bluuebunny/crossref_metadata_2025_split huggingface dataset:
How Plants Recalibrate Cellular Iron Homeostasis
Authors: Vélez-Bermúdez Isabel Cristina , Schmidt Wolfgang 
Published: November 2021

Abstract
Insufficient iron supply poses severe constraints on plants, restricting species with inefficient iron uptake mechanisms from habitats with low iron availability and causing yield losses in agricultural ecosystems. Iron deficiency also poses a severe threat on human health. Anemia resulting from insufficient iron intake is affecting one of four people in the world. It is, therefore, imperative to understand the mechanisms by which plants acquire iron against a huge soil-cell gradient and how iron is distributed within the plant to develop strategies that increase its concentration in edible plant parts. Research into the processes that are employed by plants to adjust cellular iron homeostasis revealed an astonishingly complex puzzle of signaling nodes and circuits, which are intertwined with the perception and communication of other environmental cues such as pathogens, light, nutrient availability and edaphic factors such as pH. In a recent Spotlight issue in this journal, a collection of review articles summarized the state-of-the-art in plant iron research, covering the most active and, debatably, most important topics in this field. Here, we highlight breakthroughs that were reported after the publication date of this review collection, focusing on exciting and potentially influential studies that have changed our understanding of plant iron nutrition.
The MADS-domain factor AGAMOUS-Like18 promotes somatic embryogenesis
Authors: Paul Priyanka , Joshi Sanjay , Tian Ran , Diogo Junior Rubens , Chakrabarti Manohar , Perry Sharyn E 
Published: November 2021

Abstract
AGAMOUS-Like 18 (AGL18) is a MADS domain transcription factor (TF) that is structurally related to AGL15. Here we show that, like AGL15, AGL18 can promote somatic embryogenesis (SE) when ectopically expressed in Arabidopsis (Arabidopsis thaliana). Based on loss-of-function mutants, AGL15 and AGL18 have redundant functions in developmental processes such as SE. To understand the nature of this redundancy, we undertook a number of studies to look at the interaction between these factors. We studied the genome-wide direct targets of AGL18 to characterize its roles at the molecular level using chromatin immunoprecipitation (ChIP)-SEQ combined with RNA-SEQ. The results demonstrated that AGL18 binds to thousands of sites in the genome. Comparison of ChIP-SEQ data for AGL15 and AGL18 revealed substantial numbers of genes bound by both AGL15 and AGL18, but there were also differences. Gene ontology analysis revealed that target genes were enriched for seed, embryo, and reproductive development as well as hormone and stress responses. The results also demonstrated that AGL15 and AGL18 interact in a complex regulatory loop, where AGL15 inhibited transcript accumulation of AGL18, while AGL18 increased AGL15 transcript accumulation. Co-immunoprecipitation revealed an interaction between AGL18 and AGL15 in somatic embryo tissue. The binding and expression analyses revealed a complex crosstalk and interactions among embryo TFs and their target genes. In addition, our study also revealed that phosphorylation of AGL18 and AGL15 was crucial for the promotion of SE.
Multiple linear regression and linear mixed models identify novel traits of salinity tolerance in Olea europaea L.
Authors: Sodini Mirko , Astolfi Stefania , Francini Alessandra , Sebastiani Luca 
Published: November 2021

