bluuebunny/crossref_metadata_2025_split huggingface dataset:
Corpus callosal microstructure predicts bimanual motor performance in chronic stroke survivors: A preliminary cross-sectional study
Authors: Varghese Rini , Chang Brianna , Kim Bokkyu , Liew Sook-Lei , Schweighofer Nicolas , Winstein Carolee J. 
Published: May 2021

AbstractMicrostructural changes in the corpus callosum are associated with more severe motor impairment in the paretic hand, poor recovery, and general disability. Considering its role in bimanual coordination, we suspected that these microstructural changes across the callosum may also be reflected in the performance of ecologically valid routine bimanual tasks. Thus, the purpose of this study was to determine if callosal microstructure predicts bimanual motor performance in chronic stroke survivors by examining the regions of the corpus callosum connecting both the sensorimotor and non-sensorimotor cortices. We examined the relationship between the fractional anisotropy across the CC and movement times for two self-initiated and self-paced bimanual tasks in 41 chronic stroke survivors. Using publicly available control datasets (n = 52), matched closely for acquisition parameters, we also explored the effect of stroke and age on callosal microstructure. There were two main findings: First, callosal microstructure was significantly associated with bimanual performance in chronic stroke survivors. Notably, a significant relationship was observed not only with the primary sensorimotor regions, but also regions of the premotor/supplementary motor and prefrontal regions. Second, chronic stroke survivors presented with significantly lower mean FA, compared to neurologically intact adults. We conclude that in mild-to-moderate chronic stroke survivors with relatively localized lesions to the motor areas, callosal microstructure can be expected to change in not only the primary sensorimotor region, but also more anteriorly in the secondary motor regions and the genu and is associated with performance on cooperative bimanual tasks.SignificanceA goal of rehabilitation after stroke is to promote the return to pre-stroke levels of upper limb function and use, predominantly characterized by coordinated bimanual activities. In this study, we find that in the chronic phase of stroke, microstructural disorganization within the corpus callosum predicts motor performance on real-world bimanual tasks and lends important insight into the indirect, remote effects of stroke.HighlightsWe provide initial evidence that corpus callosal microstructure predicts performance on two self-initiated and self-paced bimanual tasks.Associations were strongest for fibers connecting the primary sensorimotor cortices followed by the pre- and supplementary motor, and prefrontal cortices.Significant reductions in fractional anisotropy were observed in stroke survivors for all regions of the corpus callosum.
An updated suite of viral vectors for in vivo calcium imaging using local and retro-orbital injections
Authors: Grødem Sverre , Nymoen Ingeborg , Vatne Guro Helén , Björnsdottir Valgerdur , Lensjø Kristian Kinden , Fyhn Marianne 
Published: May 2021

ABSTRACTCalcium imaging using genetically encoded Ca2+ indicators (GECIs) is a widely adopted method to measure neural activity in modern neuroscience. Here, we explore the use of systemically administered viral vectors for brain-wide expression of GECIs, and adapt novel GECIs to optimize signal-to-noise. We show that systemic injections of PHP.eB AAVs to express GECIs is a highly promising technique for imaging neural activity and circumvent the need for transgenic GECI expressing mouse lines. We also establish the use of soma-targeted GECIs that outperform current Ca2+ indicators using both systemic and local virus injections.
RORγt serine 182 tightly regulates T cell heterogeneity to maintain mucosal homeostasis and restrict tissue inflammation
Authors: Ma Shengyun , Patel Shefali , Chen Nicholas , Patel Parth R. , Cho Benjamin S. , Abbasi Nazia , Chang John T. , Huang Wendy Jia Men 
Published: May 2021

