Barefoot Plantar Pressure Indicates Progressive Neurological Damage in Patients with Human T-Cell Lymphotropic Virus Type 1 Infection

Background

The human T-Cell Lymphotropic Virus Type 1 (HTLV-1) is a retrovirus associated with neurological alterations; individuals with HTLV-1 infection may develop HTLV-1 associated myelopathy / tropical spastic paraparesis (HAM/TSP). Frequent neurological complaints include foot numbness and leg weakness. In this study, we compared the distribution of the body weight on different areas of the foot in HTLV-1 patients with HAM/TSP, asymptomatic HTLV-1 patients, and healthy individuals.

Methodology

We studied 36 HTLV-1 infected patients, who were divided in two groups of 18 patients each based on whether or not they had been diagnosed with HAM/TSP, and 17 control subjects. The evaluation included an interview on the patient’s clinical history and examinations of the patient’s reflexes, foot skin tactile sensitivity, and risk of falling. The pressure distribution on different areas of the foot was measured with baropodometry, using a pressure platform, while the patients had their eyes open or closed.

Main Findings

The prevalence of neurological disturbances—altered reflexes and skin tactile sensitivity and increased risk of falling—was higher in HTLV-1 HAM/TSP patients than in HTLV-1 asymptomatic patients. The medium and maximum pressure values were higher in the forefoot than in the midfoot and hindfoot in both HTLV-1 groups. In addition, the pressure on the hindfoot was lower in HAM/TSP patients compared to control subjects.

Conclusions

The neurological disturbances associated with HTLV-1 infection gradually worsened from HTLV-1 asymptomatic patients to HAM/TSP patients. Baropodometry is a valuable tool to establish the extent of neurological damage in patients suffering from HTLV-1 infection.     

Whole Exome Sequencing Reveals Homozygous Mutations in RAI1, OTOF,and SLC26A4 Genes Associated with Nonsyndromic Hearing Loss in Altaian Families (South Siberia)

Hearing loss (HL) is one of the most common sensorineural disorders and several dozen genes contribute to its pathogenesis. Establishing a genetic diagnosis of HL is of great importance for clinical evaluation of deaf patients and for estimating recurrence risks for their families. Efforts to identify genes responsible for HL have been challenged by high genetic heterogeneity and different ethnic-specific prevalence of inherited deafness. Here we present the utility of whole exome sequencing (WES) for identifying candidate causal variants for previously unexplained nonsyndromic HL of seven patients from four unrelated Altaian families (the Altai Republic, South Siberia). The WES analysis revealed homozygous missense mutations in three genes associated with HL. Mutation c.2168A>G (SLC26A4) was found in one family, a novel mutation c.1111G>C (OTOF) was revealed in another family, and mutation c.5254G>A (RAI1) was found in two families. Sanger sequencing was applied for screening of identified variants in an ethnically diverse cohort of other patients with HL (n = 116) and in Altaian controls (n = 120). Identified variants were found only in patients of Altaian ethnicity (n = 93). Several lines of evidences support the association of homozygosity for discovered variants c.5254G>A (RAI1), c.1111C>G (OTOF), and c.2168A>G (SLC26A4) with HL in Altaian patients. Local prevalence of identified variants implies possible founder effect in significant number of HL cases in indigenous population of the Altai region. Notably, this is the first reported instance of patients with RAI1 missense mutation whose HL is not accompanied by specific traits typical for Smith-Magenis syndrome. Presumed association of RAI1 gene variant c.5254G>A with isolated HL needs to be proved by further experimental studies.     

How do primates affect seed germination? A meta‐analysis of gut passage effects on neotropical plants

Biotic seed dispersal is a key process maintaining biodiversity in tropical forests where most trees produce vertebrate‐dispersed seeds. Existing meta‐analyses suggest an overall positive effect of vertebrate gut passage on seed germination, but no significant effects for non‐flying mammals. However, previous meta‐analyses combined rodents (seed predators) and primates (seed dispersers) into the non‐flying mammals category, which may confound specific effects of each group on seed germination. However positive effects of monkeys on germination had previously been found in some studies. Here we disentangle the role of Neotropical primates as contributors to seed dispersal in tropical forests by running a meta‐analysis to determine the overall magnitude of gut passage effects on seed germination percentage and mean time to germination. We also compare effect sizes as a function of different feeding guilds, gut complexities, and seed size. Our results show a strong, positive effect of primates on seed germination percentage and on the number of days to first germination. Strictly frugivorous monkeys, the group most threatened by extinction, showed the highest dispersal quality, increasing germination percentage by 75%. Primates that include insects in their diets had no average effect on germination percentage or time. Gut passage had different outcomes on seeds with different sizes; both large and small seeds showed similar increases in germination percentages after gut passage, but only large seeds germinated faster than control seeds after gut passage. Our results show a relevant role for primates in providing high seed dispersal quality and as drivers of forest regeneration. The combined effects of defaunation and forest fragmentation may result in decreased regeneration of trees, which has the potential to affect negatively both forest structure and ecosystem processes. Finally, we provide general guidelines for standardizing research on seed dispersal by primates. Synthesis Consuming fleshy fruits and dispersing seeds is the main ecological service provided by vertebrates to plants. Vertebrate increases seed germination due to treatment given during digestive system passage. Previous meta‐analyses suggest an overall positive effect of vertebrate gut passage on germination, but no insights are available on its variation among different functional groups of mammals. Our analyses indicated that gut passage by Neotropical primates increased seed germination. Strict frugivores, the ones most threatened by extinction, were the most efficient. Our results show a relevant role for primates in providing high seed dispersal quality and as drivers of forest regeneration, which can be meaningful for conservation in a community scale.     

