bluuebunny/crossref_metadata_2025_split huggingface dataset:
α-Tubulin mutation Thr-239-Ile in annual bluegrass (Poa annua) induces variable responses to prodiamine and dithiopyr
Authors: Russell Eli C. , Rutland Claudia Ann , Patel Jinesh , Hall Nathan D. , Bi Bo , Li Xiao , McElroy J. Scott 
Published: July 2023

AbstractMitotic-inhibiting herbicides, like prodiamine and dithiopyr, are used to control annual bluegrass (Poa annua L.) preemergence in managed turfgrass; however, resistance to mitotic-inhibiting herbicides has evolved due to repeated applications of herbicide from a single mechanism of action. Three suspected resistant populations (R1, R2, and R3) were collected in Alabama and Florida and screened for resistance to prodiamine. Part of the α-tubulin gene was sequenced for known target-site mutations. Target-site mutations were reported in all three R populations, with each containing an amino acid substitution at position 239 from threonine to isoleucine (Thr-239-Ile). Previous research has indicated that the Thr-239-Ile mutation confers resistance to dinitroaniline herbicides in other species. Dose–response screens using prodiamine and dithiopyr were conducted and I50 values were calculated for R1, R2, and R3 using regression models based on seedling emergence. For prodiamine, I50 values for R1, R2, and R3 were 35.3, 502.7, and 91.5 g ai ha−1, respectively, resulting in 2.9-, 41.9-, and 7.6-fold resistance, respectively, when compared with a susceptible (S) population. For dithiopyr, I50 values for R1, R2, and R3 were 154.0, 114.2, and 190.1 g ai ha−1, respectively, resulting in 3.6-, 2.7-, and 4.5-fold resistance, respectively, when compared with an S population. When comparing I90 values with the highest labeled use rates, R2 had a 2.9-fold level of resistance to prodiamine, and R1, R2, and R3 had a 2.4-, 2.0-, and 3.2-fold levels of resistance to dithiopyr, respectively. This is the first report of a variable response in P. annua to prodiamine despite each R population possessing the same mutation.
Anthropogenic Climate Change Negatively Impacts Vegetation and Forage Conditions in the Greater Four Corners Region
Authors: Williams Emily L. , Funk Chris , Shukla Shraddhanand 
Published: July 2023

AbstractThe Southwestern U.S. has been in a megadrought for the past two decades, stressing vegetation across the region and leading to poor forage conditions on rangelands. How has human‐induced climate change affected air temperatures and atmospheric evaporative demand in the greater Four Corners region of the Southwest, and what have the corresponding impacts been to vegetative productivity? We address this question via a multi‐step climate change detection and attribution analysis. We first relate evaporative demand (quantified by Vapor Pressure Deficit, or VPD) and precipitation to the Normalized Difference Vegetation Index (NDVI) in six unique plant‐precipitation zones. VPD is strongly negatively related to NDVI, and the strength of this relation is similar in magnitude to precipitation. We then use a large ensemble of climate change simulations to estimate the magnitude of VPD increases attributable to human‐induced climate change. We find that modest increases in air temperatures have led to large increases in VPD, with the influence of climate change about twice the inter‐annual standard deviation by 2020. Finally, we estimate the reductions in NDVI due to increased VPD and present the reductions in terms of total annual Aboveground Net Primary Productivity. We conclude that human‐induced warming has roughly doubled the magnitude of recent vegetation deficits, especially in mid‐precipitation areas (receiving 250–500 mm of precipitation annually), concentrated in New Mexico. These results indicate that increased temperatures from human‐caused climate change are having persistent and damaging impacts on vegetation productivity, with significant implications for ranchers and other land users in the region.
Non‐Monotonic Feedback Dependence Under Abrupt CO2 Forcing Due To a North Atlantic Pattern Effect
Authors: Mitevski Ivan , Dong Yue , Polvani Lorenzo M. , Rugenstein Maria , Orbe Clara 
Published: July 2023

