bluuebunny/crossref_metadata_2025_split huggingface dataset:
Child volunteers in a women's paramilitary organization in World War II have accelerated reproductive schedules
Authors: Lynch Robert , Lummaa Virpi , Briga Michael , Chapman Simon N. , Loehr John 
Published: May 2020

AbstractUnderstanding how conditions experienced during development affect reproductive timing is of considerable cross-disciplinary interest. Life-history theory predicts that organisms will accelerate reproduction when future survival is unsure. In humans, this can be triggered by early exposure to mortality. Previous studies, however, have been inconclusive due to several confounds that are also likely to affect reproduction. Here we take advantage of a natural experiment in which a population is temporarily divided by war to analyze how exposure to mortality affects reproduction. Using records of Finnish women in World War II, we find that young girls serving in a paramilitary organization wait less time to reproduce, have shorter inter-birth intervals, and have more children than their non-serving peers or sisters. These results support the hypothesis that exposure to elevated mortality rates during development can result in accelerated reproductive schedules and adds to our understanding of how participation in warfare affects women.
Integration of multiple biological contexts reveals principles of synthetic lethality that affect reproducibility
Authors: Ku Angel A. , Hu Hsien-Ming , Zhao Xin , Shah Khyati N. , Kongara Sameera , Wu Di , McCormick Frank , Balmain Allan , Bandyopadhyay Sourav 
Published: May 2020

AbstractSynthetic lethal screens have the potential to identify new vulnerabilities incurred by specific cancer mutations but have been hindered by lack of agreement between studies. In the case of KRAS, we identify that published synthetic lethal screen hits significantly overlap at the pathway rather than gene level. Analysis of pathways encoded as protein networks could identify synthetic lethal candidates that are more reproducible than those previously reported. Lack of overlap likely stems from biological rather than technical limitations as most synthetic lethal phenotypes are strongly modulated by changes in cellular conditions or genetic context, the latter determined using a pairwise genetic interaction map that identifies numerous interactions that suppress synthetic lethal effects. Accounting for pathway, cellular and genetic context nominates a DNA repair dependency in KRAS-mutant cells, mediated by a network containing BRCA1. We provide evidence for why most reported synthetic lethals are not reproducible which is addressable using a multi-faceted testing framework.
Transient-axial-chirality controlled asymmetric rhodium-carbene C(sp2)-H functionalization for the synthesis of chiral fluorenes
Authors: Dong Kuiyong , Fan Xing , Pei Chao , Zheng Yang , Chang Sailan , Cai Ju , Qiu Lihua , Yu Zhi-Xiang , Xu Xinfang 
Published: May 2020

AbstractIn catalytic asymmetric reactions, the formation of chiral molecules generally relies on a direct chirality transfer (point or axial chirality) from a chiral catalyst to products in the stereo-determining step. Herein, we disclose a transient-axial-chirality transfer strategy to achieve asymmetric reaction. This method relies on transferring point chirality from the catalyst to a dirhodium carbene intermediate with axial chirality, namely a transient-axial-chirality since this species is an intermediate of the reaction. The transient chirality is then transferred to the final product by C(sp2)-H functionalization reaction with exceptionally high enantioselectivity. We also generalize this strategy for the asymmetric cascade reaction involving dual carbene/alkyne metathesis (CAM), a transition-metal-catalyzed method to access chiral 9-aryl fluorene frameworks in high yields with up to 99% ee. Detailed DFT calculations shed light on the mode of the transient-axial-chirality transfer and the detailed mechanism of the CAM reaction.
Peroxisomal targeting of a protein phosphatase type 2C via mitochondrial transit
Authors: Stehlik Thorsten , Kremp Marco , Kahnt Jörg , Bölker Michael , Freitag Johannes 
Published: May 2020

AbstractCorrect intracellular distribution of proteins is critical for the function of eukaryotic cells. Certain proteins are targeted to more than one cellular compartment, e.g. to mitochondria and peroxisomes. The protein phosphatase Ptc5 from Saccharomyces cerevisiae contains an N-terminal mitochondrial presequence followed by a transmembrane domain, and has been detected in the mitochondrial intermembrane space. Here we show mitochondrial transit of Ptc5 to peroxisomes. Translocation of Ptc5 to peroxisomes depended both on the C-terminal peroxisomal targeting signal (PTS1) and N-terminal cleavage by the mitochondrial inner membrane peptidase complex. Indirect targeting of Ptc5 to peroxisomes prevented deleterious effects of its phosphatase activity in the cytosol. Sorting of Ptc5 involves simultaneous interaction with import machineries of both organelles. We identify additional mitochondrial proteins with PTS1, which localize in both organelles and can increase their physical association. Thus, a tug-of-war-like mechanism can influence the interaction and communication of two cellular compartments.
The transcriptional regulator ZNF398 mediates pluripotency and epithelial character downstream of TGF-beta in human PSCs
Authors: Zorzan Irene , Pellegrini Marco , Arboit Mattia , Incarnato Danny , Maldotti Mara , Forcato Mattia , Tagliazucchi Guidantonio Malagoli , Carbognin Elena , Montagner Marco , Oliviero Salvatore , Martello Graziano 
Published: May 2020

