bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structure and dynamics of FCHo2 docking on membranes
Authors: Alaoui F. El , Casuso I. , Sanchez-Fuentes D. , André-Arpin C. , Rathar R. , Baecker V. , Castro A. , Lorca T. , Viaud J. , Vassilopoulos S. , Carretero-Genevrier A. , Picas. L. 
Published: April 2021

AbstractClathrin-mediated endocytosis (CME) is a central trafficking pathway in eukaryotic cells regulated by phosphoinositides. The plasma membrane phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) plays an instrumental role in driving CME initiation. The F-BAR domain only protein 1 and 2 complex (FCHo1/2) is among the early proteins that reach the plasma membrane, but the exact mechanisms triggering its recruitment remains elusive. Here, we show the molecular dynamics of FCHo2 self-assembly on membranes by combining bottom-up synthetic approaches on in vitro and cellular membranes. Our results indicate that PI(4,5)P2 domains assist FCHo2 docking at specific membrane regions, where it self-assembles into ring-like shape protein patches. We show that binding of FCHo2 on cellular membranes promotes PI(4,5)P2 clustering at the boundary of cargo receptors and that this accumulation enhances clathrin assembly. Thus, our results provide a mechanistic framework that could explain the recruitment of early PI(4,5)P2-interacting proteins at endocytic sites.
Pseudogene-mediated gene conversion after CRISPR-Cas9 editing demonstrated by partialCD33conversion withSIGLEC22P
Authors: Shaw Benjamin C. , Estus Steven 
Published: April 2021

AbstractAlthough gene editing workflows typically consider the possibility of off-target editing, pseudogene-directed homology repair has not, to our knowledge, been reported previously. Here, we employed a CRISPR-Cas9 strategy for targeted excision of exon 2 inCD33in U937 human monocyte cell line. Candidate clonal cell lines were screened by using a clinically relevant antibody known to label the IgV domain encoded by exon 2 (P67.6, gemtuzumab). In addition to the anticipated deletion of exon 2, we also found unexpected P67.6-negative cell lines which had apparently retained CD33 exon 2. Sequencing revealed that these lines underwent gene conversion from the nearby SIGLEC22P pseudogene during homology repair that resulted in three missense mutations relative to CD33. Ectopic expression studies confirmed that the P67.6 epitope is dependent upon these amino acids. In summation, we report that pseudogene-directed homology repair can lead to aberrant CRISPR gene editing.
Group size influences individual metabolic traits in a social fish
Authors: Chrétien Emmanuelle , Boisclair Daniel , Cooke Steven J. , Killen Shaun S. 
Published: April 2021

AbstractGroup living is widespread among animal species and yields both costs and benefits. Presence of conspecifics can restrict or enhance the expression of individual behaviour, and the recent social environment is thought to affect behavioural responses in later contexts, even when individuals are alone. However, little is known about how social dynamics influence the expression of individual physiological traits, including metabolic rates.There is some evidence that shoaling can reduce fish metabolic rates, but habitat conditions such as shelter availability may generate density-dependent influences on individual metabolic rates.We investigated how social group size and availability of shelter influence Eurasian minnowPhoxinus phoxinusmetabolic rates estimated by respirometry in the presence or absence of plant shelter. Respirometry trials were conducted before and after we housed fish for three weeks in a social treatment consisting in a specific group size (n= 4 or 8) and shelter availability (presence or absence of plant shelter in the holding tank).Minimum day-time and night-time metabolic rates estimated while in presence of plant shelter were lower than when estimated in absence of plant shelter, both before and after individuals were housed in their social group size and shelter availability treatment. Standard metabolic rate was higher for fish held in groups of four as compared to fish held in groups of eight while maximum metabolic rate showed no difference. Shelter availability during the social treatments did not influence standard or maximum metabolic rates.Our results suggest that group size may directly influence energy demands of individuals, highlighting the importance of understanding the role of social dynamics on variations in physiological traits associated with energy expenditure.
Compartmentalized control of Cdk1 drives mitotic spindle assembly
Authors: Serpico Angela Flavia , Febbraro Francesco , Pisauro Caterina , Grieco Domenico 
Published: April 2021