AbstractEffective climate sensitivity (EffCS), commonly estimated from model simulations with abrupt 4×CO2 for 150 years, has been shown to depend on the CO2 forcing level. To understand this dependency systematically, we performed a series of simulations with a range of abrupt CO2 forcing in two climate models. Our results indicate that normalized EffCS values in these simulations are a non‐monotonic function of the CO2 forcing, decreasing between 3× and 4×CO2 in CESM1‐LE (2× and 3×CO2 in GISS‐E2.1‐G) and increasing at higher CO2 levels. The minimum EffCS value, caused by anomalously negative radiative feedbacks, arises mainly from sea‐surface temperature (SST) relative cooling in the tropical and subtropical North Atlantic. This cooling is associated with the formation of the North Atlantic Warming Hole and Atlantic Meridional Overturning Circulation collapse under CO2 forcing. Our findings imply that understanding changes in North Atlantic SST patterns is important for constraining near‐future and equilibrium global warming.
Ensemble Spread Behavior in Coupled Climate Models: Insights From the Energy Exascale Earth System Model Version 1 Large Ensemble
Authors: Stevenson Samantha , Huang Xingying , Zhao Yingying , Di Lorenzo Emanuele , Newman Matthew , van Roekel Luke , Xu Tongtong , Capotondi Antonietta 
Published: July 2023

AbstractAssessing uncertainty in future climate projections requires understanding both internal climate variability and external forcing. For this reason, single‐model initial condition large ensembles (SMILEs) run with Earth System Models (ESMs) have recently become popular. Here we present a new 20‐member SMILE with the Energy Exascale Earth System Model version 1 (E3SMv1‐LE), which uses a “macro” initialization strategy choosing coupled atmosphere/ocean states based on inter‐basin contrasts in ocean heat content (OHC). The E3SMv1‐LE simulates tropical climate variability well, albeit with a muted warming trend over the twentieth century due to overly strong aerosol forcing. The E3SMv1‐LE's initial climate spread is comparable to other (larger) SMILEs, suggesting that maximizing inter‐basin ocean heat contrasts may be an efficient method of generating ensemble spread. We also compare different ensemble spread across multiple SMILEs, using surface air temperature and OHC. The Community Earth system Model version 1, the only ensemble which utilizes a “micro” initialization approach perturbing only atmospheric initial conditions, yields lower spread in the first ∼30 years. The E3SMv1‐LE exhibits a relatively large spread, with some evidence for anthropogenic forcing influencing spread in the late twentieth century. However, systematic effects of differing “macro” initialization strategies are difficult to detect, possibly resulting from differing model physics or responses to external forcing. Notably, the method of standardizing results affects ensemble spread: control simulations for most models have either large background trends or multi‐centennial variability in OHC. This spurious disequlibrium behavior is a substantial roadblock to understanding both internal climate variability and its response to forcing.
Oblique Collision of the Bahamas Platform at the Northern Boundary of the Caribbean Plate Recorded by the Late Cenozoic Coastal Terraces of SE Cuba
Authors: Authemayou Christine , Nuñez Arelis , Pedoja Kevin , Peñalver Leandro , Chauveau Denovan , Dunán‐Avila Pedro , Martin‐Izquierdo Denyse , de Gelder Gino , Husson Laurent , Castellanos Abella Enrique , Benítez Frómeta Pedro de Jesús , Pastier Anne‐Morwenn 
Published: July 2023

AbstractThe southeastern tip of Cuba Island is limited to the south by the N‐Caribbean boundary. By revisiting the impressive sequences of coastal terraces of this region, we decipher the Quaternary deformation pattern of this plate boundary. We present a detailed mapping of coastal terraces uplifted over a hundred kilometers of coastline, and U/Th dating. At Punta de Maisí, the deformation pattern shows (a) a faster uplift close to the transform boundary and (b) a northward propagation of folding produced by the convergence of the Bahamas platform toward the Caribbean plate. Along the southern coast of Punta de Maisí, the sequence displays 29 coastal terraces up to 520 m in elevation and a upper Pleistocene uplift rate of 0.23 ± 0.07 mm yr−1. We interpret this deformation as resulting from an offshore north‐dipping reverse fault near the coast. This uplift rate corresponds to 3% to 1.6% of the short‐term horizontal slip rate of Septentrional Oriente Fault Zone (10 ± 0.1 mm yr−1). Along the northern coast of Punta de Maisí, the sequence displays height coastal terraces up to 220 m in elevation and the uplift rates amount to 0.1 ± 0.05 mm yr−1 and likely result from the reverse faulting and folding associated with the offshore North Hispaniola Fault Zone. Uplift rates quickly decrease to the West, in agreement with the westward decrease in the activity of the North Hispaniola Fault Zone due to the docking of the Bahamas Platform against Cuba, while the platform more gently underthrusts Cuba to the East.
Immunoglobulin genes expressed in lymphoblastoid cell lines discern and predict lithium response in bipolar disorder patients
Authors: Mizrahi Liron , Choudhary Ashwani , Ofer Polina , Goldberg Gabriela , Milanesi Elena , Kelsoe John R. , Gurwitz David , Alda Martin , Gage Fred H. , Stern Shani 
Published: July 2023

