Architecture of viral genome-delivery molecular machines.

From the abyss of the ocean to the human gut, bacterial viruses (or bacteriophages) have colonized all ecosystems of the planet earth and evolved in sync with their bacterial hosts. Over 95% of bacteriophages have a tail that varies greatly in length and complexity. The tail complex interrupts the icosahedral capsid symmetry and provides both an entry for viral genome-packaging during replication and an exit for genome-ejection during infection. Here, we review recent progress in deciphering the structure, assembly and conformational dynamics of viral genome-delivery tail machines. We focus on the bacteriophages P22 and T7, two well-studied members of the Podoviridae family that use short, non-contractile tails to infect Gram-negative bacteria. The structure of specialized tail fibers and their putative role in host anchoring, cell-surface penetration and genome-ejection is discussed

Profile of adverse events in plateletpheresis and plasmapheresis donors in a tertiary care hospital of North India

Background: Apheresis procedures are usually well tolerated. Adverse events (AEs) associated with the use of cell separators can be due to delivery of the anticoagulant, vasovagal, allergy, venous access or machines malfunction. Aim was to study the profile of adverse events of plateletpheresis and plasmapheresis donors. Methods: Plateletpheresis and plasmapheresis procedures enrolled for donors during 2017-2018 were done after taking informed and written consent by using Trima Accel and MCS+cell separator. Donor related AEs were categorised according to severity, site and etiology. Non-donor related (NDR) AEs were kit, technique, or equipment related. Results: 2859 procedures were done, 2836 (99.19%) plateletpheresis and 23 (0.8%) plasmapheresis. All 145 (5.07%) AEs were seen in plateletpheresis. Majority of AEs, 130 (4.54%) were DR. 15 (0.52%) were NDR. Commonest DR AEs was citrate related (CR) 76 (2.6%), followed by vasovagal reaction (VVR) in 31 (1.08%) and vascular injury in 23 (0.8%). Majority of the AEs were mild in 124 (4.33%), only 6 (0.20%) were moderate. 107 (3.74%) AEs were (VI) systemic, while 23 (0.80%) were local. In local AEs, hematomas were more common. First time donors had more AEs, 62/1234 (5.02%) as compared to the repeat donors 68/1625 (4.18%). CR AEs were more in repeat donors, 46 (2.8%) as compared to first time donors, 30 (2.43%). VVRs and VIs were more in first time as compared to the repeat donors. NDR AEs were 15 (0.52%). Conclusions: Donor vigilance, trained technical personnel and specialists’ supervision are vital for donor safety hence affecting apheresis donor pool

The Role of Opacities in Stellar Pulsation

We examine the role of opacities in stellar pulsation with reference to Cepheids and RR Lyraes, and examine the effect of augmented opacities on the theoretical pulsation light curves in key temperature ranges. The temperature ranges are provided by recent experimental and theoretical work that have suggested that the iron opacities have been considerably underestimated. For Cepheids, we find that the augmented opacities have noticeable effects in certain period ranges (around $\log P \approx 1$) even though there is a degeneracy with mixing length. We also find significant effects in theoretical models of B-star pulsators.Comment: 6 pages, 3 Figures, Proceeding for the "Workshop on Astrophysical Opacities

Cytosolic Glucosylceramide regulates endolysosomal function in Niemann-Pick type C disease

