bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural and functional determinants of the archaeal 8-oxoguanine-DNA glycosylase AGOG for DNA damage recognition and processing
Authors: Franck Coste , Stéphane Goffinont , Julien Cros , Virginie Gaudon , Martine Guérin , Norbert Garnier , Fabrice Confalonieri , Didier Flament , Josef Suskiewicz Marcin , Bertrand Castaing 
Published: October 2022

Abstract
8-Oxoguanine (GO) is a major purine oxidation product in DNA. Because of its highly mutagenic properties, GO absolutely must be eliminated from DNA. To do this, aerobic and anaerobic organisms from the three kingdoms of life have evolved repair mechanisms to prevent its deleterious effect on genetic integrity. The major way to remove GO is the base excision repair pathway, usually initiated by a GO-DNA glycosylase. First identified in bacteria (Fpg) and eukaryotes (OGG1), GO-DNA glycosylases were more recently identified in archaea (OGG2 and AGOG). AGOG is the less documented enzyme and its mode of damage recognition and removing remains to be clarified at the molecular and atomic levels. This study presents a complete structural characterisation of apo AGOGs from Pyrococcus abyssi (Pab) and Thermococcus gammatolerans (Tga) and the first structure of Pab-AGOG bound to lesion-containing single- or double-stranded DNA. By combining X-ray structure analysis, site directed mutagenesis and biochemistry experiments, we identified key amino acid residues of AGOGs responsible for the specific recognition of the lesion and the base opposite the lesion and for catalysis. Moreover, a unique binding mode of GO, involving double base flipping, never observed for any other DNA glycosylases, is revealed. In addition to unravelling the properties of AGOGs, our study, through comparative biochemical and structural analysis, offers new insights into the evolutionary plasticity of DNA glycosylases across all three kingdoms of life.
The protein common assembly database (ProtCAD)—a comprehensive structural resource of protein complexes
Authors: Xu Qifang , Dunbrack Roland L 
Published: October 2022

Abstract
Proteins often act through oligomeric interactions with other proteins. X-ray crystallography and cryo-electron microscopy provide detailed information on the structures of biological assemblies, defined as the most likely biologically relevant structures derived from experimental data. In crystal structures, the most relevant assembly may be ambiguously determined, since multiple assemblies observed in the crystal lattice may be plausible. It is estimated that 10–15% of PDB entries may have incorrect or ambiguous assembly annotations. Accurate assemblies are required for understanding functional data and training of deep learning methods for predicting assembly structures. As with any other kind of biological data, replication via multiple independent experiments provides important validation for the determination of biological assembly structures. Here we present the Protein Common Assembly Database (ProtCAD), which presents clusters of protein assembly structures observed in independent structure determinations of homologous proteins in the Protein Data Bank (PDB). ProtCAD is searchable by PDB entry, UniProt identifiers, or Pfam domain designations and provides downloads of coordinate files, PyMol scripts, and publicly available assembly annotations for each cluster of assemblies. About 60% of PDB entries contain assemblies in clusters of at least 2 independent experiments. All clusters and coordinates are available on ProtCAD web site (http://dunbrack2.fccc.edu/protcad).
PROTAC-DB 2.0: an updated database of PROTACs
Authors: Weng Gaoqi , Cai Xuanyan , Cao Dongsheng , Du Hongyan , Shen Chao , Deng Yafeng , He Qiaojun , Yang Bo , Li Dan , Hou Tingjun 
Published: October 2022

AbstractProteolysis targeting chimeras (PROTACs), which harness the ubiquitin-proteasome system to selectively induce targeted protein degradation, represent an emerging therapeutic technology with the potential to modulate traditional undruggable targets. Over the past few years, this technology has moved from academia to industry and more than 10 PROTACs have been advanced into clinical trials. However, designing potent PROTACs with desirable drug-like properties still remains a great challenge. Here, we report an updated online database, PROTAC-DB 2.0, which is a repository of structural and experimental data about PROTACs. In this 2nd release, we expanded the number of PROTACs to 3270, which corresponds to a 96% expansion over the first version. Meanwhile, the numbers of warheads (small molecules targeting the proteins of interest), linkers, and E3 ligands (small molecules recruiting E3 ligases) have increased to over 360, 1500 and 80, respectively. In addition, given the importance and the limited number of the crystal target-PROTAC-E3 ternary complex structures, we provide the predicted ternary complex structures for PROTACs with good degradation capability using our PROTAC-Model method. To further facilitate the analysis of PROTAC data, a new filtering strategy based on the E3 ligases is also added. PROTAC-DB 2.0 is available online at http://cadd.zju.edu.cn/protacdb/.
Sung Shu Chien: The founder of modern Chinese botany
Authors: Liu Huan , Huang Kaijing , Yuan Xuefan , Cheng Hao 
Published: October 2022

