bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phylogenetic analyses reveal bat communities in Northwestern Mexico harbour a high diversity of novel cryptic ectoparasite species
Authors: Najera-Cortazar Laura A. , Keen Alex , Kitching Thomas , Stokes Drew , Goodman Simon J. 
Published: August 2022

AbstractBackgroundParasites are integral parts of ecosystem function and important drivers of evolutionary processes. Characterising ectoparasite diversity is fundamental to studies of host-parasite interactions, evolution, and conservation, and also for understanding emerging disease threats for some vector borne pathogens. With more than 1,400 species, bats represent the second most speciose mammalian clade, but their ectoparasite fauna are poorly known for most species.MethodsWe sequenced mitochondrial Cytochrome Oxidase C subunit I and nuclear 18S ribosomal gene fragments, and used Bayesian phylogenetic analyses to characterise ectoparasite taxon identity and diversity for 17 species of parasitized bats sampled along the Baja California peninsula and in Northwestern Mexico.ResultsThe sequence data revealed multiple novel lineages of bat bugs (Cimicidae), flies (Nycteribiidae and Streblidae) and ticks (Argasidae). Within families, the new linages showed more than 10% sequence divergence, which is consistent with separation at least at the species level. Both families of bat flies showed host specificity, particularly on Myotis species. We also identified new records for the Baja peninsula of one tick (Carios kelleyi), and of five Streblid bat flies. One Nycteribiid bat fly haplotype from Pallid bat (Antrozous pallidus) hosts was found throughout the peninsula, suggesting potential long distance co-dispersal with hosts. Different bat bug and tick communities were found in the north and south of the peninsula.ConclusionsThis study is the first systematic survey of bat ectoparasites in the Baja California peninsula, discovering highly genetically differentiated novel lineages compared to other parts of North America. For some ectoparasite species, haplotype distributions may reflect patterns of bat migration. This work is a first step in characterising ectoparasite diversity over the Baja California peninsula, and understanding how ecological and evolutionary interactions shape bat ectoparasite communities among host species in different parts of their ranges.
Simulations suggest robust microtubule attachment of kinesin and dynein in antagonistic pairs
Authors: Ma Tzu-Chen , Gicking Allison M. , Feng Qingzhou , Hancock William O. 
Published: August 2022

AbstractIntracellular transport is propelled by kinesin and cytoplasmic dynein motors that carry membrane-bound vesicles and organelles bidirectionally along microtubule tracks. Much is known about these motors at the molecular scale, but many questions remain regarding how kinesin and dynein cooperate and compete during bidirectional cargo transport at the cellular level. The goal of the present study was to use a stochastic stepping model constructed by using published load-dependent properties of kinesin-1 and dynein-dynactin-BicD2 (DDB) to identify specific motor properties that determine the speed, directionality, and transport dynamics of a cargo carried by one kinesin and one dynein motor. Model performance was evaluated by comparing simulations to recently published experiments of kinesin-DDB pairs connected by complementary oligonucleotide linkers. Plotting the instantaneous velocity distributions from kinesin-DDB experiments revealed a single peak centered around zero velocity. In contrast, velocity distributions from simulations displayed a central peak around 100 nm/s, along with two side peaks corresponding to the unloaded kinesin and DDB velocities. We hypothesized that frequent motor detachment events and relatively slow motor reattachment rates resulted in periods in which only one motor is attached. To investigate this hypothesis, we varied specific model parameters and compared the resulting instantaneous velocity distributions, and we confirmed this systematic investigation using a machine learning approach that minimized the residual sum of squares between the experimental and simulation velocity distributions. The experimental data were best recapitulated by a model in which the kinesin and dynein stall forces are matched, motor detachment rates are independent of load, and the kinesin-1 reattachment rate is 50 s-1. These results provide new insights into motor dynamics during bidirectional transport and put forth hypotheses that can be tested by future experiments.Statement of significance:Bidirectional transport of vesicles along microtubules is vital for cellular function, particularly in the highly elongated axons and dendrites of neurons, and transport defects are linked to neurodegenerative diseases. For developing future therapeutic strategies, a better understanding is needed for how motors, cargo adapters, and accessory proteins coordinate their activities to transport cargo to their proper cellular locations. We approached this problem by simulating how antagonistic kinesin and dynein motors compete in pairs. We constrain our simulations by recent experimental results and conclude that the motors spend nearly all their time attached to the microtubule and competing against one another. This behavior is not predicted by existing single-molecule experiments and thus provides new insights into bidirectional transport.
Deformable image registration for automatic muscle segmentation and the generation of augmented imaging datasets
Authors: Henson William H. , Mazzá Claudia , Dall’Ara Enrico 
Published: August 2022

