Prebiotically plausible chemoselective pantetheine synthesis in water.

Coenzyme A (CoA) is essential to all life on Earth, and its functional subunit, pantetheine, is important in many origin-of-life scenarios, but how pantetheine emerged on the early Earth remains a mystery. Earlier attempts to selectively synthesize pantetheine failed, leading to suggestions that "simpler" thiols must have preceded pantetheine at the origin of life. In this work, we report high-yielding and selective prebiotic syntheses of pantetheine in water. Chemoselective multicomponent aldol, iminolactone, and aminonitrile reactions delivered spontaneous differentiation of pantoic acid and proteinogenic amino acid syntheses, as well as the dihydroxyl, gem-dimethyl, and ß-alanine-amide moieties of pantetheine in dilute water. Our results are consistent with a role for canonical pantetheine at the outset of life on Earth.

Parasitic Eye Diseases: Nuances in Rapid Identification and Advanced Microscopy.

AIM: To study parasitic eye diseases in a tertiary institute of North-east India by live examination of parasites, rapid staining, and scanning electron microscopy (SEM). METHODS: A 12-year retrospective analysis was performed and all patients diagnosed with ocular parasitic diseases were identified. Examination under a compound microscope, fluorescein staining, and scanning electron microscopy were done. RESULTS: A total of 160 ocular parasitosis cases were identified. The cases for which rapid staining and SEM studies were done included Cysticercosis (n = 18, 11.25%), Hydatidosis (n = 5, 3.13%), Dirofilariasis (n = 5, 3.13%), Thelaziasis (n = 3, 1.87%), and Gnathostomiasis (n = 2, 1.25%). Live examination was performed in 11 cases (6.63%) and 8 cases (4.82%) underwent scanning electron microscopy. . CONCLUSION: Fluorescein staining for identification of parasites and SEM study helped in detailing microscopic and ultrastructural findings.

An immunoinformatics approach to epitope-based vaccine design against PspA in Streptococcus pneumoniae.

BACKGROUND: Streptococcus pneumoniae (SPN) is the agent responsible for causing respiratory diseases, including pneumonia, which causes severe health hazards and child deaths globally. Antibiotics are used to treat SPN as a first-line treatment, but nowadays, SPN is showing resistance to several antibiotics. A vaccine can overcome this global problem by preventing this deadly pathogen. The conventional methods of wet-laboratory vaccine design and development are an intense, lengthy, and costly procedure. In contrast, epitope-based in silico vaccine designing can save time, money, and energy. In this study, pneumococcal surface protein A (PspA), one of the major virulence factors of SPN, is used to design a multi-epitope vaccine. METHODS: For designing the vaccine, the sequence of PspA was retrieved, and then, phylogenetic analysis was performed. Several CTL epitopes, HTL epitopes, and LBL epitopes of PspA were all predicted by using several bioinformatics tools. After checking the antigenicity, allergenicity, and toxicity scores, the best epitopes were selected for the vaccine construction, and then, physicochemical and immunological properties were analyzed. Subsequently, vaccine 3D structure prediction, refinement, and validation were performed. Molecular docking, molecular dynamic simulation, and immune simulation were performed to ensure the binding between HLA and TLR4. Finally, codon adaptation and in silico cloning were performed to transfer into a suitable vector. RESULTS: The constructed multi-epitope vaccine showed a strong binding affinity with the receptor molecule TLR4. Analysis of molecular dynamic simulation, C-immune simulation, codon adaptation, and in silico cloning validated that our designed vaccine is a suitable candidate against SPN. CONCLUSION: The in silico analysis has proven the vaccine as an alternative medication to combat against S. pneumoniae. The designated vaccine can be further tested in the wet lab, and a novel vaccine can be developed.

Intraocular and neuro-cysticercosis with diffuse stromal choroiditis.

Intraocular cysticercosis with central nervous system involvement is not that rare. We report a male child with a right-sided painful blind eye who had intraocular cysticercosis and granuloma in the left frontal lobe of the brain. There was an incidental finding of chronic inflammation in the choroid of that eye supported by histopathology. Immunohistochemistry for T-cells marker and B-cells marker was variable. The patient was treated with antiparasitic, anti-epileptic medications, and oral steroids subsequently.

