Sputum versus bronchial washings for diagnosis of pulmonary tuberculosis- a prospective study of 53 patients

Background: Tuberculosis is a major global public health problem. It is caused by mycobacterium tuberculosis and it is a leading cause of death in developing countries like India. WHO recommends the detection of acid fast bacilli in sputum as the initial diagnosis of pulmonary TB. Tuberculosis is spread from person to person through air by droplet nuclei. So, early detection and prompt treatment of tuberculosis is main cornerstone to prevent transmission into community. Bronchial washing is very helpful for early detection of mycobacterium tuberculosis.Methods: This is a prospective study of 53 sputum smear negative patients underwent for bronchoscopy. After a detailed medical history and physical examination, Patients with a negative sputum smear AFB examination and a strong clinco-radiological suspicion of pulmonary tuberculosis were then counseled, consented and subjected to fiber-optic bronchoscopy with bronchial washings and bronchial biopsy in case of endobronchial lesions.Results: Our study showed mean age of patient is about 43.49 year and has predominantly male patients. Most cardinal symptoms were fever (83%) and cough (74%). Most radiological findings were consolidation and cavity lesion accordingly. Sputum culture was positive in 14 (26%) patients out of 53 patients and bronchial washing smear positive for AFB in 30 (57%) patients and bronchial washing culture positive for AFB in 40 (75%) patients out of 53 patients.Conclusions: Bronchial washings analysis for detection of AFB is much more reliable in comparison to direct smear microscopy and direct sputum culture examination

An EvoDevo Study of Salmonid Visual Opsin Dynamics and Photopigment Spectral Sensitivity

Salmonids are ideal models as many species follow a distinct developmental program from demersal eggs and a large yolk sac to hatching at an advanced developmental stage. Further, these economically important teleosts inhabit both marine- and freshwaters and experience diverse light environments during their life histories. At a genome level, salmonids have undergone a salmonid-specific fourth whole genome duplication event (Ss4R) compared to other teleosts that are already more genetically diverse compared to many non-teleost vertebrates. Thus, salmonids display phenotypically plastic visual systems that appear to be closely related to their anadromous migration patterns. This is most likely due to a complex interplay between their larger, more gene-rich genomes and broad spectrally enriched habitats; however, the molecular basis and functional consequences for such diversity is not fully understood. This study used advances in genome sequencing to identify the repertoire and genome organization of visual opsin genes (those primarily expressed in retinal photoreceptors) from six different salmonids [Atlantic salmon (Salmo salar), brown trout (Salmo trutta), Chinook salmon (Oncorhynchus tshawytcha), coho salmon (Oncorhynchus kisutch), rainbow trout (Oncorhynchus mykiss), and sockeye salmon (Oncorhynchus nerka)] compared to the northern pike (Esox lucius), a closely related non-salmonid species. Results identified multiple orthologues for all five visual opsin classes, except for presence of a single short-wavelength-sensitive-2 opsin gene. Several visual opsin genes were not retained after the Ss4R duplication event, which is consistent with the concept of salmonid rediploidization. Developmentally, transcriptomic analyzes of Atlantic salmon revealed differential expression within each opsin class, with two of the long-wavelength-sensitive opsins not being expressed before first feeding. Also, early opsin expression in the retina was located centrally, expanding dorsally and ventrally as eye development progressed, with rod opsin being the dominant visual opsin post-hatching. Modeling by spectral tuning analysis and atomistic molecular simulation, predicted the greatest variation in the spectral peak of absorbance to be within the Rh2 class, with a ∼40 nm difference in λmax values between the four medium-wavelength-sensitive photopigments. Overall, it appears that opsin duplication and expression, and their respective spectral tuning profiles, evolved to maximize specialist color vision throughout an anadromous lifecycle, with some visual opsin genes being lost to tailor marine-based vision.publishedVersio

Alleviation of alloxan-induced diabetes and its complications in rats by Actinodaphne hookeri leaf extract

Leaves of Actinodaphne hookeri Meissn (Family Lauraceae; local name: Pisa) has been in use traditionally for the treatment of diabetes and disorders of the urinary tract which are more common in Chattisgarh and eastern part of India. In the present study, leaves of A. hookeri were subjected to phytochemical investigation and evaluated for anti-diabetic activity. The ethanol and the chloroform extract were found to have significant (p<0.01) blood glucose lowering effect. The extracts also significantly (p<0.01) lowered the increased serum cholesterol and low density lipoprotein levels. Preliminary phytochemical investigation revealed the presence of alkaloids, flavonoids, triterpenoids and glycosides as the major constituents in the ethanol extract. The chloroform extract also showed significant (p<0.01) antihyperglycemic activity and contained alkaloids and triterpenes. It is concluded that the antidiabetic activity of A. hookeri may be due to the presence of alkaloids and triterpenes, and might be promising for the development of phytomedicine for diabetes mellitus along with its associated complications

The histone demethylase LSD1 regulates inner ear progenitor differentiation through interactions with Pax2 and the NuRD repressor complex

The histone demethylase LSD1 plays a pivotal role in cellular differentiation, particularly in silencing lineage-specific genes. However, little is known about how LSD1 regulates neurosensory differentiation in the inner ear. Here we show that LSD1 interacts directly with the transcription factor Pax2 to form the NuRD co-repressor complex at the Pax2 target gene loci in a mouse otic neuronal progenitor cell line (VOT-N33). VOT-N33 cells expressing a Pax2-response element reporter were GFP-negative when untreated, but became GFP positive after forced differentiation or treatment with a potent LSD inhibitor. Pharmacological inhibition of LSD1 activity resulted in the enrichment of mono- and di-methylation of H3K4, upregulation of sensory neuronal genes and an increase in the number of sensory neurons in mouse inner ear organoids. Together, these results identify the LSD1/NuRD complex as a previously unrecognized modulator for Pax2-mediated neuronal differentiation in the inner ear

