Autonomously Assembled Synthetic Transmembrane Peptide Pore.

The porinACj is an α-helical porin that spans the mycolic acid outer membrane of Gram-positive mycolate, Corynebacterium jeikeium. Here, we report that a 40-amino acid, synthetic peptide, pPorA corresponding to porin PorACj, inserts into the lipid bilayers and forms well-defined pores. By electrical recordings, we measured the single-channel properties that revealed the autonomous assembly of large conductance ion-selective synthetic pores. Further, we characterized the functional properties by blocking the peptide pores by cyclodextrins of different charge and symmetry. We deduced the subunit stoichiometry and putative structure of the pore by site-specific chemical modification in single-channel electrical recordings and gel electrophoresis. On the basis of these findings, we suggest that this is a large functional uniform transmembrane pore built entirely from short synthetic α-helical peptides. Accordingly, we propose a model demonstrating structural assembly of large α-helix-based peptide pores for understanding the action of antimicrobial peptides and for the design of pores with applications in biotechnology.

Impact of COVID-19 on heart failure hospitalization and outcome in India - A cardiological society of India study (CSI-HF in COVID 19 times study - "The COVID C-HF study").

OBJECTIVES: The presentation and outcomes of acute decompensated heart failure (ADHF) during COVID times (June 2020 to Dec 2020) were compared with the historical control during the same period in 2019. METHODS: Data of 4806 consecutive patients of acute HF admitted in 22 centres in the country were collected during this period. The admission patterns, aetiology, outcomes, prescription of guideline-directed medical therapy (GDMT) and interventions were analysed in this retrospective study. RESULTS: Admissions for acute heart failure during the pandemic period in 2020 decreased by 20% compared to the corresponding six-month period in 2019, with numbers dropping from 2675 to 2131. However, no difference in the epidemiology was seen. The mean age of presentation in 2019 was 61.75 (±13.7) years, and 59.97 (±14.6) years in 2020. There was a significant decrease in the mean age of presentation (p = 0.001). Also. the proportion of male patients decreased significantly from 68.67% to 65.84% (p = 0.037). The in-hospital mortality for acute heart failure did not differ significantly between 2019 and 2020 (4.19% and 4.,97%) respectively (p = 0.19). The proportion of patients with HFrEF did not change in 2020 compared to 2019 (76.82% vs 75.74%, respectively). The average duration of hospital stay was 6.5 days. CONCLUSION: The outcomes of ADHF patients admitted during the Covid pandemic did not differ significantly. The length of hospital stay remained the same. The study highlighted the sub-optimal use of GDMT, though slightly improving over the last few years.

Role of effective crisis communication by the government in managing the first wave Covid-19 pandemic - A study of Kerala government's success.

Effective crisis communication is critical for successful crisis management. The current study is an attempt to unravel the public communication efforts of the Kerala government in its successful Covid-19 crisis management efforts during the first wave of the pandemic. The findings of the study indicate that the government has successfully used pre-crisis communication to inoculate the stakeholders, 'steal thunder', and bolster their crisis management capabilities. Effective crisis communication, by the government, has ensured proper information management, media management, right supportive action, and direct communication with stakeholders. Effective communication has also helped the government in garnering favourable constituent attribution, positive framing, positive affect in stakeholder, and enlist active stakeholder participation in crisis management; resulting in, effective crisis management and enhanced reputation for the government. The study unravels the best practices of the Kerala government, in public crisis communication, during the pre-crisis and crisis stages of the first wave of the pandemic and proposes a Kerala model of crisis communication. The model can be used as a reference for future government communication efforts during a crisis across geographies.

Terahertz spectroscopic evidence of electron correlations in SrVO3epitaxial thin films.

Electron correlation in transition metal oxides (TMOs) is an intriguing topic in condensed matter physics, revealing a wide variety of exotic physical properties. Investigating low-energy carrier dynamics by terahertz (THz) spectroscopy is an efficient route to obtain the essential insights into electron correlation. In the present study, THz-time-domain spectroscopy is employed to probe electron correlation in SrVO3epitaxial thin films. The low energy carrier dynamics of SrVO3in the range of 0.2-6.0 meV shows a typical metallic behavior as overserved in dc transport measurements. The obtained temperature-dependent optical parameters provide evidence of mass renormalization in the low energy regime and carrier momentum relaxation happens via the electron-electron scattering mechanism. Overall, the frequency and temperature-dependent optical parameters indicate the Fermi liquid ground state in a Mott-Hubbard type correlated metal SrVO3thin film. Our results provide significant insight on low energy carrier dynamics in the correlated electron system, particularly perovskite-basedd1TMOs.

