4-fold induction after 24 h Angiotensin II-mediated miRNA-21 exp

4-fold induction after 24 h. Angiotensin II-mediated miRNA-21 expression resulted

in biologically active miRNA-21, determined using a fusion mRNA reporter system carrying miRNA-21 buy Screening Library target sequences in its 3′ untranslated region. Up-regulation of miRNA-21 intracellular levels increased aldosterone secretion but not cortisol. Elevation of miRNA-21 levels also increased cell proliferation in H295R cells. In summary, miRNA-21 is an endogenously expressed miRNA in human adrenal cells. miRNA-21 expression is up-regulated by angiotensin II, and its overexpression caused an increase in aldosterone secretion and cell proliferation. Alterations in miRNA-21 expression levels or function may be involved in dysregulation of angiotensin II signaling and abnormal aldosterone secretion by adrenal glands in humans.”
“BACKGROUND: The purpose of this study was to test a novel, dual tumour vascular endothelial cell (VEC)- and tumour cell-targeting factor VII-targeted Sn(IV) chlorin e6 photodynamic therapy (fVII-tPDT) by targeting a receptor tissue factor (TF) as an alternative treatment for chemoresistant PND-1186 molecular weight breast cancer using a multidrug resistant (MDR) breast cancer line MCF-7/MDR.\n\nMETHODS: The

TF expression by the MCF-7/MDR breast cancer cells and tumour VECs in MCF-7/MDR tumours from mice was determined separately by flow cytometry and immunohistochemistry using anti-human or anti-murine TF antibodies. The efficacy of fVII-tPDT was tested in vitro and in vivo and was compared with non-targeted PDT for treatment of chemoresistant breast cancer. The in vitro efficacy was determined by a non-clonogenic assay using crystal violet staining for monolayers, and apoptosis and necrosis were assayed to elucidate the underlying mechanisms. The in vivo efficacy of fVII-tPDT was determined in

a nude mouse model of subcutaneous MCF-7/MDR tumour xenograft by measuring tumour volume.\n\nRESULTS: To our knowledge, this is the first presentation showing that TF was expressed on tumour VECs in chemoresistant breast tumours from mice. The in vitro efficacy of fVII-tPDT was 12-fold stronger than that of ntPDT for MCF-7/MDR cancer cells, and the mechanism of action involved induction of apoptosis and necrosis. buy MCC950 Moreover, fVII-tPDT was effective and safe for the treatment of chemoresistant breast tumours in the nude mouse model.\n\nCONCLUSIONS: We conclude that fVII-tPDT is effective and safe for the treatment of chemoresistant breast cancer, presumably by simultaneously targeting both the tumour neovasculature and chemoresistant cancer cells. Thus, this dual-targeting fVII-tPDT could also have therapeutic potential for the treatment of other chemoresistant cancers. British Journal of Cancer (2011) 104, 1401-1409. doi:10.1038/bjc.2011.88 www.bjcancer.com Published online 22 March 2011 (C) 2011 Cancer Research UK”
“BACKGROUND: Early postoperative bowel obstruction is associated with considerable morbidity and mortality after colorectal surgery.

Conclusions:The group referred for specialist treatment h

\n\nConclusions:\n\nThe group referred for specialist treatment had more severe injuries and needed more complicated treatment than

the group recommended for care by general dentists. However, the rate of sequelae in permanent successors was the same in both.”
“In managing treatment for persons with mental illness, the primary care selleckchem physician (PCP) needs to communicate with mental health (MH) professionals in various settings over time to provide appropriate management and continuity of care. However, effective communication between PCPs and MH specialists is often poor. The present study reviewed evidence on the quality of information transfer between PCPs and specialist MH providers for referral requests and after inpatient discharge.

Twenty-three audit studies were identified that assessed the quality of content and nine that assessed strategies to improve quality. Results indicated that rates of item reporting were variable. Within the limited evidence on ARN-509 mw interventions to improve quality, use of structured forms showed positive results. Follow-up work can identify a minimum set of items to include in information transfers, along with item definitions and structures for holding this information. Then, methodologies for measuring data quality, including electronically generated performance metrics, can be developed.”
“Clinical effectiveness and safety of Propanorm (R) was studied in patients with arterial hypertension (A H), coronary heart disease (CND), chronic heart failure (CHF) with intact systolic left ventricular (LV) function, and atrial fibrillation (AF). Effectiveness and safety of Propanorm (R) was compared to those in Cordarone (R). Out of 137 randomised patients, 110 were included in the study (59 in the Propanorm (R) group, 51 – in the Cordarone (R) group) and followed up for 12 months. Primary end-points included all-cause mortality, cardiovascular mortality, fatal and non-fatal myocardial infarction and stroke. Secondary end-points included recurrent AF episodes, their duration, AF or decompensation-related hospitalisation NSC 123127 rates, systolic and diastolic LF function dynamics during

