bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuroendocrine control of appetite and metabolism
Authors: Yoo Eun-Seon , Yu Jieun , Sohn Jong-Woo 
Published: April 2021

AbstractBody homeostasis is predominantly controlled by hormones secreted by endocrine organs. The central nervous system contains several important endocrine structures, including the hypothalamic-pituitary axis. Conventionally, neurohormones released by the hypothalamus and the pituitary gland (hypophysis) have received much attention owing to the unique functions of the end hormones released by their target peripheral organs (e.g., glucocorticoids released by the adrenal glands). Recent advances in mouse genetics have revealed several important metabolic functions of hypothalamic neurohormone-expressing cells, many of which are not readily explained by the action of the corresponding classical downstream hormones. Notably, the newly identified functions are better explained by the action of conventional neurotransmitters (e.g., glutamate and GABA) that constitute a neuronal circuit. In this review, we discuss the regulation of appetite and metabolism by hypothalamic neurohormone-expressing cells, with a focus on the distinct contributions of neurohormones and neurotransmitters released by these neurons.
Cell-type-specific synaptic imbalance and disrupted homeostatic plasticity in cortical circuits of ASD-associated Chd8 haploinsufficient mice
Authors: Ellingford Robert A. , Panasiuk Martyna J. , de Meritens Emilie Rabesahala , Shaunak Raghav , Naybour Liam , Browne Lorcan , Basson M. Albert , Andreae Laura C. 
Published: April 2021

AbstractHeterozygous mutation of chromodomain helicase DNA binding protein 8 (CHD8) is strongly associated with autism spectrum disorder (ASD) and results in dysregulated expression of neurodevelopmental and synaptic genes during brain development. To reveal how these changes affect ASD-associated cortical circuits, we studied synaptic transmission in the prefrontal cortex of a haploinsufficient Chd8 mouse model. We report profound alterations to both excitatory and inhibitory synaptic transmission onto deep layer projection neurons, resulting in a reduced excitatory:inhibitory balance, which were found to vary dynamically across neurodevelopment and result from distinct effects of reduced Chd8 expression within individual neuronal subtypes. These changes were associated with disrupted regulation of homeostatic plasticity mechanisms operating via spontaneous neurotransmission. These findings therefore directly implicate CHD8 mutation in the disruption of ASD-relevant circuits in the cortex.
Genetically predicted circulating B vitamins in relation to digestive system cancers
Authors: Yuan Shuai , Carter Paul , Vithayathil Mathew , Kar Siddhartha , Mason Amy M. , Burgess Stephen , Larsson Susanna C. 
Published: April 2021

Abstract
Background
Folate, vitamin B6 and vitamin B12 have been associated with digestive system cancers. We conducted a two-sample Mendelian randomisation study to assess the causality of these associations.

Methods
Two, one and 14 independent single nucleotide polymorphisms associated with serum folate, vitamin B6 and vitamin B12 at the genome-wide significance threshold were selected as genetic instruments. Summary-level data for the associations of the vitamin-associated genetic variants with cancer were obtained from the UK Biobank study including 367,561 individuals and FinnGen consortium comprising up to 176,899 participants.

Results
Genetically predicted folate and vitamin B6 concentrations were not associated with overall cancer, overall digestive system cancer or oesophageal, gastric, colorectal or pancreatic cancer. Genetically predicted vitamin B12 concentrations were positively associated with overall digestive system cancer (ORSD, 1.12; 95% CI 1.04, 1.21, p = 0.003) and colorectal cancer (ORSD 1.16; 95% CI 1.06, 1.26, p = 0.001) in UK Biobank. Results for colorectal cancer were consistent in FinnGen and the combined ORSD was 1.16 (95% CI 1.08, 1.25, p < 0.001). There was no association of genetically predicted vitamin B12 with any other site-specific digestive system cancers or overall cancer.