Abstract
Sung Shu Chien (钱崇澍, 1883–1965) (Fig. 1) was a famous botanist and educator in China, one of the founders of Chinese plant taxonomy, plant physiology, geobotany, and floristics. He devoted his whole life to scientific research and education, and was a founder of modern Chinese botany. Sung Shu Chien pioneered several research fields in modern Chinese botany. In 1916, he published the first literature in Latin on the naming and classification of plants. In the following year, he published the earliest thesis on the application of modern scientific methods of plant physiology in China. He wrote the first paper in the area of plant ecology and geobotany in China. He was a pioneer in the systematic study of the families Orchidaceae, Urticaceae, Fabaceae, and Ranunculaceae in China. From 1959 to 1965, he was the chief editor of “Flora of China” and was responsible for the section on Urticaceae (Yu, 1983). Sung Shu Chien initiated the research of plant taxonomy, plant physiology and plant ecology in China, and laid a solid foundation for the extensive research of vegetation, plant zoning and plant specialties in China (Chien et al., 1956). By skillfully combining research and education, he cultivated Chinese scientific and technological talents in botany.
Inhibitor of apoptosis proteins antagonist SM164 ameliorates experimental MPO-ANCA-associated vasculitis via enhancing fatty acid oxidation in neutrophils
Authors: Wang Luo-Yi , Wang Rui-Xue , Wang Chen , Chen Su-Fang , Sun Xiao-Jing , Li Zhi-Ying , Chen Min , Little Mark A , Zhao Ming-Hui 
Published: October 2022

Abstract

Objectives
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of life-threatening autoimmune diseases. Inhibitors of apoptosis proteins (IAPs) are a class of molecules engaged in cell death and inflammation, interventions of which are proven effective in a number of inflammatory diseases. Here we tested whether targeting IAPs could ameliorate AAV and explored the potential mechanism.

Methods
We collected 19 kidney specimens from patients with myeloperoxidase (MPO)-AAV to investigate the expression of IAPs. The IAP pan-inhibitor SM164 was used to treat the experimental autoimmune vasculitis (EAV) rat model of AAV. RNA sequencing of renal cortex and enrichment analysis were developed to interpret gene expression. Functional experiments were performed to investigate the role of SM164 on neutrophils and endothelial cells.

Results
The expression of three IAPs (cIAP1, cIAP2 and XIAP) was upregulated in kidneys of AAV patients compared with normal controls. SM164 dramatically reduced renal injury in EAV rats. Transcriptomic analysis revealed prominent alterations in fatty acid oxidation and respiratory burst following SM164 treatment. Functional studies demonstrated that SM164 inhibited neutrophil activation induced by MPO-ANCA positive IgG or serum from MPO-AAV patients, and such inhibitory effect was abolished by gene silencing or pharmacological inhibition of fatty acid oxidation. SM164 also inhibited the adhesion of neutrophils to endothelial cells with little effect on the endothelial injury induced by serum from MPO-AAV patients.

Conclusion
Inhibition of IAPs with SM164 played a protective role in AAV through enhancing intracellular fatty acid oxidation in neutrophils.
Local networks from different parts of the human cerebral cortex generate and share the same population dynamic
Authors: Willumsen Alex , Midtgaard Jens , Jespersen Bo , Hansen Christoffer K K , Lam Salina N , Hansen Sabine , Kupers Ron , Fabricius Martin E , Litman Minna , Pinborg Lars , Tascón-Vidarte José D , Sabers Anne , Roland Per E 
Published: October 2022

