Chemical- and irradiation-induced mutants of indica rice IR64 for forward and reverse genetics

IR64, the most widely grown indica rice in South and Southeast Asia, possesses many positive agronomic characteristics (e.g., wide adaptability, high yield potential, tolerance to multiple diseases and pests, and good eating quality,) that make it an ideal genotype for identifying mutational changes in traits of agronomic importance. We have produced a large collection of chemical and irradiation-induced IR64 mutants with different genetic lesions that are amenable to both forward and reverse genetics. About 60,000 IR64 mutants have been generated by mutagenesis using chemicals (diepoxybutane and ethylmethanesulfonate) and irradiation (fast neutron and gamma ray). More than 38,000 independent lines have been advanced to M4 generation enabling evaluation of quantitative traits by replicated trials. Morphological variations at vegetative and reproductive stages, including plant architecture, growth habit, pigmentation and various physiological characters, are commonly observed in the four mutagenized populations. Conditional mutants such as gain or loss of resistance to blast, bacterial blight, and tungro disease have been identified at frequencies ranging from 0.01% to 0.1%. Results from pilot experiments indicate that the mutant collections are suitable for reverse genetics through PCR-detection of deletions and TILLING. Furthermore, deletions can be detected using oligomer chips suggesting a general technique to pinpoint deletions when genome-wide oligomer chips are broadly available. M4 mutant seeds are available for users for screening of altered response to multiple stresses. So far, more than 15,000 mutant lines have been distributed. To facilitate broad usage of the mutants, a mutant database has been constructed in the International Rice Information System (IRIS; http: //www.iris.irri.org) to document the phenotypes and gene function discovered by users

Re-thinking the Etiological Framework of Neurodegeneration

Neurodegenerative diseases are among the leading causes of disability and death worldwide. The disease-related socioeconomic burden is expected to increase with the steadily increasing life expectancy. In spite of decades of clinical and basic research, most strategies designed to manage degenerative brain diseases are palliative. This is not surprising as neurodegeneration progresses "silently" for decades before symptoms are noticed. Importantly, conceptual models with heuristic value used to study neurodegeneration have been constructed retrospectively, based on signs and symptoms already present in affected patients;a circumstance that may confound causes and consequences. Hence, innovative, paradigm-shifting views of the etiology of these diseases are necessary to enable their timely prevention and treatment. Here, we outline four alternative views, not mutually exclusive, on different etiological paths toward neurodegeneration. First, we propose neurodegeneration as being a secondary outcome of a primary cardiovascular cause with vascular pathology disrupting the vital homeostatic interactions between the vasculature and the brain, resulting in cognitive impairment, dementia, and cerebrovascular events such as stroke. Second, we suggest that the persistence of senescent cells in neuronal circuits may favor, together with systemic metabolic diseases, neurodegeneration to occur. Third, we argue that neurodegeneration may start in response to altered body and brain trophic interactions established via the hardwire that connects peripheral targets with central neuronal structures or by means of extracellular vesicle (E\-mediated communication. Lastly, we elaborate on how lifespan body dysbiosis may be linked to the origin of neurodegeneration. We highlight the existence of bacterial products that modulate the gut-brain axis causing neuroinflammation and neuronal dysfunction. As a concluding section, we end by recommending research avenues to investigate these etiological paths in the future. We think that this requires an integrated, interdisciplinary conceptual research approach based on the investigation of the multimodal aspects of physiology and pathophysiology. It involves utilizing proper conceptual models, experimental animal units, and identifying currently unused opportunities derived from human data. Overall, the proposed etiological paths and experimental recommendations will be important guidelines for future cross-discipline research to overcome the translational roadblock and to develop causative treatments for neurodegenerative diseases

Impact of breakfast on daily energy intake - an analysis of absolute versus relative breakfast calories