the treatment, and safety profile of Propanorm (R) and Cordarone (R) in CHF with intact systolic LF function.\n\nThe treatment of the main pathology was associated with achieving target blood pressure (BP) levels in 67,3% of the patients, reduction in functional classes (FC) of angina (70%) and CHF (94,5%), and decrease in cardiac decotnpensation-related hospitalisation rates by 72,9%.\n\nAfter 6 and 12 months of the therapy, Propanorm (R) effectiveness was as high as 67,4% and 52,9%, respectively, being similar to that for Cordarone (R) (62,7% and 52,9%, respectively). In 33,9% of the patients, Propanorm (R) therapy was associated with a reduction in clinical AF symptoms, their duration, ventricular rate during AF paroxysm, and increased number of asymptomatic AF episodes by 30,9%.

The toxicity of DH to freshwater mussels was assessed by initiati

The toxicity of DH to freshwater mussels was assessed by initiating an unprecedented 28 day, continuous exposure trial with 1 day old mussels. Results indicated that the survival and growth of Lampsilis siliquoidea was YH25448 cost not impacted by DH concentrations a parts per thousand currency sign121 mu g/L after 28 days of continuous

exposure. With the successful completion of this study, the techniques are now verified to evaluate the toxicity of waterborne compounds initiating 28-day chronic exposures with 1 day old mussels.”
“Neurons in the mouse dorsal root ganglia (DRGs) are composed of a variety of sensory modalities, such as pain-related nociceptors, itch-related pruriceptors, and thermoceptors. All these neurons are derived from late-born neurons that are initially marked by the expression of the nerve growth factor receptor TrkA. During perinatal and postnatal development, these TrkA lineage neurons are globally segregated into Ret-expressing and TrkA-expressing subtypes, and start to express a variety of sensory receptors and ion channels. The runt domain transcription factor Runx1 plays a pivotal role in controlling AP26113 cost these developmental

processes, but it remains unclear how it works. Here we showed that the homeodomain transcription factor Tlx3, expressed broadly in DRG neurons, is required to establish most Runx1-dependent phenotypes, including the segregation of TrkA-expressing versus Ret-expressing neurons and the expression of a dozen of sensory channels and receptors implicated in sensing pain, itch and temperature. Expression of Runx1 and Tlx3 is independent of each other at prenatal stages when they first establish the expression of these channels and receptors. Moreover, overexpression of Runx1 plus Tlx3 was able to induce ectopic expression of sensory channels and receptors. Collectively, these studies suggest that genetically Tlx3 acts in combination with Runx1 to control the development of a cohort of nociceptors, thermoceptors, and pruriceptors in mice.”
“Although there is evidence of associations between anxiety, depression

and cognitive function in old age, there is little work investigating relations between those variables over an extended period of time. Therefore, we used check details data from the Canberra Longitudinal Study to investigate 12-year cognitive change over four measurement points in relation to anxiety and depression symptoms. Latent growth models on over 836 community-dwelling persons aged 70 years and over, recruited from the electoral roll suggested that higher depression symptom scores were associated with poorer initial performance in processing speed, verbal fluency and episodic memory while higher anxiety symptom scores were associated with verbal fluency. We found no evidence that mental health variables affected change in cognition over time.

Orbital involvement is frequently seen in metastatic disease of t

Orbital involvement is frequently seen in metastatic disease of the paranasal sinuses and skull base, but orbital apex syndrome is rare. Early presentation with clinical AZD1480 order features of acute ethmoiditis can delay the diagnosis of metastatic disease.