Reliability of Modified Hertels Exophthalmometer as an Intraoperative Tool for Assessment of Relative Globe Position in Orbital/Zygomatic Fracture.

INTRODUCTION: Axial globe position assessment is commonly carried out with Hertels Exophthalmometer. Hertels requires an intact lateral orbital rim for its placement, which is often fractured in zygomatic fractures. Hence, to overcome this problem, we have modified the instrument for its application in zygomatic/orbital fractures. Reliability of this Modified Hertels Exopthalmometer has been already validated in normal healthy patients. Therefore, the aim of this study is to assess the efficacy of the Modified Hertels Exophthalmometer in pateints with zygomatic/orbital fracture. MATERIALS AND METHODS: This is a prospective study carried out between April 2015 and October 2017, including 20 patients with a mean age of 34 years. Enophthalmos was measured using Modified Hertels in patients with unilateral orbital/zygomatic fracture indicated for surgical intervention by a single observer. The data was collected and statistically analyzed. Paired sample t-test was done to compare the preoperative exophthalmometer reading with readings at different time points. RESULTS: A statistically significant difference was noted (P = 0.031) among the variables of Modified Hertels. We believe this instrument to be of practical use in the assessment of enophthalmos/exophthalmos in patients with lateral orbital trauma, surgery or disease and also precludes the use of rim-based exophthalmometry and other modifications of same.

A Prospective Study to Assess the Efficacy of 4% Articaine, 0.5% Bupivacaine and 2% Lignocaine using a Single Buccal Supraperiosteal Injection for Maxillary Tooth Extraction.

INTRODUCTION: The aim of this study was to demonstrate if articaine hydrochloride administered alone as a single buccal infiltration in maxillary tooth extraction can provide adequate palatal anesthesia as compared to buccal and palatal injection using lidocaine and bupivacaine. MATERIALS AND METHODS: A prospective double-blinded trial was conducted on 150 patients who required maxillary tooth extraction. The patients were divided into three different groups consisting of 50 patients each. Each group was administered with 4% articaine into buccal vestibular mucosa of the tooth to be extracted, 2% lignocaine and 0.5% bupivacaine was injected into buccal and palatal side of the tooth to be extracted, respectively. Following the tooth extraction, all patients were asked to complete a 10-score Visual Analog Scale (VAS) and 5-score facial pain scale (FPS) to assess the pain on extraction. RESULTS: According to the VAS and FPS scores, the pain on extraction between buccal infiltration of articaine and the routine buccal and palatal infiltration of lignocaine was statistically significant. CONCLUSION: The routine use of a palatal injection for extraction of maxillary teeth may not be required when articaine is used as a local anesthetic solution.

Nanopore Passport Control for Substrate-Specific Translocation.

Membrane protein pores have demonstrated applications in nanobiotechnology and single-molecule chemistry for effective detection of biomolecules. Here, we define the molecular basis of carbohydrate polymers translocation through a substrate-specific bacterial nanopore, CymA, which has a 15-residue N terminus segment inside the pore, restricting its diameter. Using single-channel recordings, we determined the kinetics of cationic cyclic oligosaccharide binding and elucidated the translocation mechanism across the pore in real-time. The cationic cyclic hexasaccharide binds to the densely packed negatively charged residues at the extracellular side of the pore with high affinity, facilitating its entry into the pore driven by the applied voltage. Further, the dissociation rate constant increased with increasing voltages, indicating unidirectional translocation toward the pore exit. Specifically, a larger cationic cyclic octasaccharide rapidly blocked the pore more effectively, resulting in the complete closure of the pore with increasing voltage, implying only strong binding. Further, we show that uncharged oligosaccharides exclusively bind to the extracellular side of the pore and the electroosmotic flow most likely drives their translocation. We propose that CymA favors selective translocation of cyclic hexasaccharide and linear maltooligosaccharides due to an asymmetrical charge pattern and the N terminus that regulates the substrate transport. We suggest that this substrate-specific nanopore with sophisticated geometry will be useful for complex biopolymer characterization.

