bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterisation of the phase-variable autotransporter Lav reveals a role in host cell adherence and biofilm formation in Non-TypeableHaemophilus influenzae
Authors: Phillips Zachary N. , Garai Preeti , Tram Greg , Husna Asma-Ul , Staples Megan , Grimwood Keith , Jennison Amy V. , Jennings Michael P. , Brockman Kenneth L. , Atack John M. 
Published: October 2021

AbstractLav is an autotransporter protein found in pathogenicHaemophilusandNeisseriaspecies. Lav in non-typeableHaemophilus influenzae(NTHi) is phase-variable: the gene reversibly switches ON-OFF via changes in length of a locus-located GCAA(n)simple DNA sequence repeat tract. The expression status oflavwas examined in carriage and invasive collections of NTHi, where it was predominantly not expressed (OFF). Phenotypic study showedlavexpression (ON) results in increased adherence to host cells, and denser biofilm formation. A survey ofHaemophilusspp. genome sequences showedlavis present in ∼60% of NTHi strains, butlavis not present in most typeableH. influenzae. Sequence analysis revealed a total of five distinct variants of the Lav passenger domain present inHaemophilusspp., with these five variants showing a distinct lineage distribution. Determining the role of Lav in NTHi will help understand the role of this protein during distinct pathologies.
A novel automated approach for improving standardization of the marble burying test enables quantification of burying bouts and activity characteristics
Authors: Wahl Lucas , Punt A. Mattijs , Arbab Tara , Willuhn Ingo , Elgersma Ype , Badura Aleksandra 
Published: October 2021

AbstractThe marble burying test is a commonly used paradigm to screen phenotypes in mouse models of neurodevelopmental and psychiatric disorders. The current methodological approach relies solely on reporting the number of buried marbles at the end of the test. By measuring the proxy of the behavior (buried marbles), rather than the behavior itself (burying bouts), many important characteristics regarding the temporal aspect of this assay are lost. Here we introduce a novel, automated method to quantify mouse behavior throughout the duration of the marble burying test with the focus on the burying bouts. Using open-source software packages, we trained a supervised machine learning algorithm (the “classifier”) to distinguish burying behavior in freely moving mice. In order to confirm the classifier’s accuracy and uncover the behavioral meaning of the marble burying test, we performed marble burying test in three mouse models: Ube3am-/p+ (Angelman Syndrome model), Shank2-/- (autism model), and Sapap3-/- (obsessive-compulsive disorder model) mice. The classifier scored burying behavior accurately and consistent with the literature in the Ube3am-/p+ mice, which showed decreased levels of burying compared to controls. Shank2-/- mice showed a similar pattern of decreased burying behavior, which was not found in Sapap3-/- mice. Tracking mouse behavior throughout the test enabled us to quantify activity characteristics, revealing hypoactivity in Ube3am-/p+ and hyperactivity in the Shank2-/- mice, indicating that mouse activity is unrelated to burying behavior. Together, we demonstrate that our classifier is an accurate method for the analysis of the marble burying test, providing more information than the currently used methods.Significance StatementThe marble burying test is widely used in phenotyping neurodevelopmental and neuropsychiatric disorder mouse models. Currently, its analysis consists of manually scoring the number of buried marbles upon the completion of the assay. This approach is not standardized across laboratories, and leaves out important variables such as movement characteristics and information about the burying bouts. This leads to divergent interpretations of the marble burying test, ranging from anxiety to cognitive impairment. We introduce a method that reliably tracks mouse behavior throughout the experiment, classifies the duration and number of the burying bouts, and is generalizable across laboratories. Using machine learning for measuring the actual burying behavior standardizes this method, and provides rich information about the burying characteristics.
Antibiotic resistance via bacterial cell shape-shifting
Authors: Ojkic Nikola , Serbanescu Diana , Banerjee Shiladitya 
Published: October 2021