Conclusions
These results provide evidence to suggest that elevated serum vitamin B12 concentrations are associated with colorectal cancer.
Vertical monolithic integration of wide- and narrow-bandgap semiconductor nanostructures on graphene films
Authors: Tchoe Youngbin , Jo Janghyun , Kim HoSung , Kim Heehun , Baek Hyeonjun , Lee Keundong , Yoo Dongha , Choi Won Jun , Kim Miyoung , Yi Gyu-Chul 
Published: April 2021

AbstractWe report monolithic integration of indium arsenide (InAs) nanorods and zinc oxide (ZnO) nanotubes using a multilayer graphene film as a suspended substrate, and the fabrication of dual-wavelength photodetectors with the hybrid configuration of these materials. For the hybrid nanostructures, ZnO nanotubes and InAs nanorods were grown vertically on the top and bottom surfaces of the graphene films by metal-organic vapor-phase epitaxy and molecular beam epitaxy, respectively. The structural, optical, and electrical characteristics of the hybrid nanostructures were investigated using transmission electron microscopy, spectral photoresponse analysis, and current–voltage measurements. Furthermore, the hybrid nanostructures were used to fabricate dual-wavelength photodetectors sensitive to both ultraviolet and mid-infrared wavelengths.
Fine-scale population structure in five rural populations from the Spanish Eastern Pyrenees using high-coverage whole-genome sequence data
Authors: Maceda Iago , Álvarez Miguel Martín , Athanasiadis Georgios , Tonda Raúl , Camps Jordi , Beltran Sergi , Camps Agustí , Fàbrega Jordi , Felisart Josefina , Grané Joan , Remón José Luis , Serra Jordi , Moral Pedro , Lao Oscar 
Published: April 2021

AbstractThe area of the Spanish Pyrenees is particularly interesting for studying the demographic dynamics of European rural areas given its orography, the main traditional rural condition of its population and the reported higher patterns of consanguinity of the region. Previous genetic studies suggest a gradient of genetic continuity of the area in the West to East axis. However, it has been shown that micro-population substructure can be detected when considering high-quality NGS data and using spatial explicit methods. In this work, we have analyzed the genome of 30 individuals sequenced at 40× from five different valleys in the Spanish Eastern Pyrenees (SEP) separated by less than 140 km along a west to east axis. Using haplotype-based methods and spatial analyses, we have been able to detect micro-population substructure within SEP not seen in previous studies. Linkage disequilibrium and autozygosity analyses suggest that the SEP populations show diverse demographic histories. In agreement with these results, demographic modeling by means of ABC-DL identify heterogeneity in their effective population sizes despite of their close geographic proximity, and suggests that the population substructure within SEP could have appeared around 2500 years ago. Overall, these results suggest that each rural population of the Pyrenees could represent a unique entity.
Improved prime editors enable pathogenic allele correction and cancer modelling in adult mice
Authors: Liu Pengpeng , Liang Shun-Qing , Zheng Chunwei , Mintzer Esther , Zhao Yan G. , Ponnienselvan Karthikeyan , Mir Aamir , Sontheimer Erik J. , Gao Guangping , Flotte Terence R. , Wolfe Scot A. , Xue Wen 
Published: April 2021

AbstractPrime editors (PEs) mediate genome modification without utilizing double-stranded DNA breaks or exogenous donor DNA as a template. PEs facilitate nucleotide substitutions or local insertions or deletions within the genome based on the template sequence encoded within the prime editing guide RNA (pegRNA). However, the efficacy of prime editing in adult mice has not been established. Here we report an NLS-optimized SpCas9-based prime editor that improves genome editing efficiency in both fluorescent reporter cells and at endogenous loci in cultured cell lines. Using this genome modification system, we could also seed tumor formation through somatic cell editing in the adult mouse. Finally, we successfully utilize dual adeno-associated virus (AAVs) for the delivery of a split-intein prime editor and demonstrate that this system enables the correction of a pathogenic mutation in the mouse liver. Our findings further establish the broad potential of this genome editing technology for the directed installation of sequence modifications in vivo, with important implications for disease modeling and correction.
Bark-dwelling methanotrophic bacteria decrease methane emissions from trees
Authors: Jeffrey Luke C. , Maher Damien T. , Chiri Eleonora , Leung Pok Man , Nauer Philipp A. , Arndt Stefan K. , Tait Douglas R. , Greening Chris , Johnston Scott G. 
Published: April 2021

