bluuebunny/crossref_metadata_2025 huggingface dataset:
Agricultural Irrigation Exacerbates Humid Heat Stress in the Mid‐Lower Reaches of the Yangtze River
Authors: Zou Liangfeng , Shao Dongguo , Zha Yuanyuan , Diao Yuqing , Chen Shu , Gu Wenquan
Published: October 2024

Massive irrigation across eastern China (EC) could reduce extreme heat by altering energy and water budgets. However, the irrigation effect on increasing humidity has often been missed, especially in humid regions, leaving its effect and mechanism on extreme humid heat (EHH) poorly characterized. We analyzed assemblies of observations and performed regional simulations with more detailed irrigation scheme to explore the irrigation impacts and potential mechanisms on EHH. We find that irrigation in EC, despite having a cooling effect of about 0.2–0.6C, leads to an increase of about 0.4–0.8C in EHH, with a more intense impact on the Middle‐Lower Yangtze Plain (MLYP) by 0.9C. Cooling effect induced by increased latent heat fluxes through irrigation contributes to air deposition, which lowers boundary layer height, raises near‐surface moist enthalpy, and ultimately exacerbates the EHH. Results mechanistically emphasized irrigation impacts on EHH and highlighted the necessity of improving irrigation modeling reality.
Observations of the Near‐Field Yellow River Plume, Multiple Fronts and Their Biogeochemical Effects
Authors: Chen Zhixing , Wang Tao , Xu Dan , Jiang Wensheng , Bian Changwei
Published: October 2024

River plumes transport fresh water into the ocean, and exhibit intense convergent and turbulent processes in the frontal regions, ultimately influencing coastal ecosystems. Satellite images show multiple fronts can be generated in river plumes. Although some efforts have been done to study the generation of multiple fronts inside river plumes by theoretical, numerical modeling and laboratory methods, their generation mechanisms and effects on biogeochemical processes remain to be clarified through in situ observational evidence. In the present study, the near‐field Yellow River plume, multiple fronts and their biogeochemical effects are investigated through moored, shipboard, and remote sensing observations. Numerical model simulations are conducted to help study the tidal movement of the Yellow River plume. The results show that the near‐field Yellow River plume is generally advected back and forth in the east‒west direction under the effects of tidal currents. Following the plume leading front, a turbulent bore is observed to be generated and mix near‐surface water with low turbidity and high concentration of dissolved oxygen into the water column. Behind the turbulent bore, a series of subfronts with distances of O (∼100 m) are formed. The generation mechanisms of these subfronts are found to be associated with internal shear instabilities. Under the effects of cross‐front shear currents and vertical mixing near the subfronts, a three‐layer structure of turbidity and surface low‐turbidity stripes form inside the plume. Multiple fronts also have significant effects on the accumulation of surface materials.
Monthly and Interannual Variations in Upwelling and Chlorophyll off the Vietnam Coast in Summer Based on Deep Learning
Authors: Lian Qiang , Lin Haiyuan , Huang Yawen , Zhang Shuwen , Chen Zhaoyun
Published: October 2024

The deep learning technique is used to automatically identify upwelling regions off the Vietnam coast using Sea Surface Temperature (SST) data from satellite imagery. After delineating these upwelling areas, this study is pioneering in deriving the upwelling probability off the Vietnam coast, pinpointing two significant upwelling hotspots. To deepen the understanding of the individual impacts of wind and sea surface height anomalies on monthly and spatial variations in upwelling probability and chlorophyll distribution, the Empirical Orthogonal Function method was employed to analyze this data set. The upwelling probability demonstrates a close relationship with wind and sea surface height anomalies, while chlorophyll concentration correlates with the strength of the southwesterly wind. The southwesterly wind, Ekman pumping, eddy dipole, and northeastward jet have been identified as key drivers of the formation and spatial variability of upwelling in summer, albeit with varying contributions to different parts of the coastal region. The distribution of upwelling probability correlates with chlorophyll variation off the northern Vietnam coast. High chlorophyll concentration off the southern Vietnam coast is primarily influenced by the southwesterly wind that carries the Mekong River plume eastward. Furthermore, two abnormal scenarios in upwelling and chlorophyll concentration during 2010 and 2018 were analyzed, attributed to the abnormal southwesterly monsoon and coastal circulation influenced by an El Niño event and a weak La Niña event with a positive Indian Ocean Dipole, respectively. This study elucidates the dynamic processes underlying the intricate chlorophyll distribution over the continental shelf, which is influenced by both the river plume and upwelling.
Vertical Carbon Export During a Phytoplankton Bloom in the Chukchi Sea: Physical Setting and Frontal Subduction
Authors: Pickart Robert S. , Spall Michael A. , Bahr Frank , Lago Loreley , Lin Peigen , Pacini Astrid , Mills Matthew , Huang Jie , Arrigo Kevin R. , van Dijken Gert , McRaven Leah T. , Roberts Steven
Published: October 2024