AbstractHuman pluripotent stem cells (hPSCs) have the capacity to give rise to all differentiated cells of the adult. TGF-beta is used routinely for expansion of conventional hPSCs as flat epithelial colonies expressing the transcription factors POU5F1/OCT4, NANOG, SOX2. Here we report a global analysis of the transcriptional programme controlled by TGF-beta followed by an unbiased gain-of-function screening in multiple hPSC lines to identify factors mediating TGF-beta activity. We identify a quartet of transcriptional regulators promoting hPSC self-renewal including ZNF398, a human-specific mediator of pluripotency and epithelial character in hPSCs. Mechanistically, ZNF398 binds active promoters and enhancers together with SMAD3 and the histone acetyltransferase EP300, enabling transcription of TGF-beta targets. In the context of somatic cell reprogramming, inhibition of ZNF398 abolishes activation of pluripotency and epithelial genes and colony formation. Our findings have clear implications for the generation of bona fide hPSCs for regenerative medicine.
Legionella effector MavC targets the Ube2N~Ub conjugate for noncanonical ubiquitination
Authors: Puvar Kedar , Iyer Shalini , Fu Jiaqi , Kenny Sebastian , Negrón Terón Kristos I. , Luo Zhao-Qing , Brzovic Peter S. , Klevit Rachel E. , Das Chittaranjan 
Published: May 2020

AbstractThe bacterial effector MavC modulates the host immune response by blocking Ube2N activity employing an E1-independent ubiquitin ligation, catalyzing formation of a γ-glutamyl-ε-Lys (Gln40Ub-Lys92Ube2N) isopeptide crosslink using a transglutaminase mechanism. Here we provide biochemical evidence in support of MavC targeting the activated, thioester-linked Ube2N~ubiquitin conjugate, catalyzing an intramolecular transglutamination reaction, covalently crosslinking the Ube2N and Ub subunits effectively inactivating the E2~Ub conjugate. Ubiquitin exhibits weak binding to MavC alone, but shows an increase in affinity when tethered to Ube2N in a disulfide-linked substrate that mimics the charged E2~Ub conjugate. Crystal structures of MavC in complex with the substrate mimic and crosslinked product provide insights into the reaction mechanism and underlying protein dynamics that favor transamidation over deamidation, while revealing a crucial role for the structurally unique insertion domain in substrate recognition. This work provides a structural basis of ubiquitination by transglutamination and identifies this enzyme’s true physiological substrate.
Locomotor rib kinematics in two species of lizards and a new hypothesis for the evolution of aspiration breathing in amniotes
Authors: Cieri Robert L. , Hatch Samuel T. , Capano John G. , Brainerd Elizabeth L. 
Published: May 2020

AbstractMost lizards walk and run with a sprawling gait in which the limbs are partly advanced by lateral undulation of the axial skeleton. Ribs and vertebrae are integral to this locomotor mode, but 3D motion of the axial skeleton has not been reported for lizard locomotion. Here, we use XROMM to quantify the relative motions of the vertebrae and ribs during slow treadmill locomotion in three savannah monitor lizards (Varanus exanthematicus) and three Argentine black and white tegus (Salvator merianae). To isolate locomotion, we selected strides with no concurrent lung ventilation. Rib rotations can be decomposed into bucket-handle rotation around a dorsoventral axis, pump-handle rotation around a mediolateral axis, and caliper rotations around a craniocaudal axis. During locomotion, every rib measured in both species rotated substantially around its costovertebral joint (8–17 degrees, summed across bucket, pump and caliper rotations). In all individuals from both species, the middle ribs rotated cranially through bucket and pump-handle motion during the propulsive phase of the ipsilateral forelimb. Axial kinematics during swing phase of the ipsilateral forelimb were mirror images of the propulsive phase. Although further work is needed to establish what causes these rib motions, active contraction of the hypaxial musculature may be at least partly responsible. Unilateral locomotor rib movements are remarkably similar to the bilateral pattern used for lung ventilation, suggesting a new hypothesis that rib motion during locomotion may have been an exaptation for the evolution of costal aspiration breathing in stem amniotes.
Aryl Hydrocarbon Receptor-Dependent inductions of omega-3 and omega-6 polyunsaturated fatty acid metabolism act inversely on tumor progression
Authors: Huerta-Yepez Sara , Tirado-Rodriguez Ana , Montecillo-Aguado Mayra R. , Yang Jun , Hammock Bruce D. , Hankinson Oliver 
Published: May 2020

