bluuebunny/crossref_metadata_2025_split huggingface dataset:
RNA expression data suggest ALDH2 inhibition as a concept for killing acute myeloid leukemia cells that are resistant to ALDH1 inhibitors: the example of NPM1 mutant AML
Authors: Dancik Garrett M , Vlahopoulos Spiros 
Published: November 2024

AbstractIn this data paper we present a study of RNA expression in association with the disease course of acute myeloid leukemia (AML). We have previously identified aldehyde dehydrogenase genesALDH1A1andALDH2as prospective actionable targets in AML. ALDH1A1 is expected to have key functions in leukemia stem-like cells that are prone to a dormant state in terms of metabolic activity and proliferation. Cells with a higher activity of metabolism as a whole and in mitochondria in particular, are likely to generate a higher abundance of formaldehyde and acetaldehyde. Cell survival necessitates removal of formaldehyde and acetaldehyde, which is to a substantial degree the function of ALDH2. AML cells with a mutantNPM1gene permit higher MYC activity which would lead to increased metabolic activity. Extended MYC activity is allowed by the mutant NPM1 protein, compared to NPM1 wild-type. Here, we show that survival analysis in patients withNPM1mutant AML yields a higher hazard ratio forALDH2RNA than forALDH1A1, which is not the case for patients with wild-type NPM1. This result is consistent with the difference in enzymatic function between ALDH2 and ALDH1A1, the latter of which is not suited for small aldehydes, especially formaldehyde. This should open the door to the examination of ALDH2 inhibitors such as the clinically approved disulfiram, for the treatment of NPM1 mutant AML that proves refractory to ALDH1A1 inhibition.
EMT, angiogenesis, and cell-cycle pathways are significantly impacted in oral cancer patients, among whom a large fraction may potentially respond to immune checkpoint therapy
Authors: Das Debodipta , Maitra Arindam , Panda Chinmay K. , Ghose Sandip , Roy Bidyut , Sarin Rajiv , Majumder Partha P. 
Published: November 2024

AbstractBackgroundOral squamous cell carcinoma of the gingivo-buccal region (OSCC-GB) has the highest incidence among males and the second highest overall among all cancers in India, emphasizing the need for precise molecular classifications to guide personalized therapy.MethodsWe performed bulk RNA sequencing on tumor and adjacent normal tissue samples from 72 OSCC-GB patients, as well as leukoplakia tissue from 25 patients with concurrent leukoplakia.FindingsOur analysis revealed activated epithelial-mesenchymal transition, angiogenesis, and cell-cycle function in OSCC-GB. We found significant enhancement of glycolysis and reduction in oxidative phosphorylation, which are hallmarks of the Warburg effect. Immune profiling indicated enriched immune-related genes and cells in tumor tissues. We identified two distinct patient subtypes, one of which exhibited higher immune cell infiltration and showed potential for greater responsiveness to immune checkpoint inhibitors.CD226,CD38, andKBTBD8were identified as potential biomarkers for classifying OSCC-GB patients and were validated in an independent cohort. Significantly more M1 macrophages and CD4+ T-cells in leukoplakia tissue than the normal indicate activated host defense mechanisms in pre-malignant lesions, highlighting the potential for early intervention to prevent malignancy. TCGA-HNSC data exhibited similar gene set enrichments, including glycolysis and immune-related pathways. However, unique profiles in a subset of TCGA-HNSC patients highlight the molecular heterogeneity of head and neck cancers.ConclusionOur findings underscore the critical role of understanding these pathways in cancer biology and immunology, essential for developing effective treatment strategies for oral cancer and immunotherapy.
Ecological synchrony in human-modified landscapes under a changing climate
Authors: Song Yiluan , Barnes Mallory , Browning Dawn M. , Bybee-Finley K. Ann , Dahlin Kyla M. , Munch Stephan B. , Ponce-Campos Guillermo E. , Youngflesh Casey , Zuckerberg Benjamin , Zhu Kai 
Published: November 2024