In order to quantify pelagic‐benthic coupling on high‐latitude shelves, it is imperative to identify the different physical mechanisms by which phytoplankton are exported to the sediments. In June–July 2023, a field program documented the evolution of an under‐ice phytoplankton bloom on the northeast Chukchi shelf. Here, we use in situ data from the cruise, a simple numerical model, historical water column data, and ocean reanalysis fields to characterize the physical setting and describe the dynamically driven vertical export of chlorophyll associated with the bloom. A water mass front separating cold, high‐nutrient winter water in the north and warmer summer waters to the south—roughly coincident with the ice edge—supported a baroclinic jet which is part of the Central Channel flow branch that veers eastward toward Barrow Canyon. A plume of high chlorophyll fluorescence extending from the near‐surface bloom in the winter water downwards along the front was measured throughout the cruise. Using a passive tracer to represent phytoplankton in the model, it was demonstrated that the plume is the result of subduction due to baroclinic instability of the frontal jet. This process, in concert with the gravitational sinking, pumps the chlorophyll downwards an order of magnitude faster than gravitational sinking alone. Particle tracking using the ocean reanalysis fields reveals that a substantial portion of the chlorophyll away from the front is advected off of the northeast Chukchi shelf before reaching the bottom. This highlights the importance of the frontal subduction process for delivering carbon to the sea floor.
Global Temperature Dependency of Biogenic HCHO Columns Observed From Space: Interpretation of TROPOMI Results Using GEOS‐Chem Model
Authors: Li Xicheng , Zhu Lei , De Smedt Isabelle , Sun Wenfu , Chen Yuyang , Shu Lei , Wang Dakang , Liu Song , Pu Dongchuan , Li Juan , Zuo Xiaoxing , Fu Weitao , Li Yali , Zhang Peng , Yan Zhuoxian , Fu Tzung‐May , Shen Huizhong , Wang Chen , Ye Jianhuai , Yang Xin
Published: October 2024

Temperature is the principal driver of global atmospheric formaldehyde (HCHO) and its primary oxidation precursor biogenic volatile organic compounds (BVOCs). We revisit such a temperature (T‐) dependency globally, leveraging TROPOMI HCHO column data. We find substantial variations in the T‐dependency of biogenic HCHO across plant functional types (PFTs), with the highest over Broadleaf Evergreen Tropical Trees (doubling every 6.0 K ± 4.1 K) and lowest over Arctic C3 Grass (doubling every 30.8 K ± 9.6 K). The GEOS‐Chem model interprets HCHO columns' T‐dependency at the PFT level (r = 0.87), with a 16% discrepancy on average. The discrepancy can be explained by BVOC emissions T‐dependency for Broadleaf Evergreen Tropical Trees and Warm C4 Grass and can be attributed to the insensitivity of HCHO columns to BVOC emissions for other PFTs. Our findings underscore a potentially magnified variation of BVOC emissions by GEOS‐Chem and MEGAN therein, particularly in regions experiencing greater temperature variations.
Divergent Responses of Organic Carbon to Sedimentary Environment Transformation in a River‐Dominated Marginal Sea
Authors: Zhang Zhuoyue , Lu Ming , Wang Chenglong , Zhang Chuchu , Lin Bingying , Liao Qihang , Qiu Penghua , Zou Xinqing
Published: October 2024

The fate of organic carbon (OC) in most river‐dominated ocean margins (RiOMars) has undergone a noticeable transformation with the increased sediment retention engineering in watersheds. In the East China Sea (ECS), transformation in sediment and the influence of bulk OC have been broadly studied. However, the response of different mechanisms of OC protection under transformation has not been investigated, hindering our understanding of the factors that control OC deposition. In this study, we isolated different OC fractions, analyzed the basic parameters of the sediments, and compared the previous study's data to reveal how OC deposition responded to transformation. Our research indicates that transformation leads to the reduction of OC associated with minerals and sorting of OC occluded by plant debris and OC associated with minerals resulting in increased decomposition and mineralization of OC. The transformation affects the mechanism of OC binding with reactive iron (FeR), increasing FeR‐protected OC content. Still, the co‐precipitation mechanism and the intense redox environment in the mud deposit decrease the FeR‐protected OC stability. Taken together, the impact of transformation is to increase the risk of OC decomposition and to weaken the OC preservation ability in RiOMars as carbon sinks. This study has implications for river‐dominated passive margins subject to increased sediment retention engineering in watersheds worldwide and deserves more attention.
Dynamic Responses of Outer Radiation Belt Electron Phase Space Densities to Geomagnetic Storms: A Statistical Analysis Based on Van Allen Probes Observations
Authors: Wang Xiaoyu , Ni Binbin , Cao Xing , Ma Xin , Lei Yuan , Dou Xiankang
Published: October 2024

Using Van Allen Probes observations from September 2012 to June 2019, we statistically investigate responses of the Earth's outer radiation belt electron phase space densities (PSDs) in the adiabatic invariant coordinates to isolated geomagnetic storms. Electron PSDs for μ = 50–5,000 MeV/G, covering energy range of seed, relativistic and ultra‐relativistic electrons, are calculated to evaluate three types of storm‐time PSD responses (i.e., enhancement, depletion, and no change). In statistics, the seed PSD variations are dominated by enhancement‐type events, the percentages of which increase from >50% for small storms (−50 nT < SYM‐Hmin ≤ −30 nT) to >70% for large storms (SYM‐Hmin ≤ −50 nT). The relativistic and ultra‐relativistic PSDs exhibit the three response types with comparable occurrence rates for small storms but present predominantly enhancement‐type variations (>50%) for large storms. Enhanced storm activity increases the enhancement‐type responses for seed PSDs at all L* and for relativistic and ultra‐relativistic PSDs at L* > 3.5. It also results in the increased depletion‐type response occurrence for relativistic and ultra‐relativistic PSDs at lower L*. Our results further indicate that the depletion‐type responses manifest evident dependence on the level of solar and geomagnetic activity and the μ‐value, implying complex physics accounting for outer zone electron losses. Improved knowledge of the storm‐time dynamics of outer radiation belt electron PSDs is valuable to in‐depth comprehension of various mechanisms responsible for the electron acceleration and loss. It has important implications for future simulations and forecasts of radiation belt electron variability, in particular, during geomagnetically disturbed periods.
Using Commercial Satellite Imagery to Reconstruct 3 m and Daily Spring Snow Water Equivalent
Authors: Pflug Justin M. , Yang Kehan , Cristea Nicoleta , Boudreau Emma T. , Vuyovich Carrie M. , Kumar Sujay V.
Published: October 2024