Computational Studies of Ion Channel Blockers and Protein Aggregation

The ion channels are important membrane bound proteins and multi-therapeutic target for a number of diseases. There are many scorpion toxins reported to bind with KV1 channels. We have identified a plant toxin. We have studied binding of two different sequence length peptides, 1-47 and 10-44 with KV1.3 and KV1.1 channels. The binding complex structures are obtained by molecular docking and stability of the complexes are checked by MD simulations. The pore inserting residue is predicted as K33. The KV1.1-toxin complexes are found to be unstable, and toxin doesn't block the pore in MD simulations. The predicted binding free energies for both complexes of KV1.3-toxin are within the range of experimental values with picomolar and nanomolar activities, respectively. Experiments have also confirmed that Toxin(1-47) does not block the current with KV1.1 channel as well. The inward-rectifier potassium (Kir) channels play significant roles in several physiological disorders. I have studied binding of honey bee toxin called tertiapin (TPN) with Kir3.x channels. K21 is predicted to be the pore inserting residue. The binding free energies are calculated and validated with experimental value. I have studied TPN complexes with Kir3.1 and Kir 3.3 and explained insensitivity of TPN to these channels. A few crystal structures of bacterial sodium channels have been determined but the crystal structures of mammalian ones have not been resolved yet. So, it is important to understand similarities and differences between the bacterial and mammalian channels. The validated homology modeled NaV1.4 complexed with GIIIA system provides a good model for such comparisons. Here I have studied the binding of GIIIA to the bacterial sodium channels NaVAb and NaVRh by combination of docking and MD simulations then the potential mean forces are constructed. Comparison of the binding mode of GIIIA between mammalian and bacterial channels. Protein aggregation affects both human physiological functions and bioengineered products so finding methods to prevent aggregation will we very useful. It is an important area of investigation which could be facilitated by a molecular-level understanding of dimer formation, which is the first step in aggregation. Here we propose a computational method based on molecular dynamics simulations that will facilitate finding aggregation-prone regions on human lysozyme HL[D67H], noting that the wild type HL doesn't aggregate

Computational study of aggregation mechanism in human lysozyme[D67H].

Aggregation of proteins is an undesired phenomena that affects both human health and bioengineered products such as therapeutic proteins. Finding preventative measures could be facilitated by a molecular-level understanding of dimer formation, which is the first step in aggregation. Here we present a molecular dynamics (MD) study of dimer formation propensity in human lysozyme and its D67H variant. Because the latter protein aggregates while the former does not, they offer an ideal system for testing the feasibility of the proposed MD approach which comprises three stages: i) partially unfolded conformers involved in dimer formation are generated via high-temperature MD simulations, ii) potential dimer structures are searched using docking and refined with MD, iii) free energy calculations are performed to find the most stable dimer structure. Our results provide a detailed explanation for how a single mutation (D67H) turns human lysozyme from non-aggregating to an aggregating protein. Conversely, the proposed method can be used to identify the residues causing aggregation in a protein, which can be mutated to prevent it

Performance Evaluation of Conventional and Neural Network-Based Decoder for an Audio of Low-Girth LDPC Code

Noise in a communication system degrades the signal level at the receiver, and as a result, the signal is not properly recovered or eliminated at the receiver side. To avoid this, it is necessary to modify the signal before transmission, which is achieved using channel coding. Channel coding provides an opportunity to recover the noisy signal at the receiver side. The low-density parity-check (LDPC) code is an example of a forward error correcting code. It offers near Shannon capacity approaching performance; however, there is a constraint regarding high-girth code design. When the low-girth LDPC code is decoded using conventional methods, an error floor can occur during iterative decoding. To address this issue, a neural network (NN)-based decoder is utilized to overcome the decoding problem associated with low-girth codes. In this work, a neural network-based decoder is developed to decode audio samples of both low- and high-girth LDPC codes. The neural network-based decoder demonstrates superior performance for low-girth codes in terms of bit error rate (BER), peak signal-to-noise-ratio (PSNR), and mean squared error (MSE) with just a single iteration. Audio samples sourced from the NOIZEUS corpus are employed to evaluate the designed neural network. Notably, when compared to a similar decoder, the decoder developed in this study exhibits an improved bit error rate for the same signal-to-noise ratio

Computational Study of Binding of �-Conotoxin GIIIA to Bacterial Sodium Channels Na<inf>V</inf>Ab and Na<inf>V</inf>Rh

© 2016 American Chemical Society. Structures of several voltage-gated sodium (Na V ) channels from bacteria have been determined recently, but the same feat might not be achieved for the mammalian counterparts in the near future. Thus, at present, computational studies of the mammalian Na V channels have to be performed using homology models based on the bacterial crystal structures. A successful homology model for the mammalian Na V 1.4 channel was recently constructed using the extensive mutation data for binding of µ-conotoxin GIIIA to Na V 1.4, which was further validated through studies of binding of other µ-conotoxins and ion permeation. Understanding the similarities and differences between the bacterial and mammalian Na V channels is an important issue, and the Na V 1.4-GIIIA system provides a good opportunity for such a comparison. To this end, we study the binding of GIIIA to the bacterial channels Na V Ab and Na V Rh. The complex structures are obtained using docking and molecular dynamics simulations, and the dissociation of GIIIA is studied through umbrella sampling simulations. The results are compared to those obtained from the Na V 1.4-GIIIA system, and the differences in the binding modes arising from the changes in the selectivity filters are highlighted