bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recent progress in the treatment of women with diminished ovarian reserve
Authors: Yin Jingwen , Chang Hsun-Ming , Li Rong , Leung Peter C.K. 
Published: November 2021

AbstractDiminished ovarian reserve (DOR) refers to a decrease in the number and/or quality of oocytes in the ovary, accompanied by a decline in reproductive potential, which is generally related to advanced age or ovarian disease. In in vitro fertilization (IVF) clinical practice, managing patients with DOR remains one of the most challenging tasks. In recent years, increased research on improving ovarian function has provided us with new insights into treating patients with DOR. Many therapeutic options have been proposed to improve the ovarian function of patients with DOR, yet they are not widely utilized in clinical practice because of limited evidence of safety and effectiveness. In this review, we focus on the mechanisms from animal models and clinical trials that have been applied to the treatment of DOR in recent years, intending to improve IVF outcomes in patients with DOR. Furthermore, new insights and perspectives on the molecular and cellular regulation of follicular development and ovarian reserve are emphasized to provide more clues for research on the treatment of DOR.
A weight-homogenous condition to the real Jacobian conjecture in
Authors: Braun Francisco , Valls Claudia 
Published: November 2021

AbstractIt is known that a polynomial local diffeomorphism $(f,\, g): {\mathbb {R}}^{2} \to {\mathbb {R}}^{2}$ is a global diffeomorphism provided the higher homogeneous terms of $f f_x+g g_x$ and $f f_y+g g_y$ do not have real linear factors in common. Here, we give a weight-homogeneous framework of this result. Our approach uses qualitative theory of differential equations. In our reasoning, we obtain a result on polynomial Hamiltonian vector fields in the plane, generalization of a known fact.
Are knowledge- and belief-reasoning automatic, and is this the right question?
Authors: Surtees Andrew D. R. , Todd Andrew R. 
Published: November 2021

Abstract
Phillips et al. conclude that current evidence supports knowledge-, but not belief-reasoning as being automatic. We suggest four reasons why this is an oversimplified answer to a question that might not have a clear-cut answer: (1) knowledge and beliefs can be incompletely equated to perceptual states, (2) sensitivity to mental states does not necessitate representation, (3) automaticity is not a single categorical feature, and (4) how we represent others' minds is dependent on social context.
Clathrin adapters AP-1 and GGA2 support expression of epidermal growth factor receptor for cell growth
Authors: Uemura Takefumi , Suzuki Takehiro , Dohmae Naoshi , Waguri Satoshi 
Published: November 2021

AbstractThe role of Golgi/endosome-localized clathrin adapters in the maintenance of steady-state cell surface epidermal growth factor receptor (EGFR) is not well known. Here, we show that EGFR associates preferentially with both AP-1 and GGA2 in vitro. AP-1 depletion caused a reduction in the EGFR protein by promoting its lysosomal degradation. Triple immunofluorescence microscopy and proximity ligation assays demonstrated that the interaction of EGFR with AP-1 or GGA2 occurred more frequently in Rab11-positive recycling endosomes than in Rab5-positive early endosomes. Biochemical recycling assay revealed that the depletion of AP-1 or GGA2 significantly suppressed EGFR recycling to the plasma membrane regardless of the EGF stimulation. Depletion of AP-1 or GGA2 also reduced cell contents of other tyrosine kinases, MET and ErbB4, and therefore, suppressed the growth of H1975 cancer cells in culture and xenograft model. Moreover, AP-1 was expressed in endosomes at higher levels in some cancer tissues. Collectively, these results suggest that AP-1 and GGA2 function in recycling endosomes to retrieve endocytosed EGFR, thereby sustaining its cell surface expression and, consequently, cancer cell growth.
Disordered photonics behavior from terahertz to ultraviolet of a three-dimensional graphene network
Authors: Tomarchio Luca , Macis Salvatore , D’Arco Annalisa , Mou Sen , Grilli Antonio , Romani Martina , Guidi Mariangela Cestelli , Hu Kailong , Kukunuri Suresh , Jeong Samuel , Marcelli Augusto , Ito Yoshikazu , Lupi Stefano 
Published: November 2021