Snow water equivalent (SWE) distribution at fine spatial scales (≤10 m) is difficult to estimate due to modeling and observational constraints. However, the distribution of SWE throughout the spring snowmelt season is often correlated to the timing of snow disappearance. Here, we show that snow cover maps generated from PlanetScope's constellation of Dove Satellites can resolve the 3 m date of snow disappearance across seven alpine domains in California and Colorado. Across a 5‐year period (2019–2023), the average uncertainty in the date of snow disappearance, or the period of time between the last date of observed snow cover and the first date of observed snow absence, was 3 days. Using a simple shortwave‐based snowmelt model calibrated at nearby snow pillows, the PlanetScope date of snow disappearance could be used to reconstruct spring SWE. Relative to lidar SWE estimates, the SWE reconstruction had a spatial coefficient of correlation of 0.75, and SWE spatial variability that was biased by 9%, on average. SWE reconstruction biases were then improved to within 0.04 m, on average, by calibrating snowmelt rates to track the spring temporal evolution of fractional snow cover observed by PlanetScope, including fractional snow cover over the full modeling domain, and across domain subsections where snowmelt rates may differ. This study demonstrates the utility of fine‐scale and high‐frequency optical observations of snow cover, and the simple and annually repeatable connections between snow cover and spring snow water resources in regions with seasonal snowpack.
GPA33 expression in colorectal cancer can be induced by WNT inhibition and targeted by cellular therapy
Authors: Börding Teresa , Janik Tobias , Bischoff Philip , Morkel Markus , Sers Christine , Horst David
Published: October 2024

GPA33 is a promising surface antigen for targeted therapy in colorectal cancer (CRC). It is expressed almost exclusively in CRC and intestinal epithelia. However, previous clinical studies have not achieved expected response rates. We investigated GPA33 expression and regulation in CRC and developed a GPA33-targeted cellular therapy. We examined GPA33 expression in CRC cohorts using immunohistochemistry and immunofluorescence. We analyzed GPA33 regulation by interference with oncogenic signaling in vitro and in vivo using inhibitors and conditional inducible regulators. Furthermore, we engineered anti-GPA33-CAR T cells and assessed their activity in vitro and in vivo. GPA33 expression showed consistent intratumoral heterogeneity in CRC with antigen loss at the infiltrative tumor edge. This pattern was preserved at metastatic sites. GPA33-positive cells had a differentiated phenotype and low WNT activity. Low GPA33 expression levels were linked to tumor progression in patients with CRC. Downregulation of WNT activity induced GPA33 expression in vitro and in GPA33-negative tumor cell subpopulations in xenografts. GPA33-CAR T cells were activated in response to GPA33 and reduced xenograft growth in mice after intratumoral application. GPA33-targeted therapy may be improved by simultaneous WNT inhibition to enhance GPA33 expression. Furthermore, GPA33 is a promising target for cellular immunotherapy in CRC.
The potential clinical utility of Whole Genome Sequencing for patients with cancer: evaluation of a regional implementation of the 100,000 Genomes Project
Authors: Leung Elaine Y. L. , Robbins Helen L. , Zaman Shafquat , Lal Neeraj , Morton Dion , Dew Lisa , Williams Anthony P. , Wallis Yvonne , Bell Jennie , Raghavan Manoj , Middleton Gary , Beggs Andrew D.
Published: October 2024

Background

The 100,000 Genomes Project established infrastructure for Whole Genome Sequencing (WGS) in the United Kingdom.

Methods

A retrospective study of cancer patients recruited to the 100,000 Genomes Project by the West Midlands Genomics Medicine Centre, evaluating clinical relevance of results.

Results

After excluding samples with no sequencing data (1678/4851; 34.6%), 3166 sample sets (germline and somatic) from 3067 participants were sequenced. Results of 1256 participants (41.0%) were interpreted (excluding participants who died (308/3067; 10.0%) or were clinically excluded (1503/3067; 49.0%)). Of these, 323 (25.7%) had no variants in genes which may alter management (Domain 1 genes). Of the remaining 933 participants, 552 (59.2%) had clinical recommendations made (718 recommendations in total). These included therapeutic recommendations (377/933; 40.4%), such as clinical trial, unlicensed or licensed therapies or high TMB recommendations, and germline variants warranting clinical genetics review (85/933; 9.1%). At the last follow up, 20.2% of all recommendations were followed (145/718). However, only a small proportion of therapeutic recommendations were followed (5.1%, 25/491).

Conclusions

The 100,000 Genomes Project has established infrastructure and regional experience to support personalised cancer care. The majority of those with successful sequencing had actionable variants. Ensuring GTAB recommendations are followed will maximise benefits for patients.
The impact of interfacial quality and nanoscale performance disorder on the stability of alloyed perovskite solar cells
Authors: Frohna Kyle , Chosy Cullen , Al-Ashouri Amran , Scheler Florian , Chiang Yu-Hsien , Dubajic Milos , Parker Julia E. , Walker Jessica M. , Zimmermann Lea , Selby Thomas A. , Lu Yang , Roose Bart , Albrecht Steve , Anaya Miguel , Stranks Samuel D.
Published: October 2024

