Cell Biology. Clogging information flow in ALS.

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is a devastating neurodegenerative disorder that causes a progressive loss of motor neurons, leading to paralysis and death typically within 2 to 5 years of onset. There are no cures and few treatments. ALS shares some genetic and pathological overlap with another neurodegenerative disease, frontotemporal dementia (FTD), which causes changes to personality and language. Mutations in the gene called chromosome 9 open reading frame 72 (C9orf72) are the most common genetic cause of both ALS and FTD. This is the author’s version of the work. It is posted here by permission of the AAAS for personal use, not for redistribution. The definitive version was published in Science on [Volume 345 on 5 September 2014], DOI: 10.1126/science.1259461

Changes in Energy Expenditure with Ingestion of High Protein, High Fat versus High Protein, Low Fat Meals among Underweight, Normal Weight, and Overweight Females.

Background: Metabolic rate is known to rise above basal levels after eating, especially following protein consumption. Yet, this postprandial rise in metabolism appears to vary among individuals. This study examined changes in energy expenditure in response to ingestion of a high protein, high fat (HPHF) meal versus an isocaloric high protein, low fat (HPLF) meal in underweight, normal weight, or overweight females (n = 21) aged 19–28 years. Methods: Energy expenditure, measured using indirect calorimetry, was assessed before and every 30 minutes for 3.5 hours following consumption of the meals on two separate occasions. Height and weight were measured using standard techniques. Body composition was measured using bioelectrical impedance analysis. Results: Significant positive correlations were found between body mass index (BMI) and baseline metabolic rate (MR) (r = 0.539; p = 0.017), between body weight and baseline MR (r = 0.567; p = 0.011), between BMI and average total change in MR (r = 0.591; p = 0.008), and between body weight and average total change in MR (r = 0.464; p = 0.045). Metabolic rate (kcal/min) was significantly higher in the overweight group than the normal weight group, which was significantly higher than the underweight group across all times and treatments. However, when metabolic rate was expressed per kg fat free mass (ffm), no significant difference was found in postprandial energy expenditure between the overweight and normal groups. Changes in MR (kcal/min and kcal/min/kg ffm) from the baseline rate did not significantly differ in the underweight (n = 3) or in the overweight subjects (n = 5) following consumption of either meal at any time. Changes in MR (kcal/min and kcal/min/kg ffm) from baseline were significantly higher in normal weight subjects (n = 11) across all times following consumption of the HPHF meal versus the HPLF meal. Conclusion: There is no diet-induced thermogenic advantage between the HPHF and HPLF meals in overweight and underweight subjects. In contrast, in normal weight subjects, ingestion of a HPHF meal significantly increases MR (69.3 kcal/3.5 hr) versus consumption of a HPLF meal and provides a short-term metabolic advantage

SYNTHESIS, CHARACTERIZATION AND BIOCIDAL ACTIVITY OF NOVEL HALOGENATED -4-[(SUBSTITUTED-BENZOTHIAZOL-2-YL) HYDRAZONO]-2- (SUBSTITUTED-PHENYL)-5-METHYL /ETHOXY -2,4-DIHYDRO-PYRAZOL-3-ONE DERIVATIVES

ABSTRACT Some new 4-[(substituted-benzothiazol-2-yl)hydrazono]-2-(substituted-phenyl)-5-methyl/ethoxy-2,4-dihydro-pyrazol-3-one(4) have been synthesized by reacting substituted 2-amino benzothiazol (1) with acetoacetic ester and malonic ester (2). 2-[(substituted-benzothiazol-2-yl)hydrazono]-3-oxo-butyric acid ethyl ester and 2-[(substituted-benzothiazol-2-yl)hydrazono]-malonic acid diethyl ester (3) react with different hydrazines to give the title compounds(4). These compounds are evaluated for their antifungal and insecticidal activity

Examining the Association between Psychiatric Illness and Suicidal Ideation in a Sample of Treatment-Seeking Canadian Peacekeeping and Combat Veterans with Posttraumatic Stress Disorder

