bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding natural selection in Holocene Europe using multi-locus genotype identity scans
Authors: Pandey Devansh , Harris Mariana , Garud Nandita R. , Narasimhan Vagheesh M. 
Published: April 2023

AbstractAncient DNA (aDNA) has been a revolutionary technology in understanding human history but has not been used extensively to study natural selection as large sample sizes to study allele frequency changes over time have thus far not been available. Here, we examined a time transect of 708 published samples over the past 7,000 years of European history using multi-locus genotype-based selection scans. As aDNA data is affected by high missingness, ascertainment bias, DNA damage, random allele calling, and is unphased, we first validated our selection scan,G12ancient,on simulated data resembling aDNA under a demographic model that captures broad features of the allele frequency spectrum of European genomes as well as positive controls that have been previously identified and functionally validated in modern European datasets on data from ancient individuals from time periods very close to the present time. We then applied our statistic to the aDNA time transect to detect and resolve the timing of natural selection occurring genome wide and found several candidates of selection across the different time periods that had not been picked up by selection scans using single SNP allele frequency approaches. In addition, enrichment analysis discovered multiple categories of complex traits that might be under adaptation across these periods. Our results demonstrate the utility of applying different types of selection scans to aDNA to uncover putative selection signals at loci in the ancient past that might have been masked in modern samples.
Permethylation as a Strategy for High Molecular Weight Polysaccharide Structure Analysis by NMR – Case Study ofXylella fastidiosaEPS
Authors: Ndukwe Ikenna E. , Black Ian , Castro Claudia A. , Vlach Jiri , Heiss Christian , Roper Caroline , Azadi Parastoo 
Published: April 2023

AbstractCurrent practices for structure analysis of extremely large molecular weight polysaccharides via solution-state NMR spectroscopy incorporate partial depolymerization protocols that enable polysaccharide solubilization in suitable solvents. Non-specific depolymerization techniques utilized for glycosidic bond cleavage, such as chemical degradation or ultrasonication, potentially generate structure fragments that can complicate the complete characterization of polysaccharide structures. Utilization of appropriate enzymes for polysaccharide degradation, on the other hand, requires prior structure information and optimal enzyme activity conditions that are not available to the analyst working with novel or unknown compounds. Herein, we describe the application of a permethylation strategy that allows the complete dissolution of the intact polysaccharides for NMR structure characterization. This approach is utilized for NMR analysis ofXylella fastidiosaEPS, which is essential for the virulence the plant pathogen that affects multiple commercial crops and is responsible for multibillion dollar losses each year.
Development of a Xylose-Inducible Promoter and Riboswitch Combination System for Manipulating Gene Expression inFusobacterium nucleatum
Authors: Bibek GC , Zhou Peng , Naha Arindam , Gu Jianhua , Wu Chenggang 
Published: April 2023

ABSTRACTInducible gene expression systems are important for studying bacterial gene function, yet most exhibit leakage. In this study, we engineered a leakage-free hybrid system for precise gene expression controls inFusobacterium nucleatumby integrating the xylose-inducible expression system with the theophylline-responsive riboswitch. This innovative method enables concurrent control of target gene expression at both transcription and translation initiation levels. Using luciferase and the indole-producing enzyme tryptophanase (TnaA) as reporters, we demonstrated that the hybrid system displays virtually no observable signal in the absence of inducers. We employed this system to express FtsX, a protein related to fusobacterial cytokinesis, in anftsXmutant strain, unveiling a dose-dependent manner in FtsX production. Without inducers, cells form long filaments, while increasing FtsX levels by increasing inducers concentrations led to a gradual reduction in cell length until normal morphology was restored. Crucially, this system facilitated essential gene investigation, identifying the signal peptidaselepBgene as vital forF. nucleatum. LepB’s essentiality stems from depletion, affecting outer membrane biogenesis and cell division. This novel hybrid system holds the potential for advancing research on essential genes and accurate gene regulation inF. nucleatum.
Spatio-temporal dynamics and drivers of Highly Pathogenic Avian Influenza H5N1 in Chile
Authors: Azat Claudio , Alvarado-Rybak Mario , Aguilera José Fernando , Benavides Julio A. 
Published: April 2023