AbstractTree stems are an important and unconstrained source of methane, yet it is uncertain whether internal microbial controls (i.e. methanotrophy) within tree bark may reduce methane emissions. Here we demonstrate that unique microbial communities dominated by methane-oxidising bacteria (MOB) dwell within bark of Melaleuca quinquenervia, a common, invasive and globally distributed lowland species. In laboratory incubations, methane-inoculated M. quinquenervia bark mediated methane consumption (up to 96.3 µmol m−2 bark d−1) and reveal distinct isotopic δ13C-CH4 enrichment characteristic of MOB. Molecular analysis indicates unique microbial communities reside within the bark, with MOB primarily from the genus Methylomonas comprising up to 25 % of the total microbial community. Methanotroph abundance was linearly correlated to methane uptake rates (R2 = 0.76, p = 0.006). Finally, field-based methane oxidation inhibition experiments demonstrate that bark-dwelling MOB reduce methane emissions by 36 ± 5 %. These multiple complementary lines of evidence indicate that bark-dwelling MOB represent a potentially significant methane sink, and an important frontier for further research.
A prevalent and culturable microbiota links ecological balance to clinical stability of the human lung after transplantation
Authors: Das Sudip , Bernasconi Eric , Koutsokera Angela , Wurlod Daniel-Adrien , Tripathi Vishwachi , Bonilla-Rosso Germán , Aubert John-David , Derkenne Marie-France , Mercier Louis , Pattaroni Céline , Rapin Alexis , von Garnier Christophe , Marsland Benjamin J. , Engel Philipp , Nicod Laurent P. 
Published: April 2021

AbstractThere is accumulating evidence that the lower airway microbiota impacts lung health. However, the link between microbial community composition and lung homeostasis remains elusive. We combine amplicon sequencing and bacterial culturing to characterize the viable bacterial community in 234 longitudinal bronchoalveolar lavage samples from 64 lung transplant recipients and establish links to viral loads, host gene expression, lung function, and transplant health. We find that the lung microbiota post-transplant can be categorized into four distinct compositional states, ‘pneumotypes’. The predominant ‘balanced’ pneumotype is characterized by a diverse bacterial community with moderate viral loads, and host gene expression profiles suggesting immune tolerance. The other three pneumotypes are characterized by being either microbiota-depleted, or dominated by potential pathogens, and are linked to increased immune activity, lower respiratory function, and increased risks of infection and rejection. Collectively, our findings establish a link between the lung microbial ecosystem, human lung function, and clinical stability post-transplant.
Indispensable role of Galectin-3 in promoting quiescence of hematopoietic stem cells
Authors: Jia Weizhen , Kong Lingyu , Kidoya Hiroyasu , Naito Hisamichi , Muramatsu Fumitaka , Hayashi Yumiko , Hsieh Han-Yun , Yamakawa Daishi , Hsu Daniel K. , Liu Fu-Tong , Takakura Nobuyuki 
Published: April 2021

AbstractHematopoietic stem cells (HSCs) in adult bone marrow (BM) are usually maintained in a state of quiescence. The cellular mechanism coordinating the balance between HSC quiescence and differentiation is not fully understood. Here, we report that galactose-binding lectin-3 (galectin-3; Gal-3) is upregulated by Tie2 or Mpl activation to maintain quiescence. Conditional overexpression of Gal-3 in mouse HSCs under the transcriptional control of Tie2 or Vav1 promoters (Gal-3 Tg) causes cell cycle retardation via induction of p21. Conversely, the cell cycle of long-term repopulating HSCs (LT-HSCs) in Gal-3-deficient (Gal-3-/-) mice is accelerated, resulting in their exhaustion. Mechanistically, Gal-3 regulates p21 transcription by forming a complex with Sp1, thus blocking cell cycle entry. These results demonstrate that Gal-3 is a negative regulator of cell-cycling in HSCs and plays a crucial role in adult hematopoiesis to prevent HSC exhaustion.
Creating enzymes and self-sufficient cells for biosynthesis of the non-natural cofactor nicotinamide cytosine dinucleotide
Authors: Wang Xueying , Feng Yanbin , Guo Xiaojia , Wang Qian , Ning Siyang , Li Qing , Wang Junting , Wang Lei , Zhao Zongbao K. 
Published: April 2021

AbstractNicotinamide adenine dinucleotide (NAD) and its reduced form are indispensable cofactors in life. Diverse NAD mimics have been developed for applications in chemical and biological sciences. Nicotinamide cytosine dinucleotide (NCD) has emerged as a non-natural cofactor to mediate redox transformations, while cells are fed with chemically synthesized NCD. Here, we create NCD synthetase (NcdS) by reprograming the substrate binding pockets of nicotinic acid mononucleotide (NaMN) adenylyltransferase to favor cytidine triphosphate and nicotinamide mononucleotide over their regular substrates ATP and NaMN, respectively. Overexpression of NcdS alone in the model host Escherichia coli facilitated intracellular production of NCD, and higher NCD levels up to 5.0 mM were achieved upon further pathway regulation. Finally, the non-natural cofactor self-sufficiency was confirmed by mediating an NCD-linked metabolic circuit to convert L-malate into D-lactate. NcdS together with NCD-linked enzymes offer unique tools and opportunities for intriguing studies in chemical biology and synthetic biology.
Discovery of fungal oligosaccharide-oxidising flavo-enzymes with previously unknown substrates, redox-activity profiles and interplay with LPMOs
Authors: Haddad Momeni Majid , Fredslund Folmer , Bissaro Bastien , Raji Olanrewaju , Vuong Thu V. , Meier Sebastian , Nielsen Tine Sofie , Lombard Vincent , Guigliarelli Bruno , Biaso Frédéric , Haon Mireille , Grisel Sacha , Henrissat Bernard , Welner Ditte Hededam , Master Emma R. , Berrin Jean-Guy , Abou Hachem Maher 
Published: April 2021