AbstractDuring cell division, dramatic microtubular rearrangements driven by cyclin B-cdk1 (Cdk1) kinase activity mark mitosis onset leading to interphase cytoskeleton dissolution and mitotic spindle assembly. Once activated by Cdc25, that reverses inhibitory phosphorylation operated by Wee1/Myt1, Cdk1 clears the cytoplasm from microtubules by inhibiting microtubule associated proteins (MAPs) with microtubule growth-promoting properties. Nevertheless, some of these MAPs are required for spindle assembly, creating quite a conundrum. We show here that a Cdk1 fraction bound to spindle structures escaped Cdc25 action and remained inhibited by phosphorylation (i-Cdk1) in mitotic human cells. Loss or restoration of i-Cdk1 inhibited or promoted spindle assembly, respectively. Furthermore, polymerizing spindle microtubules fostered i-Cdk1 by aggregating with Wee1 and excluding Cdc25. Our data reveal that spindle assembly relies on compartmentalized control of Cdk1 activity.
MBNL1 and RBFOX1 co-regulate alternative splicing events transcriptome-wide through a conserved buffering mechanism
Authors: Hale Melissa , Ellis Joseph , Meng Ryan , McDaniel Sunny , Mahady Amy , Wagner Stacey , Richardson Jared , McConnell Ona , Wang Eric , Berglund J. Andrew 
Published: April 2021

AbstractAlternative splicing (AS) is controlled bycis-regulatory elements recognized by networks oftrans-acting factors. Here we investigate modes and mechanisms of AS co-regulation by MBNL1 and RBFOX1, two RNA binding proteins (RBPs) critical for developmental AS transitions. We generated two cell models that express each RBP under separate inducible promoters. Transcriptome-wide categorization of the impacts of RBFOX1 expression on MBNL1 splicing revealed a common co-regulatory mode through which RBFOX1buffersMBNL1 dose-dependent splicing regulation by reducing the total range of exon inclusion or exclusion. Minigene mutational analysis andin vitrobinding experiments suggest that thisbufferingmechanism occurs through a sharedcis-regulatory element previously unidentified as critical for MBNL1-dependent activity. Overall, our studies define a conserved co-regulatory mechanism through which RBFOX1 and MBNL1 can fine-tune and provide redundancy for AS outcomes. These studies indicate overlapping use of RNA motifs with potential implications for when activity of RBPs is disrupted.
TheDrosophilaanterior-posterior axis is polarized by asymmetric myosin activation
Authors: Doerflinger Hélène , Zimyanin Vitaly , Johnston Daniel St 
Published: April 2021

AbstractTheDrosophilaanterior-posterior (AP) axis is specified at mid-oogenesis when Par-1 kinase is recruited to the posterior cortex of the oocyte, where it polarises the microtubule cytoskeleton to define where the axis determinants,bicoidandoskarmRNAs localise. This polarity is established in response to an unknown signal from the follicle cells, but how this occurs is unclear. Here we show that the myosin chaperone, Unc-45 and Non-Muscle Myosin II (MyoII) are required in the germ line upstream of Par-1 in polarity establishment. Furthermore, the Myosin regulatory Light Chain (MRLC) is di-phosphorylated at the oocyte posterior in response to the follicle cell signal, inducing longer pulses of myosin contractility at the posterior and increased cortical tension. Over-expression of MRLC-T21A that cannot be di-phosphorylated or acute treatment with the Myosin light chain kinase inhibitor ML-7 abolish Par-1 localisation, indicating that posterior of MRLC di-phosphorylation is essential for polarity. Thus, asymmetric myosin activation polarizes the anterior-posterior axis by recruiting and maintaining Par-1 at the posterior cortex. This raises an intriguing parallel with AP axis formation inC. eleganswhere MyoII is also required to establish polarity, but functions to localize the anterior PAR proteins rather than PAR-1.
Dielectric barrier discharge cold atmospheric plasma: Influence of processing parameters on microbial inactivation in meat and meat products
Authors: Nasiru Mustapha Muhammad , Frimpong Evans Boateng , Muhammad Umair , Qian Jing , Mustapha Abdullateef Taiye , Yan Wenjing , Zhuang Hong , Zhang Jianhao 
Published: April 2021