A new paradigm for Niemann-Pick C disease is presented where lysosomal storage leads to a deficit in cytoplasmic glucosylceramide (GlcCer) where it performs important functions. Previously it had been reported that Gaucher cells have defective endolysosomal pH. GlcCer also accumulates in Niemann-Pick C disease and also shows this defect. Niemann-Pick C cells were found to have reduced cytoplasmic glucosylceramide (GlcCer) transport. Inhibiting cytoplasmic glucocerebrosidase (GBA2), increased GlcCer, decreased endolysosomal pH in normal cells, reversed increases in endolysosomal pH and restored disrupted BODIPY-LacCer trafficking and increased expression of vATPase a subunit in Niemann-Pick C fibroblasts. The results are consistent with a model where both endolysosomal pH and Golgi targeting of BODIPY-LacCer are dependent on adequate levels of cytosolic GlcCer which are reduced in NPC disease. This work consequently suggests GBA2 and vATPase as new therapeutic targets in Niemann-Pick C and related neurodegenerative diseases. The work was in collaboration with colleagues in the Netherlands and Leicester University. The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.Niemann-Pick type C disease (NPCD) is a neurodegenerative disease associated with increases in cellular cholesterol and glycolipids and most commonly caused by defective NPC1, a late endosomal protein. Using ratiometric probes we find that NPCD cells show increased endolysosomal pH. In addition U18666A, an inhibitor of NPC1, was found to increase endolysosomal pH, and the number, size and heterogeneity of endolysosomal vesicles. NPCD fibroblasts and cells treated with U18666A also show disrupted targeting of fluorescent lipid BODIPY-LacCer to high pH vesicles. Inhibiting non-lysosomal glucocerebrosidase (GBA2) reversed increases in endolysosomal pH and restored disrupted BODIPY-LacCer trafficking in NPCD fibroblasts. GBA2 KO cells also show decreased endolysosomal pH. NPCD fibroblasts also show increased expression of a key subunit of the lysosomal proton pump vATPase on GBA2 inhibition. The results are consistent with a model where both endolysosomal pH and Golgi targeting of BODIPY-LacCer are dependent on adequate levels of cytosolic-facing GlcCer, which are reduced in NPC disease

Carrier Transport in Magnesium Diboride: Role of Nano-inclusions

Anisotropic-gap and two-band effects smear out the superconducting transition (Tc) in literature reported thermal conductivity of MgB2, where large electronic contributions also suppress anomaly-manifestation in their negligible phononic-parts. Present thermal transport results on scarcely explored specimens featuring nano-inclusions exhibit a small but clear Tc-signature, traced to relatively appreciable phononic conduction, and its dominant electronic-scattering. The self-formed MgO as extended defects strongly scatter the charge carriers and minutely the phonons with their longer-mean-free-path near Tc. Conversely, near room temperature, the shorter-dominant-wavelength phonon's transport is hugely affected by these nanoparticles, undergoing ballistic to diffusive crossover and eventually entering the Ioffe-Regel mobility threshold regime.Comment: 14 pages, 4 figures, 28 reference

Groundwater Depletion and Role of Direct Seeded Rice in Water Saving: A Move Towards Sustainable Agriculture of Punjab

Presently, out of 20 million tube wells in the country, almost 1.3 million are in Punjab, contributing to fast-paced groundwater extraction and its depletion. Direct seeding of rice has a great potential for optimizing the water-use efficiency in paddy cultivation without any disturbing and harmful effect on its productivity, if weeds are controlled properly. A significant saving of 18 per cent was achieved for irrigating one hectare of the DSR farm in basmati and non-basmati varieties as compared to non-DSR farm. The mean overall technical efficiency was more in DSR farms as compared with non-DSR farms, with difference of about 12 per cent in basmati and 5 per cent in non-basmati fields. However, this difference was 7 per cent in basmati and 14 per cent in non basmati while calculating the average technical efficiency w. r. t water-use. Popularization of this technology among farmers in a participatory mode on a comprehensive scale needs a focused attention through capacity building of farmers

Spatial heterogeneity in the radiogenic activity of the lunar interior: Inferences from CHACE and LLRI on Chandrayaan-1

In the past, clues on the potential radiogenic activity of the lunar interior have been obtained from the isotopic composition of noble gases like Argon. Excess Argon (40) relative to Argon (36), as compared to the solar wind composition, is generally ascribed to the radiogenic activity of the lunar interior. Almost all the previous estimates were based on, 'on-the-spot' measurements from the landing sites. Relative concentration of the isotopes of 40Ar and 36Ar along a meridian by the Chandra's Altitudinal Composition Explorer (CHACE) experiment, on the Moon Impact Probe (MIP) of India's first mission to Moon, has independently yielded clues on the possible spatial heterogeneity in the radiogenic activity of the lunar interior in addition to providing indicative 'antiquity' of the lunar surface along the ground track over the near side of the moon. These results are shown to broadly corroborate the independent topography measurements by the Lunar Laser Ranging Instrument (LLRI) in the main orbiter Chandrayaan-1. The unique combination of these experiments provided high spatial resolution data while indicating the possible close linkages between the lunar interior and the lunar ambience