bluuebunny/crossref_metadata_2025_split huggingface dataset:
BioLLMBench: A Comprehensive Benchmarking of Large Language Models in Bioinformatics
Authors: Sarwal Varuni , Munteanu Viorel , Suhodolschi Timur , Ciorba Dumitru , Eskin Eleazar , Wang Wei , Mangul Serghei 
Published: December 2023

AbstractLarge Language Models (LLMs) have shown great promise in their knowledge integration and problem-solving capabilities, but their ability to assist in bioinformatics research has not been systematically evaluated. To bridge this gap, we present BioLLMBench, a novel benchmarking framework coupled with a scoring metric scheme for comprehensively evaluating LLMs in solving bioinformatics tasks. Through BioLLMBench, we conducted a thorough evaluation of 2,160 experimental runs of the three most widely used models, GPT-4, Bard and LLaMA, focusing on 36 distinct tasks within the field of bioinformatics. The tasks come from six key areas of emphasis within bioinformatics that directly relate to the daily challenges and tasks faced by individuals within the field. These areas are domain expertise, mathematical problem-solving, coding proficiency, data visualization, summarizing research papers, and developing machine learning models. The tasks also span across varying levels of complexity, ranging from fundamental concepts to expert-level challenges. Each key area was evaluated using seven specifically designed task metrics, which were then used to conduct an overall evaluation of the LLM’s response. To enhance our understanding of model responses under varying conditions, we implemented a Contextual Response Variability Analysis. Our results reveal a diverse spectrum of model performance, with GPT-4 leading in all tasks except mathematical problem solving. GPT4 was able to achieve an overall proficiency score of 91.3% in domain knowledge tasks, while Bard excelled in mathematical problem-solving with a 97.5% success rate. While GPT-4 outperformed in machine learning model development tasks with an average accuracy of 65.32%, both Bard and LLaMA were unable to generate executable end-to-end code. All models faced considerable challenges in research paper summarization, with none of them exceeding a 40% score in our evaluation using the Recall-Oriented Understudy for Gisting Evaluation (ROUGE) score, highlighting a significant area for future improvement. We observed an increase in model performance variance when using a new chatting window compared to using the same chat, although the average scores between the two contextual environments remained similar. Lastly, we discuss various limitations of these models and acknowledge the risks associated with their potential misuse.
Understanding the Easterlin Paradox in China: Investigating the Psychological Stress and its Relation to Nonincome Factors
Authors: Zeng Zhaoying , Chen Youqing , Su Wenliang 
Published: December 2023

AbstractAlthough China’s economy and living conditions have improved significantly in the past few decades, previous studies have found that residents’ happiness has not kept pace with them accordingly. Such an Esterlin paradox may partly be due to the increase in psychological stress in the progress of China’s urbanization. To verify this point, we constructed an index of psychological stress (IPS) through daily internet search queries of four psychological stress-related keywords obtained from the Baidu Index from 2011 to 2021. The IPS for each province, municipality, and main city during 2018-2019 was also calculated. Meanwhile, the city level’s economic factors (GDP per capita, income of employees), living costs (housing prices, commuting time), and living environment quality (air quality, environmental noise) were employed to predict the IPS. The results showed that the IPS in China showed an upward trend from 2011 to 2021, and it was higher in the eastern coastal regions than in other regions. Housing prices and commuting time were the only significant predictors of IPS in the hierarchical regression. Our results suggested that the Easterlin paradox in China may be explained by the rising IPS linked with higher living expenses in the course of urbanization.
Predictors of COVID-19 Vaccine Hesitancy in North-Central Nigeria
Authors: Olutola Ayodotun , Gobir Ibrahim Bola , Bazira Deus , Agboola Samson , Sanni Fatimah Ohunene , Bello Azeez Akanbi , Nnadozie Havilah Onyinyechi , Adamu Aisha , Bello Fatima , Otubo Suzzy Angmun , Nyang Mercy Piring’ar 
Published: December 2023

