bluuebunny/crossref_metadata_2025_split huggingface dataset:
The human tRNA taurine modification enzyme GTPBP3 is an active GTPase linked to mitochondrial diseases
Authors: Peng Gui-Xin , Zhang Yong , Wang Qin-Qin , Li Qing-Run , Xu Hong , Wang En-Duo , Zhou Xiao-Long 
Published: February 2021

Abstract
GTPBP3 and MTO1 cooperatively catalyze 5-taurinomethyluridine (τm5U) biosynthesis at the 34th wobble position of mitochondrial tRNAs. Mutations in tRNAs, GTPBP3 or MTO1, causing τm5U hypomodification, lead to various diseases. However, efficient in vitro reconstitution and mechanistic study of τm5U modification have been challenging, in part due to the lack of pure and active enzymes. A previous study reported that purified human GTPBP3 (hGTPBP3) is inactive in GTP hydrolysis. Here, we identified the mature form of hGTPBP3 and showed that hGTPBP3 is an active GTPase in vitro that is critical for tRNA modification in vivo. Unexpectedly, the isolated G domain and a mutant with the N-terminal domain truncated catalyzed GTP hydrolysis to only a limited extent, exhibiting high Km values compared with that of the mature enzyme. We further described several important pathogenic mutations of hGTPBP3, associated with alterations in hGTPBP3 localization, structure and/or function in vitro and in vivo. Moreover, we discovered a novel cytoplasm-localized isoform of hGTPBP3, indicating an unknown potential noncanonical function of hGTPBP3. Together, our findings established, for the first time, the GTP hydrolysis mechanism of hGTPBP3 and laid a solid foundation for clarifying the τm5U modification mechanism and etiology of τm5U deficiency-related diseases.
Role of CxxC-finger protein 1 in establishing mouse oocyte epigenetic landscapes
Authors: Sha Qian-Qian , Zhu Ye-Zhang , Xiang Yunlong , Yu Jia-Li , Fan Xiao-Ying , Li Yan-Chu , Wu Yun-Wen , Shen Li , Fan Heng-Yu 
Published: February 2021

Abstract
During oogenesis, oocytes gain competence and subsequently undergo meiotic maturation and prepare for embryonic development; trimethylated histone H3 on lysine-4 (H3K4me3) mediates a wide range of nuclear events during these processes. Oocyte-specific knockout of CxxC-finger protein 1 (CXXC1, also known as CFP1) impairs H3K4me3 accumulation and causes changes in chromatin configurations. This study investigated the changes in genomic H3K4me3 landscapes in oocytes with Cxxc1 knockout and the effects on other epigenetic factors such as the DNA methylation, H3K27me3, H2AK119ub1 and H3K36me3. H3K4me3 is overall decreased after knocking out Cxxc1, including both the promoter region and the gene body. CXXC1 and MLL2, which is another histone H3 methyltransferase, have nonoverlapping roles in mediating H3K4 trimethylation during oogenesis. Cxxc1 deletion caused a decrease in DNA methylation levels and affected H3K27me3 and H2AK119ub1 distributions, particularly at regions with high DNA methylation levels. The changes in epigenetic networks implicated by Cxxc1 deletion were correlated with the transcriptional changes in genes in the corresponding genomic regions. This study elucidates the epigenetic changes underlying the phenotypes and molecular defects in oocytes with deleted Cxxc1 and highlights the role of CXXC1 in orchestrating multiple factors that are involved in establishing the appropriate epigenetic states of maternal genome.
Human gut microbial communities dictate efficacy of anti-PD-1 therapy in a humanized microbiome mouse model of glioma
Authors: Dees Kory J , Koo Hyunmin , Humphreys J Fraser , Hakim Joseph A , Crossman David K , Crowley Michael R , Nabors L Burton , Benveniste Etty N , Morrow Casey D , McFarland Braden C 
Published: February 2021

Abstract

Background
Although immunotherapy works well in glioblastoma (GBM) preclinical mouse models, the therapy has not demonstrated efficacy in humans. To address this anomaly, we developed a novel humanized microbiome (HuM) model to study the response to immunotherapy in a preclinical mouse model of GBM.

Methods
We used 5 healthy human donors for fecal transplantation of gnotobiotic mice. After the transplanted microbiomes stabilized, the mice were bred to generate 5 independent humanized mouse lines (HuM1-HuM5).

