Lack of Detectable HIV-1 Molecular Evolution during Suppressive Antiretroviral Therapy

A better understanding of changes in HIV-1 population genetics with combination antiretroviral therapy (cART) is critical for designing eradication strategies. We therefore analyzed HIV-1 genetic variation and divergence in patients' plasma before cART, during suppression on cART, and after viral rebound. Single-genome sequences of plasma HIV-1 RNA were obtained from HIV-1 infected patients prior to cART (N = 14), during suppression on cART (N = 14) and/or after viral rebound following interruption of cART (N = 5). Intra-patient population diversity was measured by average pairwise difference (APD). Population structure was assessed by phylogenetic analyses and a test for panmixia. Measurements of intra-population diversity revealed no significant loss of overall genetic variation in patients treated for up to 15 years with cART. A test for panmixia, however, showed significant changes in population structure in 2/10 patients after short-term cART (<1 year) and in 7/10 patients after long-term cART (1-15 years). The changes consisted of diverse sets of viral variants prior to cART shifting to populations containing one or more genetically uniform subpopulations during cART. Despite these significant changes in population structure, rebound virus after long-term cART had little divergence from pretherapy virus, implicating long-lived cells infected before cART as the source for rebound virus. The appearance of genetically uniform virus populations and the lack of divergence after prolonged cART and cART interruption provide strong evidence that HIV-1 persists in long-lived cells infected before cART was initiated, that some of these infected cells may be capable of proliferation, and that on-going cycles of viral replication are not evident

CoNLL 2017 Shared Task : Multilingual Parsing from Raw Text to Universal Dependencies

The Conference on Computational Natural Language Learning (CoNLL) features a shared task, in which participants train and test their learning systems on the same data sets. In 2017, one of two tasks was devoted to learning dependency parsers for a large number of languages, in a real world setting without any gold-standard annotation on input. All test sets followed a unified annotation scheme, namely that of Universal Dependencies. In this paper, we define the task and evaluation methodology, describe data preparation, report and analyze the main results, and provide a brief categorization of the different approaches of the participating systems.Peer reviewe

Molecular mechanisms of cell death:recommendations of the Nomenclature Committee on Cell Death 2018

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field.</p

ART Suppresses Plasma HIV-1 RNA to a Stable Set Point Predicted by Pretherapy Viremia

Current antiretroviral therapy is effective in suppressing but not eliminating HIV-1 infection. Understanding the source of viral persistence is essential for developing strategies to eradicate HIV-1 infection. We therefore investigated the level of plasma HIV-1 RNA in patients with viremia suppressed to less than 50–75 copies/ml on standard protease inhibitor- or non-nucleoside reverse transcriptase inhibitor-containing antiretroviral therapy using a new, real-time PCR-based assay for HIV-1 RNA with a limit of detection of one copy of HIV-1 RNA. Single copy assay results revealed that >80% of patients on initial antiretroviral therapy for 60 wk had persistent viremia of one copy/ml or more with an overall median of 3.1 copies/ml. The level of viremia correlated with pretherapy plasma HIV-1 RNA but not with the specific treatment regimen. Longitudinal studies revealed no significant decline in the level of viremia between 60 and 110 wk of suppressive antiretroviral therapy. These data suggest that the persistent viremia on current antiretroviral therapy is derived, at least in part, from long-lived cells that are infected prior to initiation of therapy

Green Edge ice camp campaigns : understanding the processes controlling the under-ice Arctic phytoplankton spring bloom

The Green Edge initiative was developed to investigate the processes controlling the primary productivity and fate of organic matter produced during the Arctic phytoplankton spring bloom (PSB) and to determine its role in the ecosystem. Two field campaigns were conducted in 2015 and 2016 at an ice camp located on landfast sea ice southeast of Qikiqtarjuaq Island in Baffin Bay (67.4797∘ N, 63.7895∘ W). During both expeditions, a large suite of physical, chemical and biological variables was measured beneath a consolidated sea-ice cover from the surface to the bottom (at 360 m depth) to better understand the factors driving the PSB. Key variables, such as conservative temperature, absolute salinity, radiance, irradiance, nutrient concentrations, chlorophyll a concentration, bacteria, phytoplankton and zooplankton abundance and taxonomy, and carbon stocks and fluxes were routinely measured at the ice camp. Meteorological and snow-relevant variables were also monitored. Here, we present the results of a joint effort to tidy and standardize the collected datasets, which will facilitate their reuse in other Arctic studies

Identifying climatically-compatible seedlots for the eastern US: building the predictive tools and knowledge to enable forest assisted migration

IntroductionGlobal climate change and associated stressors threaten forest ecosystems due to the rapid pace of climate change, which could exceed the natural migration rate of some tree species. In response, there is growing interest to research and implement forest assisted migration (FAM). Here, we used a species-independent indicator based on climate analogy, according to the sigma (dis)similarity (σd) index, to match planting sites across the eastern US with (future) climatically-compatible seedlots (CCS).MethodsWe developed CCS for a grid composed of 1 × 1° of latitude and longitude. CCS were based on future climate analogs with ≤2σd analogy to ensure CCS were representative of future climate change. CCS were located for three time periods, 2030's, 2050's, and 2090's and three emissions scenarios (SSP2-4.5, SSP3-7.0, and SSP5-8.5) from the Coupled Model Intercomparison Project phase 6 database, using 12 climate variables.ResultsCCS were identified for the majority of 1 × 1° grids based on the SSP3-7.0 scenario. Approximately 28% of 1 × 1° grid's 2090's projections included future climate novelty. The 2030's, 2050's, and 2090's CCS were located on average 222, 358, and 662 km or 1, 2, and 3 eastern seed zones away from the 1 × 1° grids, respectively. CCS were also located further south-southwest (188–197°). In addition, the average forest cover of CCS was approximately 2%, 5%, and 10% less than that of the 1 × 1° grids.DiscussionOur development and synthesis of CCS emphasized four key results: (i) average distances to 2030's and 2050's CCS were similar to seed-transfer guidelines for some tree species, but 2090's CCS exceeded current recommendations; (ii) south-southwesterly locations of CCS aligned with tree species habitat distribution dynamics; (iii) future climate novelty potentially challenges the conceptual basis of FAM if tree species are not adapted to climate change; and (iv) variation in forest cover among CCS presents potential opportunities and challenges due the presence or absence of forestland to source seed. Ultimately, our goal was to locate and synthesize CCS that could enable FAM decision support

Mortality of HIV-Infected Patients Starting Antiretroviral Therapy in Sub-Saharan Africa: Comparison with HIV-Unrelated Mortality

Comparing mortality rates between patients starting HIV treatment and the general population in four African countries, Matthias Egger and colleagues find the gap decreases over time, especially with early treatment