bluuebunny/crossref_metadata_2025_split huggingface dataset:
Field Investigations of Chemical Partitioning and Aqueous Chemistry of Freezing Closed‐Basin Lakes in Mongolia as Analogs of Subsurface Brines on Icy Bodies
Authors: Yoda Masahiro , Sekine Yasuhito , Fukushi Keisuke , Kitajima Takuma , Gankhurel Baasansuren , Davaasuren Davaadorj , Gerelmaa Tuvshin , Ganbat Shuukhaaz , Shoji Daigo , Zolotov Mikhail Y. , Takahashi Yoshio 
Published: November 2021

AbstractSeveral icy bodies (e.g., Europa and Ceres) likely possess near‐surface brine reservoirs, which are considered to be sources of salts on their surfaces. Previous studies have proposed processes whereby an overlying ice layer captures salinity from a freezing, subsurface reservoir. However, few field investigations have been conducted to investigate chemical partitioning and aqueous chemistry in freezing brine reservoirs in terrestrial analogs. Here we report results of winter field surveys to ice‐covered, closed‐basin saline lakes in the Valley of the Gobi Lakes, Mongolia. We found that the surface ice exhibited complex features, including both pressure ridges formed by compressive forces and wet cracks formed by tensile forces. The latter provides salinity to the ice layer and surface. In addition to wet cracks, saline lake bottom‐water, along with suspended matter, was continuously captured within the pores of the ice layer during downward freezing. Using a combined mass balance and low‐temperature aqueous chemistry model, we reproduced the ice salinity due to entrapment of Na+, Cl−, and SO42−, suggesting that chemical partitioning of these species in freezing brine reservoirs on icy bodies can be understood based on our current knowledge. In the lake bottom‐water, the metastable phase of carbonates (i.e., amorphous Mg‐carbonate and monohydrocalcite) play key roles in controlling the concentrations of precipitable Mg2+ and Ca2+ and alkalinity, highlighting the importance of metastable phase of carbonate in the aqueous chemistry of subsurface brine reservoirs on icy bodies. Metastable phases might be indicators of freshly erupted materials from brine reservoirs.
High‐Resolution Nudged Isotope Modeling With ECHAM6‐Wiso: Impacts of Updated Model Physics and ERA5 Reanalysis Data
Authors: Cauquoin Alexandre , Werner Martin 
Published: November 2021

AbstractWe present here results of new isotope‐enabled simulations with an enhanced ECHAM6‐wiso model version nudged to the ERA5 reanalyses, at two different spatial resolutions, for the period 1979–2018. The isotopic content of snow on sea ice is considered, yielding surface water vapor with lower isotope ratios over sea ice covered areas, and the kinetic fractionation factors for oceanic evaporation are assumed as independent of wind speed. Also, the supersaturation equation was slightly re‐tuned for a better agreement with the Antarctic isotope observations. In addition to the spatial resolution, the impacts of the improved ECHAM6 model physics and the chosen updated ERA5 reanalyses data set on our simulation results are investigated. For this purpose, detailed comparisons to simulation results obtained from the predecessor ECHAM5‐wiso model nudged to ERA5 reanalyses and from ECHAM6‐wiso nudged to ERA‐Interim are performed. Compared to the ERA‐Interim reanalyses, the nudging to ERA5 does not result in substantial changes of modeled surface isotope values on a global scale but water transport over the tropics clearly changed, with increased precipitation amounts over the Amazonian area and related changes of isotopic contents in water vapor in the high troposphere. An ECHAM6‐wiso simulation at high spatial resolution (0.9° horizontal resolution and 95 vertical levels) generally further improves the modeling of annual mean isotope values. The modeling of temporal isotopic variations at seasonal and (sub‐)daily time scales is also slightly improved for the high spatial resolution configuration. The latter will be very useful for an improved interpretation of various water isotope records.
Comparison of Denitrification Induced by Various Organic Substances—Reaction Rates, Microbiology, and Temperature Effect
Authors: Ortmeyer F. , Begerow D. , Guerreiro M. A. , Wohnlich S. , Banning A. 
Published: November 2021

