bluuebunny/crossref_metadata_2025 huggingface dataset:
The Polygenic Score Catalog: new functionality and tools to enable FAIR research
Authors: Lambert Samuel A. , Wingfield Benjamin , Gibson Joel T. , Gil Laurent , Ramachandran Santhi , Yvon Florent , Saverimuttu Shirin , Tinsley Emily , Lewis Elizabeth , Ritchie Scott C. , Wu Jingqin , Canovas Rodrigo , McMahon Aoife , Harris Laura W. , Parkinson Helen , Inouye Michael
Published: May 2024

Polygenic scores (PGS) have transformed human genetic research and have multiple potential clinical applications, including risk stratification for disease prevention and prediction of treatment response. Here, we present a series of recent enhancements to the PGS Catalog (www.PGSCatalog.org), the largest findable, accessible, interoperable, and reusable (FAIR) repository of PGS. These include expansions in data content and ancestral diversity as well as the addition of new features. We further present the PGS Catalog Calculator (pgsc_calc,https://github.com/PGScatalog/pgsc_calc), an open-source, scalable and portable pipeline to reproducibly calculate PGS that securely democratizes equitable PGS applications by implementing genetic ancestry estimation and score normalization using reference data. With the PGS Catalog & calculator users can now quantify an individual’s genetic predisposition for hundreds of common diseases and clinically relevant traits. Taken together, these updates and tools facilitate the next generation of PGS, thus lowering barriers to the clinical studies necessary to identify where PGS may be integrated into clinical practice.
Leprosy stigma in the healthcare setting: The treatment-seeking journey of persons affected by Leprosy in Niger
Authors: Alio Amina P. , Mamane Sani Ibrahim Malam , Abdou Yohanna , Gado Moussa , Harouna Issa , Celiktemur Bahadir
Published: May 2024

Leprosy-related stigma is deeply rooted in history and permeates every aspect of society, and stigmatization by healthcare professionals is no exception. This paper explores the experiences of persons affected by Leprosy with stigma in the healthcare setting throughout their treatment-seeking journey. We conducted one-on-one interviews with 112 individuals who experienced a Leprosy diagnosis and underwent treatment. Data was collected in July and August 2022, in 9 villages and 1 urban neighborhood in the region of Maradi, Niger. Over two-thirds of participants experienced some form of visible impairment due to Leprosy. Throughout their treatment-seeking journey, healthcare providers were reported to have stigmatized patients by using hurtful language, isolating patients, physically distancing from patients, or refusing to treat. The extent of the stigmatization depended on, first, whether Leprosy was recognized or not. Unfortunately, many healthcare providers did not detect the early signs of Leprosy, therefore, patients were then not able to obtain treatment prior to physical impairment. Second, the level of stigmatization varied based on the degree and type of visible physical impairments (e.g., missing fingers or toes, limbs, blindness). These negative experiences with healthcare workers made treatment-seeking and adherence to treatment regimen less likely for patients. Our findings confirm the presence of Leprosy stigma in the healthcare context in Niger. Increasing Leprosy knowledge and addressing stigma among healthcare professionals is key to early diagnosis and treatment of Leprosy.
Views and experiences of Antimicrobial Stewardship interventions in paediatric secondary care settings: A Qualitative Evidence Synthesis
Authors: Mate Nirzer , Vergnano Stefania , Cabral Christie
Published: May 2024

Objectives

Injudicious use of antimicrobial agents contributes to antimicrobial resistance. Antimicrobial Stewardship (AMS) interventions use strategies derived from evidence-based practices to ensure careful use of antibiotics. AMS is less common in paediatrics as compared to adult practice. As AMS success depends on organizational factors and individual behaviours, this study synthesizes the existing qualitative evidence exploring key barriers, facilitators, and acceptability of AMS.

Methods

Design

A systematic search of primary qualitative studies was conducted in electronic databases.

Data sources

MEDLINE, PsychINFO via OVID, CINAHL electronic database and handsearching of grey literature sources was done.

Eligibility criteria

Qualitative studies exploring parents” and/or clinicians” (doctors and nurses) views, attitudes, beliefs, and knowledge on antimicrobial stewardship programmes in paediatric and neonatal hospitals.

Data extraction and synthesis

Quality appraisal was done using the Critical Appraisal Skills Programme (CASP) tool for qualitative studies. The extracted data was then synthesised by drawing on meta-ethnography.

Results

A total of 6 studies met the inclusion criteria. 5 studies reported the views and experiences of doctors and nurses, and 1 study reported those of parents. The perceived value of AMS differed in neonatal and paediatric contexts. Structural barriers like resource allocation and hospital organization were a barrier to implementation and acceptability. Nurses reported a lack of formal education about AMS as a barrier.

Conclusion/Implications

The factors affecting AMS in paediatric secondary care vary with the stakeholders in question. This review identifies some of the factors that can be used to formulate service-level AMS interventions and programmes.

Strengths and limitations of the study

This is the first evidence synthesis of the qualitative literature exploring the beliefs and experiences of parents and clinicians regarding paediatric AMS.

The facilitators and barriers were identified from themes representative of all the included studies, increasing their validity.

While included studies were conducted across six countries, all were within the developed world which could limit the generalisability of the findings.

A limited number of studies was included due to limited number of primary studies conducted in this area.