AbstractDecontamination of meat is commonly practiced to get rid of or decrease the microbial presence on the meat surface. Dielectric barrier discharge cold atmospheric plasma (DBD‐CAP) as innovative technology is a food microbial inactivation technique considered in high regard by food scientists and engineers in present times. However, cold atmospheric plasma application is at the experimental stage, due to lack of sufficient information on its mode of action in inactivating microbes, food shelf‐life extensibility, whereas, the nutritional value of food is preserved. In this review, we have appraised recent work on DBD‐CAP concerning the decontamination treatment of meat products, highlighting the processing value results on the efficacy of the DBD‐CAP microbial inactivation technique. Also, the paper will review the configurations, proposed mechanisms, and chemistry of DBD‐CAP. Satisfactory microbial inactivation was observed. In terms of DBD‐CAP application on sensory evaluation, inferences from reviewed literature showed that DBD has no significant effect on meat color and tenderness, whereas in contrast, TBARS values of fresh and processed meat are affected. DBD seems economically efficient and environmentally sustainable.
Prey decline leads to diet shift in the largest population of Indo‐Pacific humpback dolphins?
Authors: LIN Wenzhi , KARCZMARSKI Leszek , ZHOU Ruilian , MO Yaqian , GUO Lang , YIU Sam King Fung , NING Xi , WAI Tak‐Cheung , WU Yuping 
Published: April 2021

AbstractThe Pearl River Delta (PRD) region on the southeast coast of China has long been known as a highly productive fishing ground. Since the late 1980s, fishing pressure in the PRD has been intense, which warrants concerns of potential fishery‐related impacts on the food resources and foraging ecology of apex marine predators in this region, such as the Indo‐Pacific humpback dolphin (Sousa chinensis). In this study, we examined 54 stomachs with food remains, collected from beached carcasses of humpback dolphins recovered during fifteen years between 2003 and 2017. The 6043 identified prey items represent 62 teleost taxa, primarily small estuarine fish, but also larger reef fish. The dolphins appear to be opportunistic foragers, hunting across the water‐column, with preference for shoaling and meaty fishes (e.g.Collichthys lucidusIRI% = 38.6%,Johnius belangeriiIRI% = 23.1%,Mugil cephalusIRI% = 14.0%). Our findings suggest a dietary shift in recent years, from primarily demersal (as previously reported) to greater intake of neritic and pelagic fish. Dolphin foraging group size has decreased in recent years, which corresponds with declining size and numbers of prey items retrieved from dolphin stomachs. We suggest that these are indicators of declining food resources. Faced with a shortage of preferred prey, humpback dolphins may have broadened their dietary spectrum to maintain their daily energy intake, while their foraging group size decreased in response to the altered tradeoff between the costs and benefits of group foraging.
The clinical relevance of IgM and IgA anti-pneumococcal polysaccharide ELISA assays in patients with suspected antibody deficiency
Authors: Janssen Lisanne M A , Heron Michiel , Murk Jean-Luc , Leenders Alexander C A P , Rijkers Ger T , de Vries Esther 
Published: April 2021

Summary
Unlike immunoglobulin (Ig)G pneumococcal polysaccharide (PnPS)-antibodies, PnPS IgA and IgM-antibodies are not routinely determined for the assessment of immunocompetence. It is not yet known whether an isolated inability to mount a normal IgM or IgA-PnPS response should be considered a relevant primary antibody deficiency (PAD). We studied the clinical relevance of anti-PnPS IgM and IgA-assays in patients with suspected primary immunodeficiency in a large teaching hospital in ’s-Hertogenbosch, the Netherlands. Serotype-specific-PnPS IgG assays were performed; subsequently, 23-valent-PnPS IgG assays (anti-PnPS IgG assays), and later anti-PnPS IgA and IgM assays, were performed in archived material (240 patients; 304 samples). Eleven of 65 pre- and six of 10 post-immunization samples from good responders to PnPS serotype-specific IgG testing had decreased anti-PnPS IgA and/or IgM titres. Of these, three pre- and no post-immunization samples were from patients previously classified as ‘no PAD’. Determination of anti-PnPS IgA and IgM in addition to anti-PnPS IgG did not reduce the need for serotype-specific PnPS IgG testing to assess immunocompetence [receiver operating characteristic (ROC) analysis of post-immunization samples: anti-PnPS IgA + IgG area under the curve (AUC) = 0.80, 95% confidence interval (CI) = 0.63–0.97; anti-PnPS IgM + IgG AUC 0.80, 95% CI = 0.62–0.98; anti-PnPS IgA + IgG + IgM AUC = 0.71, 95% CI = 0.51–0.91; anti-PnPS IgG AUC = 0.93, 95% CI = 0.85–1.00]. Our data show that patients classified as having an intact antibody response based on measurement of serotype-specific PnPS IgG can still display impaired anti-PnPS IgM and IgA responses, and that the additional measurement of anti-PnPS IgA and IgM could not reduce the need for serotype-specific IgG testing. Future studies are needed to investigate the clinical relevance of potential ‘specific IgA or IgM antibody deficiency’ in patients with recurrent airway infections in whom no PAD could be diagnosed according to the current definitions.
Common and distinct neural trends of allocentric and egocentric spatial coding: An ALE meta‐analysis
Authors: Derbie Abiot Y. , Chau Bolton K .H. , Wong Clive H. Y. , Chen Li‐Dian , Ting Kin‐hung , Lam Bess Y. H. , Lee Tatia M. C. , Chan Chetwyn C. H. , Smith Yoland 
Published: April 2021

