Distinct Modes Of Aged Soil Carbon Export In A Large Tropical Lake Basin Identified Using Bulk And Compound-Specific Radiocarbon Analyses Of Fluvial And Lacustrine Sediment

The 14C content of sedimentary organic matter (OM) and specific organic molecules provide valuable information on the source and age of OM stored in sediments, but these data are limited for tropical fluvial and lake sediments. We analyzed 14C in bulk OM, palmitic acid (C16), and long-chain n-alkanoic acids (C24, C26, and C28), within fluvial and lake sediments in the catchment of Lake Izabal, a large tectonic lake basin in Guatemala. We combined these measurements with bulk and compound-specific δ13C measurements, as well as sediment organic carbon to nitrogen (OC:N) ratios, to understand the source and age of sedimentary OM in different regions of the lake catchment. Most fatty acid and bulk OM samples were characterized by pre-modern carbon, indicating important input of aged carbon with residence times of hundreds to thousands of years into sediments. We identified two mechanisms leading to aged carbon export to sediments. In the high-relief and deforested Polochic catchment, older OM and fatty acids are associated with low % total organic carbon (TOC) and low OC:N, indicating aged OM associated with eroded mineral soil. In the smaller, low-relief, and largely forested Oscuro catchment, old OM and fatty acids are associated with high %TOC and high OC:N ratios, indicating export of undegraded aged plant biomass from swamp peat. The age of bulk OM and fatty acids in Lake Izabal sediments is similar to the ages observed in fluvial sediments, implying that fluvial input of aged soil carbon makes an important contribution to lake sediment carbon reservoirs in this large tropical lake

MTOR is a promising therapeutical target in a subpopulation of pancreatic adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal disease, unusually resistant against therapy. It is generally felt that stratification of patients for personalized medicine is the way forward. Here, we report that a subpopulation of PDACs shows strong activation of the mTOR signaling cassette. Moreover, we show that inhibition of mTOR in pancreatic cancer cell lines showing high levels of mTOR signaling is associated with cancer cell death. Finally, we show using fine needle biopsies the existence of a subpopulation of PDAC patients with high activation of the mTOR signaling cassette and provide evidence that inhibition of mTOR might be clinically useful for this group. Thus, our results define an unrecognized subpopulation of PDACs, characterized by high activation of mTOR and show that identification of this specific patient group in the early phase of diagnosis is feasible

Modulation of human peripheral blood mononuclear cell signaling by medicinal cannabinoids

Medical marijuana is increasingly prescribed as an analgesic for a growing number of indications, amongst which terminal cancer and multiple sclerosis. However, the mechanistic aspects and properties of cannabis remain remarkably poorly characterized. In this study we aimed to investigate the immune-cell modulatory properties of medical cannabis. Healthy volunteers were asked to ingest medical cannabis, and kinome profiling was used to generate comprehensive descriptions of the cannabis challenge on inflammatory signal transduction in the peripheral blood of these volunteers. Results were related to both short term and long term effects in patients experimentally treated with a medical marijuana preparation for suffering from abdominal pain as a result of chronic pancreatitis or other causes. The results reveal an immunosuppressive effect of cannabinoid preparations via deactivation of signaling through the pro-inflammatory p38 MAP kinase and mTOR pathways and a concomitant deactivation of the pro-mitogenic ERK pathway. However, long term cannabis exposure in two patients resulted in reversal of this effect. While these data provide a powerful mechanistic rationale for the clinical use of medical marijuana in inflammatory and oncological disease, caution may be advised with sustained use of such preparations

Oxidised cosmic acceleration

We give detailed proofs of several new no-go theorems for constructing flat four-dimensional accelerating universes from warped dimensional reduction. These new theorems improve upon previous ones by weakening the energy conditions, by including time-dependent compactifications, and by treating accelerated expansion that is not precisely de Sitter. We show that de Sitter expansion violates the higher-dimensional null energy condition (NEC) if the compactification manifold M is one-dimensional, if its intrinsic Ricci scalar R vanishes everywhere, or if R and the warp function satisfy a simple limit condition. If expansion is not de Sitter, we establish threshold equation-of-state parameters w below which accelerated expansion must be transient. Below the threshold w there are bounds on the number of e-foldings of expansion. If M is one-dimensional or R everywhere vanishing, exceeding the bound implies the NEC is violated. If R does not vanish everywhere on M, exceeding the bound implies the strong energy condition (SEC) is violated. Observationally, the w thresholds indicate that experiments with finite resolution in w can cleanly discriminate between different models which satisfy or violate the relevant energy conditions.Comment: v2: corrections, references adde

UV-B absorbing pigments in spores: biochemical responses to shade in a high-latitude birch forest and implications for sporopollenin-based proxies of past environmental change

