Biophysical parameters of the Sec14 phospholipid exchange cycle – Effect of lipid packing in membranes

Sec14, a yeast phosphatidylinositol/phosphatidylcholine transfer protein, functions at the trans-Golgi membranes. It lacks domains involved in protein-protein or protein-lipid interactions and consists solely of the Sec14 domain; hence, the mechanism underlying Sec14 function at proper sites remains unclear. In this study, we focused on the lipid packing of membranes and evaluated its association with in vitro Sec14 lipid transfer activity. Phospholipid transfer assays using pyrene-labelled phosphatidylcholine suggested that increased membrane curvature as well as the incorporation of phosphatidylethanolamine accelerated the lipid transfer. The quantity of membrane-bound Sec14 significantly increased in these membranes, indicating that “packing defects” of the membranes promote the membrane binding and phospholipid transfer of Sec14. Increased levels of phospholipid unsaturation promoted Sec14-mediated PC transfer, but had little effect on the membrane binding of the protein. Our results demonstrate the possibility that the location and function of Sec14 are regulated by the lipid packing states produced by a translocase activity at the trans-Golgi network.     

PARTAKE Survey of Public Knowledge and Perceptions of Clinical Research in India

Background

A public that is an informed partner in clinical research is important for ethical, methodological, and operational reasons. There are indications that the public is unaware or misinformed, and not sufficiently engaged in clinical research but studies on the topic are lacking. PARTAKE – Public Awareness of Research for Therapeutic Advancements through Knowledge and Empowerment is a program aimed at increasing public awareness and partnership in clinical research. The PARTAKE Survey is a component of the program.

Objective

To study public knowledge and perceptions of clinical research.

Methods

A 40-item questionnaire combining multiple-choice and open-ended questions was administered to 175 English- or Hindi-speaking individuals in 8 public locations representing various socioeconomic strata in New Delhi, India.

Results

Interviewees were 18–84 old (mean: 39.6, SD±16.6), 23.6% female, 68.6% employed, 7.3% illiterate, 26.3% had heard of research, 2.9% had participated and 58.9% expressed willingness to participate in clinical research. The following perceptions were reported (% true/% false/% not aware): ‘research benefits society’ (94.1%/3.5%/2.3%), ‘the government protects against unethical clinical research’ (56.7%/26.3%/16.9%), ‘research hospitals provide better care’ (67.2%/8.7%/23.9%), ‘confidentiality is adequately protected’ (54.1%/12.3%/33.5%), ‘participation in research is voluntary’ (85.3%/5.8%/8.7%); ‘participants treated like ‘guinea pigs’’ (20.7%/53.2%/26.0%), and ‘compensation for participation is adequate’ (24.7%/12.9%/62.3%).

Conclusions

Results suggest the Indian public is aware of some key features of clinical research (e.g., purpose, value, voluntary nature of participation), and supports clinical research in general but is unaware of other key features (e.g., compensation, confidentiality, protection of human participants) and exhibits some distrust in the conduct and reporting of clinical trials. Larger, cross-cultural surveys are required to inform educational programs addressing these issues.     

Multi-strain Inoculation with PGPR Producing ACC Deaminase is More Effective Than Single-strain Inoculation to Improve Wheat (<i>Triticum aestivum</i>) Growth and Yield

Rhizosphere bacteria that colonize plant roots and confer beneficial effects are referred as plant growth promoting rhizobacteria (PGPR). Among all PGPR, some rhizobacteria have an ability to produce ACC deaminase enzyme. This enzyme catalyzes stress ACC into a-ketobutyrate and ammonia instead of letting it to be converted to ethylene. Ethylene level rises in plants under stress conditions i.e., drought, salinity, poor soil fertility etc. As poor soil fertility is a big hurdle to achieve the optimum yield of crops, inoculation of ACC deaminase PGPR can overcome this problem to some extent. The aim of the current study was to examine the influence of multi-strain and single-strain inoculation of different ACC deaminase producing PGPR on wheat growth and yield. There were three PGPR strains, Enterobacter cloacae, Serratia ficaria and Burkholderia phytofirmans which were used as consortia and single-strain inoculations. The results showed that inoculation of E. cloacae + S. ficaria + B. phytofirmans significantly increased plant height (63%), spike length (61%), number of spikelets spike^-1 (61%), number of grains spike-1 (131%), 1000 grains weight (33%), grains yield (71%), straw yield (71%) and biological yield (68%) of wheat as compared to control. A significant improvement in N (37 and 200%), P (46 and 166%) and K (39 and 61%) of seeds and shoot respectively, validated the efficacious and more effective role of multi-strain (E. cloacae + S. ficaria + B. phytofirmans) inoculation over control. It is obviously concluded that multi-strain ACC deaminase producing PGPR inoculation is a better approach as compared to singlestrain inoculation for the improvement in growth and yield of wheat.     