AbstractMuscle segmentation is a process relied upon to gather medical image-based muscle characterisation, useful in directly assessing muscle volume and geometry, that can be used as inputs to musculoskeletal modelling pipelines. Manual or semi-automatic techniques are typically employed to segment the muscles and quantify their properties, but they require significant manual labour and incur operator repeatability issues. In this study an automatic process is presented, aiming to segment all lower limb muscles from Magnetic Resonance (MR) imaging data simultaneously using three-dimensional (3D) deformable image registration. Twenty-three of the major lower limb skeletal muscles were segmented from five subjects, with an average Dice similarity coefficient of 0.72, and average absolute relative volume error of 12.7% (average relative volume error of -2.2%) considering the optimal subject combinations. Segmented MR imaging datasets of the lower limb are not widely available in the literature, limiting the potential of new, probabilistic methods such as deep learning to be used in the context of muscle segmentation. In this work, Non-linear deformable image registration is used to generate 69 manually checked, segmented, 3D, artificial datasets, allowing access for future studies to use these new methods, with a large amount of reliable reference data.
Functional characterization of six SLCO1B1 (OATP1B1) variants observed in Finnish individuals with a psychotic disorder
Authors: Häkkinen Katja , Kiander Wilma , Kidron Heidi , Lähteenvuo Markku , Urpa Lea , Lintunen Jonne , Vellonen Kati-Sisko , Auriola Seppo , Holm Minna , Lahdensuo Kaisla , Kampman Olli , Isometsä Erkki , Kieseppä Tuula , Lönnqvist Jouko , Suvisaari Jaana , Hietala Jarmo , Tiihonen Jari , Palotie Aarno , Ahola-Olli Ari V. , Niemi Mikko ,   the SUPER-Finland researchers listed in the Acknowledgements
Published: August 2022

AbstractAimVariants in the SLCO1B1 (solute carrier organic anion transporter family member 1B1) gene encoding the OATP1B1 (organic anion transporting polypeptide 1B1) protein are associated with altered transporter function that can predispose patients to adverse drug effects with statin treatment. We explored the effect of six rare SLCO1B1 single nucleotide variants (SNVs) occurring in Finnish individuals with a psychotic disorder on expression and functionality of the OATP1B1 protein.MethodsThe SUPER-Finland study has performed exome sequencing on 9,381 individuals with at least one psychotic episode during their lifetime. SLCO1B1 SNVs were annotated with PHRED-scaled Combined Annotation-Dependent (CADD) scores and the Ensembl variant effect predictor (VEP). In vitro functionality studies were conducted for the SNVs with PHRED-scaled CADD score >10 and predicted to be missense. To estimate possible changes in transport activity caused by the variants, transport of 2’,7’-dichlorofluorescein (DCF) in OATP1B1 expressing HEK293 cells was measured. The amount of OATP1B1 in crude membrane fractions was quantified with a LC–MS/MS-based quantitative targeted absolute proteomics analysis.ResultsSix rare missense variants of SLCO1B1 were identified in the study population located in transmembrane helix 3: c.317T>C (p.106I>T), intracellular loop 2: c.629G>T (p.210G>V), c.633A>G (p.211I>M), c.639T>A (p.213N>L), transmembrane helix 6: 820A>G (p.274I>V), and the C-terminal end: 2005A>C (p.669N>H). Of these variants, SLCO1B1 c.629G>T (p.210G>V) resulted in protein loss of function, abolishing the uptake of DCF and reducing membrane protein expression to 31% of reference OATP1B1.ConclusionsOf the six rare missense variants, SLCO1B1 c.629G>T (p.210G>V) causes loss-of-function of OATP1B1 transport and severely decreases membrane protein abundance. Carriers of SLCO1B1 c.629G>T may be susceptible to altered pharmacokinetics of OATP1B1 substrate drugs and may have increased likelihood of adverse drug effects such as statin-associated musculoskeletal symptoms.Abstract Figure
agoTRIBE detects miRNA-target interactions transcriptome-wide in single cells
Authors: Sekar Vaishnovi , Mármol-Sánchez Emilio , Kalogeropoulos Panagiotis , Stanicek Laura , Sagredo Eduardo A. , Doukoumopoulos Evangelos , Bonath Franziska , Biryukova Inna , Friedländer Marc R. 
Published: August 2022