Results
Analysis of shotgun metagenomic sequencing data from fecal samples revealed a unique microbiome with significant differences in diversity and microbial composition among HuM1-HuM5 lines. All HuM mouse lines were susceptible to GBM transplantation, and exhibited similar median survival ranging from 19 to 26 days. Interestingly, we found that HuM lines responded differently to the immune checkpoint inhibitor anti-PD-1. Specifically, we demonstrate that HuM1, HuM4, and HuM5 mice are nonresponders to anti-PD-1, while HuM2 and HuM3 mice are responsive to anti-PD-1 and displayed significantly increased survival compared to isotype controls. Bray-Curtis cluster analysis of the 5 HuM gut microbial communities revealed that responders HuM2 and HuM3 were closely related, and detailed taxonomic comparison analysis revealed that Bacteroides cellulosilyticus was commonly found in HuM2 and HuM3 with high abundances.

Conclusions
The results of our study establish the utility of humanized microbiome mice as avatars to delineate features of the host interaction with gut microbial communities needed for effective immunotherapy against GBM.
The Deep-Time Digital Earth program: data-driven discovery in geosciences
Authors: Wang Chengshan , Hazen Robert M , Cheng Qiuming , Stephenson Michael H , Zhou Chenghu , Fox Peter , Shen Shu-zhong , Oberhänsli Roland , Hou Zengqian , Ma Xiaogang , Feng Zhiqiang , Fan Junxuan , Ma Chao , Hu Xiumian , Luo Bin , Wang Juanle , Schiffries Craig M 
Published: February 2021

Abstract
Current barriers hindering data-driven discoveries in deep-time Earth (DE) include: substantial volumes of DE data are not digitized; many DE databases do not adhere to FAIR (findable, accessible, interoperable and reusable) principles; we lack a systematic knowledge graph for DE; existing DE databases are geographically heterogeneous; a significant fraction of DE data is not in open-access formats; tailored tools are needed. These challenges motivate the Deep-Time Digital Earth (DDE) program initiated by the International Union of Geological Sciences and developed in cooperation with national geological surveys, professional associations, academic institutions and scientists around the world. DDE’s mission is to build on previous research to develop a systematic DE knowledge graph, a FAIR data infrastructure that links existing databases and makes dark data visible, and tailored tools for DE data, which are universally accessible. DDE aims to harmonize DE data, share global geoscience knowledge and facilitate data-driven discovery in the understanding of Earth's evolution.
Use of Temporary Rod and Intraoperative Neuroimaging for Correction of Adolescent Idiopathic Scoliosis: 2-Dimensional Operative Video
Authors: McClendon Jamal , Turcotte Evelyn L , Pai Manish G , Maiti Tanmoy , Singh Rohin , Bendok Bernard R 
Published: February 2021

Abstract
Adolescent idiopathic scoliosis (AIS) is an abnormal lateral curvature of the spine that arises during the pubescent growth spurt. AIS mainly affects females in the age group of 10 to 16 yr, with a prevalence of about 1% to 3% in the at-risk population.
1
Treatment options vary depending on disease presentation and severity. Mild curvature mainly requires periodic observation for disease progression, whereas more moderate curvature can necessitate bracing or corrective surgery.
2

Here, we present the use of a temporary rod and neuroimaging for the correction of Lenke type 1 spinal curvature in an AIS patient. An inferior facetectomy is performed, and a Lenke probe is used for entry into the pedicle and vertebral body. The channel is sounded before and after tapping to check for adequate walls prior to insertion of the pedicle screw. The ARTIS pheno is brought into the field, which uses fluoroscopy to create a 3-dimensional (3D) representation of the instrumentation within the spine. A temporary rod is placed in the concavity, and a combination of corrective techniques, including a rod roll, apical translation, and reduction, is performed to bring up the concavity, derotate the spine, and translate the spine. The permanent rod is then placed in the convexity, and compression is performed to bring down the scapular prominence. The temporary rod is then removed, and a final rod is placed to complete the 3D correction.
The patient consented to the procedure, and an informed written consent was obtained from the patient to use her photographs and video recordings for publication.
Providing psychosocial support for work-from-home educators during the COVID-19 pandemic
Authors: Muldong Venusa M , Garcia Abelardo E , Gozum Ivan Efreaim A 
Published: February 2021