ABSTRACTIntestine homeostasis is maintained by the delicate balance of Th17 effector cells and Treg cells. Dysregulation of these cell populations contributes to inflammation, tissue damage, and chronic conditions. RORγt is essential for the differentiation of Th17 and a subset of Treg (RORγt+ Treg) cells involved in intestinal inflammation. RORγt belongs to the nuclear receptor family of transcription factors with hinge regions that are highly flexible for co-activator/co-repressor interactions. Serine 182 at the hinge region of RORγt is phosphorylated. This study aims to uncover how S182 on RORγt contributes to mucosal homeostasis and diseases. We used CRISRP technology to generate a phosphor-null knock-in mutant mouse line (RORγtS182A) to assess its role in intestine physiology. scRNA-seq was performed on WT and RORγtS182A cohoused littermates to evaluate colonic T cell heterogeneity under steady state and colitis settings. Single-cell transcriptomics revealed that RORγtS182 maintains colonic T cell heterogeneity under steady state, without interfering T cell development and differentiation. In inflamed tissues, RORγtS182 simultaneously restricts IL-1β-mediated Th17 activities and promotes anti-inflammatory cytokine IL-10 production in LT-like Treg cells. Phospho-null RORγtS182A knock-in mice challenged with DSS induced colitis and EAE experienced delayed recovery and exacerbated pathology. The double switch role of RORγtS182 is critical in resolving T cell-mediated inflammation and provides a potential therapeutic target to combat autoimmune diseases.
Desert fish populations tolerate extreme salinity change to overcome hydrological constraints
Authors: Schunter Celia , Bonzi Lucrezia C. , Norstog Jessica , Sourisse Jade , Berumen Michael L. , Angel Yoseline , Parkes Stephen D. , McCabe Matthew F. , Ravasi Timothy 
Published: May 2021

AbstractThe unstable nature of freshwater ponds in arid landscapes represent a sizable challenge for strictly aquatic organisms, such as fishes. Yet the Arabian Desert, bordering the coastline of the Red Sea, plays host to a species very well adapted to such extreme environments: the Arabian pupfish, Aphanius dispar. In this study, we estimated patterns of hydrological connectivity; population structure and stable isotope for samples of A. dispar living in small, isolated ponds of nearly-freshwater in the Arabian desert and highly saline coastal lagoons along the Red Sea. The genomic and hydrological analyses indicate that populations are largely separated by drainage origin, as fish from desert ponds appear to be transported to coastal lagoons of the Red Sea along ephemeral river systems arising from flash flood events. Further, our study indicates there is an ecological change when being washed from pond environments to coastal waters, due to a significant shift in muscle stable isotopes ratios between both groups. Considering that the genetic breaks are mostly observed between drainage origin, this study suggests that A. dispar can survive large changes in salinity and ecological regimes over small time-scales.
Threonine phosphorylation regulates the molecular assembly and signaling of EGFR in cooperation with membrane lipids
Authors: Maeda Ryo , Tamagaki-Asahina Hiroko , Sato Takeshi , Yanagawa Masataka , Sako Yasushi 
Published: May 2021

AbstractThe cytoplasmic domain of the receptor tyrosine kinases (RTKs) plays roles as a phosphorylation enzyme and a protein scaffold but the allocation of these two functions is not fully understood. We here analyzed assembly of the transmembrane (TM)-juxtamembrane (JM) region of EGFR, one of the best studied species of RTKs, by combining single-pair FRET imaging and a nanodisc technique. The JM domain of EGFR contains a threonine residue (Thr654) that is phosphorylated after ligand association. We observed that the TM-JM peptides of EGFR form anionic lipid-induced dimers and cholesterol-induced oligomers. The two forms involve distinct molecular interactions, with a bias towards oligomer formation upon threonine phosphorylation. We further analyzed the functions and oligomerization of whole EGFR molecules, with or without a substitution of Thr654 to alanine, in living cells. The results suggested an autoregulatory mechanism in which Thr654 phosphorylation causes a switch of the major function of EGFR from kinase activation dimers to scaffolding oligomers.
Agrobacterium-Mediated Transient Transformation of Marchantia Liverworts
Authors: Iwakawa Hidekazu , Melkonian Katharina , Schlüter Titus , Nishihama Ryuichi , Motose Hiroyasu , Nakagami Hirofumi 
Published: May 2021

AbstractAgrobacterium-mediated transient gene expression is a rapid and useful approach for characterizing functions of gene products in planta. However, the practicability of the method in the model liverwort Marchantia polymorpha has not yet been thoroughly described. Here we report a simple and robust method for Agrobacterium-mediated transient transformation of Marchantia thalli and its applicability. When thalli of M. polymorpha were co-cultured with Agrobacterium tumefaciens carrying GUS genes, GUS staining was observed primarily in assimilatory filaments and rhizoids. GUS activity was detected 2 days after infection and saturated 3 days after infection. We were able to transiently co-express fluorescently tagged proteins with proper localizations. Furthermore, we demonstrate that our method can be used as a novel pathosystem to study liverwort-bacteria interactions. We also provide evidence that air chambers support bacterial colonization.
Linear and partially linear models of behavioral trait variation using admixture regression
Authors: Connor Gregory , Fuerst Gerard R. 
Published: May 2021