Here, we report the case of a 43-year-old woman with breast cancer who presented with orbital apex syndrome secondary to the skull base and paranasal sinus metastasis.”
“Objectives: To determine the prevalence of professional burnout among microvascular free-flap (MVFF) head and neck surgeons and to identify modifiable risk factors with the intent to reduce MVFF surgeon burnout.\n\nDesign: A cross-sectional, observational study.\n\nSetting: A questionnaire mailed to MVFF surgeons in the United States.\n\nParticipants: A total of 60 MVFF surgeons.\n\nMain Outcomes Measures: Professional burnout was quantified using the Maslach Burnout Inventory-Human Services Study questionnaire, which defines burnout as the triad of high emotional exhaustion (EE), high depersonalization (DP), and low personal accomplishment. Additional data included

demographic information and subjective assessment of professional stressors, satisfaction, self-efficacy, and support systems using Likert score scales. Potential risk factors for burnout were determined via significant association (P < .05) by Fisher exact tests and analyses of ACY-241 variance.\n\nResults: Of the 141 mailed surveys, 72 were returned, for a response rate of 51%, and 60 of the respondents were practicing MVFF surgeons. Two percent of the responding MVFF surgeons experienced high burnout (n=1); 73%, moderate burnout (n=44); and 25%, low burnout (n=15). Compared with other otolaryngology academic faculty and department chairs, MVFF surgeons had similar or lower levels of burnout. On average, MVFF surgeons had low to moderate EE and DP scores. High EE was associated with https://www.selleckchem.com/products/poziotinib-hm781-36b.html excess workload, inadequate administration time, work invading family life, inability to care for personal health, poor perception of control over professional life, and frequency

of irritable behavior toward loved ones (P<.001). On average, MVFF surgeons experienced high personal accomplishment.\n\nConclusions: Most MVFF surgeons experience moderate professional burnout secondary to moderate EE and DP. This may be a problem of proper balance between professional obligations and personal life goals. Most MVFF surgeons, nonetheless, experience a high level of personal accomplishment in their profession.”
“Leaf litter is a very important primary source of energy in woodland streams. Decomposition of leaf litter is a process mediated by many groups of microorganisms which release extracellular enzymes for the degradation of complex macromolecules. In this process, true fungi and straminipiles are considered to be among the most active groups, more active than the bacteria, at least during the early stages of the process.

Conclusion: Given the continued reliance on VA to determine c

\n\nConclusion: Given the continued reliance on VA to determine cause of death in settings Selleckchem GSK3326595 with inadequate registration systems, it is important to understand the gaps in current VA methods and explore how methods can be improved to accurately

reflect neonatal disease burden in the global community.”
“Objective. Given recently developed prediction intervals (Pis) in which a random mean effect for a new study is estimated from meta-analytic data, we used the results from our previously published meta-analysis to calculate Pis for changes in lipids and lipoproteins as a result of progressive resistance training (PRT) in adults.\n\nMethods. Twenty-nine studies representing 1329 men and women (676 exercise, 653 control) were included. The primary outcomes included total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), ratio of total cholesterol to high-density lipoprotein cholesterol (TC/HDL-C), non-high-density lipoprotein cholesterol (non-HDL-C,) low-density lipoprotein cholesterol (LDL-C), and triglycerides (TC). Separate Pis (95%) were calculated for all lipids and lipoproteins.\n\nResults.

The expected outcomes of a new study on this topic were as follows: TC, -5.5 (-24.0, 13.0) mg/dl; HDL-C, 0.7 (-8.9, 10.4) Selleckchem GS 1101 mg/dl; TC/HDL-C, -0.5 (-1.8, 0.8); non-HIDL-C, -8.7 (-35.7, 18.3) mg/dl; LDL-C, -6.1 (-28.9, 16.4) mg/dI; TG, -8.1 (-34.5, 18.3) mg/dl.\n\nConclusions. Caution may be warranted in recommending that PRT improves TC, HDL-C, TC/HDL-C, non-HDL-C, LDL-C. and TG in adults. BLZ945 Future research should continue to examine the effects of PRT on lipids and lipoproteins in adults so as to determine optimal programs and populations in which PRT may have a positive effect. (C) 2009 Elsevier Inc. All rights reserved.”
“Background. Statutory registration of Chinese Medicine (CM) practitioners was introduced in Victoria

in 2000. The application assessment process for those who were granted registration during the transitional period (2002-04) was resource intensive, as little was known about their age, education, practice and language proficiency. This study offers insights that may be useful for the planning of national registration to commence in 2012.\n\nMethods. Data were extracted from registration application forms submitted to the Chinese Medicine Registration Board of Victoria (CMRB) between 2002 and 2004, using pre-defined data collection forms.\n\nResults. In 2006, 639 ‘grandparented’ Victorian CM practitioners had been registered, with a median age of 44 years old (range 23-86). There was a higher proportion of younger female, English-speaking, acupuncturists v. a higher proportion of older male, non-English-speaking, Chinese herbalists.

