MiR-107 inhibits CDK6 expression, differentiation, and lipid storage in human adipocytes

MicroRNA-107 (miR-107) plays a regulatory role in obesity and insulin resistance, but the mechanisms of its function in adipocytes have not been elucidated in detail. Here we show that overexpression of miR-107 in pre- and mature human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes attenuates differentiation and lipid accumulation. Our results suggest that miR-107 controls adipocyte differentiation via CDK6 and Notch signaling. CDK6 is a validated target of miR-107 and was downregulated upon miR-107 overexpression. Notch3, a signaling receptor involved in adipocyte differentiation, has been shown to decrease upon CDK6 depletion; Here Notch3 and its target Hes1 were downregulated by miR-107 overexpression. In mature adipocytes, miR-107 induces a triglyceride storage defect by impairing glucose uptake and triglyceride synthesis. To conclude, our data suggests that miR-107 has distinct functional roles in preadipocytes and mature adipocytes; Its elevated expression at these different stages of adipocytes may on one hand dampen adipogenesis, and on the other, promote ectopic fatty acid accumulation and reduced glucose tolerance.Peer reviewe

Beef production from feedstuffs conserved using new technologies to reduce negative environmental impacts

End of project reportMost (ca. 86%) Irish farms make some silage. Besides directly providing feed for livestock, the provision of grass silage within integrated grassland systems makes an important positive contribution to effective grazing management and improved forage utilisation by grazing animals, and to effective feed budgeting by farmers. It can also contribute to maintaining the content of desirable species in pastures, and to livestock not succumbing to parasites at sensitive times of the year. Furthermore, the optimal recycling of nutrients collected from housed livestock can often be best achieved by spreading the manures on the land used for producing the conserved feed. On most Irish farms, grass silage will remain the main conserved forage for feeding to livestock during winter for the foreseeable future. However, on some farms high yields of whole-crop (i.e. grain + straw) cereals such as wheat, barley and triticale, and of forage maize, will be an alternative option provided that losses during harvesting, storage and feedout are minimised and that input costs are restrained. These alternative forages have the potential to reliably support high levels of animal performance while avoiding the production of effluent. Their production and use however will need to advantageously integrate into ruminant production systems. A range of technologies can be employed for crop production and conservation, and for beef production, and the optimal options need to be identified. Beef cattle being finished indoors are offered concentrate feedstuffs at rates that range from modest inputs through to ad libitum access. Such concentrates frequently contain high levels of cereals such as barley or wheat. These cereals are generally between 14% to 18% moisture content and tend to be rolled shortly before being included in coarse rations or are more finely processed prior to pelleting. Farmers thinking of using ‘high-moisture grain’ techniques for preserving and processing cereal grains destined for feeding to beef cattle need to know how the yield, conservation efficiency and feeding value of such grains compares with grains conserved using more conventional techniques. European Union policy strongly encourages a sustainable and multifunctional agriculture. Therefore, in addition to providing European consumers with quality food produced within approved systems, agriculture must also contribute positively to the conservation of natural resources and the upkeep of the rural landscape. Plastics are widely used in agriculture and their post-use fate on farms must not harm the environment - they must be managed to support the enduring sustainability of farming systems. There is an absence of information on the efficacy of some new options for covering and sealing silage with plastic sheeting and tyres, and an absence of an inventory of the use, re-use and post-use fate of plastic film on farms. Irish cattle farmers operate a large number of beef production systems, half of which use dairy bred calves. In the current, continuously changing production and market conditions, new beef systems must be considered. A computer package is required that will allow the rapid, repeatable simulation and assessment of alternate beef production systems using appropriate, standardised procedures. There is thus a need to construct, evaluate and utilise computer models of components of beef production systems and to develop mathematical relationships to link system components into a network that would support their integration into an optimal system model. This will provide a framework to integrate physical and financial on-farm conditions with models for estimating feed supply and animal growth patterns. Cash flow and profit/loss results will be developed. This will help identify optimal systems, indicate the cause of failure of imperfect systems and identify areas where applied research data are currently lacking, or more basic research is required

The association of genetic predisposition to depressive symptoms with non-suicidal and suicidal self-Injuries