Abstract
A recent article discussed the results of mental support for healthcare professionals and mental care during the COVID-19 pandemic. In the report, the researchers suggest that healthcare professionals must be given psychosocial support during and after the pandemic to prevent any long-term consequence. In this correspondence, this paper proposes that psychosocial support must also be given to educators in a work-from-home setup since they are also affected by the stresses that came with the pandemic.
The Role of Grandparents in Israeli Muslim Families with Intellectually Disabled Fathers: Social Workers’ Perspectives
Authors: Gur Ayelet , Gnaeem-Badran Leena , Stein Michael Ashley 
Published: February 2021

AbstractWithin Israeli Muslim society, men with intellectual disabilities are likely to marry nondisabled women through arranged marriages and create families. This article explores the role of grandparents with these families from the perspective of each family’s social worker. A thematic analysis was conducted of 19 semistructured interviews with Muslim social workers serving Muslim families with intellectually disabled fathers. Consistent with cultural norms, paternal grandparents are extremely involved in the lives of these couples and hold responsibilities in many aspects of these couples’ family lives. Social workers reported that the nondisabled wives, however, viewed the engagement as intrusive and controlling. Maternal grandparents’ contributions were crucially supportive, albeit limited by Muslim cultural norms that placed households under paternal family control. Social workers had conflicted feelings regarding paternal grandparent involvement. Social workers working with Muslim fathers with intellectual disabilities should promote supportive paternal grandparent involvement and ensure that such engagement does not undermine the autonomy or well-being of the nondisabled mothers. Practice guidelines are presented.
“Home Is Where Your Root Is”: Place Making, Belonging, and Community Building among Somalis in Chicago
Authors: Magan Ifrah Mahamud , Padgett Deborah K 
Published: February 2021

Abstract
This qualitative study examines the notion of home as it relates to place making, belonging, and community building. Using a phenomenological method of inquiry, data were gathered through in-depth qualitative interviews with 15 Somali Americans and subjected to transcendental phenomenological analyses. Three major themes were found: (1) the meaning of community: being Somali and Muslim; (2) “We help each other. We are connected”; and (3) “Home is where your root is.” The study findings highlight how Somali participants drew on their faith and culture as foundational to community building and drew on acts of mutual giving and receiving to bind them together even as subjective feelings of “home” could be place based or could transcend geography. Although sometimes disrupted by bias and discrimination, Somalis persevered in defining themselves and pursuing a sense of belonging both within their own community and in the city at large. This study offers an expansive and dynamic view of the meaning of place making, community building, and belonging (home) in the lives of displaced refugees. Both research and practice can benefit from special attention given to the “natural” formation of refugee communities and their role in enhancing adjustment to life in a new land.
Individual variations in “Brain age” relate to early life factors more than to longitudinal brain change
Authors: Vidal-Piñeiro D. , Wang Y. , Krogsrud SK. , Amlien IK. , Baaré WFC. , Bartrés-Faz D. , Bertram L. , Brandmaier A.M. , Drevon CA. , Düzel S. , Ebmeier KP. , Henson RN , Junque C. , Kievit RA , Kühn S. , Leonardsen E. , Lindenberger U. , Madsen KS. , Magnussen F. , Mowinckel AM. , Nyberg L. , Roe JM. , Segura B. , Smith SM. , Sørensen Ø. , Suri S. , Westerhausen R. , Zalesky A. , Zsoldos E. ,   the Australian Imaging Biomarkers and Lifestyle flagship study of ageing, Walhovd KB. , Fjell AM. 
Published: February 2021

AbstractBrain ageis a widely used index for quantifying individuals’ brain health as deviation from a normative brain aging trajectory. Higher than expectedbrain ageis thought partially to reflect above-average rate of brain aging. We explicitly tested this assumption in two large datasets and found no association between cross-sectionalbrain ageand steeper brain decline measured longitudinally. Rather,brain agein adulthood was associated with early-life influences indexed by birth weight and polygenic scores. The results call for nuanced interpretations of cross-sectional indices of the aging brain and question their validity as markers of ongoing within-person changes of the aging brain. Longitudinal imaging data should be preferred whenever the goal is to understand individual change trajectories of brain and cognition in aging.
Phellem translational landscape throughout secondary development inArabidopsisroots
Authors: Leal Ana Rita , Barros Pedro Miguel , Parizot Boris , Sapeta Helena , Vangheluwe Nick , Andersen Tonni Grube , Beeckman Tom , Oliveira M. Margarida 
Published: February 2021

