The RAG1 and RAG2 proteins are required to assemble mature Ag receptor genes in developing lymphocytes. Hypomorphic mutations in the gene encoding RAG1 are associated with Omenn syndrome, a primary immunodeficiency. We explored the biochemical defects resulting from a mutation identified in an Omenn syndrome patient which generates an amino acid substitution in the RAG1 RING finger/ubiquitin ligase domain (C325Y in murine RAG1) as well as an adjacent substitution (P326G). RAG1 C325Y demonstrated a 50-fold reduction in recombination activity in cultured pro-B cells despite the fact that its expression and localization to the nucleus were similar to the wild-type protein. The C325Y substitution severely abrogated ubiquitin ligase activity of the purified RAG1 RING finger domain, and the tertiary structure of the domain was altered. The P326G substitution also abrogated ubiquitin ligase activity but had a less severe effect on protein folding. RAG1 P326G also demonstrated a recombination impairment that was most pronounced when RAG1 levels were limiting. Thus, a correctly folded RAG1 RING finger domain is required for normal V(D)J recombination, and RAG1 ubiquitin ligase activity can contribute when the protein is present at relatively low levels.
In the absence of adequate levels of cellular acidic phospholipids, Escherichia coli remain viable but are arrested for growth. Expression of a DnaA protein that contains a single amino acid substitution in the membrane-binding domain, DnaA(L366K), in concert with expression of wild-type DnaA protein, restores growth. DnaA protein has high affinity for ATP and ADP, and in vitro lipid bilayers that are fluid and contain acidic phospholipids reactivate inert ADP-DnaA by promoting an exchange of ATP for ADP. Here, nucleotide and lipid interactions and replication activity of purified DnaA(L366K) were examined to gain insight into the mechanism of how it restores growth to cells lacking acidic phospholipids. DnaA(L366K) behaved like wildtype DnaA with respect to nucleotide binding affinities and hydrolysis properties, specificity of acidic phospholipids for nucleotide release, and origin binding. Yet, DnaA(L366K) was feeble at initiating replication from oriC unless augmented with a limiting quantity of wildtype DnaA, reflecting the in vivo requirement that both wild-type and a mutant form of DnaA must be expressed and act together to restore growth to acidic phospholipid deficient cells.
We explore the role of workplace accommodations in reducing employment barriers and improving the employment of people with disabilities. We do so using data from the 2015 Survey of Disability and Employment on people with disabilities who applied for vocational rehabilitation services in three states. The results show that at least one third of nonworking people with disabilities reported employment barriers that could be addressed by workplace accommodations, such as lack of transportation and an inaccessible workplace. We also find that receiving certain types of workplace accommodations, such as help with transportation, flexible work schedules, or a personal care attendant, is positively correlated with being employed at the time of the survey. Finally, people who are in poor health or have physical disabilities were more likely to perceive workplace inaccessibility as a barrier but less likely to have received accommodations in their current or most recent job. This suggests that people with these characteristics may be good candidates to target for greater access to workplace accommodations.
Objective To estimate the additional hospital costs associated with inpatient medical harms occurring during an index inpatient admission and costs from subsequent readmissions within 90 days. Data Source 2009 to 2011 Healthcare Cost and Utilization Project's State Inpatient Databases from 12 states. Study Design We compare hospital costs incurred by patients experiencing a specific harm during their hospital stay to the costs incurred by similar patients who did not experience that harm. Data Extraction We extracted records for adult patients admitted for a reason other than rehabilitation or mental health, were at risk of a harm, and were admitted for less than a year. Principal Findings The costliest inpatient harms, such as surgical site infections and severe pressure ulcers, are associated with approximately $30 000 in additional index stay costs per harm. Less costly harms, such as catheter‐ or hospital‐associated urinary tract infections and venous thromboembolism, can add $6000 to $13 000. Birth and obstetric traumas add as little as $100. Conclusions Our analysis represents rigorous estimates of the hospital costs of a variety of inpatient harms; these should be of interest to health care administrators and policy makers to identify areas for cost savings to the health care system.
We use the American Time Use Survey to examine the extent to which adults with disabilities-defined using both the new six-question sequence on disability and the traditional work-limitation question-spend more time on health-related activities and less time on other activities than those without disabilities. We find that men and women who both reported a work limitation and responded "yes" to any of the questions in the six-question disability sequence spend approximately 40 to 50 more minutes per week, respectively, on health-related activities. We also find that most working-age men and women who report a disability work fewer hours per day than men and women without disabilities. The largest difference is for men and women who report both types of disability; these individuals spend, on average, 5 fewer hours per day in paid work than men and women without disabilities. On average, most of the decrease in paid work time is offset by more time spent on leisure activities (defined as activities that provide direct utility, such as entertainment, social activities, attending recreational events, and general relaxation) and sleeping, which is likely due to these being default activities for individuals whose medical issues and environment constrain them from participating in other activities.
PurposeThe aim of this case study is to explore and understand the talent management innovations, practices and processes in a major telecoms company in India, Bharti Airtel.Design/methodology/approachThe paper is based on a study of the organization's talent management practices and a survey of executives, including in‐depth interviews with two key talent management executives, and a study of employees' perceptions of the organization's talent management and its impact.FindingsThe research revealed the organization's vision and methods for integrating talent management processes. Talent management is an important element of the development process for employees and is an organization‐wide practice. The process of effective management of the talent pool has led to enhanced employee engagement and reduced attrition and proportionately increased the average tenure of employees. The talent management strategy and processes have contributed in varying degrees to development and growth of employees.Research limitations/implicationsThis research is an elementary study posing the need for further research into the organization‐wide practice of managing talent.Originality/valueThe research addresses how talent management is perceived in a successful organization and examines the recognition and growing acceptance of talent management practices. Talent management is widely adopted by multinationals operating in India, however, most Indian organizations are either currently or soon to adopt the practice. They are dealing with issues such as whether talent management is an offshoot of HR processes or an independent developmental process, and how it will create a competitive advantage and enhance employee engagement. This case study shows how the adoption of talent management processes on an organization‐wide scale – not confined to the HR function – has helped the organization improve retention and development.
This paper examines the relationship between rising health insurance costs and employee compensation. I estimate the extent to which total compensation decreases with a rise in health insurance costs and decompose these changes in compensation into adjustments in wages, non-health fringe benefits, and employee contributions to health insurance premiums. I examine this relationship using the National Compensation Survey, a panel dataset on compensation and health insurance for a sample of establishments across the USA. I find that total hourly compensation reduces by $0.52 for each dollar increase in health insurance costs. This reduction in total compensation is primarily in the form of higher employee premium contributions, and there is no evidence of a change in wages and non-health fringe benefits. These findings show that workers are absorbing at least part of the increase in health insurance costs through lower compensation and highlight the importance of examining total compensation, and not just wages, when examining the relationship between health insurance costs and employee compensation. Copyright © 2016 John Wiley & Sons, Ltd.
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