MerR and ChrR mediate blue light induced photo-oxidative stress response at the transcriptional level in Vibrio cholerae

Blue light (BL) is a major environmental factor that affects the physiology, behavior, and infectivity of bacteria as it contributes to the generation of reactive oxygen species (ROS) while increasing photo-oxidative stress in cells. However, precise photo-oxidative response mechanism in non-phototrophic bacteria is yet to be elucidated. In this study, we investigated the effect of BL in Vibrio cholerae by using genetics and transcriptome profiling. Genome-wide analysis revealed that transcription of 6.3% of V. cholerae genes were regulated by BL. We further showed that BL enhances ROS production, which is generated through the oxidative phosphorylation. To understand signaling mechanisms, we generated several knockouts and analyzed their transcriptome under BL exposure. Studies with a double-knockout confirm an anti-sigma factor (ChrR) and putative metalloregulatory-like protein (MerR) are responsible for the genome-wide regulation to BL response in V. cholerae. Collectively, these results demonstrate that MerR-like proteins, in addition to ChrR, are required for V. cholerae to mount an appropriate response against photo-oxidative stress induced by BL. Outside its natural host, V. cholerae can survive for extended periods in natural aquatic environments. Therefore, the regulation of light response for V. cholerae may be a critical cellular process for its survival in these environments

Comparative RNA-seq analysis of the drought-sensitive lentil (Lens culinaris) root and leaf under short- and long-term water deficits

Drought stress is one of the main environmental factors that affects growth and productivity of crop plants, including lentil. To gain insights into the genome-wide transcriptional regulation in lentil root and leaf under short- and long-term drought conditions, we performed RNA-seq on a drought-sensitive lentil cultivar (Lens culinaris Medik. cv. Sultan). After establishing drought conditions, lentil samples were subjected to de novo RNA-seq-based transcriptome analysis. The 207,076 gene transcripts were successfully constructed by de novo assembly from the sequences obtained from root, leaf, and stems. Differentially expressed gene (DEG) analysis on these transcripts indicated that period of drought stress had a greater impact on the transcriptional regulation in lentil root. The numbers of DEGs were 2915 under short-term drought stress while the numbers of DEGs were increased to 18,327 under long-term drought stress condition in the root. Further, Gene Ontology analysis revealed that the following biological processes were differentially regulated in response to long-term drought stress: protein phosphorylation, embryo development seed dormancy, DNA replication, and maintenance of root meristem identity. Additionally, DEGs, which play a role in circadian rhythm and photoreception, were downregulated suggesting that drought stress has a negative effect on the internal oscillators which may have detrimental consequences on plant growth and survival. Collectively, this study provides a detailed comparative transcriptome response of drought-sensitive lentil strain under short- and long-term drought conditions in root and leaf. Our finding suggests that not only the regulation of genes in leaves is important but also genes regulated in roots are important and need to be considered for improving drought tolerance in lentil

Retroperitoneoscopic surgery for stone disease

ESWL has revolutionised the treatment of stone disease. While most urinary stones can be treated with ESWL and endourological techniques, open stone surgery still has a place for a limited number of patients. Retroperitoneoscopic surgery for stone disease is a good alternative to open surgery in selected patients where ESWL and endourological methods fail. Impacted and hard stones which can not be treated with these modalities can be removed by retroperitoneoscopy. Ureterolithotomy and pyelolithotomy can be performed using only 3 ports with the patients in the flank position Nephrectomy for stone disease is also possible with this technique. We believe that retroperitoneoscopic surgery for urinary stone disease has a place in urology in selected patients as an alternative to open surgery

Milp-hyperbox classification for structure-based drug design in the discovery of small molecule inhibitors of SIRTUIN6

Virtual screening of chemical libraries following experimental assays of drug candidates is a common procedure in structure-based drug discovery. However, virtual screening of chemical libraries with millions of compounds requires a lot of time for computing and data analysis. A priori classification of compounds in the libraries as low- and high-binding free energy sets decreases the number of compounds for virtual screening experiments. This classification also reduces the required computational time and resources. Data analysis is demanding since a compound can be described by more than one thousand attributes that make any data analysis very challenging. In this paper, we use the hyperbox classification method in combination with partial least squares regression to determine the most relevant molecular descriptors of the drug molecules for an efficient classification. The effectiveness of the approach is illustrated on a target protein, SIRT6. The results indicate that the proposed approach outperforms other approaches reported in the literature with 83.55% accuracy using six common molecular descriptors (SC-5, SP-6, SHBd, minHaaCH, maxwHBa, FMF). Additionally, the top 10 hit compounds are determined and reported as the candidate inhibitors of SIRT6 for which no inhibitors have so far been reported in the literature

Milp-hyperbox classification for structure-based drug design in the discovery of small molecule inhibitors of SIRTUIN6

Virtual screening of chemical libraries following experimental assays of drug candidates is a common procedure in structure-based drug discovery. However, virtual screening of chemical libraries with millions of compounds requires a lot of time for computing and data analysis. A priori classification of compounds in the libraries as low-and high-binding free energy sets decreases the number of compounds for virtual screening experiments. This classification also reduces the required computational time and resources. Data analysis is demanding since a compound can be described by more than one thousand attributes that make any data analysis very challenging. In this paper, we use the hyperbox classification method in combination with partial least squares regression to determine the most relevant molecular descriptors of the drug molecules for an efficient classification. The effectiveness of the approach is illustrated on a target protein, SIRT6. The results indicate that the proposed approach outperforms other approaches reported in the literature with 83.55% accuracy using six common molecular descriptors (SC-5, SP-6, SHBd, minHaaCH, maxwHBa, FMF). Additionally, the top 10 hit compounds are determined and reported as the candidate inhibitors of SIRT6 for which no inhibitors have so far been reported in the literature

