bluuebunny/crossref_metadata_2025_split huggingface dataset:
Soil water consumption characteristics in rain-fed apple orchards and wheat fields
Authors: Zhang Lu , Wang Yiquan , Sun Zenghui 
Published: April 2022

AbstractAgricultural production in Weibei rain-fed highland, Northwest China, is facing severe drought and water shortages. Here, soil water consumption characteristics in rain-fed orchards and farmlands were explored to ascertain the rationality of planting orchards in Weibei. Soil moisture dynamics was monitored in the 0–150-cm soil profiles of different aged ‘Red Fuji’ apple orchards (young: 7 years, mature: 13 years, and old: 22 years), and in long-term cultivated winter wheat fields during the growing season of apple trees. The over-consumption and consumption of soil water were analyzed to evaluate water stress and differential water consumption by distinct vegetation, respectively. Soil desiccation index was used to determine the occurrence of dry soil layers. Generally, there was no water stress in the 0–150-cm orchard soil profiles, while water stress was observed at the 0–70-cm soil depths in the old orchards (mid-June) and farmlands (mid-May–mid-July). Water consumption took place at deeper depths for longer periods in the older orchards than in the younger orchards. Soil desiccation was not observed in the young orchards, while mild desiccation occurred at the 0–80-cm soil depths in the mature and old orchards in mid-June. The desiccation intensity was mild at the 0–60-cm soil depths in mid-April–mid-May, intense at the soil 0–150-cm depths in mid-June, and moderate at the 20–150-cm soil depths in mid-July. In conclusion, conversion from wheat fields to apple orchards could reduce soil water stress, reduce dry soil layers, and mitigate soil desiccation in the rain-fed highland area.
Hemispheric Asymmetries of Individual Differences in Functional Connectivity
Authors: Perez Diana C. , Dworetsky Ally , Braga Rodrigo M. , Beeman Mark , Gratton Caterina 
Published: April 2022

AbstractResting-state fMRI studies have revealed that individuals exhibit stable, functionally meaningful divergences in large-scale network organization. The locations with strongest deviations (called network ‘variants’) have a characteristic spatial distribution, with qualitative evidence from prior reports suggesting that this distribution differs across hemispheres. Hemispheric asymmetries can inform us on constraints guiding the development of these idiosyncratic regions. Here, we used data from the Human Connectome Project to systematically investigate hemispheric differences in network variants. Variants were significantly larger in the right hemisphere, particularly along the frontal operculum and medial frontal cortex. Variants in the left hemisphere appeared most commonly around the temporoparietal junction. We investigated how variant asymmetries vary by functional network and how they compare with typical network distributions. For some networks, variants seemingly increase group-average network asymmetries (e.g., the group-average language network is slightly bigger in the left hemisphere and variants also appeared more frequently in that hemisphere). For other networks, variants counter the group-average network asymmetries (e.g., the default mode network is slightly bigger in the left hemisphere, but variants were more frequent in the right hemisphere). Intriguingly, left- and right-handers differed in their network variant asymmetries for the cinguloopercular and frontoparietal networks, suggesting that variant asymmetries are connected to lateralized traits. These findings demonstrate that idiosyncratic aspects of brain organization differ systematically across the hemispheres. We discuss how these asymmetries in brain organization may inform us on developmental constraints of network variants, and how they may relate to functions differentially linked to the two hemispheres.
Capped nascent RNA sequencing reveals novel therapy-responsive enhancers in prostate cancer
Authors: Cotter Kellie A. , Shah Sagar R. , Paramo Mauricio I. , Lou Shaoke , Yao Li , Rubin Philip D. , Chen You , Gerstein Mark , Rubin Mark A. , Yu Haiyuan 
Published: April 2022