Original protocol from PROSPERO

Registration number: CRD42022346842

Available from:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022346842The process for data synthesis was changed from thematic analysis to meta-ethnography to accommodate the variety of ways in which the results were reported in the included studies.
Early changes in microRNA expression in Arabidopsis plants infected with the fungal pathogenFusarium graminearum
Authors: Ferreira Savio S. , Pandey Suman , Hemminger Jesseca , Bozdag Serdar , Antunes Mauricio S.
Published: May 2024

Plants respond to biotic stressors by modulating various processes in an attempt to limit the attack by a pathogen or herbivore. Triggering these different defense processes requires orchestration of a network of proteins and RNA molecules that includes microRNAs (miRNAs). These short RNA molecules (20-22 nucleotides) have been shown to be important players in the early responses of plants to stresses because they can rapidly regulate the expression levels of a network of downstream genes. The ascomyceteFusarium graminearumis an important fungal pathogen that causes significant losses in cereal crops worldwide. Using the well-characterizedFusarium-Arabidopsispathosystem, we investigated how plants change expression of their miRNAs globally during the early stages of infection byF. graminearum. In addition to miRNAs that have been previously implicated in stress responses, we have also identified evolutionarily young miRNAs whose levels change significantly in response to fungal infection. Some of these young miRNAs have homologs present in cereals. Thus, manipulating expression of these miRNAs may provide a unique path toward development of plants with increased resistance to fungal pathogens.
Optimistic and pessimistic cognitive judgement bias modulates the stress response and cancer progression in zebrafish
Authors: Espigares Felipe , Victoria Alvarado M. , Abad-Tortosa Diana , Varela Susana A. M. , Sobral Daniel , Faísca Pedro , Paixão Tiago , Oliveira Rui F.
Published: May 2024

Cognitive judgement bias in decision-making under ambiguity occurs both in animals and humans, with some individuals interpreting ambiguous stimulus as positive (optimism) and others as negative (pessimism). We hypothesize that judgement bias is a personality trait and that individuals with a pessimistic bias would be more reactive to stressors and therefore more susceptible to stress-related diseases than optimistic ones. Here, we show that zebrafish judgment bias is a consistent behavioral trait over time, and that pessimistic and optimistic fish express phenotype-specific neurogenomic responses to stress. Furthermore, both phenotypes show differential activation of the hypothalamic-pituitary-interrenal axis in response to chronic stress, suggesting that optimists have a lower stress reactivity. Accordingly, optimists seem to be more resilient to disease than pessimists, as shown by a lower tumorigenesis in a zebrafish melanoma line [Tg(mtifa:HRAS-GFP)]. Together these results indicate that judgement bias is paralleled by differences in the stress response with implications for disease resilience.
Zebrafish (Danio rerio) behavioral phenotypes not underscored by different gut microbiota
Authors: Ayayee Paul A. , Wong Ryan Y.
Published: May 2024

Different animal behavioral phenotypes maintained and selectively bred over multiple generations may be underscored by dissimilar gut microbial community compositions or not have any significant dissimilarity in community composition. Operating within the microbiota-gut-brain axis framework, we anticipated differences in gut microbiome profiles between zebrafish (Danio rerio) selectively bred to display the bold and shy personality types. This would highlight gut microbe-mediated effects on host behavior. To this end, we amplified and sequenced a fragment of the 16S rRNA gene from the guts of bold and shy zebrafish individuals (n=10) via Miseq. We uncovered no significant difference in within-group microbial diversity nor between-group microbial community composition of the two behavioral phenotypes. Interestingly, though not statistically different, we determined that the gut microbial community of the bold phenotype was dominated byBurkholderiaceae, Micropepsaceae,andPropionibacteriaceae. In contrast, the shy phenotype was dominated byBeijerinckaceae, Pirelullacaeae, Rhizobiales_Incertis_Sedis, andRubinishaeraceae.The absence of any significant difference in gut microbiota profiles between the two phenotypes would suggest that in this species, there might exist a stable “core” gut microbiome, regardless of behavioral phenotypes, and or possibly, a limited role for the gut microbiota in modulating this selected-for host behavior. This is the first study to characterize the gut microbial community of distinct innate behavioral phenotypes of the zebrafish (that are not considered dysbiotic states) and not rely on antibiotic or probiotic treatments to induce changes in behavior. Such studies are crucial to our understanding of the modulating impacts of the gut microbiome on normative animal behavior.
Pathobiology of the autophagy-lysosomal pathway in the Huntington’s disease brain
Authors: Berg Martin J. , Veeranna  , Rosa Corrinne M. , Kumar Asok , Mohan Panaiyur S. , Stavrides Philip , Marchionini Deanna M. , Yang Dun-Sheng , Nixon Ralph A.
Published: May 2024

