HISTOPATHOLOGIAL ALTERATIONS IN BABESIA GIBSONI INFECTIONA CASE REPORT

An eight-year-old male Labrador with high fever was brought for treatment in the Veterinary Clinical Complex, Faculty of Veterinary and Animal Sciences, WBUAFS, Kolkata. Babesia gibsoni was identified in microscopical examination of the blood smear taken from the animal. The dog could not survive despite treatment and the post mortem examination revealed remarkable changes in the liver, lungs, kidneys and spleen. Histopathological examination showed congestion and edema in lungs, liver and spleen along with remarkable necrotic and degenerative changes in the tubular epithelial cell of kidneys

Search for gravitational-lensing signatures in the full third observing run of the LIGO-Virgo network

Gravitational lensing by massive objects along the line of sight to the source causes distortions of gravitational wave-signals; such distortions may reveal information about fundamental physics, cosmology and astrophysics. In this work, we have extended the search for lensing signatures to all binary black hole events from the third observing run of the LIGO--Virgo network. We search for repeated signals from strong lensing by 1) performing targeted searches for subthreshold signals, 2) calculating the degree of overlap amongst the intrinsic parameters and sky location of pairs of signals, 3) comparing the similarities of the spectrograms amongst pairs of signals, and 4) performing dual-signal Bayesian analysis that takes into account selection effects and astrophysical knowledge. We also search for distortions to the gravitational waveform caused by 1) frequency-independent phase shifts in strongly lensed images, and 2) frequency-dependent modulation of the amplitude and phase due to point masses. None of these searches yields significant evidence for lensing. Finally, we use the non-detection of gravitational-wave lensing to constrain the lensing rate based on the latest merger-rate estimates and the fraction of dark matter composed of compact objects

Search for eccentric black hole coalescences during the third observing run of LIGO and Virgo

Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass M>70 M⊙) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities 0<e≤0.3 at 0.33 Gpc−3 yr−1 at 90\% confidence level

Ultralight vector dark matter search using data from the KAGRA O3GK run

Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM

Impact of P-Site tRNA and antibiotics on ribosome mediated protein folding: studies using the Escherichia coli ribosome.

BACKGROUND: The ribosome, which acts as a platform for mRNA encoded polypeptide synthesis, is also capable of assisting in folding of polypeptide chains. The peptidyl transferase center (PTC) that catalyzes peptide bond formation resides in the domain V of the 23S rRNA of the bacterial ribosome. Proper positioning of the 3' -CCA ends of the A- and P-site tRNAs via specific interactions with the nucleotides of the PTC are crucial for peptidyl transferase activity. This RNA domain is also the center for ribosomal chaperoning activity. The unfolded polypeptide chains interact with the specific nucleotides of the PTC and are released in a folding competent form. In vitro transcribed RNA corresponding to this domain (bDV RNA) also displays chaperoning activity. RESULTS: The present study explores the effects of tRNAs, antibiotics that are A- and P-site PTC substrate analogs (puromycin and blasticidin) and macrolide antibiotics (erythromycin and josamycin) on the chaperoning ability of the E. coli ribosome and bDV RNA. Our studies using mRNA programmed ribosomes show that a tRNA positioned at the P-site effectively inhibits the ribosome's chaperoning function. We also show that the antibiotic blasticidin (that mimics the interaction between 3'-CCA end of P/P-site tRNA with the PTC) is more effective in inhibiting ribosome and bDV RNA chaperoning ability than either puromycin or the macrolide antibiotics. Mutational studies of the bDV RNA could identify the nucleotides U2585 and G2252 (both of which interact with P-site tRNA) to be important for its chaperoning ability. CONCLUSION: Both protein synthesis and their proper folding are crucial for maintenance of a functional cellular proteome. The PTC of the ribosome is attributed with both these abilities. The silencing of the chaperoning ability of the ribosome in the presence of P-site bound tRNA might be a way to segregate these two important functions

Effects of antibiotics on ribosome and domain V RNA assisted BCAII reactivation.