AbstractThe diffusion of light by random materials is a general phenomenon that appears in many different systems, spanning from colloidal suspension in liquid crystals to disordered metal sponges and paper composed of random fibers. Random scattering is also a key element behind mimicry of several animals, such as white beetles and chameleons. Here, random scattering is related to micro and nanosized spatial structures affecting a broad electromagnetic region. In this work, we have investigated how random scattering modulates the optical properties, from terahertz to ultraviolet light, of a novel functional material, i.e., a three-dimensional graphene (3D Graphene) network based on interconnected high-quality two-dimensional graphene layers. Here, random scattering generates a high-frequency pass-filter behavior. The optical properties of these graphene structures bridge the nanoworld into the macroscopic world, paving the way for their use in novel optoelectronic devices.
Self-organization of human dorsal-ventral forebrain structures by light induced SHH
Authors: De Santis Riccardo , Etoc Fred , Rosado-Olivieri Edwin A. , Brivanlou Ali H. 
Published: November 2021

AbstractOrganizing centers secrete morphogens that specify the emergence of germ layers and the establishment of the body’s axes during embryogenesis. While traditional experimental embryology tools have been instrumental in dissecting the molecular aspects of organizers in model systems, they are impractical in human in-vitro model systems to dissect the relationships between signaling and fate along embryonic coordinates. To systematically study human embryonic organizer centers, we devised a collection of optogenetic ePiggyBac vectors to express a photoactivatable Cre-loxP recombinase, that allows the systematic induction of organizer structures by shining blue-light on human embryonic stem cells (hESCs). We used a light stimulus to geometrically confine SHH expression in neuralizing hESCs. This led to the self-organization of mediolateral neural patterns. scRNA-seq analysis established that these structures represent the dorsal-ventral forebrain, at the end of the first month of development. Here, we show that morphogen light-stimulation is a scalable tool that induces self-organizing centers.
Resolving sub-angstrom ambient motion through reconstruction from vibrational spectra
Authors: Griffiths Jack , Földes Tamás , de Nijs Bart , Chikkaraddy Rohit , Wright Demelza , Deacon William M. , Berta Dénes , Readman Charlie , Grys David-Benjamin , Rosta Edina , Baumberg Jeremy J. 
Published: November 2021

AbstractMetal/organic-molecule interactions underpin many key chemistries but occur on sub-nm scales where nanoscale visualisation techniques tend to average over heterogeneous distributions. Single molecule imaging techniques at the atomic scale have found it challenging to track chemical behaviour under ambient conditions. Surface-enhanced Raman spectroscopy can optically monitor the vibrations of single molecules but understanding is limited by the complexity of spectra and mismatch between theory and experiment. We demonstrate that spectra from an optically generated metallic adatom near a molecule of interest can be inverted into dynamic sub-Å metal-molecule interactions using a comprehensive model, revealing anomalous diffusion of a single atom. Transient metal-organic coordination bonds chemically perturb molecular functional groups > 10 bonds away. With continuous improvements in computational methods for modelling large and complex molecular systems, this technique will become increasingly applicable to accurately tracking more complex chemistries.
The autophagy protein ATG9A enables lipid mobilization from lipid droplets
Authors: Mailler Elodie , Guardia Carlos M. , Bai Xiaofei , Jarnik Michal , Williamson Chad D. , Li Yan , Maio Nunziata , Golden Andy , Bonifacino Juan S. 
Published: November 2021

AbstractThe multispanning membrane protein ATG9A is a scramblase that flips phospholipids between the two membrane leaflets, thus contributing to the expansion of the phagophore membrane in the early stages of autophagy. Herein, we show that depletion of ATG9A does not only inhibit autophagy but also increases the size and/or number of lipid droplets in human cell lines andC. elegans. Moreover, ATG9A depletion blocks transfer of fatty acids from lipid droplets to mitochondria and, consequently, utilization of fatty acids in mitochondrial respiration. ATG9A localizes to vesicular-tubular clusters (VTCs) that are tightly associated with an ER subdomain enriched in another multispanning membrane scramblase, TMEM41B, and also in close proximity to phagophores, lipid droplets and mitochondria. These findings indicate that ATG9A plays a critical role in lipid mobilization from lipid droplets to autophagosomes and mitochondria, highlighting the importance of ATG9A in both autophagic and non-autophagic processes.
A national cohort study (2000–2018) of long-term air pollution exposure and incident dementia in older adults in the United States
Authors: Shi Liuhua , Steenland Kyle , Li Haomin , Liu Pengfei , Zhang Yuhan , Lyles Robert H. , Requia Weeberb J. , Ilango Sindana D. , Chang Howard H. , Wingo Thomas , Weber Rodney J. , Schwartz Joel 
Published: November 2021

