Intensified grazing affects endemic plant and gastropod diversity in alpine grasslands of the Southern Carpathian mountains (Romania)

Alpine grasslands in the Southern Carpathian Mts, Romania, harbour an extraordinarily high diversity of plants and invertebrates, including Carpathic endemics. In the past decades, intensive sheep grazing has caused a dramatic decrease in biodiversity and even led to eroded soils at many places in the Carpathians. Because of limited food resources, sheep are increasingly forced to graze on steep slopes, which were formerly not grazed by livestock and are considered as local biodiversity hotspots. We examined species richness, abundance and number of endemic vascular plants and terrestrial gastropods on steep slopes that were either grazed by sheep or ungrazed by livestock in two areas of the Southern Carpathians. On calcareous soils in the Bucegi Mts, a total of 177 vascular plant and 19 gastropod species were recorded. Twelve plant species (6.8%) and three gastropod species (15.8%) were endemic to the Carpathians. Grazed sites had lower plant and gastropod species richness than ungrazed sites. Furthermore, grazed sites harboured fewer gastropod species endemic to the Carpathians than ungrazed sites. On acid soils in the Fagaras Mts, a total of 96 vascular plant and nine gastropod species were found. In this mountain area, however, grazed and ungrazed sites did not differ in species richness, abundance and number of endemic plant and gastropod species. Our findings confirm the high biodiversity of grasslands on steep slopes in the Southern Carpathian Mts and caution against increasing grazing pressure in these refuges for relic plants and gastropods as well as for other invertebrates.     

The Pathological Links between Adiposity and the Carpal Tunnel Syndrome

An association between obesity and carpal tunnel syndrome is found in many epidemiological studies. Therefore, there is a need to evaluate the physiopathological links that could explain the association between these two entities. Ectopic adipose tissue is responsible for metabolic syndrome and inflammation, and is a major risk factor for diabetes and cardiovascular diseases. Taking these elements into consideration, we conducted an extensive literature revision of the subject, considering as ectopic fat-related mechanisms the following: (a) the direct compression and the association with the metabolic syndrome of the fat deposition around the wrist, (b) the insulin resistance, dyslipidemia, inflammatory, and oxidative mechanisms related to the central deposition of the fat, (c) the impaired muscle contraction and metabolism related to myosteatosis. Each section presents the cellular pathways which are modified by the ectopic deposition of the adipose tissue and the impact in the pathogeny of the carpal tunnel syndrome. In conclusion, the experimental and clinical data support the epidemiological findings. Efforts to reduce the obesity epidemics will improve not only cardio-metabolic health but will reduce the burden of the disability-free life expectancy due to the carpal tunnel syndrome.     

Hyaluronic capsule as one of the factors of hemolytic streptococcal pathogenicity]

Experiments were conducted on albino mice. It was shown that treatment of streptococci with testicular hyaluronidase or a single administration of the enzyme to infected animals failed to inhibit the infectious process. Injection of hyaluronidase solution to every 3 or 4 hours depressed the development of the process and increased the percentage of survived animals during its first stages. A marked intensification of the hyaluronidase action inhibiting the infectious process was observed under conditions of a moderately active or passive immunity and also in the case of preliminary treatment of streptococci with homologous immune serum. The data obtained permit to regard the hyaluronic capsule in the hemolytic streptococci as one of the pathogenicity factors of this microbial species providing survival of the causative agent after its entrance into the macroorganism.     

Investigating the effect of a single glycine to alanine substitution on interactions of antimicrobial peptide latarcin 2a with a lipid membrane

Latarcins are linear, α-helical antimicrobial peptides purified from the venom of the Central Asian spider Lachesana tarabaevi, with lytic activity against Gram-positive and Gram-negative bacteria, erythrocytes, and yeast at micromolar concentrations. In this work, we investigated the role of the hinge in latarcin 2a (ltc2a, GLFGKLIKKFGRKAISYAVKKARGKH-COOH), which adopts a helix–hinge–helix conformation in membrane-mimicking environments, on peptide–membrane interactions and its potential effect on the selective toxicity of the peptide. A modified latarcin 2a, ltc2aG11A, obtained by replacing the glycine at position 11 with alanine (ltc2aG11A, GLFGKLIKKFARKAISYAVKKARGKH-COOH), adopts a more rigid structure due to the reduced conformational flexibility. Langmuir monolayer measurements combined with atomic force microscopy and X-ray photoemission electron microscopy (X-PEEM) indicate that both peptides bind and insert preferentially into anionic compared with zwitterionic phospholipid monolayers. Modified ltc2aG11A was found to be more disruptive of supported phospholipid bilayer modeling mammalian cell membrane. However, no considerable difference in lytic activity of the two peptides toward bacterial membrane was found. Overall the data indicate that decrease in the flexibility of ltc2a induced by the modification in the hinge region is likely to increase the peptide’s nonspecific interactions with zwitterionic cell membranes and potentially increase its toxicity against eukaryotic cells.     

