bluuebunny/crossref_metadata_2025_split huggingface dataset:
Symmetry breaking of hPSCs in micropattern generates a polarized spinal cord-like organoid (pSCO) with dorsoventral organization
Authors: Seo Kyubin , Cho Subin , Lee Ju-Hyun , Kim June Hoan , Lee Boram , Jang Hwanseok , Kim Youngju , Cho Hyo Min , Lee Sanghyuk , Park Yongdoo , Kim Hee Youn , Lee Taeseob , Park Woong-Yang , Kim Yong Jun , Yang Esther , Geum Dongho , Kim Hyun , Ryu Jae Ryun , Sun Woong 
Published: September 2021

AbstractBrain organoid research is advancing, but generation of organoids with proper axis formation, which could lead to spatially ordered structures for complex brain structure and function, still remains a challenge. Axis formation and related spatial cell organization in the CNS are initiated by the symmetry breaking during the early embryo development. It has been demonstrated that the geometrically confined culture of human pluripotent stem cells (hPSCs) can be used to induce symmetry breaking and regionalized cell differentiation. In this study, we generated a polarized spinal cord organoid with a self-organized dorsoventral (DV) organization, using 2D cell patterning by geometric confinement. Initially, the application of caudalization signals to hPSCs promoted the regionalized cell differentiation along the radial axis and sprouting-like protrusion morphogenesis in cell colonies confined to ECM protein micropatterns. Detachment of colonies turned them into extended spinal cord-like organoids which maintained center- and edge-derived two poles. Further analyses including single cell RNA sequencing and spatial transcriptome analysis unveiled that these organoids contained rich repertoire of developing spinal cord cells and exhibited the spatially ordered DV domain formation along the long axis without external organizing signals. Modulation of BMP and Shh signaling can control the extent of DV coverage in organoids following the principles of embryo patterning. Our study provides a simple, and precisely controllable method to generate spatially-ordered organoids for understanding of biological principles of cell patterning and axis formation during neural development.
Lysosome-related organelles contain an expansion compartment that mediates delivery of zinc transporters to promote homeostasis
Authors: Mendoza Adelita D. , Dietrich Nicholas , Tan Chieh-Hsiang , Herrera Daniel , Kasiah Jennysue , Payne Zachary , Schneider Daniel L. , Kornfeld Kerry 
Published: September 2021

ABSTRACTLysosome-related organelles play evolutionarily conserved roles in zinc storage, but mechanisms that control zinc flow in and out are not well understood. In C. elegans intestinal cells, the CDF-2 transporter stores zinc in these organelles during excess. Here we identify ZIPT-2.3 as the transporter that releases zinc during deficiency. The expression levels of CDF-2 and ZIPT-2.3 are reciprocally regulated in zinc excess and deficiency, establishing a fundamental mechanism of homeostasis. Super-resolution microscopy demonstrated these organelles are composed of a spherical acidified compartment and a hemispherical expansion compartment. The expansion compartment inflates during zinc excess and deficiency by vesicle fusion delivering zinc transporters. These results identify an unexpected structural feature of lysosome-related organelles that facilitates rapid transitions in the composition of zinc transporters to mediate homeostasis.
SPtsAnalysis: a high-throughput super-resolution single particle trajectory analysis to reconstruct organelle dynamics and membrane re-organization
Authors: Parutto P. , Heck J. , Lu M. , Kaminski C. , Heine M. , Avezov E. , Holcman D. 
Published: September 2021

