Activity-regulated E3 ubiquitin ligase TRIM47 modulates excitatory synapse development.

The Ubiquitin Proteasome System (UPS) has been shown to regulate neuronal development and synapse formation. Activity-dependent regulation of E3 ligase, a component of the UPS that targets specific proteins for proteasome-mediated degradation, is emerging as a pivotal player for the establishment of functional synapses. Here, we identified TRIM47 as a developmentally regulated E3 ligase that is expressed in rat hippocampus during the temporal window of synapse formation. We have demonstrated that the expression of TRIM47 is regulated by the glutamate-induced synaptic activity of hippocampal neurons in culture. In addition, the activity-dependent enhancement of TRIM47 expression is recapitulated following the object location test, a hippocampus-dependent spatial memory paradigm. We observed that this enhancement of TRIM47 expression requires NMDA receptor activation. The knockdown of TRIM47 leads to an enhancement of spine density without affecting dendritic complexity. Furthermore, we observed an increase in excitatory synapse development upon loss of TRIM47 function. Comprehensively, our study identified an activity-regulated E3 ligase that drives excitatory synapse formation in hippocampal neurons.

Evaluation of Addition of Sodium Bicarbonate to Dexamethasone and Ropivacaine in Supraclavicular Brachial Plexus Block for Upper Limb Orthopedic Procedures.

BACKGROUND: Peripheral nerve blocks have taken over as the principle technique for upper limb surgeries. A number of adjuvants have been tried individually, but very few studies have investigated the cumulative effect of two or more adjuvants given together along with local anesthetic. AIM: This study aimed to evaluate the effect of addition of sodium bicarbonate to dexamethasone and ropivacaine in supraclavicular brachial plexus block. SETTINGS AND DESIGN: This was a prospective, randomized, double-blind study that comprised 90 American Society of Anaesthesiologist (ASA) 1 and 2 patients posted upper limb orthopedic procedures. MATERIALS AND METHODS: Ninety ASA 1 and 2 patients were selected and divided into three groups of 30 each: Group R received 30 mL of 0.75% ropivacaine plus 4 mL normal saline; Group RD 30 mL of 0.75% ropivacaine, 2 mL normal saline and 2 mL of dexamethasone were given; Group RB 30 mL of 0.75% ropivacaine plus 2 mL of dexamethasone and 2 mL of sodium bicarbonate. Onset and duration of sensory and motor block and postoperative pain scores were studied in each group. STATISTICAL ANALYSIS: Student's independent t-test was employed for comparing the continuous variables and Chi-square test for the categorical variables. Kruskal-Wallis test was used for postoperative pain score data. RESULTS: Addition of sodium bicarbonate to dexamethasone and ropivacaine quickens onset and prolongs duration of sensory and motor block. CONCLUSION: Sodium bicarbonate produces a synergistic and potentiating effect with dexamethasone as adjuvant in supraclavicular brachial plexus block.

Into the weeds: new insights in plant stress.

Weeds, plants that thrive in the face of disturbance, have eluded human's attempts at control for >12 000 years, positioning them as a unique group of extreme stress tolerators. The most successful weeds have a suite of traits that enable them to rapidly adapt to environments typified by stress, growing in hostile conditions or subject to massive destruction from agricultural practices. Through their ability to persist and adapt, weeds illuminate principles of evolution and provide insights into weed management and crop improvement. Here we highlight why the time is right to move beyond traditional model systems and leverage weeds to gain a deeper understanding of the mechanisms, adaptations, and genetic and physiological bases for stress tolerance.

Invasive plants negatively impact native, but not exotic, animals.

Despite our growing understanding of the impacts of invasive plants on ecosystem structure and function, important gaps remain, including whether native and exotic species respond differently to plant invasion. This would elucidate basic ecological interactions and inform management. We performed a meta-analytic review of the effects of invasive plants on native and exotic resident animals. We found that invasive plants reduced the abundance of native, but not exotic, animals. This varied by animal phyla, with invasive plants reducing the abundance of native annelids and chordates, but not mollusks or arthropods. We found dissimilar impacts among "wet" and "dry" ecosystems, but not among animal trophic levels. Additionally, the impact of invasive plants increased over time, but this did not vary with animal nativity. Our review found that no studies considered resident nativity differences, and most did not identify animals to species. We call for more rigorous studies of invaded community impacts across taxa, and most importantly, explicit consideration of resident biogeographic origin. We provide an important first insight into how native and exotic species respond differently to invasion, the consequences of which may facilitate cascading trophic disruptions further exacerbating global change consequences to ecosystem structure and function.

An Alternative Approach for Supportive Supervision and Skill Measurements of Health Workers for Integrated Management of Neonatal and Childhood Illnesses Program in 10 Districts of Haryana.