Human leukocyte antigen variants B*44 and B*57 are consistently favorable during two distinct phases of primary HIV-1 infection in sub-Saharan Africans with several viral subtypes

As part of an ongoing study of early human immunodeficiency virus type 1 (HIV-1) infection in sub-Saharan African countries, we have identified 134 seroconverters (SCs) with distinct acute-phase (peak) and early chronic-phase (set-point) viremias. SCs with class I human leukocyte antigen (HLA) variants B*44 and B*57 had much lower peak viral loads (VLs) than SCs without these variants (adjusted linear regression beta values of -1.08 ± 0.26 log(10) [mean ± standard error] and -0.83 ± 0.27 log(10), respectively; P < 0.005 for both), after accounting for several nongenetic factors, including gender, age at estimated date of infection, duration of infection, and country of origin. These findings were confirmed by alternative models in which major viral subtypes (A1, C, and others) in the same SCs replaced country of origin as a covariate (P ≤ 0.03). Both B*44 and B*57 were also highly favorable (P ≤ 0.03) in analyses of set-point VLs. Moreover, B*44 was associated with relatively high CD4(+) T-cell counts during early chronic infection (P = 0.02). Thus, at least two common HLA-B variants showed strong influences on acute-phase as well as early chronic-phase VL, regardless of the infecting viral subtype. If confirmed, the identification of B*44 as another favorable marker in primary HIV-1 infection should help dissect mechanisms of early immune protection against HIV-1 infection.     

Chemical control of metabolically-engineered voltage-gated K+ channels

Metabolic oligosaccharide engineering is a powerful approach for installing unnatural glycans with unique functional groups into the glycocalyx of living cells and animals. Using this approach, we showed that K⁺ channel complexes decorated with thiol-containing sialic acids were irreversibly inhibited with scorpion toxins bearing a pendant maleimide group. Irreversible inhibition required a glycosylated K⁺ channel subunit and was completely reversible with mild reductant when the tether connecting the toxin to the maleimide contained a disulfide bond. Cleavage of the disulfide bond not only restored function, but delivered a biotin moiety to the modified K⁺ channel subunit, providing a novel approach for preferentially labeling wild type K⁺ channel complexes functioning in cells.     

The density of macrophages in colorectal cancer is inversely correlated to TGF-β1 expression and patients’ survival

The role of macrophages in colorectal cancer tumorogenesis is complex because they can both prevent and promote tumor development. We investigated CD68-positive cell infiltration in tumor tissue and its correlations with proteins of TGF-β1 signaling pathway and survival of the patients after surgical therapy. A non-selected panel of 210 primary tumors of colorectal origin was investigated immunohistochemically with antibodies against CD68, TGF-β1, TGFβRII and Smad4. Lower CD68 infiltration in tumor stroma was associated with expression of TGF-β1 (p = 0.002) and SMAD4 (p = 0.090) in tumor cell cytoplasm and with TGFβRII expression (p = 0.017) in tumor cells membranes. The absence of SMAD4 immune deposits in tumor cell nuclei was more often seen in biopsies with low number of CD68 in the invasive front (p = 0.044). The low number of CD68-positive cells was significantly associated with several adverse clinical and histological tumor characteristics as the presence of metastases in local lymph nodes (p = 0.047), distant metastases (p = 0.0003), advanced tumor stage (p = 0.006), tumor cell invasion of blood, lymph vessels or perineural invasion (p = 0.004), higher histological types (p = 0.0002) and lower grade of inflammatory infiltration in the invasive front (p = 0.002). Moreover, the low grade of CD68 appeared to be significant unfavorable factors of prognosis of the patients with colorectal cancer. The results of our study confirm the prognostic significance of low level of tumor-associated macrophage infiltration in colorectal cancer as unfavorable marker for survival of the patients.     

Urbanicity and Lifestyle Risk Factors for Cardiometabolic Diseases in Rural Uganda: A Cross-Sectional Study

Background

Urban living is associated with unhealthy lifestyles that can increase the risk of cardiometabolic diseases. In sub-Saharan Africa (SSA), where the majority of people live in rural areas, it is still unclear if there is a corresponding increase in unhealthy lifestyles as rural areas adopt urban characteristics. This study examines the distribution of urban characteristics across rural communities in Uganda and their associations with lifestyle risk factors for chronic diseases.