AbstractDifferent aspects of ecological systems, biotic or abiotic, often fluctuate in coordinated patterns over space and time. Such high concordance between ecological processes is often referred to as ecological synchrony. Anthropogenic activities, including and beyond climate change, have the potential to alter ecological synchrony by disrupting or enhancing existing synchrony. Despite many local studies, we have a limited systematic understanding of how ecological synchrony is shaped by management in human-dominated landscapes at regional to continental scales. From a macrosystems perspective, we review how anthropogenic activities, particularly beyond climate change, alter ecological synchrony across levels of ecological organization, from the ecosystem level to the population level. For each level, we use a large-scale case study to demonstrate ways to quantify the impacts of human modifications on synchrony using big data from remote sensing, surveys, and observatory networks. For example, we detected possible homogenization of population dynamics of bird species in North America. These changes in ecological synchrony, although in different forms, often represent challenges to ecological and social systems. Collaborative research efforts that integrate emerging open data streams moving forward will be able to provide insights into the effects of different anthropogenic drivers and the consequences of changes in synchrony.
Rapid colorimetric detection ofcitrus tristeza viruscombining portable sample preparation and reverse transcription-loop mediated isothermal amplification
Authors: Liu Chia-Wei , Bodaghi Sohrab , Keremane Manjunath L. , Kalish Brent , Vidalakis Georgios , Tsutsui Hideaki 
Published: November 2024

AbstractsA sensing platform combining semi-automated sample preparation protocol and one-step reverse transcription loop-mediated isothermal amplification (RT-LAMP) is reported for rapid colorimetric detection ofcitrus tristeza virus(CTV) in a greenhouse. An OmniLyse micro-homogenizer and cellulose paper disks were integrated for quick sample preparation of total nucleic acids (<15 min). RT-LAMP assays were optimized in terms of primers’ concentrations and minimization of false positives for both CTV and cytochrome oxidase (COX) detections. Specifically, the optimal reaction time for lab-based RT-LAMP assays was determined as 40 minutes with the detection limits of CTV and COX as 43 copies/μL (equivalent to 86 copies/mg of tissue) and 5 copies/μL (equivalent to 10 copies/mg of tissue), respectively. Additionally, an in-greenhouse colorimetric RT-LAMP assay with lyophilized reaction mix for endpoint CTV detection was successfully conducted in 35 minutes without a false response in either colorimetric or fluorometric assays. Overall, this quick sample preparation protocol integrated with the lyophilized RT-LAMP assays showed high efficiency and reliability in plant pathogen detection in a greenhouse. This strategy holds great potential to be integrated into a portable, autonomous system and be universally adopted for in-field diagnosis of different pathogens.
Understanding pollination in urban food production: the importance of data validation and participant feedback for citizen science project design
Authors: Nicholls Elizabeth , Salm Leah , Castellanos Maria Clara , Basu Parthib , Chaterjee Soumik , Ely Adrian , Howe Helena , Goulson Dave 
Published: November 2024

SummaryThere is a significant knowledge gap regarding the pollination needs of urban farming, partly due to barriers for researchers in accessing these growing spaces. Involving growers in data collection offers a potential solution but presents other challenges in terms of data accuracy and participant retention.We developed a citizen science methodology for monitoring plant-pollinator interactions in urban food systems and evaluated the accuracy of data collected by growers by comparison to data collected by a professionally trained researcher. We also collected feedback from participants at the mid- and endpoints of the project regarding their experiences of taking part.While there was some agreement between the datasets in terms of the crops most (raspberries and squash) and least attractive (tomatoes) to insects, relying only on the dataset collected by growers themselves (citizen scientists) would lead to an overestimation of the generality of relationships between crops and pollinating insects in urban food production. Possible reasons for discrepancies between the datasets include species misidentification and non-reporting of surveys where no insects were observed by citizen scientists.Citizen scientists reported lack of time, concerns about data accuracy and too complex methods as barriers to participation. Implementation of their suggestions for improvements led to a 66% increase in participation in the following year, demonstrating the importance of maintaining a two-way dialogue between participants and project organisers. Citizen scientists also reported an increased appreciation and understanding of insect pollinations following participation, highlighting an additional benefit of involving urban growers in data collection.Social Impact StatementGrowing food in urban areas can contribute towards sustainable food production. We know little about urban crop pollination, and data collection can be challenging due to restricted access to growing spaces. We developed and tested the effectiveness of a method for urban growers themselves to collect data on insects visiting their crops. Comparing data to that collected by a professional researcher, we found similarities in terms of the most and least attractive crops to pollinators, but there were also large discrepancies in the datasets that mean there are limitations to relying on grower-collected data alone to understand urban plant-pollinator interactions.
Reducing functionally defective old HSCs alleviates aging-related phenotypes in old recipient mice
Authors: Wang Yuting , Zhang Wenhao , Zhang Chao , Van Hoang Tran , Seino Takashi , Zhang Yi 
Published: November 2024