AbstractAdmixture regression methodology exploits the natural experiment of random mating between individuals with different ancestral backgrounds to infer the environmental and genetic components to trait variation across racial and ethnic groups. This paper provides a statistical framework for admixture regression based on the linear polygenic index model and applies it to neuropsychological performance data from the Adolescent Brain Cognitive Development (ABCD) database. We develop and apply a new test of the differential impact of multi-racial identities on trait variation, an orthogonalization procedure for added explanatory variables, and a partially linear semiparametric functional form. We find a statistically significant genetic component to neuropsychological performance differences across racial identities, and find some possible evidence of nonlinearity in the link between admixture and neuropsychological performance scores in the ABCD data.
EvolvedBmp6enhancer alleles drive spatial shifts in gene expression during tooth development in sticklebacks
Authors: Stepaniak Mark D. , Square Tyler A. , Miller Craig T. 
Published: May 2021

ABSTRACTMutations in enhancers have been shown to often underlie natural variation but the evolved differences between enhancer activity can be difficult to identifyin vivo. Threespine sticklebacks (Gasterosteus aculeatus) are a robust system for studying enhancer evolution due to abundant natural genetic variation, a diversity of evolved phenotypes between ancestral marine and derived freshwater forms, and the tractability of transgenic techniques. Previous work identified a series of polymorphisms within an intronic enhancer of theBone morphogenetic protein 6(Bmp6) gene that are associated with evolved tooth gain, a derived increase in freshwater tooth number that arises late in development. Here we use a bicistronic reporter construct containing a genetic insulator and a pair of reciprocal two-color transgenic reporter lines to compare enhancer activity of marine and freshwater alleles of this enhancer. In older fish the two alleles drive partially overlapping expression in both mesenchyme and epithelium of developing teeth, but the freshwater enhancer drives a reduced mesenchymal domain and a larger epithelial domain relative to the marine enhancer. In younger fish these spatial shifts in enhancer activity are less pronounced. ComparingBmp6expression byin situhybridization in developing teeth of marine and freshwater fish reveals similar evolved spatial shifts in gene expression. Together, these data support a model in which the polymorphisms within this enhancer underlie evolved tooth gain by shifting the spatial expression ofBmp6during tooth development, and provide a general strategy to identify spatial differences in enhancer activityin vivo.
The structure of hippocampal circuitry relates to rapid category learning in humans
Authors: Schlichting Margaret L. , Gumus Melisa , Zhu Teresa , Mack Michael L. 
Published: May 2021

AbstractPrior work suggests that complementary white matter pathways within the hippocampus differentially support learning of specific versus general information. In particular, while the trisynaptic pathway (TSP) rapidly forms memories for specific experiences, the monosynaptic pathway (MSP) slowly learns generalities. However, despite the theorized significance of such circuitry, characterizing how information flows within hippocampus (HPC) to support learning in humans remains a challenge. We leveraged diffusion-weighted imaging as a proxy for individual differences in white matter structure linking key regions along TSP (HPC subfields CA3 and CA1) and MSP (entorhinal cortex and CA1) and related these differences in hippocampal structure to category learning ability. We hypothesized that learning to categorize the “exception” items that deviated from category rules would benefit from TSP-supported mnemonic specificity. Participant-level estimates of TSP- and MSP-related integrity were constructed from HPC subfield connectomes of white matter streamline density. Consistent with theories of TSP-supported learning mechanisms, we found a specific association between the integrity of CA3-CA1 white matter connections and exception learning. These results highlight the significant role of HPC circuitry in complex human learning.
More sustainable vegetable oil: balancing productivity with carbon storage opportunities
Authors: Alcock Thomas D , Salt David E , Wilson Paul , Ramsden Stephen J 
Published: May 2021