ABSTRACTHighly pathogenic avian influenza A H5N1 clade 2.3.4.4b (hereafter H5N1) is causing vast impacts on biodiversity and poultry around the globe. In Chile it was first reported on December 7th, 2022, in a pelican (Pelecanus thagus) found dead in the northern city of Arica. In the following months, lethal H5N1 cases were reported in a wide range of wild bird species, marine mammals, backyard and industrial poultry, and in a human. Despite its high impact and spread, it is not well-known what environmental factors are associated with outbreaks. This study describes the spatio-temporal patterns of the current epizootic of H5N1 in Chile and test ecological and anthropogenic drivers that could be associated with outbreak occurrence. We used H5N1 cases reported by the Chilean national animal health authority to the World Animal Health Information System (WAHIS) from December 9th, 2022, to March 3rd, 2023. These included bird cases confirmed through avian influenza specific real-time PCR assay (qPCR), obtained from passive and active surveillance. Data was analyzed to detect the presence of H5N1 clusters under space-time permutation probability modelling, H5N1 association between distance and days since first outbreak through linear regression, and correlation between H5N1 presence with a range of ecological and anthropogenic variables by general linear modelling. From the 197 H5N1 identified outbreaks, involving 478 individual cases among wild and domestic birds, a wave-like steady spread of H5N1 from north to south was identified, that can help predict hotspots of outbreak risk and establish targeted preventive measures. For instance, 14 statistically significant clusters were identified, with the largest located in central Chile (18-29 km in radius) where poultry production is concentrated. Also, one of the clusters was identified in Tocopilla, location where the H5N1 human case occurred time later. In addition, the presence of H5N1 outbreaks was positively correlated with bird richness, human footprint, precipitation of the wettest month, minimum temperature of the coldest month, and mean diurnal temperature. In contrast, presence of H5N1 was negatively correlated to distance to the closest urban center, precipitation seasonality and isothermality. Preventive actions based on our modeling approach include developing wildlife surveillance diagnostic capabilities in Chilean regions concentrating outbreaks. It is urgent that scientists, the poultry sector, local communities and national health authorities co-design and implement science-based measures from a One Health perspective to avoid further H5N1 spillover from wildlife to domestic animals and humans, including rapid removal and proper disposal of wild dead animals, and the closure of public areas (i.e., beaches) reporting high wildlife mortalities.
Contributions of attention to learning in multidimensional reward environments
Authors: Wang Michael Chong , Soltani Alireza 
Published: April 2023

AbstractReal-world choice options have many features or attributes, whereas the reward outcome from those options only depends on a few features/attributes. It has been shown that humans learn and combine feature-based with more complex conjunction-based learning to tackle challenges of learning in complex reward environments. However, it is unclear how different learning strategies interact to determine what features should be attended and control choice behavior, and how ensuing attention modulates future learning and/or choice. To address these questions, we examined human behavior during a three-dimensional learning task in which reward outcomes for different stimuli could be predicted based on a combination of an informative feature and conjunction. Using multiple approaches, we first confirmed that choice behavior and reward probabilities estimated by participants were best described by a model that learned the predictive values of both the informative feature and the informative conjunction. In this model, attention was controlled by the difference in these values in a cooperative manner such that attention depended on the integrated feature and conjunction values, and the resulting attention weights modulated learning by increasing the learning rate on attended features and conjunctions. However, there was little effect of attention on decision making. These results suggest that in multidimensional environments, humans direct their attention not only to selectively process reward-predictive attributes, but also to find parsimonious representations of the reward contingencies for more efficient learning.Significance StatementFrom trying exotic recipes to befriending new social groups, outcomes of real-life actions depend on many factors, but how do we learn the predictive values of those factors based on feedback we receive? It has been shown that humans simplify this problem by focusing on individual factors that are most predictive of the outcomes but can extend their learning strategy to include combinations of factors when necessary. Here, we examined interaction between attention and learning in a multidimensional reward environment that requires learning about individual features and their conjunctions. Using multiple approaches, we found that learning about features and conjunctions control attention in a cooperative manner and that the ensuing attention mainly modulates future learning and not decision making.
Conserved neural dynamics and computations across species in olfaction
Authors: Ling Doris , Moss Elizabeth H , Smith Cameron L , Kroeger Ryan , Reimer Jacob , Raman Baranidharan , Arenkiel Benjamin R 
Published: April 2023

AbstractInterpreting chemical information and translating it into ethologically relevant output is a common challenge of olfactory systems across species. Are computations performed by olfactory circuits conserved across species to overcome these common challenges? To understand this, we compared odor responses in the locust antennal lobe (AL) and mouse olfactory bulb (OB). We found that odors activated nearly mutually exclusive neural ensembles during stimulus presentation (‘ON response’) and after stimulus termination (‘OFF response’). Strikingly, ON and OFF responses evoked by a single odor were anticorrelated with each other. ‘Inverted’ OFF responses enhanced contrast between odors experienced close together in time. Notably, OFF responses persisted long after odor termination in both AL and OB networks, indicating a form of short-term memory. Taken together, our results reveal key neurodynamic features underlying olfactory computations that are conserved across insect and mammalian olfactory systems.
Dysregulated expression ofHoxa1isoforms in hematopoietic stem and progenitor cells causes myelodysplastic syndromes
Authors: Tan ShuhYing , Joseph Chacko , Chalk Alistair M. , Hendy Jean , Fabb Stewart , Schleibs Kelli , Lee Samuel C. , Tjin Gavin , Grace Clea S. , Madugalle Vinodini , Smeets Monique F. , Maluenda Ana C. , Rice Kim L. , Baker Emma K. , Nandurkar Harshal , Slape Christopher I. , Parker Michael W , Unnikrishnan Ashwin , Mufti Ghulam J. , Tobiasson Magnus , Hellstrom-Lindberg Eva , Pimanda John E. , Gudas Lorraine J. , Holien Jessica K. , Walkley Carl R. , Wall Meaghan , Purton Louise E. 
Published: April 2023