B1CTcu5: A frog-derived brevinin-1 peptide with anti-tuberculosis activity.

Tuberculosis (TB) is a devastating infectious disease that causes a high rate of mortality. Drugs with new modes of action are needed to overcome this scenario. Cationic antibacterial peptides can serve as a potential alternative to existing TB drugs as they target the entire bacterial membrane for activity, thereby reducing the probability of development of drug resistance. In this study, we report anti-tuberculosis activity of B1CTcu5, a peptide that belongs to brevinin-1 family of antimicrobial peptides. This peptide possesses potent in vitro inhibitory activity against M. tuberculosis at 12.5 µg/mL but was not active against M. smegmatis. B1CTcu5 successfully eliminated intracellular mycobacteria without inducing cytotoxicity to the human macrophages at the concentrations tested. This peptide can be used as a template to design peptide-based anti-tubercular agents.

Hyper production of cellulase-free xylanase by Thermomyces lanuginosus SSBP on bagasse pulp and its application in biobleaching.

A cellulase-free xylanase production by Thermomyces lanuginosus SSBP using bagasse pulp was examined under submerged (SmC) and solid-state cultivation (SSC). Higher level of xylanase activity (19,320 +/- 37 U g(-1) dried carbon source) was obtained in SSC cultures than in SmC (1,772 +/- 15 U g(-1) dried carbon source) after 120 h with 10% inoculum. The biobleaching efficacy of crude xylanase was tested on bagasse pulp, and the maximum brightness of 46.1 +/- 0.06% was observed with 50 U of crude xylanase per gram of pulp, which was 3.8 points higher than the brightness of untreated samples. Reducing sugars (26 +/- 0.1 mg g(-1)) and UV-absorbing lignin-derived compounds in the pulp filtrates were observed as maximum in 50 U of crude xylanase-treated samples. T. lanuginosus SSBP has potential applications due to its high productivity of xylanase and its efficiency in pulp bleaching.

Solitary angiokeratoma of tongue: A case report and review of the literature.

Angiokeratoma is a benign cutaneous lesion of capillaries. It is characterized by large dilated blood vessels in the superficial dermis and hyperkeratosis of extremities. It is mostly seen in generalized form affecting the extremity of the body, but we report this case of solitary angiokeratoma of the tongue which is a very rare type.

Intra-alveolar extraction of impacted distoangular mandibular third molars: A novel technique.

Recent trends in maxillofacial surgery are to reduce the trauma to the adjacent soft tissue. The distoangular impaction presents a challenge to the maxillofacial surgeon and also results in more surgical morbidity. Here, we present a minimally invasive extraction technique for the distoangular mandibular third molar impaction.

UCN-SiO2-GO: a core shell and conjugate system for controlling delivery of doxorubicin by 980 nm NIR pulse.

Herein, graphene oxide (GO) has been attached with core-shell upconversion-silica (UCN-SiO2) nanoparticles (NPs) to form a GO-UCN-SiO2 hybrid nanocomposite and used for controlled drug delivery. The formation of the nanocomposite has been confirmed by various characterization techniques. To date, a number of reports are available on GO and its drug delivery applications, however, the synergic properties that arise due to the combination of GO, UCNPs and SiO2 can be used for controlled drug delivery. New composite UCN@SiO2-GO has been synthesized through a bio-conjugation approach and used for drug delivery applications to counter the lack of quantum efficiency of the upconversion process and control sustained release. A model anticancer drug (doxorubicin, DOX) has been loaded to UCNPs, UCN@SiO2 NPs and the UCN@SiO2-GO nanocomposite. The photosensitive release of DOX from the UCN@SiO2-GO nanocomposite has been studied with 980 nm NIR laser excitation and the results obtained for UCNPs and UCN@SiO2 NPs compared. It is revealed that the increase in the NIR laser irradiation time from 1 s to 30 s leads to an increase in the amount of DOX release in a controlled manner. In vitro studies using model cancer cell lines have been performed to check the effectiveness of our materials for controlled drug delivery and therapeutic applications. Obtained results showed that the designed UCN@SiO2-GO nanocomposite can be used for controlled delivery based therapeutic applications and for cancer treatment.