AbstractOxidative plant cell-wall processing enzymes are of great importance in biology and biotechnology. Yet, our insight into the functional interplay amongst such oxidative enzymes remains limited. Here, a phylogenetic analysis of the auxiliary activity 7 family (AA7), currently harbouring oligosaccharide flavo-oxidases, reveals a striking abundance of AA7-genes in phytopathogenic fungi and Oomycetes. Expression of five fungal enzymes, including three from unexplored clades, expands the AA7-substrate range and unveils a cellooligosaccharide dehydrogenase activity, previously unknown within AA7. Sequence and structural analyses identify unique signatures distinguishing the strict dehydrogenase clade from canonical AA7 oxidases. The discovered dehydrogenase directly is able to transfer electrons to an AA9 lytic polysaccharide monooxygenase (LPMO) and fuel cellulose degradation by LPMOs without exogenous reductants. The expansion of redox-profiles and substrate range highlights the functional diversity within AA7 and sets the stage for harnessing AA7 dehydrogenases to fine-tune LPMO activity in biotechnological conversion of plant feedstocks.
Ocean surface energy balance allows a constraint on the sensitivity of precipitation to global warming
Authors: Wang Wei , Chakraborty T. C. , Xiao Wei , Lee Xuhui 
Published: April 2021

AbstractClimate models generally predict higher precipitation in a future warmer climate. Whether the precipitation intensification occurred in response to historical warming continues to be a subject of debate. Here, using observations of the ocean surface energy balance as a hydrological constraint, we find that historical warming intensified precipitation at a rate of 0.68 ± 0.51% K−1, which is slightly higher than the multi-model mean calculation for the historical climate (0.38 ± 1.18% K−1). The reduction in ocean surface albedo associated with melting of sea ice is a positive contributor to the precipitation temperature sensitivity. On the other hand, the observed increase in ocean heat storage weakens the historical precipitation. In this surface energy balance framework, the incident shortwave radiation at the ocean surface and the ocean heat storage exert a dominant control on the precipitation temperature sensitivity, explaining 91% of the inter-model spread and the spread across climate scenarios in the Intergovernmental Panel on Climate Change Fifth Assessment Report.
Varying demands for cognitive control reveals shared neural processes supporting semantic and episodic memory retrieval
Authors: Vatansever Deniz , Smallwood Jonathan , Jefferies Elizabeth 
Published: April 2021

AbstractThe categorisation of long-term memory into semantic and episodic systems has been an influential catalyst for research on human memory organisation. However, the impact of variable cognitive control demands on this classical distinction remains to be elucidated. Across two independent experiments, here we directly compare neural processes for the controlled versus automatic retrieval of semantic and episodic memory. In a multi-session functional magnetic resonance imaging experiment, we first identify a common cluster of cortical activity centred on the left inferior frontal gyrus and anterior insular cortex for the retrieval of both weakly-associated semantic and weakly-encoded episodic memory traces. In an independent large-scale individual difference study, we further reveal a common neural circuitry in which reduced functional interaction between the identified cluster and ventromedial prefrontal cortex, a default mode network hub, is linked to better performance across both memory types. Our results provide evidence for shared neural processes supporting the controlled retrieval of information from functionally distinct long-term memory systems.
IL-33 expression in response to SARS-CoV-2 correlates with seropositivity in COVID-19 convalescent individuals
Authors: Stanczak Michal A. , Sanin David E. , Apostolova Petya , Nerz Gabriele , Lampaki Dimitrios , Hofmann Maike , Steinmann Daniel , Krohn-Grimberghe Marvin , Thimme Robert , Mittler Gerhard , Waller Cornelius F. , Pearce Edward J. , Pearce Erika L. 
Published: April 2021

