prophase progression delay, a high level of germline apoptosis, and production of almost no functional gametes. Transcriptomic analysis and ChIP-seq data show that LSL-1 binds to promoters and acts as a transcriptional activator of germline genes involved in various processes, including homologous chromosome pairing, recombination, and genome stability. Furthermore, we show that LSL-1 functions by antagonizing the action of the heterochromatin proteins HPL-2/HP1 and LET-418/Mi2 known to be involved in the repression of germline genes in somatic cells. Based on our results, we propose LSL-1 to be a major regulator of the germline transcriptional program during development.
Isolation disrupts social interactions and destabilizes brain development in bumblebees
Authors: Wang Z Yan , McKenzie-Smith Grace C. , Liu Weijie , Cho Hyo Jin , Pereira Talmo , Dhanerawala Zahra , Shaevitz Joshua W. , Kocher Sarah D. 
Published: December 2021

SummarySocial isolation, particularly in early life, leads to deleterious physiological and behavioral outcomes. Few studies, if any, have been able to capture the behavioral and neurogenomic consequences of early life social isolation together in a single social animal system. Here, we leverage new high-throughput tools to comprehensively investigate the impact of isolation in the bumblebee (Bombus impatiens) from behavioral, molecular, and neuroanatomical perspectives. We reared newly emerged bumblebees either in complete isolation, small groups, or in their natal colony, and then analyzed their behaviors while alone or paired with another bee. We find that when alone, individuals of each rearing condition show distinct behavioral signatures. When paired with a conspecific, bees reared in small groups or in the natal colony express similar behavioral profiles. Isolated bees, however, showed increased social interactions. To identify the neurobiological correlates of these differences, we quantified brain gene expression and measured the volumes of key brain regions for a subset of individuals from each rearing condition. Overall, we find that isolation increases social interactions and disrupts gene expression and brain development. Limited social experience in small groups is sufficient to preserve typical patterns of brain development and social behavior.
Seed-coat thickness explains contrasting germination responses to smoke and heat by Leucadendron species
Authors: Lamont Byron B. , Barreiro Pablo Gómez , Newton Rosemary J. 
Published: December 2021

AbstractFire stimulates germination of most seeds in fire-prone vegetation. Fruits of Leucadendron (Proteaceae) are winged achenes or nutlets that correlate with their requirements for smoke and/or heat in promoting germination. We describe five possible smoke–heat dormancy-release/germination syndromes among plants, of which Leucadendron displays three (no response, smoke only, smoke and heat). As seed-coat thickness varies with seed-storage location (plant or soil) and morphology (winged or wingless), we tested its possible role in water uptake and germination. Species with winged seeds achieved 100% germination in the absence of smoke/heat, seed coats were an order of magnitude thinner, and their permeability greatly exceeded that of nutlets. As seed-coat thickness increased a) imbibitional water uptake declined at a decreasing rate, and b) the response to smoke, and to a lesser extent heat, increased linearly to reach levels of germination approaching those of winged seeds. For species responsive to smoke and heat, there was no additive effect when applied together, suggesting that they may have promoted the same physiological process. By what mechanisms a) the smoke response is greater the thicker the seed coat, and b) smoke chemicals could increase water permeability to explain the non-additive effect of smoke and heat, warrant further investigation.HighlightWe show Leucadendron seeds are either plant-stored with thin, highly permeable seed-coats that germinate readily; or soil-stored and the thicker their seed-coat, the lower their permeability and greater their need for smoke/heat to promote germination.
SMAD4 and TGFβ are architects of inverse genetic programs during fate-determination of antiviral memory CD8 T cells
Authors: Chandiran K. , Suarez-Ramirez J.E. , Hu Y. , Jellison E.R. , Ugur Z. , Low J.S. , McDonald B. , Kaech S.M. , Cauley L.S. 
Published: December 2021