AbstractBacteria have evolved to develop multiple strategies for antibiotic resistance by effectively reducing intra-cellular antibiotic concentrations or antibiotic binding affinities, but the role of cell morphology on antibiotic resistance remains poorly characterized. By analyzing cell morphological data of different bacterial species under antibiotic stress, we find that bacterial cells robustly reduce surface-to-volume ratio in response to most types of antibiotics. Using quantitative modelling we show that by reducing surface-to-volume ratio, bacteria can effectively reduce intracellular antibiotic concentration by decreasing antibiotic influx. The model predicts that bacteria can increase surface-to-volume ratio to promote antibiotic dilution if efflux pump activity is reduced, in agreement with data on membrane-transport inhibitors. Using the particular example of ribosome-targeting antibiotics, we present a systems-level model for the regulation of cell shape under antibiotic stress, and discuss feedback mechanisms that bacteria can harness to increase their fitness in the presence of antibiotics.
Dynamic Functional Brain Reconfiguration During Sustained Pain
Authors: Lee Jae-Joong , Lee Sungwoo , Lee Dong Hee , Woo Choong-Wan 
Published: October 2021

AbstractPain is constructed through complex interactions among multiple brain systems, but it remains unclear how functional brain network representations are dynamically reconfigured over time while experiencing pain. Here, we investigated the dynamic changes in the functional brain networks during 20-min capsaicin-induced sustained orofacial pain. In the early stage, the orofacial areas of the primary somatomotor cortex were separated from the other primary somatomotor cortices and integrated with subcortical and frontoparietal regions, constituting a brain-wide pain supersystem. As pain decreased over time, the subcortical and frontoparietal regions were separated from this pain supersystem and connected to multiple cerebellar regions. Machine-learning models based on these dynamic network features showed significant predictions of changes in pain experience across two independent datasets (n = 48 and 74). This study provides new insights into how multiple brain systems dynamically interact to construct and modulate pain experience, potentially advancing our mechanistic understanding of chronic pain.
Intermittent fasting induces rapid hepatocyte proliferation to restore the hepatostat in the mouse liver
Authors: Sarkar Abby , Jin Yinhua , DeFelice Brian C. , Logan Catriona , Yang Yan , Anbarchian Teni , Wu Peng , Morri Maurizio , Neff Norma , Nguyen Huy , Rulifson Eric , Fish Matt , Martínez Jaimes Azalia M. , Nusse Roel 
Published: October 2021

AbstractNutrient availability fluctuates in most natural populations, forcing organisms to undergo periods of fasting and re-feeding. It is unknown how dietary changes influence liver homeostasis. Here, we show that a switch from ad libitum feeding to intermittent fasting, IF, promotes rapid hepatocyte proliferation. Mechanistically, IF-induced hepatocyte proliferation is driven by the combined action of intestinally produced, systemic endocrine FGF15 and localized WNT signaling. Hepatocyte proliferation during periods of fasting and re-feeding re-establishes a constant liver-to-body-mass ratio, thus maintaining the hepatostat. This study provides the first example of dietary influence on adult hepatocyte proliferation and challenges the widely held view that liver tissue is mostly quiescent unless chemically or mechanically injured.
A plasma membrane-localized polycystin-1/polycystin-2 complex in endothelial cells elicits vasodilation
Authors: Mackay Charles E. , Floen Miranda , Leo M. Dennis , Hasan Raquibul , Fernández-Peña Carlos , Singh Purnima , Malik Kafait U. , Jaggar Jonathan H. 
Published: October 2021

AbstractPolycystin-1 (PC-1, PKD1), a receptor-like protein expressed by the Pkd1 gene, is present in a wide variety of cell types, but its cellular location, signaling mechanisms and physiological functions are poorly understood. Here, by studying tamoxifen-inducible, endothelial cell (EC)-specific Pkd1 knockout (Pkd1 ecKO) mice, we show that flow activates PC-1-mediated, Ca2+-dependent cation currents in ECs. EC-specific PC-1 knockout attenuates flow-mediated arterial hyperpolarization and vasodilation. PC-1-dependent vasodilation occurs over the entire functional shear stress range and primarily via the activation of nitric oxide synthase (NOS), with a smaller contribution from small-conductance Ca2+-activated K+ (SK) channels. EC-specific PC-1 knockout increases systemic blood pressure without altering kidney anatomy. PC-1 coimmunoprecipitates with polycystin-2 (PC-2, PKD2), a TRP polycystin channel, and clusters of both proteins locate in nanoscale proximity in the EC plasma membrane. Knockout of either PC-1 or PC-2 (Pkd2 ecKO mice) abolishes surface clusters of both PC-1 and PC-2 in ECs. Single knockout of PC-1 or PC-2 or double knockout of PC-1 and PC-2 (Pkd1/Pkd2 ecKO mice) similarly attenuates flow-mediated vasodilation. Flow stimulates non-selective cation currents in ECs that are similarly inhibited by either PC-1 or PC-2 knockout or by interference peptides corresponding to the C-terminus coiled-coil domains present in PC-1 or PC-2. In summary, we show that PC-1 regulates arterial contractility and demonstrate that this occurs through the formation of an interdependent signaling complex with PC-2 in endothelial cells. Flow stimulates PC-1/PC-2 clusters in the EC plasma membrane, leading to Ca2+ influx, NOS and SK channel activation, vasodilation and a reduction in blood pressure.
Roxadustat (FG‐4592) protects against ischaemia/reperfusion‐induced acute kidney injury through inhibiting the mitochondrial damage pathway in mice
Authors: Zhang Mei , Dong Rong , Yuan Jing , Da Jingjing , Zha Yan , Long Yanjun 
Published: October 2021