AbstractBipolar disorder (BD) is a neuropsychiatric mood disorder manifested by recurrent episodes of mania and depression. More than half of BD patients are non-responsive to lithium, the first-line treatment drug, complicating BD clinical management. Given its unknown etiology, it is pertinent to understand the genetic signatures that lead to variability in lithium response. We discovered a set of differentially expressed genes (DEGs) from the lymphoblastoid cell lines (LCLs) of 10 controls and 19 BD patients belonging mainly to the immunoglobulin gene family that can be used as potential biomarkers to diagnose and treat BD. Importantly, we trained machine learning algorithms on our datasets that predicted the lithium response of BD subtypes with minimal errors, even when used on a different cohort of 24 BD patients acquired by a different laboratory. This proves the scalability of our methodology for predicting lithium response in BD and for a prompt and suitable decision on therapeutic interventions.
How electroconvulsive therapy works in the treatment of depression: is it the seizure, the electricity, or both?
Authors: Deng Zhi-De , Robins Pei L. , Regenold William , Rohde Paul , Dannhauer Moritz , Lisanby Sarah H. 
Published: July 2023

AbstractWe have known for nearly a century that triggering seizures can treat serious mental illness, but what we do not know is why. Electroconvulsive Therapy (ECT) works faster and better than conventional pharmacological interventions; however, those benefits come with a burden of side effects, most notably memory loss. Disentangling the mechanisms by which ECT exerts rapid therapeutic benefit from the mechanisms driving adverse effects could enable the development of the next generation of seizure therapies that lack the downside of ECT. The latest research suggests that this goal may be attainable because modifications of ECT technique have already yielded improvements in cognitive outcomes without sacrificing efficacy. These modifications involve changes in how the electricity is administered (both where in the brain, and how much), which in turn impacts the characteristics of the resulting seizure. What we do not completely understand is whether it is the changes in the applied electricity, or in the resulting seizure, or both, that are responsible for improved safety. Answering this question may be key to developing the next generation of seizure therapies that lack these adverse side effects, and ushering in novel interventions that are better, faster, and safer than ECT.
RAD51C-XRCC3 structure and cancer patient mutations define DNA replication roles
Authors: Longo Michael A. , Roy Sunetra , Chen Yue , Tomaszowski Karl-Heinz , Arvai Andrew S. , Pepper Jordan T. , Boisvert Rebecca A. , Kunnimalaiyaan Selvi , Keshvani Caezanne , Schild David , Bacolla Albino , Williams Gareth J. , Tainer John A. , Schlacher Katharina 
Published: July 2023

AbstractRAD51C is an enigmatic predisposition gene for breast, ovarian, and prostate cancer. Currently, missing structural and related functional understanding limits patient mutation interpretation to homology-directed repair (HDR) function analysis. Here we report the RAD51C-XRCC3 (CX3) X-ray co-crystal structure with bound ATP analog and define separable RAD51C replication stability roles informed by its three-dimensional structure, assembly, and unappreciated polymerization motif. Mapping of cancer patient mutations as a functional guide confirms ATP-binding matching RAD51 recombinase, yet highlights distinct CX3 interfaces. Analyses of CRISPR/Cas9-edited human cells with RAD51C mutations combined with single-molecule, single-cell and biophysics measurements uncover discrete CX3 regions for DNA replication fork protection, restart and reversal, accomplished by separable functions in DNA binding and implied 5’ RAD51 filament capping. Collective findings establish CX3 as a cancer-relevant replication stress response complex, show how HDR-proficient variants could contribute to tumor development, and identify regions to aid functional testing and classification of cancer mutations.
Glial Draper signaling triggers cross-neuron plasticity in bystander neurons after neuronal cell death in Drosophila
Authors: Wang Yupu , Zhang Ruiling , Huang Sihao , Valverde Parisa Tajalli Tehrani , Lobb-Rabe Meike , Ashley James , Venkatasubramanian Lalanti , Carrillo Robert A. 
Published: July 2023

