Monovalent ions modulate the flux through multiple folding pathways of an RNA pseudoknot

The functions of RNA pseudoknots (PKs), which are minimal tertiary structural motifs and an integral part of several ribozymes and ribonucleoprotein complexes, are determined by their structure, stability and dynamics. Therefore, it is important to elucidate the general principles governing their thermodynamics/folding mechanisms. Here, we combine experiments and simulations to examine the folding/unfolding pathways of the VPK pseudoknot, a variant of the Mouse Mammary Tumor Virus (MMTV) PK involved in ribosomal frameshifting. Fluorescent nucleotide analogs (2-aminopurine and pyrrolocytidine) placed at different stem/loop positions in the PK, and laser temperature-jump approaches serve as local probes allowing us to monitor the order of assembly of VPK with two helices with different intrinsic stabilities. The experiments and molecular simulations show that at 50 mM KCl the dominant folding pathway populates only the more stable partially folded hairpin. As the salt concentration is increased a parallel folding pathway emerges, involving the less stable hairpin structure as an alternate intermediate. Notably, the flux between the pathways is modulated by the ionic strength. The findings support the principle that the order of PK structure formation is determined by the relative stabilities of the hairpins, which can be altered by sequence variations or salt concentrations. Our study not only unambiguously demonstrates that PK folds by parallel pathways, but also establishes that quantitative description of RNA self-assembly requires a synergistic combination of experiments and simulations.Comment: Supporting Information include

Role of Lateral Anal Sphincterotomy Versus Maximal Anal Dilatation in Reducing Post Operative Pain after Open Hemorrhoidectomy: A Comparative study

INTRODUCTION: Haemorrhoids are one of the most frequent anorectal disorders to affect humans. They are the most common cause of bleeding per rectum and cause considerable pain and suffering. Numerous features have been appealed to be the aetiologies of haemorrhoidal progress and enlargement, which includes constipation and sustained straining while defecation. Lateral Anal Sphincterotomy (LAS) after a Milligan Morgan Haemorrhoidectomy significantly reduces pain in the first post-operative period. High anal pressures are common in patients with haemorrhoids suggesting that they may have a pathogenic role. Internal Sphincterotomy avoids pain, urinary retention and stenosis and is safe. Maximal Anal Dilatation (MAD) is based on careful but firm dilatation of the anal canal in order to reduce the anal canal pressure for management of Fissure in ano. This study was conducted to compare the post-operative pain in two groups of patients treated with Lateral Anal Sphincterotomy and Maximal Anal Dilatation following a Milligan Morgan Haemorrhoidectomy. AIMS AND OBJECTIVES: To assess and compare the outcomes of the postoperative pain in Lateral anal sphincterotomy against Maximal Anal Dilatation following a Milligan-Morgan Haemorrhoidectomy in terms of Postoperative pain. METHODS: 50 patients with a diagnosis of grade 2, 3 or 4 hemorrhoids were taken into the study. Each patient was randomly allotted into one of 2 groups: a) Group A: Patients subjected to Lateral anal sphincterotomy b) Group B: Patients subjected to Maximal anal dilatation All patients underwent Milligan Morgan hemorrhoidectomy followed by either Lateral Anal sphincterotomy or Maximal anal dilatation based on the group allotted. All patients received antibiotics in the form of Inj. Cipro 500mg TDS and Inj. Metrogyl 500mg TDS with first dose given at time of anesthesia. All patients were advised SITZ BATH following removal of anal pack post operatively. Post operative pain, pain during the first postoperative bowel motion, early postoperative complications, (urinary retention/reactionary bleeding/flatus or faeces incontinence) and duration of hospital stay were evaluated. Severity of post-operative pain was assessed according to the frequency of administration of analgesic, needed to control the pain for a patient and using visual analog scale as given below. Objective Pain level was categorised as ‘Mild’ (1 point) if required analgesics were 02/48hours to control the pain, ‘Moderate’(2 points) if numbers were 3-4/48hours and ‘Severe’ (3 points) when analgesics were >4 in numbers. Subjective pain score will be assessed on the 2ndpost operative day using Wong Baker’s Faces pain rating scale. A combined total score is calculated by adding up objective and subjective pain scores. On the 7th postoperative day a careful digital-rectal examination (DRE) was done in all the patients to assess the anal tone and anal stenosis if present. RESULTS: Out of 50 patients, 25 (50%) of them were manages using Lateral Anal Sphincterotomy and 25 of them (50%) were managed using Maximal Anal Dilatation. • Among 50 patients, 33 (66%) of them had normal sphincter tone on day 7 while 8 (16%) of them had low sphincter tone and 9 (n=18%) of them had high sphincter tone. • One-way ANOVA showed that pain management was better using Lateral Anal Sphincterotomy and varies from the group that had maximum anal dilatation. ANOVA was significant with F=60.293 and p-value very highly significant. CONCLUSION: With the above factors and the study results it is safe to conclude that Lateral Anal Sphincterotomy is far better than Maximal Anal Dilatation as an adjunct to Open hemorrhoidectomy to overcome the post operative pain severity