Objective: Our study examines the association between suicidal ideation and and self-reported symptoms of posttraumatic stress disorder (PTSD), major depressive disorder (MDD), generalized anxiety disorder (GAD), and alcohol use disorder (AUD) in a sample of treatment-seeking Canadian combat and peacekeeping veterans; and identifies potential predictors of suicidal ideation. Methods: Actively serving Canadian Forces and Royal Canadian Mounted Police members and veterans seeking treatment at the Parkwood Hospital Operational Stress Injury Clinic (n = 250) completed measures including the Primary Care Evaluation of Mental Disorders Patient Health Questionnaire, the Alcohol Use Disorder Identification Test, and the PTSD Checklist—Military Version (PCL-M) between January 2002 and December 2010. Regression analyses were used to determine the respective impact of PTSD, and self-reported symptoms of MDD, GAD, AUD, and anxiety on suicidal ideation. Results: Most people met PCL-M screening criteria for PTSD (73.6%, n = 184), while 70.8% (n = 177) screened positively for a probable major depressive episode. PTSD symptom was significantly associated with suicidal ideation (β = 0.412, P \u3c 0.001). After controlling for self-reported depressive symptom severity, AUD severity, and generalized anxiety, PTSD severity was no longer significantly associated with suicidal ideation (β = 0.043, P = 0.58). Conclusions: Although PTSD alone is associated with suicidal ideation, after controlling for common comorbid psychiatric illnesses, self-reported depressive symptom severity emerged as the most significant predictor of suicidal ideation. These findings support the importance of screening for comorbidities, particularly an MDD, as potentially modifiable conditions that are strongly related to suicidal ideation in military personnel\u27s endorsing criteria for PTSD

Projective simulation for artificial intelligence

We propose a model of a learning agent whose interaction with the environment is governed by a simulation-based projection, which allows the agent to project itself into future situations before it takes real action. Projective simulation is based on a random walk through a network of clips, which are elementary patches of episodic memory. The network of clips changes dynamically, both due to new perceptual input and due to certain compositional principles of the simulation process. During simulation, the clips are screened for specific features which trigger factual action of the agent. The scheme is different from other, computational, notions of simulation, and it provides a new element in an embodied cognitive science approach to intelligent action and learning. Our model provides a natural route for generalization to quantum-mechanical operation and connects the fields of reinforcement learning and quantum computation.Comment: 22 pages, 18 figures. Close to published version, with footnotes retaine

Identifying precursors and aqueous organic aerosol formation pathways during the SOAS campaign

Aqueous multiphase chemistry in the atmosphere can lead to rapid transformation of organic compounds, forming highly oxidized, low-volatility organic aerosol and, in some cases, light-absorbing (brown) carbon. Because liquid water is globally abundant, this chemistry could substantially impact climate, air quality, and health. Gas-phase precursors released from biogenic and anthropogenic sources are oxidized and fragmented, forming water-soluble gases that can undergo reactions in the aqueous phase (in clouds, fogs, and wet aerosols), leading to the formation of secondary organic aerosol (SOA$_{AQ}$). Recent studies have highlighted the role of certain precursors like glyoxal, methylglyoxal, glycolaldehyde, acetic acid, acetone, and epoxides in the formation of SOA$_{AQ}$. The goal of this work is to identify additional precursors and products that may be atmospherically important. In this study, ambient mixtures of watersoluble gases were scrubbed from the atmosphere into water at Brent, Alabama, during the 2013 Southern Oxidant and Aerosol Study (SOAS). Hydroxyl (OH ·) radical oxidation experiments were conducted with the aqueous mixtures collected from SOAS to better understand the formation of SOA through gas-phase followed by aqueous-phase chemistry. Total aqueous-phase organic carbon concentrations for these mixtures ranged from 92 to 179 μM-C, relevant for cloud and fog waters. Aqueous OH-reactive compounds were primarily observed as odd ions in the positive ion mode by electrospray ionization mass spectrometry (ESI-MS). Ultra highresolution Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) spectra and tandem MS (MS– MS) fragmentation of these ions were consistent with the presence of carbonyls and tetrols. Products were observed in the negative ion mode and included pyruvate and oxalate, which were confirmed by ion chromatography. Pyruvate and oxalate have been found in the particle phase in many locations (as salts and complexes). Thus, formation of pyruvate/oxalate suggests the potential for aqueous processing of these ambient mixtures to form SOA$_{AQ}$