<p>(<b>A</b>) Dose dependent inhibition of ribosome's chaperoning ability due to binding antibiotics blasticidin and puromycin. <i>E. coli</i> ribosome was allowed to bind to increasing concentrations of the antibiotics in their respective buffers (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0101293#pone.0101293.s003" target="_blank">Table S1</a>). Reactivation of BCAII by ribosome-antibiotic complexes with antibiotics blasticidin (▪) and puromycin (•) are plotted against the log [antibiotics] (as indicated in x-axis of <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0101293#pone-0101293-g003" target="_blank">Fig. 3A</a>). The refolding experiments were repeated at least 3 times and the average values were plotted. The graph was fitted by Boltzmann fit. (<b>B</b>) Dose dependent inhibition of ribosome's chaperoning ability due to binding of macrolide antibiotics. The ribosome was allowed to bind to erythromycin or josamycin in their respective buffers (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0101293#pone.0101293.s003" target="_blank">Table S1</a>). Reactivation of BCAII by ribosome-antibiotic complexes with antibiotics erythromycin (▪) and josamycin (•) bound ribosome were plotted against the log [antibiotics] (as indicated in x-axis of <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0101293#pone-0101293-g003" target="_blank">Fig. 3B</a>).The refolding experiments were repeated at least 3 times and the average values were plotted. The graph was fitted by Boltzmann distribution fit. (<b>C</b>) A comparison of BCAII reactivation in presence of bDV RNA and bDV RNA complexed with total <i>E. coli</i> tRNA (15 µM), blasticidin (BLS; 3 mM), puromycin (PURO; 6 mM), erythromycin (ERY; 1.5 mM) and josamycin (JOSA; 2 mM) are shown in the bar diagram.</p

The Ribosome Can Prevent Aggregation of Partially Folded Protein Intermediates: Studies Using the <i>Escherichia coli</i> Ribosome

<div><p>Background</p><p>Molecular chaperones that support de novo folding of proteins under non stress condition are classified as chaperone ‘foldases’ that are distinct from chaperone’ holdases’ that provide high affinity binding platform for unfolded proteins and prevent their aggregation specifically under stress conditions. Ribosome, the cellular protein synthesis machine can act as a foldase chaperone that can bind unfolded proteins and release them in folding competent state. The peptidyl transferase center (PTC) located in the domain V of the 23S rRNA of <i>Escherichia coli</i> ribosome (bDV RNA) is the chaperoning center of the ribosome. It has been proposed that via specific interactions between the RNA and refolding proteins, the chaperone provides information for the correct folding of unfolded polypeptide chains.</p><p>Results</p><p>We demonstrate using <i>Escherichia coli</i> ribosome and variants of its domain V RNA that the ribosome can bind to partially folded intermediates of bovine carbonic anhydrase II (BCAII) and lysozyme and suppress aggregation during their refolding. Using mutants of domain V RNA we demonstrate that the time for which the chaperone retains the bound protein is an important factor in determining its ability to suppress aggregation and/or support reactivation of protein.</p><p>Conclusion</p><p>The ribosome can behave like a ‘holdase’ chaperone and has the ability to bind and hold back partially folded intermediate states of proteins from participating in the aggregation process. Since the ribosome is an essential organelle that is present in large numbers in all living cells, this ability of the ribosome provides an energetically inexpensive way to suppress cellular aggregation. Further, this ability of the ribosome might also be crucial in the context that the ribosome is one of the first chaperones to be encountered by a large nascent polypeptide chains that have a tendency to form partially folded intermediates immediately following their synthesis.</p></div

Effects of tRNA on chaperoning ability of non-programmed ribosome.

<p>(<b>A</b>) Dose dependent inhibition of ribosome's chaperoning ability due to binding of total <i>E. coli</i> tRNA. <i>E. coli</i> ribosome was allowed to bind to increasing concentrations of total <i>E. coli</i> tRNA in Buffer-P (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0101293#pone.0101293.s003" target="_blank">Table S1</a>). Reactivation of BCAII by the ribosome-tRNA complex was plotted (▪) against increasing total <i>E. coli</i> tRNA (▪) concentrations. The refolding experiments were repeated at least 3 times and the average values were plotted. The graph was fitted by Boltzmann fit. (<b>B</b>) Percent (%) reactivation of BCAII in presence of total <i>E. coli</i> tRNA and Met-tRNA bound to 70S ribosome in Buffer-A and Buffer-P (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0101293#pone.0101293.s003" target="_blank">Table S1</a>) are represented. (<b>C</b>) Effects of tetracycline on tRNA bound ribosome assisted refolding; Bar diagram represents a comparison of the BCAII reactivation (%) of; Self (1), 70S ribosome (2), 70S ribosome + tetracycline (3) 70S ribosome +5 µM total <i>E. coli</i> tRNA (4), 70S ribosome + tetracycline +5 µM total <i>E. coli</i> tRNA (5), 70S ribosome +5 µM deacylated Met-tRNA (6) and 70S ribosome + tetracycline +5 µM deacylated Met-tRNA (7). BCAII reactivation in absence of chaperone is marked as ‘Self’ in the figure.</p