Microscopy provides a proxy for assessing the operation of perovskite solar cells, yet most works in the literature have focused on bare perovskite thin films, missing charge transport and recombination losses present in full devices. Here we demonstrate a multimodal operando microscopy toolkit to measure and spatially correlate nanoscale charge transport losses, recombination losses and chemical composition. By applying this toolkit to the same scan areas of state-of-the-art, alloyed perovskite cells before and after extended operation, we show that devices with the highest macroscopic performance have the lowest initial performance spatial heterogeneity—a crucial link that is missed in conventional microscopy. We show that engineering stable interfaces is critical to achieving robust devices. Once the interfaces are stabilized, we show that compositional engineering to homogenize charge extraction and to minimize variations in local power conversion efficiency is critical to improve performance and stability. We find that in our device space, perovskites can tolerate spatial disorder in chemistry, but not charge extraction.
Vertical bedrock shifts reveal summer water storage in Greenland ice sheet
Authors: Ran Jiangjun , Ditmar Pavel , van den Broeke Michiel R. , Liu Lin , Klees Roland , Khan Shfaqat Abbas , Moon Twila , Li Jiancheng , Bevis Michael , Zhong Min , Fettweis Xavier , Liu Junguo , Noël Brice , Shum C. K. , Chen Jianli , Jiang Liming , van Dam Tonie
Published: October 2024

The Greenland ice sheet (GrIS) is at present the largest single contributor to global-mass-induced sea-level rise, primarily because of Arctic amplification on an increasingly warmer Earth1–5. However, the processes of englacial water accumulation, storage and ultimate release remain poorly constrained. Here we show that a noticeable amount of the summertime meltwater mass is temporally buffered along the entire GrIS periphery, peaking in July and gradually reducing thereafter. Our results arise from quantifying the spatiotemporal behaviour of the total mass of water leaving the GrIS by analysing bedrock elastic deformation measured by Global Navigation Satellite System (GNSS) stations. The buffered meltwater causes a subsidence of the bedrock close to GNSS stations of at most approximately 5 mm during the melt season. Regionally, the duration of meltwater storage ranges from 4.5 weeks in the southeast to 9 weeks elsewhere. We also show that the meltwater runoff modelled from regional climate models may contain systematic errors, requiring further scaling of up to about 20% for the warmest years. These results reveal a high potential for GNSS data to constrain poorly known hydrological processes in Greenland, forming the basis for improved projections of future GrIS melt behaviour and the associated sea-level rise6.
Leptin-activated hypothalamic BNC2 neurons acutely suppress food intake
Authors: Tan Han L. , Yin Luping , Tan Yuqi , Ivanov Jessica , Plucinska Kaja , Ilanges Anoj , Herb Brian R. , Wang Putianqi , Kosse Christin , Cohen Paul , Lin Dayu , Friedman Jeffrey M.
Published: October 2024

Leptin is an adipose tissue hormone that maintains homeostatic control of adipose tissue mass by regulating the activity of specific neural populations controlling appetite and metabolism1. Leptin regulates food intake by inhibiting orexigenic agouti-related protein (AGRP) neurons and activating anorexigenic pro-opiomelanocortin (POMC) neurons2. However, whereas AGRP neurons regulate food intake on a rapid time scale, acute activation of POMC neurons has only a minimal effect3–5. This has raised the possibility that there is a heretofore unidentified leptin-regulated neural population that rapidly suppresses appetite. Here we report the discovery of a new population of leptin-target neurons expressing basonuclin 2 (Bnc2) in the arcuate nucleus that acutely suppress appetite by directly inhibiting AGRP neurons. Opposite to the effect of AGRP activation, BNC2 neuronal activation elicited a place preference indicative of positive valence in hungry but not fed mice. The activity of BNC2 neurons is modulated by leptin, sensory food cues and nutritional status. Finally, deleting leptin receptors in BNC2 neurons caused marked hyperphagia and obesity, similar to that observed in a leptin receptor knockout in AGRP neurons. These data indicate that BNC2-expressing neurons are a key component of the neural circuit that maintains energy balance, thus filling an important gap in our understanding of the regulation of food intake and leptin action.
Clonal dynamics after allogeneic haematopoietic cell transplantation
Authors: Spencer Chapman Michael , Wilk C. Matthias , Boettcher Steffen , Mitchell Emily , Dawson Kevin , Williams Nicholas , Müller Jan , Kovtonyuk Larisa , Jung Hyunchul , Caiado Francisco , Roberts Kirsty , O’Neill Laura , Kent David G. , Green Anthony R. , Nangalia Jyoti , Manz Markus G. , Campbell Peter J.
Published: October 2024