Characterising variation in wheat traits under hostile soil conditions in India

Intensive crop breeding has increased wheat yields and production in India. Wheat improvement in India typically involves selecting yield and component traits under non-hostile soil conditions at regional scales. The aim of this study is to quantify G*E interactions on yield and component traits to further explore site-specific trait selection for hostile soils. Field experiments were conducted at six sites (pH range 4.5-9.5) in 2013-14 and 2014-15, in three agro-climatic regions of India. At each site, yield and component traits were measured on 36 genotypes, representing elite varieties from a wide genetic background developed for different regions. Mean grain yields ranged from 1.0 to 5.5 t ha⁻¹ at hostile and non-hostile sites, respectively. Site (E) had the largest effect on yield and component traits, however, interactions between genotype and site (G*E) affected most traits to a greater extent than genotype alone. Within each agro-climatic region, yield and component traits correlated positively between hostile and non-hostile sites. However, some genotypes performed better under hostile soils, with site-specific relationships between yield and component traits, which supports the value of ongoing site-specific selection activities

A putative heat-responsive transcription factor (TaHD97) and its targets in wheat (Triticum aestivum) providing thermotolerance

214-223Transcription factors (TFs) are protein, which perform their role at transcriptional level by affecting the expression of various genes associated with metabolic pathways, growth and stress-associated genes (SAGs) at different developmental stages. Here, we identified 38 novel heat-responsive transcription factor genes from wheat cv. HD2985 by mining the de novo transcriptome data derived from heat shock (HS) treated wheat. Based on digital gene expression (DGE), a putative transcript (TaHD97) of ~1.1 kbas amplified and cloned from wheat cv. HD2985. The presence of heat stress transcription factor (HSF) DNA binding domain was observed in the amino acid sequence. Differential expression of TaHD97 was observed in HD2985 (thermotolerant) and HD2329 (thermosensitive) under heat stress. Tissue specific expression analysis showed up-regulation of TaHD97 in leaves, stem and endospermic tissues and down-regulation in root under HS. A positive correlation was established between the expression of TaHD97 and its target gene (HSP17 and HSP90) in wheat under heat stress. HSP17 transcripts were observed more in leaves of HD2985, as compared to HD2329. Thermotolerance related biochemical enzymes (SOD, CAT, GPX and TBARS) were observed higher in wheat cv. HD2985 showing maximum expression of TaHD97 under heat stress. There is a need for the functional validation of the gene TaHD97 in order to use it for the regulation of sHSP (catalytic chaperone) - a novel approach towards augmenting thermotolerance in wheat under heat stress

Flavivirus-induced antibody cross-reactivity

Dengue viruses (DENV) cause countless human deaths each year, whilst West Nile virus (WNV) has re-emerged as an important human pathogen. There are currently no WNV or DENV vaccines licensed for human use, yet vaccines exist against other flaviviruses. To investigate flavivirus cross-reactivity, sera from a human cohort with a history of vaccination against tick-borne encephalitis virus (TBEV), Japanese encephalitis virus (JEV) and yellow fever virus (YFV) were tested for antibodies by plaque reduction neutralization test. Neutralization of louping ill virus (LIV) occurred, but no significant neutralization of Murray Valley encephalitis virus was observed. Sera from some individuals vaccinated against TBEV and JEV neutralized WNV, which was enhanced by YFV vaccination in some recipients. Similarly, some individuals neutralized DENV-2, but this was not significantly influenced by YFV vaccination. Antigenic cartography techniques were used to generate a geometric illustration of the neutralization titres of selected sera against WNV, TBEV, JEV, LIV, YFV and DENV-2. This demonstrated the individual variation in antibody responses. Most sera had detectable titres against LIV and some had titres against WNV and DENV-2. Generally, LIV titres were similar to titres against TBEV, confirming the close antigenic relationship between TBEV and LIV. JEV was also antigenically closer to TBEV than WNV, using these sera. The use of sera from individuals vaccinated against multiple pathogens is unique relative to previous applications of antigenic cartography techniques. It is evident from these data that notable differences exist between amino acid sequence identity and mapped antigenic relationships within the family Flaviviridae