AbstractThe uniqueness of neural processes between allocentric and egocentric spatial coding has been controversial. The distinctive paradigms used in previous studies for manipulating spatial coding could have attributed for the inconsistent results. This study was aimed to generate converging evidence from previous functional brain imaging experiments for collating neural substrates associated with these two types of spatial coding. An additional aim was to test whether test‐taking processes would have influenced the results. We obtained coordinate‐based functional neuroimaging data for 447 subjects and performed activation likelihood estimation (ALE) meta‐analysis. Among the 28 experiments, the results indicate two common clusters of convergence. They were the right precuneus and the right superior frontal gyrus as parts of the parieto‐frontal circuit. Between‐type differences were in the parieto‐occipital circuit, with allocentric showing convergence in the superior occipital gyrus (SOG) cluster compared with egocentric showing convergence in the middle occipital gyrus (MOG) cluster. Task‐specific influences were only found in allocentric spatial coding. Spatial judgment‐oriented tasks seem to increase the demands on manipulating spatial relationships among the visual objects, while spatial navigation tasks seem to increase the demands on maintaining object representations. Our findings address the theoretical controversies on spatial coding that both the allocentric and egocentric types are common in their processes mediated by the parieto‐frontal network, while unique and additional processes in the allocentric type are mediated by the parieto‐occipital network. The positive results on possible task‐specific confound offer insights into the future design of spatial tasks for eliciting spatial coding processes.
A thermal trade‐off between viral production and degradation drives virus‐phytoplankton population dynamics
Authors: Demory David , Weitz Joshua S. , Baudoux Anne‐Claire , Touzeau Suzanne , Simon Natalie , Rabouille Sophie , Sciandra Antoine , Bernard Olivier 
Published: April 2021

AbstractMarine viruses interact with microbial hosts in dynamic environments shaped by variation in abiotic factors, including temperature. However, the impacts of temperature on viral infection of phytoplankton are not well understood. Here we coupled mathematical modelling with experiments to explore the effect of temperature on virus‐phytoplankton interactions. Our model shows the negative consequences of high temperatures on infection and suggests a temperature‐dependent threshold between viral production and degradation. Modelling long‐term dynamics in environments with different average temperatures revealed the potential for long‐term host‐virus coexistence, epidemic free or habitat loss states. We generalised our model to variation in global sea surface temperatures corresponding to present and future seas and show that climate change may differentially influence virus‐host dynamics depending on the virus‐host pair. Temperature‐dependent changes in the infectivity of virus particles may lead to shifts in virus‐host habitats in warmer oceans, analogous to projected changes in the habitats of macro‐, microorganisms and pathogens.
The American robin (Turdus migratorius): A focal species for anti‐parasitic egg rejection studies among hosts of the brown‐headed cowbird (Molothrus ater)
Authors: Turner Abbigail M. , Hauber Mark E. 
Published: April 2021

AbstractObligate avian brood parasites lay their eggs in the nest of other species and impose reproductive costs upon their hosts. In response, many hosts have evolved a variety of defenses to avoid or reduce the costs associated with parasitism, including the rejection of parasitic eggs. Here, we review the different sensory and contextual cues involved in egg rejection by the American robin (Turdus migratorius), one of the handful of rejecter host species of the brood parasitic brown‐headed cowbird (Molothrus ater) in North America. Robins are an open‐cup nesting species whose eggs dramatically differ in appearance from the cowbirds' eggs; therefore, we expect that visual cues would be the primary sensory modality used when rejecting foreign eggs. The results of our comprehensive review confirm that visual cues, including eggshell color and maculation, are strong predictors of robins' egg rejection responses. Egg size, egg shape, and other contextual traits (including clutch composition, maternal status, and sympatry with the parasite) also affect egg rejection in this host species. Future research into this species' egg rejection mechanisms would benefit from comparisons to other strongly and moderately egg rejecter host species of brown‐headed cowbirds, as well as from seeking to understand further why so many hosts of this particular parasitic lineage accept foreign eggs. We also discuss the implications of this review for other egg rejecter and non‐rejecter hosts of diverse avian brood parasites.
Hepatic stellate cell as a Mac‐2‐binding protein‐producing cell in patients with liver fibrosis
Authors: Gantumur Dolgormaa , Harimoto Norifumi , Muranushi Ryo , Hoshino Kouki , Batbayar Chingun , Hagiwara Kei , Yamanaka Takahiro , Ishii Norihiro , Tsukagoshi Mariko , Igarashi Takamichi , Watanabe Akira , Kubo Norio , Araki Kenichiro , Yokobori Takehiko , Aishima Shinichi , Shirabe Ken 
Published: April 2021