Accumulated levels of mutant huntingtin protein (mHTT) and its fragments are considered contributors to the pathogenesis of Huntington’s disease (HD). Although lowering mHTT by stimulating autophagy has been considered a possible therapeutic strategy, the role and competence of autophagy-lysosomal pathway (ALP) during HD progression in the human disease remains largely unknown. Here, we used multiplex confocal and ultrastructural immunocytochemical analyses of ALP functional markers in relation to mHTT aggresome pathology in striatum and the less affected cortex of HD brains staged from HD2 to HD4 by Vonsattel neuropathological criteria compared to controls. Immunolabeling revealed the localization of HTT/mHTT in ALP vesicular compartments labeled by autophagy-related adaptor proteins p62/SQSTM1 and ubiquitin, and cathepsin D (CTSD) as well as HTT-positive inclusions. Although comparatively normal at HD2, neurons at later HD stages exhibited progressive enlargement and clustering of CTSD-immunoreactive autolysosomes/lysosomes and, ultrastructurally, autophagic vacuole/lipofuscin granules accumulated progressively, more prominently in striatum than cortex. These changes were accompanied by rises in levels of HTT/mHTT and p62/SQSTM1, particularly their fragments, in striatum but not in the cortex, and by increases of LAMP1 and LAMP2 RNA and LAMP1 protein. Importantly, no blockage in autophagosome formation and autophagosome-lysosome fusion was detected, thus pinpointing autophagy substrate clearance deficits as a basis for autophagic flux declines. The findings collectively suggest that upregulated lysosomal biogenesis and preserved proteolysis maintain autophagic clearance in early-stage HD, but failure at advanced stages contributes to progressive HTT build-up and potential neurotoxicity. These findings support the prospect that ALP stimulation applied at early disease stages, when clearance machinery is fully competent, may have therapeutic benefits in HD patients.
Enhancing lipid production in plant cells through high-throughput genome editing and phenotyping via a scalable automated pipeline
Authors: Dong Jia , Croslow Seth W. , Lane Stephan T. , Castro Daniel C. , Blanford Jantana , Zhou Shuaizhen , Park Kiyoul , Burgess Steven , Root Mike , Cahoon Edgar , Shanklin John , Sweedler Jonathan V. , Zhao Huimin , Hudson Matthew E.
Published: May 2024

Plant bioengineering is a time-consuming and labor-intensive process, with no guarantee of achieving the desired trait. Here we report a fast, automated, scalable, high-throughput pipeline for plant bioengineering (FAST-PB). FAST-PB achieves gene cloning, genome editing, and product characterization by integrating automated biofoundry engineering of callus and protoplast cells with single cell matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). We first demonstrate that FAST-PB can streamline the Golden Gate cloning process, with the capacity to construct 96 vectors in parallel. To prove the concept, using FAST-PB, we first found that PEG2050 significantly increases transfection efficiency by over 45%. To validate the pipeline, we established a reporter-gene-free method for CRISPR editing via mutation ofHCF136, affecting cellular chlorophyll fluorescence. Next, we applied this pipeline for lipid production and found that diverse lipids were significantly enhanced up to sixfold through introducing multi-gene cassettes via CRISPR activation, and regenerated plant using this platform. Lastly, we harnessed FAST-PB to achieve high-throughput single-cell lipid profiling through the integration of MALDI-MS with the biofoundry, and differentiated engineered and unengineered cells using the single-cell lipidomics. These innovations massively increase the throughput of synthetic biology, genome editing, and metabolic engineering, and change what is possibly using single-cell metabolomics in plants.
Data Independent Acquisition to Inform the Development of Targeted Proteomics Assays Using a Triple Quadrupole Mass Spectrometer
Authors: Plubell Deanna L. , Huang Eric , Spencer Sandra E. , Poston Kathleen , Montine Thomas J. , MacCoss Michael J.
Published: May 2024

Mass spectrometry based targeted proteomics methods provide sensitive and high-throughput analysis of selected proteins. To develop a targeted bottom-up proteomics assay, peptides must be evaluated as proxies for the measurement of a protein or proteoform in a biological matrix. Candidate peptide selection typically relies on predetermined biochemical properties, data from semi-stochastic sampling, or by empirical measurements. These strategies require extensive testing and method refinement due to the difficulties associated with prediction of peptide response in the biological matrix of interest. Gas-phase fractionated (GPF) narrow window data-independent acquisition (DIA) aids in the development of reproducible selected reaction monitoring (SRM) assays by providing matrix-specific information on peptide detectability and quantification by mass spectrometry. To demonstrate the suitability of DIA data for selecting peptide targets, we reimplement a portion of an existing assay to measure 98 Alzheimer’s disease proteins in cerebrospinal fluid (CSF). Peptides were selected from GPF-DIA based on signal intensity and reproducibility. The resulting SRM assay exhibits similar quantitative precision to published data, despite the inclusion of different peptides between the assays. This workflow enables development of new assays without additional up-front data acquisition, demonstrated here through generation of a separate assay for an unrelated set of proteins in CSF from the same dataset.
Time from treatment initiation to HIV viral suppression in public care facilities in Brazil: a nationwide linked databases cohort
Authors: Nemes Maria Ines Battistella , Sayuri Sato Ana Paula , Reis-Santos Barbara , Alves Ana Maroso , Parra do Nascimento Felipe , Agins Bruce
Published: May 2024

Objectives

To analyze the time between antiretroviral therapy (ART) initiation and the first HIV viral load (VL) test <40 copies—time to suppression (TS)—in a cohort of persons aged ≥15 years, between 2015-2018 in outpatient HIV care facilities of the Brazilian Unified Health System, as well as to analyze whether individual and facility characteristics accelerate or delay TS.

Methods

This was a cohort study with data from a linkage of national HIV databases, following a previously published procedure. Two types of variables were examined: individual-level (sex, age group, race/skin color, education, baseline CD4 cell count and VL, initial ART regimen, adherence, ART regimen change and number of VL tests until suppression) and facility-level (national and metropolitan region, caseload). Multilevel parametric accelerated failure time survival models were used. Fixed and random effects were analyzed through null, sociodemographic, combined sociodemographic and clinical, and facility-related variables, adjusted for the number of VL tests until suppression. Likelihood, interquartile range, and proportion of change in variance were used for comparisons.