AbstractCOVID-19 vaccine hesitancy has emerged as a major challenge to global efforts to control the pandemic, particularly in Nigeria, where hesitancy to other effective vaccines such as polio and measles has been widely reported. Several individual, societal, and structural factors contribute to this behaviour and prevent the effectiveness of COVID-19 prevention efforts.ObjectivesThis study sought to assess the factors associated with COVID-19 vaccine hesitancy in the six states of north-central Nigeria.MethodsA population-based cross-sectional online survey was conducted among residents using a semi-structured questionnaire adapted from the WHO SAGE vaccine hesitancy scale and distributed via social media networks over 8-weeks.ResultsA total of 1,999 responses were received, of which 570 were set aside comprising 512 respondents that resided outside the study area, 12 respondents that reported no knowledge of the COVID-19 vaccine, and 46 entries with missing data. Of 1,429 included in the analysis, 1,008 (70.5%) were willing to be vaccinated and/or already vaccinated and 421 (29.5%) were unwilling to receive the COVID-19 vaccine. Post-secondary education (AOR: 0.51, 0.37-0.69), household income above the minimum wage of 30,000 Naira per month (AOR: 0.68, 0.50-0.94) and people of the Islamic faith (AOR: 0.69, 0.53-0.90) were found to be associated with lower levels of hesitancy. The dominant reasons for hesitancy were concerns about side effects (37.5%), doubt about the existence of COVID-19 (11.0%), and the perception of time required to receive the vaccine (9.6%). Hesitant respondents relied on health workers (33.0%) and social media (23.3%) as their trusted sources of health information, and less than a third (31.4%) followed the advice of their religious and community leaders.ConclusionAll three factors of confidence, complacency and convenience influenced hesitancy in our study. Socioeconomic factors are major drivers of hesitancy. Therefore, hesitancy is as much a social issue as health and requires a multisectoral approach to educating communities and building trust in health and social institutions.
“Endless Opportunities”: A qualitative exploration of facilitators and barriers to scale-up of two-way texting follow-up after voluntary medical male circumcision in Zimbabwe
Authors: Elkins Chelsea , Kokera Sandra B. , Vumbugwa Phiona , Gavhera Jacqueline , West Kathleen M. , Wilson Katherine S. , Makunike-Chikwinya Batsirai , Masimba Lewis , Holec Marianne , Barnhart Scott , Matinu Sulemana , Wassuna Beatrice , Feldacker Caryl 
Published: December 2023

ABSTRACTIn Zimbabwe, the ZAZIC consortium employs two-way, text-based (2wT) follow-up to strengthen post-operative care for voluntary medical male circumcision (VMMC). 2wT scaled nationally with evidence of client support and strengthened follow-up. However, 2wT uptake remains suboptimal. Understanding the gap between mobile health (mHealth) potential for innovation expansion and scale-up realization is critical for 2wT and other mHealth innovations. Therefore, we conducted an exploratory qualitative study with the objective of identifying 2wT program strengths, challenges, and suggestions for scale up as part of routine VMMC services. A total of 16 in-depth interviews (IDIs) with diverse 2wT stakeholders were conducted, including nurses, monitoring & evaluation teams, and technology partners – a combination of perspectives that provide new insights. We used both inductive and deductive coding for thematic analysis. Among 2wT drivers of expansion success, interviewees noted: 2wT care benefits for clients; effective hands-on 2wT training; ease of app use for providers; 2wT saved time and money; and 2wT strengthened client/provider interaction. For 2wT scale-up challenges, staff shortages; network infrastructure constraints; client costs; duplication of paper and electronic reporting; and complexity of digital tools integration. To improve 2wT robustness, respondents suggested: more staff training to offset turnover; making 2wT free for clients; using 2wT to replace paper VMMC reporting; integrating with routine VMMC reporting systems; and expanding 2wT to other health areas. High stakeholder participation in app design, implementation strengthening, and evaluation were appreciated. Several 2wT improvements stemmed from this study, including enrollment of multiple people on one number to account for phone sharing; 2wT inclusion of minors ages 15+; clients provided with $1 to offset SMS costs; and reduced SMS messages to clients. Continued 2wT mentoring for staff, harmonization of 2wT with Ministry e-health data systems, and increased awareness of 2wT’s client and provider benefits will help ensure successful 2wT scale-up.
Chemical genetic interaction linking eIF5A hypusination and mitochondrial integrity
Authors: Matsumoto Ken , Kurokawa Rumi , Takase Megumi , Schneider-Poetsch Tilman , Ling Feng , Suzuki Takehiro , Han Peixun , Wakigawa Taisei , Suzuki Masato , Tariq Mohammad , Ito Akihiro , Higashi Kyohei , Iwasaki Shintaro , Dohmae Naoshi , Yoshida Minoru 
Published: December 2023

