bluuebunny/crossref_metadata_2025_split huggingface dataset:
Designing and validating a staircase to leverage floor mounted force plates
Authors: Hullfish Todd J. , Baxter Josh R. 
Published: July 2019

AbstractNavigating stairs is a challenging task for many patient populations. Unfortunately, assessing lower extremity kinetics is not practical in many laboratories due in part to methodologic constraints. In this study, we designed, fabricated, and calibrated a staircase that accurately measured ground reaction forces applied to the second and fourth step. This implementation met several design criteria that included low-cost, ability to quickly move the staircase in and out of motion capture spaces, stable and safe staircase, and easily modifiable to meet the constraints of different lab layouts. We built the staircase as an outer and inner staircase assembly constructed using a modular aluminum framing system. Once positioned on our force plates that were embedded in the lab floor, we used an instrumented pole to apply known loads to a series of surface locations on the force plates and steps that were resting on top of the force plates. This calibration procedure reduced the center of pressure errors by approximately 50% for the embedded force plates and lower step (step 2) and 3-fold for the higher step (step 4). Next, we demonstrated that these steps can be integrated into a clinical gait analysis workflow. A single healthy-young adult navigated the stairs, the ground reaction forces were transformed into stair reaction forces, and these external loads were used to solve the inverse dynamics problem. This staircase provides other researchers with a new tool to assess stair navigation biomechanics. In this study, we provided the bill of materials, mechanical drawings, and calibration code necessary to modify and implement this staircase paradigm into other lab layouts.
Bifidobacteriumis enriched in gut microbiome of Kashmiri women with polycystic ovary syndrome
Authors: Hassan Saqib , Kaakinen Marika A , Draisma Harmen , Ganie Mohd Ashraf , Rashid Aafia , Balkhiyarova Zhanna , Kiran George Seghal , Vogazianos Paris , Shammas Christos , Selvin Joseph , Antoniades Athos , Demirkan Ayse , Prokopenko Inga 
Published: July 2019

AbstractPolycystic ovary syndrome (PCOS) is a common endocrine condition in women of reproductive age understudied in non-European populations. In India, PCOS affects the life of up to 19.4 million women of age 14-25 years. Gut microbiome composition might contribute to PCOS susceptibility. We profiled the microbiome in DNA isolated from faecal samples by 16S rRNA sequencing in 19/20 women with/without PCOS from Kashmir, India. We assigned genera to sequenced species with an average 121k reads depth and included bacteria detected in at least 1/3 of the subjects or with average relative abundance ≥0.1%. We compared the relative abundances of 40/58 operational taxonomic units in family/genus level between cases and controls, and in relation to 33 hormonal and metabolic factors, by multivariate analyses adjusted for confounders, and corrected for multiple testing. Seven genera were significantly enriched in PCOS cases:Sarcina, AlkalibacteriumandMegasphaera, and previously reported for PCOSBifidobacterium, Collinsella, ParaprevotellaandLactobacillus. We identified significantly increased relative abundance ofBifidobacteriaceae(median 6.07% vs. 2.77%) andAerococcaceae(0.03% vs. 0.004%), whereas we detected lower relative abundancePeptococcaceae(0.16% vs. 0.25%) in PCOS cases. For the first time, we identified a significant direct association between butyrate producingEubacteriumand follicle-stimulating hormone levels. We observed increased relative abundance ofCollinsellaandParaprevotellawith higher fasting blood glucose levels, andParaprevotellaandAlkalibacteriumwith larger hip and waist circumference, and weight. We show a relationship between gut microbiome composition and PCOS linking it to specific reproductive health metabolic and hormonal predictors in Indian women.
Role and impact of the gut microbiota in aDrosophilamodel for parkinsonism
Authors: Feltzin Virzhiniya , Wan Kenneth H. , Celniker Susan E. , Bonini Nancy M. 
Published: July 2019

ABSTRACTDrosophilais poised to be a powerful model organism for studies of the gut-brain axis due to the relative simplicity of its microbiota, similarity to mammals, and efficient methods to rear germ-free flies. We examined the gut-brain axis inDrosophilamodels of autosomal recessive parkinsonism and discovered a relationship between the gut microbiota andparkinloss of function. The number of live bacteria was increased approximately five-fold in the gut of agedparkinnull animals. Conditional RNAi showed thatparkinis required in gut enterocytes and not in neurons or muscle to maintain microbial load homeostasis. To examine the significance of gut microbiota, we reared germ-freeparkinflies and discovered that removal of microbes in the gut improves the animals’ resistance to paraquat. Sequencing of 16S rDNA revealed microbial species with altered relative abundance inparkinnull flies compared to controls. These data reveal a role forparkinactivity in maintaining microbial composition and abundance in the gut, suggesting a relationship betweenparkinfunction and the gut microbiota, and deepening our understanding ofparkinand the impacts upon loss ofparkinfunction.
Social interaction with an alcohol-intoxicated or cocaine-injected peer selectively alters social behaviors and drinking in adolescent male and female rats
Authors: Gamble Danielle M. , Josefson Chloe C. , Hennessey Mary K. , Davis Ashley M. , Waters Renee C. , Jones Brooke N. , Belton Destiny M. , Hall Nzia I. , Costen Taylor J. , Kirstein Cheryl L. , Maldonado-Devincci Antoniette M. 
Published: July 2019