Current distribution of the invasive earthworm Pontoscolex corethrurus (Müller, 1857) after a century of its first report from Kerala state, India

Pontoscolex corethrurus (Müller, 1857) is an important peregrine earthworm species in the humid tropics and is found in land disturbed by human activities. Its presence in Kerala state was first reported by Michaelsen in 1910. So far the occurrence of 14 exotic earthworm species has been reported from Kerala state. However present distribution status of any of these exotic species is not yet thoroughly studied. Now P. corethrurus is naturalized in forests, degraded areas, and agroecosystems from the higher altitude areas to the coastal zones. Here, the current distribution pattern of P. corethrurus in the state after a period of 100 years is highlighted

A new species of Moniligaster Perrier, 1872 (Annelida, Moniligastridae) from India, with status revision of M. deshayesi minor Michaelsen, 1913

The genus Moniligaster Perrier, 1872 is restricted to the Western Ghats mountain regions of the southern Peninsular India. A new species, Moniligaster julkai Narayanan & Paliwal, sp. nov., is described and illustrated using samples found in the Kerala districts of Kottayam and Pathanamthitta. Apart from that, the status of Moniligaster deshayesi minor Michaelsen, 1913 is critically reviewed, and it is upgraded to species rank as Moniligaster minor Michaelsen, 1913, based on a collection made near its type locality. Furthermore, new distributional records for other Moniligaster species are provided. With this discovery, the genus Moniligaster now has a total of 14 recognised species

First record of the exotic earthworm Metaphire bahli (Gates, 1945) (Oligochaeta: Megascolecidae) from India

The occurrence of the exotic earthworm species Metaphire bahli (Gates, 1945) of the family Megascolecidae is recorded for the first time from India. Specimens were collected from the Alappuzha District of Kerala State. Its detailed description along with geographical distribution is provided

Earthworm (Clitellata, Megadrili) fauna of Kuttanad wetland, southern part of Vembanad-Kol Ramsar site, India

The earthworm fauna of the wetlands of India is highly undocumented. We have carried out a survey of earthworms in the Kuttanad wetland, an integral part of the Vembanad-Kol Ramsar Site, India’s largest wetland of international importance. Current investigation has documented 17 species belonging to 7 families. Megascolex travancorensis pentagonalis Stephenson, 1916 and Glyphidrilus fluviatilis Rao, 1922 were reported for the first time since their original descriptions. Based on the current study, M. t. pentagonalis is raised to species rank as M. pentagonalis from the subspecies status. G. fluviatilis and Lennogaster chittagongensis (Stephenson, 1917) are new records for the state of Kerala. Present results provide a more complete picture of the earthworm fauna of Kuttanad wetland

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

IMPACT OF BUFFER SIZE ON PQRS AND D-PQRS SCHEDULING ALGORITHMS

Most of the internet applications required high speed internet connectivity. Crosspoint Buffered Switches are widely used switching architectures and designing a scheduling algorithm is a major challenge. PQRS and D-PQRS are the two most successful schedulers used in Crosspoint Buffered Switches under unicast traffic. In this paper, we analysed the performance of PQRS and DPQRS algorithms by varying the crosspoint buffer size. Simulation result shows the delay performance of the switch increases if the size of the buffer increases

New species and new records of earthworms of the genus Drawida from Kerala part of the Western Ghats biodiversity hotspot, India (Oligochaeta, Moniligastridae)

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