Results

Of 132,540 participants, 89.4% (114,696) achieved viral suppression: 20.8% within three months, and 56.4% within six months. Median TS was 161 days, varying from 31 to 1,426 days, depending on the time interval between initiation and VL testing. Among those who had VL testing within 66 days, median TS was 55 days. All individual and facility-related variables were associated with TS, explaining the 16.2% and 13.2% variability, respectively.

Conclusions

This was the first Brazilian nationwide cohort to analyze TS. It is also one of the largest operational cohorts globally to assess healthcare facility characteristics. The findings indicated that both individual and facility-related characteristics contribute to TS. Strengthening VL monitoring should be included as part of a coordinated effort to improve the quality of care provided for people living with HIV/AIDS in Brazil.
Design nonrepetitive and diverse activity single-guide RNA by deep learning
Authors: Xia Yan , Liang Zeyu , Du Xiaowen , Cao Dengtian , Li Jing , Sun Lichao , Huo Yi-Xin , Guo Shuyuan
Published: May 2024

Multiplex and precise control of the gene expression based on CRISPR/Cas9 is important to metabolic regulation in synthetic biology. However, employing single guide RNAs (sgRNAs) that possess repetitive DNA sequences and exhibit uniform activity could detrimentally affect the editing process, undermining both its stability and regulatory potential. In this study, we developed a deep generative model based on a decoder-only Transformer architecture (sgRNAGen) for thede novogeneration of a series of nonrepetitive and diverse sgRNAs with activity. To assess the quality of sgRNAs generated by sgRNAGen, we evaluated their activity by targeting essential genes, with the results indicating that 98% of the generated sgRNAs were active inBacillus subtilis. The generated sgRNAs were further validated for applications in single-gene editing, large fragment knockouts, and multiplex editing. Notably, the efficiency of knocking out long fragments up to 169.5 kb reached 100%, and targeting multiple sites allowed for the creation of strains with various combinations of mutations in a single editing. Furthermore, we developed a CRISPRi system utilizing the designed sgRNAs to regulate gene expression with desired strength and high precision. SgRNAGen offers a method for devising nonrepetitive and diverse activity sgRNAs, enhancing metabolic control and advancing applications within synthetic biology.

TOC
Subtleties in Clathrin Heavy Chain Binding Boxes provide selectivity among Adaptor Proteins of Budding Yeast
Authors: Defelipe Lucas A. , Veith Katharina , Burastero Osvaldo , Kupriianova Tatiana , Bento Isabel , Skruzny Michal , Köbel Knut , Uetrecht Charlotte , Thuenauer Roland , García-Alai Maria M.
Published: May 2024

Clathrin, forming the triskelion network, orchestrates highly regulated cellular processes facilitating cargo internalization and trafficking in eukaryotes, with its N-terminal domain (NTD) pivotal for adaptor protein (AP) interactions. The NTD contains up to four AP-binding sites, and their roles in preferential occupancy by APs have not been addressed. Here, employing a combination of integrative biophysical and structural approaches together within vivofunctional experiments, we investigated the binding hierarchy and selectivity of adaptors for clathrin, aiming to understand the evolutionary conservation of redundant APs and their specialized roles in endocytosis and cellular trafficking mechanisms. We found that yeast epsin Ent5 displayed the highest affinity for clathrin, indicating its significant role in cellular trafficking processes. Epsins Ent1 and Ent2, which are crucial for endocytosis but described to have redundant functions, revealed distinct binding patterns; Ent1 demonstrated stronger interactions with clathrin than Ent2, explaining its functional divergence towards actin binding. Despite both having actin anchoring domains, since Ent1 is actually more stably recruited by clathrin, it would provide a better actin anchoring function. These results offer molecular insights into AP selectivity, suggesting they competitively bind clathrin while also targeting different clathrin sites.
2’-Fucosyllactose Inhibits Human Norovirus Replication in Human Intestinal Enteroids
Authors: Patil Ketki , Ayyar B. Vijayalakshmi , Neill Frederick H. , Bode Lars , Estes Mary K. , Atmar Robert L. , Ramani Sasirekha
Published: May 2024

Human noroviruses (HuNoVs) are the leading cause of acute gastroenteritis worldwide. Currently, there are no targeted antivirals for the treatment of HuNoV infection. Histo-blood group antigens (HBGAs) on the intestinal epithelium are cellular attachment factors for HuNoVs; molecules that block the binding of HuNoVs to HBGAs thus have the potential to be developed as antivirals. Human milk oligosaccharides (HMOs) are glycans in human milk with structures analogous to HBGAs. HMOs have been shown to act as decoy receptors to prevent the attachment of multiple enteric pathogens to host cells. Previous X-ray crystallography studies have demonstrated the binding of HMO 2’-fucosyllactose (2’FL) in the same pocket as HBGAs for some HuNoV strains. We evaluated the effect of 2’FL on the replication of a globally dominant GII.4 Sydney [P16] HuNoV strain using human intestinal enteroids (HIEs) from adults and children. A significant reduction in GII.4 Sydney [P16] replication was seen in duodenal and jejunal HIEs from multiple adult donors, all segments of the small intestine from an adult organ donor and in two pediatric duodenal HIEs. However, 2’FL did not inhibit HuNoV replication in two infant jejunal HIEs that had significantly lower expression of α1-2-fucosylated glycans. 2’FL can be synthesized in large scale, and safety and tolerance have been assessed previously. Our data suggest that 2’FL has the potential to be developed as a therapeutic for HuNoV gastroenteritis.