Allogeneic haematopoietic cell transplantation (HCT) replaces the stem cells responsible for blood production with those from a donor1,2. Here, to quantify dynamics of long-term stem cell engraftment, we sequenced genomes from 2,824 single-cell-derived haematopoietic colonies of ten donor–recipient pairs taken 9–31 years after HLA-matched sibling HCT3. With younger donors (18–47 years at transplant), 5,000–30,000 stem cells had engrafted and were still contributing to haematopoiesis at the time of sampling; estimates were tenfold lower with older donors (50–66 years). Engrafted cells made multilineage contributions to myeloid, B lymphoid and T lymphoid populations, although individual clones often showed biases towards one or other mature cell type. Recipients had lower clonal diversity than matched donors, equivalent to around 10–15 years of additional ageing, arising from up to 25-fold greater expansion of stem cell clones. A transplant-related population bottleneck could not explain these differences; instead, phylogenetic trees evinced two distinct modes of HCT-specific selection. In pruning selection, cell divisions underpinning recipient-enriched clonal expansions had occurred in the donor, preceding transplant—their selective advantage derived from preferential mobilization, collection, survival ex vivo or initial homing. In growth selection, cell divisions underpinning clonal expansion occurred in the recipient’s marrow after engraftment, most pronounced in clones with multiple driver mutations. Uprooting stem cells from their native environment and transplanting them to foreign soil exaggerates selective pressures, distorting and accelerating the loss of clonal diversity compared to the unperturbed haematopoiesis of donors.
Progressive plasticity during colorectal cancer metastasis
Authors: Moorman Andrew , Benitez Elizabeth K. , Cambulli Francesco , Jiang Qingwen , Mahmoud Ahmed , Lumish Melissa , Hartner Saskia , Balkaran Sasha , Bermeo Jonathan , Asawa Simran , Firat Canan , Saxena Asha , Wu Fan , Luthra Anisha , Burdziak Cassandra , Xie Yubin , Sgambati Valeria , Luckett Kathleen , Li Yanyun , Yi Zhifan , Masilionis Ignas , Soares Kevin , Pappou Emmanouil , Yaeger Rona , Kingham T. Peter , Jarnagin William , Paty Philip B. , Weiser Martin R. , Mazutis Linas , D’Angelica Michael , Shia Jinru , Garcia-Aguilar Julio , Nawy Tal , Hollmann Travis J. , Chaligné Ronan , Sanchez-Vega Francisco , Sharma Roshan , Pe’er Dana , Ganesh Karuna
Published: October 2024

As cancers progress, they become increasingly aggressive—metastatic tumours are less responsive to first-line therapies than primary tumours, they acquire resistance to successive therapies and eventually cause death1,2. Mutations are largely conserved between primary and metastatic tumours from the same patients, suggesting that non-genetic phenotypic plasticity has a major role in cancer progression and therapy resistance3–5. However, we lack an understanding of metastatic cell states and the mechanisms by which they transition. Here, in a cohort of biospecimen trios from same-patient normal colon, primary and metastatic colorectal cancer, we show that, although primary tumours largely adopt LGR5+ intestinal stem-like states, metastases display progressive plasticity. Cancer cells lose intestinal cell identities and reprogram into a highly conserved fetal progenitor state before undergoing non-canonical differentiation into divergent squamous and neuroendocrine-like states, a process that is exacerbated in metastasis and by chemotherapy and is associated with poor patient survival. Using matched patient-derived organoids, we demonstrate that metastatic cells exhibit greater cell-autonomous multilineage differentiation potential in response to microenvironment cues compared with their intestinal lineage-restricted primary tumour counterparts. We identify PROX1 as a repressor of non-intestinal lineage in the fetal progenitor state, and show that downregulation of PROX1 licenses non-canonical reprogramming.
Tissue spaces are reservoirs of antigenic diversity for Trypanosoma brucei
Authors: Beaver Alexander K. , Keneskhanova Zhibek , Cosentino Raúl O. , Weiss Brian L. , Awuoche Erick O. , Smallenberger Gretchen M. , Buenconsejo Gracyn Y. , Crilly Nathan P. , Smith Jaclyn E. , Hakim Jill M. C. , Zhang Bailin , Bobb Bryce , Rijo-Ferreira Filipa , Figueiredo Luisa M. , Aksoy Serap , Siegel T. Nicolai , Mugnier Monica R.
Published: October 2024

The protozoan parasite Trypanosoma brucei evades clearance by the host immune system through antigenic variation of its dense variant surface glycoprotein (VSG) coat, periodically ‘switching’ expression of the VSG using a large genomic repertoire of VSG-encoding genes1–6. Recent studies of antigenic variation in vivo have focused near exclusively on parasites in the bloodstream6–8, but research has shown that many, if not most, parasites reside in the interstitial spaces of tissues9–13. We sought to explore the dynamics of antigenic variation in extravascular parasite populations using VSG-seq7, a high-throughput sequencing approach for profiling VSGs expressed in populations of T. brucei. Here we show that tissues, not the blood, are the primary reservoir of antigenic diversity during both needle- and tsetse bite-initiated T. brucei infections, with more than 75% of VSGs found exclusively within extravascular spaces. We found that this increased diversity is correlated with slower parasite clearance in tissue spaces. Together, these data support a model in which the slower immune response in extravascular spaces provides more time to generate the antigenic diversity needed to maintain a chronic infection. Our findings reveal the important role that extravascular spaces can have in pathogen diversification.
A multi-modal single-cell and spatial expression map of metastatic breast cancer biopsies across clinicopathological features
Authors: Klughammer Johanna , Abravanel Daniel L. , Segerstolpe Åsa , Blosser Timothy R. , Goltsev Yury , Cui Yi , Goodwin Daniel R. , Sinha Anubhav , Ashenberg Orr , Slyper Michal , Vigneau Sébastien , Jané‐Valbuena Judit , Alon Shahar , Caraccio Chiara , Chen Judy , Cohen Ofir , Cullen Nicole , DelloStritto Laura K. , Dionne Danielle , Files Janet , Frangieh Allison , Helvie Karla , Hughes Melissa E. , Inga Stephanie , Kanodia Abhay , Lako Ana , MacKichan Colin , Mages Simon , Moriel Noa , Murray Evan , Napolitano Sara , Nguyen Kyleen , Nitzan Mor , Ortiz Rebecca , Patel Miraj , Pfaff Kathleen L. , Porter Caroline B. M. , Rotem Asaf , Strauss Sarah , Strasser Robert , Thorner Aaron R. , Turner Madison , Wakiro Isaac , Waldman Julia , Wu Jingyi , Gómez Tejeda Zañudo Jorge , Zhang Diane , Lin Nancy U. , Tolaney Sara M. , Winer Eric P. , Boyden Edward S. , Chen Fei , Nolan Garry P. , Rodig Scott J. , Zhuang Xiaowei , Rozenblatt-Rosen Orit , Johnson Bruce E. , Regev Aviv , Wagle Nikhil
Published: October 2024