AbstractThe eukaryotic translation factor eIF5A plays an important role in translation elongation, especially across stretches of prolines and charged amino acids, and in translation termination. eIF5A undergoes hypusination, a post-translational modification unique to this protein, although the role of hypusination in the function of eIF5A remains elusive. Here, we investigated the cellular defects induced by the hypusination inhibitor GC7 (N1-guanyl-1,7-diaminoheptane). Proteome, translatome, and transcriptome analyses indicated that GC7 downregulated a subset of mitochondrial proteins and DNA, causing mitochondrial stress and eliciting the integrated stress response. Chemical genomic screening using barcoded shRNA libraries identified genes encoding proteins involved in polyamine metabolism/transport andMPV17L2, a mitochondrial disease gene homologue whose product regulates mitochondrial translation. Depletion of MPV17L2 caused hypersensitivity to GC7 and phenocopied the effects of GC7 treatment. These results suggest that eIF5A hypusination and MPV17L2 synthetically regulate mitochondrial molecular synthesis and integrity.
ciliR: an R package for determining ciliary beat frequency using fast Fourier transformation
Authors: Grant Oriane , Larken Isobel , Reitemeier Samuel C. , Mitchison Hannah M. , Dawes William , Phillips Angus , Cortina-Borja Mario , Smith Claire M. 
Published: December 2023

AbstractCilia are motile hair-like structures that play a vital role in our body. Accurate assessment of ciliary beat frequency is pivotal for investigating ciliary dynamics and diagnosing ciliopathies. This study aims to develop software for accurately measuring the beat frequency of cilia captured using high-speed video microscopy.To achieve this, we developed theciliRpackage in R, which was validated against manual counting and three other automated methods of counting cilia beat frequency. The results showed thatciliRproduced results that were comparable to manual counting. The accuracy ofciliRwas defined by its ability to reduce noise, including only counting data in a biologically significant range (0-60 Hz).Our software is a valuable tool for researchers in the field of ciliobiology as it offers a reliable method for detailed ciliary function analysis, thereby contributing to the broader understanding of mechanisms underlying ciliary-related disease.We encourage researchers to try this package and feed-back their findings to the authors. Instructions for use and processes for providing feedback are provided in supplementary material.SummaryciliR is a novel R package designed for analysing ciliary beat frequency (CBF) via ImageJ and RStudio. The advantage of the ciliR system, lies in its integration with the R environment, increasing processing speed and access to data visualization tools and analysis pipelines available in other R packages. The open-source platform invites community feedback to refine functionality, aiming to advance ciliopathy research with an accessible, comprehensive toolkit.
P-NADs:PUX-basedNAnobody Degraders for Ubiquitin-Independent Degradation of Target Proteins
Authors: Wang Jun , Chistov Georgy , Zhang Junrui , Huntington Brandon , Salem Israa , Sandholu Anandsukeerthi , Arold Stefan T. 
Published: December 2023