SummaryThe phellem is a specialized boundary tissue providing the first line of defense against abiotic and biotic stresses in organs undergoing secondary growth. Phellem cells undergo several differentiation steps, which include cell wall suberization, cell expansion and programmed cell death. Yet, the molecular players acting particularly in phellem cell differentiation remain poorly described, particularly in the widely used model plantArabidopsis thaliana.Using specific marker lines we followed the onset and progression of phellem differentiation inA. thalianaroots, and further targeted the translatome of new developed phellem cells using Translating Ribosome Affinity Purification followed by mRNA sequencing (TRAP-SEQ).We showed that phellem suberization is initiated early after phellogen (cork cambium) division. The specific translational landscape was organized in three main domains related to energy production, synthesis and transport of cell wall components, and response to stimulus. Novel players in phellem differentiation, related to suberin monomer transport and assembly, as well as novel transcription regulators were identified.This strategy provided an unprecedented resolution of the transcriptome of developing phellem cells, giving a detailed and specific view on the molecular mechanisms controlling cell differentiation in periderm tissues of the model plantArabidopsis.Significance statementTo improve the understanding of phellem differentiation into a suberized protective layer, we followed the establishment of periderm inArabidopsisroots and sequenced the phellem-specific translatome. We found that phellem suberization occurs shortly after pericycle cell divisions with the induction of pivotal suberin biosynthesis genes. In parallel, we detected the activation of three central genetic modules acting throughout the phellem differentiation. This study provides a unique and targeted genetic resource for further functional studies of phellem tissues.
Infant brain regional cerebral blood flow dynamics supporting emergence of vital functional networks
Authors: Yu Qinlin , Ouyang Minhui , Detre John A. , Kang Huiying , Hu Di , Hong Bo , Fang Fang , Peng Yun , Huang Hao 
Published: February 2021

ABSTRACTHuman infancy is characterized by most rapid cerebral blood flow (rCBF) increases across lifespan and emergence of a fundamental brain system default-mode network (DMN). However, how infant rCBF change spatiotemporally across the brain and how the rCBF dynamics support emergence of vital functional networks such as DMN remains unknown. Here, by acquiring cutting-edge multi-modal MRI including pseudo-continuous arterial-spin-labeled perfusion MRI and resting-state functional MRI of infants aged 0 to 24 months, we elucidated unprecedented 4D spatiotemporal infant rCBF framework and region-specific physiology-function coupling across infancy. We found faster rCBF increases in the DMN than other regions. We also found strongly coupled increases of rCBF and network strength specifically in the DMN, suggesting faster local blood flow increase to meet extra neuronal metabolic demands in the DMN maturation. These results offer insights into physiological mechanism of brain functional network emergence and have important implications in altered network maturation in brain disorders.
Efficacy of CDK4/6 inhibitors in preclinical models of malignant pleural mesothelioma
Authors: Aliagas Elisabet , Alay Ania , Martínez-Iniesta Maria , Hernández-Madrigal Miguel , Cordero David , Gausachs Mireia , Pros Eva , Saigí Maria , Busacca Sara , Sharkley Annabel J. , Dawson Alan , Palmero Ramón , Padrones Susana , Aso Samantha , Escobar Ignacio , Ramos Ricard , Llatjós Roger , Vidal August , Varela Mar , Sánchez-Céspedes Montse , Fennell Dean , Muñoz-Pinedo Cristina , Villanueva Alberto , Solé Xavi , Nadal Ernest 
Published: February 2021

AbstractThere is no effective therapy for patients with malignant pleural mesothelioma (MPM) who progressed to platinum-based chemotherapy and immunotherapy. Here, we investigate the antitumor activity of CDK4/6 inhibitors usingin vitroandin vivopreclinical models of MPM. Based on publicly available transcriptomic data of MPM, patients withCDK4orCDK6overexpression had shorter overall survival. Treatment with abemaciclib or palbociclib at 100 nM significantly decreased cell proliferation in all cell models. Both CDK4/6 inhibitors significantly induced G1 cell cycle arrest thereby increasing cell senescence and increased the expression of interferon signaling pathway and tumor antigen presentation process in culture models of MPM.In vivopreclinical studies showed that palbociclib significantly reduced tumor growth and prolonged overall survival in a platinum-naïve and platinum resistant MPM mouse model. Treatment of MPM with CDK4/6 inhibitors decreased cell proliferation, mainly by promoting cell cycle arrest at G1 and by induction of cell senescence. Our preclinical studies provide evidence for evaluating CDK4/6 inhibitors in the clinic for the treatment of MPM.
Mechanisms of GPCR hijacking byStaphylococcus aureus
Authors: Grison Claire M. , Leyrat Cédric , Lambey Paul , Jeannot Sylvain , Del Nero Elise , Fontanel Simon , Peysson Fanny , Heuninck Joyce , Sounier Rémy , Durroux Thierry , Granier Sébastien , Bechara Cherine 
Published: February 2021