AbstractNeuronal cell death and subsequent brain dysfunction are hallmarks of aging and neurodegeneration, but how the nearby healthy neurons (bystanders) respond to the death of their neighbors is not fully understood. In the Drosophila larval neuromuscular system, bystander motor neurons can structurally and functionally compensate for the loss of their neighbors by increasing their terminal bouton number and activity. We term this compensation as cross-neuron plasticity, and in this study, we demonstrate that the Drosophila engulfment receptor, Draper, and the associated kinase, Shark, are required for cross-neuron plasticity. Overexpression of the Draper-I isoform boosts cross-neuron plasticity, implying that the strength of plasticity correlates with Draper signaling. In addition, we find that functional cross-neuron plasticity can be induced at different developmental stages. Our work uncovers a role for Draper signaling in cross-neuron plasticity and provides insights into how healthy bystander neurons respond to the loss of their neighboring neurons.
Construction of C-B axial chirality via dynamic kinetic asymmetric cross-coupling mediated by tetracoordinate boron
Authors: Yang Kai , Mao Yanfei , Zhang Zhihan , Xu Jie , Wang Hao , He Yong , Yu Peiyuan , Song Qiuling 
Published: July 2023

AbstractCatalytic dynamic kinetic asymmetric transformation (DyKAT) provides a powerful tool to access chiral stereoisomers from racemic substrates. Such transformation has been widely employed on the construction of central chirality, however, the application in axial chirality remains underexplored because its equilibrium of substrate enantiomers is limited to five-membered metalacyclic intermediate. Here we report a tetracoordinate boron-directed dynamic kinetic asymmetric cross-coupling of racemic, configurationally stable 3-bromo-2,1-azaborines with boronic acid derivatives. A series of challenging C-B axially chiral compounds were prepared with generally good to excellent enantioselectivities. Moreover, this transformation can also be extended to prepare atropisomers bearing adjacent C-B and C-C diaxes with excellent diastereo- and enantio-control. The key to the success relies on the rational design of a reversible tetracoordinate boron intermediate, which is supported by theoretical calculations that dramatically reduces the rotational barrier of the original C-B axis and achieves the goal of DyKAT.
Bacteroides ovatus accelerates metformin-induced vitamin B12 deficiency in type 2 diabetes patients by accumulating cobalamin
Authors: Chen Manyun , Shu Yan , Li Qing , Kang Zhiqiang , Liu Tao , Zhou Honghao , Huang Weihua , Zhang Wei 
Published: July 2023

AbstractVitamin B12 (VB12) deficiency, which may lead to hematologic and neurologic symptoms, has been associated with metformin use, but the underlying mechanism is unclear. Here we report the B. ovatus as an effective VB12 catcher which was enriched in the type 2 diabetes patients suffered from VB12 deficiency after 3 to 6 months of metformin treatment. Colonization of B. ovatus increased the plasma levels of methylmalonic acid and homocysteine in high-fat diet (HFD)-fed mice treated with metformin, and compromised the efficacy of metformin against the HFD-induced metabolic disorders. Mechanistically, metformin increased the intracellular accumulation of VB12 in B. ovatus via btuB upregulation and promoted ATP production for energy-dependent translocation of VB12 transporters at the inner membrane, leading to an enhanced colonization of B. ovatus to compete for VB12 with hosts and subsequently an aggravated VB12 deficiency in the host. Our findings illustrate a previously unappreciated mechanism of metformin leads to host VB12 deficiency by acting directly on gut bacteria to increase their VB12 uptake and consumption, and suggest that inter-host-microbe competition for nutrients may broadly impact human health and drug safety.
Chemical generation of checkpoint inhibitory T cell engagers for the treatment of cancer
Authors: Szijj Peter A. , Gray Melissa A. , Ribi Mikaela K. , Bahou Calise , Nogueira João C. F. , Bertozzi Carolyn R. , Chudasama Vijay 
Published: July 2023