The primary objective was to define the maximum tolerated dose (M

The primary objective was to define the maximum tolerated dose (MTD) of Bortezomib when combined with ECarboX. Results 18 patients received bortezomib 0.7 (n = 6), 1.0 (n = 3), 1.3 (n = 6) and 1.6 mg m(-2) (n = 3) and a protocol amendment reducing the capecitabine dose to 500 mg m(-2) BD was enacted due to myelotoxicity. Common treatment-related non-haematological adverse events of any grade were fatigue (83.3

%), anorexia (55.6 %), constipation (55.6 %) and nausea (55.6 %). Common Grade 3/4 haematological toxicities were neutropenia (77.8 %) Dactolisib in vitro and thrombocytopenia (44.4 %). Objective responses were achieved in 6 patients (33.3 %) and a further 5 patients (27.8 %) had stable disease for bigger than 8 weeks. Conclusions The addition of Bortezomib to ECarboX is well tolerated and response rates are comparable with standard chemotherapy.”
“The purpose of this study was to evaluate the inhibitory effect of renierol, extracted from marine sponge Halicdona. SP., on xanthine oxidase (XO) and its hypouricemic effect in vivo. Renierol and a positive control, allopurinol, were tested for their effects on XO activity by measuring the formation

of uric acid and superoxide radical from xanthine. Renierol inhibited XO in a concentration-dependent and competitive manner. IC50 value was 1.85 mu g.ml(-1) through the measuring AG-014699 molecular weight of uric acid and was 1.36 mu g.ml(-1) through the measuring of superoxide radical. Renierol was found to have an in vivo hypouricemic activity against potassium oxonate-induced hyperuricaemia in mice. After oral administration of renierol at doses of 10, 20 and 30 mg.kg(-1), there was a significant decrease in the serum urate level (4.08 +/- 0.09 mg.dl(-1), P < 0.01), (3.47 +/- 0.11 mg.dl(-1), P < 0.01) and (3.12 +/- 0.08 mg.dl(-1), P < 0.01), when compared to the hyperuricaemic control

(6.74 +/- 0.23 mg.dl(-1)). Renierol was a potent XO inhibitor with hypouricemic CP-456773 cost activity in mice.”
“Several biologically significant parameters that are related to rice tillering are closely associated with rice grain yield. Although identification of the genes that control rice tillering and therefore influence crop yield would be valuable for rice production management and 3 genetic improvement, these genes remain largely unidentified. In this study, we carried out functional mapping of quantitative trait loci (QTLs) for rice tillering in 129 doubled haploid lines, which were derived from a cross between IR64 and Azucena. We measured the average number of tillers in each plot at seven developmental stages and fit the growth trajectory of rice tillering with the Wang-Lan-Ding mathematical model.

In conclusion, the negative results of cytotoxicity, genotoxicity

In conclusion, the negative results of cytotoxicity, genotoxicity and mutagenicity indicated that all the membranes can be employed for medical supplies, mainly in bone tissue engineering/regeneration, due to their osteoinductive properties.”
“The Central Nervous System (CNS) function was shown to be fueled exclusively by oxidative phosphorylation (OXPHOS). This is in line with the sensitivity

of brain to hypoxia, but less with the scarcity of the mitochondria in CNS. Consistently with the ectopic expression of FoF1-ATP synthase and the electron transfer chain in myelin, we have reported data demonstrating GDC-0994 MAPK inhibitor that isolated myelin vesicles (IMV) conduct OXPHOS. It may suggest that myelin sheath could be a site for the whole aerobic degradation of glucose.\n\nIn this paper, we assayed the functionality of glycolysis and of TCA cycle enzymes in IMV purified from bovine forebrain. We found the presence and activity of all of the glycolytic and TCA cycle enzymes, comparable to those in mitochondria-enriched selleck compound fractions, in the same experimental conditions. IMV also contain consistent carbonic anhydrase activity.\n\nThese data suggest

that myelin may be a contributor in energy supply for the axon, performing an extra-mitochondrial aerobic OXPHOS. The vision of myelin as the site of aerobic metabolism may shed a new light on many demyelinating pathologies, https://www.selleckchem.com/products/ferrostatin-1-fer-1.html that cause an a yet unresolved axonal degeneration and whose clinical onset coincides with myelin