AbstractMicroRNAs are gene regulatory molecules that play important roles in numerous biological processes including human health. The function of a given microRNA is defined by its selection of target transcripts, yet current state-of-the-art experimental methods to identify microRNA targets are laborious and require millions of cells. We have overcome these limitations by fusing the microRNA effector protein Argonaute2 to the RNA editing domain of ADAR2, allowing for the first time the detection of microRNA targets transcriptome-wide in single cells. Our agoTRIBE method reports functional microRNA targets which are additionally supported by evolutionary sequence conservation. As a proof-of-principle, we study microRNA interactions in single cells, and find substantial differential targeting across the cell cycle. Lastly, agoTRIBE additionally provides transcriptome-wide measurements of RNA abundance and will allow the deconvolution of microRNA targeting in complex samples such as tissues at the single-cell level.
Membrane remodeling properties of the Parkinson’s disease protein LRRK2
Authors: Wang Xinbo , Espadas Javier , Wu Yumei , Cai Shujun , Ge Jinghua , Shao Lin , Roux Aurélien , Camilli Pietro De 
Published: August 2022

AbstractMutations in Leucine-rich repeat kinase 2 (LRRK2) are responsible for late-onset autosomal dominant Parkinson’s disease (PD). LRRK2 has been implicated in a wide range of physiological processes including membrane repair in the endolysosomal system. Here, using cell free systems, we report that purified LRRK2 directly binds acidic lipid bilayers with a preference for highly curved bilayers. While this binding is nucleotide independent, LRRK2 can also deform low curvature liposomes into narrow tubules in a guanylnucleotide-dependent but ATP-independent way. Moreover, assembly of LRRK2 into scaffolds at the surface of lipid tubules can constrict them. We suggest that an interplay between the membrane remodeling and signaling properties of LRRK2 may be key to its physiological function. LRRK2, via its kinase activity, may achieve its signaling role at sites where membrane remodeling occurs.Significance StatementLRRK2 is one of the most frequently mutated gene in familial Parkinson’s disease. While much has been learned about its molecular properties, upstream regulators and protein substrates of its kinase activity, its precise function remains unclear. Recent evidence has pointed to a role of LRRK2 in membrane repair in the endo/lysosomal system. Here we show that purified LRRK2 has membrane remodeling properties. We suggest that its ability to sense and induce membrane curvature may be key to its function in membrane dynamics. These properties may help coordinate a direct role of LRRK2 at the membrane interface with its the signaling role of its kinase domain.
Nanomolar inhibition of SARS-CoV-2 infection by an unmodified peptide targeting the pre-hairpin intermediate of the spike protein
Authors: Yang Kailu , Wang Chuchu , Kreutzberger Alex J. B. , Ojha Ravi , Kuivanen Suvi , Couoh-Cardel Sergio , Muratcioglu Serena , Eisen Timothy J. , White K. Ian , Held Richard G. , Subramanian Subu , Marcus Kendra , Pfuetzner Richard A. , Esquivies Luis , Doyle Catherine A. , Kuriyan John , Vapalahti Olli , Balistreri Giuseppe , Kirchhausen Tomas , Brunger Axel T. 
Published: August 2022