AbstractAging is a process accompanied by functional decline in tissues and organs with great social and medical consequences. Developing effective anti-aging strategies is of great significance. In this study, we demonstrated that transplantation of young hematopoietic stem cells (HSCs) into old mice can mitigate aging phenotypes, underscoring the crucial role of HSCs in the aging process. Through comprehensive molecular and functional analyses, we identified a subset of HSCs in aged mice that exhibit “younger” molecular profiles and functions, marked by low levels of CD150 expression. Mechanistically, CD150lowHSCs from old mice can effectively differentiate into downstream lineage cells but not their CD150highcounterparts. Notably, transplantation of old CD150lowHSCs attenuates aging phenotypes and prolongs lifespan of elderly mice compared to those transplanted with unselected or CD150highHSCs. Importantly, reducing the dysfunctional CD150highHSCs can alleviate aging phenotypes in old recipient mice. Thus, our study demonstrates the presence of “younger” HSCs in old mice, and aging-associated functional decline can be mitigated by reducing dysfunctional HSCs.
Sex-dependent additive effects of dorzagliatin and incretin on insulin secretion in a novel mouse model ofGCK-MODY
Authors: Salazar Shadai , Delgadillo-Silva Luis Fernando , Carapeto Priscila , Dakessian Karen , Melhem Rana , Provencher-Girard Audrey , Ostinelli Giada , Turgeon Julie , Kaci Imane , Migneault Francis , Huising Mark O. , Hébert Marie-Josée , Rutter Guy A. 
Published: November 2024

AbstractGlucokinase (GK) catalyses the key regulatory step in glucose-stimulated insulin secretion. Correspondingly, hetero– and homozygous mutations in humanGCKcause maturity-onset diabetes of the young (GCK-MODY) and permanent neonatal diabetes (PNDM), respectively. To explore the possible utility of glucokinase activators (GKA) and of glucagon–like receptor-1 (GLP-1) agonists in these diseases, we have developed a novel hypomorphicGckallele in mice encoding an aberrantly spliced mRNA deleted for exons 2 and 3. In islets from homozygous knock-in (GckKI/KI) mice, GK immunoreactivity was reduced by >85%, and glucose-stimulated insulin secretion eliminated. Homozygous GckKI/KImice were smaller than wildtype littermates and displayed frank diabetes (fasting blood glucose >18 mmol/L; HbA1c ∼12%), ketosis and nephropathy. Heterozygous GckKI/+mice were glucose intolerant (HbA1c ∼5.5%). Abnormal glucose-stimulated Ca2+dynamics and beta cell-beta cell connectivity in GckKI/+islets were completely reversed by the recently-developed GKA, dorzagliatin, which was largely inactive in homozygous GckKI/KImouse islets. The GLP-1 receptor agonist exendin-4 improved glucose tolerance in male GckKI/+mice, an action potentiated by dorzagliatin, in male but not female mice. Sex-dependent additive effects of these agents were also observed on insulin secretionin vitro. Combined treatment with GKA and incretin may thus be useful inGCK-MODY orGCK-PNDM.Article Highlightsa.Glucokinase deficiency can drive maturity-onset diabetes of the young (GCK-MODY;heterozygotes) and permanent neonatal diabetes (GCK-PNDM;homozygotes)b.We describe a hypomorphicGckallele where aberrant splicing in islets lowers GK activity to by ∼85%. We use these mice to explore the effects of the glucokinase activator, dorzagliatin, and incretin on insulin secretionc.Whereas heterozygous mutant mice are mildly hyperglycemic, homozygotes have frank diabetes but survive to adulthood. Dorzagliatin potentiates the effects of GLP-1 receptor activation sex-dependently in heterozygotesd.Combined use of these drugs may be useful in some forms ofGCKdiabetes
Florigen and antiflorigen gene expression correlates with reproductive state in a marine angiosperm,Zostera marina
Authors: Nolan Christine T. , Campbell Ian , Farrell-Sherman Anna , Briones Ortiz Bryan A. , Naish Kerry A. , Di Stilio Verónica , Kaldy James E. , Donoghue Cinde , Ruesink Jennifer L. , Imaizumi Takato 
Published: November 2024