AbstractIschaemia–reperfusion (I/R) is one of the main factors of acute kidney injury (AKI). mitochondrial damage pathway are important features of I/R induced‐acute kidney injury (IRI‐AKI). Hypoxia‐inducible factor (HIF) expression in renal tubule segments is up‐regulated during AKI. Herein, we investigated the role of FG‐4592 in a mouse model of IRI‐AKI to confirm whether FG‐4592 is beneficial in AKI. We found that pretreatment with FG‐4592 significantly ameliorated renal function and renal histological damage in mice after IRI. Furthermore, these results suggest that pretreatment with FG‐4592 significantly reduced the tubular cells apoptosis (decreased TUNEL‐positive cells, Bax, caspase12 levels), attenuated mitochondrial damage (increased ATPβ, PPARγ, mitochondrial DNA copy number, and decreased cytoplasmic cytochrome C), and alleviated DNA damage after IRI. In conclusion, pretreatment with FG‐4592 may effectively prevent kidney from IRI possibly by via diminishing tubular cells injuries and protection of mitochondrial damage pathway. These results further validate that FG‐4592 may be an effective drug in the clinical treatment of IRI‐AKI.
Prior punishments and cumulative disadvantage: How supervision status impacts prison sentences*
Authors: Hickert Audrey , Bushway Shawn D. , Harding David J. , Morenoff Jeffrey D. 
Published: October 2021

AbstractThis article explores one way prior punishments may contribute to cumulative disadvantage: through more severe sentencing of those under criminal justice supervision. We examine the impact of being on supervision in Michigan on receiving a sentence of imprisonment—comparing the magnitude of the impact reflected in the formal sentencing guideline recommendation with deviations made by court actors. We find that the formal penalty for supervision status is modest, whereas court actors place substantially more weight on current parole status than do the guidelines when deciding to sentence a defendant to prison. They do not seem to give current probation status extra weight in a consistent way. As such, parole is more likely to contribute to cumulative disadvantage stemming from prior punishments. This disproportionately impacts Black defendants because of their higher rates of parole—not through disproportionate sentencing conditional on parole status. Findings suggest that attempts to address factors contributing to cumulative disadvantage will need to consider not only formal rules but also how informal discretion contributes to prison sentences.
Public fear of protesters and support for protest policing: An experimental test of two theoretical models*
Authors: Metcalfe Christi , Pickett Justin T. 
Published: October 2021

AbstractAs protests erupted across the United States in recent years over racialized issues (e.g., Black Lives Matter and Confederate monuments), so too did questions about when and how police should respond. Understanding public attitudes toward protest policing is important for police legitimacy and policy. One theory is that citizens are willing to trade civil liberties, such as the right to assemble, for security, and thus disruptive or dangerous protest tactics should increase support for police control by elevating public fear. Another theory is that citizens view protests through the lens of group position, and thus, they should be more supportive of repression when protest goals conflict with preexisting racial beliefs and threaten racial interests. To test these theories, we embedded an experiment in a nationwide survey fielded in 2020 after George Floyd's killing sparked the broadest protests in U.S. history. We randomized protest tactics (e.g., weapon carrying) and goals, as well as other contextual characteristics (e.g., protest size). We found that the public generally opposed repressive protest policing. Certain protest tactics, however, increased support for repression by elevating fear. Protest goals (e.g., pro‐Black Lives Matter and pro‐immigrants) also impacted support for repression, but the effect depended on respondents’ racial beliefs.
Both human and soya bean ferritins highly improve the accumulation of bioavailable iron and contribute to extend the chronological life in budding yeast
Authors: Pujol‐Carrion Nuria , Gonzalez‐Alfonso Alma , Puig Sergi , de la Torre‐Ruiz Maria Angeles 
Published: October 2021