AbstractThe Western diet contains a high ratio of omega-6 (ω6) to omega-3 (ω3) polyunsaturated fatty acids (PUFA). The prototypical aryl hydrocarbon receptor (AHR) ligand, 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), induces CYP1 family enzymes, which can metabolize PUFA to epoxides. Mice fed ω3-rich or ω6-rich diets were treated with TCDD and injected subcutaneously with AHR-competent Hepa1-GFP hepatoma cells or AHR-deficient LLC lung cancer cells. TCDD reduced the growth rates of the resulting tumors in ω3-fed mice and inhibited their metastasis to the liver and/or lung, but had the opposite effects in mice fed ω6 PUFA. These responses were likely attributable to the corresponding PUFA epoxides generated in tumor cells and/or host, since many depended upon co-administration of a soluble epoxide hydrolase (EPHX2) inhibitor in males, and/or were associated with increases in epoxide levels in tumors and sites of metastasis. Equivalent effects occurred in females in the absence of EPHX2 inhibition, probably because this sex expressed reduced levels of EPHX2. The responses elicited by TCDD were associated with effects on tumor vascularity, tumor cell proliferation and/or apoptosis. Thus environmental AHR agonists, and potentially also endogenous, nutritional, and microbiome-derived agonists, may reduce or enhance cancer progression depending on the composition of dietary PUFA, particularly in females.
Eye-tracking reveals agency in assisted autistic communication
Authors: Jaswal Vikram K. , Wayne Allison , Golino Hudson 
Published: May 2020

AbstractAbout one-third of autistic people have limited ability to use speech. Some have learned to communicate by pointing to letters of the alphabet. But this method is controversial because it requires the assistance of another person—someone who holds a letterboard in front of users and so could theoretically cue them to point to particular letters. Indeed, some scientists have dismissed the possibility that any nonspeaking autistic person who communicates with assistance could be conveying their own thoughts. In the study reported here, we used head-mounted eye-tracking to investigate communicative agency in a sample of nine nonspeaking autistic letterboard users. We measured the speed and accuracy with which they looked at and pointed to letters as they responded to novel questions. Participants pointed to about one letter per second, rarely made spelling errors, and visually fixated most letters about half a second before pointing to them. Additionally, their response times reflected planning and production processes characteristic of fluent spelling in non-autistic typists. These findings render a cueing account of participants’ performance unlikely: The speed, accuracy, timing, and visual fixation patterns suggest that participants pointed to letters they selected themselves, not letters they were directed to by the assistant. The blanket dismissal of assisted autistic communication is therefore unwarranted.
Detection of low-frequency resistance-mediating SNPs in next-generation sequencing data of Mycobacterium tuberculosis complex strains with binoSNP
Authors: Dreyer Viola , Utpatel Christian , Kohl Thomas A. , Barilar Ivan , Gröschel Matthias I. , Feuerriegel Silke , Niemann Stefan 
Published: May 2020

AbstractAccurate drug resistance detection is key for guiding effective tuberculosis treatment. While genotypic resistance can be rapidly detected by molecular methods, their application is challenged by mixed mycobacterial populations comprising both susceptible and resistant cells (heteroresistance). For this, next-generation sequencing (NGS) based approaches promise the determination of variants even at low frequencies. However, accurate methods for a valid detection of low-frequency variants in NGS data are currently lacking. To tackle this problem, we developed the variant detection tool binoSNP which allows the determination of low-frequency single nucleotide polymorphisms (SNPs) in NGS datasets from Mycobacterium tuberculosis complex (MTBC) strains. By taking a reference-mapped file as input, binoSNP evaluates each genomic position of interest using a binomial test procedure. binoSNP was validated using in-silico, in-vitro, and serial patient isolates datasets comprising varying genomic coverage depths (100-500×) and SNP allele frequencies (1-30%). Overall, the detection limit for low-frequency SNPs depends on the combination of coverage depth and allele frequency of the resistance-associated mutation. binoSNP allows for valid detection of resistance associated SNPs at a 1% frequency with a coverage ≥400×. In conclusion, binoSNP provides a valid approach to detect low-frequency resistance-mediating SNPs in NGS data from clinical MTBC strains. It can be implemented in automated, end-user friendly analysis tools for NGS data and is a step forward towards individualized TB therapy.
Genetic Polymorphisms, Mediterranean Diet and Microbiota-Associated Urolithin Metabotypes can Predict Obesity in Childhood-Adolescence
Authors: Cortés-Martín Adrián , Colmenarejo Gonzalo , Selma María Victoria , Espín Juan Carlos 
Published: May 2020