SUMMARYFlorigen and antiflorigen genes within the phosphatidylethanolamine-binding protein (PEBP) family regulate flowering in angiosperms. In eelgrass (Zostera marina), a marine foundation species threatened by climate change, flowering and seed production are crucial for population resilience. Yet, the molecular mechanism underpinning flowering remains unknown.Using phylogenetic analysis and functional assays inArabidopsis, we identified thirteenPEBPgenes inZ. marina(ZmaPEBP) and showed that four genes altered flowering phenotypes when overexpressed. We used quantitative RT-PCR onZ. marinashoots from perennial and annual populations in Willapa Bay, USA to assess expression of these four genes in different tissue and expression changes throughout the growth season.We demonstrated thatZmaFT2andZmaFT4promote flowering, andZmaFT9andZmaTFL1arepress flowering inArabidopsis. Across five natural sites exhibiting different degrees of population genetic structure,ZmaFT2andZmaFT4were expressed in leaves of vegetative and reproductive shoots and in stems and rhizomes of reproductive shoots.ZmaFT9was distinctively expressed in leaves of vegetative and juvenile shoots, whileZmaTFL1alevels increased after flowering shoots emerged.Our results suggest thatZmaFT2andZmaFT4may promote flowering, whileZmaFT9may inhibit a floral transition in eelgrass. We speculate thatZmaTFL1amay be involved in flowering shoot architecture.
KaMLs for Predicting Protein pKaValues and Ionization States: Are Trees All You Need?
Authors: Shen Mingzhe , Kortzak Daniel , Ambrozak Simon , Bhatnagar Shubham , Buchanan Ian , Liu Ruibin , Shen Jana 
Published: November 2024

AbstractDespite its importance in understanding biology and computer-aided drug discovery, the accurate prediction of protein ionization states remains a formidable challenge. Physics-based approaches struggle to capture the small, competing contributions in the complex protein environment, while machine learning (ML) is hampered by scarcity of experimental data. Here we report the development of pKaML (KaML) models based on decision trees and graph attention networks (GAT), exploiting physicochemical understanding and a new experiment pKadatabase (PKAD-3) enriched with highly shifted pKa’s. KaML-CBtree significantly outperforms the current state of the art in predicting pKavalues and ionization states across all six titratable amino acids, notably achieving accurate predictions for deprotonated cysteines and lysines – a blind spot in previous models. The superior performance of KaMLs is achieved in part through several innovations, including separate treatment of acid and base, data augmentation using AlphaFold structures, and model pretraining on a theoretical pKadatabase. We also introduce the classification of protonation states as a metric for evaluating pKaprediction models. A meta-feature analysis suggests a possible reason for the lightweight tree model to outperform the more complex deep learning GAT. We release an end-to-end pKapredictor based on KaML-CBtree and the new PKAD-3 database, which facilitates a variety of applications and provides the foundation for further advances in protein electrostatics research.TOC Graphic
Vascular Transcription Factor TMO5 Regulates PIN1 Polarity and Organogenesis Downstream of MONOPTEROS in the Shoot Meristem
Authors: Kareem Abdul , Ohno Carolyn , Heisler Marcus G. 
Published: November 2024

AbstractPlants continuously produce lateral organs, such as leaves and flowers, from the shoot apical meristem (SAM). This process is guided by the accumulation of the plant hormone auxin and the polar localization of the efflux protein PIN-FORMED1 (PIN1). The transcription factor MONOPTEROS (MP) plays a crucial role in orienting PIN1 polarity, thereby facilitating auxin-driven organogenesis. In this study, we investigated how MP regulates PIN1 polarity and organogenesis, discovering that the downstream vascular transcription factor TMO5 regulates PIN1 polarity non-cell-autonomously and promotes organ initiation in the SAM. Furthermore, we find that exogenous auxin and cytokinin can partially rescue the organ defects associated with loss of MP and TMO5 activity. Collectively, these findings uncover a novel role for TMO5 in controlling PIN1 polarity and driving organogenesis by coordinating hormonal signalling.
Isolation of bacteria that catabolize abiotically synthesized tetroses via the formose reaction
Authors: Kawasaki Kosei , Igarashi Kensuke , Tabata Hiro , Nishijima Hiroaki , Nakanishi Shuji , Kato Souichiro 
Published: November 2024

