Monomeric cohesin state revealed by live-cell single-molecule spectroscopy.

The cohesin complex plays an important role in the maintenance of genome stability. Cohesin is composed of four core subunits and a set of regulatory subunits that interact with the core subunits. Less is known about cohesin dynamics in live cells and on the contribution of individual subunits to the overall complex. Understanding the tethering mechanism of cohesin is still a challenge, especially because the proposed mechanisms are still not conclusive. Models proposed to describe tethering depend on either the monomeric cohesin ring or a cohesin dimer. Here, we investigate the role of cohesin dynamics and stoichiometry in live yeast cells at single-molecule resolution. We explore the effect of regulatory subunit deletion on cohesin mobility and found that depletion of different regulatory subunits has opposing effects. Finally, we show that cohesin exists mostly as a canonical monomer throughout the cell cycle, and its monomeric form is independent of its regulatory factors. Our results demonstrate that single-molecule tools have the potential to provide new insights into the cohesin mechanism of action in live cells.

Chromosome loading of cohesin depends on conserved residues in Scc3.

Cohesin is essential for sister chromatid cohesion, which ensures equal segregation of the chromatids to daughter cells. However, the molecular mechanism by which cohesin mediates this function is elusive. Scc3, one of the four core subunits of cohesin, is vital to cohesin activity. However, the mechanism by which Scc3 contributes to the activity and identity of its functional domains is not fully understood. Here, we describe an in-frame five-amino acid insertion mutation after glutamic acid 704 (scc3-E704ins) in yeast Scc3, located in the middle of the second armadillo repeat. Mutated cohesin-scc3-E704ins complexes are unable to establish cohesion. Detailed molecular and genetic analyses revealed that the mutated cohesin has reduced affinity to the Scc2 loader. This inhibits its enrichment at centromeres and chromosomal arms. Mutant complexes show a slow diffusion rate in live cells suggesting that they induce a major conformational change in the complex. The analysis of systematic mutations in the insertion region of Scc3 revealed two conserved aspartic acid residues that are essential for the activity. The study offers a better understanding of the contribution of Scc3 to cohesin activity and the mechanism by which cohesin tethers the sister chromatids during the cell cycle.

Investigating power styles and behavioural compliance for effective hospital administration.

PURPOSE: The purpose of this paper is to examine the use of power tactics by hospital administrators in order to gain employee compliance. It attempts to understand the influence of power bases of hospital administrators on the employee compliance using an analytic hierarchy process (AHP) technique. DESIGN/METHODOLOGY/APPROACH: The study adopted a mixed method technique and was conducted in two phases. In the first phase, qualitative analysis was carried out through content analysis of the anecdotes collected from the employees working in tertiary hospitals. Content analysis of responses aided in obtaining a list of criteria and sub-criteria affecting employee behavioural compliance. In the second phase, quantitative analysis was carried out using the AHP technique. While applying AHP, the issue pertaining to employee behavioural compliance with hospital's policies, procedures and related instructions was formulated in form of a hierarchy of one objective, two criteria, six sub-criteria and five alternatives established through literature review and content analysis. Furthermore, the subject matter experts were asked to conduct pairwise comparison wherein priority rankings were achieved. FINDINGS: The results indicated that reward power (25 per cent) is the most significant power style exercised by effective hospital administrators in achieving employee behavioural compliance followed by expert (24 per cent), referent (22 per cent) and legitimate powers (17 per cent). As coercive (12 per cent) came out to be the least preferred power style, it should be cautiously exercised by hospital administrators in the present day scenario. RESEARCH LIMITATIONS/IMPLICATIONS: The major limitation of this study is that the sample was drawn only from three tertiary hospitals in Jammu district that limits the generalizability of the findings in all the hospital settings across different regions. No attempt is made in this study to understand the variations with regard to demographics of the respondents that can be taken as a future research study. This study is cross-sectional in nature and provides the perspective of specific time. A longitudinal study could further provide insights into different time variations and the comparison and henceforth can be more comprehensive, thus supporting the generalizability of this study. PRACTICAL IMPLICATIONS: The study empirically identifies the relative importance of exercising power styles in order to gain employee behavioural compliance. The study helps in understanding the complex problem of behavioural compliance in hospital setting by examining the intensity of each factor affecting employee behavioural compliance. This knowledge is very critical in effective hospital management and getting the work done. The priority rankings obtained for power styles can be used for developing selection batteries and performance records of hospital administrators. As the behaviour of the employees is not static, there may exist the inherent limitations of adopted cross-sectional design for the present study. Furthermore, longitudinal study can be conducted at different time periods, to understand the variations in the patterns of employee's compliance behaviour and associated practiced power styles by hospital administrators. ORIGINALITY/VALUE: This is perhaps the first study that has scientifically attempted to integrate the power styles and analyzed their effective use in hospital administration. This research study has attempted to develop an elementary base for academicians, scholars as well as management practitioners on the effective use of power styles for achieving employee behavioural compliance in hospitals.

