The role of diet and nutrition on mental health and wellbeing

Mental, neurological and substance-use disorders presently represent the greatest global burden of disease. Likewise, depression and other psychopathologies are elevated risk comorbidities of other health hazards, such as obesity. Nutrition has been implicated in behaviour, mood and in the pathology and treatment of mental illness. In this brief editorial, we aim to set the scale of the problem in context and overview advances and recent evidence linking nutrition to psychological outcomes. The purpose of the 2016 Nutrition Society Winter Meeting, 'Diet, nutrition and mental health and wellbeing' was to review where the evidence is strong, where there are unmet needs for research and to draw together the communities working in this area to share their findings. The papers presented demonstrated clear advancements that are being made in this field. The meeting illustrated compelling support for nutrition as a modifiable risk factor. The present research in the field and evidence presented at the 2016 Nutrition Society Winter Meeting lead us to postulate that even interventions with relatively modest effect sizes may plausibly and significantly curtail the disease burden of mental and neurological disease by food- and nutrient-based approaches

Three complete mitochondrial genomes of shortfin mako sharks, Isurus oxyrinchus, from the Atlantic and Pacific Oceans

We present complete mitogenome sequences of three shortfin mako sharks (Isurus oxyrinchus) sampled from the western Pacific, and eastern and western Atlantic oceans. Mitogenome sequence lengths ranged between 16,699 bp and 16,702 bp, and all three mitogenomes contained one non-coding control region, two rRNA genes, 22 tRNA genes, and 13 protein-coding genes. Comparative assessment of five mitogenomes from globally distributed shortfin makos (the current three and two previously published mitogenomes) yielded 98.4% identity, with the protein-coding genes ATP8, ATP6, and ND5 as the most variable regions (sequence identities of 96.4%, 96.5%, and 97.6%, respectively). These mitogenome sequences contribute resources for assessing the genetic population dynamics of this endangered oceanic apex predator

Dietary Cholesterol Concentration and Duration Degrade Long-Term Memory of Classical Conditioning of the Rabbit's Nictitating Membrane Response

A rabbit model of Alzheimer's disease based on feeding a cholesterol diet for eight weeks shows sixteen hallmarks of the disease, including learning and memory changes. Although we have shown 2% cholesterol and copper in water can retard learning, other studies show feeding dietary cholesterol before learning can improve acquisition whereas feeding cholesterol after learning can degrade long-term memory. We explored this issue by manipulating cholesterol concentration and duration following classical trace conditioning of the rabbit's nictitating membrane response and assessed conditioned responding after eight weeks on cholesterol. First, rabbits given trace classical conditioning followed by 0.5%, 1%, or 2% cholesterol for eight weeks showed body weight and serum cholesterol levels that were a function of dietary cholesterol. Although all concentrations of cholesterol showed some sign of retarding long-term memory, the level of memory retardation was correlated with serum cholesterol levels. Second, rabbits given trace conditioning followed by different durations of a 2% cholesterol diet combined with different durations of a 0% control diet for 8 weeks showed duration and timing of a 2% cholesterol diet were important in affecting recall. The data support the idea that dietary cholesterol may retard long-term memory

Correlation Between Caregiver Reports of Physical Function and Performance-based Measures in a Cohort of Older Adults With Alzheimer Disease

The objectives of this report are to determine the association between performance-based measures of physical function with caregiver reports of physical function in older adults with Alzheimer disease (AD) and to examine whether those associations vary by the level of patients' cognitive functioning. Subjects included 180 patient-caregiver dyads who are enrolled in a clinical trial testing the impact of an occupational therapy intervention plus guideline-level care to delay functional decline among older adults with AD. The primary caregiver-reported measure is the Alzheimer's Disease Cooperative Study Group Activities of Daily Living Inventory (ADCS-ADL). Performance-based measures include the Short Physical Performance Battery and the Short Portable Sarcopenia Measure. Analysis of covariance (ANCOVA) models were used to determine the associations of each physical performance measure with ADCS-ADL, adjusting for cognition function and other covariates. We found significant correlations between caregiver reports and observed performance-based measures across all levels of cognitive function, with patients in the lowest cognitive group showing the highest correlation. These findings support the use of proxy reports to assess physical function among older adults with AD

Metabolic Roles of Uncultivated Bacterioplankton Lineages in the Northern Gulf of Mexico "Dead Zone".

This is the final version of the article. Available from American Society for Microbiology via the DOI in this record.Marine regions that have seasonal to long-term low dissolved oxygen (DO) concentrations, sometimes called "dead zones," are increasing in number and severity around the globe with deleterious effects on ecology and economics. One of the largest of these coastal dead zones occurs on the continental shelf of the northern Gulf of Mexico (nGOM), which results from eutrophication-enhanced bacterioplankton respiration and strong seasonal stratification. Previous research in this dead zone revealed the presence of multiple cosmopolitan bacterioplankton lineages that have eluded cultivation, and thus their metabolic roles in this ecosystem remain unknown. We used a coupled shotgun metagenomic and metatranscriptomic approach to determine the metabolic potential of Marine Group II Euryarchaeota, SAR406, and SAR202. We recovered multiple high-quality, nearly complete genomes from all three groups as well as candidate phyla usually associated with anoxic environments-Parcubacteria (OD1) and Peregrinibacteria Two additional groups with putative assignments to ACD39 and PAUC34f supplement the metabolic contributions by uncultivated taxa. Our results indicate active metabolism in all groups, including prevalent aerobic respiration, with concurrent expression of genes for nitrate reduction in SAR406 and SAR202, and dissimilatory nitrite reduction to ammonia and sulfur reduction by SAR406. We also report a variety of active heterotrophic carbon processing mechanisms, including degradation of complex carbohydrate compounds by SAR406, SAR202, ACD39, and PAUC34f. Together, these data help constrain the metabolic contributions from uncultivated groups in the nGOM during periods of low DO and suggest roles for these organisms in the breakdown of complex organic matter.IMPORTANCE Dead zones receive their name primarily from the reduction of eukaryotic macrobiota (demersal fish, shrimp, etc.) that are also key coastal fisheries. Excess nutrients contributed from anthropogenic activity such as fertilizer runoff result in algal blooms and therefore ample new carbon for aerobic microbial metabolism. Combined with strong stratification, microbial respiration reduces oxygen in shelf bottom waters to levels unfit for many animals (termed hypoxia). The nGOM shelf remains one of the largest eutrophication-driven hypoxic zones in the world, yet despite its potential as a model study system, the microbial metabolisms underlying and resulting from this phenomenon-many of which occur in bacterioplankton from poorly understood lineages-have received only preliminary study. Our work details the metabolic potential and gene expression activity for uncultivated lineages across several low DO sites in the nGOM, improving our understanding of the active biogeochemical cycling mediated by these "microbial dark matter" taxa during hypoxia