AbstractMounting evidence suggests that enhancer RNA (eRNA) transcription start sites (TSSs) provide higher sensitivity and specificity for enhancer identification than histone modifications and chromatin accessibility. The extent to which changes in eRNA transcription correspond to changes in enhancer activity, however, remains unclear. Here, we used precision run-on and capped RNA sequencing (PRO-cap) to assess changes in enhancer activity in response to treatment with the androgen receptor signaling inhibitor, enzalutamide (ENZ). We identified 6,189 high-confidence candidate enhancers in the human prostate cancer cell line, LNCaP; 853 of which demonstrated significant changes in activity in response to drug treatment. Notably, we found that 67% and 54% of drug-responsive enhancers did not show similar changes in activity in previous studies that utilized ChIP-seq and ATAC-seq, respectively. Strikingly, 79% of regions with increased eRNA transcription showed no other biochemical alterations, implying that PRO-cap can capture a set of precise changes in enhancer activity that classical approaches lack the sensitivity to detect. We performed in vivo functional validations of candidate enhancers and found that CRISPRi targeting of PRO-cap-specific drug-responsive enhancers impaired ENZ regulation of downstream target genes, suggesting that changes in eRNA TSSs mark true biological changes in enhancer activity with high sensitivity. Our study highlights the utility of using PRO-cap as a complementary approach to canonical biochemical methods for detecting precise changes in enhancer activity and, in particular, for better understanding disease progression and responses to treatment.
Mutational scan inferred binding energetics and structure in intrinsically disordered protein CcdA
Authors: Chandra Soumyanetra , Manjunath Kavyashree , Asok Aparna , Varadarajan Raghavan 
Published: April 2022

AbstractUnlike globular proteins, mutational effects on the function of Intrinsically Disordered Proteins (IDPs) are not well-studied. Deep Mutational Scanning of a yeast surface displayed mutant library yields insights into sequence-function relationships in the CcdA IDP. The approach enables facile prediction of interface residues and local structural signatures of the bound conformation. In contrast to previous titration-based approaches which use a number of ligand concentrations, we show that use of a single rationally chosen ligand concentration can provide quantitative estimates of relative binding constants for large numbers of protein variants. This is because the extended interface of IDP ensures that energetic effects of point mutations are spread over a much smaller range than for globular proteins. Our data also provides insights into the much-debated role of helicity and disorder in partner binding of IDPs. Based on this exhaustive mutational sensitivity dataset, a model was developed to predict mutational effects on binding affinity of IDPs that form alpha-helical structures upon binding.
Cannabinoid 1/2 Receptor Activation Induces Strain-Dependent Behavioral and Neurochemical Changes in GAERS and NEC rats
Authors: De Deurwaerdère Philippe , Casarrubea Maurizio , Cassar Daniel , Radic Manuela , Puginier Emilie , Chagraoui Abdeslam , Crescimanno Giuseppe , Crunelli Vincenzo , Di Giovanni Giuseppe 
Published: April 2022

ABSTRACTChildhood absence epilepsy (CAE) is characterized by absence seizures which are episodes of lack of consciousness accompanied by electrographic spike-wave discharges. About 60% of children and adolescents with ASs are affected by major neuropsychological comorbidities, including anxiety. Endocannabinoids and monoamines are likely involved in the pathophysiology of these CAE psychiatric comorbidities.Here, we show that the synthetic cannabinoid receptor type 1/2 (CB1/2R) agonist WIN 55,212-2 (2 mg/kg, i.p.) has a strain-dependent effect on anxiety-like and motor behavior and cerebral monoaminergic levels in Genetic Absence Epilepsy Rats from Strasbourg (GAERS) and their non-epileptic control (NEC) rat strain. Using quantitative and Temporal-Pattern analysis, we found that WIN 55,212-2 did not affect the emotional status of GAERS but it was anxiolytic in NEC. Conversely, WIN 55,212-2 had a sedative effect in GAERS but was ineffective in NEC. Moreover, vehicle-treated GAERS are more motivated to explore by implementing more complex and articulated strategies. These behavioral changes correlate with the reduction of 5-HT in the hippocampus and substantia nigra (SN) and noradrenaline (NA) in the entopeduncular nucleus (EPN) in vehicle-treated GAERS compared to NEC rats which could contribute to their low anxiety status and hypermotility, respectively. On the other hand, the increased level of NA in the EPN and 5-HT in the SN is consistent with an activation of the basal ganglia output-mediated motor suppression observed in WIN 55,212-2-treated GAERS rats.These data support the view of a strain-dependent alteration of the endocannabinoid system by adding evidence of lower emotional responsiveness and a basal ganglia hypersensitivity to cannabinoids in GAERS compared to NEC rats.
A multi-omic dissection of super-enhancer driven oncogenic gene expression programs in ovarian cancer
Authors: Kelly Michael R. , Wisniewska Kamila , Regner Matthew J. , Lewis Michael W. , Perreault Andrea A. , Davis Eric S. , Phanstiel Douglas H. , Parker Joel S. , Franco Hector L. 
Published: April 2022

