The G-308A variant of the Tumor Necrosis Factor-α (TNF-α) gene is not associated with obesity, insulin resistance and body fat distribution

BACKGROUND: Tumor Necrosis Factor-α (TNF-α) has been implicated in the pathogenesis of insulin resistance and obesity. The increased expression of TNF-α in adipose tissue has been shown to induce insulin resistance, and a polymorphism at position -308 in the promoter region ofTNF-α has been shown to increase transcription of the gene in adipocytes. Aim of this study is to investigate the role of the G-308A TNFα variant in obesity and to study the possible influence of this mutation on body fat distribution and on measures of obesity (including Fat Free Mass, Fat Mass, basal metabolic rate), insulin resistance (measured as HOMA(IR)), and lipid abnormalities. The G-308A TNFα polymorphism has been studied in 115 patients with obesity (mean BMI 33.9 ± 0.5) and in 79 normal lean subjects (mean BMI 24.3 ± 0.3). METHODS: The G-308A variant, detected by PCR amplification and Nco-1 digestion, determines the loss of a restriction site resulting in a single band of 107 bp [the (A) allele]. RESULTS: The (A) allele frequencies of the G-308A TNFα polymorphism were 13.1% in the obese group and 14.6% in the lean subjects, with no significant difference between the two groups. Furthermore, no association was found with BMI classes, body fat distribution, HOMA(IR), and metabolic abnormalities. CONCLUSIONS: Our study did not detect any significant association of the G-308A TNFα polymorphism with obesity or with its clinical and metabolic abnormalities in this population. Our data suggests that, in our population, the G-308A TNFα polymorphism is unlikely to play a major role in the pathogenesis of these conditions

Selective gene silencing by viral delivery of short hairpin RNA

RNA interference (RNAi) technology has not only become a powerful tool for functional genomics, but also allows rapid drug target discovery and in vitro validation of these targets in cell culture. Furthermore, RNAi represents a promising novel therapeutic option for treating human diseases, in particular cancer. Selective gene silencing by RNAi can be achieved essentially by two nucleic acid based methods: i) cytoplasmic delivery of short double-stranded (ds) interfering RNA oligonucleotides (siRNA), where the gene silencing effect is only transient in nature, and possibly not suitable for all applications; or ii) nuclear delivery of gene expression cassettes that express short hairpin RNA (shRNA), which are processed like endogenous interfering RNA and lead to stable gene down-regulation. Both processes involve the use of nucleic acid based drugs, which are highly charged and do not cross cell membranes by free diffusion. Therefore, in vivo delivery of RNAi therapeutics must use technology that enables the RNAi therapeutic to traverse biological membrane barriers in vivo. Viruses and the vectors derived from them carry out precisely this task and have become a major delivery system for shRNA. Here, we summarize and compare different currently used viral delivery systems, give examples of in vivo applications, and indicate trends for new developments, such as replicating viruses for shRNA delivery to cancer cells

Temperature/precipitation extreme relationship in North-Western Mediterranean: HyMeX/MED-CORDEX simulation and observation analysis

International audienc

Paleoindian cave dwellers in the Amazon: thepPeopling of the Americas

A Paleoindian campsite has been uncovered in stratified prehistoric deposits in Caverna da Pedra Pintada at Monte Alegre in the Brazilian Amazon. Fifty-six radiocarbon dates on carbonized plant remains and 13 luminescence dates on lithics and sediment indicate a late Pleistocene age contemporary with North American Paleoindians. Paintings, triangular bifacial spear points, and other tools in the cave document a culture distinct from North American cultures. Carbonized tree fruits and wood and faunal remains reveal a broad-spectrum economy of humid tropical forest and riverine foraging. The existence of this and related cultures east of the Andes changes understanding of the migrations and ecological adaptations of early foragers

Soil loss risk and habitat quality in streams of a meso-scale river basin Risco de perda de solo e qualidade do habitat numa bacia hidrográfica de meso-escala