SummaryFerritin proteins have an enormous capacity to store iron in cells. In search for the best conditions to accumulate and store bioavailable iron, we made use of a double mutant null for the monothiol glutaredoxins GRX3 and GRX4. The strain grx3grx4 accumulates high iron concentrations in the cytoplasm, making the metal easily available for ferritin chelation. Here, we perform a comparative study between human (L and H) and soya bean ferritins (H1 and H2) function in the eukaryotic system Saccharomyces cerevisiae. We demonstrate that the four human and soya bean ferritin chains are successfully expressed in our model system. Upon coexpression of either both human or soya bean ferritin chains, respiratory conditions along with iron supplementation led us to obtain the maximum yields of iron stored in yeast described to date. Human and soya bean ferritin chains are functional and present equivalent properties as promoters of cell survival in iron overload conditions. The best system revealed that the four human and soya bean ferritins possess a novel function as anti‐ageing proteins in conditions of iron excess. In this respect, both ferritin chains with oxidoreductase capacity (human‐H and soya bean‐H2) bear the highest capacity to extend life suggesting the possibility of an evolutionary conservation.
An appraisal of graph embeddings for comparing trophic network architectures
Authors: Botella Christophe , Dray Stéphane , Matias Catherine , Miele Vincent , Thuiller Wilfried 
Published: October 2021

Abstract

Comparing the architecture of interaction networks in space or time is essential for understanding the assembly, trajectory, functioning and persistence of species communities. Graph embedding methods, which position networks into a vector space where nearby networks have similar architectures, could be ideal tools for this purposes.

Here, we evaluated the ability of seven graph embedding methods to disentangle architectural similarities of interactions networks for supervised and unsupervised posterior analytic tasks. The evaluation was carried out over a large number of simulated trophic networks representing variations around six ecological properties and size.

We did not find an overall best method and instead showed that the performance of the methods depended on the targeted ecological properties and thus on the research questions. We also highlighted the importance of normalising the embedding for network sizes for meaningful posterior unsupervised analyses.

We concluded by orientating potential users to the most suited methods given the question, the targeted network ecological property, and outlined links between those ecological properties and three ecological processes: robustness to extinction, community persistence and ecosystem functioning. We hope this study will stimulate the appropriation of graph embedding methods by ecologists.
Democratization, Elections, and Public Goods: The Evidence from Deforestation
Authors: Sanford Luke 
Published: October 2021

AbstractThis article shows that over the last three decades, competitive elections were associated with increased deforestation. Protection of forested areas provides long‐term public goods, while their destruction provides short‐term private goods for particular voters. Politicians facing a competitive election offer voters access to forested areas mainly for small‐scale farming or commercial use of timber in exchange for electoral support. I test this theory of political deforestation using satellite generated global forest cover data and the results of over 1,000 national‐level elections between 1982 and 2016. I find that countries that undergo a democratic transition lose an additional 0.8 percentage points of their forest cover each year, that years with close elections have over 1 percentage point per year higher forest cover loss compared to nonelection years, and that as the margin of victory in an election decreases by 10 points, the amount of deforestation increases by 0.7 percentage points per year. These increases are on the order of 5–10 times the average rate of forest loss globally. This suggests democratization is associated with underprovision of environmental public goods and contested elections are partially responsible for this underprovision.
Novel disease‐causing variants and phenotypic features of X‐linked megalocornea
Authors: Dudakova Lubica , Tuft Stephen , Cheong Sek‐Shir , Skalicka Pavlina , Jedlickova Jana , Fichtl Marek , Hlozanek Martin , Filous Ales , Vaneckova Manuela , Vincent Andrea L. , Hardcastle Alison J. , Davidson Alice E. , Liskova Petra 
Published: October 2021