AbstractBackgroundDrinking alcohol is facilitated by social interactions with peers, especially during adolescence. The importance of peer social influences during adolescence on alcohol and substance use have recently received more attention. We have shown that social interaction with an alcohol-intoxicated peer influences adolescent alcohol drinking differently in male and female rats using the demonstrator-observer paradigm. The present set of experiments analyzed the social interaction session to determine behaviors that influence alcohol drinking in adolescent male and female rats.MethodsSpecifically, in experiment one we determined which behaviors were altered during social interaction with an alcohol-intoxicated demonstrator and assessed changes in ethanol intake in adolescent observers. Experiment two examined changes in voluntary saccharin consumption to determine if social interaction with an alcohol-intoxicated demonstrator altered consumption of a palatable solution. In experiment three, we administered a low (5 mg/kg) or high (20 mg/kg) dose of cocaine to the demonstrator and assessed changes in the adolescent observers to determine if social interaction with a ‘drugged’ peer altered social behaviors and voluntary ethanol intake.ResultsWe showed that social interaction with an alcohol-intoxicated demonstrator (1) decreased social play and increased social investigation and social contact in adolescent male and female observers, (2) did not alter non-social behaviors, (3) did not alter saccharin consumption and (4) increased voluntary ethanol intake in adolescent female but not male observers. When the peer was injected with cocaine (1) social play was dose-dependently decreased, (2) there were no changes in other social or non-social behaviors, and (3) voluntary ethanol intake in adolescent male and female observers was unaffected.ConclusionsThe present results are consistent and extend our previous work showing that social interaction with an alcohol-intoxicated peer selectively alters social behaviors and alcohol-drinking in adolescent rats. Females appear to be more sensitive to elevating effects of social interaction on voluntary ethanol consumption.
Alternative splicing of circadian clock genes correlates with temperature in field-grown sugarcane
Authors: Dantas Luíza L. B. , Calixto Cristiane P. G. , Dourado Maira M. , Carneiro Monalisa S. , Brown John W. S. , Hotta Carlos T. 
Published: July 2019

AbstractAlternative Splicing (AS) is a mechanism that generates different mature transcripts from precursor mRNAs (pre-mRNAs) of the same gene. In plants, a wide range of physiological and metabolic events are related to AS, as well as fast responses to changes in temperature. AS is present in around 60% of intron-containing genes in Arabidopsis, 46% in rice and 38% in maize and it is widespread among the circadian clock genes. Little is known about how AS influences the circadian clock of C4 plants, like commercial sugarcane, a C4 crop with a complex hybrid genome. This work aims to test if the daily dynamics of AS forms of circadian clock genes are regulated by environmental factors, such as temperature, in the field. A systematic search for AS in five sugarcane clock genes, ScLHY, ScPRR37, ScPRR73, ScPRR95 and ScTOC1 using different organs of sugarcane sampled during winter, with 4 months old plants, and during summer, with 9 months old plants, revealed temperature- and organ-dependent expression of at least one alternatively spliced isoform in all genes. Expression of AS isoforms varied according to the season. Our results suggest that AS events in circadian clock genes are correlated with temperature.
Integrative genomics identifies a convergent molecular subtype that links epigenomic with transcriptomic differences in autism
Authors: Ramaswami Gokul , Won Hyejung , Gandal Michael J. , Haney Jillian , Wang Jerry C. , Wong Chloe C.Y. , Sun Wenjie , Prabhakar Shyam , Mill Jonathan , Geschwind Daniel H. 
Published: July 2019

AbstractAutism spectrum disorder (ASD) is a phenotypically and genetically heterogeneous neurodevelopmental disorder. Despite this heterogeneity, previous studies have shown patterns of molecular convergence in post-mortem brain tissue from autistic subjects. Here, we integrate genome-wide measures of mRNA expression, miRNA expression, DNA methylation, and histone acetylation from ASD and control brains to identify a convergent molecular subtype of ASD with shared dysregulation across both the epigenome and transcriptome. Focusing on this convergent subtype, we substantially expand the repertoire of differentially expressed genes in ASD and identify a component of upregulated immune processes that are associated with hypomethylation. We utilize eQTL and chromosome conformation datasets to link differentially acetylated regions with their cognate genes and identify an enrichment of ASD genetic risk variants in hyperacetylated noncoding regulatory regions linked to neuronal genes. These findings help elucidate how diverse genetic risk factors converge onto specific molecular processes in ASD.
Nek8445, a protein kinase required for microtubule regulation and cytokinesis inGiardia lamblia
Authors: Hennessey Kelly M. , Alas Germain C.M. , Rogiers Ilse , Li Renyu , Merritt Ethan A. , Paredez Alexander R. 
Published: July 2019