Non-suicidal and suicidal self-injury are very destructive, yet surprisingly common behaviours. Depressed mood is a major risk factor for non-suicidal self-injury (NSSI), suicidal ideation and suicide attempts. We conducted a genetic risk prediction study to examine the polygenic overlap of depressive symptoms with lifetime NSSI, suicidal ideation, and suicide attempts in a sample of 6237 Australian adult twins and their family members (3740 females, mean age\ua0=\ua042.4\ua0years). Polygenic risk scores for depressive symptoms significantly predicted suicidal ideation, and some predictive ability was found for suicide attempts; the polygenic risk scores explained a significant amount of variance in suicidal ideation (lowest p\ua0=\ua00.008, explained variance ranging from 0.10 to 0.16\ua0%) and, less consistently, in suicide attempts (lowest p\ua0=\ua00.04, explained variance ranging from 0.12 to 0.23\ua0%). Polygenic risk scores did not significantly predict NSSI. Results highlight that individuals genetically predisposed to depression are also more likely to experience suicidal ideation/behaviour, whereas we found no evidence that this is also the case for NSSI

Carbon dioxide and ocean acidification observations in UK waters. Synthesis report with a focus on 2010–2015

Key messages: 1.1 The process of ocean acidification is now relatively well-documented at the global scale as a long-term trend in the open ocean. However, short-term and spatial variability can be high. 1.2 New datasets made available since Charting Progress 2 make it possible to greatly improve the characterisation of CO2 and ocean acidification in UK waters. 3.1 Recent UK cruise data contribute to large gaps in national and global datasets. 3.2 The new UK measurements confirm that pH is highly variable, therefore it is important to measure consistently to determine any long term trends. 3.3 Over the past 30 years, North Sea pH has decreased at 0.0035±0.0014 pH units per year. 3.4 Upper ocean pH values are highest in spring, lowest in autumn. These changes reflect the seasonal cycles in photosynthesis, respiration (decomposition) and water mixing. 3.5 Carbonate saturation states are minimal in the winter, and lower in 7 more northerly, colder waters. This temperature-dependence could have implications for future warming of the seas. 3.6 Over the annual cycle, North-west European seas are net sinks of CO2. However, during late summer to autumn months, some coastal waters may be significant sources. 3.7 In seasonally-stratified waters, sea-floor organisms naturally experience lower pH and saturation states; they may therefore be more vulnerable to threshold changes. 3.8 Large pH changes (0.5 - 1.0 units) can occur in the top 1 cm of sediment; however, such effects are not well-documented. 3.9 A coupled forecast model estimates the decrease in pH trend within the North Sea to be -0.0036±0.00034 pH units per year, under a high greenhouse gas emissions scenario (RCP 8.5). 3.10 Seasonal estimates from the forecast model demonstrate areas of the North Sea that are particularly vulnerable to aragonite undersaturation

Label-free fibre optic Raman spectroscopy with bounded simplex-structured matrix factorization for the serial study of serum in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease in urgent need of disease biomarkers for the assessment of promising therapeutic candidates in clinical trials. Raman spectroscopy is an attractive technique for identifying disease related molecular changes due to its simplicity. Here, we describe a fibre optic fluid cell for undertaking spontaneous Raman spectroscopy studies of human biofluids that is suitable for use away from a standard laboratory setting. Using this system, we examined serum obtained from patients with ALS at their first presentation to our centre (n = 66) and 4 months later (n = 27). We analysed Raman spectra using bounded simplex-structured matrix factorization (BSSMF), a generalisation of non-negative matrix factorisation which uses the distribution of the original data to limit the factorisation modes (spectral patterns). Biomarkers associated with ALS disease such as measures of symptom severity, respiratory function and inflammatory/immune pathways (C3/C-reactive protein) correlated with baseline Raman modes. Between visit spectral changes were highly significant (p = 0.0002) and were related to protein structure. Comparison of Raman data with established ALS biomarkers as a trial outcome measure demonstrated a reduction in required sample size with BSSMF Raman. Our portable, simple to use fibre optic system allied to BSSMF shows promise in the quantification of disease-related changes in ALS over short timescales

Self-collected saliva for SARS-CoV-2 detection: A prospective study in the emergency room