SUMMARYAtypical chemokine receptor 1 (ACKR1) is a G protein-coupled receptor (GPCR) targeted byStaphylococcus aureus(SA) bi-component pore-forming leukotoxins to promote bacterial growth and immune evasion. Here we have developed an integrative molecular pharmacology and structural biology approach in order to characterize the effect of leukotoxins HlgA and HlgB on ACKR1 structure and function. Interestingly, we found that both components HlgA and HlgB compete with endogenous chemokines through a direct binding to ACKR1 captured by native mass spectrometry (MS). Unexpectedly, HDX-MS analysis revealed that toxin binding allosterically modulates the intracellular G protein-binding domain of the receptor, resulting in dissociation of ACKR1–G protein complexes in living cells. Altogether, our study brings important molecular insights into the initial steps of leukotoxins targeting a host GPCR. Our findings may open the way to develop antibiotics inhibiting host receptors binding, a mechanism of action less prone to resistance.
Whole genome 6-methyladenosine sequencing (6-mA-Seq) enables bacterial epigenomics studies
Authors: Spurbeck Rachel R. , Minard-Smith Angela T. , Catlin Lindsay A. , Murdoch Robert W. , Chou Rich M. , Albrecht Kristy Montoya 
Published: February 2021

AbstractMethylation sequencing using bisulfite treatment has revolutionized the field of molecular biology for eukaryotic systems, unveiling levels of intricacy in regulation of gene expression in response to different environmental conditions. While bacteria also utilize methylation to regulate gene expression, bisulfite sequencing does not work as well in bacteria as in eukaryotes, because bacteria methylate adenosine instead of cytosine. Therefore, global bacterial methylation patterns cannot be studied using common Illumina sequencers. In this work, we demonstrate 6mA-seq, a method that can be used to identify patterns in bacteria that methylate adenosines at GATC sites. Furthermore, this method was used onEscherichia colicultured on four different carbon sources to demonstrate different methylation patterns due to carbon utilization. 6mA-seq can increase the speed in which epigenetic research is conducted in bacteria.
Calculating likelihoods and likelihood ratios at SNPs-based mixtures. A reappraisal of the binomial inference, as applied to forensic identity tests
Authors: Pascali Vincenzo L. 
Published: February 2021

AbstractSingle nucleotide polymorphisms (SNPs) are useful forensic markers. When a SNPs-based forensic protocol targets a body fluid stain, it returns elementary evidence regardless of the number of individuals that might have contributed to the stain deposition. Therefore, drawing inference from a mixed stain with SNPs is different than drawing it while using multinomial polymorphisms. We here revisit this subject, with a view to contribute to a fresher insight into it. First, we manage to model conditional semi-continuous likelihoods in terms of matrices of genotype permutations vs number of contributors (NTZsc). Secondly, we redefine some algebraic formulas to approach the semi-continuous calculation. To address allelic dropouts, we introduce a peak height ratio index (‘h’, or: the minor read divided by the major read at any NGS-based typing result) into the semi-continuous formulas, for they to act as an acceptable proxy of the ‘split drop’ (Haned et al, 2012) model of calculation. Secondly, we introduce a new, empirical method to deduct theexpectedquantitative ratio at which the contributors of a mixture have originally mixed and theobservedratio generated by each genotype combination at each locus. Compliance between observed and expected quantity ratios is measured in terms of (1-χ2) values at each state of a locus deconvolution. These probability values are multiplied, along with the h index, to the relevant population probabilities to weigh the overall plausibility of each combination according to the quantitative perspective. We compare calculation performances of our empirical procedure (NITZq) with those of the EUROFORMIX software ver.3.0.3. NITZq generates LR values a few orders of magnitude lower than EUROFORMIX when true contributors are used as POIs, but much lower LR values when false contributors are used as POIs. NITZ calculation routines may be useful, especially in combination with mass genomics typing protocols.