AbstractTransforming growth factor β (TGFβ) is a morphogenic protein that augments antiviral immunity by altering the functional properties of pathogen-specific memory CD8 T cells. During infection TGFβ inhibits formation of effector (TEFF) and central memory CD8 T cells (TCM), while encouraging tissue-resident memory CD8 T cells (TRM) to settle in peripheral tissues. SMAD proteins are signaling intermediates that are used by members of the TGF cytokine family to modify gene expression. For this study, RNA-sequencing was used to explore how regulation via SMAD4 alters the transcriptional profile of antiviral CTLs during infection. We show that SMAD4 and TGFβ cooperatively regulate a collection of genes that determine whether specialized populations of pathogen-specific CTLs circulate around the body, or settle in peripheral tissue. The target genes include multiple homing receptors (CD103, KLRG1 and CD62L) and transcription factors (Hobit and EOMES) that support memory formation. While TGFβ uses a canonical SMAD-dependent signaling pathway to induce CD103 expression on TRM cells, an alternative SMAD4-dependent mechanism is required for formation of TEFF and TCM cells in the circulation.Graphical abstractTGFβ and SMAD4 modulate gene expression in reciprocal directions during differentiation of antiviral CTLs.
IFN-γ-independent control ofM. tuberculosisrequires CD4 T cell-derived GM-CSF and activation of HIF-1α
Authors: Van Dis Erik , Morrison Huntly M , Fines Daniel M , Babirye Janet Peace , McCann Lily H , Rawal Sagar , Cox Jeffery S , Stanley Sarah A 
Published: December 2021

AbstractThe prevailing model of protective immunity to tuberculosis is that CD4 T cells produce the cytokine IFN-γ to activate bactericidal mechanisms in infected macrophages. Recent evidence has expanded this model, and it is now clear that CD4 T cells can controlM. tuberculosisinfection in the absence of IFN-γ production. To identify factors and pathways involved in IFN-γ-independent control, we developed a co-culture model using CD4 T cells isolated from the lungs of infected mice andM. tuberculosis-infectedmurine bone marrow-derived macrophages (BMDMs). We show that IFN-γ-independent control is primarily mediated by CD4 T cell production of the cytokine GM-CSF and requires activation of the macrophage transcription factor HIF-1α. HIF-1α activation drives a metabolic shift toward aerobic glycolysis and leads to the production of lipid droplets, both of which support host defense against infection. Surprisingly, recombinant GM-CSF is insufficient to rescue the absence of control by GM-CSF-deficient CD4 T cells during co-culture with BMDMs. In peritoneal macrophages, GM-CSF is sufficient to control growth, induces lipid droplet biogenesis, and requires HIF-1α expression for control. While HIF-1α-mediated control following IFN-γ stimulation requires nitric oxide, we find that HIF-1α activation by CD4 T cells and recombinant GM-CSF is nitric oxide-independent, implying a distinct pathway of activation. In addition to GM-CSF, CD4 T cells produce a factor that helps maintain phagosome membrane integrity during infection and blocks bacterial access to host lipids, a primary nutrient source. These results advance our understanding of CD4 T cell-mediated immunity toM. tuberculosis, clarify the role of nitric oxide as primarily immunomodulatory duringM. tuberculosisinfection, and reveal a novel mechanism for the activation of HIF-1α. Furthermore, we establish a previously unknown functional link between GM-CSF and HIF-1α and provide evidence that CD4 T cell-derived GM-CSF is a potent bactericidal effector.
Centromere identity is dependent on nuclear spatial organization
Authors: Wu Weifang , McHugh Toni , Kelly David A. , Pidoux Alison L. , Allshire Robin C. 
Published: December 2021