AbstractPurposeThe aim of the study was to describe the phenotype and molecular genetic causes of X‐linked megalocornea (MGC1). We recruited four British, one New Zealand, one Vietnamese and four Czech families.MethodsAll probands and three female carriers underwent ocular examination and Sanger sequencing of the CHRDL1 gene. Two of the probands also had magnetic resonance imaging (MRI) of the brain.ResultsWe identified nine pathogenic or likely pathogenic and one variant of uncertain significance in CHRDL1, of which eight are novel. Three probands had ocular findings that have not previously been associated with MGC1, namely pigmentary glaucoma, unilateral posterior corneal vesicles, unilateral keratoconus and unilateral Fuchs heterochromic iridocyclitis. The corneal diameters of the three heterozygous carriers were normal, but two had abnormally thin corneas, and one of these was also diagnosed with unilateral keratoconus. Brain MRI identified arachnoid cysts in both probands, one also had a neuroepithelial cyst, while the second had a midsagittal neurodevelopmental abnormality (cavum septum pellucidum et vergae).ConclusionThe study expands the spectrum of pathogenic variants and the ocular and brain abnormalities that have been identified in individuals with MGC1. Reduced corneal thickness may represent a mild phenotypic feature in some heterozygous female carriers of CHRDL1 pathogenic variants.
C/EBPβ induces B‐cell acute lymphoblastic leukemia and cooperates with BLNK mutations
Authors: Kurata Morito , Onishi Iichiro , Takahara Tomoko , Yamazaki Yukari , Ishibashi Sachiko , Goitsuka Ryo , Kitamura Daisuke , Takita Junko , Hayashi Yasuhide , Largaesapda David A , Kitagawa Masanobu , Nakamura Takuro 
Published: October 2021

AbstractBLNK (BASH/SLP‐65) encodes an adaptor protein that plays an important role in B‐cell receptor (BCR) signaling. Loss‐of‐function mutations in this gene are observed in human pre‐B acute lymphoblastic leukemia (ALL), and a subset of Blnk knock‐out (KO) mice develop pre‐B‐ALL. To understand the molecular mechanism of the Blnk mutation‐associated pre‐B‐ALL development, retroviral tagging was applied to KO mice using the Moloney murine leukemia virus (MoMLV). The Blnk mutation that significantly accelerated the onset of MoMLV‐induced leukemia and increased the incidence of pre‐B‐ALL Cebpb was identified as a frequent site of retroviral integration, suggesting that its upregulation cooperates with Blnk mutations. Transgenic expression of the liver‐enriched activator protein (LAP) isoform of Cebpb reduced the number of mature B‐lymphocytes in the bone marrow and inhibited differentiation at the pre‐BI stage. Furthermore, LAP expression significantly accelerated leukemogenesis in Blnk KO mice and alone acted as a B‐cell oncogene. Furthermore, an inverse relationship between BLNK and C/EBPβ expression was also noted in human pre‐B‐ALL cases, and the high level of CEBPB expression was associated with short survival periods in patients with BLNK‐downregulated pre‐B‐ALL. These results indicate the association between the C/EBPβ transcriptional network and BCR signaling in pre‐B‐ALL development and leukemogenesis. This study gives insight into ALL progression and suggests that the BCR/C/EBPβ pathway can be a therapeutic target.
Synthesis, QSAR modeling, and molecular docking of novel fused 7‐deazaxanthine derivatives as adenosine A2A receptor antagonists
Authors: Muzychka Liubov V. , Verves Evgenii V. , Yaremchuk Iryna O. , Zinchenko Anna M. , Shishkina Svitlana V. , Semenyuta Ivan V. , Hodyna Diana M. , Metelytsia Larysa O. , Kovalishyn Vasyl , Smolii Oleg B. 
Published: October 2021

AbstractPredictive QSAR models for the search of new adenosine A2A receptor antagonists were developed by using OCHEM platform. The predictive ability of the regression models has coefficient of determination q2 = 0.65−0.71 with cross‐validation and independent test set. The inhibition activities of novel fused 7‐deazaxanthine compounds were predicted by the developed QSAR models. A preparative method for the synthesis of pyrimido[5′,4′:4,5]pyrrolo[1,2‐a][1,4]diazepine derivatives was developed, and 11 new adenosine A2A receptor antagonists were obtained. Preliminary investigations into the toxicology of fused 7‐deazaxanthine compounds toward commonly used model organism to assess toxicity invertebrate cladoceran D. magna were also described.