AbstractSuper-resolution imaging can generate thousands of single-particle trajectories. These data can potentially reconstruct subcellular organization and dynamics, as well as measure disease-linked changes. However, computational methods that can derive quantitative information from such massive datasets are currently lacking. Here we present data analysis and algorithms that are broadly applicable to reveal local binding and trafficking interactions and organization of dynamic sub-cellular sites. We applied this analysis to the endoplasmic reticulum and neuronal membrane. The method is based on spatio-temporal time window segmentation that explores data at multiple levels and detects the architecture and boundaries of high density regions in areas that are hundreds of nanometers. By statistical analysis of a large number of datapoints, the present method allows measurements of nano-region stability. By connecting highly dense regions, we reconstructed the network topology of the ER, as well as molecular flow redistribution, and the local space explored by trajectories. Segmenting trajectories at appropriate scales extracts confined trajectories, allowing quantification of dynamic interactions between lysosomes and the ER. A final step of the method reveals the motion of trajectories relative to the ensemble, allowing reconstruction of dynamics in normal ER and the atlastin-null mutant. Our approach allows users to track previously inaccessible large scale dynamics at high resolution from massive datasets. The SPtsAnalysis algorithm is available as an ImageJ plugin that can be applied by users to large datasets of overlapping trajectories and offer a standard of SPTs metrics.
Sex differences in cardio-pulmonary pathology of SARS-CoV2 infected and Trypanosoma cruzi co-infected mice
Authors: Dhanyalayam Dhanya , Lizardo Kezia , Oswal Neelam , Thangavel Hariprasad , Dolgov Enriko , Perlin David S. , Nagajyothi Jyothi F. 
Published: September 2021

ABSTRACTBackgroundCoronavirus disease-2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2; CoV2) is a deadly contagious infectious disease. For those who survived COVID-19, post-COVID cardiac damage poses a major threat for the progression of cardiomyopathy and heart failure. Currently, the number of COVID-related cases and deaths are increasing in Latin America, where a major COVID comorbidity is Chagas’ heart disease (caused by the parasite Trypanosoma cruzi). Here, we investigated the effect of T. cruzi infection on the pathogenesis and severity of CoV2 infection and, conversely, the effect of CoV2 infection on heart pathology during coinfection.Methodology/findingsWe used transgenic human angiotensin-converting enzyme 2 (huACE2) mice infected with CoV2, T. cruzi, or coinfected with both in this study. Our study shows for the first time that white adipose tissue (WAT) serves as a reservoir for CoV2 and the persistence of CoV2 in WAT alters adipose tissue morphology and adipocyte physiology. Our data demonstrate a correlation between the loss of fat cells and the pulmonary adipogenic signaling (via adiponectin isomers) and pathology in CoV2 infection. The viral load in the lungs is inversely proportional to the viral load in WAT, which differs between male and female mice. Our findings also suggest that adiponectin-PPAR signaling may differently regulate Chagas cardiomyopathy in coinfected males and females.ConclusionWe conclude that adipogenic signaling may play important roles in cardio-pulmonary pathogenesis during CoV2 infection and T. cruzi coinfection. The levels of adiponectin isomers differ between male and female mice during CoV2 infection and coinfection with T. cruzi, which may differently regulate inflammation, viral load, and pathology in the lungs of both the sexes. Our findings are in line with other clinical observations that reported that males are more susceptible to COVID-19 than females and suffer greater pulmonary damage.
Robust effects of working memory demand during naturalistic language comprehension in language-selective cortex
Authors: Shain Cory , Blank Idan A. , Fedorenko Evelina , Gibson Edward , Schuler William 
Published: September 2021

AbstractA standard view of human language processing is that comprehenders build richly structured mental representations of natural language utterances, word by word, using computationally costly memory operations supported by domain-general working memory resources. However, three core claims of this view have been questioned, with some prior work arguing that (1) rich word-by-word structure building is not a core function of the language comprehension system, (2) apparent working memory costs are underlyingly driven by word predictability (surprisal), and/or (3) language comprehension relies primarily on domain-general rather than domain-specific working memory resources. In this work, we simultaneously evaluate all three of these claims using naturalistic comprehension in fMRI. In each participant, we functionally localize (a) a language-selective network and (b) a ‘multiple-demand’ network that supports working memory across domains, and we analyze the responses in these two networks of interest during naturalistic story listening with respect to a range of theory-driven predictors of working memory demand under rigorous surprisal controls. Results show robust surprisal-independent effects of word-by-word memory demand in the language network and no effect of working memory demand in the multiple demand network. Our findings thus support the view that language comprehension (1) entails word-by-word structure building using (2) computationally intensive memory operations that are not explained by surprisal. However, these results challenge (3) the domain-generality of the resources that support these operations, instead indicating that working memory operations for language comprehension are carried out by the same neural resources that store linguistic knowledge.Significance StatementThis study uses fMRI to investigate signatures of working memory (WM) demand during naturalistic story listening, using a broad range of theoretically motivated estimates of WM demand. Results support a strong effect of WM demand in language-selective brain regions but no effect of WM demand in “multiple demand” regions that have previously been associated with WM in non-linguistic domains. We further show evidence that WM effects in language regions are distinct from effects of word predictability. Our findings support a core role for WM in incremental language processing, using WM resources that are specialized for language.
WDR60-mediated dynein-2 loading into cilia powers retrograde IFT and transition zone crossing
Authors: De-Castro Ana R. G. , Rodrigues Diogo R. M. , De-Castro Maria J. G. , Vieira Neide , Vieira Cármen , Carvalho Ana X. , Gassmann Reto , Abreu Carla M. , Dantas Tiago J. 
Published: September 2021