AbstractIntensive cultivation and post-harvest vegetable oil production stages are major sources of greenhouse gas (GHG) emissions. Variation between production systems and reporting disparity have resulted in discordance in previous emissions estimates. To assess systems-wide GHG implications of meeting increasing edible oil demand, we performed a unified re-analysis of life cycle input data from diverse oil palm, soybean, rapeseed, and sunflower production systems, from a saturating search of published literature. The resulting dataset reflects almost 6,000 producers in 38 countries, and is representative of over 74% of global vegetable oil production. Determination of the carbon cost of agricultural land occupation revealed that carbon storage potential drives variation in production GHG emissions, and indicates that expansion of production in low carbon storage potential land, whilst reforesting areas of high carbon storage potential, could reduce net GHG emissions whilst boosting productivity. Nevertheless, there remains considerable scope to improve sustainability within current production systems.
Portable low-cost optical density meter
Authors: Puccinelli Robert R. , Cabrera Joana P. , Huynh Emily , Lebel Paul M. , Gómez-Sjöberg Rafael 
Published: May 2021

AbstractMeasuring optical density (OD) is a very common technique in biological laboratories to determine the concentration of a substance in solution or of bacteria (or microscopic particles) in suspension. For example, bacterial cultures engineered to produce (express) a protein or compound of interest are a workhorse of modern molecular biology laboratories. Commonly, the expression of the product is triggered (induced) by a chemical signal added to the culture at the proper time in the growth curve of the culture (typically in the middle of the exponential growth phase, at an OD value of ∼0.6). The most common tool for measuring OD is a spectrophotometer. However, most spectrophotometers are sophisticated, non-portable and expensive laboratory instruments, costing tens of thousands of dollars. Even a very low cost spectrophotometer for educational use costs at least US$1,000. Because of the cost, even well resourced labs have only one instrument, which becomes a bottleneck when multiple bacterial cultures need to be monitored simultaneously. The problem is more acute in developing countries, where multiple labs have to share a single spectrophotometer, or there’s no such instrument at all. Having a cheap and simple device to measure OD would enable multiple people in a laboratory to monitor their bacterial cultures independently, even in resource-limited settings. At the same time, a portable OD meter could be useful for field work. Here we present the detailed build instructions and characterization of a very simple OD meter that costs only US$60, and can measure OD values from ∼0.05 to 2.0.Specifications table
zmiz1a zebrafish mutants have defective erythropoiesis, altered expression of autophagy genes, and a deficient response to vitamin D
Authors: Castillo-Castellanos Francisco , Ramírez Laura , Lomelí Hilda 
Published: May 2021

ABSTRACTZMIZ1 is a transcriptional coactivator that is related to members of the protein inhibitor of activated STAT (PIAS) family. ZMIZ1 regulates the activity of various transcription factors including the androgen receptor, p53, and Smad3. ZMIZ1 also interacts with Notch1 and selectively regulates Notch1 target genes relevant for T cell development and leukemogenesis in mammals. Human ZMIZ1 is additionally characterized as a latitude-dependent autoimmune disease (LDAD) risk gene, as it is responsive to vitamin D and has been associated with at least eleven blood cell traits.To address the function of ZMIZ1 in fish, we introduced CRISPR/Cas9 mutations in the zmiz1a gene in zebrafish. We observed that inactivation of zmiz1a in developing zebrafish larvae results in lethality at 15 dpf and delayed erythroid maturation. Differential gene expression analysis indicated that 15 dpf zmiz1a-null larvae had altered expression of autophagy genes, and erythrocytes that lacked Zmiz1a function exhibited an accumulation of mitochondrial DNA. Furthermore, we observed that autophagy gene expression was dysregulated at earlier stages of development, which suggests the involvement of Zmiz1a in the regulation of autophagy genes beyond the process of red blood cell differentiation. Finally, we showed that the loss of Zmiz1a decreased the capacity of the embryos to respond to vitamin D, indicating additional participation of Zmiz1a as a mediator of vitamin D activity.
Development of antibiotic resistance reveals diverse evolutionary pathways to face the complex and dynamic environment of a long-term treated patient
Authors: Colque Claudia A. , Tomatis Pablo E. , Albarracín Orio Andrea G. , Dotta Gina , Moreno Diego M. , Hedemann Laura G. , Hickman Rachel A. , Sommer Lea M. , Feliziani Sofía , Moyano Alejandro J. , Bonomo Robert A. , Johansen Helle K. , Molin Søren , Vila Alejandro J. , Smania Andrea M. 
Published: May 2021

