GMMIP (v1.0) contribution to CMIP6: Global Monsoons Model Inter-comparison Project

The Global Monsoons Model Inter-comparison Project (GMMIP) has been endorsed by the panel of Coupled Model Inter-comparison Project (CMIP) as one of the participating MIPs in the sixth phase of CMIP (CMIP6). The focus of GMMIP is on monsoon climatology, variability, prediction and projection, which is relevant to four of the “Grand Challenges” proposed by the World Climate Research Programme. At present, 21 international modelling groups are committed to joining GMMIP. This overview paper introduces the motivation behind GMMIP and the scientific questions it intends to answer. Three tiers of experiments, of decreasing priority, are designed to examine: (a) model skill in simulating the climatology and interannual-to-multidecadal variability of global monsoons in SST-forced experiments of the historical climate period; (b) the roles of the Interdecadal Pacific Oscillation and Atlantic Multidecadal Oscillation in driving variations of the global and regional monsoons; and (c) the effects of large orographic terrain on the establishment of the monsoons. The outputs of the CMIP6 DECK, “historical” simulation and endorsed MIPs will also be used in the diagnostic analysis of GMMIP to give a comprehensive understanding of the roles played by different external forcings, potential improvements in the simulation of monsoon rainfall at high resolution and reproducibility at decadal time scales. The implementation of GMMIP will improve our understanding of the fundamental physics of changes in the global and regional monsoons over the past 140 years and ultimately benefit monsoons prediction and projection in the current century

Resting Regulatory CD4 T Cells: A Site of HIV Persistence in Patients on Long-Term Effective Antiretroviral Therapy

BACKGROUND: In HIV-infected patients on long-term HAART, virus persistence in resting long-lived CD4 T cells is a major barrier to curing the infection. Cell quiescence, by favouring HIV latency, reduces the risk of recognition and cell destruction by cytotoxic lymphocytes. Several cell-activation-based approaches have been proposed to disrupt cell quiescence and then virus latency, but these approaches have not eradicated the virus. CD4+CD25+ regulatory T cells (Tregs) are a CD4+ T-cell subset with particular activation properties. We investigated the role of these cells in virus persistence in patients on long-term HAART. METHODOLOGY/PRINCIPAL FINDINGS: We found evidence of infection of resting Tregs (HLADR(-)CD69(-)CD25(hi)FoxP3+CD4+ T cells) purified from patients on prolonged HAART. HIV DNA harbouring cells appear more abundant in the Treg subset than in non-Tregs. The half-life of the Treg reservoir was estimated at 20 months. Since Tregs from patients on prolonged HAART showed hyporesponsiveness to cell activation and inhibition of HIV-specific cytotoxic T lymphocyte-related functions upon activation, therapeutics targeting cell quiescence to induce virus expression may not be appropriate for purging the Treg reservoir. CONCLUSIONS: Our results identify Tregs as a particular compartment within the latent reservoir that may require a specific approach for its purging

Lipid hydroperoxides and oxylipins are mediators of denervation induced muscle atrophy

Loss of innervation is a key driver of age associated muscle atrophy and weakness (sarcopenia). Our laboratory has previously shown that denervation induced atrophy is associated with the generation of mitochondrial hydroperoxides and lipid mediators produced downstream of cPLA2 and 12/15 lipoxygenase (12/15-LOX). To define the pathological impact of lipid hydroperoxides generated in denervation-induced atrophy in vivo, we treated mice with liproxstatin-1, a lipid hydroperoxide scavenger. We treated adult male mice with 5mg/kg liproxstain-1 or vehicle one day prior to sciatic nerve transection and daily for 7 days post-denervation before tissue analysis. Liproxstatin-1 treatment protected gastrocnemius mass and fiber cross sectional area (∼40% less atrophy post-denervation in treated versus untreated mice). Mitochondrial hydroperoxide generation was reduced 80% in vitro and by over 65% in vivo by liproxstatin-1 treatment in denervated permeabilized muscle fibers and decreased the content of 4-HNE by ∼25% post-denervation. Lipidomic analysis revealed detectable levels of 25 oxylipins in denervated gastrocnemius muscle and significantly increased levels for eight oxylipins that are generated by metabolism of fatty acids through 12/15-LOX. Liproxstatin-1 treatment reduced the level of three of the eight denervation-induced oxylipins, specifically 15-HEPE, 13-HOTrE and 17-HDOHE. Denervation elevated protein degradation rates in muscle and treatment with liproxstatin-1 reduced rates of protein breakdown in denervated muscle. In contrast, protein synthesis rates were unchanged by denervation. Targeted proteomics revealed a number of proteins with altered expression after denervation but no effect of liproxstain-1. Transcriptomic analysis revealed 203 differentially expressed genes in denervated muscle from vehicle or liproxstatin-1 treated mice, including ER stress, nitric oxide signaling, Gαi signaling, glucocorticoid receptor signaling, and other pathways. Overall, these data suggest lipid hydroperoxides and oxylipins are key drivers of increased protein breakdown and muscle loss associated with denervation induced atrophy and a potential target for sarcopenia intervention

The CLIVAR C20C Project: Which components of the Asian-Australian monsoon circulation variations are forced and reproducible?

