Early SIV and HIV infection promotes the LILRB2/MHC-I inhibitory axis in cDCs

Classical dendritic cells (cDCs) play a pivotal role in the early events that tip the immune response toward persistence or viral control. In vitro studies indicate that HIV infection induces the dysregulation of cDCs through binding of the LILRB2 inhibitory receptor to its MHC-I ligands and the strength of this interaction was proposed to drive disease progression. However, the dynamics of the LILRB2/MHC-I inhibitory axis in cDCs during early immune responses against HIV are yet unknown. Here, we show that early HIV-1 infection induces a strong and simultaneous increase of LILRB2 and MHC-I expression on the surface of blood cDCs. We further characterized the early dynamics of LILRB2 and MHC-I expression by showing that SIVmac251 infection of macaques promotes coordinated up-regulation of LILRB2 and MHC-I on cDCs and monocytes/macrophages, from blood and lymph nodes. Orientation towards the LILRB2/MHC-I inhibitory axis starts from the first days of infection and is transiently induced in the entire cDC population in acute phase. Analysis of the factors involved indicates that HIV-1 replication, TLR7/8 triggering, and treatment by IL-10 or type I IFNs increase LILRB2 expression. Finally, enhancement of the LILRB2/MHC-I inhibitory axis is specific to HIV-1 and SIVmac251 infections, as expression of LILRB2 on cDCs decreased in naturally controlled chikungunya virus infection of macaques. Altogether, our data reveal a unique up-regulation of LILRB2 and its MHC-I ligands on cDCs in the early phase of SIV/HIV infection, which may account for immune dysregulation at a critical stage of the anti-viral response.     

Elucidating the diel and seasonal calling behaviour of Elachistocleis matogrosso (Anura: Microhylidae)

ABSTRACT

Acoustic monitoring provides the opportunity to study ecological processes that are difficult to assess with traditional surveys. Elachistocleis matogrosso is an anuran species, described in 2010, for which limited biological information is available. This study investigated the calling activity of the species in the north-eastern portion of the Pantanal, Brazil, a wetland area with marked seasonality between the dry and wet seasons. The calling activity of E. matogrosso was monitored using automated digital recorders in combination with automated signal recognition software over two different annual cycles. The species was vocally active only during the wet season (October – April), with a peak in November-December during the 2013–2014 annual cycle and in February-March during the 2015–2016 annual cycle. The peak calling activity occurred at dusk. This species has nocturnal habits and an explosive breeding activity. The detection of the species was intermittent, which suggests that environmental predictors or site-specific conditions might play an important role in species detection. Moreover, this intermittent occupancy indicated that surveys that employ traditional field techniques would likely fail to detect this species. We describe an effective protocol for detecting E. matogrosso with acoustic monitoring, which requires recording during 20 days in February from 17:01 to 05:00. Our procedure would be easy to adapt to other anuran species, and it could be used for investigating new localities and assessing population changes over time.     

Evidence of G-protein-coupled receptor and substrate transporter heteromerization at a single molecule level

G-protein-coupled receptors (GPCRs) can constitute complexes with non-GPCR integral membrane proteins, while such interaction has not been demonstrated at a single molecule level so far. We here investigated the potential interaction between the thyrotropin receptor (TSHR) and the monocarboxylate transporter 8 (MCT8), a member of the major facilitator superfamily (MFS), using fluorescence cross-correlation spectroscopy (FCCS). Both the proteins are expressed endogenously on the basolateral plasma membrane of the thyrocytes and are involved in stimulation of thyroid hormone production and release. Indeed, we demonstrate strong interaction between both the proteins which causes a suppressed activation of G_q/11 by TSH-stimulated TSHR. Thus, we provide not only evidence for a novel interaction between the TSHR and MCT8, but could also prove this interaction on a single molecule level. Moreover, this interaction forces biased signaling at the TSHR. These results are of general interest for both the GPCR and the MFS research fields.     

Enhancing momentum investment strategy using leverage

Previous studies examine investment strategies based on leverage and momentum; none investigates both variables jointly as an investment strategy. This paper is the first incorporating leverage and momentum together. We show that low past returns (losers) forecast future negative abnormal returns only among stocks with high leverage levels, but not among stocks with low leverage levels. However, high past returns (winners) forecast future positive abnormal returns independently of leverage level. As a result, the negative relation between leverage and future abnormal returns is only observed among loser stocks, and the positive relation between past returns and future abnormal returns is only shown among non‐low leverage stocks. Our results are important in achieving better investment strategies: buying winners' stocks (independently of their level of leverage) and short‐selling losers' stocks with high leverage yield higher abnormal returns than strategies based on only one of these variables. Our two‐dimensional strategy yields risk‐adjusted abnormal returns of 15.66% per annum, whereas the single leverage or momentum strategies yield 7.70% and 7.96% per annum, respectively. The difference is nearly 8% and economically significant. If leverage is considered as proxy for default risk, our results, contrary to previous evidence, show that momentum profits are not exclusive of default stocks, and that momentum returns are not only driven by negative returns yielded by distress stocks.     

