bluuebunny/crossref_metadata_2025_split huggingface dataset:
H3K27me3 is dispensable for early differentiation but required to maintain differentiated cell identity
Authors: Miller Sara A. , Damle Manashree , Kingston Robert E. 
Published: June 2020

AbstractPolycomb repressive complex 2 (PRC2) catalyzes trimethylation of histone H3 on lysine 27 and is required for normal development of complex eukaryotes. The requirement for H3K27me3 in various aspects of mammalian differentiation is not clear. Though associated with repressed genes, the modification is not sufficient to induce gene repression, and in some instances is not required. To examine the role of the modification in mammalian differentiation, we blocked trimethylation of H3K27 with both a small molecule inhibitor, GSK343, and by introducing a point mutation into EZH2, the catalytic subunit of PRC2. We found that cells with substantively decreased H3K27 tri-methylation were able to differentiate, which contrasts with EZH2 null cells. Different PRC2 targets had varied requirements for H3K27me3 in repressive regulation with a subset that maintained normal levels of repression in the absence of methylation. The primary cellular phenotype when H3K27 tri-methylation was blocked was an inability of the altered cells to maintain a differentiated state when challenged. This phenotype was determined by H3K27me3 deposition both in embryonic stem cells and in the first four days of differentiation. H3K27 tri-methylation therefore was not necessary for formation of differentiated cell states but was required to maintain a stable differentiated state.
Dynamic extrinsic pacing of theHOXclock in human axial progenitors controls motor neuron subtype specification
Authors: Mouilleau Vincent , Vaslin Célia , Gribaudo Simona , Robert Rémi , Nicolas Nour , Jarrige Margot , Terray Angélique , Lesueur Léa , Mathis Mackenzie W. , Croft Gist , Daynac Mathieu , Rouiller-Fabre Virginie , Wichterle Hynek , Ribes Vanessa , Martinat Cécile , Nedelec Stéphane 
Published: June 2020

SUMMARYRostro-caudal patterning of vertebrates depends on the temporally progressive activation ofHOXgenes within axial stem cells that fuel axial embryo elongation. WhetherHOXgenes sequential activation, the “HOXclock”, is paced by intrinsic chromatin-based timing mechanisms or by temporal changes in extrinsic cues remains unclear. Here, we studiedHOXclock pacing in human pluripotent stem cells differentiating into spinal cord motor neuron subtypes which are progenies of axial progenitors. We show that the progressive activation of caudalHOXgenes in axial progenitors is controlled by a dynamic increase in FGF signaling. Blocking FGF pathway stalled induction ofHOXgenes, while precocious increase in FGF alone, or with GDF11 ligand, accelerated theHOXclock. Cells differentiated under acceleratedHOXinduction generated appropriate posterior motor neuron subtypes found along the human embryonic spinal cord. TheHOXclock is thus dynamically paced by exposure parameters to secreted cues. Its manipulation by extrinsic factors alleviates temporal requirements to provide unprecedented synchronized access to human cells of multiple, defined, rostro-caudal identities for basic and translational applications.
Genome-wide CRISPRi/a screens in human neurons link lysosomal failure to ferroptosis
Authors: Tian Ruilin , Abarientos Anthony , Hong Jason , Hashemi Sayed Hadi , Yan Rui , Dräger Nina , Leng Kun , Nalls Mike A. , Singleton Andrew B. , Xu Ke , Faghri Faraz , Kampmann Martin 
Published: June 2020

AbstractSingle-cell transcriptomics provide a systematic map of gene expression in different human cell types. The next challenge is to systematically understand cell-type specific gene function. The integration of CRISPR-based functional genomics and stem cell technology enables the scalable interrogation of gene function in differentiated human cells. Here, we present the first genomewide CRISPR interference and CRISPR activation screens in human neurons.We uncover pathways controlling neuronal response to chronic oxidative stress, which is implicated in neurodegenerative diseases. Unexpectedly, knockdown of the lysosomal protein prosaposin strongly sensitizes neurons, but not other cell types, to oxidative stress by triggering the formation of lipofuscin, a hallmark of aging, which traps iron, generating reactive oxygen species and triggering ferroptosis. We also determine transcriptomic changes in neurons following perturbation of genes linked to neurodegenerative diseases. To enable the systematic comparison of gene function across different human cell types, we establish a data commons named CRISPRbrain.
Antifungal activity of 2,3-diphenyl-2,3-dihydro-1,3-thiaza-4-ones againsttwohuman pathogenic fungi
Authors: Liporagi-Lopes Livia , Sobhi Hany F. , Silverberg Lee J. , Cordero Radames J.B. , Casadevall Arturo 
Published: June 2020