Dealer-customer partnership in rice production demonstration: Assessment of private extension system in Bangladesh.

Traditional public extension worker-farmer cooperation in rice production demonstration is not working efficiently, therefore, private partnership-based demonstration has been attempted to introduce as its alternative very recently involving dealer-customer farmer. The study evaluated the private extension services rendered through dealer-customer farmer cooperation in Bangladesh. Thirty-three rice seed dealers and ninety-two customer farmers formed the samples for the study. Face-to-face interviews were employed as a quantitative method while focus group discussion was used as a qualitative method in the present study. Involving in the private rice production demonstration approach, customer farmers indicated high profit, greater involvement in decision-making, and improved marketing skills as the major advantages; while the dealers stressed the benefit received by the small farmers, improvement in their decision-making capacity and increased local rice production. However, the slow distribution of inputs during the production period was a weakness in the arrangement, which was mostly because of the dealers' lack of understanding of the customer farmers' needs. The private extension system being a new concept in the country may be observed over a period and gradually extended to the nooks and crannies of the country.

Elephantoloemus indicus Austen, 1930 (Diptera: Calliphoridae) as the cause of cutaneous myiasis in captive Indian elephants from Assam, India.

Elephantoloemus indicus Austen, 1930, a dipteran calliphorid fly is known to cause by its larval stage obligatory cutaneous myiasis in Indian subspecies of Asian elephants (Elephas maximus indicus Cuvier, 1798) in Myanmar and Thailand. The present study was undertaken on morphological identification of some specimens of fly larvae which were recovered from the warbles detected on the skin of captive Indian elephants at the Nameri National Park and Kaziranga National Park both situated in the state of Assam, India. The larval specimens were whitish to creamy white in colour and body conformation varied from cylindrical to barrel shaped depending on their measured size (Av 6.12 ± 0.28 × 2.35 ± 0.12 mm). Microscopic examination of processed larvae revealed presence of numerous single pointed spines uniformly distributed on entire body surface, well developed mouth hooks and cephalopharyngeal skeleton at the anterior end and posterior spiracles each with lightly sclerotized peritreme enclosing three short and straight respiratory slits. Based on geographical distribution of the fly, host relation, larval parasitism and morphological characters, the larvae were determined as of the genus Elephantoloemus which is represented by E. indicus as the only species described so far. This finding seems to be the first record in India after its report from Myanmar and Thailand.

Prebiotic Catalytic Peptide Ligation Yields Proteinogenic Peptides by Intramolecular Amide Catalyzed Hydrolysis Facilitating Regioselective Lysine Ligation in Neutral Water.

The prebiotic origin of catalyst-controlled peptide synthesis is fundamental to understanding the emergence of life. Building on our recent discovery that thiols catalyze the ligation of amino acids, amides, and peptides with amidonitriles in neutral water, we demonstrate the outcome of ligation depends on pH and that high pKa primary thiols are the ideal catalysts. While the most rapid thiol catalyzed peptide ligation occurs at pH 8.5-9, the most selective peptide ligation, that tolerates all proteinogenic side chains, occurs at pH 7. We have also identified the highly selective mechanism by which the intermediate peptidyl amidines undergo hydrolysis to α-peptides while demonstrating that the hydrolysis of amidines with nonproteinogenic structures, such as ß- and γ-peptides, displays poor selectivity. Notably, this discovery enables the highly α-selective protecting-group-free ligation of lysine peptides at neutral pH while leaving the functional ε-amine side chain intact.

Synergistic Strengthening in Graphene Oxide and Oxidized Single-walled Carbon Nanotube Hybrid Material for use as Electrolytes in Proton Exchange Membrane Fuel Cells.

Herein, we report an efficient proton exchange membrane formed from a synergistic combination of graphene oxide (GO) and oxidized single-walled carbon nanotube (CNTOX) by the freeze-drying route that gives rise to enhanced fuel cell power density. At 25 °C and 100% relative humidity (RH), the 3DGO-CNTOX hybrid shows remarkably high out-of-plane and in-plane proton conductivities of 6.64×10-2 and 5.08 S cm-1 , respectively. Additionally, the measured performance using prepared films as proton conduction membranes in a proton exchange membrane fuel cell (PEMFC) exhibited a peak power density of 117.21 mW cm-2 . The high performance of these films can be ascribed to the freeze-dried-driven structural morphology of 3DGO-CNTOX that facilitates higher water retention capacity as well as the synergistic strengthening effect between GO and CNTOX with a highly interconnected proton conduction network. The current results imply that the new 3DGO-CNTOX hybrid material has potential for wide application as a proton exchange membrane.