AbstractWidespread groundwater pollution with nitrate (NO3−) and the finite and decreasing geogenic NO3− degradation capacity in aquifers require a better understanding of potential treatment methods. This project aimed at exploring and comparing the efficiency of four organic substances as electron donors for heterotrophic denitrification. Circulation column experiments using sediment without NO3− degradation capacity and high agricultural NO3− groundwater were conducted. Acetate, glucose, ascorbic acid, and ethanol were added to these columns in three concentration steps to induce biological denitrification, whereby also temperature dependence of denitrification rates (room temperature and typical groundwater temperature of 10°C) was taken into account. Results show denitrification with all four carbon (C) sources with intensities varying considerably between electron donors. Comparison of the two temperature approaches shows substantial differences between applied organic substances and indicates T as an important variable for denitrification. Ethanol is clearly the most effective electron donor for biodenitrification in groundwater investigated in this study, with a stronger and more effective NO3− degradation at 10°C than at room temperature. In contrast, much higher reaction rates are achieved with glucose at room temperature, compared to 10°C. Denitrification with ascorbic acid is very low at both temperatures; its addition produces biomass which repeatedly led to column clogging. In the entire test series, nitrite (NO2−) accumulation occurred more frequently and in higher concentrations at 10°C. Analysis of microorganisms shows a strong modification in microbial community in reaction to the addition of different organic C as well as between the two temperature approaches.
A systematic review and meta-analysis of the association between maternal polycystic ovary syndrome and neuropsychiatric disorders in children
Authors: Dubey Pallavi , Thakur Bhaskar , Rodriguez Sheryl , Cox Jessika , Sanchez Sheralyn , Fonseca Anacani , Reddy Sireesha , Clegg Deborah , Dwivedi Alok Kumar 
Published: November 2021

AbstractThere is emerging evidence demonstrating an association between maternal polycystic ovary syndrome (PCOS) and autism spectrum disorder (ASD) in children, however, the cumulative effect of maternal PCOS on the development of ASD or other neuropsychiatry disorders (NPD) in children and separately for males and females has not been examined. We sought to systematically evaluate the influence of maternal PCOS on a wide range of NPD including ASD, attention deficit hyperactivity disorder (ADHD), chronic tic disorder (CDT), other behavior disorders, anxiety, depression, bipolar disorder, schizophrenia in children as well as in women of reproductive age only. We queried electronic databases including PubMed, EMBASE, and Google Scholar, until March 2021. We used DerSimonian and Laird (D-L) random effects method to compute pooled effect size in terms of odds ratio (OR). Nineteen studies (1667851 mothers, 2260622 children) were included in this study. Mothers with PCOS had an increased odds of children diagnosed with ASD (OR = 1.40,p < 0.001), ADHD (OR = 1.42,p < 0.001), CTD (OR = 1.44,p = 0.001), anxiety (OR = 1.33,p < 0.001), as well as other behavioral symptoms (OR = 1.45,p < 0.001) in the adjusted analysis. The association between maternal PCOS and ASD (OR: 1.43 vs. 1.66), ADHD (OR: 1.39 vs. 1.54), and CTD (OR: 1.42 vs. 1.51) was found to be significantly consistent between males and females, respectively. Our data do not suggest increased fetal testosterone exposure is associated with increased autistic traits in children. However, PCOS was significantly associated with increased odds of a wide range of NPD in women themselves. Maternal PCOS is a risk factor for various NPD with a similar extent in their children regardless of their underlying comorbidities. Managing PCOS is essential for women’s health as well as for their children’s health. More research is needed to determine the mechanisms and links between maternal PCOS and NPD in children.
Brain-wide functional connectivity patterns support general cognitive ability and mediate effects of socioeconomic status in youth
Authors: Sripada Chandra , Angstadt Mike , Taxali Aman , Clark D. Angus , Greathouse Tristan , Rutherford Saige , Dickens Joseph R. , Shedden Kerby , Gard Arianna M. , Hyde Luke W. , Weigard Alexander , Heitzeg Mary 
Published: November 2021