AbstractVariants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) challenge currently available COVID-19 vaccines and monoclonal antibody therapies through epitope change on the receptor binding domain of the viral spike glycoprotein. Hence, there is a specific urgent need for alternative antivirals that target processes less likely to be affected by mutation, such as the membrane fusion step of viral entry into the host cell. One such antiviral class includes peptide inhibitors which block formation of the so-called HR1HR2 six-helix bundle of the SARS-CoV-2 spike (S) protein and thus interfere with viral membrane fusion. Here we performed structural studies of the HR1HR2 bundle, revealing an extended, well-folded N-terminal region of HR2 that interacts with the HR1 triple helix. Based on this structure, we designed an extended HR2 peptide that achieves single-digit nanomolar inhibition of SARS-CoV-2 in cell-based fusion, VSV-SARS-CoV-2 chimera, and authentic SARS-CoV-2 infection assays without the need for modifications such as lipidation or chemical stapling. The peptide also strongly inhibits all major SARS-CoV-2 variants to date. This extended peptide is ~100-fold more potent than all previously published short, unmodified HR2 peptides, and it has a very long inhibition lifetime after washout in virus infection assays, suggesting that it targets a pre-hairpin intermediate of the SARS-CoV-2 S protein. Together, these results suggest that regions outside the HR2 helical region may offer new opportunities for potent peptide-derived therapeutics for SARS-CoV-2 and its variants, and even more distantly related viruses, and provide further support for the pre-hairpin intermediate of the S protein.Significance StatementSARS-CoV-2 infection requires fusion of viral and host membranes, mediated by the viral spike glycoprotein (S). Due to the importance of viral membrane fusion, S has been a popular target for developing vaccines and therapeutics. We discovered a simple peptide that inhibits infection by all major variants of SARS-CoV-2 with nanomolar efficacies. In marked contrast, widely used shorter peptides that lack a key N-terminal extension are about 100 x less potent than this peptide. Our results suggest that a simple peptide with a suitable sequence can be a potent and cost-effective therapeutic against COVID-19 and they provide new insights at the virus entry mechanism.
Interfering with nucleotide excision by the coronavirus 3’-to-5’ exoribonuclease
Authors: Chinthapatla Rukesh , Sotoudegan Mohamad , Anderson Thomas , Moustafa Ibrahim M. , Passow Kellan T. , Kennelly Samantha A. , Moorthy Ramkumar , Dulin David , Feng Joy Y. , Harki Daniel A. , Kirchdoerfer Robert , Cameron Craig E. , Arnold Jamie J. 
Published: August 2022

AbstractSome of the most efficacious antiviral therapeutics are ribonucleos(t)ide analogs. The presence of a 3’-to-5’ proofreading exoribonuclease (ExoN) in coronaviruses diminishes the potency of many ribonucleotide analogs. The ability to interfere with ExoN activity will create new possibilities for control of SARS-CoV-2 infection. ExoN is formed by a 1:1 complex of nsp14 and nsp10 proteins. We have purified and characterized ExoN using a robust, quantitative system that reveals determinants of specificity and efficiency of hydrolysis. Double-stranded RNA is preferred over single-stranded RNA. Nucleotide excision is distributive, with only one or two nucleotides hydrolyzed in a single binding event. The composition of the terminal basepair modulates excision. A stalled SARS-CoV-2 replicase in complex with either correctly or incorrectly terminated products prevents excision, suggesting that a mispaired end is insufficient to displace the replicase. Finally, we have discovered several modifications to the 3’-RNA terminus that interfere with or block ExoN-catalyzed excision. While a 3’-OH facilitates hydrolysis of a nucleotide with a normal ribose configuration, this substituent is not required for a nucleotide with a planar ribose configuration such as that present in the antiviral nucleotide produced by viperin. Design of ExoN-resistant, antiviral ribonucleotides should be feasible.
Electronic payment system and financial sustainability of tertiary institutions in Nigeria
Authors: Madu Frances Nwamaka , Onodugo Vincent A. , Isichei Ejikeme Emmanuel 
Published: August 2022