Phase II Trial of IL-12 Plasmid Transfection and PD-1 Blockade in Immunologically Quiescent Melanoma.

PurposeTumors with low frequencies of checkpoint positive tumor-infiltrating lymphocytes (cpTIL) have a low likelihood of response to PD-1 blockade. We conducted a prospective multicenter phase II trial of intratumoral plasmid IL-12 (tavokinogene telseplasmid; "tavo") electroporation combined with pembrolizumab in patients with advanced melanoma with low frequencies of checkpoint positive cytotoxic lymphocytes (cpCTL).Patients and methodsTavo was administered intratumorally days 1, 5, and 8 every 6 weeks while pembrolizumab (200 mg, i.v.) was administered every 3 weeks. The primary endpoint was objective response rate (ORR) by RECIST, secondary endpoints included duration of response, overall survival and progression-free survival. Toxicity was evaluated by the CTCAE v4. Extensive correlative analysis was done.ResultsThe combination of tavo and pembrolizumab was well tolerated with adverse events similar to those previously reported with pembrolizumab alone. Patients had a 41% ORR (n = 22, RECIST 1.1) with 36% complete responses. Correlative analysis showed that the combination enhanced immune infiltration and sustained the IL-12/IFNγ feed-forward cycle, driving intratumoral cross-presenting dendritic cell subsets with increased TILs, emerging T cell receptor clones and, ultimately, systemic cellular immune responses.ConclusionsThe combination of tavo and pembrolizumab was associated with a higher than expected response rate in this poorly immunogenic population. No new or unexpected toxicities were observed. Correlative analysis showed T cell infiltration with enhanced immunity paralleling the clinical activity in low cpCTL tumors

Migraine attacks the Basal Ganglia

<p>Abstract</p> <p>Background</p> <p>With time, episodes of migraine headache afflict patients with increased frequency, longer duration and more intense pain. While episodic migraine may be defined as 1-14 attacks per month, there are no clear-cut phases defined, and those patients with low frequency may progress to high frequency episodic migraine and the latter may progress into chronic daily headache (> 15 attacks per month). The pathophysiology of this progression is completely unknown. Attempting to unravel this phenomenon, we used high field (human) brain imaging to compare functional responses, functional connectivity and brain morphology in patients whose migraine episodes did not progress (LF) to a matched (gender, age, age of onset and type of medication) group of patients whose migraine episodes progressed (HF).</p> <p>Results</p> <p>In comparison to LF patients, responses to pain in HF patients were significantly lower in the caudate, putamen and pallidum. Paradoxically, associated with these lower responses in HF patients, gray matter volume of the right and left caudate nuclei were significantly larger than in the LF patients. Functional connectivity analysis revealed additional differences between the two groups in regard to response to pain.</p> <p>Conclusions</p> <p>Supported by current understanding of basal ganglia role in pain processing, the findings suggest a significant role of the basal ganglia in the pathophysiology of the episodic migraine.</p

Identification of a novel ligand for the ATAD2 bromodomain with selectivity over BRD4 through a fragment growing approach

Structure-guided expansion of a fragment hit for the ATAD2 bromodomain enabled improvement in ATAD2 inhibition and selectivity over BRD4.</p

TEMPLATES: A Robust Outlier Rejection Method for JWST/NIRSpec Integral Field Spectroscopy

We describe a custom outlier rejection algorithm for JWST/NIRSpec integral field spectroscopy. This method uses a layered sigma clipping approach that adapts clipping thresholds based upon the spatial profile of the science target. We find that this algorithm produces a robust outlier rejection while simultaneously preserving the signal of the science target. Originally developed as a response to unsatisfactory initial performance of the jwst pipeline outlier detection step, this method works either as a standalone solution, or as a supplement to the current pipeline software. Comparing leftover (i.e., not flagged) artifacts with the current pipeline's outlier detection step, we find that our method results in one fifth as many residual artifacts as the jwst pipeline. However, we find a combination of both methods removes nearly all artifacts -- an approach that takes advantage of both our algorithm's robust outlier rejection and the pipeline's use of individual dithers. This combined approach is what the TEMPLATES Early Release Science team has converged upon for our NIRSpec observations. Finally, we publicly release the code and Jupyter notebooks for the custom outlier rejection algorithm.Comment: 10 pages, including 5 figures. Submitted to the Publications of the Astronomical Society of the Pacific (PASP). Code associated with paper released at https://github.com/aibhleog/baryon-swee