Cation disorder and epitaxial strain modulated Drude-Smith type terahertz conductivity and Hall-carrier switching in Ca1-x Ce x RuO3 thin films.

The CaRuO3 is a non-Fermi liquid pseudo-cubic perovskite with a magnetic ground state on the verge of phase transition and it lies in the vicinity of the quantum critical point. To understand the sensitivity of its ground state, the effects of subtle aliovalent chemical disorder on the static and high frequency dynamic conductivity in the coherently strained structures were explored. The Ce-doped Ca1-x Ce x RuO3 (0 ⩽ x ⩽ 0.1) thin films were deposited on LaAlO3 (1 0 0) and SrTiO3 (1 0 0) substrates and studies for low-energy terahertz (THz) carrier dynamics, dc transport and Hall effect. These compositions exhibited a very effective and unusual Hall-carrier switching in both compressive and tensile strain induced epitaxial thin films. The dc resistivity depicts a switching from a non-Fermi liquid to a Fermi liquid behavior without any magnetic phase transition. A discernible and gradual crossover from Drude to Drude-Smith THz dynamic optical conductivity was observed while traversing from pure to 10% Ce-doped CaRuO3 films. Overall, a nearly Fermi liquid behavior, effective carrier switching and unusual features in THz conductivity, were all novel features realized for the first time in physically and/or chemically modified CaRuO3. These new phases highlight the novel subtleties and versatility of the systems lying near the quantum critical point.

TM1-IR680 peptide for assessment of surgical margin and lymph node metastasis in murine orthotopic model of oral cancer.

Treatment outcome after surgical removal in oral carcinoma is poor due to inadequate methodologies available for marking surgical margins. Even though some methodologies for intraoperative margin assessment are under clinical and preclinical trials for other solid tumours, a promising modality for oral cancer surgery is not developed. Fluorescent-based optical imaging using Near Infrared (NIR) dyes tagged to tumour specific target will be an optimal tool for this purpose. One such target, Gastrin Releasing Peptide Receptor (GRPR) was selected for the study, and its binding peptide, TM1-IR680, was tested for its efficacy for surgical margin prediction in murine orthotopic model of oral cancer, derived from primary samples. Here, for the first time in a preclinical analysis, we show that the size and margin of oral cancer can be predicted, as revealed by 3D-imaging. Interestingly, the peptide was sensitive enough to detect lymph nodes that harboured dispersed tumour cells before colonization, which was impossible to identify by conventional histopathology. We recommend the use of TM1-NIR dyes alone or in combination with other technologies to improve the clinical outcome of oral cancer surgery.

Structure-Activity Relationship and Mode of Action of a Frog Secreted Antibacterial Peptide B1CTcu5 Using Synthetically and Modularly Modified or Deleted (SMMD) Peptides.

All life forms are equipped with rapidly acting, evolutionally conserved components of an innate immune defense system that consists of a group of unique and diverse molecules known as host defense peptides (HDPs). A Systematic and Modular Modification and Deletion (SMMD) approach was followed to analyse the structural requirement of B1CTcu5, a brevinin antibacterial peptide amide identified from the skin secretion of frog Clinotarsus curtipes, India, to show antibacterial activity and to explore the active core region. Seventeen SMMD-B1CTcu5 analogs were designed and synthesised by C and N-terminal amino acid substitution or deletion. Enhancement in cationicity by N-terminal Lys/Arg substitution or hydrophobicity by Trp substitution produced no drastic change in bactericidal nature against selected bacterial strains except S. aureus. But the sequential removal of N-terminal amino acids had a negative effect on bactericidal potency. Analog B1CTcu5-LIAG obtained by the removal of four N-terminal amino acids displayed bactericidal effect comparable to, or in excess of, the parent peptide with reduced hemolytic character. Its higher activity was well correlated with the improved inner membrane permeabilisation capacity. This region may act as the active core of B1CTcu5. Presence of C-terminal disulphide bond was not a necessary condition to display antibacterial activity but helped to promote hemolytic nature. Removal of the C-terminal rana box region drastically reduced antibacterial and hemolytic activity of the peptide, showing that this region is important for membrane targeting. The bactericidal potency of the D-peptide (DB1CTcu5) helped to rule out the stereospecific interaction with the bacterial membrane. Our data suggests that both the C and N-terminal regions are necessary for bactericidal activity, even though the active core region is located near the N-terminal of B1CTcu5. A judicious modification at the N-terminal region may produce a short SMMD analog with enhanced bactericidal activity and low toxicity against eukaryotic cells.