ABSTRACTThe human genome contains regulatory elements, such as enhancers, that are often rewired by cancer cells for the activation of genes that promote tumorigenesis and resistance to therapy. This is especially true for cancers that have little or no known driver mutations within protein coding genes, such as ovarian cancer. Herein, we have utilized an integrated set of genomic and epigenomic datasets to identify clinically relevant super-enhancers that are preferentially amplified in ovarian cancer patients. We have systematically probed the top 86 super-enhancers, using CRISPR-interference and CRISPR-deletion assays coupled to RNA-sequencing, to nominate two salient super-enhancers that drive proliferation and migration of cancer cells. Utilizing Hi-C, we constructed chromatin interaction maps that enabled the annotation of direct target genes for these super-enhancers and later confirmed their activity specifically within the cancer cell compartment of human tumors using single-cell genomics data. Together, our multi-omic approach has examined a number of fundamental questions about how regulatory information encoded into super-enhancers drives gene expression networks that underlie the biology of ovarian cancer.
Brain resident memory T cells rapidly expand and initiate neuroinflammatory responses following CNS injury and viral infection
Authors: Ayasoufi K , Wolf DM , Namen SL , Tritz ZP , Jin F , Pfaller CK , Goddery EN , Fain CE , Gulbicki LR , Khadka RH , Yokanovich LT , Hansen MJ , Johnson AJ 
Published: April 2022

AbstractThe contribution of circulating verses tissue resident memory T cells (TRM) to clinical neuropathology is an enduring question due to a lack of mechanistic insights. The prevailing view is TRM cells are protective against pathogens in the brain. However, the extent antigen-specific TRM cells can induce neuropathology upon reactivation has not been determined. Using the described phenotype of TRMs, we found that brains of naïve mice harbor populations of CD69+ CD103− T cells. Notably, numbers of CD69+ CD103− TRM cells rapidly increase following neurological insults of physical, cancerous, or viral origins. This TRM expansion precedes infiltration of virus specific CD8 T cells and is due to proliferation of T cells within the brain. In contrast, the CD69+ CD103+ TRMs in the brain are generated after the initial expansion of CD69+ CD103− cells following injury and are antigen-specific. We next evaluated the capacity of antigen-specific TRMs in the brain to induce significant neuroinflammation post virus clearance, including infiltration of inflammatory monocytes, activation of T cells in the brain, and significant blood brain barrier disruption. These neuroinflammatory events were induced by TRMs, as depletion of peripheral T cells or blocking T cell trafficking using FTY720 did not change the neuroinflammatory course. Reactivation of antigen-specific TRMs in the brain also induced profound lymphopenia within the blood compartment. We have therefore determined that antigen-specific TRMs can induce significant neuroinflammation, neuropathology, and peripheral immune suppression. Importantly, understanding functions of brain TRMs is crucial in investigating their role in neurodegenerative disorders, CNS cancers, and long-term complications associated with viral infections including COVID-19.Graphical AbstractHealthy brain harbors populations of resident memory T cells (TRM). These TRM cells rapidly proliferate in response to CNS insults of various origins. Following clearance of the insult, populations of TRM cells in the brain decline, but an antigen-specific TRM subset remains within the brain. Antigen-specific reactivation of brain TRMs mediates neuroinflammatory sequalae involving activation and blasting of resident T cells, infiltration of inflammatory monocytes and blood brain barrier disruption. Severe neuroinflammation within the brain following antigen-specific TRM reactivation is concurrent with profound lymphopenia within the blood compartment.
Pan-cancer quantification of neoantigen-mediated immunoediting in cancer evolution
Authors: Wu Tao , Wang Guangshuai , Wang Xuan , Wang Shixiang , Zhao Xiangyu , Wu Chenxu , Ning Wei , Tao Ziyu , Chen Fuxiang , Liu Xue-Song 
Published: April 2022