Abstract
A major goal of neuroscience is to reveal mechanisms supporting collaborative actions of neurons in local and larger-scale networks. However, no clear overall principle of operation has emerged despite decades-long experimental efforts. Here, we used an unbiased method to extract and identify the dynamics of local postsynaptic network states contained in the cortical field potential. Field potentials were recorded by depth electrodes targeting a wide selection of cortical regions during spontaneous activities, and sensory, motor, and cognitive experimental tasks. Despite different architectures and different activities, all local cortical networks generated the same type of dynamic confined to one region only of state space. Surprisingly, within this region, state trajectories expanded and contracted continuously during all brain activities and generated a single expansion followed by a contraction in a single trial. This behavior deviates from known attractors and attractor networks. The state-space contractions of particular subsets of brain regions cross-correlated during perceptive, motor, and cognitive tasks. Our results imply that the cortex does not need to change its dynamic to shift between different activities, making task-switching inherent in the dynamic of collective cortical operations. Our results provide a mathematically described general explanation of local and larger scale cortical dynamic.
Comparison of Long-Term Microscopic and Endoscopic Audiologic Results After Total Ossicular Replacement Prosthesis Surgery
Authors: Baazil Adrianus H.A. , Ebbens Fenna A. , van Spronsen Erik , De Wolf Maarten J.F. , Dikkers Frederik G. 
Published: October 2022

Objective
To compare short-term and long-term outcomes after transcanal endoscope-assisted with microscope-assisted ossiculoplasty using the Fisch titanium total prosthesis (FTTP).

Study Design
Retrospective chart review.

Setting
Tertiary referral center.

Patients
Pediatric (<18 yr of age) and adult patients undergoing ossiculoplasty with the FTTP between January 2016 and December 2019.

Intervention
Transcanal endoscope-assisted (n = 30) or microscope-assisted (n = 76) ossiculoplasty with the FTTP. In the microscopic group, 48 were performed through the ear canal and 28 by retroauricular approach.

Main Outcome Measure
Short-term (3 mo) and long-term (average 20.2 mo) PTA0.5-2kHz air and bone conduction thresholds were evaluated.

Results
In total, 106 patients were included. Nine of 30 (30.0%) of endoscopic and 15 of 76 (19.7%) of microscopic patients were pediatric. Endoscopic preoperative air conduction PTA0.5-2kHz was 52.1 ± 15.8 dB and 52.2 ± 17.9 dB for the microscopic group (p > 0.05). Three months postoperative endoscopic air conduction PTA0.5-2kHz was 37.6 ± 17.4 dB (14.5 dB improvement) and 44.6 ± 19.9 dB (7.6 dB improvement) in the microscopic group (p > 0.05). Three months postoperative endoscopic PTA0.5-2kHz ABG was 26.8 ± 16.6 dB and 28.4 ± 14.7 dB in the microscopic group (p > 0.05). Latest follow-up endoscopic air conduction PTA0.5-2kHz audiogram (mean follow-up, 20.6 ± 10.4 mo) was 36.1 ± 18.2 dB (16.0 dB improvement) and 40.1 ± 16.8 dB (12.1 dB improvement) in the microscopic group (mean follow-up, 19.9 ± 10.3 mo)(p > 0.05). For endoscopic air conduction PTA0.5-2kHz, between the 3 months and latest follow-up audiogram, 25.0% showed improvement, 50.0% remained stable, and 25.0% deteriorated. In the microscopic group, 26.7% improved, 46.6% remained stable, and 26.7% deteriorated (p > 0.05).

Conclusion
Our study shows that hearing results with the Fisch titanium total prosthesis are in line with literature. Endoscope-assisted total ossiculoplasty proves to be a suitable technique with comparable results to the microscopic approach.
Improving child care through healthy eating and physical activity
Authors: Payes Roshelle M. , Chong Caliste , Botsko Christopher 
Published: October 2022

Purpose of review
Most young children in the United States spend a significant portion of their time in early care and education (ECE) settings, commonly known as child care. This review highlights recent literature to support a continued focus and increased investment in embedding nutrition and physical activity standards within ECE settings and systems as a critical strategy for child obesity prevention. Pediatricians can support the promotion of these standards by understanding their local child care settings and sharing information with families about the importance of healthy eating and physical activity in early childhood.

Recent findings
The child care sector is fragile and complex, but quality improvement efforts have been successful in improving healthy eating and physical activity. Diverse child care providers, including family child care homes, can effectively embed nutrition and physical activity standards in their environments to promote healthy eating and active play, limit screen time, and support breastfeeding families. A small but growing body of evidence also demonstrates how these standards can be embedded in broader state systems to stimulate change across a state.

