Polymorphism analysis of the CTLA-4 gene in paracoccidioidomycosis patients

The CTLA-4 protein is expressed in activated T cells and plays an essential role in the immune response through its regulatory effect on T cell activation. Polymorphisms of the CTLA-4 gene have been correlated with autoimmune, neoplastic and infectious illnesses. This work aimed to verify possible associations between single nucleotide polymorphisms (SNPs) in CTLA-4, -318C/T in the promoter and +49A/G in exon 1 and paracoccidioidomycosis (PCM) caused by Paracoccidioides brasiliensis. For this purpose, 66 chronic form PCM patients and 76 healthy controls had their allele, genotype and haplotype frequencies determined. The genetic admixture structure of the patients and controls was evaluated to eliminate ancestral bias. The comparison of frequencies indicated no significant differences between patients and controls that could link the SNPs to PCM. Groups were admixture matched with no difference observed in population ancestry inference, indicating that the absence of association between CTLA-4 polymorphisms and PCM could not be attributed to ancestral bias. This study showed that there was no association between the CTLA-4 SNPs -318 and +49 and the resistance or susceptibility to PCM

IGF2, LEPR, POMC, PPARG, and PPARGC1 gene variants are associated with obesity-related risk phenotypes in Brazilian children and adolescents.

Association studies of genetic variants and obesity and/or obesity-related risk factors have yielded contradictory results. The aim of the present study was to determine the possible association of five single-nucleotide polymorphisms (SNPs) located in the IGF2, LEPR, POMC, PPARG, and PPARGC1 genes with obesity or obesity-related risk phenotypes. This case-control study assessed overweight (n=192) and normal-weight (n=211) children and adolescents. The SNPs were analyzed using minisequencing assays, and variables and genotype distributions between the groups were compared using one-way analysis of variance and Pearson?s chi-square or Fisher?s exact tests. Logistic regression analysis adjusted for age and gender was used to calculate the odds ratios (ORs) for selected phenotype risks in each group. No difference in SNP distribution was observed between groups. In children, POMC rs28932472(C) was associated with lower diastolic blood pressure (P=0.001), higher low-density lipoprotein (LDL) cholesterol (P=0.014), and higher risk in overweight children of altered total cholesterol (OR=7.35, P=0.006). In adolescents, IGF2 rs680(A) was associated with higher glucose (P=0.012) and higher risk in overweight adolescents for altered insulin (OR=10.08, P=0.005) and homeostasis model of insulin resistance (HOMA-IR) (OR=6.34, P=0.010). PPARG rs1801282(G) conferred a higher risk of altered insulin (OR=12.31, P=0.003), and HOMA-IR (OR=7.47, P=0.005) in overweight adolescents. PARGC1 rs8192678(A) was associated with higher triacylglycerols (P=0.005), and LEPR rs1137101(A) was marginally associated with higher LDL cholesterol (P=0.017). LEPR rs1137101(A) conferred higher risk for altered insulin, and HOMA-IR in overweight adolescents. The associations observed in this population suggested increased risk for cardiovascular diseases and/or type 2 diabetes later in life for individuals carrying these allele