AbstractGiardiahas 198 Nek kinases whereas humans have only 11.Giardiahas a complex microtubule cytoskeleton that includes eight flagella and several unique microtubule arrays that are utilized for parasite attachment and facilitation of rapid mitosis and cytokinesis. The need to regulate these structures may explain the parallel expansion of the number of Nek family kinases. Here we use live and fixed cell imaging to uncover the role of Nek8445 in regulatingGiardiacell division. We demonstrate that Nek8445 localization is cell cycle regulated and this kinase has a role in regulating overall microtubule organization. Nek8445 depletion results in short flagella, aberrant ventral disc organization, loss of the funis, defective axoneme exit and altered cell shape. The axoneme exit defect is specific to the caudal axonemes, which exit from the posterior of the cell, and this defect correlates with rounding of the cell posterior and loss of the funis. Our findings implicate a role for the funis in establishingGiardia’scell shape and guiding axoneme docking. On a broader scale our results support the emerging view that Nek family kinases have a general role in regulating microtubule organization.
Engineered Th17 cell differentiation using a photo-activatable immune modulator
Authors: Parasar Bibudha , Chang Pamela V. 
Published: July 2019

AbstractT helper 17 (Th17) cells, an important subset of CD4+ T cells, help to eliminate extracellular infectious pathogens that have invaded our tissues. Despite the critical roles of Th17 cells in immunity, how the immune system regulates the production and maintenance of this cell type remains poorly understood. In particular, the plasticity of these cells, or their dynamic ability to trans-differentiate into other CD4+ T cell subsets, remains mostly uncharacterized. Here, we report a synthetic immunology approach using a photo-activatable immune modulator (PIM) to increase Th17 cell differentiation on demand with spatial and temporal precision to help elucidate this important and dynamic process. In this chemical strategy, we developed a latent agonist that, upon photochemical activation, releases a small-molecule ligand that targets the aryl hydrocarbon receptor (AhR) and ultimately induces Th17 cell differentiation. We used this chemical tool to control AhR activation with spatiotemporal precision within cells and to modulate Th17 cell differentiation on demand by using UV light illumination. We envision that this approach will enable an understanding of the dynamic functions and behaviors of Th17 cells in vivo during immune responses and in mouse models of inflammatory disease.
Age-dependent effects of reduced mTor signalling on life expectancy through distinct physiology
Authors: Simons Mirre J P , Hartshorne Laura , Trooster Suzan , Thomson Jessica , Tatar Marc 
Published: July 2019

AbstractResearch on the mechanisms of ageing has identified ways via which lifespan can be extended in model organisms, increasing the potential for translation of these findings to our own species. However, the large majority of research on animal models involves dietary, genetic or pharmacological treatments throughout life – limiting translational potential and ignoring age-dependent effects. Previously, we have suggested using demographic meta-analysis that reduced mTor signalling has the potential to instantly rejuvenate. We have now tested this prediction experimentally using large-scale demographic data (N > 10,000) combined with conditional knockdown of mTor in Drosophila melanogaster. Indeed, reduced mTor decreased mortality rate when applied during old age. Interestingly, we found that transient treatment during early adult life had long-lasting benefits. Age-dependent deep-RNAseq indicated that these effects arose from distinct physiology and implicate alternative splicing as a potential mechanism for the long-lasting benefits of transient mTor reduction. These findings suggest that reducing mTor short term or during old age could be used to combat ageing. In addition, our findings suggest that the results from experimental research on mTor signalling, and potentially other mechanisms of ageing, that employ life-long interventions are likely to be a complex composite of age-dependent effects that counteract or enhance each other.
Matrix-matched calibration curves for assessing analytical figures of merit in quantitative proteomics
Authors: Pino Lindsay K , Yang Han-Yin , Noble William Stafford , Searle Brian C , Hoofnagle Andrew N , MacCoss Michael J 
Published: July 2019

AbstractMass spectrometry is a powerful tool for quantifying protein abundance in complex samples. Advances in sample preparation and the development of data independent acquisition (DIA) mass spectrometry approaches have increased the number of peptides and proteins measured per sample. Here we present a series of experiments demonstrating how to assess whether a peptide measurement is quantitative by mass spectrometry. Our results demonstrate that increasing the number of detected peptides in a proteomics experiment does not necessarily result in increased numbers of peptides that can be measured quantitatively.
Modeling predicts that CRISPR-based activators, unlike CRISPR-based repressors, scale well with increasing gRNA competition and dCas9 bottlenecking
Authors: Clamons Samuel , Murray Richard 
Published: July 2019