AbstractThe homeobox gene,Hoxa1, has two different isoforms generated by alternative splicing: a full-length homeodomain-containingHoxa1(Hoxa1-FL), and a truncatedHoxa1(Hoxa1-T), that lacks the homeodomain. Oncoretroviral overexpression of wildtypeHoxa1cDNA (WT-Hoxa1), which generates bothHoxa1isoforms, in murine hematopoietic stem and progenitor cells (HSPCs) perturbed hematopoiesis, resulting in myelodysplastic syndromes (MDS) in mice. Overexpression of a mutatedHoxa1cDNA (MUT-Hoxa1) that generatesHoxa1-FLbut notHoxa1-Tled to a more severe MDS capable of transforming to secondary acute myeloid leukemia (sAML). Similar to human MDS, DNA damage repair pathways were downregulated inHoxa1-overexpressing hematopoietic progenitor cells. Conditional knock-in mouse models revealed aHoxa1-FLdosage-dependent effect on MDS disease severity. Our data reveal that increased expression ofHoxa1-FLin HSPCs is sufficient to initiate MDS in mice. CD34+ cells from up to 50% of patients with MDS had elevatedHOXA1-FLexpression, highlighting the clinical relevance of our mouse models.Statement of SignificanceOur study demonstrates thatHoxa1is a key regulator of HSPCs and that increased expression of the transcriptionally activeHoxa1-FLcan initiate MDS in mice. Furthermore,HOXA1-FLexpression is upregulated in a significant proportion of human MDS patients and likely contributes to the disease in these patients.
What outcomes are important when evaluating people with hand scars? Results of an international clinician and researcher survey
Authors: Kennedy Donna L. , Chism-Balangue Tracy , Dereham Lucy , Furniss Dominic 
Published: April 2023

ABSTRACTBackgroundOutcome evaluation in people with hand and wrist scars is not standardised. To improve clinical care and research rigour, the authors are developing a core outcome set (COS) for the evaluation of hand scars. This survey identified what international clinicians and academics consider important outcomes for inclusion when evaluating people with hand scarring.MethodsAn electronic survey was developed, peer reviewed and disseminated via professional networks and social media. Professionals of diverse clinical backgrounds and geographical location with experience in the evaluation of hand and wrist scar outcomes in adults were invited to participate. The survey opened in February and closed in May 2022.Results162 participants, representing all World Health Organisation geographical regions, completed the survey. 32% of respondents reported using standardised scar patient reported outcome measures (PROMs); 31% using standardised scar clinician reported outcome measures (CROMs). In assessing physical symptoms of scar, sensitivity/hypersensitivity received the highest importance rating, and 36 additional physical symptom constructs were added as free text items by 72 participants. Regarding physical characteristic of scar, evaluation of adhesions was rated as most important and 19 additional physical characteristics were reported by 21 participants. Active range of motion was rated the most important impairment evaluation. In the domain of psychological impact of scarring, satisfaction with scarring and appearance acceptability were rated equally important. Sixty percent of participants reported using a standardised patient-reported outcome measure (PROM) for evaluating the functional impact of scars in the hand and wrist.DiscussionThis survey identified items for inclusion in the first round of a stakeholder Delphi consensus study, to agree a COS for the evaluation of hand and wrist scars. Frequency of importance ratings for evaluation constructs were determined to gauge the priorities of survey participants, not to exclude constructs. The disparate outcomes reported by free text within outcome domains highlights the lack of an agreed scar evaluation taxonomy, an important consideration for future consensus work. 107 (66%) of survey respondents consented to contact regarding further scar outcome evaluation consensus work, highlighting this work as a clinical priority.
Microstructure predicts non-motor outcomes following Deep Brain Stimulation in Parkinson’s disease
Authors: Loehrer Philipp A. , Bopp Miriam H. A. , Dafsari Haidar S. , Seltenreich Sieglinde , Knake Susanne , Nimsky Christopher , Timmermann Lars , Pedrosa David J. , Belke Marcus 
Published: April 2023