<p>Abstract</p> <p>Objective</p> <p>The role of breakfast energy in total daily energy intake is a matter of debate. Acute feeding experiments demonstrated that high breakfast energy leads to greater overall intake supported by cross-sectional data of a free-living population. On the other hand, a large intraindividual analysis has indicated that a high proportion of breakfast to overall intake is associated with lower daily energy intake. To evaluate these apparently contradictory results in greater detail both ways of analysis were applied to the same data set of dietary records.</p> <p>Methods</p> <p>On an intraindividual basis total daily energy intake was related to the absolute values of breakfast energy intake or to the ratio of breakfast to overall intake, respectively. Food intake of 280 obese and 100 normal weight subjects was analyzed who recorded over 10 (obese) or 14 (normal weight) consecutive days, respectively.</p> <p>Results</p> <p>Increasing breakfast energy was associated with greater overall intake in normal weight and obese subjects. The increasing ratio of breakfast to total daily energy intake was associated with a significant reduction of overall intake on days where post-breakfast energy was significantly reduced. Correlational and multiple regression analysis support the concept that absolute breakfast calories have the strongest influence on daily energy intake.</p> <p>Conclusion</p> <p>Reduced breakfast energy intake is associated with lower total daily intake. The influence of the ratio of breakfast to overall energy intake largely depends on the post-breakfast rather than breakfast intake pattern. Therefore, overweight and obese subjects should consider the reduction of breakfast calories as a simple option to improve their daily energy balance.</p

Impact of bleeding-related complications and/or blood product transfusions on hospital costs in inpatient surgical patients

<p>Abstract</p> <p>Background</p> <p>Inadequate surgical hemostasis may lead to transfusion and/or other bleeding-related complications. This study examines the incidence and costs of bleeding-related complications and/or blood product transfusions occurring as a consequence of surgery in various inpatient surgical cohorts.</p> <p>Methods</p> <p>A retrospective analysis was conducted using Premier's Perspective™ hospital database. Patients who had an inpatient procedure within a specialty of interest (cardiac, vascular, non-cardiac thoracic, solid organ, general, reproductive organ, knee/hip replacement, or spinal surgery) during 2006-2007 were identified. For each specialty, the rate of bleeding-related complications (including bleeding event, intervention to control for bleeding, and blood product transfusions) was examined, and hospital costs and length of stay (LOS) were compared between surgeries with and without bleeding-related complications. Incremental costs and ratios of average total hospital costs for patients with bleeding-related complications vs. those without complications were estimated using ordinary least squares (OLS) regression, adjusting for demographics, hospital characteristics, and other baseline characteristics. Models using generalized estimating equations (GEE) were also used to measure the impact of bleeding-related complications on costs while accounting for the effects related to the clustering of patients receiving care from the same hospitals.</p> <p>Results</p> <p>A total of 103,829 cardiac, 216,199 vascular, 142,562 non-cardiac thoracic, 45,687 solid organ, 362,512 general, 384,132 reproductive organ, 246,815 knee/hip replacement, and 107,187 spinal surgeries were identified. Overall, the rate of bleeding-related complications was 29.9% and ranged from 7.5% to 47.4% for reproductive organ and cardiac, respectively. Overall, incremental LOS associated with bleeding-related complications or transfusions (unadjusted for covariates) was 6.0 days and ranged from 1.3 to 9.6 days for knee/hip replacement and non-cardiac thoracic, respectively. The incremental cost per hospitalization associated with bleeding-related complications and adjusted for covariates was highest for spinal surgery ($17,279) followed by vascular ($15,123), solid organ ($13,210), non-cardiac thoracic ($13,473), cardiac ($10,279), general ($4,354), knee/hip replacement ($3,005), and reproductive organ ($2,805).</p> <p>Conclusions</p> <p>This study characterizes the increased hospital LOS and cost associated with bleeding-related complications and/or transfusions occurring as a consequence of surgery, and supports implementation of blood-conservation strategies.</p

A comparative analysis of colour–emotion associations in 16–88‐year‐old adults from 31 countries

As people age, they tend to spend more time indoors, and the colours in their surroundings may significantly impact their mood and overall well-being. However, there is a lack of empirical evidence to provide informed guidance on colour choices, irrespective of age group. To work towards informed choices, we investigated whether the associations between colours and emotions observed in younger individuals also apply to older adults. We recruited 7,393 participants, aged between 16 and 88 years and coming from 31 countries. Each participant associated 12 colour terms with 20 emotion concepts and rated the intensity of each associated emotion. Different age groups exhibited highly similar patterns of colour-emotion associations (average similarity coefficient of 0.97), with subtle yet meaningful age-related differences. Adolescents associated the greatest number but the least positively biased emotions with colours. Older participants associated a smaller number but more intense and more positive emotions with all colour terms, displaying a positivity effect. Age also predicted arousal and power biases, varying by colour. Findings suggest parallels in colour-emotion associations between younger and older adults, with subtle but significant age-related variations. Future studies should next assess whether colour-emotion associations reflect what people actually feel when exposed to colour