Suppression of Soft Tissue Sarcoma Growth by a Host Defense-Like Lytic Peptide

BACKGROUND: Soft tissue sarcoma (STS) is an anatomically and histologically heterogeneous neoplasia that shares a putative mesenchymal cell origin. The treatment with common chemotherapeutics is still unsatisfying because of association with poor response rates. Although evidence is accumulating for potent oncolytic activity of host defense peptides (HDPs), their potential therapeutic use is often limited by poor bioavailability and inactivation in serum. Therefore, we tested the designer host defense-like lytic D,L-amino acid peptide [D]-K3H3L9 on two STS cell lines in vitro and also in an athymic and syngeneic mouse model. In recent studies the peptide could show selectivity against prostate carcinoma cells and also an active state in serum. METHODS: In vitro the human synovial sarcoma cell line SW982, the murine fibrosarcoma cell line BFS-1 and primary human fibroblasts as a control were exposed to [D]-K3H3L9, a 15mer D,L-amino acid designer HDP. Cell vitality in physiological and acidic conditions (MTT-assay), cell growth (BrdU) and DNA-fragmentation (TUNEL) were investigated. Membrane damage at different time points could be analyzed with LDH assay. An antibody against the tested peptide and recordings using scanning electron microscopy could give an inside in the mode of action. In vivo [D]-K3H3L9 was administered intratumorally in an athymic and syngeneic (immunocompetent) mouse model with SW982 and BFS-1 cells, respectively. After three weeks tumor sections were histologically analyzed. RESULTS: The peptide exerts rapid and high significant cytotoxicity and antiproliferating activity against the malignant cell lines, apparently via a membrane disrupting mode of action. The local intratumoral administration of [D]-K3H3L9 in the athymic and syngeneic mice models significantly inhibited tumor progression. The histological analyses of the tumor sections revealed a significant antiproliferative, antiangiogenic activity of the treatment group. CONCLUSION: These findings demonstrate the in vitro and in vivo oncolytic activity of [D]-K3H3L9 in athymic and syngeneic mouse models

Executive cash compensation and tax aggressiveness of Chinese firms

We examine the influence of corporate compensation policies on firms’ tax aggressiveness in an emerging market where executive compensation is primarily in cash form. Based on a hand-collected dataset of 958 firm-year observations of Chinese listed firms for the 2006-2012 period, we find that firms paying higher executive cash compensation are associated with lower tax aggressiveness. This relationship also holds for the excess cash compensation measures which control for executive shareholding, firm profitability, size, growth opportunity, and board independence. We further document that mutual funds ownership pressure firms paying higher compensation to reduce their tax aggressiveness, suggesting adverse selection by mutual funds on firms exhibiting risky tax avoidance activities. High leverage offsets the negative link between cash compensation and tax aggressiveness, indicating a complementary effect between debt and tax avoidance, and, hence, suggesting that creditor monitoring is weak. These results are robust to the system-GMM estimation, which simultaneously account for the endogeneity of executive compensation, tax aggressiveness, ownership and control, leverage, and corporate governance. Our findings on Chinese firms have important policy implications for developing countries around the world with concentrated ownership structure, weak institutional environment, widespread corruption, ineffective rule of law, and ongoing significant social and political transformation

Growth and Demography of the Solitary Scleractinian Coral Leptopsammia pruvoti along a Sea Surface Temperature Gradient in the Mediterranean Sea

The demographic traits of the solitary azooxanthellate scleractinian Leptopsammia pruvoti were determined in six populations on a sea surface temperature (SST) gradient along the western Italian coasts. This is the first investigation of the growth and demography characteristics of an azooxanthellate scleractinian along a natural SST gradient. Growth rate was homogeneous across all populations, which spanned 7 degrees of latitude. Population age structures differed between populations, but none of the considered demographic parameters correlated with SST, indicating possible effects of local environmental conditions. Compared to another Mediterranean solitary scleractinian, Balanophyllia europaea, zooxanthellate and whose growth, demography and calcification have been studied in the same sites, L. pruvoti seems more tolerant to temperature increase. The higher tolerance of L. pruvoti, relative to B. europaea, may rely on the absence of symbionts, and thus the lack of an inhibition of host physiological processes by the heat-stressed zooxanthellae. However, the comparison between the two species must be taken cautiously, due to the likely temperature differences between the two sampling depths. Increasing research effort on determining the effects of temperature on the poorly studied azooxanthellate scleractinians may shed light on the possible species assemblage shifts that are likely to occur during the current century as a consequence of global climatic change

Inter-domain Communication Mechanisms in an ABC Importer: A Molecular Dynamics Study of the MalFGK2E Complex

