A neuronal network of mitochondrial dynamics regulates metastasis.

The role of mitochondria in cancer is controversial. Using a genome-wide shRNA screen, we now show that tumours reprogram a network of mitochondrial dynamics operative in neurons, including syntaphilin (SNPH), kinesin KIF5B and GTPase Miro1/2 to localize mitochondria to the cortical cytoskeleton and power the membrane machinery of cell movements. When expressed in tumours, SNPH inhibits the speed and distance travelled by individual mitochondria, suppresses organelle dynamics, and blocks chemotaxis and metastasis, in vivo. Tumour progression in humans is associated with downregulation or loss of SNPH, which correlates with shortened patient survival, increased mitochondrial trafficking to the cortical cytoskeleton, greater membrane dynamics and heightened cell invasion. Therefore, a SNPH network regulates metastatic competence and may provide a therapeutic target in cancer

Projected drought risk in 1.5°C and 2°C warmer climates

The large socioeconomic costs of droughts make them a crucial target for impact assessments of climate change scenarios. Using multiple drought metrics and a set of simulations with the Community Earth System Model targeting 1.5°C and 2°C above preindustrial global mean temperatures, we investigate changes in aridity and the risk of consecutive drought years. If warming is limited to 2°C, these simulations suggest little change in drought risk for the U.S. Southwest and Central Plains compared to present day. In the Mediterranean and central Europe, however, drought risk increases significantly for both 1.5°C and 2°C warming targets, and the additional 0.5°C of the 2°C climate leads to significantly higher drought risk. Our study suggests that limiting anthropogenic warming to 1.5°C rather than 2°C, as aspired to by the Paris Climate Agreement, may have benefits for future drought risk but that such benefits may be regional and in some cases highly uncertain

Transcription profiling reveals potential mechanisms of dysbiosis in the oral microbiome of rhesus macaques with chronic untreated SIV infection.

A majority of individuals infected with human immunodeficiency virus (HIV) have inadequate access to antiretroviral therapy and ultimately develop debilitating oral infections that often correlate with disease progression. Due to the impracticalities of conducting host-microbe systems-based studies in HIV infected patients, we have evaluated the potential of simian immunodeficiency virus (SIV) infected rhesus macaques to serve as a non-human primate model for oral manifestations of HIV disease. We present the first description of the rhesus macaque oral microbiota and show that a mixture of human commensal bacteria and "macaque versions" of human commensals colonize the tongue dorsum and dental plaque. Our findings indicate that SIV infection results in chronic activation of antiviral and inflammatory responses in the tongue mucosa that may collectively lead to repression of epithelial development and impact the microbiome. In addition, we show that dysbiosis of the lingual microbiome in SIV infection is characterized by outgrowth of Gemella morbillorum that may result from impaired macrophage function. Finally, we provide evidence that the increased capacity of opportunistic pathogens (e.g. E. coli) to colonize the microbiome is associated with reduced production of antimicrobial peptides

Development of a multiplex DNA-based traceability tool for crop plant materials

The authenticity of food is of increasing importance for producers, retailers and consumers. All groups benefit from the correct labelling of the contents of food products. Producers and retailers want to guarantee the origin of their products and check for adulteration with cheaper or inferior ingredients. Consumers are also more demanding about the origin of their food for various socioeconomic reasons. In contrast to this increasing demand, correct labelling has become much more complex because of global transportation networks of raw materials and processed food products. Within the European integrated research project ‘Tracing the origin of food’ (TRACE), a DNA-based multiplex detection tool was developed—the padlock probe ligation and microarray detection (PPLMD) tool. In this paper, this method is extended to a 15-plex traceability tool with a focus on products of commercial importance such as the emmer wheat Farro della Garfagnana (FdG) and Basmati rice. The specificity of 14 plant-related padlock probes was determined and initially validated in mixtures comprising seven or nine plant species/varieties. One nucleotide difference in target sequence was sufficient for the distinction between the presence or absence of a specific target. At least 5% FdG or Basmati rice was detected in mixtures with cheaper bread wheat or non-fragrant rice, respectively. The results suggested that even lower levels of (un-)intentional adulteration could be detected. PPLMD has been shown to be a useful tool for the detection of fraudulent/intentional admixtures in premium foods and is ready for the monitoring of correct labelling of premium foods worldwide