Summary
The literature demonstrates progress supporting diverse child care settings to embed high-impact standards into their environments. There is a small but growing body of evidence around systems-change efforts as well. Greater attention is needed on embedding physical activity standards in facilities, especially family child care homes, and state systems.
Early Surgical Intervention of Congenital Syngnathia
Authors: Kang Dong Ohk , Ahn Jaemyung , Paeng Jun-Young 
Published: October 2022

Congenital syngnathia is a rarely reported malformation when there is a fusion between the maxilla and the mandible. It is necessary to modify it in childhood because congenital syngnathia causes incongruity in pronunciation, diet, and esthetics during the growth process. In this case report, 1 case of syngnathia, a rare craniofacial anomaly, is presented with a review of reports. Prompt diagnosis and surgery were performed right after birth for the present case. A partial limitation point was resolved for further growth. Herein, the authors present the case of a female infant (7 d after birth) diagnosed with congenital syngnathia and treated by early surgical intervention.
Talin1 dysfunction is genetically linked to systemic capillary leak syndrome
Authors: Elefant Naama , Nikolopoulou Pinelopi A , Vassiliki Papadaki V , Oz-Levi Danit , Rouni Georgia , Sion-Sarid Racheli , Edwards William JS , Arapatzi Christina , Yanovsky-Dagan Shira , Cowell Alana R , Meiner Vardiella , Vainstein Vladimir , Grammenoudi Sofia , Lancet Doron , Goult Benjamin T , Harel Tamar , Kostourou Vassiliki 
Published: October 2022

ABSTRACTSystemic capillary leak syndrome (SCLS) is a rare life-threatening disorder due to profound vascular leak. The trigger and the cause of the disease is currently unknown and there is no specific treatment. Here, we identified a rare heterozygous splice-site variant in theTLN1gene in a familial SCLS case, suggestive of autosomal dominant inheritance with incomplete penetrance. Talin1 has a key role in cell adhesions by activating and linking integrins to the actin cytoskeleton. This variant causes in-frame skipping of exon 54 and is predicted to affect talin’s c-terminal actin binding site (ABS3). Modelling the SCLS-TLN1variant by mimicking the actin-binding disruption inTLN1heterozygous endothelial cells resulted in disorganized endothelial adherens junctions. Mechanistically, we established that disruption of talin’s ABS3 sequestrates talin’s interacting partner, vinculin, at cell-extracellular matrix adhesions, leading to destabilization of the endothelial barrier. We propose that pathogenic variant inTLN1underlie SCLS, providing insight into the molecular mechanism of the disease which can be explored for future therapeutic interventions.SUMMARYSystemic capillary leak syndrome (SCLS) is a rare potentially lethal disease with unknown etiology and non-specific treatment. Here, we established a heterozygous splice variant of talin1, a key cell adhesion protein, as a genetic link to a familial SCLS case.
CD4+T cell subset imbalances in rheumatoid arthritis
Authors: Mulhearn B , Marshall L , Sutcliffe M , Hannes SK , Fonseka C , Hussell T , Raychaudhuri S , Barton A , Viatte S 
Published: October 2022

AbstractBackgroundDespite the report of an imbalance between CD4+T helper (Th) cell subsets in rheumatoid arthritis (RA), patient stratification for precision medicine has been hindered by the discovery of ever more Th cell subsets, as well as contradictory association results.ObjectivesTo capture previously reported Th imbalance in RA with deep immunophenotyping techniques; to compare hypothesis-free unsupervised automated clustering with hypothesis-driven conventional biaxial gating and explore if Th cell heterogeneity accounts for conflicting association results.MethodsUnstimulated and stimulated peripheral blood mononuclear cells from RA patients and controls were immunophenotyped with a 37-marker panel by mass cytometry (chemokine receptors, intra-cellular cytokines, intra-nuclear transcription factors). First, conventional biaxial gating and standard definitions of Th cell subsets were applied to compare subset frequencies between cases and controls. Second, unsupervised clustering was performed with FlowSOM and analysed using mixed-effects modelling of Associations of Single Cells (MASC).ResultsConventional analytical techniques fail to identify classical Th subset imbalance, while unsupervised automated clustering, by allowing for unusual marker combinations, identified an imbalance between pro- and anti-inflammatory subsets. For example, a pro-inflammatory Th1-like (IL-2+T-bet+) subset and an unconventional but pro-inflammatory IL-17+T-bet+subset were significantly enriched in RA (odds ratio=5.7, p=2.2 × 10−3; odds ratio=9.7, p=1.5×10−3, respectively). In contrast, a FoxP3+IL-2+HLA-DR+Treg subset was reduced in RA (odds ratio=0.1, p=7.7×10−7).ConclusionsInnovative approaches capture known CD4+T cell subset imbalances in RA blood.
Investigating inequalities in HIV testing in sub-Saharan Africa: insights from a spatial analysis of 25 countries
Authors: Ante-Testard Pearl Anne , Carrasco-Escobar Gabriel , Benmarhnia Tarik , Temime Laura , Jean Kévin 
Published: October 2022

