Characterization of In Vivo Keratin 19 Phosphorylation on Tyrosine-391

Keratin polypeptide 19 (K19) is a type I intermediate filament protein that is expressed in stratified and simple-type epithelia. Although K19 is known to be phosphorylated on tyrosine residue(s), conclusive site-specific characterization of these residue(s) and identification potential kinases that may be involved has not been reported.In this study, biochemical, molecular and immunological approaches were undertaken in order to identify and characterize K19 tyrosine phosphorylation. Upon treatment with pervanadate, a tyrosine phosphatase inhibitor, human K19 (hK19) was phosphorylated on tyrosine 391, located in the 'tail' domain of the protein. K19 Y391 phosphorylation was confirmed using site-directed mutagenesis and cell transfection coupled with the generation of a K19 phospho (p)-Y391-specific rabbit antibody. The antibody also recognized mouse phospho-K19 (K19 pY394). This tyrosine residue is not phosphorylated under basal conditions, but becomes phosphorylated in the presence of Src kinase in vitro and in cells expressing constitutively-active Src. Pervanadate treatment in vivo resulted in phosphorylation of K19 Y394 and Y391 in colonic epithelial cells of non-transgenic mice and hK19-overexpressing mice, respectively.Human K19 tyrosine 391 is phosphorylated, potentially by Src kinase, and is the first well-defined tyrosine phosphorylation site of any keratin protein. The lack of detection of K19 pY391 in the absence of tyrosine phosphatase inhibition suggests that its phosphorylation is highly dynamic

Genetic parameters and selection strategies for soybean genotypes resistant to the stink bug-complex

Soybean genotypes resistant to stink bugs are derived from complex breeding processes obtained through indirect selection. The aim of the present work was to estimate genetic parameters for guiding selection strategies towards resistant genotypes, based on those traits associated with responses to pod-attacking stink bugs, such as the grain filling period (GFP), leaf retention (LR), percentage index of pod damage (PIPD) and percentage of spotted seeds (PSS). We assessed the parental lines IAC-100 (resistant) and FT-Estrela (susceptible), the progenies F2 and F 4 , 30 progenies F 2:3 , 30 progenies BC 1 F 2:3 and 30 progenies BC 2 F 2:3 , besides the cultivars BRS Celeste and MGBR-46 (Conquista). Three field experiments, using randomized complete block design with three replications, were installed in Goiânia-GO, in the 2002/03 season. Each experiment consisted of 36 treatments (6 common and 30 regular). Heritability estimates were: 74.6 and 36.1 (GFP); 51.9 and 19.9 (LR); 49.6 and 49.6 (PIPD) and 55.8 and 20.3 (PSS), in both the broad and narrow senses, respectively. Based on these results, we concluded that the best strategy for obtaining stink bug-resistant genotypes consists of selecting the PIPD trait in early generations (F 3 or F 4 ), followed by selection for the GFP, LR and PSS traits in generations with higher endogamy levels

The limitations of employment as a tool for social inclusion

<p>Abstract</p> <p>Background</p> <p>One important component of social inclusion is the improvement of well-being through encouraging participation in employment and work life. However, the ways that employment contributes to wellbeing are complex. This study investigates how poor health status might act as a barrier to gaining good quality work, and how good quality work is an important pre-requisite for positive health outcomes.</p> <p>Methods</p> <p>This study uses data from the PATH Through Life Project, analysing baseline and follow-up data on employment status, psychosocial job quality, and mental and physical health status from 4261 people in the Canberra and Queanbeyan region of south-eastern Australia. Longitudinal analyses conducted across the two time points investigated patterns of change in employment circumstances and associated changes in physical and mental health status.</p> <p>Results</p> <p>Those who were unemployed and those in poor quality jobs (characterised by insecurity, low marketability and job strain) were more likely to remain in these circumstances than to move to better working conditions. Poor quality jobs were associated with poorer physical and mental health status than better quality work, with the health of those in the poorest quality jobs comparable to that of the unemployed. For those who were unemployed at baseline, pre-existing health status predicted employment transition. Those respondents who moved from unemployment into poor quality work experienced an increase in depressive symptoms compared to those who moved into good quality work.</p> <p>Conclusions</p> <p>This evidence underlines the difficulty of moving from unemployment into good quality work and highlights the need for social inclusion policies to consider people's pre-existing health conditions and promote job quality.</p