MILP-HYPERBOX CLASSIFICATION FOR STRUCTURE-BASED DRUG DESIGN IN THE DISCOVERY OF SMALL MOLECULE INHIBITORS OF SIRTUIN6

Virtual screening of chemical libraries following experimental assays of drug candidates is a common procedure in structure-based drug discovery. However, virtual screening of chemical libraries with millions of compounds requires a lot of time for computing and data analysis. A priori classification of compounds in the libraries as low-and high-binding free energy sets decreases the number of compounds for virtual screening experiments. This classification also reduces the required computational time and resources. Data analysis is demanding since a compound can be described by more than one thousand attributes that make any data analysis very challenging. In this paper, we use the hyperbox classification method in combination with partial least squares regression to determine the most relevant molecular descriptors of the drug molecules for an efficient classification. The effectiveness of the approach is illustrated on a target protein, SIRT6. The results indicate that the proposed approach outperforms other approaches reported in the literature with 83.55% accuracy using six common molecular descriptors (SC-5, SP-6, SHBd, minHaaCH, maxwHBa, FMF). Additionally, the top 10 hit compounds are determined and reported as the candidate inhibitors of SIRT6 for which no inhibitors have so far been reported in the literature

mRNA and tRNA modification states influence ribosome speed and frame maintenance during poly(lysine) peptide synthesis.

Ribosome speed is dictated by multiple factors including substrate availability, cellular conditions, and product (peptide) formation. Translation slows during the synthesis of cationic peptide sequences, potentially influencing the expression of thousands of proteins. Available evidence suggests that ionic interactions between positively charged nascent peptides and the negatively charged ribosome exit tunnel impede translation. However, this hypothesis was difficult to test directly because of inability to decouple the contributions of amino acid charge from mRNA sequence and tRNA identity/abundance in cells. Furthermore, it is unclear if other components of the translation system central to ribosome function (e.g., RNA modification) influence the speed and accuracy of positively charged peptide synthesis. In this study, we used a fully reconstituted Escherichia coli translation system to evaluate the effects of peptide charge, mRNA sequence, and RNA modification status on the translation of lysine-rich peptides. Comparison of translation reactions on poly(lysine)-encoding mRNAs conducted with either Lys-tRNA(Lys) or Val-tRNA(Lys) reveals that that amino acid charge, while important, only partially accounts for slowed translation on these transcripts. We further find that in addition to peptide charge, mRNA sequence and both tRNA and mRNA modification status influence the rates of amino acid addition and the ribosome’s ability to maintain frame (instead of entering the −2, −1, and +1 frames) during poly(lysine) peptide synthesis. Our observations lead us to expand the model for explaining how the ribosome slows during poly(lysine) peptide synthesis and suggest that posttranscriptional RNA modifications can provide cells a mechanism to precisely control ribosome movements along an mRNA

RNA-seq analysis of the transcriptional response to blue and red light in the extremophilic red alga, Cyanidioschyzon merolae

Light is one of the main environmental cues that affects the physiology and behavior of many organisms. The effect of light on genome-wide transcriptional regulation has been well-studied in green algae and plants, but not in red algae. Cyanidioschyzon merolae is used as a model red algae, and is suitable for studies on transcriptomics because of its compact genome with a relatively small number of genes. In addition, complete genome sequences of the nucleus, mitochondrion, and chloroplast of this organism have been determined. Together, these attributes make C. merolae an ideal model organism to study the response to light stimuli at the transcriptional and the systems biology levels. Previous studies have shown that light significantly affects cell signaling in this organism, but there are no reports on its blue light- and red light-mediated transcriptional responses. We investigated the direct effects of blue and red light at the transcriptional level using RNA-seq. Blue and red lights were found to regulate 35 % of the total genes in C. merolae. Blue light affected the transcription of genes involved in protein synthesis while red light specifically regulated the transcription of genes involved in photosynthesis and DNA repair. Blue or red light regulated genes involved in carbon metabolism and pigment biosynthesis. Overall, our data showed that red and blue light regulate the majority of the cellular, cell division, and repair processes in C. merolae

Retroperitoneal mass presenting as recurrent inguinal hernia: A case report

Introduction: Retroperitoneal masses presenting as an inguinal hernia are rare conditions. Presentation of case: A 53 year old male admitted with the symptoms of weight loss, abdominal discomfort and left sided recurrent inguinal hernia. Physical examination demonstrated an abdominal mass in the left flank and an irreducible, painless scrotal mass. He had a history of left sided inguinal hernia surgery six years ago. Computed tomography revealed a large enhancing left sided retroperitoneal mass invading the colon, pancreas and kidney and it was going down towards the left scrotum. Unblock tumor resection including the neighboring organs (left kidney, left colon, distal pancreas with spleen) was performed. Scrotal extension of the tumor was also excised and the inguinal canal was repaired primarily. Histopathology of the mass was myxoid-liposarcoma. The patient has disease free, without hernia recurrence but poor in renal function after twenty months follow-up. Discussion: Large retroperitoneal tumors may grow towards the inguinal region and they can mimic an inguinal hernia. An irreducible, painless and hard scrotal mass should be considered from this perspective