Abstract
Olive can be considered as moderately tolerant to salinity, with marked differences among cultivars. In the present study, two olive cultivars with different salt tolerance, ‘Leccino’ (sensitive) and ‘Frantoio’ (tolerant), were treated with 120 mM of NaCl for 30 days. We measured the expression of genes involved in the management of sodium in the leaves, such as NHX, SOS1 and H+ ATPase, and the concentration of Na+, K+, Mn2+, Mg2+ and Ca2+ in the roots, bark, xylem and leaves of the olive plants. The results were analyzed with multiple linear models and mixed models. Furthermore, we utilized the analysis of covariance to find significant relationships in our data. Both cultivars significantly reduced net photosynthesis and increased water-use efficiency after 30 days of treatment. Sodium accumulated significantly in the roots of both cultivars, and ‘Leccino’ plants were also able to translocate it to the leaves and the bark. The NHX and vacuolar ATPase subunit E genes were significantly overexpressed in both the cultivars treated with NaCl. The SOS1, ATPase11 and ATPase8 genes were overexpressed in ‘Frantoio’. The covariance between gene expression and element concentrations data was analyzed to identify significant interactions between cultivars and treatments. Na+ accumulation in the roots of ‘Frantoio’ was positively related to the accumulation of K+, Mn2+, Mg2+ and Ca2+ in the xylem, bark and leaves. ‘Frantoio’ capability to mobilize elements, especially Ca2+, together with the overexpression of key genes for sodium management, could be crucial for salt tolerance.
Herpes simplex viruses (1 and 2) and varicella-zoster virus infections in an adult population with aseptic meningitis or encephalitis
Authors: Lee Gha-Hyun , Kim Jiyoung , Kim Hyun-Woo , Cho Jae Wook 
Published: November 2021

Abstract
Three α-herpesviruses are known to be associated with central nervous system (CNS) infection; however, there are limited data on the incidence and clinical characteristics of α-herpesviruses CNS infections. This study aimed to assess the clinical manifestations, laboratory findings, and outcomes in patients with human herpes simplex virus 1 (HSV-1), human herpes simplex virus 2 (HSV-2), and varicella-zoster virus (VZV) CNS infections.
We identified cases of HSV-1, HSV-2, and VZV CNS infections and reviewed their clinical and laboratory characteristics. The study population was drawn from patients with HSV-1, HSV-2, and VZV polymerase chain reaction positivity in cerebrospinal fluid (CSF) who visited Pusan National University Hospital between 2010 and 2018.
During the 9-year study period, a total of 727 CSF samples were examined, with 72.2% (525/727) patients identified as having a CNS infection. Of 471 patients with aseptic meningitis and encephalitis, the causative virus was identified in 145 patients, and no virus was detected in 337 patients. A total of 15.2% (80/525) were diagnosed with one of the 3 herpesviruses as causative agents, 59 patients had meningitis, and 21 patients had encephalitis. Eleven patients with HSV-1, 27 patients with HSV-2, and 42 patients with VZV CNS infections were included. The distribution of cases by age showed different patterns depending on the type of herpesvirus infection. Compared with the HSV-1 group, the median age in the HSV-2 group was younger (HSV-1: 58 years; HSV-2: 38 years; P = .004), and patients with VZV infections showed a bimodal age distribution. Encephalitis was more common in the HSV-1 group, and HSV-1 infection was associated with a poor prognosis at discharge. CSF white blood cell counts were significantly lower in patients infected with HSV-1 (117 × 106 cells/L) than in patients infected with VZV (301 × 106 cells/L) (P = .008).
These 3 herpesviruses are important causes of CNS infections regardless of immunologic status. HSV-1 infection was commonly associated with encephalitis and poor prognosis; HSV-2 and VZV CNS infections were associated with a low risk of mortality and neurological sequelae.
Community Resilience: A Dynamic Model for Public Health 3.0
Authors: Ellis Wendy , Dietz William H. , Chen Kuan-Lung Daniel 
Published: November 2021

Objective:
To establish a model for Public Health 3.0 in order to define and measure community resilience (CR) as a method to measure equity, address structural racism, and improve population health.

Design:
To develop the CR model, we conducted a literature review in medicine, psychology, early childhood development, neurobiology, and disaster preparedness and response and applied system dynamics modeling to analyze the complex interactions between public systems, policies, and community.

Main Outcome Measures:
The CR model focuses on community and population health outcomes associated with the policies and practices of the housing, public education, law enforcement, and criminal justice sectors as CR measures. The model demonstrates how behaviors of these systems interact and produce outcome measures such as employment, homelessness, educational attainment, incarceration, and mental and physical health.