Current diagnostic standards involve severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection in nasopharyngeal swabs (NPS), but saliva is an attractive and noninvasive option for diagnosis. The objectives were to determine the performance of saliva in comparison with NPS for detecting SARS-CoV-2 and to compare the optimized home brew reverse-transcription polymerase chain reaction (RT-PCR) with a commercial RT-PCR. Paired NPS and saliva specimens were prospectively collected and tested by RT-PCR from patients presenting at an emergency room with signs and symptoms compatible with coronavirus disease-2019. A total of 348 samples from 174 patients were tested by RT-PCR assays. Among 174 patients with symptoms, 63 (36%) were SARS-CoV-2 positive in NPS using the optimized home-brew PCR. Of these 63 patients, 61 (98%) were also positive in saliva. An additional positive SARS-CoV-2 saliva was detected in a patient with pneumonia. Kappa Cohen´s coefficient agreement between NPS and saliva was 0.96 (95% confidence interval [CI], 0.90?0.99). Median Ct values in NPS versus saliva were 18.88 (interquartile range [IQR], 15.60?23.58; range, 11.97?38.10) versus 26.10 (IQR, 22.75?30.06; range, 13.78?39.22), respectively (p <.0001). The optimized home-brew RT-PCR demonstrated higher analytical and clinical sensitivity compared with the commercial RT-PCR assay. A high sensitivity (98%) and agreement (kappa 0.96) in saliva samples compared to NPS was demonstrated when using an optimized home-brew PCR even when the viral load in saliva was lower than in NPS. This noninvasive sample is easy to collect, requires less consumable and avoids discomfort to patients. Importantly, self-collection of saliva can diminish exposure to healthcare personnel.Fil: Echavarría, Marcela Silvia. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Reyes, Noelia Soledad. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; ArgentinaFil: Rodriguez, Pamela Elizabeth. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ypas, Martin. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; ArgentinaFil: Ricarte, Joaquina Carmen. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rodriguez, María P.. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; ArgentinaFil: Pérez, Matías Gastón. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Seoane, Alejandro. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; ArgentinaFil: Martinez, Alfredo. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; ArgentinaFil: Videla, Cristina Mónica. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Stryjewski, Martin E.. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; ArgentinaFil: Carballal, Guadalupe. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Vav Regulates Peptide-specific Apoptosis in Thymocytes

The protooncogene Vav functions as a GDP/GTP exchange factor (GEF) for Rho-like small GTPases involved in cytoskeletal reorganization and cytokine production in T cells. Gene-targeted mice lacking Vav have a severe defect in positive and negative selection of T cell antigen receptor transgenic thymocytes in vivo, and vav−/− thymocytes are completely resistant to peptide-specific and anti-CD3/anti-CD28–mediated apoptosis. Vav acts upstream of mitochondrial pore opening and caspase activation. Biochemically, Vav regulates peptide-specific Ca2+ mobilization and actin polymerization. Peptide-specific cell death was blocked both by cytochalasin D inhibition of actin polymerization and by inhibition of protein kinase C (PKC). Activation of PKC with phorbol ester restored peptide-specific apoptosis in vav−/− thymocytes. Vav was found to bind constitutively to PKC-θ in thymocytes. Our results indicate that peptide-triggered thymocyte apoptosis is mediated via Vav activation, changes in the actin cytoskeleton, and subsequent activation of a PKC isoform

Congenital diaphragmatic hernia in the preterm infant.