AbstractGeneral cognitive ability (GCA) is an individual difference dimension linked to important academic, occupational, and health-related outcomes and its development is strongly linked to differences in socioeconomic status (SES). Complex abilities of the human brain are realized through interconnections among distributed brain regions, but brain-wide connectivity patterns associated with GCA in youth, and the influence of SES on these connectivity patterns, are poorly understood. The present study examined functional connectomes from 5937 9- and 10-year-olds in the Adolescent Brain Cognitive Development (ABCD) multi-site study. Using multivariate predictive modeling methods, we identified whole-brain functional connectivity patterns linked to GCA. In leave-one-site-out cross-validation, we found these connectivity patterns exhibited strong and statistically reliable generalization at 19 out of 19 held-out sites accounting for 18.0% of the variance in GCA scores (cross-validated partialη2). GCA-related connections were remarkably dispersed across brain networks: across 120 sets of connections linking pairs of large-scale networks, significantly elevated GCA-related connectivity was found in 110 of them, and differences in levels of GCA-related connectivity across brain networks were notably modest. Consistent with prior work, socioeconomic status was a strong predictor of GCA in this sample, and we found that distributed GCA-related brain connectivity patterns significantly statistically mediated this relationship (mean proportion mediated: 15.6%,p < 2 × 10−16). These results demonstrate that socioeconomic status and GCA are related to broad and diffuse differences in functional connectivity architecture during early adolescence, potentially suggesting a mechanism through which socioeconomic status influences cognitive development.
Proteomic analysis of necroptotic extracellular vesicles
Authors: Shlomovitz Inbar , Erlich Ziv , Arad Gali , Edry-Botzer Liat , Zargarian Sefi , Cohen Hadar , Manko Tal , Ofir-Birin Yifat , Cooks Tomer , Regev-Rudzki Neta , Gerlic Motti 
Published: November 2021

AbstractNecroptosis is a regulated and inflammatory form of cell death. We, and others, have previously reported that necroptotic cells release extracellular vesicles (EVs). We have found that necroptotic EVs are loaded with proteins, including the phosphorylated form of the key necroptosis-executing factor, mixed lineage kinase domain-like kinase (MLKL). However, neither the exact protein composition, nor the impact, of necroptotic EVs have been delineated. To characterize their content, EVs from necroptotic and untreated U937 cells were isolated and analyzed by mass spectrometry-based proteomics. A total of 3337 proteins were identified, sharing a high degree of similarity with exosome proteome databases, and clearly distinguishing necroptotic and control EVs. A total of 352 proteins were significantly upregulated in the necroptotic EVs. Among these were MLKL and caspase-8, as validated by immunoblot. Components of the ESCRTIII machinery and inflammatory signaling were also upregulated in the necroptotic EVs, as well as currently unreported components of vesicle formation and transport, and necroptotic signaling pathways. Moreover, we found that necroptotic EVs can be phagocytosed by macrophages to modulate cytokine and chemokine secretion. Finally, we uncovered that necroptotic EVs contain tumor neoantigens, and are enriched with components of antigen processing and presentation. In summary, our study reveals a new layer of regulation during the early stage of necroptosis, mediated by the secretion of specific EVs that influences the microenvironment and may instigate innate and adaptive immune responses. This study sheds light on new potential players in necroptotic signaling and its related EVs, and uncovers the functional tasks accomplished by the cargo of these necroptotic EVs.
IL-17A injury to retinal ganglion cells is mediated by retinal Müller cells in diabetic retinopathy
Authors: Qiu Ao-Wang , Huang Da-Rui , Li Bin , Fang Yuan , Zhang Wei-Wei , Liu Qing-Huai 
Published: November 2021

AbstractDiabetic retinopathy (DR), the most common and serious ocular complication, recently has been perceived as a neurovascular inflammatory disease. However, role of adaptive immune inflammation driven by T lymphocytes in DR is not yet well elucidated. Therefore, this study aimed to clarify the role of interleukin (IL)-17A, a proinflammatory cytokine mainly produced by T lymphocytes, in retinal pathophysiology particularly in retinal neuronal death during DR process. Ins2Akita (Akita) diabetic mice 12 weeks after the onset of diabetes were used as a DR model. IL-17A-deficient diabetic mice were obtained by hybridization of IL-17A-knockout (IL-17A-KO) mouse with Akita mouse. Primarily cultured retinal Müller cells (RMCs) and retinal ganglion cells (RGCs) were treated with IL-17A in high-glucose (HG) condition. A transwell coculture of RGCs and RMCs whose IL-17 receptor A (IL-17RA) gene had been silenced with IL-17RA-shRNA was exposed to IL-17A in HG condition and the cocultured RGCs were assessed on their survival. Diabetic mice manifested increased retinal microvascular lesions, RMC activation and dysfunction, as well as RGC apoptosis. IL-17A-KO diabetic mice showed reduced retinal microvascular impairments, RMC abnormalities, and RGC apoptosis compared with diabetic mice. RMCs expressed IL-17RA. IL-17A exacerbated HG-induced RMC activation and dysfunction in vitro and silencing IL-17RA gene in RMCs abolished the IL-17A deleterious effects. In contrast, RGCs did not express IL-17RA and IL-17A did not further alter HG-induced RGC death. Notably, IL-17A aggravated HG-induced RGC death in the presence of intact RMCs but not in the presence of RMCs in which IL-17RA gene had been knocked down. These findings establish that IL-17A is actively involved in DR pathophysiology and particularly by RMC mediation it promotes RGC death. Collectively, we propose that antagonizing IL-17RA on RMCs may prevent retinal neuronal death and thereby slow down DR progression.
Bacterial chromosomal mobility via lateral transduction exceeds that of classical mobile genetic elements
Authors: Humphrey Suzanne , Fillol-Salom Alfred , Quiles-Puchalt Nuria , Ibarra-Chávez Rodrigo , Haag Andreas F. , Chen John , Penadés José R. 
Published: November 2021