ABSTRACTThe dynein-2 motor complex drives retrograde intraflagellar transport (IFT), playing a pivotal role in the assembly and functions of cilia. However, the mechanisms that regulate dynein-2 motility remain poorly understood. Here, we identify the Caenorhabditis elegans WDR60 homolog (WDR-60) and dissect the roles of this intermediate chain using genome editing and live imaging of endogenous dynein-2/IFT components. We find that loss of WDR-60 impairs dynein-2 recruitment to cilia and its incorporation onto anterograde IFT trains, reducing the availability of the retrograde motor at the ciliary tip. Consistently, we show that less dynein-2 motors power WDR-60-deficient retrograde IFT trains, which move at reduced velocities and fail to exit cilia, accumulating on the distal side of the transition zone. Remarkably, disrupting the transition zone’s NPHP module almost fully restores ciliary exit of underpowered retrograde trains in wdr-60 mutants. This work establishes WDR-60 as a major contributor to IFT and the NPHP module as a roadblock to dynein-2 passage through the transition zone.
Cochlear organoids reveal epigenetic and transcriptional programs of postnatal hair cell differentiation from supporting cells
Authors: Kalra Gurmannat , Lenz Danielle , Abdul-Aziz Dunia , Hanna Craig , Herb Brian R. , Colantuoni Carlo , Milon Beatrice , Saxena Madhurima , Shetty Amol C. , Hertzano Ronna P. , Shivdasani Ramesh A. , Ament Seth A. , Edge Albert S. B. 
Published: September 2021

ABSTRACTWe explored the transcriptional and epigenetic programs underlying the differentiation of hair cells from postnatal progenitor cells in cochlear organoids. Heterogeneity in the cells including cells with the transcriptional signatures of mature hair cells allowed a full picture of possible cell fates. Construction of trajectories identified Lgr5+ cells as progenitors for hair cells and the genomic data revealed gene regulatory networks leading to hair cells. We validated these networks, demonstrating dynamic changes both in expression and predicted binding sites of these transcription factors during organoid differentiation. We identified known regulators of hair cell development, Atoh1, Pou4f3, and Gfi1, and predicted novel regulatory factors, Tcf4, an E-protein and heterodimerization partner of Atoh1, and Ddit3, a CCAAT/enhancer-binding protein (C/EBP) that represses Hes1 and activates transcription of Wnt signaling-related genes. Deciphering the signals for hair cell regeneration from mammalian cochlear supporting cells reveals candidates for HC regeneration which is limited in the adult.
Tracking animal reservoirs of pathogenic Leptospira: the right test for the right claim
Authors: Gomard Yann , Dellagi Koussay , Goodman Steve Michael , Mavingui Patrick , Tortosa Pablo 
Published: September 2021