AbstractSynthetic transcriptional networks built from CRISPR-based repressors (CRISPRi) rely on shared use of a core dCas9 protein. In E. coli, CRISPRi cannot support more than about a dozen simultaneous gRNAs before the fold repression of any individual gRNA drops below 10x. We show with a simple model based on previous characterization of competition in CRISPRi that activation by CRISPR-based activators (CRISPRa) is much less sensitive to dCas9 bottle-necking than CRISPRi. We predict that E. coli should be able to support dozens to hundreds of CRISPRa gRNAs at >10-fold activation.
Musical expertise generalizes to superior temporal scaling in a Morse code tapping task
Authors: Slayton Matthew A. , Romero-Sosa Juan L. , Shore Katrina , Buonomano Dean V. , Viskontas Indre V. 
Published: July 2019

ABSTRACTA key feature of the brain’s ability to tell time and generate complex temporal patterns is its capacity to produce similar temporal patterns at different speeds. For example, humans can tie a shoe, type, or play an instrument at different speeds or tempi—a phenomenon referred to as temporal scaling. While it is well established that training improves timing precision and accuracy, it is not known whether expertise improves temporal scaling. We quantified temporal scaling and timing precision in musicians and non-musicians as they learned to tap a Morse code sequence. We found that controls improved significantly over the course of days of training at the standard speed. In contrast, musicians exhibited a high level of temporal precision on the first day, which did not improve significantly with training. Although there was no significant difference in performance at the end of training at the standard speed, musicians were significantly better at temporal scaling—i.e., at reproducing the learned Morse code pattern at faster and slower speeds. Interestingly, both musicians and non-musicians exhibited a Weber-speed effect, where absolute temporal precision sharpened when producing patterns at the faster speed. These results are the first to establish that the ability to generate the same motor patterns at different speeds improves with extensive training and generalizes to non-musical domains.
The Relationship between Resilient Mangroves and Fish Populations in the Largest Marine Reserve in Belize: A Case for Conservation
Authors: Osborne Chetwynd , Cho-Ricketts Leandra , Salazar Jané 
Published: July 2019

AbstractMangrove forests are one of the most bio-diverse and productive wetland environments on earth. However, these unique tropical forest environments that occupy coastal areas are among the most threatened habitats globally. Approximately one-third of the world’s mangrove forests in tropical and subtropical coastlines have been lost to logging, conversion of land for agriculture and mariculture, and degradation due to general pollution over the past 50 years. The large population of mangroves occupying the Turneffe Atoll area in Belize face growing anthropogenic threats such as permanent clearing of land for housing and infrastructural development as well as pollution and natural factors (climate change). Despite these threats, mangroves have high resilience due to their fast rates of microbial decomposition and nutrient flux, large storage of nutrients below-ground, numerous feedbacks, keystone species redundancy and self-design, and highly efficient biotic controls. Given the few formal studies done to evaluate mangrove resilience at Turneffe Atoll, the purpose of this study was to evaluate mangrove resilience and nursery functions in the Turneffe Atoll Marine Reserve. Mangrove fish abundance, forest structure, and prop root length was assessed by means of visual census and point centred quarter method (PCQM) for 11 sites that span across conservation and general use zones. This study found that resilient mangroves (lower vulnerability ranks, higher standing biomass, and higher fish biomass and abundance) exist in conservation and general use zones and warrant the need for improved mangrove conservation measures. Some conservation measures include: greater reduction of non-climate stressors, establishment of more mangrove conservation areas, and implementation of more outreach and educational programmes.
Cdc24, the source of active Cdc42, transiently interacts with septins to create a positive feedback between septin assembly and bud site formation in yeast cells
Authors: Chollet Julian , Dünkler Alexander , Bäuerle Anne , Vivero-Pol Laura , Gronemeyer Thomas , Johnsson Nils 
Published: July 2019

AbstractYeast cells select at the beginning of each cell cycle the position of their new bud. The recruitment of the septins to this prospective bud site (PBS) is one of the critical events in a complex assembly pathway that culminates in the outgrowth of a new daughter cell. The septin-rods follow hereby the high concentration of Cdc42GTPthat is generated by the focused location of its GEF Cdc24. We show that Cdc24 not only activates Cdc42 but temporarily interacts shortly before budding with Cdc11, the subunit that caps septin rods at its both ends. Mutations in Cdc24 that reduce the affinity to Cdc11 impair septin assembly and decrease the stability of the polarity patch. The interaction between septins and Cdc24 thus reinforces bud assembly at sites where septin structures are formed. Once the septins polymerize into the ring, Cdc24 transfers to its center and directs from there the further outgrowth of the membrane.