AbstractBackgroundMac‐2 binding protein (M2BP) glycosylated isomer (M2BPGi) is a serum marker of liver fibrosis; M2BPGi is a glycosylated form of M2BP. Hepatocytes and hepatic stellate cells (HSCs) have been studied to determine the source of M2BP. This study proposes to identify the origin of M2BP in fibrotic liver.MethodsUsing liver fibrosis tissue specimens from 15 patients with liver cancer, M2BP mRNA and M2BP were detected by in situ hybridization and immunohistochemistry, respectively. The expression levels of M2BP mRNA were evaluated with scores of 3, 2, and 1. Fluorescent in situ hybridization was carried out to evaluate the distribution of M2BP mRNA and the activated‐HSC marker αSMA mRNA; multicolor fluorescent immunohistochemistry was used for protein localization of M2BP, αSMA, and CD68. The Kruskal–Wallis test analyzed the relationship between M2BP mRNA expression and existing serum fibrosis markers.ResultsM2BP mRNA was expressed in spindle‐shaped cells along the fibrous septa and in the perisinusoidal area of the fibrotic liver. The HSC markers αSMA mRNA and M2BP mRNA were colocalized in the spindle‐shaped cells; on the protein level, M2BP was expressed in Kupffer cells. M2BP mRNA expression was positively correlated with serum M2BPGi levels. Aspartate transaminase‐to‐platelet ratio index, Fibrosis‐4, hyaluronic acid, and the 15‐minute indocyanine green retention rate were significantly correlated with M2BP mRNA expression.ConclusionsM2BP mRNA transcription in fibrotic liver was primarily observed in HSCs but not at the M2BP level, which suggests that HSCs might produce and introduce M2BP to Kupffer cells and serum.
Changes in alanine aminotransferase levels after switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) in HIV‐positive people without viral hepatitis in the Swiss HIV Cohort Study
Authors: Kovari H , Surial B , Tarr PE , Cavassini M , Calmy A , Schmid P , Bernasconi E , Rauch A , Wandeler G , Ledergerber B ,   the Swiss HIV Cohort Study
Published: April 2021

ObjectivesWe previously demonstrated an association between tenofovir disoproxil fumarate (TDF) and chronic liver enzyme elevation in the D:A:D study. The objective of the study was to assess changes in alanine aminotransferase (ALT) levels after switching from TDF to tenofovir alafenamide (TAF).MethodsWe included Swiss HIV Cohort Study participants who switched from TDF to TAF with two or more ALT values in the 24 months before and two or more values in the 24 months after replacing TDF with TAF. Individuals with replicating viral hepatitis were excluded. Uni‐ and multivariable linear mixed models were used to explore changes in ALT values associated with switching from TDF to TAF, and to assess potential modifying effects.ResultsA total of 1712 participants were included, contributing 6169 ALT values before and 5482 after switching. Median (interquartile range, IQR) age was 50 (42–57) years, and 75% were male. Median (IQR) ALT was 28 (22–38) U/L before and 24 (19–32) U/L after replacing TDF with TAF. ALT values decreased by 3.7 U/L (95% confidence interval: 3.2–4.2) after the switch. The median drop was larger in patients with chronic ALT elevation (defined as two or more elevated values for ≥ 6 months) compared with patients with normal ALT values (17.8 vs. 3.3 U/L, P < 0.001). We did not identify any major effect modifications of the ALT change with any of the potential variables studied.ConclusionsReplacing TDF with TAF in HIV‐monoinfected people led to a significant decrease in ALT values. Findings were not significantly affected by known risk factors for hepatotoxicity.