ABSTRACTAntibiotic resistance development has been studied using approaches that range from laboratory experimental evolution, surveillance and epidemiology, to clinical isolate sequencing. However, evolutionary trajectories depend on the environment in which selection takes place, compelling to address evolutionary analyses in antibiotic-treated patients, to embrace the whole inherent environmental complexities as well as their dynamics over time. Herein, we address the complexity of the bacterial adaptive response to changing antibiotic selective pressures by studying the long-term in-patient evolution of a broad diversity of β-lactam resistant Pseudomonas aeruginosa clones. By using mutational and ultra-deep amplicon sequencing, we analyzed multiple generations of a P. aeruginosa hypermutator strain persisting for more than 26 years of chronic infection in the airways of a cystic fibrosis (CF) patient. We identified the accumulation of multiple alterations targeting the chromosomally encoded class C β-lactamase (blaPDC), providing structural and functional protein changes that resulted in a continuous enhancement of its catalytic efficiency and high level of cephalosporin resistance. This evolution was linked to the persistent treatment with ceftazidime, which we demonstrate selected for variants with robust catalytic activity against this expanded-spectrum cephalosporin. Surprisingly, “a gain of function” of collateral resistance towards ceftolozane, a more recently introduced cephalosporin that was not prescribed to this patient, was also observed and the biochemical basis of this cross-resistance phenomenon was elucidated. This work unveils the diversity of evolutionary trajectories driven by bacteria in the natural CF environmental setting, towards a multidrug resistant phenotype after years of antibiotic treatment against a formidable pathogen.
Excess mortality during the COVID-19 pandemic: a geospatial and statistical analysis in Mogadishu, Somalia
Authors: Warsame Abdihamid , Bashiir Farah , Freemantle Terri , Williams Chris , Vazquez Yolanda , Reeve Chris , Aweis Ahmed , Ahmed Mohamed , Checchi Francesco , Dalmar Abdirisak 
Published: May 2021

AbstractBackgroundWhile the impact of the COVID-19 pandemic has been well documented in high-income countries, much less is known about its impact in Somalia where health systems are weak and vital registration is under developed.MethodsWe used remote sensing and geospatial analysis to quantify the number of burials from January 2017 to September 2020 in Mogadishu. We imputed missing grave counts using surface area data. Simple interpolation and a generalised additive mixed growth model were used to predict both actual and counterfactual burial rates by cemetery and across Mogadishu during the most likely period of COVID-19 excess mortality and to compute excess burials. We also undertook a qualitative survey of key informants to determine the drivers of COVID-19 excess mortality.ResultsBurial rates increased during the pandemic period with a ratio to pre-pandemic levels averaging 1.5-fold and peaking at 2.2-fold. When scaled to plausible range of baseline Crude Death Rates (CDR), excess death toll between January and September 2020 ranged between 3,200 and 11,800. When compared to burial records of the Barakaat Cemetery Committee our estimates were found to be lower.ConclusionsOur study points to considerable under estimation of COVID-19 impact in Banadir and an overburdened public health system struggling to deal with the increasing severity of the epidemic in 2020.
Reagent- and actuator-free analysis of individual erythrocytes using three-dimensional quantitative phase imaging and capillary microfluidics
Authors: Ryu DongHun , Nam Hyeono , Jeon Jessie S. , Park YongKeun 
Published: May 2021

AbstractHistopathological examination of blood cells plays a crucial role in the diagnosis of various diseases. However, it involves time-consuming and laborious staining procedures required for microscopic review by medical experts and is not directly applicable for point-of-care diagnosis in resource-limited locations. This study reports a dilution-, actuation- and label-free method for the analysis of individual red blood cells (RBCs) using a capillary microfluidic device and quantitative phase imaging. Blood, without any sample treatment, is directly loaded into a micrometer-thick channel such that it forms a quasi-monolayer inside the channel. The morphological and biochemical properties of RBCs, including hemoglobin concentration, hemoglobin content, and corpuscular volume, were retrieved using the refractive index tomograms of individual RBCs measured using 3D quantitative phase imaging. The deformability of individual RBCs was also obtained by measuring the dynamic membrane fluctuations. The proposed framework applies to other imaging modalities and biomedical applications, facilitating rapid and cost-effective diagnosis and prognosis of diseases.