Results:
The policies and practices within housing, public schools, law enforcement, and criminal justice can suppress resilience for families and communities because they are shaped by structural racism and influence the character and nature of resources that promote optimal community health and well-being.

Conclusions:
Community resilience is relational and place-based and varies depending on the demographic makeup of residents, historical patterns of place-based racism and discrimination, jurisdictional policy, and investment priorities—all influenced by structural racism.

Implications for Policy and Practice:
Using system dynamics modeling and the CR approach, chief health strategists can convene partners from multiple sectors to systematically identify, measure, and address inequities produced by structural racism that result in and contribute to adverse childhood and community experiences.
Leveraging Collective Impact to Address Structural Racism in Buncombe County, North Carolina
Authors: Hunter Dawn M. , Mpofu Zo 
Published: November 2021

Buncombe County, North Carolina, was recognized in 2014 as a Robert Wood Johnson Foundation Culture of Health Prize Winner for its work fostering collaboration and partnership to address community health needs. As part of this work, Buncombe County Health and Human Services (HHS) convened a cross-sector Public Health Advisory Council that supported community-based initiatives and ensured that community members were involved in identifying and implementing solutions to issues such as poverty and child well-being.
Leveraging existing relationships and past efforts, Buncombe County has continued to build collaborative networks for systems change using a collective impact framework. Bringing together partners across sectors, including the faith community, Black fraternities and sororities, community health workers, consulates, and others, Buncombe County HHS is supporting efforts to train and equip community members to lead health promotion efforts and community conversations on historical trauma and racial healing; engage community members in the policymaking process through town halls; and archive the community's pandemic journey through storytelling. The collective impact framework has shaped an environment that supports community change by centering community aspirations and values. This environment informed recent declarations by Buncombe County HHS and the Board of Commissioners that racism is a public health crisis, as well as a resolution by the city of Asheville supporting community reparations.
This article explores how the collective impact framework has been used in Buncombe County to engage and continually invest in communities of color and reviews steps taken to develop and implement an equity action plan to address structural racism.
Predictors of Mortality in Neonatal Shock: A Retrospective Cohort Study
Authors: Saini Shiv Sajan , Shrivastav Amit Kumar , Kumar Jogender , Sundaram Venkataseshan , Mukhopadhyay Kanya , Dutta Sourabh , Ray Pallab , Kumar Praveen 
Published: November 2021

ABSTRACT

Objectives:
To study the incidence, clinical profile, and predictors of mortality in neonatal shock.

Methods:
We enrolled consecutive inborn neonates, who developed shock during hospital stay (between January 1, 2018 to December 31, 2019) at a tertiary-care, research center of northern India. We retrieved the clinical data from our electronic database, case record files, nursing charts, and laboratory investigations from the hospital's Health Information System. Non-survivors were compared with survivors to identify independent predictors of mortality.

Results:
We had 3,271 neonatal admissions during the study period. We recorded 415 episodes of neonatal shock in 392 neonates [incidence 12.0% (95% confidence interval: 10.9%–13.2%)]. Of 415 episodes, 237 (57%) episodes were identified as septic shock, 67 (16%) episodes as cardiogenic shock, and six (1.4%) episodes as obstructive shock. Remaining 105 (25%) episodes were contributed by more than one etiology of shock. There were 242 non-survivors among 392 neonates with shock (case fatality rate: 62%). On univariate analysis, gestational age, birth weight, incidence of hyaline membrane disease, early-onset sepsis, Acinetobacter sepsis, and cardiogenic shock were significantly different between survivors and non-survivors. Female gender and small for gestational age (SGA) neonates showed a trend of significance. On multivariable regression analysis, we found gestational age, SGA neonates, female gender, and Acinetobacter sepsis to have an independent association with mortality.