Seroepidemiology of Human Bocavirus Infection in Jamaica

Human bocavirus (HBoV) is a newly identified human parvovirus. HBoV is associated with upper and lower respiratory tract infections and gastroenteritis in children. Little is known about the seroepidemiology of HBoV in populations in the Caribbean.In a cross-sectional study conducted at the University Hospital of the West Indies in Kingston, Jamaica, 287 blood samples were collected from pediatric patients and tested for the presence of HBoV-specific antibody using a virus-like-particle based enzyme-linked immunosorbent assay (ELISA).HBoV-specific antibodies were found to be present in 220/287 (76.7%) of samples collected from the pediatric population. Seroprevalence of HBoV was highest in those ≥2 years old. The seroepidemiological profile suggests that most children are exposed to HBoV during the first two years of life in Jamaica.HBoV infection is common in children in Jamaica. HBoV seroprevalence rates in the Caribbean are similar to those previously reported in other areas of the world

Patterns of adiposity, vascular phenotypes and cognitive function in the 1946 British Birth Cohort.

BACKGROUND: The relationship between long-term exposure to whole body or central obesity and cognitive function, as well as its potential determinants, remain controversial. In this study, we assessed (1) the potential impact of 30 years exposure to different patterns of whole body and central adiposity on cognitive function at 60-64 years, (2) whether trajectories of central adiposity can provide additional information on later cognitive function compared to trajectories of whole body adiposity, and (3) the influence of vascular phenotypes on these associations. METHODS: The study included 1249 participants from the prospective cohort MRC National Survey of Health and Development. Body mass index (BMI), waist circumference (WC), and vascular (carotid intima-media thickness, carotid-femoral pulse wave velocity) and cognitive function (memory, processing speed, reaction time) data, at 60-64 years, were used to assess the associations between different patterns of adult WC or BMI (from 36 years of age) and late midlife cognitive performance, as well as the proportion of this association explained by cardiovascular phenotypes. RESULTS: Longer exposure to elevated WC was related to lower memory performance (p < 0.001 for both) and longer choice reaction time (p = 0.003). A faster gain of WC between 36 and 43 years of age was associated with the largest change in reaction time and memory test (P < 0.05 for all). Similar associations were observed when patterns of WC were substituted with patterns of BMI, but when WC and BMI were included in the same model, only patterns of WC remained significantly associated with cognitive function. Participants who dropped one BMI category and maintained a lower BMI had similar memory performance to those of normal weight during the whole follow-up. Conversely, those who dropped and subsequently regained one BMI category had a memory function similar to those with 30 years exposure to elevated BMI. Adjustment for vascular phenotypes, levels of cardiovascular risk factors, physical activity, education, childhood cognition and socioeconomic position did not affect these associations. CONCLUSIONS: Longer exposure to elevated WC or BMI and faster WC or BMI gains between 36 and 43 years are related to lower cognitive function at 60-64 years. Patterns of WC in adulthood could provide additional information in predicting late midlife cognitive function than patterns of BMI. The acquisition of an adverse cardiovascular phenotype associated with adiposity is unlikely to account for these relationships

Position of the Third Na+ Site in the Aspartate Transporter GltPh and the Human Glutamate Transporter, EAAT1

Glutamate transport via the human excitatory amino acid transporters is coupled to the co-transport of three Na+ ions, one H+ and the counter-transport of one K+ ion. Transport by an archaeal homologue of the human glutamate transporters, GltPh, whose three dimensional structure is known is also coupled to three Na+ ions but only two Na+ ion binding sites have been observed in the crystal structure of GltPh. In order to fully utilize the GltPh structure in functional studies of the human glutamate transporters, it is essential to understand the transport mechanism of GltPh and accurately determine the number and location of Na+ ions coupled to transport. Several sites have been proposed for the binding of a third Na+ ion from electrostatic calculations and molecular dynamics simulations. In this study, we have performed detailed free energy simulations for GltPh and reveal a new site for the third Na+ ion involving the side chains of Threonine 92, Serine 93, Asparagine 310, Aspartate 312, and the backbone of Tyrosine 89. We have also studied the transport properties of alanine mutants of the coordinating residues Threonine 92 and Serine 93 in GltPh, and the corresponding residues in a human glutamate transporter, EAAT1. The mutant transporters have reduced affinity for Na+ compared to their wild type counterparts. These results confirm that Threonine 92 and Serine 93 are involved in the coordination of the third Na+ ion in GltPh and EAAT1