ABSTRACTInvasive fungal diseases are prevalent in immunocompromised individuals in whom current therapies often provide suboptimal results. Additionally, the increased resistance to the available antifungal drugs necessitates a search for new compounds. This study reports the antifungal activity of six 5-, 6-, and 7-membered 2,3-diphenyl-2,3-dihydro-1,3-thiaza-4-ones againstLomentospora prolificansandCryptococcus neoformans. Our data showed that some of the compounds tested had a low MIC and damage on the cell surface of the tested fungal species.
The epidemiology of autoimmune liver disease varies with geographic latitude
Authors: Webb Gwilym J , Ryan Ronan P , Marshall Tom P , Hirschfield Gideon M 
Published: June 2020

AbstractBackground & aimsThe epidemiology of autoimmune liver disease (AILD) is challenging to study because of the diseases’ rarity and because of cohort selection bias. Increased incidence further from the Equator is reported for multiple sclerosis, another autoimmune. We assessed the incidence of primary biliary cholangitis (PBC), primary biliary cholangitis (PSC), and autoimmune hepatitis (AIH) in relation to latitude.MethodsRetrospective cohort study using anonymised UK primary care records 2002-01-01 to 2016-05-10. All adults without a baseline diagnosis of autoimmune liver disease were included and followed until first occurrence of an AILD diagnosis, death, or they left the database. Latitude was measured as registered general practice rounded down to whole degrees.ResultsThe cohort included 8 590 421 records with 53.3 107 years follow-up from 694 practices.There were 1314 incident cases of PBC, 396 of PSC, and 1034 of AIH. Crude incidences (95% confidence interval) was: PBC 2.47 (2.34-2.60), PSC 0.74 (0.67-0.82), and AIH 1.94 (1.83-2.06)/100 000/year. PBC incidence correlated with female sex, smoking, and deprivation; PSC incidence correlated with male sex and not smoking; AIH incidence correlated with female sex and deprivation.More northerly latitude was strongly associated with incidence of PBC: 2.16 (1.79-2.60) to 4.86 (3.93-6.00) from 50-57°N (p=0.002) and AIH 2.00 (1.65-2.43) to 3.28 (2.53-4.24)(p=0.003), but not PSC 0.82 (0.60-1.11) to 1.02 (0.64-1.61)(p=0.473).Incidence after adjustment for age, sex, smoking, and deprivation status showed similar positive correlations for PBC and AIH with latitude, but not PSC. Incident AIH cases were younger at greater latitude.ConclusionsWe describe a novel association between increased latitude and the incidence of PBC and AIH that requires both confirmation and explanation.
Evidence of associative blocking during foraging in the social wasp Vespula germanica
Authors: Moreyra Sabrina , D'Adamo Paola , Lozada Mariana 
Published: June 2020

AbstractWhile foraging, Vespula germanica usually return to abundant food sites. During this relocation behavior, these wasps learn to identify contextual cues associated with food position. We analyzed associative blocking in this species, that is, how an association with a conditioned stimulus (CS1) blocks subsequent learning when a novel stimulus (CS2) is added on a second foraging visit. Three groups of wasps (A, B, and C; total 74 individual wasps) were observed while collecting meat during one or two consecutive visits. In group A, an environmental cue (CS1) was paired with food placed at a specific site, and on the second visit, a second cue (CS2) was added while food remained in the same position. In a subsequent testing phase, CS1 was removed and the food source displaced nearby. We then recorded the number of hovers performed over the empty dish (previously baited). Group A wasps appeared to ignore the addition of CS2 on their second visit because they performed fewer hovers over the learned site. For group A, the duration of the decision‐making process to finally fly toward the baited dish was shorter than when CS1 and CS2 were presented together on their first visit (group B). This is the first study to demonstrate the occurrence of associative blocking in vespids, confirming that a prior foraging experience influences subsequent food relocation in V. germanica. Our findings reveal that first learning episodes block further associations with novel contextual cues, contributing to understanding of complex cognitive processes involved in V. germanica´s foraging behavior.
Characterisation of bird cherry‐oat aphid (Rhopalosiphum padi L.) behaviour and aphid host preference in relation to partially resistant and susceptible wheat landraces
Authors: Singh Beant , Simon Amma , Halsey Kirstie , Kurup Smita , Clark Suzanne , Aradottir Gudbjorg Inga 
Published: June 2020