ABSTRACTTargeted protein degradation (TPD) allows cells to maintain a functional proteome and to rapidly adapt to changing conditions. Methods that repurpose TPD for the deactivation of specific proteins have demonstrated significant potential in therapeutic and research applications. Most of these methods are based on proteolysis targeting chimaera (PROTAC) which link the protein target to an E3 ubiquitin ligase binding moiety, resulting in the ubiquitin-based degradation of the target protein. In this study, we introduce a method for ubiquitin-independent TPD based on nanobody-conjugated plant ubiquitin regulatory X domain-containing (PUX) adaptor proteins. We show that thePUX-basedNAnobodyDegraders (P-NADs) can unfold a target protein through the Arabidopsis and human orthologues of the CDC48 unfoldase without the need for ubiquitination or initiating motifs. Despite originating from plants, P-NAD plasmids can be transfected into a human cell line, where produced proteins use the endogenous CDC48 machinery for ubiquitin-independent TPD. Thus, P-NADs pave the road for ubiquitin-independent therapeutic TPD approaches. The P-NAD design combined with establishedin vitroand cellular assays make this system also a versatile platform for elucidating functional aspects of CDC48-based TPD in plants and animals.
Natural variation inArabidopsis thalianaidentifies GlyoxalaseI;2 as key for the detoxification of glucose-derived reactive carbonyl species
Authors: Balparda Manuel , Kerim Aylin , Bouzid Maroua , Alvarez Clarisa E. , Alseekh Saleh , Fernie Alisdair R. , Maurino Veronica G. 
Published: December 2023

AbstractReactive carbonyl species (RCS) are highly toxic molecules produced during normal metabolism and increased under conditions of oxidative stress. Here we show thatArabidopsis thalianaecotypes exhibit natural variation in the degree of detoxification of RCS. We have isolated the ecotype IP-Pal-0 as an ecotype that has evolved a higher resistance to the toxic effects of glucose-derived RCS by acquiring a higher activity of the glyoxalase system through increased expression of some of its components. In particular, Viridiplantae-specific GLXI;2, GLXII;4 and GLXII;5 isoforms are highly expressed when plants are grown in the presence of 2-keto-D-glucose (KDG; glucosone) or methylglyoxal. We found that specific motif/cis-regulatory elements of the Col-0 and IP-Pal-0 GLXI;2 promoter regions may be involved in the differences in GLXI;2 gene expression associated with KDG detoxification. IP-Pal-0 GLXI;2 contains two different amino acids compared to Col-0, but these do not affect the basic kinetics of the protein. Interestingly, we found that the simultaneous change of these amino acids also occurs together in the GLXI proteins of some other organisms, suggesting a convergence in the simultaneous change of both amino acid residues. Our study of natural variants ofA. thalianasuggests that the Viridiplantae-specific isoforms of the glyoxalase system are involved in the detoxification of glucose-derived RCS, particularly KDG.
A myristoyl switch at the plasma membrane triggers cleavage and oligomerization of Mason-Pfizer monkey virus matrix protein
Authors: Častorálová Markéta , Sýs Jakub , Prchal Jan , Pavlů Anna , Prokopová Lucie , Briki Zina , Hubálek Martin , Ruml Tomáš 
Published: December 2023

AbstractFor most retroviruses, including HIV, association with the plasma membrane (PM) promotes the assembly of immature particles, which occurs simultaneously with budding and maturation. In these viruses, maturation is initiated by oligomerization of polyprotein precursors. In contrast, several retroviruses, such as Mason-Pfizer monkey virus (M-PMV), assemble in the cytoplasm into immature particles that are transported across the PM. Therefore, protease activation and specific cleavage must not occur until the preassembled particle interacts with the PM. This interaction is triggered by a bipartite signal consisting of a cluster of basic residues in the matrix (MA) domain of Gag polyprotein and a myristoyl moiety N-terminally attached to MA. Here, we provide evidence that myristoyl exposure from the MA core and its insertion into the PM occurs in M-PMV. By a combination of experimental methods, we show that this results in a structural change at the C-terminus of MA allowing efficient cleavage of MA from the downstream region of Gag. This suggests that, in addition to the known effect of the myristoyl switch of HIV-1 MA on the multimerization state of Gag and particle assembly, the myristoyl switch may have a regulatory role in initiating sequential cleavage of M-PMV Gag in immature particles.
Xylosyltransferase Bump-and-hole Engineering to Chemically Manipulate Proteoglycans in Mammalian Cells
Authors: Li Zhen , Di Vagno Lucia , Chawla Himanshi , Ni Cheallaigh Aisling , Critcher Meg , Sammon Douglas , Briggs David C. , Chung Nara , Chang Vincent , Mahoney Keira E. , Cioce Anna , Murphy Lloyd D. , Chen Yen-Hsi , Narimatsu Yoshiki , Miller Rebecca L. , Willems Lianne I. , Malaker Stacy A. , Huang Mia L. , Miller Gavin J. , Hohenester Erhard , Schumann Benjamin 
Published: December 2023