ATP-Binding Cassette transporters are ubiquitous membrane proteins that convert the energy from ATP-binding and hydrolysis into conformational changes of the transmembrane region to allow the translocation of substrates against their concentration gradient. Despite the large amount of structural and biochemical data available for this family, it is still not clear how the energy obtained from ATP hydrolysis in the ATPase domains is “transmitted” to the transmembrane domains. In this work, we focus our attention on the consequences of hydrolysis and inorganic phosphate exit in the maltose uptake system (MalFGK2E) from Escherichia coli. The prime goal is to identify and map the structural changes occurring during an ATP-hydrolytic cycle. For that, we use extensive molecular dynamics simulations to study three potential intermediate states (with 10 replicates each): an ATP-bound, an ADP plus inorganic phosphate-bound and an ADP-bound state. Our results show that the residues presenting major rearrangements are located in the A-loop, in the helical sub-domain, and in the “EAA motif” (especially in the “coupling helices” region). Additionally, in one of the simulations with ADP we were able to observe the opening of the NBD dimer accompanied by the dissociation of ADP from the ABC signature motif, but not from its corresponding P-loop motif. This work, together with several other MD studies, suggests a common communication mechanism both for importers and exporters, in which ATP-hydrolysis induces conformational changes in the helical sub-domain region, in turn transferred to the transmembrane domains via the “coupling helices”

Predictors of Enhancing Human Physical Attractiveness: Data from 93 Countries

People across the world and throughout history have gone to great lengths to enhance their physical appearance. Evolutionary psychologists and ethologists have largely attempted to explain this phenomenon via mating preferences and strategies. Here, we test one of the most popular evolutionary hypotheses for beauty-enhancing behaviors, drawn from mating market and parasite stress perspectives, in a large cross-cultural sample. We also test hypotheses drawn from other influential and non-mutually exclusive theoretical frameworks, from biosocial role theory to a cultural media perspective. Survey data from 93,158 human participants across 93 countries provide evidence that behaviors such as applying makeup or using other cosmetics, hair grooming, clothing style, caring for body hygiene, and exercising or following a specific diet for the specific purpose of improving ones physical attractiveness, are universal. Indeed, 99% of participants reported spending \u3e10 min a day performing beauty-enhancing behaviors. The results largely support evolutionary hypotheses: more time was spent enhancing beauty by women (almost 4 h a day, on average) than by men (3.6 h a day), by the youngest participants (and contrary to predictions, also the oldest), by those with a relatively more severe history of infectious diseases, and by participants currently dating compared to those in established relationships. The strongest predictor of attractiveness-enhancing behaviors was social media usage. Other predictors, in order of effect size, included adhering to traditional gender roles, residing in countries with less gender equality, considering oneself as highly attractive or, conversely, highly unattractive, TV watching time, higher socioeconomic status, right-wing political beliefs, a lower level of education, and personal individualistic attitudes. This study provides novel insight into universal beauty-enhancing behaviors by unifying evolutionary theory with several other complementary perspectives

Predictors of enhancing human physical attractiveness: Data from 93 countries

People across the world and throughout history have gone to great lengths to enhance their physical appearance. Evolutionary psychologists and ethologists have largely attempted to explain this phenomenon via mating preferences and strategies. Here, we test one of the most popular evolutionary hypotheses for beauty-enhancing behaviors, drawn from mating market and parasite stress perspectives, in a large cross-cultural sample. We also test hypotheses drawn from other influential and non-mutually exclusive theoretical frameworks, from biosocial role theory to a cultural media perspective. Survey data from 93,158 human participants across 93 countries provide evidence that behaviors such as applying makeup or using other cosmetics, hair grooming, clothing style, caring for body hygiene, and exercising or following a specific diet for the specific purpose of improving ones physical attractiveness, are universal. Indeed, 99% of participants reported spending >10 min a day performing beauty-enhancing behaviors. The results largely support evolutionary hypotheses: more time was spent enhancing beauty by women (almost 4 h a day, on average) than by men (3.6 h a day), by the youngest participants (and contrary to predictions, also the oldest), by those with a relatively more severe history of infectious diseases, and by participants currently dating compared to those in established relationships. The strongest predictor of attractiveness-enhancing behaviors was social media usage. Other predictors, in order of effect size, included adhering to traditional gender roles, residing in countries with less gender equality, considering oneself as highly attractive or, conversely, highly unattractive, TV watching time, higher socioeconomic status, right-wing political beliefs, a lower level of education, and personal individualistic attitudes. This study provides novel insight into universal beauty-enhancing behaviors by unifying evolutionary theory with several other complementary perspectives