development completion. (C) 2013 Elsevier Masson SAS. All rights reserved.”
“Background: The aim of this study was to determine whether immobilization of an arm has detrimental effects on driving performance.\n\nMethods: Thirty-six healthy officers-in-training were assigned a sequence of fiberglass splints (left and right-sided above-the-elbow thumb spica and below-the-elbow splints) with use of a randomized higher-order crossover design. Runs were scored on a cone-marked driving course used for officer certification with predetermined passing requirements. Driving time, the number of cones hit per course section, and the cone-adjusted total time (a five-second penalty per hit cone) were recorded. A linear mixed-effect model with random environmental and learning effects for cone-adjusted time analysis was used. Participants rated perceived driving difficulty and safety with each splint, and ratings were compared with the Wilcoxon signed-rank test.\n\nResults: Thirty participants completed the entire set of runs. Analysis of total cone-adjusted time 432 revealed a significant performance decrease with the left arm in an above-the-elbow thumb spica splint (average, 22.2 seconds; p < 0.001) and with the left arm in a below-the-elbow splint (average, 16.2; p = 0.007).

In addition, apnea – and the consequent lack

of inhibitio

In addition, apnea – and the consequent lack

of inhibition of the sympathetic system that occurs with lung inflation during normal breathing – potentiates central sympathetic outflow. Sympathetic activation persists into the daytime, and is thought to contribute to hypertension and other adverse cardiovascular outcomes. This review discusses chemoreflex physiology and sympathetic modulation during normal sleep, as well as the sympathetic dysregulation seen in OSA, its extension into wakefulness, and changes after treatment. Evidence supporting the role of the peripheral chemoreflex in the sympathetic dysregulation seen in OSA, including in the context of comorbid obesity, metabolic syndrome, and systemic hypertension, is reviewed. Finally, alterations in cardiovascular variability and other potential mechanisms that Crenolanib may play a role in the autonomic imbalance in OSA are also discussed.”
“A growing body of evidence now suggested INCB018424 inhibitor that cyclosporine A (CycA)-induced nephrotoxicity is a crucial clinical problem and oxidative stress is importantly responsible for

its toxicity. Ceftriaxone induced antioxidant effect in brain and neuronal tissues against oxidative damage although its antioxidant potential effect on kidney has not been clarified. The aim of this study was to evaluate whether ceftriaxone protects CycA-induced oxidative stress kidney injury in rats. Twenty-four rats were equally divided into four groups. First group was used as control. Ceftriaxone (200 mg/kg) and CycA (15 mg/kg) were administrated to second and third groups for 10 days, respectively. The ceftriaxone and CycA combination was given to rats constituting the fourth group for 10 days. Lipid peroxidation (LP), urea nitrogen and 3 lactate dehydrogenase selleck (LDH) levels

were higher in CycA group than in control and ceftriaxone groups although LP, urea nitrogen and LDH levels were lower in ceftriaxone + CycA group than in control and ceftriaxone groups. Glutathione peroxidase and catalase activities were lower in CycA group than in control whereas their activities were increased in control and ceftriaxone groups. Superoxide dismutase activity did not change by the treatments. Ceftriaxone administration recovered also CycA-induced atrophy, vacuolization and exfoliations of tubular epithelium and glomerular collapse in histopathological evaluation of kidney. In conclusion, we observed that ceftriaxone is beneficial on CycA-induced oxidative stress in kidney of rats by modulating oxidative and antioxidant system. Copyright (C) 2011 John Wiley & Sons, Ltd.”
“Electrochemistry of cytochrome c (cyt c) immobilized on a cardiolipin (CL)/phosphatidylcholine (PC) film supported on a glassy carbon electrode was investigated using variable-frequency AC voltammetry. At low ionic strength, we observed two redox-active subpopulations characterized by distinct values of potential (E-1/2) and electron transfer rate constant (k(ET)).