Improving the detection of infectious diseases in at-risk migrants with an innovative integrated multi-infection screening digital decision support tool (IS-MiHealth) in primary care : a pilot cluster-randomized-controlled trial

There are major shortfalls in the identification and screening of at-risk migrant groups. This study aims to evaluate the effectiveness of a new digital tool (IS-MiHealth) integrated into the electronic patient record system of primary care centres in detecting prevalent migrant infections. IS-MiHealth provides targeted recommendations to health professionals for screening multiple infections, including human immunodeficiency virus (HIV), hepatitis B and C, active tuberculosis (TB), Chagas disease, strongyloidiasis and schistosomiasis, based on patient characteristics (including variables of country of origin, age and sex). A pragmatic pilot cluster-randomized-controlled trial was deployed from March to December 2018. Eight primary care centres in Catalonia, Spain, were randomly allocated 1:1 to use of the digital tool for screening, or to routine care. The primary outcome was the monthly diagnostic yield of all aggregated infections. Intervention and control sites were compared before and after implementation with respect to their monthly diagnostic yield using regression models. This study is registered on international standard randomised controlled trial number (ISRCTN) (ISRCTN14795012). A total of 15 780 migrants registered across the eight centres had at least one visit during the intervention period (March-December 2018), of which 14 598 (92.51%) fulfilled the criteria to be screened for at least one infection. There were 210 (2.57%) individuals from the intervention group with new diagnoses compared with 113 (1.49%) from the control group [odds ratio: 2.08, 95% confidence interval (CI) 1.63-2.64, P < 0.001]. The intervention centres raised their overall monthly diagnosis rate to 5.80 (95% CI 1.23-10.38, P = 0.013) extra diagnoses compared with the control centres. This monthly increase in diagnosis in intervention centres was also observed if we consider all cases together of HIV, hepatitis B and C, and active TB cases [2.72 (95% CI 0.43-5.00); P = 0.02] and was observed as well for the parasitic infections' group (Chagas disease, strongyloidiasis and schistosomiasis) 2.58 (95% CI 1.60-3.57; P < 0.001). The IS-MiHealth increased screening rate and diagnostic yield for key infections in migrants in a population-based primary care setting. Further testing and development of this new tool is warranted in larger trials and in other countries

Obesity, Metabolic Factors and Risk of Different Histological Types of Lung Cancer: A Mendelian Randomization Study

Background Assessing the relationship between lung cancer and metabolic conditions is challenging because of the confounding effect of tobacco. Mendelian randomization (MR), or the use of genetic instrumental variables to assess causality, may help to identify the metabolic drivers of lung cancer. Methods and findings We identified genetic instruments for potential metabolic risk factors and evaluated these in relation to risk using 29,266 lung cancer cases (including 11,273 adenocarcinomas, 7,426 squamous cell and 2,664 small cell cases) and 56,450 controls. The MR risk analysis suggested a causal effect of body mass index (BMI) on lung cancer risk for two of the three major histological subtypes, with evidence of a risk increase for squamous cell carcinoma (odds ratio (OR) [95% confidence interval (CI)] = 1.20 [1.01–1.43] and for small cell lung cancer (OR [95%CI] = 1.52 [1.15–2.00]) for each standard deviation (SD) increase in BMI [4.6 kg/m2]), but not for adenocarcinoma (OR [95%CI] = 0.93 [0.79–1.08]) (Pheterogeneity = 4.3x10-3). Additional analysis using a genetic instrument for BMI showed that each SD increase in BMI increased cigarette consumption by 1.27 cigarettes per day (P = 2.1x10-3), providing novel evidence that a genetic susceptibility to obesity influences smoking patterns. There was also evidence that low-density lipoprotein cholesterol was inversely associated with lung cancer overall risk (OR [95%CI] = 0.90 [0.84–0.97] per SD of 38 mg/dl), while fasting insulin was positively associated (OR [95%CI] = 1.63 [1.25–2.13] per SD of 44.4 pmol/l). Sensitivity analyses including a weighted-median approach and MR-Egger test did not detect other pleiotropic effects biasing the main results. Conclusions Our results are consistent with a causal role of fasting insulin and low-density lipoprotein cholesterol in lung cancer etiology, as well as for BMI in squamous cell and small cell carcinoma. The latter relation may be mediated by a previously unrecognized effect of obesity on smoking behavior