Although metastatic disease is the leading cause of cancer-related deaths, its tumor microenvironment remains poorly characterized due to technical and biospecimen limitations. In this study, we assembled a multi-modal spatial and cellular map of 67 tumor biopsies from 60 patients with metastatic breast cancer across diverse clinicopathological features and nine anatomic sites with detailed clinical annotations. We combined single-cell or single-nucleus RNA sequencing for all biopsies with a panel of four spatial expression assays (Slide-seq, MERFISH, ExSeq and CODEX) and H&E staining of consecutive serial sections from up to 15 of these biopsies. We leveraged the coupled measurements to provide reference points for the utility and integration of different experimental techniques and used them to assess variability in cell type composition and expression as well as emerging spatial expression characteristics across clinicopathological and methodological diversity. Finally, we assessed spatial expression and co-localization features of macrophage populations, characterized three distinct spatial phenotypes of epithelial-to-mesenchymal transition and identified expression programs associated with local T cell infiltration versus exclusion, showcasing the potential of clinically relevant discovery in such maps.
Human prolyl hydroxylase domain 2 reacts with O2 and 2-oxoglutarate to enable formation of inactive Fe(III).2OG.hypoxia-inducible-factor α complexes
Authors: Fiorini Giorgia , Marshall Stephen A. , Figg William D. , Myers William K. , Brewitz Lennart , Schofield Christopher J.
Published: October 2024

Hypoxia inducible transcription factors (HIFs) mediate the hypoxic response in metazoans. When sufficient O2 is present, Fe(II)/2-oxoglutarate (2OG)-dependent oxygenases (human PHD1-3) promote HIFα degradation via prolyl-hydroxylation. We report crystallographic, spectroscopic, and biochemical characterization of stable and inactive PHD2.Fe(III).2OG complexes. Aerobic incubation of PHD2 with Fe(II) and 2OG enables formation of PHD2.Fe(III).2OG complexes which bind HIF1-2α to give inactive PHD2.Fe(III).2OG.HIF1-2α complexes. The Fe(III) oxidation state in the inactive complexes was shown by EPR spectroscopy. L-Ascorbate hinders formation of the PHD2.Fe(III).2OG.(+/-HIFα) complexes and slowly regenerates them to give the catalytically active PHD2.Fe(II).2OG complex. Crystallographic comparison of the PHD2.Fe(III).2OG.HIF2α complex with the analogous anaerobic Fe(II) complex reveals near identical structures. Exposure of the anaerobic PHD2.Fe(II).2OG.HIF2α crystals to O2 enables in crystallo hydroxylation. The resulting PHD2.product structure, manifests conformational changes compared to the substrate structures. The results have implications for the role of the PHDs in hypoxia sensing and open new opportunities for inhibition of the PHDs and other 2OG dependent oxygenases by promoting formation of stable Fe(III) complexes.
Exploring the role of different cell types on cortical folding in the developing human brain through computational modeling
Authors: Zarzor Mohammad Saeed , Ma Qiang , Almurey Median , Kainz Bernhard , Budday Silvia
Published: October 2024

The human brain’s distinctive folding pattern has attracted the attention of researchers from different fields. Neuroscientists have provided insights into the role of four fundamental cell types crucial during embryonic development: radial glial cells, intermediate progenitor cells, outer radial glial cells, and neurons. Understanding the mechanisms by which these cell types influence the number of cortical neurons and the emerging cortical folding pattern necessitates accounting for the mechanical forces that drive the cortical folding process. Our research aims to explore the correlation between biological processes and mechanical forces through computational modeling. We introduce cell-density fields, characterized by a system of advection-diffusion equations, designed to replicate the characteristic behaviors of various cell types in the developing brain. Concurrently, we adopt the theory of finite growth to describe cortex expansion driven by increasing cell density. Our model serves as an adjustable tool for understanding how the behavior of individual cell types reflects normal and abnormal folding patterns. Through comparison with magnetic resonance images of the fetal brain, we explore the correlation between morphological changes and underlying cellular mechanisms. Moreover, our model sheds light on the spatiotemporal relationships among different cell types in the human brain and enables cellular deconvolution of histological sections.
Tandem dye-sensitized solar cells achieve 12.89% efficiency using novel organic sensitizers
Authors: Badawy Safa A. , Abdel-Latif Ehab , Elmorsy Mohamed R.
Published: October 2024

This study presents a significant advancement in tandem dye-sensitized solar cells (T-DSSCs) through the strategic synthesis of novel triazatruxene (TAT) sensitizers MS-1 and MS-2. These organic sensitizers demonstrate exceptional light-harvesting capacity and overall performance, pushing the boundaries of power conversion efficiency (PCE) in DSSCs. The MS-1-based DSSCs achieved an impressive PCE of 12.81%, while MS-2 sensitizers reached a notable 10.92%. These efficiencies represent significant improvements over the conventional N719 dye (7.60%), demonstrating the potential of metal-free organic sensitizers in DSSC technology. The key to these noteworthy results lies in the molecular design of the organic sensitizers. The triazatruxene donor segment in the MS-1 and MS-2 dyes, featuring a rigid structure and efficient intramolecular charge transfer (ICT), proved to be a game-changer for photovoltaic properties. Building on these results, we explored an innovative parallel tandem cell (PT-DSSC) configuration. By connecting separate cells containing N719 and MS-1 sensitizers, we achieved a record efficiency of 12.89% with enhanced short-circuit current density (JSC) and open-circuit voltage (VOC)compared to single-dye cells. This study highlights the potential of molecular engineering in organic sensitizers and device optimization to enhance DSSC performance, paving the way for further advancements in solar cell technology.
FCGR3A V158F gene polymorphism and trastuzumab response in HER2-positive breast cancer patients
Authors: Abdel-Wahed Marwa A. , Sabbour Ghada Sadek , Hamed Amira I. , EL Kady Mohammed Sabry , Mohammed Shaimaa Khalil , Shaaban Menat Allah Ali Mahmoud
Published: October 2024

