The overlooked significance of plasma volume for successful adaptation to high altitude in Sherpa and Andean natives

In contrast to Andean natives, high altitude Tibetans present with a lower hemoglobin concentration that correlates with reproductive success and exercise capacity. Decades of physiological and genomic research have assumed that the lower hemoglobin concentration in Himalayan natives results from a blunted erythropoietic response to hypoxia (i.e. no increase in total hemoglobin mass). In contrast, herein we test the hypothesis that the lower hemoglobin concentration is the result of greater plasma volume, rather than an absence of increased hemoglobin production. We assessed hemoglobin mass, plasma volume and blood volume in lowlanders at sea level, lowlanders acclimatized to high altitude, Himalayan Sherpa and Andean Quechua, and explored the functional relevance of volumetric hematological measures to exercise capacity. Hemoglobin mass was highest in Andeans, but also elevated in Sherpa compared to lowlanders. Sherpa demonstrated a larger plasma volume than Andeans, resulting in a comparable total blood volume at a lower hemoglobin concentration. Hemoglobin mass was positively related to exercise capacity in lowlanders at sea level and Sherpa at high altitude, but not in Andean natives. Collectively, our findings demonstrate a unique adaptation in Sherpa that reorientates attention away from hemoglobin concentration and towards a paradigm where hemoglobin mass and plasma volume may represent phenotypes with adaptive significance at high altitude

The relation of plasmacytoid dendritic cells (pDCs) and regulatory t-cells (Tregs) with HPV persistence in HIV-Infected and HIV-Uninfected women

Other than CD4+ count, the immunologic factors that underlie the relationship of HIV/AIDS with persistent oncogenic HPV (oncHPV) and cervical cancer are not well understood. Plasmacytoid dendritic cells (pDCs) and regulatory T-cells (Tregs) are of particular interest. pDCs have both effector and antigen presenting activity and, in HIV-positive patients, low pDC levels are associated with opportunistic infections. Tregs downregulate immune responses, and are present at high levels in HIV-positives. The current pilot study shows for the first time that low pDC and high Treg levels may be significantly associated with oncHPV persistence in both HIV-positive and HIV-negative women. Larger studies are now warranted

Recombinant plants provide a new approach to the production of bacterial polysaccharide for vaccines

Bacterial polysaccharides have numerous clinical or industrial uses. Recombinant plants could offer the possibility of producing bacterial polysaccharides on a large scale and free of contaminating bacterial toxins and antigens. We investigated the feasibility of this proposal by cloning and expressing the gene for the type 3 synthase (cps3S) of Streptococcus pneumoniae in Nicotinia tabacum, using the pCambia2301 vector and Agrobacterium tumefaciens-mediated gene transfer. In planta the recombinant synthase polymerised plant-derived UDP-glucose and UDP-glucuronic acid to form type 3 polysaccharide. Expression of the cps3S gene was detected by RT-PCR and production of the pneumococcal polysaccharide was detected in tobacco leaf extracts by double immunodiffusion, Western blotting and high-voltage paper electrophoresis. Because it is used a component of anti-pneumococcal vaccines, the immunogenicity of the plant-derived type 3 polysaccharide was tested. Mice immunised with extracts from recombinant plants were protected from challenge with a lethal dose of pneumococci in a model of pneumonia and the immunised mice had significantly elevated levels of serum anti-pneumococcal polysaccharide antibodies. This study provides the proof of the principle that bacterial polysaccharide can be successfully synthesised in plants and that these recombinant polysaccharides could be used as vaccines to protect against life-threatening infections

Liver Fibrosis Linked to Cognitive Performance in HIV and Hepatitis C

Since HIV impairs gut barriers to pathogens, HIV-infected adults may be vulnerable to Minimal Hepatic Encephalopathy (MHE) in the absence of cirrhosis