Epidemiology of pelvic fractures in adult: Our experience at two tertiary care hospital in Dhaka, Bangladesh.

PURPOSE: In Bangladesh the incidence of pelvic fracture is increasing day by day due to suboptimal roads and heavy traffic. However, there is no epidemiological study of these injuries in Bangladesh. Our aim was to study the epidemiology of patients admitted with pelvic fractures at two tertiary care hospital in Dhaka, Bangladesh. METHODS: This was a prospective study carried out on trauma patients with pelvic fracture at two level 1 trauma care center of two tertiary care hospital in Dhaka, Bangladesh. The study period was from July 2015 to June 2019 (48 months). Patient's data including demography of patients, mechanism of injuries, fracture types, associated injuries, method of treatment, post-operative complications, length of hospital stay were recorded according to a unified protocol. RESULTS: The study population was comprised of 696 patients, where 556 (79.88%) were male and 140 (20.12%) were female. Mean age was 37.75 years and road traffic accidents were the most common mode of injuries. Lateral compression fractures were the most common injuries and Urethral injuries were the most common associated injuries. Death was the outcome in 3.5% of the cases due to high energy trauma. CONCLUSION: This study revealed that pelvic fractures were significantly more frequent in men. Most frequent cause was road traffic accident. The majority of these cases did not required surgery. Mortality was associated with high velocity trauma with severe injuries.

Prebiotic synthesis of cysteine peptides that catalyze peptide ligation in neutral water.

Peptide biosynthesis is performed by ribosomes and several other classes of enzymes, but a simple chemical synthesis may have created the first peptides at the origins of life. α-Aminonitriles-prebiotic α-amino acid precursors-are generally produced by Strecker reactions. However, cysteine's aminothiol is incompatible with nitriles. Consequently, cysteine nitrile is not stable, and cysteine has been proposed to be a product of evolution, not prebiotic chemistry. We now report a high-yielding, prebiotic synthesis of cysteine peptides. Our biomimetic pathway converts serine to cysteine by nitrile-activated dehydroalanine synthesis. We also demonstrate that N-acylcysteines catalyze peptide ligation, directly coupling kinetically stable-but energy-rich-α-amidonitriles to proteinogenic amines. This rare example of selective and efficient organocatalysis in water implicates cysteine as both catalyst and precursor in prebiotic peptide synthesis.

Author Correction: Peptide ligation by chemoselective aminonitrile coupling in water.

An Amendment to this paper has been published and can be accessed via a link at the top of the paper.

Bio-nanoparticle assembly: a potent on-site biolarvicidal agent against mosquito vectors.

Background: Vector-borne diseases such as malaria, dengue, yellow fever, encephalitis and filariasis are considered serious human health concerns in the field of medical entomology. Controlling the population of mosquito vectors is one of the best strategies for combating such vector-borne diseases. However, the use of synthetic insecticides for longer periods of time increases mosquito resistance to the insecticides. Recently, the search for new environmentally friendly and efficient insecticides has attracted major attention globally. With the evolution of material sciences, researchers have reported the effective control of such diseases using various sustainable resources. The present investigation demonstrates a potent on-site biolarvicidal agent against different mosquito vectors such as Aedes albopictus, Anopheles stephensi and Culex quinquefasciatus. Methods: Stable and photo-induced colloidal silver nanoparticles were generated via the surface functionalization of the root extract of Cyprus rotundas. Characterizations of the nanoparticles were performed using assorted techniques, such as UV-visible spectroscopy, FTIR spectroscopy, DLS and HRTEM. The bioefficacy of the synthesized nanoparticles was investigated against different species of mosquito larvae through the evaluation of their life history trait studies, fecundity and hatchability rate of the treated larvae. Histopathological and polymerase chain reaction-random amplified polymorphic DNA (RAPD) analyses of the treated larvae were also examined to establish the cellular damage. Results: The synthesized nanoparticles showed remarkable larvicidal activity against mosquito larvae in a very low concentration range (0.001-1.00) mg L-1. The histopathological study confirmed that the present nanoparticles could easily enter the cuticle membrane of mosquito larvae and subsequently obliterate their complete intestinal system. Furthermore, RAPD analysis of the treated larvae could assess the damage of the DNA banding pattern. Conclusion: The present work demonstrates a potent biolarvicidal agent using sustainable bioresources of the aqueous Cyprus rotundas root extract. The results showed that the synthesized nanoparticles were stable under different physiological conditions such as temperature and photo-induced oxidation. The effectiveness of these materials against mosquito larvae was quantified at very low dose concentrations. The present biolarvicidal agent can be considered as an environmentally benign material to control the mosquito vectors with an immense potential for on-site field applications.