BACKGROUND: Congenital diaphragmatic hernia (CDH) remains a significant cause of death in newborns. With advances in neonatal critical care and ventilation strategies, survival in the term infant now exceeds 80% in some centers. Although prematurity is a significant risk factor for morbidity and mortality in most neonatal diseases, its associated risk with infants with CDH has been described poorly. We sought to determine the impact of prematurity on survival using data from the Congenital Diaphragmatic Hernia Registry (CDHR). METHODS: Prospectively collected data from live-born infants with CDH were analyzed from the CDHR from January 1995 to July 2009. Preterm infants were defined as \u3c37 weeks estimated gestational age at birth. Univariate and multivariate logistic regression analysis were\u3eperformed. RESULTS: During the study period, 5,069 infants with CDH were entered in the registry. Of the 5,022 infants with gestational age data, there were 3,895 term infants (77.6%) and 1,127 preterm infants (22.4%). Overall survival was 68.7%. A higher percentage of term infants were treated with extracorporeal membrane oxygenation (ECMO) (33% term vs 25.6% preterm). Preterm infants had a greater percentage of chromosomal abnormalities (4% term vs 8.1% preterm) and major cardiac anomalies (6.1% term vs 11.8% preterm). Also, a significantly higher percentage of term infants had repair of the hernia (86.3% term vs 69.4% preterm). Survival for infants that underwent repair was high in both groups (84.6% term vs 77.2% preterm). Survival decreased with decreasing gestational age (73.1% term vs 53.5% preterm). The odds ratio (OR) for death among preterm infants adjusted for patch repair, ECMO, chromosomal abnormalities, and major cardiac anomalies was OR 1.68 (95% confidence interval [CI], 1.34-2.11). CONCLUSION: Although outcomes for preterm infants are clearly worse than in the term infant, more than 50% of preterm infants still survived. Preterm infants with CDH remain a high-risk group. Although ECMO may be of limited value in the extremely premature infant with CDH, most preterm infants that live to undergo repair will survive. Prematurity should not be an independent factor in the treatment strategies of infants with CDH

The Role of Citizens in Detecting and Responding to a Rapid Marine Invasion

Documenting and responding to species invasions requires innovative strategies that account for ecological and societal complexities. We used the recent expansion of Indo-Pacific lionfish (Pterois volitans/miles) throughout northern Gulf of Mexico coastal waters to evaluate the role of stakeholders in documenting and responding to a rapid marine invasion. We coupled an online survey of spearfishers and citizen science monitoring programs with traditional fishery-independent data sources and found that citizen observations documented lionfish 1–2 years earlier and more frequently than traditional reef fish monitoring programs. Citizen observations first documented lionfish in 2010 followed by rapid expansion and proliferation in 2011 (+367%). From the survey of spearfishers, we determined that diving experience and personal observations of lionfish strongly influenced perceived impacts, and these perceptions were powerful predictors of support for initiatives. Our study demonstrates the value of engaging citizens for assessing and responding to large-scale and time-sensitive conservation problems

Evidence of a dissolution effect on benthic foraminiferal shell chemistry: δ¹³C, Cd/Ca, Ba/Ca, and Sr/Ca results from the Ontong Java Plateau

Core-top benthic foraminifera (Cibicidoides wuellerstorfi) from a depth transect of Soutar box cores from the Ontong-Java Plateau (1.6 – 4.4 km) were analyzed for cadmium, barium, and strontium (Cd/Ca, Ba/Ca, and Sr/Ca) and for their stable isotopic composition (δ¹³C and δ¹⁸O). We also measure bottom water δ¹³C, Cd, and Ba at these sites. Foraminiferal δ¹³C values remain roughly constant over the entire depth range while bottom water δ¹³C values increase slightly, such that the δ¹³C difference between C. wuellerstorfi and bottom water ranges from about +0.2 ‰ in cores above 2.5 km to about -0.2 ‰ in cores below 4 km. This apparent depth dependence has not been previously reported, but this range in Δδ¹³C values is comparable to the uncertainty in published δ¹³C calibration studies We observe strong decreases in foraminiferal Cd/Ca, Ba/Ca, and Sr/Ca ratios (50, 25, and 15 percent, respectively) at water depths greater than about 2.5 km. These decreases are substantially larger than the corresponding changes in bottom water trace element concentrations, and they are not correlated with variations in pore water Cd and Ba concentrations at these sites. Together, the foraminiferal and bottom water Cd/Ca, Ba/Ca, and Sr/Ca data yield decreases in the apparent distribution coefficients for these metals into calcite with increasing water depth, again a pattern which has not been previously reported. These results when combined with the data from published core-top calibration studies suggest that a preferential loss of Cd, Ba, and Sr occurs during the dissolution of benthic foraminiferal calcite on the sea floor and raise the possibility of a dissolution-driven decrease in benthic foraminiferal δ¹³C values