HIV Tropism and Decreased Risk of Breast Cancer

During the first two decades of the U.S. AIDS epidemic, and unlike some malignancies, breast cancer risk was significantly lower for women with human immunodeficiency virus (HIV) infection compared to the general population. This deficit in HIV-associated breast cancer could not be attributed to differences in survival, immune deficiency, childbearing or other breast cancer risk factors. HIV infects mononuclear immune cells by binding to the CD4 molecule and to CCR5 or CXCR4 chemokine coreceptors. Neoplastic breast cells commonly express CXCR4 but not CCR5. In vitro, binding HIV envelope protein to CXCR4 has been shown to induce apoptosis of neoplastic breast cells. Based on these observations, we hypothesized that breast cancer risk would be lower among women with CXCR4-tropic HIV infection.We conducted a breast cancer nested case-control study among women who participated in the WIHS and HERS HIV cohort studies with longitudinally collected risk factor data and plasma. Cases were HIV-infected women (mean age 46 years) who had stored plasma collected within 24 months of breast cancer diagnosis and an HIV viral load≥500 copies/mL. Three HIV-infected control women, without breast cancer, were matched to each case based on age and plasma collection date. CXCR4-tropism was determined by a phenotypic tropism assay. Odds ratios (OR) and 95% confidence intervals (CI) for breast cancer were estimated by exact conditional logistic regression. Two (9%) of 23 breast cancer cases had CXCR4-tropic HIV, compared to 19 (28%) of 69 matched controls. Breast cancer risk was significantly and independently reduced with CXCR4 tropism (adjusted odds ratio, 0.10, 95% CI 0.002-0.84) and with menopause (adjusted odds ratio, 0.08, 95% CI 0.001-0.83). Adjustment for CD4+ cell count, HIV viral load, and use of antiretroviral therapy did not attenuate the association between infection with CXCR4-tropic HIV and breast cancer.Low breast cancer risk with HIV is specifically linked to CXCR4-using variants of HIV. These variants are thought to exclusively bind to and signal through a receptor that is commonly expressed on hyperplastic and neoplastic breast duct cells. Additional studies are needed to confirm these observations and to understand how CXCR4 might reduce breast cancer risk

Resource Heterogeneity Moderates the Biodiversity-Function Relationship in Real World Ecosystems

Numerous recent studies have tested the effects of plant, pollinator, and predator diversity on primary productivity, pollination, and consumption, respectively. Many have shown a positive relationship, particularly in controlled experiments, but variability in results has emphasized the context-dependency of these relationships. Complementary resource use may lead to a positive relationship between diversity and these processes, but only when a diverse array of niches is available to be partitioned among species. Therefore, the slope of the diversity-function relationship may change across differing levels of heterogeneity, but empirical evaluations of this pattern are lacking. Here we examine three important functions/properties in different real world (i.e., nonexperimental) ecosystems: plant biomass in German grasslands, parasitism rates across five habitat types in coastal Ecuador, and coffee pollination in agroforestry systems in Indonesia. We use general linear and structural equation modeling to demonstrate that the effect of diversity on these processes is context dependent, such that the slope of this relationship increases in environments where limiting resources (soil nutrients, host insects, and coffee flowers, respectively) are spatially heterogeneous. These real world patterns, combined with previous experiments, suggest that biodiversity may have its greatest impact on the functioning of diverse, naturally heterogeneous ecosystems

Microwave Radiometry at Frequencies From 500 to 1400 MHz: An Emerging Technology for Earth Observations

icrowave radiometry has provided valuable spaceborne observations of Earth’s geophysical properties for decades. The recent SMOS, Aquarius, and SMAP satellites have demonstrated the value of measurements at 1400 MHz for observ- ing surface soil moisture, sea surface salinity, sea ice thickness, soil freeze/thaw state, and other geophysical variables. However, the information obtained is limited by penetration through the subsur- face at 1400 MHz and by a reduced sensitivity to surface salinity in cold or wind-roughened waters. Recent airborne experiments have shown the potential of brightness temperature measurements from 500–1400 MHz to address these limitations by enabling sensing of soil moisture and sea ice thickness to greater depths, sensing of temperature deep within ice sheets, improved sensing of sea salinity in cold waters, and enhanced sensitivity to soil moisture under veg- etation canopies. However, the absence of significant spectrum re- served for passive microwave measurements in the 500–1400 MHz band requires both an opportunistic sensing strategy and systems for reducing the impact of radio-frequency interference. Here, we summarize the potential advantages and applications of 500–1400 MHz microwave radiometry for Earth observation and review recent experiments and demonstrations of these concepts. We also describe the remaining questions and challenges to be addressed in advancing to future spaceborne operation of this technology along with recommendations for future research activities