AbstractThe bird cherry‐oat aphid (Rhopalosiphum padi L.) is a major pest of wheat (Triticum aestivum L.) and can cause up to 30% yield losses. Heritable plant resistance to aphids is both an economically and ecologically sound method for managing aphids. Here we report how the behaviour and performance of R. padi differs on two resistant, one susceptible wheat landrace and a susceptible elite wheat variety. Feeding behaviour differed among the genotypes, with aphids on resistant lines spending longer in the pathway phase and less time phloem feeding. These behaviours suggest that both inter‐ and intracellular factors encountered during pathway and phloem feeding phases could be linked to the observed aphid resistance. Locomotion and antennal positioning choice tests also revealed a clear preference for susceptible lines. Although feeding studies revealed differences in the first probe indicating that the resistance factors might also be located in the peripheral layers of the plant tissue, scanning electron microscopy revealed no difference in trichrome length and density on the surface of leaves. Aphids are phloem feeders and limiting the nutrient uptake by the aphids may negatively affect their growth and development as shown here in lower weight and survival of nymphs on resistant genotypes and decreased reproductive potential, with lowest mean numbers of nymphs produced by aphids on W064 (54.8) compared to Solstice (71.9). The results indicate that resistant lines markedly alter the behaviour, reproduction and development potential of R. padi and possess both antixenosis and antibiosis type of resistance.
Borderline patients have difficulties describing feelings; bipolar II patients describe difficult feelings. An alexithymia study
Authors: Bøen E. , Hummelen B. , Boye B. , Elvsåshagen T. , Malt U. F. 
Published: June 2020

ObjectiveApparent similarities between borderline personality disorder (BPD) and bipolar II disorder (BIP‐II) contribute to clinical difficulties in distinguishing between the disorders. Here, we aimed to explore how subjective Difficulties with the Identification and Description of Feelings (DIDF), a major constituent of the alexithymia construct and assessed as a part of the Toronto Alexithymia Scale (TAS), are related to relationship problems and health complaints in these groups.MethodsTwenty‐two patients with BPD; 22 patients with BIP‐II; and 23 healthy controls (HC) completed TAS. Health complaints, including symptoms associated with mood swings, were assessed with the Giessener Subjective Complaints List (Giessener Beschwerdebogen—GBB), and relationship problems with the Health of the Nation Outcome scale, Relationship item (HoNOSR). Bivariate correlations were run.ResultsBoth patient groups had high DIDF and GBB scores. In BPD only, there was a significant positive correlation between DIDF and HoNOSR. In BIP‐II only, there was a significant positive correlation between DIDF and GBB total score. In BIP‐II, DIDF correlated highly with those GBB subscales assessing symptoms typically occurring during bipolar mood swings (cardiovascular and gastrointestinal symptoms, exhaustion).ConclusionOur results suggest that in BPD, high DIDF scores represent genuine problems with identifying and describing emotions which are expected to correlate with relationship problems. In BIP‐II, high DIDF scores could potentially represent difficulties with understanding the unpredictable symptoms of bipolar mood swings. The findings suggest that difficulties with identifying and describing feelings in patients should be carefully explored to increase the validity of the diagnostic evaluation.
Low androgen status inhibits erectile function by inducing eNOS uncoupling in rat corpus cavernosum
Authors: Xiong Wenju , Kong Xiangjun , Jiang Jun , Yang Zhihui , Jiang Rui 
Published: June 2020