AbstractLeptospirosis, caused by a pathogenic Leptospira bacteria, is the most prevalent zoonosis worldwide and in this context has been extensively investigated through a One Health framework. Diagnosis of human leptospirosis includes molecular and serological tools, with serological Microscopic Agglutination Test (MAT) still being considered as a gold standard. Mammals considered as biological reservoirs include species or populations that are able to maintain chronic infection and shed the bacteria via their urine in the environment. Leptospira bacteria are often investigated using the same diagnosis tool, serological MAT. However, MAT testing of putative animal reservoirs can lead to mis-interpretations as it can signal previous infection and not necessarily bring in robust information regarding the capacity of such sero-positive animals to maintain chronic infection. We use previously published data and present new results on introduced and endemic small mammals to show that MAT should not be used for the identification of reservoirs. By contrast, serological data are informative on the level of exposure of animals occupying a specific environment. Finally, we present a sequential methodology to investigate human leptospirosis in a One Health framework that associates molecular detection in humans and animals, together with MAT of human samples using Leptospira isolates obtained from reservoir animals occurring in the same environment.
An energy-aware approach for resources allocating in the internet of things using a forest optimization algorithm
Authors: Wu Minning , Zhang Feng , Rui X. 
Published: September 2021

Purpose
Internet of things (IoT) is essential in technical, social and economic domains, but there are many challenges that researchers are continuously trying to solve. Traditional resource allocation methods in IoT focused on the optimal resource selection process, but the energy consumption for allocating resources is not considered sufficiently. This paper aims to propose a resource allocation technique aiming at energy and delay reduction in resource allocation. Because of the non-deterministic polynomial-time hard nature of the resource allocation issue and the forest optimization algorithm’s success in complex problems, the authors used this algorithm to allocate resources in IoT.

Design/methodology/approach
For the vast majority of IoT applications, energy-efficient communications, sustainable energy supply and reduction of latency have been major goals in resource allocation, making operating systems and applications more efficient. One of the most critical challenges in this field is efficient resource allocation. This paper has provided a new technique to solve the mentioned problem using the forest optimization algorithm. To simulate and analyze the proposed technique, the MATLAB software environment has been used. The results obtained from implementing the proposed method have been compared to the particle swarm optimization (PSO), genetic algorithm (GA) and distance-based algorithm.

Findings
Simulation results show that the proper performance of the proposed technique. The proposed method, in terms of “energy” and “delay,” is better than other ones (GA, PSO and distance-based algorithm).

Practical implications
The paper presents a useful method for improving resource allocation methods. The proposed method has higher efficiency compared to the previous methods. The MATLAB-based simulation results have indicated that energy consumption and delay have been improved compared to other algorithms, which causes the high application of this method in practical projects. In the future, the focus will be on resource failure and reducing the service level agreement violation rate concerning the number of resources.

Originality/value
The proposed technique can solve the mentioned problem in the IoT with the best resource utilization, low delay and reduced energy consumption. The proposed forest optimization-based algorithm is a promising technique to help enterprises participate in IoT initiatives and develop their business.
The role of sociomaterial assemblage on entrepreneurship in coworking-spaces
Authors: Aslam Muhammad Mahmood , Bouncken Ricarda , Görmar Lars 
Published: September 2021

PurposeCoworking-spaces are considered as a new formula to facilitate autonomy, creativity, self-efficacy, work satisfaction and innovation, yet they also might overburden their users who in that course intend to limit social interaction and collaboration in the workspace. Thus, the question is how coworking-spaces shape entrepreneurial ventures.Design/methodology/approachThis study used an inductive research methodology based on data from three different data sources, including observations, archives and interviews from managers and entrepreneurs.FindingsThe findings suggest that the materiality in the form of spatial architectures (working, socialization and support structures) shared facilities and infrastructures (utilities, luxuries and specialties), and integrated digital technologies (applications and platforms) influence the flow of communication, internal and external linkages, as well as functional uniformity and distinctiveness. However, there exists an inherent dualism in sociomaterial assemblage in coworking-spaces, which can lead to instrumental and detrimental outcomes for entrepreneurs.Originality/valueThis study explains the role of sociomaterial assemblage on the working of entrepreneurs in shared workspaces.
Epidemiology and outcomes of dialysis requiring acute kidney injury: A single‐center study
Authors: Jaryal Ajay , Vikrant Sanjay , Gupta Dalip 
Published: September 2021