Taxonomic status and composition of stem bark oil of a variant of Cinnamomum bejolghota (Lauraceae) from Northeast India

Cinnamomum bejolghota var. jarainum , var. nov., is illustrated and described as new. The essential oil composition of stem bark oil of the taxon is also analyzed and reported.     

Comparative study on floristic diversity of protected and unprotected Forests of Sathan Gali,District Mansehra,KP, Pakistan

This first ever study was carried out to explore the floristic composition of protected and unprotected forests of Sathan Gali, District Mansehra, KP, Pakistan. The study area being the part of the Western Himalayas harbours rich floristic diversity. In the current investigation, an effort was made to record primary data about floral diversity of the area. The study area was visited recurrently during 2013 and 2014. Plants were collected from different sampling sites, identified, preserved and deposited in Herbarium of Hazara University, Mansehra. A total of 127 plants species including 59 common and 68 different were found in 13 stands of reserved forest. The different species were only confined with this forest whereas common plant species were distributed in both forests. The dominant family was Asteraceae (13 species, 10.7%) followed by Labiateae (10 species, 7.75%), Poaceae and Rosaceae (8 species, 6.2%) each, Polygonaceae and Pteridaceae by (5 species, 3.87%) each. Angiosperms were represented by 118 (92.91%), plant species, Pteridophytes 5(3.93%) species and Gymnosperms 4 (3.14%) species were recorded in reserved forest. Only single species of climber was documented. The number of herbs, shrubs and trees species recorded were 73.64%, 13.17% and 10.07% respectively. A total of 103 plant species of 55 families including 61 common in both forest types and 42 species different to guzara Forest. These plant species were recorded from 22 sampling stands. Angiosperms by (92.3%) plant species, Gymnosperms (2.88%) and Pteridophytes (4.8%) were recorded. The dominant family was Poaceae by 11 plant species followed by Asteraceae and Rosaceae each represented by 10 species and Pteridaceae by 5 plant species. Habit wise 69.23% were herbs, 14.42% shrubs and 16.34% species of tree were reported. This study will assist ecologists, botanists, taxonomist, conservationists and policy makers to mend, and manage the current vegetation status and sustainability for upcoming generations. The present investigation will also serves as base line for future researches on the Himalaya regions.     

The small GTPases RhoA and Rac1 regulate cerebellar development by controlling cell morphogenesis,migration and foliation

The small GTPases RhoA and Rac1 are key cytoskeletal regulators that function in a mutually antagonistic manner to control the migration and morphogenesis of a broad range of cell types. However, their role in shaping the cerebellum, a unique brain structure composed of an elaborate set of folia separated by fissures of different lengths, remains largely unexplored. Here we show that dysregulation of both RhoA and Rac1 signaling results in abnormal cerebellar ontogenesis. Ablation of RhoA from neuroprogenitor cells drastically alters the timing and placement of fissure formation, the migration and positioning of granule and Purkinje cells, the alignment of Bergmann glia, and the integrity of the basement membrane, primarily in the anterior lobules. Furthermore, in the absence of RhoA, granule cell precursors located at the base of fissures fail to undergo cell shape changes required for fissure initiation. Many of these abnormalities can be recapitulated by deleting RhoA specifically from granule cell precursors but not postnatal glia, indicating that RhoA functions in granule cell precursors to control cerebellar morphogenesis. Notably, mice with elevated Rac1 activity due to loss of the Rac1 inhibitors Bcr and Abr show similar anterior cerebellar deficits, including ectopic neurons and defects in fissure formation, Bergmann glia organization and basement membrane integrity. Together, our results suggest that RhoA and Rac1 play indispensable roles in patterning cerebellar morphology.     

Synthesis,estrogen receptor binding affinity and molecular docking of pyrimidine-piperazine-chromene and -quinoline conjugates

Substituted 2-amino-7-((6-(4-(2-hydroxyethyl) piperazin-1-yl)-2-methylpyrimidin-4-yl)oxy)-4-phenyl-4H-chromene-3-carbonitriles and 2-amino-7-((6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-yl)oxy)-4-phenyl-1,4-dihydroquinoline-3-carbonitriles were synthesized via an efficient multi-component one pot synthesis under mild conditions. These compounds 1–20 were evaluated against human breast cancer cell lines (MCF-7) and human embryonic kidney cells (HEK293) for cytotoxic activities. Among them, compounds 6, 7, 15, 17 and 19 showed better anti-proliferative activities as (IC₅₀ value 48 ± 1.70, 65 ± 1.13, 92 ± 1.18, 30 ± 1.17 and 16 ± 1.10 µM) than curcumin drug (48 ± 1.11 µM). Molecular docking was also performed with active compounds 6, 7 and 15 against Bcl-2 protein which gave good binding affinity (ΔG = ?9.08, ?8.29 and ?7.70 kcal/mol) respectively. Furthermore, the structure-activity relationship (SAR) analysis revealed that the chromene and quinoline moieties, when attached with pyrimide and piperazine moieties, enhanced anti-proliferative activities.