rs3027580 (NG_007119 1:g 4292G>C), and two SNPs in the GLA 5′-

rs3027580 (NG_007119.1:g.4292G>C), and two SNPs in the GLA 5′-untranslated region, rs2071225 (NM_000169.2:c.-10C>T) and rs3027585 (NM_000169.2:c.-12G>A), were identified with similar frequencies in sporadic PD patients and healthy controls. A novel variant (NG_007119.1:g.4488C>G) within the promoter region, at the 573 site upstream of the translation start codon (ATG), was found in one male PD patient, but not in female PD patients or healthy controls. Our data suggest that the sequence variant may affect GLA gene expression selleck kinase inhibitor by altering transcription

factor binding sites, contributing to the pathogenesis of sporadic PD. (C) 2011 Elsevier Ireland Ltd. All rights reserved.”
“We derive an analytical expression of the second virial coefficient of d-dimensional hard sphere fluids confined to slit pores by applying Speedy and Reiss’ interpretation of cavity space. We confirm that this coefficient is identical to the one obtained from the Mayer cluster expansion up to second order with respect to fugacity. The key step of both approaches is to evaluate either the surface area or the volume of the d-dimensional exclusion sphere confined to a slit pore. We, further, present an analytical form of thermodynamic functions

such as entropy and pressure tensor as a function of the size of the slit pore. Molecular dynamics simulations are performed for d = 2 and d = 3, and the results are compared with

analytically obtained equations of state. They agree satisfactorily in the low density regime, and, for Selleckchem HSP990 given density, the agreement of the results becomes excellent as the width of the slit pore gets smaller, because the higher order virial coefficients become unimportant. (C) 2011 American Institute of Physics. [doi: 10.1063/1.3564917]“
“P>Background\n\nWe lack population-based estimates of the rate of decompensation in people with compensated cirrhosis as well as estimates of the manner in which click here the disease progresses once identified.\n\nAim\n\nTo determine the rate of decompensation and clinical progression of disease in patients with cirrhosis based upon clinical symptoms recorded electronically in general practice data.\n\nMethods\n\nUsing Cox proportional hazards regression, we modelled the rate of decompensation for patients from the UK General Practice Research Database with a diagnosis of cirrhosis between 1987 and 2002. We determined the clinical progression in the first year following diagnosis and subsequently categorizing patients through time according to a simple clinical staging system agreed at the Baveno IV consensus conference.\n\nResults\n\nThe rate of decompensation in patients with compensated cirrhosis was found to be 11% overall. The rate of decompensation was higher in the first year (at 31% compared with 7.3% afterwards) and in patients with an alcoholic aetiology.

The binding interface was probed with point mutations, none of wh

The binding interface was probed with point mutations, none of which had a noticeable effect on dimer formation; however deletion

of the C-terminal tail region prevented dimer formation in vivo. The structure provides a template for future biochemical studies and modelling of ICP27 homologs from other herpesviruses.”
“The turtle body plan, with its solid shell, deviates radically from those of other tetrapods. The dorsal part of the turtle shell, or the carapace, consists mainly of costal and neural bony plates, which are continuous with the underlying thoracic ribs and vertebrae, respectively. Because of their superficial position, the evolutionary origins of these costo-neural elements have long remained elusive. Here we show, through comparative morphological and embryological analyses, that the major part of the carapace is derived Selleck LDN-193189 purely from endoskeletal ribs. We examine turtle embryos and find that the costal and neural plates develop not within the dermis, but within deeper connective tissue where the rib and intercostal muscle anlagen

develop. We also examine the fossils of an outgroup of turtles to confirm that Z-VAD-FMK order the structure equivalent to the turtle carapace developed independently of the true osteoderm. Our results highlight the hitherto unravelled evolutionary course of the turtle shell.”
“DNA replication in eukaryotes is a highly conserved process marked by the licensing of multiple origins, with pre-replication complex assembly in G1 phase, followed by the onset of replication at these origins in S phase. The two strands replicate by different mechanisms, CFTRinh 172 and DNA synthesis is brought about by the activity of the replicative DNA polymerases Pol delta and Pol epsilon. Proliferating cell nuclear antigen (PCNA) augments the processivity of these polymerases by serving as a DNA sliding clamp protein. This study reports the cloning

of PCNA from the protozoan Leishmania donovani, which is the causative agent of the systemic disease visceral leishmaniasis. PCNA was demonstrated to be robustly expressed in actively proliferating L. donovani promastigotes. We found that the protein was present primarily in the nucleus throughout the cell cycle, and it was found in both proliferating procyclic and metacyclic promastigotes. However, levels of expression of PCNA varied through cell cycle progression, with maximum expression evident in G1 and S phases. The subnuclear pattern of expression of PCNA differed in different stages of the cell cycle; it formed distinct subnuclear foci in S phase, while it was distributed in a more diffuse pattern in G2/M phase and post-mitotic phase cells.