Visceral leishmaniasis masquerading as chronic liver disease.

We report a patient with fever, progressive jaundice and abdominal distension, having marked pallor, icterus, ascites and hepatosplenomegaly. Investigations revealed pancytopenia and deranged liver functions. Doppler study revealed portal hypertension and endoscopy showed grade II oesophageal varices. Liver biopsy suggested leishmanial hepatitis and bone marrow demonstrated multiple LD bodies. Diagnosis of "visceral leishmaniasis with leishmanial hepatitis with portal hypertension" was made. The case is being reported because of its rarity apart from it being an unusual presentation of kala-azar.

Staphylococcal pericarditis in a chronic renal failure patient.

A 34-year-old female with end-stage renal disease was admitted for severe metabolic acidosis, uremic encephalopathy, pericarditis and severe anemia following a bout of acute gastroenteritis. She improved on aggressive medical management including intensive hemodialysis and was initiated onto maintenance heparin-free hemodialysis (twelve hours per week) and discharged. After a week, she presented with fever with chills and rigors for three days, was toxic, severely orthopenic and had a pulsus paradoxus of 36 mmHg. Echocardiography suggested cardiac tamponade. Aspiration revealed frank pus with polymorphonuclear predominance and Staphylococcus aureus on culture. CT of the thorax revealed pericardial effusion. In the absence of any obvious septic foci, concomitant pleuro-pulmonary sepsis, mediastinal or intra-abdominal pathology; a diagnosis of "acute primary purulent pericarditis" was made. Patient was put on parenteral antibiotics-ceftriaxone and metrogyl. Vancomycin was added after sensitivity results. Pericardial drainage was required initially. After toxemia improved, paradox decreased and fever subsided, the pericardial catheter was removed and antibiotics continued for a period of four weeks. Maintenance hemodialysis was continued during hospital stay and after discharge.

Aplastic anemia complicating systemic lupus erythematosus: successful management with cyclosporine.

Anemia is common with connective tissue disorders, but pancytopenia is rare. We report a 22-year-old female who presented with menorrhagia, seizures, anemia, leukocytosis, thrombocytopenia, pericardial effusion, positive ANA, and evidence of vasculitis on CT head scan and was diagnosed with systemic lupus erythematosus (SLE). After 7 months of remission, she was readmitted with menorrhagia and pancytopenia. Investigations revealed aplastic anemia. She survived on transfusion support for 6 weeks, during which period she received methylprednisolone and cyclophosphamide pulses, and phenytoin was omitted but to no avail. Cyclosporine (300 mg/day) was started and the aplastic anemia responded. After 4 months of therapy, the cyclosporine was gradually tapered over the next 2 months. The patient has been on 10 mg/day of prednisolone for the last 6 months. Aplastic anemia is rare in SLE and the response to immunosuppressants is variable, but here is a success story.