Synthesis of a shark repellent peptide toxin, Pardaxin (16-33) on a highly flexible polymer support: CLPSER.

A high swelling resin, CLPSER has been developed and utilized for the solid phase synthesis of Pardaxin, which is an 18-residue peptide. The resin was characterized by gel phase (13)C NMR, IR and SEM. The utility of the new polymer support in polypeptide synthesis was further established by the comparative synthesis of pardaxin with commercially available Merrifield resin. The MALDI TOF MS, amino acid analysis and the HPLC revealed the superior quality of CLPSER.

Chemical synthesis of NS-1 region of hepatitis C-viral polyprotein fragments: a comparison of PS-BDODMA resin and merrifield resin.

Three peptide fragments selected from the NS-1 region of hepatitis C-viral polyprotein (Leu-Ile-Asn-Thr-Asn-Ala-Ser-Trp-His-Ala-Asn-Arg-Thr-Ala-Leu-Ser Asn-Asp Ser-Lys Leu Asn Thr-Gly Ala NH(2), Leu-lle Asn Thr Asn Ala Ser-Trp-His-Ala-Asn-Arg-Thr Ala NH(2) and Leu-Asn-Cys(Acm)-Asn-Asp-Ser-Leu-Asn-Thr-Ala-NH(2)) have been synthesized on PS-BDODMA resin. The synthetic capability of the resin PS-BDODMA resin was compared with Merrifield resin. The peptides were synthesized by the stepwise fluoren-9-yl methoxycarbonyl (Fmoc) solid-phase method. The synthesized peptides were purified by HPLC and the identity of the peptides was established by mass spectrum and amino acid analysis. The synthesis of these peptides illustrates the application of the PS-BDODMA resin for the synthesis of long chain peptides in high yield and homogeneity compared to the Merrifield resin.

Klippel-Trenaunay syndrome and gestational trophoblastic neoplasm.

BACKGROUND: Klippel-Trenaunay syndrome is a non-heritable venous malformation with bone and soft tissue hypertrophy and cutaneous nevi. CASE CHARACTERISTICS: Neonate with Klippel Trenaunay syndrome born to a mother with past history of Gestational trophoblastic neoplasm. OBSERVATION: Antenatally, a fetal vascular malformation was identified ultrasonologically at 29 weeks gestation. Acute myeloid leukemia was diagnosed in mother at 33 weeks gestation. MESSAGE: A rare association of Klippel Trenaunay syndrome and gestational trophoblastic neoplasm with the possible role of either hyperglycosylated Human Chorionic Gonadotropin or chemotherapy as a link is highlighted.

Novel antibacterial peptides from the skin secretion of the Indian bicoloured frog Clinotarsus curtipes.

HPLC elution profile and MALDI TOF MS analysis of electro-stimulated skin secretion of the Indian Ranid frog Clinotarsus curtipes of the Western Ghats confirmed the presence of multiple peptides. Peptides eluted out of the C18 column at higher hydrophobic solvent region showed antibacterial activity against diverse bacterial strains, including the clinical isolates of V. cholerae and methicillin resistant Staphylococcus aureus (MRSA). Peptidomic analysis of the most potent chromatographic effluent fraction identified five novel peptide amides having sequence homology with brevinin family. These peptides are named as brevinin1CTcu1 (B1CTcu1) to brevinin1CTcu5 (B1CTcu5). Peptide B1CTcu1 is non-haemolytic while the others are haemolytic in nature but all elicited potential antibacterial activity. B1CTcu5 is a twenty-one residue peptide amide having proline hinge region in the middle and the typical C-terminal intramolecular disulfide-bridged hepta peptide domain (Rana box) that is present in most of the brevinin peptides. Analysis of their killing kinetics with E. coli and S. aureus and the ability to induce membrane depolarization proved that these are two independent events. These novel multifunctional peptides play an important role to protect C. curtipes from invading pathogenic microorganisms present in the environment.