SummaryThe establishment of centromere-specific CENP-A chromatin is influenced by epigenetic and genetic processes. Central domain sequences from fission yeast centromeres are preferred substrates for CENP-ACnp1 incorporation, but their use is context dependent, requiring adjacent heterochromatin. CENP-ACnp1 overexpression bypasses heterochromatin dependency, suggesting heterochromatin ensures exposure to conditions or locations permissive for CENP-ACnp1 assembly. Centromeres cluster around spindle-pole bodies (SPBs). We show that heterochromatin-bearing minichromosomes localize close to SPBs, consistent with this location promoting CENP-ACnp1 incorporation. We demonstrate that heterochromatin-independent de novo CENP-ACnp1 chromatin assembly occurs when central domain DNA is placed near, but not far from, endogenous centromeres or neocentromeres. Moreover, direct tethering of central domain DNA at SPBs permits CENP-ACnp1 assembly, suggesting that the nuclear compartment surrounding SPBs is permissive for CENP-ACnp1 incorporation because target sequences are exposed to high levels of CENP-ACnp1 and associated assembly factors. Thus, nuclear spatial organization is a key epigenetic factor that influences centromere identity.
SARS-CoV-2 lineage dynamics in England from September to November 2021: high diversity of Delta sub-lineages and increased transmissibility of AY.4.2
Authors: Eales Oliver , Page Andrew J. , de Oliveira Martins Leonardo , Wang Haowei , Bodinier Barbara , Haw David , Jonnerby Jakob , Atchison Christina ,   The COVID-19 Genomics UK (COG-UK) Consortium, Ashby Deborah , Barclay Wendy , Taylor Graham , Cooke Graham , Ward Helen , Darzi Ara , Riley Steven , Chadeau-Hyam Marc , Donnelly Christl A. , Elliott Paul 
Published: December 2021

AbstractSince the emergence of SARS-CoV-2, evolutionary pressure has driven large increases in the transmissibility of the virus. However, with increasing levels of immunity through vaccination and natural infection the evolutionary pressure will switch towards immune escape. Here we present phylogenetic relationships and lineage dynamics within England (a country with high levels of immunity), as inferred from a random community sample of individuals who provided a self-administered throat and nose swab for rt-PCR testing as part of the REal-time Assessment of Community Transmission-1 (REACT-1) study. From 9 to 27 September 2021 (round 14) and 19 October to 5 November 2021 (round 15), all lineages sequenced within REACT-1 were Delta or a Delta sub-lineage with 44 unique lineages identified. The proportion of the original Delta variant (B.1.617.2) was found to be increasing between September and November 2021, which may reflect an increasing number of sub-lineages which have yet to be identified. The proportion of B.1.617.2 was greatest in London, which was further identified as a region with an increased level of genetic diversity. The Delta sub-lineage AY.4.2 was found to be robustly increasing in proportion, with a reproduction number 15% (8%, 23%) greater than its parent and most prevalent lineage, AY.4. Both AY.4.2 and AY.4 were found to be geographically clustered in September but this was no longer the case by late October/early November, with only the lineage AY.6 exhibiting clustering towards the South of England. Though no difference in the viral load based on cycle threshold (Ct) values was identified, a lower proportion of those infected with AY.4.2 had symptoms for which testing is usually recommend (loss or change of sense of taste, loss or change of sense of smell, new persistent cough, fever), compared to AY.4 (p = 0.026). The evolutionary rate of SARS-CoV-2, as measured by the mutation rate, was found to be slowing down during the study period, with AY.4.2 further found to have a reduced mutation rate relative to AY.4. As SARS-CoV-2 moves towards endemicity and new variants emerge, genomic data obtained from random community samples can augment routine surveillance data without the potential biases introduced due to higher sampling rates of symptomatic individuals.
Participatory Research: A Priority Setting Partnership for Chronic Musculoskeletal Pain in Denmark
Authors: Lyng KD , Larsen JB , Birnie K , Stinson J , Hoegh M , Olesen AE , Arendt-Nielsen L , Ehlers L , Fonager K , Jensen MB , Würtzen H , Palsson TS , Poulin P , Handberg G , Ziegler C , Møller LB , Olsen J , Heise L , Rathleff MS 
Published: December 2021