AbstractAir pollution may increase risk of Alzheimer’s disease and related dementias (ADRD) in the U.S., but the extent of this relationship is unclear. Here, we constructed two national U.S. population-based cohorts of those aged ≥65 from the Medicare Chronic Conditions Warehouse (2000–2018), combined with high-resolution air pollution datasets, to investigate the association of long-term exposure to ambient fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone (O3) with dementia and AD incidence, respectively. We identified ~2.0 million incident dementia cases (N = 12,233,371; dementia cohort) and ~0.8 million incident AD cases (N = 12,456,447; AD cohort). Per interquartile range (IQR) increase in the 5-year average PM2.5 (3.2 µg/m3), NO2 (11.6 ppb), and warm-season O3 (5.3 ppb) over the past 5 years prior to diagnosis, the hazard ratios (HRs) were 1.060 (95% confidence interval [CI]: 1.054, 1.066), 1.019 (95% CI: 1.012, 1.026), and 0.990 (95% CI: 0.987, 0.993) for incident dementias, and 1.078 (95% CI: 1.070, 1.086), 1.031 (95% CI: 1.023, 1.039), and 0.982 (95%CI: 0.977, 0.986) for incident AD, respectively, for the three pollutants. For both outcomes, concentration-response relationships for PM2.5 and NO2 were approximately linear. Our study suggests that exposures to PM2.5 and NO2 are associated with incidence of dementia and AD.
BST1 regulates nicotinamide riboside metabolism via its glycohydrolase and base-exchange activities
Authors: Yaku Keisuke , Palikhe Sailesh , Izumi Hironori , Yoshida Tomoyuki , Hikosaka Keisuke , Hayat Faisal , Karim Mariam , Iqbal Tooba , Nitta Yasuhito , Sato Atsushi , Migaud Marie E. , Ishihara Katsuhiko , Mori Hisashi , Nakagawa Takashi 
Published: November 2021

AbstractNicotinamide riboside (NR) is one of the orally bioavailable NAD+ precursors and has been demonstrated to exhibit beneficial effects against aging and aging-associated diseases. However, the metabolic pathway of NR in vivo is not yet fully understood. Here, we demonstrate that orally administered NR increases NAD+ level via two different pathways. In the early phase, NR was directly absorbed and contributed to NAD+ generation through the NR salvage pathway, while in the late phase, NR was hydrolyzed to nicotinamide (NAM) by bone marrow stromal cell antigen 1 (BST1), and was further metabolized by the gut microbiota to nicotinic acid, contributing to generate NAD+ through the Preiss–Handler pathway. Furthermore, we report BST1 has a base-exchange activity against both NR and nicotinic acid riboside (NAR) to generate NAR and NR, respectively, connecting amidated and deamidated pathways. Thus, we conclude that BST1 plays a dual role as glycohydrolase and base-exchange enzyme during oral NR supplementation.
Dysbiosis of human gut microbiome in young-onset colorectal cancer
Authors: Yang Yongzhi , Du Lutao , Shi Debing , Kong Cheng , Liu Jianqiang , Liu Guang , Li Xinxiang , Ma Yanlei 
Published: November 2021

AbstractThe incidence of sporadic young-onset colorectal cancer (yCRC) is increasing. A significant knowledge gap exists in the gut microbiota and its diagnostic value for yCRC patients. Through 16S rRNA gene sequencing, 728 samples are collected to identify microbial markers, and an independent cohort of 310 samples is used to validate the results. Furthermore, species-level and functional analysis are performed by metagenome sequencing using 200 samples. Gut microbial diversity is increased in yCRC. Flavonifractor plautii is an important bacterial species in yCRC, while genus Streptococcus contains the key phylotype in the old-onset colorectal cancer. Functional analysis reveals that yCRC has unique characteristics of bacterial metabolism characterized by the dominance of DNA binding and RNA-dependent DNA biosynthetic process. The random forest classifier model achieves a powerful classification potential. This study highlights the potential of the gut microbiota biomarkers as a promising non-invasive tool for the accurate detection and distinction of individuals with yCRC.
Moving beyond bimetallic-alloy to single-atom dimer atomic-interface for all-pH hydrogen evolution
Authors: Kumar Ashwani , Bui Viet Q. , Lee Jinsun , Wang Lingling , Jadhav Amol R. , Liu Xinghui , Shao Xiaodong , Liu Yang , Yu Jianmin , Hwang Yosep , Bui Huong T. D. , Ajmal Sara , Kim Min Gyu , Kim Seong-Gon , Park Gyeong-Su , Kawazoe Yoshiyuki , Lee Hyoyoung 
Published: November 2021