AbstractIntroductionWe aim to explore spatial variations in socioeconomic inequalities in self-reported recent HIV testing uptake in sub-Saharan Africa (SSA) at different geographical scales, in order to identify potential geographical hotspots of inequalities. Additionally, to evaluate the potential benefits of HIV testing programs, we assess whether local levels of HIV testing match the local levels of HIV prevalence.MethodsWe analyzed data from 25 countries in SSA with Demographic and Health Surveys between 2011 and 2019. We quantified socioeconomic inequalities in self-reported HIV testing in the last 12 months with both the Slope Index of Inequality (SII) and Relative Index of Inequality (RII) in different geographical scales to capture sex-specific within-country spatial variations. We also conducted sampling cluster-level analyses based on the Local Indicator of Spatial Association to consider the autocorrelation in SII and RII across SSA countries. To assess the spatial efficiency of HIV testing programs, we measured the correlation between recent HIV testing uptake and HIV prevalence through Pearson correlation across geographical scales.ResultsWe observed pro-rich inequalities on both absolute and relative scales in recent HIV testing in the majority of SSA countries in female and male participants at the national level. We also identified inequalities at subnational levels. Within- and between-country heterogeneities in sex-specific inequalities on both inequality scales and their respective spatial distributions varied depending on the scale used. Clustering of high absolute and relative inequalities were mostly observed in Western and Central Africa with a few regions in Eastern and Southern Africa. Despite significant sex-specific correlations between HIV testing and HIV prevalence in all countries when assessed at the national level, we report an absence of such a correlation at fine scale in 39 of 50 sex-country combinations.ConclusionsThese findings highlight the importance of investigating the spatial variability of various HIV indicators and related inequalities. Results may help local, national and international policymakers to prioritize areas and socioeconomic subgroups in need of HIV testing services. Our results also show the need to monitor efficiency of HIV testing programs in relation to HIV risk at subnational levels as a complementary to national estimates.
Genomic epidemiology of the rotavirus G2P[4] strains in coastal Kenya pre- and post-rotavirus vaccine introduction, 2012 – 2018
Authors: Makori Timothy O. , Bargul Joel L. , Lambisia Arnold W. , Mwanga Mike J. , Murunga Nickson , de Laurent Zaydah R. , Lewa Clement S. , Mutunga Martin , Kellam Paul , Cotten Matthew , Nokes D. James , Phan My , Agoti Charles N. 
Published: October 2022

ABSTRACTThe introduction of rotavirus vaccines into the national immunization programme in many countries has led to a decline of childhood diarrhoea disease burden. Coincidentally, the incidence of some rotavirus group A (RVA) genotypes, has increased, which may result from non-vaccine-type replacement. Here we investigate the evolutionary genomics of rotavirus G2P[4] which has shown an increase in countries that introduced the monovalent Rotarix® vaccine. We examined the 63 RVA G2P[4] strains sampled from children (aged below 13 years) admitted to Kilifi County Hospital, Coastal Kenya, pre- (2012 to June 2014) and post- (July 2014-2018) rotavirus vaccine introduction. All the 63 genome sequences showed a typical DS-1 like genome constellation G2-P[4]-I2-R2-C2-M2-A2-N2-T2-E2-H2. G2 sub-lineage IVa-3 strains predominated in the pre-vaccine era co-circulating with low numbers of G2 sub-lineage IVa-1 strains, whereas sub-lineage IVa-3 strains dominated the post-vaccine period. In addition, in the pre-vaccine period, P[4] sub-lineage IVa strains co-circulated with low numbers of P[4] lineage II strains, but P[4] sub-lineage IVa strains predominated in the post-vaccine period. On the global phylogeny, the Kenyan pre- and post-vaccine G2P[4] strains clustered separately, suggesting that different virus populations circulated in the two periods. However, the strains from both periods exhibited conserved amino acid changes in the known antigenic epitopes, suggesting that replacement of the predominant G2P[4] cluster was unlikely a result of immune escape. Our findings demonstrate that the pre- and post-vaccine G2P[4] strains circulating in Kilifi, coastal Kenya, differed genetically, but likely were antigenically similar. This information informs the discussion on the consequences of rotavirus vaccination on rotavirus diversity.