Degradation of the mitochondrial complex I assembly factor TMEM126B under chronic hypoxia

Cell stress such as hypoxia elicits adaptive responses, also on the level of mitochondria, and in part is mediated by the hypoxia-inducible factor (HIF) 1α. Adaptation of mitochondria towards acute hypoxic conditions is reasonably well understood, while regulatory mechanisms, especially of respiratory chain assembly factors, under chronic hypoxia remains elusive. One of these assembly factors is transmembrane protein 126B (TMEM126B). This protein is part of the mitochondrial complex I assembly machinery. We identified changes in complex I abundance under chronic hypoxia, in association with impaired substrate-specific mitochondrial respiration. Complexome profiling of isolated mitochondria of the human leukemia monocytic cell line THP-1 revealed HIF-1α-dependent deficits in complex I assembly and mitochondrial complex I assembly complex (MCIA) abundance. Of all mitochondrial MCIA members, we proved a selective HIF-1-dependent decrease of TMEM126B under chronic hypoxia. Mechanistically, HIF-1α induces the E3-ubiquitin ligase F-box/WD repeat-containing protein 1A (β-TrCP1), which in turn facilitates the proteolytic degradation of TMEM126B. Attenuating a functional complex I assembly appears critical for cellular adaptation towards chronic hypoxia and is linked to destruction of the mitochondrial assembly factor TMEM126B.     

Spatiotemporal characteristics of freezing and thawing of the active layer in the source areas of the Yellow River （SAYR）

Based on the analysis of data on temperatures and moisture of soils in the active layer at four different permafrost sites in the source areas of the Yellow River(SAYR)in 2010–2012,the freeze–thaw processes of soils in the active layer were compared and contrasted for understanding the spatiotemporal variations.At the four studied sites,the thickness and mean annual temperature of permafrost are different.The temperatures at the top of permafrost(TTOP),i.e.,the maximum depth(s)of seasonal frost and/or thaw penetration,are-1.9°C at the Chalaping site(CLP),-0.9°C at the site on the southern bank of the Zhaling Lake(ZLH),-0.4°C at the Maduo Town site(MDX),and 1.1°C at the site on the northern bank of the Eling Lake(ELH).Differences in the mean annual ground temperature of permafrost and TTOPs may be responsible for the differentiations in the freeze–thaw processes of soils in the active layer.With rising TTOPs,the ground thawing started earlier:CLP in early June,ZLH in late May,MDX in early May,and ELH in mid-April,while the freezing began later:CLP in early October,ZLH in early to midOctober,MDX in mid-October,and ELH in the mid-to late October.With increasing TTOPs,the freeze-up periods for permafrost sites were shortened:202 days at CLP,130 days at ZLH,100 days at MDX,and the period of complete thaw was 89 days at ELH.At the CLP and ZLH sites,the two-directional ground freezing(downwards from ground surfaces and upwards from the permafrost table)and thawing finished in the same year,but the ground freezing at the MDX continued to the end of the nextJanuary,with very slow freezing rates in the end.At the ELH site,ground freezing kept on until early May when thawing began on the surface,and upward and downward thawing became increasingly stable in late June to early July.At each site,with rising TTOPs,the downward freezing accelerated in comparison with the upward freezing,and with an increasing proportion of downward frozen depth,and with the larger ratios of freezing to thawing duration.In summary,the patterns of thawing and freezing processes in the active layer in the SAYR differ from those in other parts of the Qinghai–Tibet Plateau to a noticeable extent.     

Combinational electroporation and transplantation approach to studying gene functions in avian embryos

Gene transfection is an indispensable approach for studying gene function since it provides important information on gain- and/or loss-of-function. Chick embryos are also extensively employed for studying bio- logical function since they are easily accessible and can be maintained alive after manipulation. The combination of both techniques presents a powerful approach to under- standing how genes regulate embryo development. Fur- thermore, combining these approaches with tissue transplant techniques make even more attractive for elu- cidate gene function. Electroporation, employing parallelly fashioned electrodes, has been widely used in chick embryos. However, experimenters have been frustrated by unsuccessfully transfection in some embryonic tissue of interest because the electrodes were improperly positioned.We presently demonstrated the different patterns of orga- nizing and positioning the electrodes, in combination with tissue transplantation, to efficiently and specifically trans- fect the chick embryonic head, trunk neural tube, heart tube, somites and neural crest cells with the GFP reporter gene.     

Retrievals of atmospheric boundary layer temperature and moisture profiles by using Atmospheric Emitted Radiance Interferometer （AERI） measurements in Shouxian

The ground-based Atmospheric Emitted Radi- ance Interferometer （AERI） was deployed in Shouxian, China in 2008 to measure down-welling infrared radiances with high resolution. Based on AERI observations, we propose a new method for retrieving vertical temperature and water vapor profiles in the planetary boundary layer （PBL）. The method exclusively uses NCEP-2, a global reanalysis data as a first-guess profile in an iterative recursive algorithm. The PBL profiles of temperature and moisture under clear sky conditions in Shouxian have been retrieved using this new method. Compared with coinci- dent radiosonde measurements, we find that AERI is able to obtain more accurate temperature and water vapor pro- files in the PBL. The retrieval results with high temporal resolution can be used to monitor the PBL stability and evolution.