Alternative conformations of the archaeal Nop56/58-fibrillarin complex imply flexibility in box C/D RNPs

The Nop56/58-fibrillarin heterocomplex is a core protein complex of the box C/D ribonucleoprotein particles that modify and process ribosomal RNAs. The previous crystal structure of the Archaeoglobus fulgidus complex revealed a symmetric dimer of two Nop56/58-fibrillarin complexes linked by the coiled-coil domains of the Nop56/68 proteins. However, because the A. fulgidus Nop56/58 protein lacks some domains found in most other species, it was thought that the bipartite architecture of the heterocomplex was not likely a general phenomenon. Here we report the crystal structure of the Nop56/58-fibrillarin complex bound with methylation cofactor, S-adenosyl-L-methionine from Pyrococcus furiosus, at 2.7 A. The new complex confirms the generality of the previously observed bipartite arrangement. In addition however, the conformation of Nop56/58 in the new structure differs substantially from that in the earlier structure. The distinct conformations of Nop56/58 suggest potential flexibility in Nop56/58. Computational normal mode analysis supports this view. Importantly, fibrillarin is repositioned within the two complexes. We propose that hinge motion within Nop56/58 has important implications for the possibility of simultaneously positioning two catalytic sites at the two target sites of a bipartite box C/D guide RNA.     

Slow loris (Nycticebus borneanus) consumption by a wild Bornean orangutan (Pongo pygmaeus wurmbii)

Primates - Vertebrate predation and consumption by wild Bornean orangutans (Pongo pygmaeus spp.) is rare. In contrast to recorded observations of slow loris consumption by Sumatran orangutans...     

Elaphomyces tropicalis sp. nov.: A new ectomycorrhizal fungus associated with dipterocarps from tropical Indonesia

A hypogeous, sequestrate, ectomycorrhizal fungus belonging to Elaphomyces was found in a Shorea plantation at Haurbentes Research Forest, West Java, Indonesia. Elaphomyces tropicalis is described as a new species based on morphological characters and molecular phylogenetic analysis of the ITS rDNA sequence. Sequences of E. tropicalis formed a distinct clade close to E. hassiacus, and sister to E. granulatus and E. asperulus. Elaphomyces tropicalis is not closely related to the E. papillatus clade. Morphologically, E. tropicalis is similar to E. (subsect Papillati) papillatus var. striatosporus with its crested spore ornamentation, but differs by having larger ascomata and different associated hosts. Shorea selanica and S. leprosula are the presumed hosts of E. tropicalis. This is the first report of an Elaphomyces species with Shorea species thus widening the previously known Elaphomyces host range.     

Species-specificity of oospore dimensions in three ecorticate species of Chara (Charales,Charophyceae)

Dimensions of oospores such as length, width, fossa-breadth, length-to-width ratio and number of striae were considered for morphological identification of the members of Charales. Oospores were collected from natural stands of three species, viz. Chara braunii, C. corallina and C. wallichii in ponds in West Bengal (India). Oospore dimensions (length, width and fossa-breadth) correlated well: though the fossa breadth–length relation of C. braunii showed lower correlation coefficient (r² = 0.076, p < 0.001), all other five breadth or width–length relationships showed r² ≥ 0.23, p < 0.001. These bivariate patterns were significantly different among the species (one-way ANCOVA of length–width ratio to fossa-breadth: adjusted means and slopes both p < 0.001), C. braunii and C. corallina has similar length to width ratios, C. wallichii and C. corallina were similar in width, whereas the species differed in breadth and length in the order C. braunii, C. wallichii, and C. corallina.     