IMPORTANCE

Human noroviruses infect the gastrointestinal tract and are a leading cause of acute gastroenteritis worldwide. Common symptoms of norovirus include diarrhea, vomiting and stomach cramps. Virus shedding and symptoms are prolonged and debilitating in immunocompromised patients. Currently, there are no approved vaccines or targeted antivirals for treating human norovirus infection. Human intestinal enteroids derived from intestinal stem cells allow the successful replication of norovirus in the laboratory and can be used as a physiologically relevant model system to evaluate antivirals. We discovered that 2’fucosyllactose (2’FL), an oligosaccharide naturally occurring in human milk, inhibits norovirus replication in HIEs from multiple donors and thus has the potential to be developed as a therapeutic for human norovirus. These findings have high translational potential since 2’FL from several manufacturers have GRAS (generally recognized as safe) status and can be synthesized on a large scale for immediate application.
Cognitive Computational Model Reveals Repetition Bias in a Sequential Decision-Making Task
Authors: Legler Eric , Rivera Darío Cuevas , Schwöbel Sarah , Wagner Ben J. , Kiebel Stefan
Published: May 2024

Humans tend to repeat past actions due to rewarding outcomes. Recent computational models propose that the probability of selecting a specific action is also, in part, based on how often this action was selected before, independent of previous outcomes or reward. However, these new models so far lack empirical support. Here, we present evidence of a repetition bias using a novel sequential decision-making task and computational modeling to reveal the influence of choice frequency on human value-based choices. Specifically, we find that value-based decisions can be best explained by concurrent influence of both goal-directed reward seeking and a repetition bias. We also show that participants differ substantially in their repetition bias strength, and relate these measures to task performance. The new task enables a novel way to measure the influence of choice repetition on decision-making. These findings can serve as a basis for further experimental studies on the interplay between rewards and choice history in human decision-making.
The Chemokine Receptor CCR8 is Not a High-affinity Receptor for the Human Chemokine CCL18
Authors: Hussain Khansa , Lim Herman D. , Devkota Shankar Raj , Kemp-Harper Barbara K. , Lane J. Robert , Canals Meritxell , Pease James E. , Stone Martin J.
Published: May 2024

The primate-specific chemokine CCL18 is a potent chemoattractant for T cells and is expressed at elevated levels in several inflammatory diseases. However, the cognate receptor for CCL18 remains unconfirmed. Here, we describe attempts to validate a previous report that the chemokine receptor CCR8 is the human CCL18 receptor (Islam et al.J Exp Med.2013,210:1889-98). Two mouse pre-B cell lines (4DE4 and L1.2) exogenously expressing CCR8 exhibited robust migration in response to the known CCR8 ligand CCL1 but not to CCL18. Similarly, CCL1 but not CCL18 induced internalization of CCR8 on 4DE4 cells. CCR8 expressed on Chinese hamster ovarian (CHO) cells mediated robust G protein activation, inhibition of cAMP synthesis and β-arrestin2 recruitment in response to CCL1 but not CCL18. Several N- and C-terminal variants of CCL18 also failed to stimulate CCR8 activation. On the other hand, and as previously reported, CCL18 inhibited CCL11-stimulated migration of 4DE4 cells expressing the receptor CCR3. These data suggest that CCR8, at least in the absence of unidentified cofactors, does not function as a high affinity receptor for CCL18.
Ohmic analogies and metaphorical circuits: Vascular partitioning of leaf air spaces and stomatal patchiness can create apparent undersaturation and gradient inversion
Authors: Rockwell Fulton E.
Published: May 2024

Rationale

Analyses of leaf gas exchange rely on an Ohmic analogy that arrays single stomatal, internal air space, and mesophyll conductances in series. Such models underlie inferences of mesophyll conductance and the relative humidity of leaf airspaces, reported to fall as low as 80%. An unresolved question is whether such Ohmic models are biased with respect to real leaves, whose internal air spaces are chambered at various scales by vasculature.

Description

To test whether undersaturation could emerge from modeling artifacts, we compared Ohmic model estimates with true parameter values for a chambered leaf with varying distributions and magnitudes of leaf surface conductance (“patchiness”).

Key Results

Distributions of surface conductance can create large biases in gas exchange calculations. Both apparent unsaturation and internalCO2gradient inversion can be produced by the evolution of particular distributions of stomatal apertures consistent with a decrease in surface conductance, as might occur under increasing vapor pressure deficit.