Conclusions:
Septic shock was the commonest cause of neonatal shock at our center. Neonatal shock had very high case fatality rate. Gestational age, SGA, female gender, and Acinetobacter sepsis independently predicted mortality in neonatal shock.
Disentangling signatures of selection before and after European colonization in Latin Americans
Authors: Mendoza-Revilla Javier , Chacón-Duque Juan Camilo , Fuentes-Guajardo Macarena , Ormond Louise , Wang Ke , Hurtado Malena , Villegas Valeria , Granja Vanessa , Acuña-Alonzo Victor , Jaramillo Claudia , Arias William , Lozano Rodrigo Barquera , Gómez-Valdés Jorge , Villamil-Ramírez Hugo , Silva de Cerqueira Caio C. , Badillo Rivera Keyla M. , Nieves-Colón Maria A. , Gignoux Christopher R. , Wojcik Genevieve L. , Moreno-Estrada Andrés , Hunemeier Tábita , Ramallo Virginia , Schuler-Faccini Lavinia , Gonzalez-José Rolando , Bortolini Maria-Cátira , Canizales-Quinteros Samuel , Gallo Carla , Poletti Giovanni , Bedoya Gabriel , Rothhammer Francisco , Balding David , Fumagalli Matteo , Adhikari Kaustubh , Ruiz-Linares Andrés , Hellenthal Garrett 
Published: November 2021

AbstractThroughout human evolutionary history, large-scale migrations have led to intermixing (i.e., admixture) between previously separated human groups. While classical and recent work have shown that studying admixture can yield novel historical insights, the extent to which this process contributed to adaptation remains underexplored. Here, we introduce a novel statistical model, specific to admixed populations, that identifies loci under selection while determining whether the selection likely occurred post-admixture or prior to admixture in one of the ancestral source populations. Through extensive simulations we show that this method is able to detect selection, even in recently formed admixed populations, and to accurately differentiate between selection occurring in the ancestral or admixed population. We apply this method to genome-wide SNP data of ~4,000 individuals in five admixed Latin American cohorts from Brazil, Chile, Colombia, Mexico and Peru. Our approach replicates previous reports of selection in the HLA region that are consistent with selection post-admixture. We also report novel signals of selection in genomic regions spanning 47 genes, reinforcing many of these signals with an alternative, commonly-used local-ancestry-inference approach. These signals include several genes involved in immunity, which may reflect responses to endemic pathogens of the Americas and to the challenge of infectious disease brought by European contact. In addition, some of the strongest signals inferred to be under selection in the Native American ancestral groups of modern Latin Americans overlap with genes implicated in energy metabolism phenotypes, plausibly reflecting adaptations to novel dietary sources available in the Americas.
Transcription Factor Gene Pea3 Regulates Erectile Function in Mice
Authors: Weinrich Jarret A.P. , Tyagi Aanchal , Kenney Megan C. , DiCasoli Richard J. , Kaltschmidt Julia A. 
Published: November 2021

ABSTRACTBackgroundMale mice with homozygous loss of function mutations of the ETS transcription factor gene Pea3 (Pea3 null) are infertile due to their inability to deposit semen plugs, however the specific deficits in male sexual behaviors that drive this phenotype are unknown.AimTo investigate the regulatory role of the Pea3 gene in organizing gross sexual behaviors and erectile functioning during active copulation.MethodsThe copulatory behavior of male mice (Pea3 null and control) with hormonally primed ovariectomized females was monitored via high-speed and high-resolution digital videography to assess for differences in female-directed social behaviors, gross sexual behaviors (mounting, thrusting), and erectile and ejaculatory function.OutcomesPea3 null male mice have dramatically reduced erectile function during sexual intercourse, however other aspects of male sexual behaviors are largely intact.ResultsPea3 null male mice exhibit greatly reduced erectile function, with 44% of males displaying no visible erections during mounting behaviors, and none achieving sustained erections. As such, Pea3 null males are incapable of intromission, and semen plug deposition, despite displaying largely normal female-directed social behaviors, mounting behaviors, and ejaculatory grasping behavior. Additionally, the coordination of the timing of thrusting trains is impaired in Pea3 null males.Clinical ImplicationsThe identification of the transcription factor Pea3 in regulating erectile function in mice may provide a useful target for understanding the genetics of male sexual dysfunction in human patients.Strengths and LimitationsHigh-speed and high-resolution videography allows for a detailed analysis of male sexual behaviors and erectile functioning in Pea3 null and control mice. How disruption of the Pea3 gene translates to erectile dysfunction is still unknown.ConclusionThe transcription factor gene Pea3 regulates the ability to achieve and maintain erections in male mice.
Intrinsic bursts facilitate learning of Lévy flight movements in recurrent neural network models
Authors: Ohta Morihiro , Asabuki Toshitake , Fukai Tomoki 
Published: November 2021