Breast cancer is considered a multifactorial disease, with genetic factors playing an important role in diagnosis and treatment. FCGR3A encodes the receptor for the Fc portion of immunoglobulin G that has been linked to the trastuzumab response. Our study aimed to investigate the association of FCGR3A-V158F gene polymorphism with breast cancer and to evaluate the impact of FCGR3A-V158F gene polymorphism on trastuzumab response in HER2-positive breast cancer patients. The study was conducted on eighty breast cancer patients who were collected from the Department of Oncology at Ain Shams University Hospitals; in addition, twenty age-matched healthy subjects were taken as a healthy control group. Patients were further sub-classified according to their responses. The study showed that there were no statistically significant differences between patients and controls regarding FCGR3A-V158F gene polymorphism genotypes. However, there was a significant association between the concordance of this polymorphism and the response to trastuzumab therapy among the patient’s group. V/V is associated with better treatment response and overall survival (OS) compared to F/V and F/F alleles. Assessment of FCGR3A-V158F gene polymorphism might be useful in making a treatment decision in HER2-positive breast cancer patients.
Binaural beats at 0.25 Hz shorten the latency to slow-wave sleep during daytime naps
Authors: Fan Zhiwei , Zhu Yunyao , Suzuki Chihiro , Suzuki Yoko , Watanabe Yumi , Watanabe Takahiro , Abe Takashi
Published: October 2024

Binaural beats can entrain neural oscillations and modulate behavioral states. However, the effect of binaural beats, particularly those with slow frequencies (< 1 Hz), on sleep remains poorly understood. We hypothesized that 0.25-Hz beats can entrain neural oscillations and enhance slow-wave sleep by shortening its latency or increasing its duration. To investigate this, we included 12 healthy participants (six women; mean age, 25.4 ± 2.6 years) who underwent four 90-min afternoon nap sessions, comprising a sham condition (without acoustic stimulation) and three binaural-beat conditions (0, 0.25, or 1 Hz) with a 250-Hz carrier tone. The acoustic stimuli, delivered through earphones, were sustained throughout the 90-min nap period. Both N2- and N3- latencies were shorter in the 0.25-Hz binaural beats condition than in the sham condition. We observed no significant results regarding neural entrainment at slow frequencies, such as 0.25 and 1 Hz, and the modulation of sleep oscillations, including delta and sigma activity, by binaural beats. In conclusion, this study demonstrated the potential of binaural beats at slow frequencies, specifically 0.25 Hz, for inducing slow-wave sleep in generally healthy populations.
Understanding the heterogeneous performance of variant effect predictors across human protein-coding genes
Authors: Fawzy Mohamed , Marsh Joseph A.
Published: October 2024

Variant effect predictors (VEPs) are computational tools developed to assess the impacts of genetic mutations, often in terms of likely pathogenicity, employing diverse algorithms and training data. Here, we investigate the performance of 35 VEPs in the discrimination between pathogenic and putatively benign missense variants across 963 human protein-coding genes. We observe considerable gene-level heterogeneity as measured by the widely used area under the receiver operating characteristic curve (AUROC) metric. To investigate the origins of this heterogeneity and the extent to which gene-level VEP performance is predictable, for each VEP, we train random forest models to predict the gene-level AUROC. We find that performance as measured by AUROC is related to factors such as gene function, protein structure, and evolutionary conservation. Notably, intrinsic disorder in proteins emerged as a significant factor influencing apparent VEP performance, often leading to inflated AUROC values due to their enrichment in weakly conserved putatively benign variants. Our results suggest that gene-level features may be useful for identifying genes where VEP predictions are likely to be more or less reliable. However, our work also shows that AUROC, despite being independent of class balance, still has crucial limitations when used for comparing VEP performance across different genes.
The effect of nitrogen management on seed yield and quality in traditional and canola-quality white mustard
Authors: Jankowski Krzysztof Józef , Szatkowski Artur , Załuski Dariusz
Published: October 2024

The article presents the results of a three-year field study that was conducted in Poland to evaluate the yield and quality of seeds and oil from traditional (SAM) and canola-quality white mustard (SAC) in response to different N fertilizer rates (0, 40, 80, 120, and 160 kg ha–1). Seed yields were 25% higher in SAM than SAC. The seeds of SAC contained more crude fat (by 3%) and crude fiber (by 6%) than the seeds of SAM. In turn, the seeds of SAM were a richer source of total protein (by 7%). The content of glucosinolates (GSLs) was 8–10 times lower in the seeds of SAC than SAM. The seeds of both mustard cultivars were most abundant in γ-tocopherol (γ-T) (90–94%). The seeds of SAC were characterized by a higher content of γ-T and a lower α-T/γ-T ratio than SAM seeds. White mustard oil contained mostly MUFAs (69–75%). However, C22:1 accounted for more than 50% of MUFAs in the oil SAM. In the oil SAC, the proportion of C22:1 did not exceed 6%, whereas C18:1 accounted for nearly 85% of total MUFAs. Nitrogen fertilization induced a significant increase in seed yields (by 33%), a decrease in crude fat content (by 3–4%), and an increase in total protein content (by 4%), and crude fiber content (by 7%). Nitrogen decreased GSL levels by 31% in SAM seeds. In SAC, N fertilization induced differences in the qualitative composition of GSLs, but did not affect the total GSL content of seeds. Higher N rates increased the content of α-T and γ-T, the α-T/γ-T ratio, and total T content. Nitrogen fertilization decreased the content of C18:3 in the seeds of the SAM. In SAC, the application of N decreased the content of C18, C18:1, and C18:3, and increased the biosynthesis of C18:2, C20:1, and C22:1.
Real-time imaging of cGMP signaling shows pronounced differences between glomerular endothelial cells and podocytes
Authors: Rutkowski Nelli , Görlitz Frederik , Wiesner Eva , Binz-Lotter Julia , Feil Susanne , Feil Robert , Benzing Thomas , Hackl Matthias J.
Published: October 2024