A multi-model set of atmospheric simulations forced by historical sea surface temperature (SST) or SSTs plus Greenhouse gases and aerosol forcing agents for the period of 1950-1999 is studied to identify and understand which components of the Asian-Australian monsoon (A-AM) variability are forced and reproducible. The analysis focuses on the summertime monsoon circulations, comparing model results against the observations. The priority of different components of the A-AM circulations in terms of reproducibility is evaluated. Among the subsystems of the wide A-AM, the South Asian monsoon and the Australian monsoon circulations are better reproduced than the others, indicating they are forced and well modeled. The primary driving mechanism comes from the tropical Pacific. The western North Pacific monsoon circulation is also forced and well modeled except with a slightly lower reproducibility due to its delayed response to the eastern tropical Pacific forcing. The simultaneous driving comes from the western Pacific surrounding the maritime continent region. The Indian monsoon circulation has a moderate reproducibility, partly due to its weakened connection to June-July-August SSTs in the equatorial eastern Pacific in recent decades. Among the A-AM subsystems, the East Asian summer monsoon has the lowest reproducibility and is poorly modeled. This is mainly due to the failure of specifying historical SST in capturing the zonal land-sea thermal contrast change across the East Asia. The prescribed tropical Indian Ocean SST changes partly reproduce the meridional wind change over East Asia in several models. For all the A-AM subsystem circulation indices, generally the MME is always the best except for the Indian monsoon and East Asian monsoon circulation indices

The CLIVAR C20C Project: Which components of the Asian-Australian monsoon circulation variations are forced and reproducible?

A multi-model set of atmospheric simulations forced by historical sea surface temperature (SST) or SSTs plus Greenhouse gases and aerosol forcing agents for the period of 1950–1999 is studied to identify and understand which components of the Asian–Australian monsoon (A–AM) variability are forced and reproducible. The analysis focuses on the summertime monsoon circulations, comparing model results against the observations. The priority of different components of the A–AM circulations in terms of reproducibility is evaluated. Among the subsystems of the wide A–AM, the South Asian monsoon and the Australian monsoon circulations are better reproduced than the others, indicating they are forced and well modeled. The primary driving mechanism comes from the tropical Pacific. The western North Pacific monsoon circulation is also forced and well modeled except with a slightly lower reproducibility due to its delayed response to the eastern tropical Pacific forcing. The simultaneous driving comes from the western Pacific surrounding the maritime continent region. The Indian monsoon circulation has a moderate reproducibility, partly due to its weakened connection to June–July–August SSTs in the equatorial eastern Pacific in recent decades. Among the A–AM subsystems, the East Asian summer monsoon has the lowest reproducibility and is poorly modeled. This is mainly due to the failure of specifying historical SST in capturing the zonal land-sea thermal contrast change across the East Asia. The prescribed tropical Indian Ocean SST changes partly reproduce the meridional wind change over East Asia in several models. For all the A–AM subsystem circulation indices, generally the MME is always the best except for the Indian monsoon and East Asian monsoon circulation indices

The CLIVAR C20C Project: Which components of the Asian-Australian monsoon circulation variations are forced and reproducible?

A multi-model set of atmospheric simulations forced by historical sea surface temperature (SST) or SSTs plus Greenhouse gases and aerosol forcing agents for the period of 1950-1999 is studied to identify and understand which components of the Asian-Australian monsoon (A-AM) variability are forced and reproducible. The analysis focuses on the summertime monsoon circulations, comparing model results against the observations. The priority of different components of the A-AM circulations in terms of reproducibility is evaluated. Among the subsystems of the wide A-AM, the South Asian monsoon and the Australian monsoon circulations are better reproduced than the others, indicating they are forced and well modeled. The primary driving mechanism comes from the tropical Pacific. The western North Pacific monsoon circulation is also forced and well modeled except with a slightly lower reproducibility due to its delayed response to the eastern tropical Pacific forcing. The simultaneous driving comes from the western Pacific surrounding the maritime continent region. The Indian monsoon circulation has a moderate reproducibility, partly due to its weakened connection to June-July-August SSTs in the equatorial eastern Pacific in recent decades. Among the A-AM subsystems, the East Asian summer monsoon has the lowest reproducibility and is poorly modeled. This is mainly due to the failure of specifying historical SST in capturing the zonal land-sea thermal contrast change across the East Asia. The prescribed tropical Indian Ocean SST changes partly reproduce the meridional wind change over East Asia in several models. For all the A-AM subsystem circulation indices, generally the MME is always the best except for the Indian monsoon and East Asian monsoon circulation indices.Submitted3.7. Dinamica del clima e dell'oceanoJCR Journalope