TOI-2196 b : Rare planet in the hot Neptune desert transiting a G-type star

Funding: C.M.P., M.F., I.G., and J.K. gratefully acknowledge the support of the Swedish National Space Agency (DNR 65/19, 174/18, 177/19, 2020-00104). L.M.S and D.G. gratefully acknowledge financial support from the CRT foundation under Grant No. 2018.2323 “Gaseous or rocky? Unveiling the nature of small worlds”. P.K. acknowledges support from grant LTT-20015. E.G. acknowledge the support of the Thüringer Ministerium für Wirtschaft, Wissenschaft und Digitale Gesellschaft. J.S.J. gratefully acknowledges support by FONDECYT grant 1201371 and from the ANID BASAL projects ACE210002 and FB210003. H.J.D. acknowledges support from the Spanish Research Agency of the Ministry of Science and Innovation (AEI-MICINN) under grant PID2019-107061GBC66, DOI: 10.13039/501100011033. D.D. acknowledges support from the TESS Guest Investigator Program grants 80NSSC21K0108 and 80NSSC22K0185. M.E. acknowledges the support of the DFG priority program SPP 1992 "Exploring the Diversity of Extrasolar Planets" (HA 3279/12-1). K.W.F.L. was supported by Deutsche Forschungsgemeinschaft grants RA714/14-1 within the DFG Schwerpunkt SPP 1992, Exploring the Diversity of Extrasolar Planets. N.N. acknowledges support from JSPS KAKENHI Grant Number JP18H05439, JST CREST Grant Number JPMJCR1761. M.S.I.P. is funded by NSF.The hot Neptune desert is a region hosting a small number of short-period Neptunes in the radius-instellation diagram. Highly irradiated planets are usually either small (R ≲ 2 R⊕) and rocky or they are gas giants with radii of ≳1 RJ. Here, we report on the intermediate-sized planet TOI-2196 b (TIC 372172128.01) on a 1.2 day orbit around a G-type star (V = 12.0, [Fe/H] = 0.14 dex) discovered by the Transiting Exoplanet Survey Satellite in sector 27. We collected 41 radial velocity measurements with the HARPS spectrograph to confirm the planetary nature of the transit signal and to determine the mass. The radius of TOI-2196 b is 3.51 ± 0.15 R⊕, which, combined with the mass of 26.0 ± 1.3 M⊕, results in a bulk density of 3.31−0.43+0.51 g cm−3. Hence, the radius implies that this planet is a sub-Neptune, although the density is twice than that of Neptune. A significant trend in the HARPS radial velocity measurements points to the presence of a distant companion with a lower limit on the period and mass of 220 days and 0.65 MJ, respectively, assuming zero eccentricity. The short period of planet b implies a high equilibrium temperature of 1860 ± 20 K, for zero albedo and isotropic emission. This places the planet in the hot Neptune desert, joining a group of very few planets in this parameter space discovered in recent years. These planets suggest that the hot Neptune desert may be divided in two parts for planets with equilibrium temperatures of ≳1800 K: a hot sub-Neptune desert devoid of planets with radii of ≈ 1.8−3 R⊕ and a sub-Jovian desert for radii of ≈5−12 R⊕. More planets in this parameter space are needed to further investigate this finding. Planetary interior structure models of TOI-2196 b are consistent with a H/He atmosphere mass fraction between 0.4% and 3%, with a mean value of 0.7% on top of a rocky interior. We estimated the amount of mass this planet might have lost at a young age and we find that while the mass loss could have been significant, the planet had not changed in terms of character: it was born as a small volatile-rich planet and it remains one at present.Publisher PDFPeer reviewe

JAK2 V617F Constitutive Activation Requires JH2 Residue F595: A Pseudokinase Domain Target for Specific Inhibitors

The JAK2 V617F mutation present in over 95% of Polycythemia Vera patients and in 50% of Essential Thrombocythemia and Primary Myelofibrosis patients renders the kinase constitutively active. In the absence of a three-dimensional structure for the full-length protein, the mechanism of activation of JAK2 V617F has remained elusive. In this study, we used functional mutagenesis to investigate the involvement of the JH2 αC helix in the constitutive activation of JAK2 V617F. We show that residue F595, located in the middle of the αC helix of JH2, is indispensable for the constitutive activity of JAK2 V617F. Mutation of F595 to Ala, Lys, Val or Ile significantly decreases the constitutive activity of JAK2 V617F, but F595W and F595Y are able to restore it, implying an aromaticity requirement at position 595. Substitution of F595 to Ala was also able to decrease the constitutive activity of two other JAK2 mutants, T875N and R683G, as well as JAK2 K539L, albeit to a lower extent. In contrast, the F595 mutants are activated by erythropoietin-bound EpoR. We also explored the relationship between the dimeric conformation of EpoR and several JAK2 mutants. Since residue F595 is crucial to the constitutive activation of JAK2 V617F but not to initiation of JAK2 activation by cytokines, we suggest that small molecules that target the region around this residue might specifically block oncogenic JAK2 and spare JAK2 wild-type