CONTEXT: "Integrated Management of Neonatal and Childhood Illnesses" (IMNCI) needs regular supportive supervision (SS). AIMS: The aim of this study was to find suitable SS model for implementing IMNCI. SETTINGS AND DESIGN: This was a prospective interventional study in 10 high-focus districts of Haryana. SUBJECTS AND METHODS: Two methods of SS were used: (a) visit to subcenters and home visits (model 1) and (b) organization of IMNCI clinics/camps at primary health center (PHC) and community health center (CHC) (model 2). Skill scores were measured at different time points. Routine IMNCI data from study block and randomly selected control block of each district were retrieved for 4 months before and after the training and supervision. STATISTICAL ANALYSIS USED: Change in percentage mean skill score difference and percentage difference in median number of children were assessed in two areas. RESULTS: Mean skill scores increased significantly from 2.1 (pretest) to 7.0 (posttest 1). Supportive supervisory visits sustained and improved skill scores. While model 2 of SS could positively involve health system officials, model 1 was not well received. Outcome indicator in terms of number of children assessed showed a significant improvement in intervention areas. CONCLUSIONS: SS in IMNCI clinics/camps at PHC/CHC level and innovative skill scoring method is a promising approach.

Blood donor selection and deferral pattern as an important tool for blood safety in a tertiary care hospital.

CONTEXT: Blood donor selection criteria based on science and regulatory rules influence donor as well recipient safety and demographics. AIM: To evaluate and analyze the blood donor deferral pattern and its causes among blood donors in a tertiary care hospital blood bank and to review its influence on blood safety. SETTINGS AND DESIGN: Hospital based blood bank, retrospective analysis. SUBJECTS AND METHODS: The data available as donor deferral record over a period of 13 years from 2001 to 2013 was analyzed. RESULTS: The blood donor deferral rate was 11.5%, the deferral rate in various categories was 4.8%, 4.7%, 1.6%, and 0.3% in Category 1, Category 2, Category 3, and Category 4, respectively. The majority of deferrals were temporary deferrals (62.8%) of young donors. The maximum number of donors deferred (28.2%) due to a history of jaundice (permanent) followed by 19.4% due to low hemoglobin (temporary). History of malaria, intake of medicines, infections, underweight, last blood donation within 3 months (temporary deferral), and history of heart and lung diseases, diabetes, and with suspicious identity (permanent deferral) were other major causes identified. CONCLUSION: The pattern of donor deferral identified is an important tool for blood safety and also provides key areas to focus on a region or policy formulation nationally for donor selection as well ensure donor safety. The value of determining donor deferral pattern by the categories described is in calling back donors deferred due to temporary reasons and can help retain pool of motivated blood donors.

Epidermal Growth Factor Receptor (EGFR) and its Cross-Talks with Topoisomerases: Challenges and Opportunities for Multi-Target Anticancer Drugs.

BACKGROUND: The interactions of Epidermal Growth Factor Receptor (EGFR) and topoisomerases have been seen in various cancer including brain, breast, ovarian, colorectal, gastric, etc. METHODS: The studies in adenocarcinoma patients, chromogenic in situ hybridization, western blotting, receptor binding assay and electromobility shift assays, etc. threw light on the biophysical and biochemical features of EGFR and Topoisomerase cross-talks. RESULTS: It has been revealed that both the isomers of topoisomerase (Topo I and Topo II) interact via different mechanisms with EGFR. Topo II and HER2 share the same location i.e. 17q12-21 regions which could be a possible cause of predominant interactions seen between them. Topo I and EGFR interactions are mechanically related to the nucleolar translocation of heparenase by EGF and c-Jun. CONCLUSION: We compiled literature findings including the mechanistic interventions, signaling pathways, patents, in vitro and in vivo data of tested inhibitors and combinations in clinical trials, which provide convincing confirmations for the interactions of EGFR and topoisomerases. These interactions may be used for deriving a consistent route of mechanism, design and development of standard drug combinations and dual or multi inhibitors.

Efficacy of pine leaves as an alternative bedding material for broiler chicks during summer season.

AIM: The aim was to assess the efficacy of pine leaves as an alternative bedding material on the performance of broiler chicks. MATERIALS AND METHODS: The present study was conducted in summer. Total 120, day old Vencobb straight run chicks were procured, and after 5 days of brooding, chicks were randomly distributed into four treatment groups viz. paddy husk (Group I), paddy straw (Group II), pine leaves (Group III), and combination of paddy straw and pine leaves (Group IV), each having 30 chicks with 3 replicates of 10 chicks each. Chicks were reared under intensive conditions in houses that have a semi-controlled environment, with optimum temperature and adequate ventilation. Food and water were provided as per NRC (1994) requirement. RESULTS: The average body weight after 6 weeks of the experiment was 2018.83±31.11, 1983.80±33.27, 2007.36±35.73, and 1938.43±36.35 g. The bedding type had no significant effect on the carcass characteristics viz. evisceration rate and proportion of cut-up parts of the carcass except giblet yield. The experiment suggested that performance of broiler chicks reared on paddy straw and pine leaves as litter material, had improved body weight and feed conversion ratio as compared to rearing on paddy husk as bedding material. Bacterial count, parasitic load and the N, P, K value of manure of different bedding material shows no significant difference. CONCLUSION: Pine leaves have a potential to be used as an alternative source of litter material to economize poultry production in a sustainable way, so as to make poultry farming as a profitable entrepreneur.