AbstractEnvironmental and genetic factors are associated with pandemic obesity since childhood. However, the association of overweight-obesity with these factors, acting as a consortium, has been scarcely studied in children. We aimed here to assess the probabilities of being overweighed-obese in a randomly recruited cohort of Spanish children and adolescents (n = 415, 5−17 years-old) by estimating the odds ratios for different predictor variables, and their relative importance in the prediction. The predictor variables were ethnicity, age, sex, adherence to the Mediterranean diet (KIDMED), physical activity, urolithin metabotypes (UM-A, UM-B and UM-0) as biomarkers of the gut microbiota, and 53 single-nucleotide polymorphisms (SNPs) from 43 genes mainly related to obesity and cardiometabolic diseases. A proportional-odds logistic ordinal regression, validated through bootstrap, was used to model the data. While every variable was not independently associated with overweight-obesity, however, the ordinal logistic model revealed that overweight-obesity prevalence was related to being a young boy with either UM-B or UM-0, low KIDMED score and high contribution of a consortium of 24 SNPs, being rs1801253-ADRB1, rs4343-ACE, rs8061518-FTO, rs1130864-CRP, rs659366-UCP2, rs6131-SELP, rs12535708-LEP, rs1501299-ADIPOQ, rs708272-CETP and rs2241766-ADIPOQ the top-ten contributing SNPs. Additional research should confirm and complete this model by including dietary interventions and the individuals’ gut microbiota composition.
Association between serum uric acid and metabolic syndrome: a cross-sectional study in Bangladeshi adults
Authors: Ali Nurshad , Miah Rakib , Hasan Mahmudul , Barman Zitu , Mou Ananya Dutta , Hafsa Jaasia Momtahena , Trisha Aporajita Das , Hasan Akibul , Islam Farjana 
Published: May 2020

AbstractElevated levels of serum uric acid (SUA) have been suggested to associate with cardiovascular disease, diabetes and metabolic syndrome (MetS). However, information is limited on the association between SUA and MetS in general adults. This study aimed to assess the relationship of SUA with MetS and its components in general adults in Bangladesh. A total of 420 participants were enrolled in this study and biochemical parameters including SUA, fasting blood glucose (FBG) and lipid profile were analyzed using standard methods. The NECP criteria were applied to define MetS. The association of SUA with MetS and its components were evaluated by multinomial logistic regression models. The overall prevalence of MetS was 22% with 21.9% in males and 22.1% in female participants. Male subjects had a high prevalence of elevated components of MetS than in the female subjects (p < 0.05 for all cases). The mean concentration of SUA was significantly higher in subjects of the MetS group compared to the non-MetS group (p < 0.05). The components of MetS were raised with the increasing concentrations of SUA across the quartiles. In regression analysis, SUA was significantly associated with the prevalence of MetS in Bangladeshi adults. In conclusion, elevated SUA was significantly associated with the prevalence of MetS and its components.
Struktur und Efferenzen der Substantia nigra pars compacta beim idiopathischen Parkinson-Syndrom
Authors: Urban Peter , Falkenburger Bjorn , Jost Wolfgang H. , Ransmayr Gerhard , Riederer Peter , Winkler Christian 
Published: May 2020

ZusammenfassungEs besteht Konsens, dass das neuropathologische Merkmal des idiopathischen Parkinson-Syndroms (IPS) der neuronale Zellverlust der Substantia nigra pars compacta (SNc) in Verbindung mit einer Lewy-Pathologie ist. Die transsynaptische Ausbreitung der Lewy-Pathologie wird als wesentlich in der Parkinson-Pathogenese angesehen. Daher ist die Kenntnis präexistenter neuroanatomischer Verbindungen der SNc wesentlich. Wir beschreiben hier neuere tierexperimentelle Befunde zu den afferenten und efferenten Projektionen der SNc und diskutieren die Evidenz für und gegen die sequentielle transsynaptische Ausbreitung der Lewy-Pathologie in der Pathogenese des IPS.
Der kardiogene Schock
Authors: Samol Alexander , Lebiedz Pia 
Published: May 2020