Extremely divergent host plant acceptance with gene flow between sympatric host races of the phytophagous ladybird beetle Henosepilachna diekei

Ecological divergence alone can prevent the majority of gene flow in the absence of other forms of reproductive isolation. Although the importance of ecological divergence in promoting reproductive isolation has been broadly recognized, its net impact on speciation has rarely been estimated in the wild. The phytophagous ladybird beetle Henosepilachna diekei Jadwiszczak & Wegrzynowicz includes two sympatric host races that are reproductively isolated solely by extreme specialization to either of the host plants Mikania micrantha Kunth (Asteraceae) or Leucas lavandulifolia Sm. (Lamiaceae) in West Java, Indonesia. To investigate the impact of differential host use as an isolating barrier, we carried out adult host acceptance tests and molecular population genetic analyses based on mitochondrial ND2 and nucleic ITS2 gene sequences using 13 wild populations of the host races, including four sympatric population pairs. Almost all individuals of these host races persistently accepted only the original host plant. We detected restricted but a degree of gene flow between these host races. A migration event occurred only in very recent time compared to their divergence time, indicating recent secondary contact of these host races in the surveyed area. These results reveal the remarkably large impact of host‐plant shift over almost the entire process of speciation and illustrate that ecological divergence has been maintained even under the presence of a certain degree of gene flow.     

Molecular process of glucose uptake and glycogen storage due to hamamelitannin via insulin signalling cascade in glucose metabolism

Molecular Biology Reports - Understanding the mechanism by which the exogenous biomolecule modulates the GLUT-4 signalling cascade along with the information on glucose metabolism is essential for...     

Life‐cycle and cost of goods assessment of fed‐batch and perfusion‐based manufacturing processes for mAbs

Life‐cycle assessment (LCA) is an environmental assessment tool that quantifies the environmental impact associated with a product or a process (e.g., water consumption, energy requirements, and solid waste generation). While LCA is a standard approach in many commercial industries, its application has not been exploited widely in the bioprocessing sector. To contribute toward the design of more cost‐efficient, robust and environmentally‐friendly manufacturing process for monoclonal antibodies (mAbs), a framework consisting of an LCA and economic analysis combined with a sensitivity analysis of manufacturing process parameters and a production scale‐up study is presented. The efficiency of the framework is demonstrated using a comparative study of the two most commonly used upstream configurations for mAb manufacture, namely fed‐batch (FB) and perfusion‐based processes. Results obtained by the framework are presented using a range of visualization tools, and indicate that a standard perfusion process (with a pooling duration of 4 days) has similar cost of goods than a FB process but a larger environmental footprint because it consumed 35% more water, demanded 17% more energy, and emitted 17% more CO₂ than the FB process. Water consumption was the most important impact category, especially when scaling‐up the processes, as energy was required to produce process water and water‐for‐injection, while CO₂ was emitted from energy generation. The sensitivity analysis revealed that the perfusion process can be made more environmentally‐friendly than the FB process if the pooling duration is extended to 8 days. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1324–1335, 2016     

Application of Microneedle Arrays for Enhancement of Transdermal Permeation of Insulin: <Emphasis Type="Italic">In Vitro</Emphasis> Experiments,Scaling Analyses and Numerical Simulations

The aim of this investigation is to study the effect of donor concentration and microneedle (MN) length on permeation of insulin and further evaluating the data using scaling analyses and numerical simulations. Histological evaluation of skin sections was carried to evaluate the skin disruption and depth of penetration by MNs. Scaling analyses were done using dimensionless parameters like concentration of drug (C _t/C _s), thickness (h/L) and surface area of the skin (S _a/L ²). Simulation studies were carried out using MATLAB and COMSOL software to simulate the insulin permeation using histological sections of MN-treated skin and experimental parameters like passive diffusion coefficient. A 1.6-fold increase in transdermal flux and 1.9-fold decrease in lag time values were observed with 1.5 mm MN when compared with passive studies. Good correlation (R ²?>?0.99) was observed between different parameters using scaling analyses. Also, the in vitro and simulated permeations profiles were found to be similar (f ₂?≥?50). Insulin permeation significantly increased with increase in donor concentration and MN length (p?<?0.05). The developed scaling correlations and numerical simulations were found to be accurate and would help researchers to predict the permeation of insulin with new dimensions of MN in optimizing insulin delivery. Overall, it can be inferred that the application of MNs can significantly enhance insulin permeation and may be an efficient alternative for injectable insulin therapy in humans.