Methods and Findings

Using data collected in 2011, we examined cross-sectional associations between urbanicity and lifestyle risk factors in rural communities in Uganda, with 7,340 participants aged 13 y and above across 25 villages. Urbanicity was defined according to a multi-component scale, and Poisson regression models were used to examine associations between urbanicity and lifestyle risk factors by quartile of urbanicity. Despite all of the villages not having paved roads and running water, there was marked variation in levels of urbanicity across the villages, largely attributable to differences in economic activity, civil infrastructure, and availability of educational and healthcare services. In regression models, after adjustment for clustering and potential confounders including socioeconomic status, increasing urbanicity was associated with an increase in lifestyle risk factors such as physical inactivity (risk ratio [RR]: 1.19; 95% CI: 1.14, 1.24), low fruit and vegetable consumption (RR: 1.17; 95% CI: 1.10, 1.23), and high body mass index (RR: 1.48; 95% CI: 1.24, 1.77).

Conclusions

This study indicates that even across rural communities in SSA, increasing urbanicity is associated with a higher prevalence of lifestyle risk factors for cardiometabolic diseases. This finding highlights the need to consider the health impact of urbanization in rural areas across SSA. Please see later in the article for the Editors'' Summary     

Age,Gender, and Cancer but Not Neurodegenerative and Cardiovascular Diseases Strongly Modulate Systemic Effect of the Apolipoprotein E4 Allele on Lifespan

Enduring interest in the Apolipoprotein E (ApoE) polymorphism is ensured by its evolutionary-driven uniqueness in humans and its prominent role in geriatrics and gerontology. We use large samples of longitudinally followed populations from the Framingham Heart Study (FHS) original and offspring cohorts and the Long Life Family Study (LLFS) to investigate gender-specific effects of the ApoE4 allele on human survival in a wide range of ages from midlife to extreme old ages, and the sensitivity of these effects to cardiovascular disease (CVD), cancer, and neurodegenerative disorders (ND). The analyses show that women''s lifespan is more sensitive to the e4 allele than men''s in all these populations. A highly significant adverse effect of the e4 allele is limited to women with moderate lifespan of about 70 to 95 years in two FHS cohorts and the LLFS with relative risk of death RR = 1.48 (p = 3.6×10⁻⁶) in the FHS cohorts. Major human diseases including CVD, ND, and cancer, whose risks can be sensitive to the e4 allele, do not mediate the association of this allele with lifespan in large FHS samples. Non-skin cancer non-additively increases mortality of the FHS women with moderate lifespans increasing the risks of death of the e4 carriers with cancer two-fold compared to the non-e4 carriers, i.e., RR = 2.07 (p = 5.0×10⁻⁷). The results suggest a pivotal role of non-sex-specific cancer as a nonlinear modulator of survival in this sample that increases the risk of death of the ApoE4 carriers by 150% (p = 5.3×10⁻⁸) compared to the non-carriers. This risk explains the 4.2 year shorter life expectancy of the e4 carriers compared to the non-carriers in this sample. The analyses suggest the existence of age- and gender-sensitive systemic mechanisms linking the e4 allele to lifespan which can non-additively interfere with cancer-related mechanisms.     

GLT-1 Transport Stoichiometry Is Constant at Low and High Glutamate Concentrations when Chloride Is Substituted by Gluconate

Glutamate is the major excitatory neurotransmitter, but prolonged exposure even at micromolar concentrations causes neuronal death. Extracellular glutamate is maintained at nanomolar level by glutamate transporters, which, however, may reverse transport and release glutamate. If and when the reverse occurs depends on glutamate transport stoichiometry (GTS). Previously we found that in the presence of chloride, the coupled GLT-1 glutamate transporter current and its relationship to radiolabeled glutamate flux significantly decreased when extracellular glutamate concentration increased above 0.2 mM, which implies a change in GTS. Such high concentrations are feasible near GLT-1 expressed close to synaptic release site during excitatory neurotransmission. The aim of this study was to determine GLT-1 GTS at both low (19–75 μM) and high (300–1200 μM) glutamate concentration ranges. GTS experiments were conducted in the absence of chloride to avoid contributions by the GLT-1 uncoupled chloride conductance. Mathematical analysis of the transporter thermodynamic equilibrium allowed us to derive equations revealing the number of a particular type of ion transported per elementary charge based on the measurements of the transporter reversal potential. We found that GLT-1a expressed in COS-7 cells co-transports 1.5 Na⁺, 0.5 Glu^-, 0.5 H⁺ and counter-transports 0.6 K⁺ per elementary charge in both glutamate concentration ranges, and at both 37°C and 26°C temperatures. The thermodynamic parameter Q ₁₀ = 2.4 for GLT-1 turnover rate of 19 s^-1 (37°C, -50 mV) remained constant in the 10 μM–10 mM glutamate concentration range. Importantly, the previously reported decrease in the current/flux ratio at high glutamate concentration was not seen in the absence of chloride in both COS-7 cells and cultured rat neurons. Therefore, only in the absence of chloride, GLT-1 GTS remains constant at all glutamate concentrations. Possible explanations for why apparent GTS might vary in the presence of chloride are discussed.