Warming in mountain regions is projected to occur three times faster than the global average. Recently, a small number of observational studies have reported species loss in mountain plant ...communities and have explored mechanisms facilitating the colonization by novel species. We monitored translocated mountain plant communities and their novel competitor interactions following five years of exposure to downslope climates. We found increasing species turnover under two future climate scenarios with time. Local loss of native species was followed by the colonization by novel species after a severe drought year in the third year after translocation. Here, the assumed mechanism facilitating novel species colonization in mountain communities is direct environmental filtering. We find a time lag between the local loss of native species and the colonization by novel species, which can be explained by interacting climate stressors-that is, warming and drought-pushing communities across a threshold of resistance to colonization. Interestingly, despite significant changes in species identity and strong colonization by novel species, the proportional contribution of plant functional groups to aboveground biomass stayed stable across both sites of origin and over time. Our study provides experimental evidence of local species loss in mountain plant communities prone to severe climatic change, revealing abrupt threshold dynamics.
Integer-valued autoregressive (INAR) processes form a very useful class of processes suitable to model time series of counts. Several practically relevant estimators based on INAR data are known to ...be systematically biased away from their population values, e.g. sample autocovariances, sample autocorrelations, or the dispersion index. We propose to do bias correction for such estimators by using a recently proposed INAR-type bootstrap scheme that is tailor-made for INAR processes, and which has been proven to be asymptotically consistent under general conditions. This INAR bootstrap allows an implementation with and without parametrically specifying the innovations' distribution. To judge the potential of corresponding bias correction, we compare these bootstraps in simulations to several competitors that include the AR bootstrap and block bootstrap. Finally, we conclude with an illustrative data application.
•Hepatitis B virus (HBV) infection continues to be a major global burden.•Gaps remain in addressing HBV infections in the developing world.•Risk factors for incident HBV infections in blood donors ...are not well described.•Risk factors for incident HBV infections differ between males and females.•Sexual behaviors are key risks for incident HBV in blood donors in South Africa.
Hepatitis B virus (HBV) infection remains a global health problem. Risk factors for HBV infection are usually assessed in prevalent rather than incident infections. To identify demographic and behavioral risks associated with incident HBV among South African blood donors.
A case-control study was performed between November 2014 and January 2018. Cases were blood donors testing positive for HBV DNA with or without hepatitis B surface antigen but negative for antibody to hepatitis B core antigen. Participants completed an audio computer-assisted structured interview on exposures during the previous 6 months. Sex-specific multivariable logistic regression yielded independent associations between risks and HBV infection.
56 females and 37 males with incident HBV were compared to 438 female and 439 male controls, respectively. For females, risk factors were accepting money or goods for sex, using agents to prepare one's anus prior to anal sex, penetrating injury, non-Black race, and lower educational status. Men reporting homosexual or bisexual orientation or sex with other men, previous injury, referral for HBV testing, or lack of medical insurance were at increased risk. For both sexes, having more than two male sexual partners increased risk.
Sexual behaviors predominated over parenteral exposures as risks for incident HBV in both female and male blood donors.
In March 2019, a scientific meeting was held at the University of California, Los Angeles (UCLA) Luskin Center to discuss approaches to expedite the translation of neurobiological insights to ...advances in the treatment of alcohol use disorder (AUD). A guiding theme that emerged was that while translational research in AUD is clearly a challenge, it is also a field ripe with opportunities. Herein, we seek to summarize and disseminate the recommendations for the future of translational AUD research using four sections. First, we briefly review the current landscape of AUD treatment including the available evidence‐based treatments and their uptake in clinical settings. Second, we discuss AUD treatment development efforts from a translational science viewpoint. We review current hurdles to treatment development as well as opportunities for mechanism‐informed treatment. Third, we consider models of translational science and public health impact. Together, these critical insights serve as the bases for a series of recommendations and future directions. Towards the goal of improving clinical care and population health for AUD, scientists are tasked with bolstering the clinical applicability of their research findings so as to expedite the translation of knowledge into patient care.
This manuscript summarizes and disseminates recommendations for the future of translational research in alcohol use disorder. It reviews the landscape of alcohol use disorder treatment and discusses treatment development opportunities. It also considers various models of translational science and provides a series of recommendations for research in the field.
Cerebellar cortical throughput involved in motor control comprises granule cells (GCs) and Purkinje cells (PCs), both of which receive inhibitory GABAergic input from interneurons. The GABAergic ...input to PCs is essential for learning and consolidation of the vestibulo‐ocular reflex, but the role of GC excitability remains unclear. We now disrupted the Kcc2 K‐Cl cotransporter specifically in either cell type to manipulate their excitability and inhibition by GABAA‐receptor Cl− channels. Although Kcc2 may have a morphogenic role in synapse development, Kcc2 disruption neither changed synapse density nor spine morphology. In both GCs and PCs, disruption of Kcc2, but not Kcc3, increased Cl−i roughly two‐fold. The reduced Cl− gradient nearly abolished GABA‐induced hyperpolarization in PCs, but in GCs it merely affected excitability by membrane depolarization. Ablation of Kcc2 from GCs impaired consolidation of long‐term phase learning of the vestibulo‐ocular reflex, whereas baseline performance, short‐term gain‐decrease learning and gain consolidation remained intact. These functions, however, were affected by disruption of Kcc2 in PCs. GC excitability plays a previously unknown, but specific role in consolidation of phase learning.