AbstractOur understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still developing. We perform an observational study to investigate seroprevalence and immune responses in subjects professionally exposed to SARS-CoV-2 and their family members (155 individuals; ages 5–79 years). Seropositivity for SARS-CoV-2 Spike glycoprotein aligns with PCR results that confirm the previous infection. Anti-Spike IgG/IgM titers remain high 60 days post-infection and do not strongly associate with symptoms, except for fever. We analyze PBMCs from a subset of seropositive and seronegative adults. TLR7 agonist-activation reveals an increased population of IL-6+TNF-IL-1β+ monocytes, while SARS-CoV-2 peptide stimulation elicits IL-33, IL-6, IFNa2, and IL-23 expression in seropositive individuals. IL-33 correlates with CD4+ T cell activation in PBMCs from convalescent subjects and is likely due to T cell-mediated effects on IL-33-producing cells. IL-33 is associated with pulmonary infection and chronic diseases like asthma and COPD, but its role in COVID-19 is unknown. Analysis of published scRNAseq data of bronchoalveolar lavage fluid (BALF) from patients with mild to severe COVID-19 reveals a population of IL-33-producing cells that increases with the disease. Together these findings show that IL-33 production is linked to SARS-CoV-2 infection and warrant further investigation of IL-33 in COVID-19 pathogenesis and immunity.
Comparison of oncologic and functional outcomes between radical nephroureterectomy and segmental ureterectomy for upper urinary tract urothelial carcinoma
Authors: Kim Tae Heon , Lee Chung Un , Kang Minyong , Jeon Hwang Gyun , Jeong Byong Chang , Seo Seong Il , Jeon Seong Soo , Lee Hyun Moo , Sung Hyun Hwan 
Published: April 2021

AbstractThis study aims to compare oncologic and functional outcomes after radical nephroureterectomy (RNU) and segmental ureterectomy (SU) in patients with upper urinary tract urothelial carcinoma (UTUC). We retrospectively collected data on patients who underwent either RNU or SU of UTUC. Propensity score matching was performed among 394 cases to yield a final cohort of 40 RNU and 40 SU cases. Kaplan–Meier analysis and the log-rank test were used to compare overall survival (OS), cancer-specific survival (CSS), progression-free survival (PFS), and intravesical recurrence-free survival (IVRFS) between the groups. We also compared the change in postoperative estimated glomerular filtration rate (eGFR). There was no significant difference in terms of CSS, PFS, and IVRFS between the RNU and SU groups, but the RNU group had a better OS than the SU group (p = 0.032). Postoperative eGFR was better preserved in the SU group than in the RNU group (p < 0.001). SU provides comparable CSS, PFS, and IVRFS for patients with UTUC compared to RNU, even in patients with advanced-stage and/or high-grade cancer. Further, SU achieves better preservation of renal function.
IL-4 rs2243250 polymorphism associated with susceptibility to allergic rhinitis: a meta-analysis
Authors: Jiang Feifei , Yan Aihui 
Published: April 2021

Abstract
Objective: The relationship between IL-4 rs2243250 polymorphism and the risk of allergic rhinitis is not clear at present. The present study aims to evaluate the exact association between IL-4 rs2243250 polymorphism and susceptibility to allergic rhinitis by a meta-analysis.
Methods: The studies about IL-4 rs2243250 polymorphism associated with susceptibility to allergic rhinitis were searched using PubMed, Excerpta Medica Database (EMBASE), Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI) and China Wanfang databases. The last search time was on March 1, 2021. Data analysis was performed using Stata 15.0 software.
Results: Nine documents were enrolled, from which 1709 patients with allergic rhinitis were included. Among them, six genotype frequencies in the control group conformed to Hardy–Weinberg Equilibrium (HWE). The meta-analysis of all included studies showed significant heterogeneity of each gene model. After omitting the studies whose genotype frequency in the control group did not meet the requirements of HWE, no significant heterogeneity was found in each gene model. The meta-analysis results of the control group genotypes in line with the HWE showed statistically significant differences in the pooled odds ratio (OR) of allele model (T vs. C), recessive model (TT vs. TC+CC) and homozygous model (TT vs. CC), which were 1.19 (95%CI: 1.04–1.35), 1.28 (95%CI: 1.06–1.55) and 1.56 (95%CI: 1.13–2.17), respectively. No statistically significant difference was observed in dominant and heterozygous genetic models.
Conclusion: IL-4 rs2243250 single nucleotide polymorphism associated with susceptibility to allergic rhinitis, allele T and genotype TT could increase the risk of allergic rhinitis.