AbstractImmunoediting, which includes three temporally distinct stages, termed elimination, equilibrium, and escape, has been proposed to explain the interactions between cancer cells and the immune system during the evolution of cancer. However the status of immunoediting in cancer remains unclear, and the existence of neoantigen depletion signal in untreated cancer has been debated. Here we developed a distribution pattern based method for quantifying neoantigen mediated negative selection in cancer evolution. Our method provides a robust and reliable quantification for immunoediting signal in an individual cancer patient. The prevalence of immunoediting signal in immunotherapy untreated cancer genome has been demonstrated with this method. Importantly, the elimination and escape stages of immunoediting can be quantified separately, tumor types with strong immunoediting-elimination tend to have weak immunoediting-escape signal, and vice versa. Quantified immunoediting-elimination signal predicts cancer immunotherapy clinical response. Immunoediting quantification provides an evolutional perspective for evaluating the antigenicity of neoantigen, and reveals a potential biomarker for cancer precision immunotherapy.
Manipulating the 3D organization of the largest synthetic yeast chromosome
Authors: Zhang Weimin , Lazar-Stefanita Luciana , Yamashita Hitoyoshi , Shen Michael J. , Mitchell Leslie A. , Kurasawa Hikaru , Lobzaev Evgenii , Fanfani Viola , Haase Max A. B. , Sun Xiaoji , Jiang Qingwen , Goldberg Gregory W. , Ichikawa David M. , Lauer Stephanie L. , McCulloch Laura H. , Easo Nicole , Jiaming Lin S. , Camellato Brendan R. , Zhu Yinan , Cai Jitong , Xu Zhuwei , Zhao Yu , Sacasa Maya , Accardo Ryan , Ahn Ju Young , Annadanam Surekha , Brammer Basta Leighanne A. , Bello Nicholas R. , Cai Lousanna , Cerritos Stephanie , Cornwell MacIntosh , D’Amato Anthony , Hacker Maria , Hersey Kenneth , Kennedy Emma , Kianercy Ardeshir , Kim Dohee , Lim Hong Seo , McCutcheon Griffin , McGirr Kimiko , Meaney Nora , Meyer Lauren , Moyer Ally , Nimer Maisa , Sabbatini Carla , Shores Lucas S. , Silvestrone Cassandra , Snee Arden , Spina Antonio , Staiti Anthony , Stuver Matt , Tian Elli , Whearty Danielle , Zhao Calvin , Zheng Tony , Zhou Vivian , Scheifele Lisa , Zeller Karen , Noyes Marcus B. , Bader Joel S. , Deutsch Samuel , Stracquadanio Giovanni , Aizawa Yasunori , Dai Junbiao , Boeke Jef D. 
Published: April 2022

SummaryWhether synthetic genomes can power life has attracted broad interest in the synthetic biology field, especially when the synthetic genomes are extensively modified with thousands of designer features. Here we reportde novosynthesis of the largest eukaryotic chromosome thus far,synIV, a 1,454,621-bpSaccharomyces cerevisiaechromosome resulting from extensive genome streamlining and modification. During the construction ofsynIV, we developed megachunk assembly combined with a hierarchical integration strategy, which significantly increased the accuracy and flexibility of synthetic chromosome construction and facilitated chromosome debugging. In addition to the drastic sequence changes made tosynIVby rewriting it, we further manipulated the three-dimensional structure ofsynIVin the yeast nucleus to explore spatial gene regulation within the nuclear space. Surprisingly, we found few gene expression changes, suggesting that positioning inside the yeast nucleoplasm plays a minor role in gene regulation. Lastly, we tetheredsynIVto the inner nuclear membrane via its hundreds ofloxPsymsites and observed transcriptional repression of the entire chromosome, demonstrating chromosome-wide transcription manipulation without changing the DNA sequences. Our manipulation of the spatial structure of the largest synthetic yeast chromosome shed light on higher-order architectural design of the synthetic genomes.Graphical abstractHighlightsDe novosynthesis of the largest eukaryotic chromosome,synIVSynIVshows similar 3D structure to wild-type IV, despite thousands of changes made to it“Inside-out” repositioning ofsynIVin nucleus shows minor transcriptional changesMultipoint tetheringsynIVto inner nuclear membrane represses transcription of whole chromosome
Deterministic evolution and stringent selection during pre-neoplasia
Authors: Karlsson Kasper , Przybilla Moritz J. , Kotler Eran , Khan Aziz , Xu Hang , Karagyozova Kremena , Sockell Alexandra , Wong Wing H. , Liu Katherine , Mah Amanda , Lo Yuan-Hung , Lu Bingxin , Houlahan Kathleen E. , Ma Zhicheng , Suarez Carlos J. , Barnes Chris P. , Kuo Calvin J. , Curtis Christina 
Published: April 2022