BackgroundPatient and stakeholder engagements in research have increasingly gained attention in healthcare and healthcare-related research. A common and rigorous approach to establish research priorities based on input from people and stakeholders is the James Lind Alliance Priority Setting Partnership (JLA-PSP). The aim of this study was to establish research priorities for chronic musculoskeletal (MSK) pain by engaging with humans living with chronic MSK pain, relatives to humans living with chronic MSK pain, healthcare professionals (HCP), and researchers working with chronic MSK pain.MethodsThis JLA-PSP included a nation-wide survey in Denmark, an interim prioritisation, and an online consensus building workshop. The information gained from this was the basis for developing the final list of specific research priorities within chronic MSK pain.ResultsIn the initial survey, 1010 respondents (91% people living with chronic MSK pain/relatives, 9% HCPs/researchers) submitted 3121 potential questions. These were summarised into 19 main themes and 36 sub-themes. In the interim prioritisation exercise, 51% people living with pain/relatives and 49% HCPs/researchers reduced the list to 33 research questions prior to the final priority setting workshop. 23 participants attended the online workshop (12 people/relatives, 10 HCPs, and 1 researcher) who reached consensus for the most important research priorities after two rounds of discussion of each question.ConclusionThis study identified several specific research questions generated by people living with chronic MSK pain, relatives, HCPs, and researchers. The stakeholders proposed prioritization of the healthcare system’s ability to support patients, focus on developing coherent pathways between sectors and education for both patients and HCP. These research questions can form the basis for future studies, funders, and be used to align research with end-users’ priorities
Single-shot experiments at the soft X-FEL FERMI using a back-side-illuminated scientific CMOS detector
Authors: Léveillé Cyril , Desjardins Kewin , Popescu Horia , Vondungbo Boris , Hennes Marcel , Delaunay Renaud , Jal Emmanuelle , De Angelis Dario , Pancaldi Matteo , Pedersoli Emanuele , Capotondi Flavio , Jaouen Nicolas 
Published: December 2021

The latest Complementary Metal Oxide Semiconductor (CMOS) 2D sensors now rival the performance of state-of-the-art photon detectors for optical application, combining a high-frame-rate speed with a wide dynamic range. While the advent of high-repetition-rate hard X-ray free-electron lasers (FELs) has boosted the development of complex large-area fast CCD detectors in the extreme ultraviolet (EUV) and soft X-ray domains, scientists lacked such high-performance 2D detectors, principally due to the very poor efficiency limited by the sensor processing. Recently, a new generation of large back-side-illuminated scientific CMOS sensors (CMOS-BSI) has been developed and commercialized. One of these cost-efficient and competitive sensors, the GSENSE400BSI, has been implemented and characterized, and the proof of concept has been carried out at a synchrotron or laser-based X-ray source. In this article, we explore the feasibility of single-shot ultra-fast experiments at FEL sources operating in the EUV/soft X-ray regime with an AXIS-SXR camera equipped with the GSENSE400BSI-TVISB sensor. We illustrate the detector capabilities by performing a soft X-ray magnetic scattering experiment at the DiProi end-station of the FERMI FEL. These measurements show the possibility of integrating this camera for collecting single-shot images at the 50 Hz operation mode of FERMI with a cropped image size of 700 × 700 pixels. The efficiency of the sensor at a working photon energy of 58 eV and the linearity over the large FEL intensity have been verified. Moreover, on-the-fly time-resolved single-shot X-ray resonant magnetic scattering imaging from prototype Co/Pt multilayer films has been carried out with a time collection gain of 30 compared to the classical start-and-stop acquisition method performed with the conventional CCD-BSI detector available at the end-station.
The going-concern opinion and the adverse credit rating: an analysis of their relationship
Authors: Strickett Matthew , Hay David C. , Lau David 
Published: December 2021

Purpose
The purpose of this study is to examine the relationship between going-concern (GC) opinions issued by the Big 4 audit firms and adverse credit ratings from the two largest credit rating agencies (CRAs) – Standard & Poor’s (S&P) and Moody’s. This question is relevant because there have been suggestions that auditors and CRAs should become more similar to each other, and because the two largest CRAs have different ownership structures that could affect their ratings.