Main conclusion

In gas exchange experiments, the behaviors of derived quantities defined by simple Ohmic models are highly sensitive to the true partitioning of flux and stomatal apertures across leaf surfaces. We need new methods to disentangle model artifacts from real biological responses.
Arginine impacts aggregation, biofilm formation, and antibiotic susceptibility inEnterococcus faecalis
Authors: Snell Alex , Manias Dawn A. , Elbehery Reham R. , Dunny Gary M. , Willett Julia L. E.
Published: May 2024

Enterococcus faecalisis a commensal bacterium in the gastrointestinal tract (GIT) of humans and other organisms.E. faecalisalso causes infections in root canals, wounds, the urinary tract, and on heart valves.E. faecalismetabolizes arginine through the arginine deiminase (ADI) pathway, which converts arginine to ornithine and releases ATP, ammonia, and CO2.E. faecalisarginine metabolism also affects virulence of other pathogens during co-culture.E. faecalismay encounter elevated levels of arginine in the GIT or the oral cavity, where arginine is used as a dental therapeutic. Little is known about howE. faecalisresponds to growth in arginine in the absence of other bacteria. To address this, we used RNAseq and additional assays to measure growth, gene expression, and biofilm formation inE. faecalisOG1RF grown in arginine. We demonstrate that arginine decreasesE. faecalisbiofilm production and causes widespread differential expression of genes related to metabolism, quorum sensing, and polysaccharide synthesis. Growth in arginine also increases aggregation ofE. faecalisand promotes decreased susceptibility to the antibiotics ampicillin and ceftriaxone. This work provides a platform for understanding of how the presence of arginine in biological niches affectsE. faecalisphysiology and virulence of surrounding microbes.
Aggressive high-grade NF2 mutant meningiomas downregulate oncogenic YAP signaling via the upregulation of VGLL4 and FAT3/4
Authors: Parrish Abigail G , Arora Sonali , Thirimanne H. Nayanga , Rudoy Dmytro , Schmid Sebastian , Sievers Philipp , Sahm Felix , Holland Eric C , Szulzewsky Frank
Published: May 2024

Meningiomas are the most common primary brain tumors in adults. Although generally benign, a subset of meningiomas is of higher grade, shows aggressive growth behavior and recurs even after multiple surgeries. Around half of all meningiomas harbor inactivating mutations in NF2. While benign low-grade NF2 mutant meningiomas exhibit few genetic events in addition to NF2 inactivation, aggressive high-grade NF2 mutant meningiomas frequently harbor a highly aberrant genome. We and others have previously shown that NF2 inactivation leads to YAP1 activation and that YAP1 acts as the pivotal oncogenic driver in benign NF2 mutant meningiomas. Using bulk and single-cell RNA-Seq data from a large cohort of human meningiomas, we show that aggressive NF2 mutant meningiomas harbor decreased levels YAP1 activity compared to their benign counterparts. Decreased expression levels of YAP target genes are significantly associated with an increased risk of recurrence. We then identify the increased expression of the YAP1 competitor VGLL4 as well as the YAP1 upstream regulators FAT3/4 as a potential mechanism for the downregulation of YAP activity in aggressive NF2 mutant meningiomas. High expression of these genes is significantly associated with an increased risk of recurrence. In vitro, overexpression of VGLL4 resulted in the downregulation of YAP activity in benign NF2 mutant meningioma cells, confirming the direct link between VGLL4 expression and decreased levels of YAP activity observed in aggressive NF2 mutant meningiomas. Our results shed new insight on the biology of benign and aggressive NF2 mutant meningiomas and may have important implications for the efficacy of therapies targeting oncogenic YAP1 activity in NF2 mutant meningiomas.
PEX14 functions as a molecular link between optineurin and pexophagy in human cells
Authors: Li Hongli , Chen Suyuan , Lismont Celien , Vandewinkel Bram , Hussein Mohamed A. F. , Costa Cláudio F. , Imberechts Dorien , Liu Yiyang , Azevedo Jorge E , Vandenberghe Wim , Verhelst Steven , Baes Myriam , Fransen Marc
Published: May 2024

Pexophagy, the selective degradation of peroxisomes, is essential for removing excess or dysfunctional peroxisomes, and its dysregulation is linked to various diseases. Previous research has shown that optineurin (OPTN), an autophagy receptor involved in mitophagy, aggrephagy, and xenophagy, can induce pexophagy in HEK-293 cells. However, the underlying mechanism remains unclear. In this study, we used proximity labeling to identify PEX14, a peroxisomal membrane protein, as a neighboring partner of OPTN. Biochemical analyses revealed that PEX14 and OPTN interact through their respective coiled-coil and ubiquitin-binding domains. Further analyses demonstrated that the C-terminal half of overexpressed OPTN triggers pexophagy, likely by forming oligomers with endogenous OPTN. The co-localization of PEX14-OPTN complexes with LC3, combined with the suppression of OPTN-mediated peroxisome degradation by bafilomycin A1, supports a model in which PEX14 acts as a docking site for OPTN on the peroxisomal membrane, enabling the recruitment of the autophagic machinery for OPTN-mediated pexophagy.

This study uncovers and defines the peroxisomal membrane protein PEX14 as a key player in optineurin-driven pexophagy, advancing our mechanistic understanding of this cellular process. These findings open new avenues for developing therapeutic strategies targeting diseases associated with defective pexophagy.
Non-disruptive inducible labeling of ER-membrane contact sites using the Lamin B Receptor
Authors: Downie Laura , Ferrandiz Nuria , Jones Megan , Royle Stephen J.
Published: May 2024