AbstractIsolated spikes and bursts of spikes are thought to provide the two major modes of information coding by neurons. Bursts are known to be crucial for fundamental processes between neuron pairs, such as neuronal communications and synaptic plasticity. Deficits in neuronal bursting can also impair higher cognitive functions and cause mental disorders. Despite these findings on the roles of bursts, whether and how bursts have an advantage over isolated spikes in the network-level computation remains elusive. Here, we demonstrate in a computational model that not isolated spikes but intrinsic bursts can greatly facilitate learning of Lévy flight random walk trajectories by synchronizing burst onsets across neural population. Lévy flight is a hallmark of optimal search strategies and appears in cognitive behaviors such as saccadic eye movements and memory retrieval. Our results suggest that bursting is a crucial component of sequence learning by recurrent neural networks in the brain.
cSurvival: a web resource for biomarker interactions in cancer outcomes
Authors: Cheng Xuanjin , Liu Yongxing , Wang Jiahe , Chen Yujie , Robertson A. Gordon , Zhang Xuekui , Jones Steven J. M. , Taubert Stefan 
Published: November 2021

ABSTRACTSurvival analysis is a technique to identify prognostic biomarkers and genetic vulnerabilities in cancer studies. Large-scale consortium-based projects have profiled >11,000 adult and >4,000 paediatric tumor cases with clinical outcomes and multi-omics approaches. This provides a resource for investigating molecular-level cancer etiologies using clinical correlations. Although cancers often arise from multiple genetic vulnerabilities and have deregulated gene sets (GSs), existing survival analysis protocols can report only on individual genes. Additionally, there is no systematic method to connect clinical outcomes with experimental (cell line) data. To address these gaps, we developed cSurvival (https://tau.cmmt.ubc.ca/cSurvival). cSurvival provides a user-adjustable analytical pipeline with a curated, integrated database, and offers three main advances: (a) joint analysis with two genomic predictors to identify interacting biomarkers, including new algorithms to identify optimal cutoffs for two continuous predictors; (b) survival analysis not only at the gene, but also the GS level; and (c) integration of clinical and experimental cell line studies to generate synergistic biological insights. To demonstrate these advances, we report three case studies. We confirmed findings of autophagy-dependent survival in colorectal cancers and of synergistic negative effects between high expression of SLC7A11 and SLC2A1 on outcomes in several cancers. We further used cSurvival to identify high expression of the Nrf2-antioxidant response element pathway as a main indicator for lung cancer prognosis and for cellular resistance to oxidative stress-inducing drugs. Together, these analyses demonstrate cSurvival’s ability to support biomarker prognosis and interaction analysis via gene- and GS-level approaches and to integrate clinical and experimental biomedical studies.Key pointsWe developed cSurvival, an advanced framework using clinical correlations to study biomarker interactions in cancers, with source code and curated datasets freely available for allcSurvival includes new algorithms to identify optimal cutoffs for two continuous predictors to stratify patients into risk groups, enabling for the first time joint analysis with two genomic predictors;cSurvival allows survival analysis at the gene set (GS) level with comprehensive and up-to-date GS librariesThe cSurvival pipeline integrates clinical outcomes and experimental cancer cell line data to generate synergistic biological insights and to mine for appropriate preclinical cell line toolscSurvival is built on a manually curated cancer outcomes database