AbstractSingle-atom-catalysts (SACs) afford a fascinating activity with respect to other nanomaterials for hydrogen evolution reaction (HER), yet the simplicity of single-atom center limits its further modification and utilization. Obtaining bimetallic single-atom-dimer (SAD) structures can reform the electronic structure of SACs with added atomic-level synergistic effect, further improving HER kinetics beyond SACs. However, the synthesis and identification of such SAD structure remains conceptually challenging. Herein, systematic first-principle screening reveals that the synergistic interaction at the NiCo-SAD atomic interface can upshift the d-band center, thereby, facilitate rapid water-dissociation and optimal proton adsorption, accelerating alkaline/acidic HER kinetics. Inspired by theoretical predictions, we develop a facile strategy to obtain NiCo-SAD on N-doped carbon (NiCo-SAD-NC) via in-situ trapping of metal ions followed by pyrolysis with precisely controlled N-moieties. X-ray absorption spectroscopy indicates the emergence of Ni-Co coordination at the atomic-level. The obtained NiCo-SAD-NC exhibits exceptional pH-universal HER-activity, demanding only 54.7 and 61 mV overpotentials at −10 mA cm−2 in acidic and alkaline media, respectively. This work provides a facile synthetic strategy for SAD catalysts and sheds light on the fundamentals of structure-activity relationships for future applications.
Transcriptomic evidence for versatile metabolic activities of mercury cycling microorganisms in brackish microbial mats
Authors: Vigneron Adrien , Cruaud Perrine , Aubé Johanne , Guyoneaud Rémy , Goñi-Urriza Marisol 
Published: November 2021

AbstractMethylmercury, biomagnifying through food chains, is highly toxic for aquatic life. Its production and degradation are largely driven by microbial transformations; however, diversity and metabolic activity of mercury transformers, resulting in methylmercury concentrations in environments, remain poorly understood. Microbial mats are thick biofilms where oxic and anoxic metabolisms cooccur, providing opportunities to investigate the complexity of the microbial mercury transformations over contrasted redox conditions. Here, we conducted a genome-resolved metagenomic and metatranscriptomic analysis to identify putative activity of mercury reducers, methylators and demethylators in microbial mats strongly contaminated by mercury. Our transcriptomic results revealed the major role of rare microorganisms in mercury cycling. Mercury methylators, mainly related to Desulfobacterota, expressed a large panel of metabolic activities in sulfur, iron, nitrogen, and halogen compound transformations, extending known activities of mercury methylators under suboxic to anoxic conditions. Methylmercury detoxification processes were dissociated in the microbial mats with methylmercury cleavage being carried out by sulfide-oxidizing Thiotrichaceae and Rhodobacteraceae populations, whereas mercury reducers included members of the Verrucomicrobia, Bacteroidetes, Gammaproteobacteria, and different populations of Rhodobacteraceae. However most of the mercury reduction was potentially carried out anaerobically by sulfur- and iron-reducing Desulfuromonadaceae, revising our understanding of mercury transformers ecophysiology.
Interplay between copy number alterations and immune profiles in the early breast cancer Scandinavian Breast Group 2004-1 randomized phase II trial: results from a feasibility study
Authors: Zerdes Ioannis , Simonetti Michele , Matikas Alexios , Harbers Luuk , Acs Balazs , Boyaci Ceren , Zhang Ning , Salgkamis Dimitrios , Agartz Susanne , Moreno-Ruiz Pablo , Bai Yalai , Rimm David L. , Hartman Johan , Mezheyeuski Artur , Bergh Jonas , Crosetto Nicola , Foukakis Theodoros 
Published: November 2021

AbstractEmerging data indicate that genomic alterations can shape immune cell composition in early breast cancer. However, there is a need for complementary imaging and sequencing methods for the quantitative assessment of combined somatic copy number alteration (SCNA) and immune profiling in pathological samples. Here, we tested the feasibility of three approaches—CUTseq, for high-throughput low-input SCNA profiling, multiplexed fluorescent immunohistochemistry (mfIHC) and digital-image analysis (DIA) for quantitative immuno-profiling- in archival formalin-fixed paraffin-embedded (FFPE) tissue samples from patients enrolled in the randomized SBG-2004-1 phase II trial. CUTseq was able to reproducibly identify amplification and deletion events with a resolution of 100 kb using only 6 ng of DNA extracted from FFPE tissue and pooling together 77 samples into the same sequencing library. In the same samples, mfIHC revealed that CD4 + T-cells and CD68 + macrophages were the most abundant immune cells and they mostly expressed PD-L1 and PD-1. Combined analysis showed that the SCNA burden was inversely associated with lymphocytic infiltration. Our results set the basis for further applications of CUTseq, mfIHC and DIA to larger cohorts of early breast cancer patients.
Identification of ligand binding sites in intrinsically disordered proteins with a differential binding score
Authors: Chen Qiao-Hong , Krishnan V. V. 
Published: November 2021