AbstractIt is commonly assumed that the horizontal transfer of most bacterial chromosomal genes is limited, in contrast to the frequent transfer observed for typical mobile genetic elements. However, this view has been recently challenged by the discovery of lateral transduction in Staphylococcus aureus, where temperate phages can drive the transfer of large chromosomal regions at extremely high frequencies. Here, we analyse previously published as well as new datasets to compare horizontal gene transfer rates mediated by different mechanisms in S. aureus and Salmonella enterica. We find that the horizontal transfer of core chromosomal genes via lateral transduction can be more efficient than the transfer of classical mobile genetic elements via conjugation or generalized transduction. These results raise questions about our definition of mobile genetic elements, and the potential roles played by lateral transduction in bacterial evolution.
Nascent chains can form co-translational folding intermediates that promote post-translational folding outcomes in a disease-causing protein
Authors: Plessa Elena , Chu Lien P. , Chan Sammy H. S. , Thomas Oliver L. , Cassaignau Anaïs M. E. , Waudby Christopher A. , Christodoulou John , Cabrita Lisa D. 
Published: November 2021

AbstractDuring biosynthesis, proteins can begin folding co-translationally to acquire their biologically-active structures. Folding, however, is an imperfect process and in many cases misfolding results in disease. Less is understood of how misfolding begins during biosynthesis. The human protein, alpha-1-antitrypsin (AAT) folds under kinetic control via a folding intermediate; its pathological variants readily form self-associated polymers at the site of synthesis, leading to alpha-1-antitrypsin deficiency. We observe that AAT nascent polypeptides stall during their biosynthesis, resulting in full-length nascent chains that remain bound to ribosome, forming a persistent ribosome-nascent chain complex (RNC) prior to release. We analyse the structure of these RNCs, which reveals compacted, partially-folded co-translational folding intermediates possessing molten-globule characteristics. We find that the highly-polymerogenic mutant, Z AAT, forms a distinct co-translational folding intermediate relative to wild-type. Its very modest structural differences suggests that the ribosome uniquely tempers the impact of deleterious mutations during nascent chain emergence. Following nascent chain release however, these co-translational folding intermediates guide post-translational folding outcomes thus suggesting that Z’s misfolding is initiated from co-translational structure. Our findings demonstrate that co-translational folding intermediates drive how some proteins fold under kinetic control, and may thus also serve as tractable therapeutic targets for human disease.
Demethylating therapy increases anti-CD123 CAR T cell cytotoxicity against acute myeloid leukemia
Authors: El Khawanky Nadia , Hughes Amy , Yu Wenbo , Myburgh Renier , Matschulla Tony , Taromi Sanaz , Aumann Konrad , Clarson Jade , Vinnakota Janaki Manoja , Shoumariyeh Khalid , Miething Cornelius , Lopez Angel F. , Brown Michael P. , Duyster Justus , Hein Lutz , Manz Markus G. , Hughes Timothy P. , White Deborah L. , Yong Agnes S. M. , Zeiser Robert 
Published: November 2021

AbstractSuccessful treatment of acute myeloid leukemia (AML) with chimeric antigen receptor (CAR) T cells is hampered by toxicity on normal hematopoietic progenitor cells and low CAR T cell persistence. Here, we develop third-generation anti-CD123 CAR T cells with a humanized CSL362-based ScFv and a CD28-OX40-CD3ζ intracellular signaling domain. This CAR demonstrates anti-AML activity without affecting the healthy hematopoietic system, or causing epithelial tissue damage in a xenograft model. CD123 expression on leukemia cells increases upon 5′-Azacitidine (AZA) treatment. AZA treatment of leukemia-bearing mice causes an increase in CTLA-4negative anti-CD123 CAR T cell numbers following infusion. Functionally, the CTLA-4negative anti-CD123 CAR T cells exhibit superior cytotoxicity against AML cells, accompanied by higher TNFα production and enhanced downstream phosphorylation of key T cell activation molecules. Our findings indicate that AZA increases the immunogenicity of AML cells, enhancing recognition and elimination of malignant cells by highly efficient CTLA-4negative anti-CD123 CAR T cells.
An engram of intentionally forgotten information
Authors: Ten Oever Sanne , Sack Alexander T. , Oehrn Carina R. , Axmacher Nikolai 
Published: November 2021

