Lung C-fiber CNS reflex: role in the respiratory consequences of extended environmental tobacco smoke exposure in young guinea pigs.

Environmental tobacco smoke (ETS) exposure harms the respiratory health of children and is associated with an increased risk of asthma and sudden infant death syndrome (SIDS). The mechanisms by which ETS causes these effects are not understood. We hypothesized that one mechanism is an upregulation of the lung C-fiber central nervous system (CNS) reflex responses, which would result in exaggerated reflex responses of apnea, bronchoconstriction, and mucous hypersecretion. The purpose of this work is to highlight evidence obtained in an animal model of postnatal ETS exposure supporting the hypothesis and present data suggesting that actions of the neuropeptide substance P in the nucleus tractus solitarius (NTS) may contribute. Exposing young guinea pigs to sidestream smoke, the surrogate for ETS, for 5 weeks during the equivalent of human childhood, increased the excitability of afferent lung C fibers and NTS neurons in the CNS reflex pathway and prolonged the expiratory apnea. The findings suggest that an increased excitability of NTS neurons that can augment reflex output may contribute to respiratory symptoms in children exposed to ETS. Besides ETS exposure, substance P can also excite NTS neurons and augment lung C-fiber CNS reflex responses. Others have shown that substance P synthesis in lung C fibers is upregulated by another environmental stimulant, allergen. Thus, an upregulation of the substance P system at NTS synapses could contribute to the increased NTS excitability and enhanced reflex responses to lung C-fiber stimulation, providing a potential mechanism to help explain the association of ETS exposure with respiratory symptoms and SIDS

A Comparative Study of the Valence Electronic Excitations of N_2 by Inelastic X-ray and Electron Scattering

Bound state, valence electronic excitation spectra of N_2 are probed by nonresonant inelastic x-ray and electron scattering. Within the usual theoretical treatments, dynamical structure factors derived from the two probes should be identical. However, we find strong disagreements outside the dipole scattering limit, even at high probe energies. This suggests an unexpectedly important contribution from intra-molecular multiple scattering of the probe electron from core electrons or the nucleus. These effects should grow progressively stronger as the atomic number of the target species increases.Comment: Submitted to Physical Review Letters April 27, 2010. 12 pages including 2 figure pages

Obesity prevention in the early years: a mapping study of national policies in England from a behavioural science perspective

Background Evidence indicates that early life is critical for determining future obesity risk. A sharper policy focus on pregnancy and early childhood could help improve obesity prevention efforts. This study aimed to systematically identify and categorise policy levers used in England with potential to influence early lifecourse (pregnancy, 0-5 years) and identify how these interface with energy balance behaviours. The objective is to identify gaps and where further policy actions could most effectively focus. Methods A behavioural science approach was taken using the Capability-Opportunity-Motivation-Behaviour (COM-B) model and Behaviour Change Wheel (BCW) framework. The key determinants of energy balance in the early years were identified from the Foresight Systems Map. Policy actions were scoped systematically from available literature, including any health or non-health policies which could impact on energy balance behaviours. Foresight variables and policy actions were considered in terms of COM-B and the BCW to determine approaches likely to be effective for obesity prevention and treatment. Existing policies were overlaid across the map of key risk factors to identify gaps in obesity prevention and treatment provision. Results A wide range of policy actions were identified (n=115) to address obesity-relevant risk factors. These were most commonly educational or guidelines relating to environmental restructuring (i.e. changing the physical or social context). Scope for strengthening policies relating to the food system (e.g. the market price of food) and psychological factors contributing to obesity were identified. Policies acted via all aspects of the COM-B model, but there was scope for improving policies to increase capability through skills acquisition and both reflective and automatic motivation. Conclusions There is substantial policy activity to address early years obesity but much is focused on education. Scope exists to strengthen actions relating to upstream policies which act on food systems and those targeting psychological factors contributing to obesity risk

Tailored for Real-World: A Whole Slide Image Classification System Validated on Uncurated Multi-Site Data Emulating the Prospective Pathology Workload.