AbstractScreening ligands directly binding to an ensemble of intrinsically disordered proteins (IDP) to discover potential hits or leads for new drugs is an emerging but challenging area as IDPs lack well-defined and ordered 3D-protein structures. To explore a new IDP-based rational drug discovery strategy, a differential binding score (DIBS) is defined. The basis of DIBS is to quantitatively determine the binding preference of a ligand to an ensemble of conformations specified by IDP versus such preferences to an ensemble of random coil conformations of the same protein. Ensemble docking procedures performed on repeated sampling of conformations, and the results tested for statistical significance determine the preferential ligand binding sites of the IDP. The results of this approach closely reproduce the experimental data from recent literature on the binding of the ligand epigallocatechin gallate (EGCG) to the intrinsically disordered N-terminal domain of the tumor suppressor p53. Combining established approaches in developing a new method to screen ligands against IDPs could be valuable as a screening tool for IDP-based drug discovery.
Interference of dissolved organic matter and its constituents on the accurate determination of hydrogen peroxide in water
Authors: Peng Jianbiao , Zhang Ya , Li Jianhua , Wu Xinan , Wang Mengjie , Gong Zhimin , Gao Shixiang 
Published: November 2021

AbstractHydrogen peroxide (H2O2) is ubiquitous in natural waters, and plays an important role in both biological and chemical processes. This study investigated the influence of dissolved organic matter (DOM) and its substituents on the accurate measurement of H2O2 by peroxidase-mediated depletion of scopoletin fluorescence method which is one of the most widely used methods for the determination of low concentration H2O2 in water. Six DOM and its 24 substituents interfered the determination of H2O2 at environmentally relevant concentration of 200 nM with different levels except 2,6-dimethoxy-1,4-benzoquinone and benzoic acid, which may be associated with origin and types of DOM, and numbers and position of active functional groups in DOM constituents. Each substance concentration and the corresponding decreasing ratio to the measured H2O2 concentration was fitted well to the linear model (R2 > 0.9), and the obtained interfering ratios (k, (mgC L−1)−1), expressing the degree of DOM or its substituents per unit concentration to the measurement of H2O2, were approximate for DOM, but the order of magnitude of k values of DOM constituents took on a large span from 10–3 to 10–7. When DOM levels exceed 0.1 mgC L−1 or its substituent concentration is at nM level (low to 20 nM), the H2O2 content will be underestimated substantially. A quantitative structure–activity relationship model with remarkable stability and strong predictability for the k of DOM substituents to H2O2 measurement was established, and the k was related to the electron transfer capacity, hydrophobicity and stability of these compounds.
Trends, relationships and case attribution of antibiotic resistance between children and environmental sources in rural India
Authors: Mitchell Joseph , Purohit Manju , Jewell Chris P. , Read Jonathan M. , Marrone Gaetano , Diwan Vishal , Stålsby Lundborg Cecilia 
Published: November 2021

AbstractBacterial antibiotic resistance is an important global health threat and the interfaces of antibiotic resistance between humans, animals and the environment are complex. We aimed to determine the associations and overtime trends of antibiotic resistance between humans, animals and water sources from the same area and time and estimate attribution of the other sources to cases of human antibiotic resistance. A total of 125 children (aged 1–3 years old) had stool samples analysed for antibiotic-resistant bacteria at seven time points over two years, with simultaneous collection of samples of animal stools and water sources in a rural Indian community. Newey–West regression models were used to calculate temporal associations, the source with the most statistically significant relationships was household drinking water. This is supported by use of SourceR attribution modelling, that estimated the mean attribution of cases of antibiotic resistance in the children from animals, household drinking water and wastewater, at each time point and location, to be 12.6% (95% CI 4.4–20.9%), 12.1% (CI 3.4–20.7%) and 10.3% (CI 3.2–17.3%) respectively. This underlines the importance of the ‘one health’ concept and requires further research. Also, most of the significant trends over time were negative, suggesting a possible generalised improvement locally.