AbstractObjectivesAcute kidney injury (AKI) is a common diagnosis in hospitalized patients. Dialysis requiring AKI (AKI‐D) is associated with adverse outcomes. This study aims to know the clinical profile and short‐term outcomes at 3 months, in patients with AKI‐D, at our center.MethodsA prospective observational study was done of all the patients admitted with AKI‐D for 2 years, from July 2018 to June 2020. We recorded clinical parameters at baseline and postdischarge follow‐up at 3 months.ResultsOne hundred twenty‐eight patients had AKI‐D over 2 years. Then, 116 (90.6%) patients had community‐acquired AKI (CAAKI), and 12 (9.4%) patients had hospital‐acquired AKI. The underlying causes of AKI‐D were: toxins in 48 (37.5%), sepsis in 31 (24.2%), acute kidney disease in 15 (11.7%), acute gastroenteritis (AGE) in 9 (7%), and cardiogenic shock in 7 (5.5%) patients. The mean values of intact parathyroid hormone (available in 32% of patients) were 268 pg/mL. Intermittent hemodialysis was the commonest mode of dialysis (85.2%). A kidney biopsy was done in 23 (18%) patients. The most common diagnosis on kidney biopsy was glomerulonephritis (GN) in 12 patients (crescentic GN‐9 and IgA nephropathy‐3), followed by acute tubule‐interstitial nephritis in 6 patients. In‐hospital mortality was 29.7%. Overall, 39% regained serum creatinine in the normal range at 3 months, 36.7% died, 14.1% reached chronic kidney disease (CKD), 7.8% lost to follow‐up, and 2.3% had reached end‐stage renal disease.ConclusionThe majority of AKI‐D at our center was CAAKI. A significant chunk of AKI‐D (68.7%) was caused by preventable causes like toxins, sepsis, and AGE. Dysregulation of mineral metabolism was conspicuous. In chemical toxin vs. biological toxins and undifferentiated sepsis vs. the identifiable cause of sepsis, formers had significantly more in‐hospital mortality than the latter ones. AKI‐D is associated with high in‐hospital mortality, total mortality, and risk of progression to CKD at 3 months.
Banking structure change and corporate innovation: evidence from Chinese city‐branch data
Authors: Xin Fu , Zhang Jie , Guo Yue , Liang Shangkun 
Published: September 2021

AbstractThis paper documents empirical support for a key micro‐level channel – banking structure change induced by entry of small banks – through which financial sector deregulation affects corporate innovation. Using China’s banking deregulation on city commercial banks in 2006, we find robust evidence that banking structural change induced by the entry of small banks stimulates local industrial patent output. Furthermore, we find that the stimulating effects of small bank entry on local industrial patent output are more pronounced when the local banking system is previously dominated by large state‐owned banks and when the small banks have entered a city with more small and medium‐sized enterprises (SMEs). Our study suggests that banking structure change induced by small banks crucially affects the real economy.
Rates of switching stimulants in consecutively referred medication naïve adults with ADHD
Authors: Biederman Joseph , DiSalvo Maura , Green Allison , Woodworth K. Yvonne , Gilfix Talia , Law Cecilia , Gabrieli John , Faraone Stephen V. 
Published: September 2021

AbstractObjectiveTo evaluate the frequency and correlates of needing to switch the initial treatment with a stimulant medication to the alternative family in newly referred, untreated adults with ADHD initiating treatment.MethodsSubjects were consecutively referred unmedicated adults with DSM‐5 ADHD who initiated stimulant treatment. Before assessment with an expert clinician, participants completed a battery of self‐report measures to assess psychopathology, executive functioning, emotional dysregulation, and mind wandering. The rate of switching was examined using information from electronic medical records for up to three clinical follow‐up visits. Those who did and did not need to switch were compared on baseline demographic and clinical characteristics.ResultsTwenty‐four percent (N = 21/86) of ADHD patients needed to switch from their initially prescribed stimulant family within 60 days of initiating treatment due to poor tolerability. While the rate of switching was significantly higher in those initially prescribed MPH, the rate of patients requiring changes in formulation or additional antianxiety or antidepressant treatment was higher in those taking AMPH. There were some hints about predictive risk factors for switching by the presence of emotional dysregulation and depressive symptoms, depending on age and sex.ConclusionsThese findings call for improved efforts to help identify predictors of response to stimulant treatment in adults with ADHD to avoid unnecessary delays in identifying safe and effective treatments for these patients.