A Decline in CCL3-5 Chemokine Gene Expression during Primary Simian-Human Immunodeficiency Virus Infection

BACKGROUND: The CC-chemokines CCL3, CCL4 and CCL5 have been found to block the entry of CCR5-tropic HIV into host cells and to suppress the viral replication in vitro, but the in vivo role of endogenous CC-chemokines in HIV-1 infection is still incompletely understood. METHODOLOGY/PRINCIPLE FINDINGS: In this study, the primate host CCL3, CCL4 and CCL5 gene expression was evaluated in response to simian-human immunodeficiency virus (SHIV) infection in rhesus macaque model. Five rhesus macaques were inoculated with CCR5-tropic SHIV(SF162P4). The mRNA levels of CCL3, CCL4 and CCL5 were measured by real-time PCR at post inoculation day (PID) 0, 7, 14, 21, 35, 56 and 180 in peripheral blood. In addition, a selected subset of samples from CXCR4-tropic SHIV(Ku1)-infected macaques was included with objective to compare the differences in CC-chemokine down-regulation caused by the two SHIVs. Gut-associated lymphoid tissues (GALT) collected from SHIV(SF162P4)-infected animals were also tested by flow cytometry and confocal microscopy to corroborate the gene expression results. Predictably, higher viral loads and CD4+ T cell losses were observed at PID 14 in macaques infected with SHIV(Ku1) than with SHIV(SF162P4). A decline in CC-chemokine gene expression was also found during primary (PID 7-21), but not chronic (PID 180) stage of infection. CONCLUSIONS: It was determined that A) SHIV(SF162P4) down-regulated the CC-chemokine gene expression during acute stage of infection to a greater extent (p<0.05) than SHIV(Ku1), and B) such down-regulation was not paralleled with the CD4+ T cell depletion. Evaluation of CC-chemokine enhancing immunomodulators such as synthetic CpG-oligonucleotides could be explored in future HIV vaccine studies

Partial Regulatory T Cell Depletion Prior to Acute Feline Immunodeficiency Virus Infection Does Not Alter Disease Pathogenesis

Feline immunodeficiency virus (FIV) infection in cats follows a disease course similar to HIV-1, including a short acute phase characterized by high viremia, and a prolonged asymptomatic phase characterized by low viremia and generalized immune dysfunction. CD4+CD25hiFoxP3+ immunosuppressive regulatory T (Treg) cells have been implicated as a possible cause of immune dysfunction during FIV and HIV-1 infection, as they are capable of modulating virus-specific and inflammatory immune responses. Additionally, the immunosuppressive capacity of feline Treg cells has been shown to be increased during FIV infection. We have previously shown that transient in vivo Treg cell depletion during asymptomatic FIV infection reveals FIV-specific immune responses suppressed by Treg cells. In this study, we sought to determine the immunological influence of Treg cells during acute FIV infection. We asked whether Treg cell depletion prior to infection with the highly pathogenic molecular clone FIV-C36 in cats could alter FIV pathogenesis. We report here that partial Treg cell depletion prior to FIV infection does not significantly change provirus, viremia, or CD4+ T cell levels in blood and lymphoid tissues during the acute phase of disease. The effects of anti-CD25 mAb treatment are truncated in cats acutely infected with FIV-C36 as compared to chronically infected cats or FIV-naïve cats, as Treg cell levels were heightened in all treatment groups included in the study within two weeks post-FIV infection. Our findings suggest that the influence of Treg cell suppression during FIV pathogenesis is most prominent after Treg cells are activated in the environment of established FIV infection

North American Climate in CMIP5 Experiments: Part III: Assessment of Twenty-First-Century Projections

In part III of a three-part study on North American climate in phase 5 of the Coupled Model Intercomparison Project (CMIP5) models, the authors examine projections of twenty-first-century climate in the representative concentration pathway 8.5 (RCP8.5) emission experiments. This paper summarizes and synthesizes results from several coordinated studies by the authors. Aspects of North American climate change that are examined include changes in continental-scale temperature and the hydrologic cycle, extremes events, and storm tracks, as well as regional manifestations of these climate variables. The authors also examine changes in the eastern North Pacific and North Atlantic tropical cyclone activity and North American intraseasonal to decadal variability, including changes in teleconnections to other regions of the globe. Projected changes are generally consistent with those previously published for CMIP3, although CMIP5 model projections differ importantly from those of CMIP3 in some aspects, including CMIP5 model agreement on increased central California precipitation. The paper also highlights uncertainties and limitations based on current results as priorities for further research. Although many projected changes in North American climate are consistent across CMIP5 models, substantial intermodel disagreement exists in other aspects. Areas of disagreement include projections of changes in snow water equivalent on a regional basis, summer Arctic sea ice extent, the magnitude and sign of regional precipitation changes, extreme heat events across the northern United States, and Atlantic and east Pacific tropical cyclone activity