Brain-derived neurotrophic factor and early-life stress: Multifaceted interplay

The brain-derived neurotrophic factor (BDNF) is a key regulator of neural development and plasticity. Long-term changes in the BDNF pathway are associated with childhood adversity and adult depression symptoms. Initially, stress-induced decreases in the BDNF pathway were found in some studies, but subsequent reports indicated the relationship between stress and BDNF to be much more complex, and the concept was significantly revised. In the present mini-review, we focus on the structure and regulation of the Bbnf gene as well as on the stress–BDNF interactions under early-life adverse conditions.     

Phytomass change in natural phytocenosis as an indicator of technogenic pollution of soils with heavy metals

This study considered the possibility of using plant community phytomass for the assessment of soil pollution with heavy metals (HM) from industrial wastes. The three-year-long field experiment was run under the regional natural meadow vegetation; the polymetallic galvanic slime was used as an industrial waste contaminant. It is shown that soil contamination primarily causes decrease of phytomass in the growing phytocenosis. The vegetation experiments determined nonlinear dependence of cultivated and wild plant biomass on the level of soil contamination; it is described by the equations of logistic and Gaussian regression. In the absence of permanent contaminants, the soil is self-cleaned over time. It reproduces phytomass mainly due to the productivity increase of the most pollution-tolerant species in the remaining phytocenosis. This phenomenon is defined as environmental hysteresis. Soil pollution by industrial waste leads to the loss of plant biodiversity. The research shows that the study of the HM impact on ecosystems is expedient given the consideration of the “soil–phytocenosis–pollutant” complex in the “dose–response” aspect. The reaction of phytocenosis on HM showing decline in phytomass leads to serious limitations in the choice of accumulating plants, because the adsorbed HM are rejected through phytomass.     

Genome‐wide association study identifies loci associated with liability to alcohol and drug dependence that is associated with variability in reward‐related ventral striatum activity in African‐ and European‐Americans

Genetic influences on alcohol and drug dependence partially overlap, however, specific loci underlying this overlap remain unclear. We conducted a genome‐wide association study (GWAS) of a phenotype representing alcohol or illicit drug dependence (ANYDEP) among 7291 European‐Americans (EA; 2927 cases) and 3132 African‐Americans (AA: 1315 cases) participating in the family‐based Collaborative Study on the Genetics of Alcoholism. ANYDEP was heritable (h ² in EA = 0.60, AA = 0.37). The AA GWAS identified three regions with genome‐wide significant (GWS; P < 5E‐08) single nucleotide polymorphisms (SNPs) on chromosomes 3 (rs34066662, rs58801820) and 13 (rs75168521, rs78886294), and an insertion‐deletion on chromosome 5 (chr5:141988181). No polymorphisms reached GWS in the EA. One GWS region (chromosome 1: rs1890881) emerged from a trans‐ancestral meta‐analysis (EA + AA) of ANYDEP, and was attributable to alcohol dependence in both samples. Four genes (AA: CRKL, DZIP3, SBK3; EA: P2RX6) and four sets of genes were significantly enriched within biological pathways for hemostasis and signal transduction. GWS signals did not replicate in two independent samples but there was weak evidence for association between rs1890881 and alcohol intake in the UK Biobank. Among 118 AA and 481 EA individuals from the Duke Neurogenetics Study, rs75168521 and rs1890881 genotypes were associated with variability in reward‐related ventral striatum activation. This study identified novel loci for substance dependence and provides preliminary evidence that these variants are also associated with individual differences in neural reward reactivity. Gene discovery efforts in non‐European samples with distinct patterns of substance use may lead to the identification of novel ancestry‐specific genetic markers of risk.