ZUSAMMENFASSUNGBei einem kardiogenen Schock kommt es durch ein akut reduziertes Herzzeitvolumen zu einer peripheren Minderdurchblutung. Die häufigste Ursache für einen kardiogenen Schock ist eine akute myokardiale Ischämie. Die Diagnose des kardiogenen Schocks wird klinisch (Akrenzyanose, Kaltschweißigkeit etc.), laborchemisch (BNP, Laktat) und apparativ (Echokardiografie, erweitertes hämodynamisches Monitoring) gestellt. Therapeutisch ist die schnellstmögliche Beseitigung der zugrunde liegenden Pathologie entscheidend. Dies beinhaltet die myokardiale Revaskularisierung bei Ischämie, aber auch die sofortige Punktion bzw. Drainage bei einer Perikardtamponade oder die Lysetherapie bei der Lungenarterienembolie. Zusätzlich kann die Kreislaufdepression beim kardiogenen Schock durch kreislaufunterstützende Medikamente wie z. B. Katecholamine therapiert werden. In den letzten Jahren kommen zunehmend öfter mechanische intra- oder extrakorporale Unterstützungssysteme zum Einsatz. Trotz Verbesserung der Therapiemöglichkeit bleibt die Letalität des kardiogenen Schocks unverändert hoch bei ca. 40–50 %.
Das akute Lungenversagen (ARDS) und Einsatzspektrum der ECMO-Unterstützung
Authors: Fuehner Thomas 
Published: May 2020

ZUSAMMENFASSUNGÜber viele Jahrzehnte galt die invasive Beatmung als die letzte Eskalationsstufe intensivmedizinischer Maßnahmen für Patienten mit einem akuten Lungenversagen. In den letzten 2 Jahrzehnten kamen als weitere Maßnahmen vermehrt extrakorporale Gasaustauschsysteme „künstliche Lungen“ zum Einsatz (Extracorporeal-life-support, ECLS-Systeme). Die Anzahl der Anwendungen hat in den letzten Jahren bei schwerstkranken Patienten deutlich zugenommen, trotz einer qualitativ geringen wissenschaftlichen Datenlage. Befürworter des Verfahrens betonen, dass es sich um ein Lungenersatzverfahren handelt und um keine Therapie im eigentlichen Sinne. Damit wird auf die sensible Indikationsstellung hingewiesen, die das vermeintliche Regenerationspotenzial des akuten Lungenversagens richtig einschätzen muss. Ein häufiges Problem von klinischen Studien im Bereich der Intensivmedizin ist das heterogene Patientenkollektiv. Die meisten Intensivpatienten sind hochkomplex erkrankt, sodass entweder die Kohorten sehr klein sind oder doch eine Verzerrung diskutiert werden muss. Dieses Problem hatten bisher natürlich auch ECMO-Studien. Die aktuell ablaufende SARS-Coronavirus-2-Pandemie bietet eventuell die Gelegenheit einer homogenen ARDS-Patientengruppe. Extrakorporale Gasaustauschsysteme sollten in spezialisierten Zentren mit ausreichender Erfahrung angewendet werden für eine kritische Indikationsstellung und eine möglichst komplikationsarme technische Durchführung.
An Unusual Granular Ulcer Secondary Oral Tuberculosis of Vestibule Mandibular Mucosa
Authors: Valenzuela-Narváez Rocío , Valenzuela Daniel A. , Valenzuela Daniel R. , Bailón Aguilar , Machco Heriberto , Mena Carla , Córdova María , Mejía Cris , Estrada Ana 
Published: May 2020

AbstractTuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis. In the oral cavity, clinical manifestations are considered atypical lesions. The aim of this study was to report an unusual granular ulcer secondary oral TB that does not heal, chronic, had irregular appearance with deep depression of 2 cm in diameter, and was located in buccal mucosa of the premolar area–the left mandibular arch, of a 42-year-old woman. The patient was subjected to surgical excision of ulcer in its entirety and accordingly a periodontal plastic surgery in the area of the lesion was performed positioning an autograft subepithelial connective tissue. We obtained optimal results in improving oral health, function, and patient’s comfort, in postoperative controls at 15, 30, and 60 days, respectively.