ABSTRACTSugars synthesized through abiotic processes, specifically the formose reaction, are promising candidates for next-generation feedstocks for biomanufacturing due to their significantly higher productivity compared to cultivated crops. One of the significant challenges associated with the utilization of abiotically synthesized sugars via the formose reaction is the presence of unusual sugars, which are not metabolized by typical microorganisms. This study aimed to identify microorganisms capable of catabolizing tetroses, which are among the unusual sugars present in the abiotically synthesized sugars. Four model bacteria commonly used in biomanufacturing, includingEscherichia coli, were unable to catabolize tetroses and their growth was completely inhibited by 2 to 4 g/L of D-erythrose or 0.5 to 1 g/L of L-erythrulose. We successfully isolated eight phylogenetically diverse bacterial strains from river sediments, capable of utilizing D-erythrose and L-erythrulose as the sole carbon sources. These isolates exhibited higher tolerances to tetroses compared to the model bacteria. The isolates exhibited the ability to grow in high concentrations of the abiotically synthesized sugars, which inhibit the growth of typical microorganisms, and to consume tetroses contained therein. Further investigation into the molecular mechanisms of tetrose metabolisms in the isolates will facilitate the development of biomanufacturing processes utilizing the abiotically synthesized sugars.
Deep Learning with Evolutionary Scale Modeling to discover Antibiotic-Resistance Drug against Klebsiella Pneumoniae
Authors: Jin Linxiao , Lei Zhihao , Lin Peng , Ma Cong , Zhang Wen , Zhou Jiali , Meng Sijun , Jiang Zhenghua , Bu Yemei , Xu Yingfan , Wei Nijun , Hsu Tsehao , Qin Glen , Qiu Hesong 
Published: November 2024

AbstractThe development of effective antibiotics is crucial in combating antibiotic-resistant pathogens such as Klebsiella pneumoniae (KP). This study utilizes deep learning, specifically Evolutionary Scale Modeling (ESM), to identify potential drug candidates. By analyzing molecular similarities between known drugs and KP strains, we aim to accelerate the discovery of new treatments and reduce the risks associated with clinical trials. This approach may shed new lights in the field of drug repositioning.
Root metaxylem area influences drought tolerance and transpiration in pearl millet in a soil texture dependent manner
Authors: Affortit Pablo , Faye Awa , Jones Dylan H. , Benson Ezenwoko , Sine Bassirou , Burridge James , Ndoye Mame Sokhatil , Barry Luke , Moukouanga Daniel , Barnard Stephanie , Bhosale Rahul , Pridmore Tony , Gantet Pascal , Vadez Vincent , Cubry Philippe , Kane Ndjido , Bennett Malcolm , Atkinson Jonathan A. , Laplaze Laurent , Wells Darren M. , Grondin Alexandre 
Published: November 2024

SummaryPearl millet is a key cereal for food security in drylands but its yield is strongly impacted by drought. We investigated how root anatomical traits contribute to mitigating the effects of vegetative drought stress in pearl millet.We examined associations between root anatomical traits and agronomical performance in a pearl millet diversity panel under irrigated and vegetative drought stress treatments in field trials. The impact of associated anatomical traits on transpiration was assessed using subpanels grown in different soil within a greenhouse.In the field, total metaxylem area was positively correlated with grain weight and its maintenance under drought. In the greenhouse, genotypes with larger metaxylem area grown in sandy soil exhibited a consumerist water use strategy under irrigation, which shifted to a conservative strategy under drought. Water savings was mediated by transpiration restriction under high evaporative demand. This mechanism was dependent on soil hydraulics as it was not observed in peat soil with higher hydraulic conductivity upon soil drying.We propose that water savings under drought, mediated by large metaxylem area and its interaction with soil hydraulics, help mitigate vegetative drought stress. Our findings highlight the role of soil hydraulic properties in shaping plant hydraulics and drought tolerance.