Recent clinical trials of drugs enhancing cyclic guanosine monophosphate (cGMP) signaling for cardiovascular diseases have renewed interest in cGMP biology within the kidney. However, the role of cGMP signaling in glomerular endothelial cells (GECs) and podocytes remains largely unexplored. Using acute kidney slices from mice expressing the FRET-based cGMP biosensor cGi500 in endothelial cells or podocytes enabled real-time visualization of cGMP. Stimulation with atrial natriuretic peptide (ANP) or SNAP (NO donor) and various phosphodiesterase (PDE) inhibitors elevated intracellular cGMP in both cell types. GECs showed a transient cGMP response upon particulate or soluble guanylyl cyclase activation, while the cGMP response in podocytes reached a plateau following ANP administration. Co-stimulation (ANP + SNAP) led to an additive response in GECs. The administration of PDE inhibitors revealed a broader basal PDE activity in GECs dominated by PDE2a. In podocytes, basal PDE activity was mainly restricted to PDE3 and PDE5 activity. Our data demonstrate the existence of both guanylyl cyclase pathways in GECs and podocytes with cell-specific differences in cGMP synthesis and degradation, potentially suggesting new therapeutic options for kidney diseases.
Psychometric properties of the Persian version of the workplace fun scale among nurses: a cross-sectional study
Authors: Hashemian Moghadam Azam , Imashi Reza , Yaghoobi Saghezchi Roghayeh , Mirzaei Alireza
Published: October 2024

Previous research has highlighted the importance of workplace fun in enhancing employee satisfaction and performance, particularly in high-stress professions like nursing. However, a notable gap exists in understanding how workplace fun is perceived and measured among nurses in Persian-speaking countries. This study addresses this gap by translating the Workplace Fun Scale and assessing its psychometric properties among nurses. The findings will provide insights into the scale’s applicability in these contexts and pave the way for healthcare organizations to significantly explore ways to enhance nurses’ enjoyment of work in Persian-speaking countries. This survey, which involved 321 nurses from medical education centers in Ardabil, was conducted with a meticulous and rigorous methodology. Standard questionnaires collected the data, including a demographic form and the translated Workplace Fun Scale. The study examined the three aspects of workplace fun: fun activities, coworker socializing, and manager support for fun. Confirmatory factor analysis was used to validate the structure, and reliability was assessed through retest coefficients, Cronbach’s alpha coefficients, and composite reliability coefficients. The data were analyzed using SPSS version 14 and LISREL version 8.8, ensuring the highest research standards. The validity of both form and content was confirmed through translation and reverse translation. The Workplace Fun Scale showed high internal consistency and reliability, with significant Cronbach’s alpha coefficients, composite reliability, and two-week retest coefficients of 0.859, 0.885, and 0.459, respectively (all at the p < 0.01 level). Fit indices, including GFI (0.97), AGFI (0.94), CFI (0.99), NFI (0.98), TLI (0.97), and SRMR (0.04), indicated a good fit of the measurement model, confirming the validity of the scale in assessing workplace fun. The confirmatory factor analysis results indicated that the translated version of the workplace fun scale, adapted from Tews, exhibited a robust factor structure and internal homogeneity within the Iranian sample. Furthermore, the scale demonstrated positive internal validity and reliability in Persian translation. These findings suggest that the scale possesses acceptable psychometric properties, making it a valuable tool for assessing workplace fun among nurses in Persian-speaking countries.
NOTE: non-parametric oversampling technique for explainable credit scoring
Authors: Han Seongil , Jung Haemin , Yoo Paul D. , Provetti Alessandro , Cali Andrea
Published: October 2024

Credit scoring models are critical for financial institutions to assess borrower risk and maintain profitability. Although machine learning models have improved credit scoring accuracy, imbalanced class distributions remain a major challenge. The widely used Synthetic Minority Oversampling TEchnique (SMOTE) struggles with high-dimensional, non-linear data and may introduce noise through class overlap. Generative Adversarial Networks (GANs) have emerged as an alternative, offering the ability to model complex data distributions. Conditional Wasserstein GANs (cWGANs) have shown promise in handling both numerical and categorical features in credit scoring datasets. However, research on extracting latent features from non-linear data and improving model explainability remains limited. To address these challenges, this paper introduces the Non-parametric Oversampling Technique for Explainable credit scoring (NOTE). The NOTE offers a unified approach that integrates a Non-parametric Stacked Autoencoder (NSA) for capturing non-linear latent features, cWGAN for oversampling the minority class, and a classification process designed to enhance explainability. The experimental results demonstrate that NOTE surpasses state-of-the-art oversampling techniques by improving classification accuracy and model stability, particularly in non-linear and imbalanced credit scoring datasets, while also enhancing the explainability of the results.