The cerebellar circuitry underlying motor control and learning consists of granule cells (GCs) and Purkinje cells (PCs). Deletion of the Kcc2 K‐Cl cotransporter ablates Cl− extrusion in both cell types. Unexpectedly, a critical role for GC excitability in the consolidation of motor learning is uncovered.
Meiosis generates four haploid daughters from a diploid parental cell. Central steps of meiosis are the pairing and recombination of homologous chromosomes followed by their segregation in two rounds ...of cell division. Meiotic recombination is monitored by a specialized DNA damage checkpoint pathway and is guided by a unique chromosomal structure called synaptonemal complex (SC), but how these events are coordinated is unclear. Here, we identify the SC protein Red1 as a crucial regulator of early meiosis. Red1 interacts with two subunits of the 9-1-1 checkpoint complex via two distinct 9-1-1 subunit-specific motifs. Association of 9-1-1 with Red1 is essential not only for meiotic checkpoint activation but for SC formation. Moreover, Red1 becomes SUMO-modified, which fosters interaction of Red1 with the central SC element Zip1, thereby securing timely SC formation. Thus, Red1, in addition to its structural role in the SC, is a crucial coordinator of meiosis by coupling checkpoint signaling to SC formation.
Increasingly, restoration ecologists and managers are challenged to restore ecological processes that lead to self-sustaining ecosystem dynamics. Due to changing environmental conditions, however, ...restoration goals need to include novel regimes beyond prior reference conditions or reference dynamics. In face of these fundamental challenges in process-based restoration ecology, disturbance ecology can offer useful insights. Here, I discuss the contribution of disturbance ecology to understanding assembly rules, ecosystem dynamics, regime shifts, and nonlinear dynamics. Using the patch and multipatch concept, all insights are organized according to two spatial and two temporal categories: "patch-event,""patch-multievent,""multipatch-event," and "multipatch-multievent." This concept implies the consideration of both spatial patterns and temporal rhythms inside and outside of a restoration site. Emerging issues, such as uncoupling of internal and external dynamics, are considered.
Popular models for time series of count data are integer-valued autoregressive (INAR) models, for which the literature mainly deals with parametric estimation. In this regard, a semiparametric ...estimation approach is a remarkable exception which allows for estimation of the INAR models without any parametric assumption on the innovation distribution. However, for small sample sizes, the estimation performance of this semiparametric estimation approach may be inferior. Therefore, to improve the estimation accuracy, we propose a penalized version of the semiparametric estimation approach, which exploits the fact that the innovation distribution is often considered to be smooth, i.e. two consecutive entries of the PMF differ only slightly from each other. This is the case, for example, in the frequently used INAR models with Poisson, negative binomially or geometrically distributed innovations. For the data-driven selection of the penalization parameter, we propose two algorithms and evaluate their performance. In Monte Carlo simulations, we illustrate the superiority of the proposed penalized estimation approach and argue that a combination of penalized and unpenalized estimation approaches results in overall best INAR model fits.
In modelling seasonal time series data, periodically (non‐)stationary processes have become quite popular over the last years and it is well known that these models may be represented as ...higher‐dimensional stationary models. In this article, it is shown that the spectral density matrix of this higher‐dimensional process exhibits a certain structure if and only if the observed process is covariance stationary. By exploiting this relationship, a new L2‐type test statistic is proposed for testing whether a multivariate periodically stationary linear process is even covariance stationary. Moreover, it is shown that this test may also be used to test for periodic stationarity. The asymptotic normal distribution of the test statistic under the null is derived and the test is shown to have an omnibus property. The article concludes with a simulation study, where the small sample performance of the test procedure is improved by using a suitable bootstrap scheme.
The functions of some CLC Cl− channels are evident from human diseases that result from their mutations, but the role of the broadly expressed ClC‐2 Cl− channel is less clear. Several important ...functions have been attributed to ClC‐2, but contrary to these expectations ClC‐2‐deficient mice lacked overt abnormalities except for a severe degeneration of the retina and the testes, which led to selective male infertility. Seminiferous tubules did not develop lumina and germ cells failed to complete meiosis. Beginning around puberty there was a massive death of primary spermatocytes and later also of spermatogonia. Tubules were filled with abnormal Sertoli cells, which normally express ClC‐2 in patches adjacent to germ cells. In the retina, photoreceptors lacked normal outer segments and degenerated between days P10 and P30. The current across the retinal pigment epithelium was severely reduced at P36. Thus, ClC‐2 disruption entails the death of two cell types which depend on supporting cells that form the blood–testes and blood–retina barriers. We propose that ClC‐2 is crucial for controlling the ionic environment of these cells.
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