Membrane contact sites (MCSs) are areas of close proximity between organelles that allow the exchange of material, among other roles. The endoplasmic reticulum (ER) has MCSs with a variety of organelles in the cell. MCSs are dynamic, responding to changes in cell state, and are therefore best visualized through inducible labeling methods. However, existing methods typically distort ER-MCSs, by expanding contacts or creating artificial ones. Here we describe a new method for inducible labeling of ER-MCSs using the Lamin B receptor (LBR) and a generic anchor protein on the partner organelle. TermedLaBeRling, this versatile, one-to-many approach allows labeling of different types of ER-MCSs (mitochondria, plasma membrane, lysosomes, early endosomes, lipid droplets and Golgi), on-demand, in interphase or mitotic cells. LaBeRling is non-disruptive and does not change ER-MCSs in terms of the contact number, extent or distance measured; as determined by light microscopy or a deep-learning volume electron microscopy approach. We applied this method to study the changes in ER-MCSs during mitosis and to label novel ER-Golgi contact sites at different mitotic stages in live cells.
Magnetic properties of Sohncke-type Pb(TiO)
Cu4(PO4)4
exposed by resonant x-ray Bragg diffraction
Authors: Lovesey S. W.
Published: May 2024

The enantiomorphous (chiral) crystal class of Sohncke-type Pb(TiO)Cu4(PO4)4 permits the rotation of the plane of polarization of light (optical activity). Copper ions participate in noncollinear antiferromagnetic order below a temperature ≈ 7 K, with magnetoelectric and piezomagnetic effects permitted. Crystal and magnetic symmetries of Pb(TiO)Cu4(PO4)4 are fully incorporated in calculated resonant x-ray Bragg diffraction patterns that are successfully compared with existing limited experimental data [Misawa , ]. Specifically, there is additional intensity of a Bragg spot (a chiral signature) from circular polarization (helicity) in the primary beam of x rays. The chiral signature is shown to arise from Cu axial magnetic dipoles, with the prospect of future experiments revealing interference between magnetic dipoles and (Templeton-Templeton) chargelike quadrupoles. An expression for the additional intensity used by Misawa does not respect magnetic symmetry, and our symmetry-informed answer overturns their principal conclusions about chirality and magnetic order. Dirac quadrupoles and octupoles are potentially strong sources of diffraction when the reflection vector is parallel to the unique direction in the tetragonal lattice. Notably, a Dirac quadrupole is a parity- and time-odd atomic multipole unlike a multisite spin entity previously mentioned in the context of Pb(TiO)Cu4(PO4)4 [Kimura , ].

Published by the American Physical Society
2024
Strong decays of the
Λc(2910)
and
Λc(2940)
in the
ND*
molecular frame
Authors: Yue Zi-Li , Guo Quan-Yun , Chen Dian-Yong
Published: May 2024

Stimulated by the observation of a new structure, named Λc(2910), in the Σc(2455)0,++π+,− decay channel from B meson decay process by the Belle Collaboration, and the similarity of the Λc(2910)/Λc(2940) and Pc states, we investigate the decay behavior of the Λc(2910) and Λc(2940) in the ND* molecular frame with the possible JP quantum numbers to be 1/2− and 3/2−. We employ an effective Lagrangian approach to evaluate the partial widths of ND, Σcπ, and Σc*π channels. The estimations in the present work indicate that the JP quantum numbers of Λc(2910) and Λc(2940) are preferred to be 1/2− and 3/2−, respectively. From the present estimations, we also find the branching ratio of Λc(3/2)→Σc*π is much larger than that of Λc(1/2)→Σc*π, thus Σc*π could be a good channel to distinguish the JP quantum numbers of Λc(2910) and Λc(2940). Therefore, we suggest searching for the structure in Σc*π invariant mass distribution in Belle II.

Published by the American Physical Society
2024
Volumetric visualization of vanishing vortices in wind turbine wakes
Authors: Hillestad Johannes N. , Yadala Srikar , Neunaber Ingrid , Li Leon , Hearst R. Jason , Worth Nicholas A.
Published: May 2024

Volumetric velocimetry is used to investigate the evolution of tip vortices in the wake of a model wind turbine. The power spectral density of streamwise velocity fluctuations is estimated at several downstream locations, and changes in the magnitude of the frequency peaks corresponding to the blade-pass and turbine rotational frequency are observed. Full volumetric visualization of the coherent structures depicts the vortex merging process responsible for the change in detected frequency peaks, capturing the physical mechanism likely responsible for many similar previous observations.

Published by the American Physical Society
2024
Controllable Manipulation of Semifluxon States in Phase-Shifted Josephson Junctions
Authors: Hovhannisyan Razmik A. , Golod Taras , Krasnov Vladimir M.
Published: May 2024

The utilization of Josephson vortices as information carriers in superconducting digital electronics is hindered by the lack of reliable displacement and localization mechanisms. In this Letter, we experimentally investigate planar Nb junctions with an intrinsic phase shift and nonreciprocity induced by trapped Abrikosov vortices. We demonstrate that the entrance of a single Josephson vortex into such junctions triggers the switching between metastable ±π semifluxon states. We showcase controllable manipulation between these states using short current pulses and achieve a nondestructive readout by a nearby junction. Our observations pave the way toward ultrafast and energy-efficient digital Josephson electronics.