Standard of care diagnostic procedure for suspected skin cancer is microscopic examination of hematoxylin & eosin stained tissue by a pathologist. Areas of high inter-pathologist discordance and rising biopsy rates necessitate higher efficiency and diagnostic reproducibility. We present and validate a deep learning system which classifies digitized dermatopathology slides into 4 categories. The system is developed using 5,070 images from a single lab, and tested on an uncurated set of 13,537 images from 3 test labs, using whole slide scanners manufactured by 3 different vendors. The system\u27s use of deep-learning-based confidence scoring as a criterion to consider the result as accurate yields an accuracy of up to 98%, and makes it adoptable in a real-world setting. Without confidence scoring, the system achieved an accuracy of 78%. We anticipate that our deep learning system will serve as a foundation enabling faster diagnosis of skin cancer, identification of cases for specialist review, and targeted diagnostic classifications

Muscle p70S6K phosphorylation in response to soy and dairy rich meals in middle aged men with metabolic syndrome: a randomised crossover trial

The mammalian target of rapamycin (mTOR) pathway is the primary regulator of muscle protein synthesis. Metabolic syndrome (MetS) is characterized by central obesity and insulin resistance; little is known about how MetS affects the sensitivity of the mTOR pathway to feeding

Superscaling in inclusive electron-nucleus scattering

We investigate the degree to which the scaling functions $F(\psi')$ derived from cross sections for inclusive electron-nucleus quasi-elastic scattering define the same function for different nuclei. In the region where the scaling variable $\psi'< 0$, we find that this superscaling is experimentally realized to a high degree.Comment: Corrected previously mislabeled figures and cross references; 9 pages, 4 color figures, using BoxedEPS and REVTeX; email correspondence to [email protected]

Harnessing insulin- and leptin-induced oxidation of PTP1B for therapeutic development

The protein tyrosine phosphatase PTP1B is a major regulator of glucose homeostasis and energy metabolism, and a validated target for therapeutic intervention in diabetes and obesity. Nevertheless, it is a challenging target for inhibitor development. Previously, we generated a recombinant antibody (scFv45) that recognizes selectively the oxidized, inactive conformation of PTP1B. Here, we provide a molecular basis for its interaction with reversibly oxidized PTP1B. Furthermore, we have identified a small molecule inhibitor that mimics the effects of scFv45. Our data provide proof-of-concept that stabilization of PTP1B in an inactive, oxidized conformation by small molecules can promote insulin and leptin signaling. This work illustrates a novel paradigm for inhibiting the signaling function of PTP1B that may be exploited for therapeutic intervention in diabetes and obesity

Plant Genetic Resources and Germplasm Use in India

Plant genetic resource (PGR) scientists now recognize the importance of shifting from a singular focus on conservation to a focus on both conservation and utilization of germplasm in order to meet future challenges. This paper analyzes the patterns of distribution of pearl millet, six small millets, chickpea and pigeonpea germplasm over the last 10 years at the two major genebanks functioning in India: the National Genebank at the National Bureau of Plant Genetic Resources (NBPGR) and a Consultative Group for International Agricultural Research (CGIAR) Genebank at the International Crops Research Institute for the Semi-Arid Tropics (ICRISAT), as well as the patterns of use of germplasm by millet breeders in India. Between the years of 1999-2009, ICRISAT distributed approximately 48 per cent of all its collections to breeders in India whereas NBPGR distributed 36 per cent of their collection. A total of 20 responses (30 per cent of surveys sent) were collected through this study. Sixty-five percent of respondents said that they rarely (<50 per cent of the time) use germplasm from genebanks in their breeding programs. It is important that both genebanks look into several issues in order to improve levels of distribution and utilization, collection, duplication, engagement of the private sector, access to information, and pre-breeding