AbstractBackgroundDeep brain stimulation of the subthalamic nucleus (STN-DBS) is an effective treatment for motor and non-motor symptoms in advanced Parkinson’s disease (PD). However, considerable interindividual variability of outcomes exists. Neuroimaging based biomarkers, such as neurite orientation dispersion and density imaging (NODDI), a biophysical model based MRI-technique, have been proposed to predict clinical outcomes and therefore inform preoperative patient counselling.ObjectiveTo detect microstructural properties of brain areas associated with short-term non-motor outcomes following STN-DBS in PD.MethodsIn this prospective open-label study, 37 PD patients underwent diffusion MRI and comprehensive clinical assessments at preoperative baseline and 6-month follow-up. Neurite density index (NDI), orientation dispersion index (ODI), and fractional anisotropy (FA) were derived. Whole brain voxel-wise analysis assessed associations between microstructural metrics and non-motor outcomes corrected for multiple comparisons using a permutation-based approach.ResultsIntact microstructure within specific areas including right insular cortex, right putamen, right cingulum, and bilateral corticospinal tract were associated with greater postoperative improvement of non-motor symptom burden. Furthermore, microstructural properties of distinct brain regions were associated with postoperative changes in sleep, attention/memory, and urinary symptoms.ConclusionMicrostructural properties of distinct brain areas predict non-motor outcomes in DBS for PD. Therefore, diffusion MRI can support preoperative patient counselling and treatment selection by identifying patients with above-or below-average non-motor responses.
Voltage imaging reveals that hippocampal interneurons tune memory-encoding pyramidal sequences
Authors: Taxidis Jiannis , Madruga Blake , Melin Maxwell D , Lin Michael Z , Golshani Peyman 
Published: April 2023

ABSTRACTHippocampal spiking sequences encode and link behavioral information across time. How inhibition sculpts these sequences remains unknown. We performed longitudinal voltage imaging of CA1 parvalbumin- and somatostatin-expressing interneurons in mice during an odor-cued working memory task, before and after training. During this task, pyramidal odor-specific sequences encode the cue throughout a delay period. In contrast, most interneurons encoded odor delivery, but not odor identity, nor delay time. Population inhibition was stable across days, with constant field turnover, though some cells retained odor-responses for days. At odor onset, a brief, synchronous burst of parvalbumin cells was followed by widespread membrane hyperpolarization and then rebound theta-paced spiking, synchronized across cells. Two-photon calcium imaging revealed that most pyramidal cells were suppressed throughout the odor. Positive pyramidal odor-responses coincided with interneuronal rebound spiking; otherwise, they had weak odor-selectivity. Therefore, inhibition increases the signal-to-noise ratio of cue representations, which is crucial for entraining downstream targets.
Efficacy of a phage cocktail preparation for chronic lung infection withPseudomonas aeruginosain mice
Authors: Gao Ru-yue , Tan Xin , Pan Yong-jun , Yu Jia-lin , Ma Ying-fei 
Published: April 2023

AbstractPseudomonas aeruginosais a leading cause of hospital-acquired infections, and the emergence of multi-drug resistant strains has prompted the search for alternative treatments such as phage therapy. In this study, we combined host range and genomic information to design a four-phage cocktail that effectively killed several clinical strains (79%, 23/29) ofP. aeruginosa. We demonstrated that the cocktail, composed of three novel phages (PA_ZH1, PA_GL1, and PA_CQ9) and one previously characterized phage (PA_LZ7), was able to lyseP. aeruginosaboth in planktonic cultures and in alginate microbeads (an in vivo-like biofilm model). Additionally, we showed that the phage cocktail administered intranasally or intraperitoneally effectively rescued mice from chronic lung infection withP. aeruginosa. Our work explores the potential use of phages as an alternative therapeutic agent against chronic lung infections caused byP. aeruginosastrains.
What is in a game? The impact of advergame design and reward elements on gamers' brand patronage
Authors: Sarkar Juhi Gahlot , Sarkar Abhigyan , Sreejesh S. 
Published: April 2023

PurposeThis research investigates how advergame design elements (fantasy vs realistic advergame experiences) may impact players' brand patronage (BP), under the influence of mediators (hot and cold brand relationship quality [BRQ]) and moderators (advergame reward system and brand personality).Design/methodology/approachThis research comprises of a survey (study 1) and a lab experiment (study 2).FindingsStudy 1 shows that fantasy (reality) based advergame experience leads to brand patronage through strong mediation of hot (cold) BRQ and weak mediation of cold (hot) BRQ. Introducing a utilitarian (hedonic) advergame reward system positively moderates the effect of fantasy (reality) based advergame experience on cold (hot) BRQ. Study 2 shows that an advergame that elicits fantasy (realistic) experience and offers hedonic (utilitarian) rewards for a brand having affective (vs cognitive) brand personality strongly impacts hot (cold) BRQ.Originality/valueThis research is an effort to understand how gamification as leisure information systems may be used to create gamers' advergame experiences that elicit BP by strategically designing advergame reward systems specific to brand personality types.