Published by the American Physical Society
2024
2-Oxo-2H-chromen-4-yl 3,3-dimethylbutanoate
Authors: Bationo Valentin , Ziki Eric , Sombié Charles Bavouma , Semdé Rasmané , Djandé Abdoulaye
Published: May 2024

In the crystal of the title compound, C15H16O4, the molecules are connected through C—H...O hydrogen bonds, generating [100] chains, which are crosslinked by weak π–π stacking interactions.
Charging forward: unveiling the dynamics of consumer EV adoption in Asia's transition to green mobility
Authors: Han Chien-Shan , Hsu Yu-Ming , Hsu Han-Jen
Published: May 2024

Purpose

This study aims to explore the determinants influencing consumer purchase intentions towards electric vehicles (EVs) within the Asian market. It specifically examines how perceived value and perceived risk interact with the moderating effects of environmental, policy, and social factors to shape consumer behaviors towards EV adoption. The purpose is to delineate the intricate mechanisms driving consumer intentions in the context of sustainable mobility solutions.

Design/methodology/approach

Adopting a quantitative research design, this investigation collected data via a survey targeting consumers across various Asian countries. The study utilized Structural Equation Modeling (SEM) to analyze the responses, enabling a robust examination of the relationships between perceived value, perceived risk, and the potential moderating roles of external factors on consumer purchase intentions towards EVs.

Findings

The analysis revealed that both perceived value and perceived risk significantly influence consumers' intentions to purchase EVs. It was also found that environmental factors effectively moderate the relationship between perceived risk and purchase intentions, while social factors moderate the relationship between perceived risk and purchase intentions, highlighting the complex influence of external elements on consumer decisions. Contrarily, policy factors did not exhibit a significant moderating impact on the relationships examined.

Originality/value

This research enriches the domain of sustainable technology adoption by providing nuanced insights into the factors driving consumer intentions towards EVs in the Asian context. It underscores the critical roles of perceived value and risk, along with the distinct moderating effects of environmental and social factors, offering strategic implications for stakeholders within the EV ecosystem. The study's findings contribute to the broader discourse on consumer behavior in green technology adoption, laying groundwork for future investigations across diverse settings.
Artificial intelligence schemes to predict the mechanical performance of lignocellulosic fibers with unseen data to enhance the reliability of biocomposites
Authors: Al-Jarrah Rami , AL-Oqla Faris M.
Published: May 2024

Purpose

This work introduces an integrated artificial intelligence schemes to enhance accurately predicting the mechanical properties of cellulosic fibers towards boosting their reliability for more sustainable industries.

Design/methodology/approach

Fuzzy clustering and stacked method approach were utilized to predict the mechanical performance of the fibers. A reference dataset contains comprehensive information regarding mechanical behavior of the lignocellulosic fibers was compiled from previous experimental investigations on mechanical properties for eight different fiber materials. Data encompass three key factors: Density of 0.9–1.6 g/cm3, Diameter of 5.9–1,000 µm, and Microfibrillar angle of 2–49 deg were utilized. Initially, fuzzy clustering technique was utilized for the data. For validating proposed model, ultimate tensile strength and elongation at break were predicted and then examined against unseen new data that had not been used during model development.

Findings

The output results demonstrated remarkably accurate and highly acceptable predictions results. The error analysis for the proposed method was discussed by using statistical criteria. The stacked model proved to be effective in significantly reducing level of uncertainty in predicting the mechanical properties, thereby enhancing model’s reliability and precision. The study demonstrates the robustness and efficacy of the stacked method in accurately estimating mechanical properties of lignocellulosic fibers, making it a valuable tool for material scientists and engineers in various applications.

Originality/value

Cellulosic fibers are essential for biomaterials to enhance developing green sustainable bio-products. However, such fibers have diverse characteristics according to their types, chemical composition and structure causing inconsistent mechanical performance. This work introduces an integrated artificial intelligence schemes to enhance accurately predicting the mechanical properties of cellulosic fibers towards boosting their reliability for more sustainable industries. Fuzzy clustering and stacked method approach were utilized to predict the mechanical performance of the fibers.
Beyond the Griliches biases
Authors: Andini Corrado , Andini Monica
Published: May 2024

Purpose

The paper investigates the determinants of the Ordinary Least Squares (OLS) bias of the wage return to graduate education for high-school workers in Portugal.

Design/methodology/approach

The study uses matched employer-employee data for Portugal, over the 2002–2012 period, to estimate a wage-schooling model that controls not only for individual observed characteristics, firm observed characteristics and year fixed effects, but also for three high-dimensional vectors of fixed effects – one for employees, one for employers and one for job titles.

Findings

The main results are the following. First, disregarding individual fixed effects is highly problematic, accounting for 48.5% of the OLS bias. Second, disregarding firm fixed effects is also problematic, accounting for 12.3% of the OLS bias.

Research limitations/implications

The implication for the studies in the labor-supply literature that estimate, by means of instrumental variables, the wage returns to in-school work or to on-the-job schooling is that an instrument dealing with employee’s unobserved ability only may fail to meet the exclusion restriction.

Practical implications

Take the typical instrument based on a policy reform that changes the compulsory schooling level in the population. This instrument may well be argued to be correlated with the education of the employee and uncorrelated with the unobserved ability of the employee, but unfortunately it cannot be seen as orthogonal to the unobserved ability of the employer because of its correlation with the (unobserved) education of the manager. This is a simple corollary of the fact that the employee and the manager belong, in general, to the same population.

Social implications

Individuals invest a considerable amount of resources in education, which is seen to have positive effects on several dimensions of individual life. Yet, the estimation of these effects is still surrounded by technical difficulties.

Originality/value

To the best of the authors’ knowledge, this is the first study that uses the Gelbach decomposition to investigate the determinants of the OLS bias of the wage return to graduate education for high-school workers.