AbstractSuccessful forgetting of unwanted memories is crucial for goal-directed behavior and mental wellbeing. While memory retention strengthens memory traces, it is unclear what happens to memory traces of events that are actively forgotten. Using intracranial EEG recordings from lateral temporal cortex, we find that memory traces for actively forgotten information are partially preserved and exhibit unique neural signatures. Memory traces of successfully remembered items show stronger encoding-retrieval similarity in gamma frequency patterns. By contrast, encoding-retrieval similarity of item-specific memory traces of actively forgotten items depend on activity at alpha/beta frequencies commonly associated with functional inhibition. Additional analyses revealed selective modification of item-specific patterns of connectivity and top-down information flow from dorsolateral prefrontal cortex to lateral temporal cortex in memory traces of intentionally forgotten items. These results suggest that intentional forgetting relies more on inhibitory top-down connections than intentional remembering, resulting in inhibitory memory traces with unique neural signatures and representational formats.
The history and geographic distribution of a KCNQ1 atrial fibrillation risk allele
Authors: Hateley Shannon , Lopez-Izquierdo Angelica , Jou Chuanchau J. , Cho Scott , Schraiber Joshua G. , Song Shiya , Maguire Colin T. , Torres Natalia , Riedel Michael , Bowles Neil E. , Arrington Cammon B. , Kennedy Brett J. , Etheridge Susan P. , Lai Shuping , Pribble Chase , Meyers Lindsay , Lundahl Derek , Byrnes Jake , Granka Julie M. , Kauffman Christopher A. , Lemmon Gordon , Boyden Steven , Scott Watkins W. , Karren Mary Anne , Knight Stacey , Brent Muhlestein J. , Carlquist John F. , Anderson Jeffrey L. , Chahine Kenneth G. , Shah Khushi U. , Ball Catherine A. , Benjamin Ivor J. , Yandell Mark , Tristani-Firouzi Martin 
Published: November 2021

AbstractThe genetic architecture of atrial fibrillation (AF) encompasses low impact, common genetic variants and high impact, rare variants. Here, we characterize a high impact AF-susceptibility allele, KCNQ1 R231H, and describe its transcontinental geographic distribution and history. Induced pluripotent stem cell-derived cardiomyocytes procured from risk allele carriers exhibit abbreviated action potential duration, consistent with a gain-of-function effect. Using identity-by-descent (IBD) networks, we estimate the broad- and fine-scale population ancestry of risk allele carriers and their relatives. Analysis of ancestral migration routes reveals ancestors who inhabited Denmark in the 1700s, migrated to the Northeastern United States in the early 1800s, and traveled across the Midwest to arrive in Utah in the late 1800s. IBD/coalescent-based allele dating analysis reveals a relatively recent origin of the AF risk allele (~5000 years). Thus, our approach broadens the scope of study for disease susceptibility alleles to the context of human migration and ancestral origins.
Spatiotemporal prediction of COVID-19 cases using inter- and intra-county proxies of human interactions
Authors: Vahedi Behzad , Karimzadeh Morteza , Zoraghein Hamidreza 
Published: November 2021

AbstractMeasurements of human interaction through proxies such as social connectedness or movement patterns have proved useful for predictive modeling of COVID-19, which is a challenging task, especially at high spatial resolutions. In this study, we develop a Spatiotemporal autoregressive model to predict county-level new cases of COVID-19 in the coterminous US using spatiotemporal lags of infection rates, human interactions, human mobility, and socioeconomic composition of counties as predictive features. We capture human interactions through 1) Facebook- and 2) cell phone-derived measures of connectivity and human mobility, and use them in two separate models for predicting county-level new cases of COVID-19. We evaluate the model on 14 forecast dates between 2020/10/25 and 2021/01/24 over one- to four-week prediction horizons. Comparing our predictions with a Baseline model developed by the COVID-19 Forecast Hub indicates an average 6.46% improvement in prediction Mean Absolute Errors (MAE) over the two-week prediction horizon up to 20.22% improvement in the four-week prediction horizon, pointing to the strong predictive power of our model in the longer prediction horizons.