AbstractBispecific T cell engagers (BiTEs), a subset of bispecific antibodies (bsAbs), can promote a targeted cancer cell’s death by bringing it close to a cytotoxic T cell. Checkpoint inhibitory T cell engagers (CiTEs) comprise a BiTE core with an added immunomodulatory protein, which serves to reverse cancer-cell immune-dampening strategies, improving efficacy. So far, protein engineering has been the main approach to generate bsAbs and CiTEs, but improved chemical methods for their generation have recently been developed. Homogeneous fragment-based bsAbs constructed from fragment antigen-binding regions (Fabs) can be generated using click chemistry. Here we describe a chemical method to generate biotin-functionalized three-protein conjugates, which include two CiTE molecules, one containing an anti-PD-1 Fab and the other containing an immunomodulatory enzyme, Salmonella typhimurium sialidase. The CiTEs’ efficacy was shown to be superior to that of the simpler BiTE scaffold, with the sialidase-containing CiTE inducing substantially enhanced T cell-mediated cytotoxicity in vitro. The chemical method described here, more generally, enables the generation of multi-protein constructs with further biological applications.
Trastuzumab deruxtecan in metastatic breast cancer with variable HER2 expression: the phase 2 DAISY trial
Authors: Mosele Fernanda , Deluche Elise , Lusque Amelie , Le Bescond Loïc , Filleron Thomas , Pradat Yoann , Ducoulombier Agnes , Pistilli Barbara , Bachelot Thomas , Viret Frederic , Levy Christelle , Signolle Nicolas , Alfaro Alexia , Tran Diep T. N. , Garberis Ingrid Judith , Talbot Hugues , Christodoulidis Stergios , Vakalopoulou Maria , Droin Nathalie , Stourm Aurelie , Kobayashi Maki , Kakegawa Tomoya , Lacroix Ludovic , Saulnier Patrick , Job Bastien , Deloger Marc , Jimenez Marta , Mahier Celine , Baris Vianney , Laplante Pierre , Kannouche Patricia , Marty Virginie , Lacroix-Triki Magali , Diéras Veronique , André Fabrice 
Published: July 2023

AbstractThe mechanisms of action of and resistance to trastuzumab deruxtecan (T-DXd), an anti-HER2–drug conjugate for breast cancer treatment, remain unclear. The phase 2 DAISY trial evaluated the efficacy of T-DXd in patients with HER2-overexpressing (n = 72, cohort 1), HER2-low (n = 74, cohort 2) and HER2 non-expressing (n = 40, cohort 3) metastatic breast cancer. In the full analysis set population (n = 177), the confirmed objective response rate (primary endpoint) was 70.6% (95% confidence interval (CI) 58.3–81) in cohort 1, 37.5% (95% CI 26.4–49.7) in cohort 2 and 29.7% (95% CI 15.9–47) in cohort 3. The primary endpoint was met in cohorts 1 and 2. Secondary endpoints included safety. No new safety signals were observed. During treatment, HER2-expressing tumors (n = 4) presented strong T-DXd staining. Conversely, HER2 immunohistochemistry 0 samples (n = 3) presented no or very few T-DXd staining (Pearson correlation coefficient r = 0.75, P = 0.053). Among patients with HER2 immunohistochemistry 0 metastatic breast cancer, 5 of 14 (35.7%, 95% CI 12.8–64.9) with ERBB2 expression below the median presented a confirmed objective response as compared to 3 of 10 (30%, 95% CI 6.7–65.2) with ERBB2 expression above the median. Although HER2 expression is a determinant of T-DXd efficacy, our study suggests that additional mechanisms may also be involved. (ClinicalTrials.gov identifier NCT04132960.)
Unravelling geospatial distribution and genetic diversity of greenhouse whitefly, Trialeurodes vaporariorum (Westwood) from Himalayan Region
Authors: Paschapur Amit Umesh , Singh Ashish Kumar , Buski Ramesh , Guru P. N. , Jeevan B. , Mishra K. K. , Kant Lakshmi 
Published: July 2023

AbstractThe Greenhouse whitefly (GWF), Trialeurodes vaporariorum (Westwood) (Hemiptera: Aleyrodidae), is a destructive pest that affects protected cultivation worldwide. The Indian Himalayan region is particularly vulnerable to GWF introduction, invasion, and spread due to the expansion of protected cultivation and climate change. In this study, we collected 32 naturally occurring GWF populations, mainly from the Uttarakhand state in the Indian Himalayan region, to investigate the distribution pattern and genetic diversity of T. vaporariorum. Our sampling was representative of the region's vegetation diversity and geographical location, and we collected samples from multiple sites within each locality to account for local variations. The mtCOI gene was used to accurately detect and identify GWF and to sequence haplotypes prevalent in the Uttarakhand state. The maximum likelihood method used for phylogenetic studies revealed that all 32 whitefly samples in this study belonged to T. vaporariorum and were prevalent in all the collected localities. Our population genetic study using mtCOI showed variation within T. vaporariorum populations, with 20 distinct haplotypes present. Notably, haplotype 2 (H2) was the most dominant haplotype among the sampled populations. These results provide fundamental knowledge for understanding the geographical distribution and ecology of T. vaporariorum in the Uttarakhand state of the Indian Himalayan region. The discovery of geospatial and genetic diversity of GWF in the Himalayan region underscores the importance of pest alertness, research prioritization, and the development of sustainable management strategies to protect crops.