AbstractMammalian cells orchestrate signalling through interaction events on their surfaces. Proteoglycans are an intricate part of these interactions, carrying large glycosaminoglycan polysaccharides that recruit signalling molecules. Despite their importance in development, cancer and neurobiology, a relatively small number of proteoglycans have been identified. In addition to the complexity of glycan extension, biosynthetic redundancy in the first protein glycosylation step by two xylosyltransferase isoenzymes XT1 and XT2 complicates annotation of proteoglycans. Here, we develop a chemical genetic strategy that manipulates the glycan attachment site of cellular proteoglycans. By employing a tactic termed bump- and-hole engineering, we engineer the two isoenzymes XT1 and XT2 to specifically transfer a chemically modified xylose analogue to target proteins. The chemical modification contains a bioorthogonal tag, allowing the ability to visualise and profile target proteins modified by both transferases in mammalian cells. The versatility of our approach allows pinpointing glycosylation sites by tandem mass spectrometry, and exploiting the chemical handle to manufacture proteoglycans with defined GAG chains for cellular applications. Engineered XT enzymes permit a view into proteoglycan biology that is orthogonal to conventional techniques in biochemistry.
High-resolution structures illuminate key principles underlying voltage and LRRC26 regulation of Slo1 channels
Authors: Kallure Gopal S. , Pal Kamalendu , Zhou Yu , Lingle Christopher J. , Chowdhury Sandipan 
Published: December 2023

AbstractMulti-modal regulation of Slo1 channels by membrane voltage, intracellular calcium, and auxiliary subunits enables its pleiotropic physiological functions. Our understanding of how voltage impacts Slo1 conformational dynamics and the mechanisms by which auxiliary subunits, particularly of the LRRC (Leucine Rich Repeat containing) family of proteins, modulate its voltage gating remain unresolved. Here, we used single particle cryo-electron microscopy to determine structures of human Slo1 mutants which functionally stabilize the closed pore (F315A) or the activated voltage-sensor (R207A). Our structures, obtained under calcium-free conditions, reveal that a key step in voltage-sensing by Slo1 involves a rotameric flip of the voltage-sensing charges (R210 and R213) moving them by ∼6 Å across a hydrophobic gasket. Next we obtained reconstructions of a complex of human Slo1 with the human LRRC26 (γ1) subunit in absence of calcium. Together with extensive biochemical tests, we show that the extracellular domains of γ1 form a ring of interlocked dominos that stabilizes the quaternary assembly of the complex and biases Slo1:γ1 assembly towards high stoichiometric complexes. The transmembrane helix of γ1 is kinked and tightly packed against the Slo1 voltage-sensor. We hypothesize that γ1 subunits exert relatively small effects on early steps in voltage-gating but structurally stabilize non-S4 helices of Slo1 voltage-sensor which energetically facilitate conformational rearrangements that occur late in voltage stimulated transitions.
The S-component fold: A link between bacterial transporters and receptors
Authors: Partipilo Michele , Slotboom Dirk Jan 
Published: December 2023

AbstractThe processes of nutrient uptake and signal sensing are crucial for microbial survival and adaptation. Membrane-embedded proteins involved in these functions (transporters and receptors) are commonly regarded as unrelated in terms of sequence, structure, mechanism of action and evolutionary history. Here, we analyze the protein structural universe using recently developed artificial intelligence-based structure prediction tools, and find an unexpected link between prominent groups of microbial transporters and receptors. The so-called S-components of energy-coupling factor (ECF) transporters, and the membrane domains of sensor histidine kinases of the 5TMR cluster share a structural fold. The discovery of their relatedness manifests a widespread case of prokaryotic “transceptors” (related proteins with transport or receptor function), showcases how artificial intelligence-based structure predictions reveal unchartered evolutionary connections between proteins, and provides new avenues for engineering transport and signaling functions in bacteria.