Design/methodology/approach
Univariate and multivariate analyses are performed using a sample of firms that filed for bankruptcy between January 1, 2002 and December 31, 2013 that also had an audit opinion signed during the 12 months prior to bankruptcy, along with a credit rating issued by either or both S&P and Moody’s. Both influence each other. The likelihood of an auditor issuing a GC opinion is related to the credit rating issued by both S&P and Moody’s in the month prior to the audit report signing. The results also show differences between the CRAs. S&P reacted in the month after an auditor issued a GC opinion by downgrading its ratings 68% of the time. However, Moody’s did not react as strongly as S&P, downgrading its ratings only 24% of the time.

Findings
Both audit reports and credit ratings influence each other. The likelihood of an auditor issuing a GC opinion is related to the credit rating issued by both S&P and Moody’s in the month prior to the audit report signing. The results also show differences between the CRAs. S&P reacted in the month after an auditor issued a GC opinion by downgrading its ratings 68% of the time. However, Moody’s did not react as strongly as S&P, downgrading its ratings only 24% of the time.

Originality/value
Auditors are more likely to issue GC opinions when there is a downgrade to the credit rating, and CRAs are more likely to downgrade their ratings when there is a GC opinion. The study highlights that CRAs with different ownership structures provide different credit rating outcomes.
Pregnancy-related health information behaviour of Estonian women
Authors: Ojaperv Kadri , Virkus Sirje 
Published: December 2021

Purpose
This study aims to increase the understanding of the pregnancy-related information behavior (IB) of pregnant women in Estonia.

Design/methodology/approach
The research involved a quantitative research methodology consisting of a semi-structured questionnaire. Data was collected from pregnant Estonian women through a self-administered Web-based questionnaire using a convenience sampling during the period from January to February 2019. A total of 300 pregnant women answered the questionnaire. The data were analysed using statistical analysis and the results of the study were compared with the results of previous studies.

Findings
The three topics on which information was most frequently sought were: fetal development, use of medicines during pregnancy and symptoms of pregnancy. The main sources of information were the internet and the midwife. The most reliable and valuable source of information was a midwife. Health-related information was sought mainly because it helped women make decisions related to pregnancy and childbirth. A number of factors facilitate the information seeking process. In addition, widespread access to the internet and technological skills facilitated IB. The following factors hindered the search for information: the controversy and/or ambiguity of information published on the internet and the time spent searching for information. Most women used wearable technologies during pregnancy.

Research limitations/implications
This study has several limitations. First, the weakness of online surveys is the potential lack of representativeness, as it excludes from the survey those who do not have access to or ability to use the internet for various reasons (Evans and Mathur, 2005; Limbu et al., 2021). Second, as most recruitment for the study took place online, there was a risk that those who did not use the internet could be excluded from the survey. Third, as the questionnaire was also shared in the Facebook news feed by the Women’s Clinic and Maternity Hospital of the East Tallinn Central Hospital, it may be that the respondents recruited through it more often used the support provided by medical professionals. Fourth, due to the volume limits of the study, it is not possible to present all the results of the study on the basis of socio-demographic characteristics and stage of pregnancy. Therefore, the findings cannot be generalized to the broader population and future studies should explore a larger and more representative populations.

Practical implications
This study will give some useful information to help to improve the services offered for pregnant women in Estonia.

Social implications
The findings of this study may inform how to better support this target group.

Originality/value
There is a lack of research in Estonia that focuses on the IB of pregnant women and this research fills this gap.