PurposeAddressing the challenges of financial sustainability in tertiary institutions through the adoption of technology was the central motivation of this study. Hence, the authors assessed the direct effect of the adoption of electronic payment system (EPS) on financial sustainability and the indirect mediating influence of technological capabilities on this relation.Design/methodology/approachSample of 223 non-academic employees in twelve higher institutions were selected. The authors used primary data through the use of a questionnaire for data collection. Partial least square structural equation model (SmartPLSv3) was used for the analysis of the study.FindingsThe adoption of electronic payment system was shown to have a significantly positive effect on financial sustainability of tertiary institutions. It was also found that technological capabilities affect financial sustainability of tertiary institutions and technological capabilities mediate the relationship between the adoption of electronic payment solution and financial sustainability of tertiary institutions.Practical implicationsThe study advances the need for incorporating technology as a measure in advancing the internal financial management practices of tertiary institutions in developing economies.Originality/valueThe authors developed a model that advances a new perspective to higher education financial sustainability through advocating for technological capabilities development as a channel to ensure liquidity and solvency of higher education, most especially in developing economies.
Perceived insider status and employees' innovative behavior: the role of knowledge sharing and organizational innovation climate
Authors: Zhang Guangning , Zhang Xinxin , Wang Yingying 
Published: August 2022

PurposeThis study aims to investigate the effect of perceived insider status to employees' innovative behavior, the mediating role of knowledge sharing and the moderating role of organizational innovation climate in the relationship between knowledge sharing and employees' innovative behavior.Design/methodology/approachThis study adopted questionnaires to gather data. The sample of 341 employees working in diverse organizations in China was applied to examine the hypotheses.FindingsThe results indicate that perceived insider status is positively related to employees' innovative behavior and knowledge sharing mediates the relationship between perceived insider status and employees' innovative behavior. In addition, organizational innovation climate enhances the relationship of knowledge sharing and employees' innovative behavior.Originality/valueThis study builds a system from psychological aspect to behavior, which includes the mechanism of the influence of perceived insider status on employees' innovative behavior and a cross-level analysis of the influence of organizational innovation climate on employees' innovative behavior, breaking through the previous research paradigm of a single level of climate and employee behavior.
Influence of stratospheric aerosol geoengineering on temperature mean and precipitation extremes indices in Africa
Authors: Obahoundje Salomon , N'guessan Bi Vami Hermann , Diedhiou Arona , Kravitz Ben , Moore John C. 
Published: August 2022

Purpose
Three Coupled Model Intercomparison Project Phase 5 models involved in the G4 experiment of the Geoengineering Model Inter-comparison Project (GeoMIP) project were used to investigate the impact of stratospheric aerosol injection (SAI) on the mean surface air temperature and precipitation extremes in Africa.

Design/methodology/approach
This impact was examined under G4 and Representative Concentration Pathway (RCP) 4.5 scenarios on the total precipitation, the number of rainy days (RR1) and of days with heavy rainfall (R20 mm), the rainfall intensity (SDII), the maximum length of consecutive wet (CWD) and dry (CDD) days and on the maximum rainfall in five consecutive days (Rx5day) across four regions: Western Africa (WAF), Eastern Africa (EAF), Northern Africa and Southern Africa (SAF).

Findings
During the 50 years (2020–2069) of SAI, mean continental warming is −0.40°C lower in G4 than under RCP4.5. During the post-injection period (2070–2090), the temperature continues to increase, but at a lower rate (−0.19°C) than in RCP4.5. During SAI, annual rainfall in G4 is significantly greater than in RCP4.5 over the high latitudes (especially over SAF) and lower over the tropics. The termination of SAI leads to a significant increase of rainfall over Sahel and EAF and a decrease over SAF and Guinea Coast (WAF).

Practical implications
Compared to RCP4.5, SAI will contribute to reducing significantly regional warming but with a significant decrease of rainfall in the tropics where rainfed agriculture account for a large part of the economies. After the SAI period, the risk of drought over the extratropical regions (especially in SAF) will be mitigated, while the risk of floods will be exacerbated in the Central Sahel.

Originality/value
To meet the Paris Agreement, African countries will implement mitigation measures to contribute to keep the surface air temperature below 2°C. Geoengineering with SAI is suggested as an option to meet this challenge, but its implication on the African climate system needs a deep investigation in the aim to understand the impacts on temperature and precipitation extremes. To the best of the authors’ knowledge, this study is the first to investigate the potential impact of SAI using the G4 experiment of GeoMIP on temperature and precipitation extremes of the African continent.