Hitting Hotspots: Spatial Targeting of Malaria for Control and Elimination

Teun Bousema and colleagues argue that targeting malaria “hotspots” is a highly efficient way to reduce malaria transmission at all levels of transmission intensity

Operative versus non-operative management of pediatric medial epicondyle fractures: a systematic review

There is ongoing debate about the management of medial epicondyle fractures in the pediatric population. This systematic review evaluated non-operative versus operative treatment of medial epicondyle fractures in pediatric and adolescent patients over the last six decades. A systematic review of the available literature was performed. Frequency-weighted mean union times were used to compare union rates for closed versus open treatments. Moreover, functional outcomes and range-of-motion variables were correlated with varying treatment modalities. Any complications, including ulnar nerve symptoms, pain, instability, infection, and residual deformity, were cataloged. Fourteen studies, encompassing 498 patients, met the inclusion/exclusion criteria. There were 261 males and 132 female patients; the frequency-weighted average age was 11.93 years. The follow-up range was 6–216 months. Under the cumulative random effects model, the odds of union with operative fixation was 9.33 times the odds of union with non-operative treatment (P &lt; 0.0001). There was no significant difference between operative and non-operative treatments in terms of pain at final follow-up (P = 0.73) or ulnar nerve symptoms (P = 0.412). Operative treatment affords a significantly higher union rate over the non-operative management of medial epicondyle fractures. There was no difference in pain at final follow-up between operative and non-operative treatments. As surgical indications evolve, and the functional demands of pediatric patients increase, surgical fixation should be strongly considered to achieve stable fixation and bony union

Subliminal Semantic Priming in Speech

Numerous studies have reported subliminal repetition and semantic priming in the visual modality. We transferred this paradigm to the auditory modality. Prime awareness was manipulated by a reduction of sound intensity level. Uncategorized prime words (according to a post-test) were followed by semantically related, unrelated, or repeated target words (presented without intensity reduction) and participants performed a lexical decision task (LDT). Participants with slower reaction times in the LDT showed semantic priming (faster reaction times for semantically related compared to unrelated targets) and negative repetition priming (slower reaction times for repeated compared to semantically related targets). This is the first report of semantic priming in the auditory modality without conscious categorization of the prime

Subliminal Semantic Priming in Speech

Numerous studies have reported subliminal repetition and semantic priming in the visual modality. We transferred this paradigm to the auditory modality. Prime awareness was manipulated by a reduction of sound intensity level. Uncategorized prime words (according to a post-test) were followed by semantically related, unrelated, or repeated target words (presented without intensity reduction) and participants performed a lexical decision task (LDT). Participants with slower reaction times in the LDT showed semantic priming (faster reaction times for semantically related compared to unrelated targets) and negative repetition priming (slower reaction times for repeated compared to semantically related targets). This is the first report of semantic priming in the auditory modality without conscious categorization of the prime

Cytokine preconditioning of engineered cartilage provides protection against interleukin-1 insult

Research reported in this publication was supported in part by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health under Award Number R01AR60361, R01AR061988, P41EB002520). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. ART was supported by a National Science Foundation Graduate Fellowship

UP States Protect Ongoing Cortical Activity from Thalamic Inputs

Cortical neurons in vitro and in vivo fluctuate spontaneously between two stable membrane potentials: a depolarized UP state and a hyperpolarized DOWN state. UP states temporally correspond with multineuronal firing sequences which may be important for information processing. To examine how thalamic inputs interact with ongoing cortical UP state activity, we used calcium imaging and targeted whole-cell recordings of activated neurons in thalamocortical slices of mouse somatosensory cortex. Whereas thalamic stimulation during DOWN states generated multineuronal, synchronized UP states, identical stimulation during UP states had no effect on the subthreshold membrane dynamics of the vast majority of cells or on ongoing multineuronal temporal patterns. Both thalamocortical and corticocortical PSPs were significantly reduced and neuronal input resistance was significantly decreased during cortical UP states – mechanistically consistent with UP state insensitivity. Our results demonstrate that cortical dynamics during UP states are insensitive to thalamic inputs