Soil loss expectation and possible relationships among soil erosion, riparian vegetation and water quality were studied in the São José dos Dourados River basin, State of São Paulo, Brazil. Through Geographic Information System (GIS) resources and technology, Soil Loss Expectation (SLE) data obtained using the Universal Soil Loss Equation (USLE) model were analyzed. For the whole catchment area and for the 30 m buffer strips of the streams of 22 randomly selected catchments, the predominant land use and habitat quality were studied. Owing mainly to the high soil erodibility, the river basin is highly susceptible to erosive processes. Habitat quality analyses revealed that the superficial water from the catchments is not chemically impacted but suffers physical damage. A high chemical purity is observed since there are no urban areas along the catchments. The water is physically poor because of high rates of sediment delivery and the almost nonexistence of riparian vegetation.<br>Expectativa de perda de solo e possíveis relações entre erosão, vegetação ripária e qualidade da água foram estudados na bacia do rio São José dos Dourados (SP). Através de recursos de geoprocessamento e da Equação Universal de Perda de Solos, os dados sobre expectativa de perda de solo foram levantados. Para a área de drenagem total e a faixa tampão dos corpos d'água de 22 sub-bacias aleatoriamente selecionadas, analisou-se a cobertura do solo predominante e qualidade do habitat. Devido principalmente à alta erodibilidade do solo, a área estudada é altamente suscetível ao processo erosivo. As análises de qualidade da água revelaram que as águas superficiais das sub-bacias estão quimicamente não impactadas, mas fisicamente degradadas. A alta pureza química deve-se, possivelmente, à ausência de áreas urbanizadas ao longo das sub-bacias e as alterações nas características físicas são, possivelmente, decorrentes das altas taxas de transferência de sedimento aos corpos d'água e à quase ausência de mata ciliar

A systematic critical review of epidemiological studies on public health concerns of municipal solid waste handling

AIMS : The ultimate aim of this review was to summarise the epidemiological evidence on the association between municipal solid waste management operations and health risks to populations residing near landfills and incinerators, waste workers and recyclers. To accomplish this, the sub-aims of this review article were to (1) examine the health risks posed by municipal solid waste management activities, (2) determine the strengths and gaps of available literature on health risks from municipal waste management operations and (3) suggest possible research needs for future studies.METHODS : The article reviewed epidemiological literature on public health concerns of municipal solid waste handling published in the period 1995-2014. The PubMed and MEDLINE computerised literature searches were employed to identify the relevant papers using the keywords solid waste, waste management, health risks, recycling, landfills and incinerators. Additionally, all references of potential papers were examined to determine more articles that met the inclusion criteria. RESULTS : A total of 379 papers were identified, but after intensive screening only 72 met the inclusion criteria and were reviewed. Of these studies, 33 were on adverse health effects in communities living near waste dumpsites or incinerators, 24 on municipal solid waste workers and 15 on informal waste recyclers. Reviewed studies were unable to demonstrate a causal or non-causal relationship due to various limitations. CONCLUSION : In light of the above findings, our review concludes that overall epidemiological evidence in reviewed articles is inadequate mainly due to methodological limitations and future research needs to develop tools capable of demonstrating causal or non-causal relationships between specific waste management operations and adverse health endpoints.http://pph.sagepub.comhb2017School of Health Systems and Public Health (SHSPH

Levy-like movement patterns of metastatic cancer cells revealed in microfabricated systems and implicated in vivo

Metastatic cancer cells differ from their non-metastatic counterparts not only in terms of molecular composition and genetics, but also by the very strategy they employ for locomotion. Here, we analyzed large-scale statistics for cells migrating on linear microtracks to show that metastatic cancer cells follow a qualitatively different movement strategy than their non-invasive counterparts. The trajectories of metastatic cells display clusters of small steps that are interspersed with long &quot;flights&quot;. Such movements are characterized by heavy-tailed, truncated power law distributions of persistence times and are consistent with the Levy walks that are also often employed by animal predators searching for scarce prey or food sources. In contrast, non-metastatic cancerous cells perform simple diffusive movements. These findings are supported by preliminary experiments with cancer cells migrating away from primary tumors in vivo. The use of chemical inhibitors targeting actin-binding proteins allows for &quot;reprogramming&quot; the Levy walks into either diffusive or ballistic movements