AbstractThe earliest events during human tumor initiation, while poorly characterized, may hold clues to malignancy detection and prevention1. Here we model occult pre-neoplasia by bi-allelically inactivatingTP53, a common early event in gastric cancer, in human gastric organoids. Causal relationships between this initiating genetic lesion and resulting phenotypes were established using experimental evolution in multiple clonally derived cultures over two years.TP53loss elicited progressive aneuploidy, including copy number alterations and structural variants prevalent in gastric cancers, with evident preferred orders. Longitudinal single cell sequencing ofTP53deficient gastric organoids similarly indicates progression towards malignant transcriptional programs. Moreover, high-throughput lineage tracing with expressed cellular barcodes demonstrates reproducible dynamics whereby initially rare subclones with shared transcriptional programs repeatedly attain clonal dominance. This powerful platform for experimental evolution exposes stringent selection, clonal interference, and a striking degree of phenotypic convergence in pre-malignant epithelial organoids. These data imply predictability in the earliest stages of tumorigenesis and reveal evolutionary constraints and barriers to malignant transformation with implications for earlier detection and interception of aggressive, genome instable tumors.
Structure of phage λ Redβ177 annealase shows how it anneals DNA strands during single-strand annealing homologous DNA recombination
Authors: Newing Timothy , Brewster Jodi L. , Yu Haibo , Johnston Nikolas P. , Fitschen Lucy J. , Tolun Gökhan 
Published: April 2022

AbstractThe bacteriophage λ red recombination system catalyzes the single-strand annealing homologous DNA recombination reaction, in which Redβ annealase protein plays a critical role. Using cryogenic electron microscopy, we were able to determine a structure of a C-terminally truncated Redβ with the residues 1-177 bound to two complementary 27mer oligonucleotides forming an annealing intermediate, to a final resolution of 3.3 Å. This structure validates and rationalizes decades of experimental observations on the biochemistry of Redβ. Definition of the interaction surfaces between subunits explains not only the DNA binding properties of Redβ, but also its propensity to oligomerize into long helical filaments, which are also formed by almost all annealases and are known to be functionally important. In addition, this annealing intermediate structure provides a detailed picture of the hydrogen bonding network that positions the DNA strands in a planar orientation to facilitate base pairing. Residues 133-138, which are missing from our structure, form a flexible loop. Molecular dynamics simulations were used to model the range of motion of the flexible loop, which suggested that it has a crucial role in keeping the DNA strands in the DNA-binding groove long enough to allow homology searching. The combination of structural and computational observations has allowed us to propose a detailed mechanism for the action of Redβ. More than half a century after its discovery, our work shines a light not only on the structure and mechanisms of Redβ, but also of other proteins within the annealase superfamilies.Significance StatementSingle-strand annealing homologous DNA recombination is a process that is conserved throughout evolution from bacteriophages to humans, highlighting its importance and indispensability. It is a process that repairs double-stranded DNA breaks and is particularly vital in dsDNA viruses. The Redβ protein from the bacteriophage lambda is the archetypal annealase protein, forming the basis of our knowledge about this class of proteins. Along with the exonuclease λExo, these two proteins not only form the model system for single-strand annealing homologous recombination, but are also used in thousands of laboratories worldwide for performing genetic manipulations. After its discovery in 1966, we report the first structure of the DNA-binding and oligomerization domain of Redβ, providing details about the mechanism of homologous DNA annealing.
Life-long Dietary Restrictions have Negligible or Damaging Effects on Late-life Cognitive Performance: A Key Role for Genetics in Outcomes
Authors: Ouellette Andrew R. , Hadad Niran , Deighan Andrew , Robinson Laura , O’Connell Kristen , Freund Adam , Churchill Gary A. , Kaczorowski Catherine C. 
Published: April 2022

AbstractSeveral studies report that caloric restriction (CR) or intermittent fasting (IF) can improve cognition, while others report limited or no cognitive benefits. Here, we compare the effects of 20% CR, 40% CR, 1-day IF, and 2-day IF feeding paradigms to ad libitum controls (AL) on Y-maze working memory and contextual fear memory (CFM) in a large population of Diversity Outbred mice that model the genetic diversity of humans. While CR and IF interventions improve lifespan, we observed no enhancement of working memory or CFM in mice on these feeding paradigms, and report 40% CR to be damaging in the context of long-term memory. Using Quantitative Trait Loci mapping, we identified the gene Slc16a7 to be associated with late-life long-term memory outcomes in mice on lifespan promoting feeding paradigms. Limited utility of dieting and fasting on memory in mice that recapitulate genetic diversity in the human population highlights the need for anti-aging therapeutics that promote cognitive function, with a neuronal monocarboxylate transporter encoded by Slc16a7 highlighted as novel target.