AbstractBackgroundThe number of erectile dysfunction (ED) patients is increasing annually. How to improve the effectiveness of ED treatment is an important issue for the field of andrology.ObjectivesTo investigate whether low androgen status impairs the erectile function of rats by regulated endothelial nitric oxide synthase (eNOS) uncoupling.Materials and methodsThirty‐six 8‐week‐old male Sprague Dawley (SD) rats were randomly divided into six groups as follows: 4‐week sham‐operated group (4w‐sham), 4‐week castration group (4w‐cast), 4‐week castration + testosterone (T) group (4w‐cast + T), 8‐week sham‐operated group (8w‐sham), 8‐week castration group (8w‐cast), and 8‐week castration + T group (8w‐cast + T). Three mg/kg of T was subcutaneously injected every other day in castration + T groups. The ratio of the maximum intracavernous pressure/the mean arterial pressure (ICPmax/MAP), the level of serum T, dihydrobiopterin(BH2), tetrahydrobiopterin (BH4), nitric oxygen(NO), 3‐nitrotyrosine(3NT), dihydrofolate reductase (DHFR), guanosine triphosphate cyclohydrolase 1 (GTPCH1), nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2), and eNOS monomers/dimers in the corpus cavernosum were detected.ResultsThe ratio of ICPmax/MAP and BH4/BH2, the level of serum T, NO, and GTPCH1 decreased significantly in castration groups compared with sham‐operated groups and castration + T groups (P < .05) and decreased significantly in 8w‐cast group compared with 4w‐cast group (P < .05). The expression of 3NT and NOX2 and the ratio of eNOS monomers/dimers increased significantly in castration groups compared with sham‐operated groups and castration + T groups (P < .01) and increased significantly in 8w‐cast group compared with 4w‐cast group (P < .01). The expression of DHFR in 4w‐cast group was significantly higher than that in 4w‐sham group and 4w‐cast + T group (P < .01) and in 8w‐cast group was significantly lower than that in 8w‐sham group and 8w‐cast + T group (P < .01).Discussion and ConclusionLow androgen status induces eNOS uncoupling by reducing BH4/BH2 and increasing 3NT. Due to the decreased NO production, the erectile function of the rats was impaired.
Comparison of infection in cemented, cementless and hybrid primary total knee arthroplasty: a network meta‐analysis and systematic review of randomized clinical trials
Authors: Onggo James , Onggo Jason , Phan Kevin , Wilson Christopher 
Published: June 2020

AbstractBackgroundProsthetic joint infection (PJI) is a serious complication of joint replacement surgeries. Surgeons often take extra measures to reduce the risk of PJI. Whilst many studies have compared between cemented, cementless and hybrid fixation (femoral cementless, tibial cemented), most focus on survivorship, clinical and function outcome scores as primary endpoints. This meta‐analysis aims to study the association between fixation methods and risk of PJI in primary total knee arthroplasty (TKA).MethodsA systematic review and network meta‐analysis of randomized controlled trials (RCT) were performed according to Preferred Reporting Items for Systematic reviews and Meta‐Analyses guidelines. Data from studies assessing prevalence of PJI in each fixation type were extracted and analysed.ResultsTwelve RCT comprising a total of 1573 knees were included. Six RCT compared between cemented (n = 486 knees) and cementless (n = 440 knees) fixation, while six RCT compared between hybrid (n = 324 knees) and cementless (n = 323 knees) fixation. Network meta‐analysis did not reveal any fixation type that significantly increased the infection rate in TKA. Rate of all infection was lowest in cemented TKA as compared to cementless (odds ratio (OR) 0.90, 95% confidence interval (CI) 0.35–2.28) and hybrid (OR 0.63, 95%CI 0.13–2.99) TKA. Rate of PJI requiring revision surgery was lowest in cementless TKA as compared to cemented (OR 0.89, 95%CI 0.30–2.41) and hybrid (OR 0.57, 95%CI 0.09–2.71) TKA. Rate of PJI not requiring revision surgery was lowest in cemented TKA as compared to hybrid (OR 0.56, 95%CI 0.06–6.10) and cementless (OR 0.55, 95% 0.14–5.63).ConclusionUnlike total hip arthroplasties, fixation method is not a predisposing risk factor for infections in TKA. However, this meta‐analysis may not have sufficient statistical power to show a significant difference between fixation types. It is recommended that prophylactic precautions against other known risk factors for infection should still be clinically practiced. Level of evidence: Level I, meta‐analysis of randomized controlled trials.
Safe surgery during the coronavirus disease 2019 crisis
Authors: Tivey David R. , Davis Sean S. , Kovoor Joshua G. , Babidge Wendy J. , Tan Lorwai , Hugh Thomas J. , Collinson Trevor G. , Hewett Peter J. , Padbury Robert T. A. , Maddern Guy J. 
Published: June 2020

AbstractBackgroundCoronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has created a global pandemic. Surgical care has been impacted, with concerns raised around surgical safety, especially in terms of laparoscopic versus open surgery. Due to potential aerosol transmission of SARS‐CoV‐2, precautions during aerosol‐generating procedures and production of surgical plume are paramount for the safety of surgical teams.MethodsA rapid review methodology was used with evidence sourced from PubMed, Departments of Health, surgical colleges and other health authorities. From this, a working group of expert surgeons developed recommendations for surgical safety in the current environment.ResultsPre‐operative testing of surgical patients with reverse transcription‐polymerase chain reaction does not guarantee lack of infectivity due to a demonstrated false‐negative rate of up to 30%. All bodily tissues and fluids should therefore be treated as a potential source of COVID‐19 infection during operative management. Caution must be taken, especially when using an energy source that produces surgical plumes, and an appropriate capture device should also be used. Limiting the use of such devices or using lower energy devices is desirable. To reduce perceived risks association with desufflation of pneumoperitoneum during laparoscopic surgery, an appropriate suction irrigator system, attached to a high‐efficiency particulate air filter, should be used. Additionally, appropriate use of personal protective equipment by the surgical team is necessary during high‐risk aerosol‐generating procedures.ConclusionsAs a result of the rapid review, evidence‐based guidance has been produced to support safe surgical practice.
Nuclear microenvironment in cancer: Control through liquid‐liquid phase separation
Authors: Nozawa Ryu‐Suke , Yamamoto Tatsuro , Takahashi Motoko , Tachiwana Hiroaki , Maruyama Reo , Hirota Toru , Saitoh Noriko 
Published: June 2020

AbstractThe eukaryotic nucleus is not a homogenous single‐spaced but a highly compartmentalized organelle, partitioned by various types of membraneless structures, including nucleoli, PML bodies, paraspeckles, DNA damage foci and RNA clouds. Over the past few decades, these nuclear structures have been implicated in biological reactions such as gene regulation and DNA damage response and repair, and are thought to provide “microenvironments,” facilitating these reactions in the nucleus. Notably, an altered morphology of these nuclear structures is found in many cancers, which may relate to so‐called “nuclear atypia” in histological examinations. While the diagnostic significance of nuclear atypia has been established, its nature has remained largely enigmatic and awaits characterization. Here, we review the emerging biophysical principles that govern biomolecular condensate assembly in the nucleus, namely, liquid‐liquid phase separation (LLPS), to investigate the nature of the nuclear microenvironment. In the nucleus, LLPS is typically driven by multivalent interactions between proteins with intrinsically disordered regions, and is also facilitated by protein interaction with nucleic acids, including nuclear non–coding RNAs. Importantly, an altered LLPS leads to dysregulation of nuclear events and epigenetics, and often to tumorigenesis and tumor progression. We further note the possibility that LLPS could represent a new therapeutic target for cancer intervention.
Physically Based Simulation and Rendering of Urban Thermography
Authors: Aguerre José Pedro , García‐Nevado Elena , Acuña Paz y Miño Jairo , Fernández Eduardo , Beckers Benoit 
Published: June 2020

AbstractUrban thermography is a non‐invasive measurement technique commonly used for building diagnosis and energy efficiency evaluation. The physical interpretation of thermal images is a challenging task because they do not necessarily depict the real temperature of the surfaces, but one estimated from the measured incoming radiation. In this sense, the computational rendering of a thermal image can be useful to understand the results captured in a measurement campaign. The computer graphics community has proposed techniques for light rendering that are used for its thermal counterpart. In this work, a physically based simulation methodology based on a combination of the finite element method (FEM) and ray tracing is presented. The proposed methods were tested using a highly detailed urban geometry. Directional emissivity models, glossy reflectivity functions and importance sampling were used to render thermal images. The simulation results were compared with a set of measured thermograms, showing good agreement between them.