Current attempts to develop a proxy for Earth’s surface ultraviolet-B (UV-B) flux focus on the organic chemistry of pollen and spores because their constituent biopolymer, sporopollenin, contains UV-B absorbing pigments whose relative abundance may respond to the ambient UV-B flux. Fourier transform infrared (FTIR) microspectroscopy provides a useful tool for rapidly determining the pigment content of spores. In this paper, we use FTIR to detect a chemical response of spore wall UV-B absorbing pigments that correspond with levels of shade beneath the canopy of a high-latitude Swedish birch forest. A 27% reduction in UV-B flux beneath the canopy leads to a significant (p<0.05) 7.3% reduction in concentration of UV-B absorbing compounds in sporopollenin. The field data from this natural flux gradient in UV-B further support our earlier work on sporopollenin-based proxies derived from sedimentary records and herbaria collections

Cohort Randomised Controlled Trial of a Multifaceted Podiatry Intervention for the Prevention of Falls in Older People (The REFORM Trial)

BACKGROUND: Falls are a major cause of morbidity among older people. A multifaceted podiatry intervention may reduce the risk of falling. This study evaluated such an intervention. DESIGN: Pragmatic cohort randomised controlled trial in England and Ireland. 1010 participants were randomised (493 to the Intervention group and 517 to Usual Care) to either: a podiatry intervention, including foot and ankle exercises, foot orthoses and, if required, new footwear, and a falls prevention leaflet or usual podiatry treatment plus a falls prevention leaflet. The primary outcome was the incidence rate of self-reported falls per participant in the 12 months following randomisation. Secondary outcomes included: proportion of fallers and those reporting multiple falls, time to first fall, fear of falling, Frenchay Activities Index, Geriatric Depression Scale, foot pain, health related quality of life, and cost-effectiveness. RESULTS: In the primary analysis were 484 (98.2%) intervention and 507 (98.1%) control participants. There was a small, non statistically significant reduction in the incidence rate of falls in the intervention group (adjusted incidence rate ratio 0.88, 95% CI 0.73 to 1.05, p = 0.16). The proportion of participants experiencing a fall was lower (49.7 vs 54.9%, adjusted odds ratio 0.78, 95% CI 0.60 to 1.00, p = 0.05) as was the proportion experiencing two or more falls (27.6% vs 34.6%, adjusted odds ratio 0.69, 95% CI 0.52 to 0.90, p = 0.01). There was an increase (p = 0.02) in foot pain for the intervention group. There were no statistically significant differences in other outcomes. The intervention was more costly but marginally more beneficial in terms of health-related quality of life (mean quality adjusted life year (QALY) difference 0.0129, 95% CI -0.0050 to 0.0314) and had a 65% probability of being cost-effective at a threshold of £30,000 per QALY gained. CONCLUSION: There was a small reduction in falls. The intervention may be cost-effective. TRIAL REGISTRATION: ISRCTN ISRCTN68240461

Genetic Sharing with Cardiovascular Disease Risk Factors and Diabetes Reveals Novel Bone Mineral Density Loci.

Bone Mineral Density (BMD) is a highly heritable trait, but genome-wide association studies have identified few genetic risk factors. Epidemiological studies suggest associations between BMD and several traits and diseases, but the nature of the suggestive comorbidity is still unknown. We used a novel genetic pleiotropy-informed conditional False Discovery Rate (FDR) method to identify single nucleotide polymorphisms (SNPs) associated with BMD by leveraging cardiovascular disease (CVD) associated disorders and metabolic traits. By conditioning on SNPs associated with the CVD-related phenotypes, type 1 diabetes, type 2 diabetes, systolic blood pressure, diastolic blood pressure, high density lipoprotein, low density lipoprotein, triglycerides and waist hip ratio, we identified 65 novel independent BMD loci (26 with femoral neck BMD and 47 with lumbar spine BMD) at conditional FDR < 0.01. Many of the loci were confirmed in genetic expression studies. Genes validated at the mRNA levels were characteristic for the osteoblast/osteocyte lineage, Wnt signaling pathway and bone metabolism. The results provide new insight into genetic mechanisms of variability in BMD, and a better understanding of the genetic underpinnings of clinical comorbidity

Transcranial electrical and magnetic stimulation (tES and TMS) for addiction medicine: A consensus paper on the present state of the science and the road ahead

There is growing interest in non-invasive brain stimulation (NIBS) as a novel treatment option for substance-use disorders (SUDs). Recent momentum stems from a foundation of preclinical neuroscience demonstrating links between neural circuits and drug consuming behavior, as well as recent FDA-approval of NIBS treatments for mental health disorders that share overlapping pathology with SUDs. As with any emerging field, enthusiasm must be tempered by reason; lessons learned from the past should be prudently applied to future therapies. Here, an international ensemble of experts provides an overview of the state of transcranial-electrical (tES) and transcranial-magnetic (TMS) stimulation applied in SUDs. This consensus paper provides a systematic literature review on published data – emphasizing the heterogeneity of methods and outcome measures while suggesting strategies to help bridge knowledge gaps. The goal of this effort is to provide the community with guidelines for best practices in tES/TMS SUD research. We hope this will accelerate the speed at which the community translates basic neuroscience into advanced neuromodulation tools for clinical practice in addiction medicine