Peptide ligation by chemoselective aminonitrile coupling in water.

Amide bond formation is one of the most important reactions in both chemistry and biology1-4, but there is currently no chemical method of achieving α-peptide ligation in water that tolerates all of the 20 proteinogenic amino acids at the peptide ligation site. The universal genetic code establishes that the biological role of peptides predates life's last universal common ancestor and that peptides played an essential part in the origins of life5-9. The essential role of sulfur in the citric acid cycle, non-ribosomal peptide synthesis and polyketide biosynthesis point towards thioester-dependent peptide ligations preceding RNA-dependent protein synthesis during the evolution of life5,9-13. However, a robust mechanism for aminoacyl thioester formation has not been demonstrated13. Here we report a chemoselective, high-yielding α-aminonitrile ligation that exploits only prebiotically plausible molecules-hydrogen sulfide, thioacetate12,14 and ferricyanide12,14-17 or cyanoacetylene8,14-to yield α-peptides in water. The ligation is extremely selective for α-aminonitrile coupling and tolerates all of the 20 proteinogenic amino acid residues. Two essential features enable peptide ligation in water: the reactivity and pKaH of α-aminonitriles makes them compatible with ligation at neutral pH and N-acylation stabilizes the peptide product and activates the peptide precursor to (biomimetic) N-to-C peptide ligation. Our model unites prebiotic aminonitrile synthesis and biological α-peptides, suggesting that short N-acyl peptide nitriles were plausible substrates during early evolution.

Heated gas bubbles enrich, crystallize, dry, phosphorylate and encapsulate prebiotic molecules.

Non-equilibrium conditions must have been crucial for the assembly of the first informational polymers of early life, by supporting their formation and continuous enrichment in a long-lasting environment. Here, we explore how gas bubbles in water subjected to a thermal gradient, a likely scenario within crustal mafic rocks on the early Earth, drive a complex, continuous enrichment of prebiotic molecules. RNA precursors, monomers, active ribozymes, oligonucleotides and lipids are shown to (1) cycle between dry and wet states, enabling the central step of RNA phosphorylation, (2) accumulate at the gas-water interface to drastically increase ribozymatic activity, (3) condense into hydrogels, (4) form pure crystals and (5) encapsulate into protecting vesicle aggregates that subsequently undergo fission. These effects occur within less than 30 min. The findings unite, in one location, the physical conditions that were crucial for the chemical emergence of biopolymers. They suggest that heated microbubbles could have hosted the first cycles of molecular evolution.

Clinical characteristics and outcomes of ST-segment elevation myocardial infarction in a low income setting in rural Bangladesh.

BACKGROUND: In rural areas of Bangladesh, the majority of patients with ST segment elevation myocardial infarction (STEMI) have little access to reperfusion therapy. Even though thrombolysis can be an affordable life-saving treatment in a low income setting, there are few publications in regards to the clinical and socioeconomic features of STEMI with thrombolytic therapy in rural Bangladesh. METHOD: The information of the patients who were admitted for STEMI between 2010 and 2016 from one rural hospital were collected and reviewed. This audit evaluated clinical outcomes and socioeconomic characteristics of the patients. RESULT: 164 patients with STEMI were identified in the period and 136 patients (82.93%) underwent thrombolysis. The mean pain-to-door time was 472 min (7.87 h ±â€¯12.40). Only 5.49% of the patients traveled to hospital by ambulances. Overall in-hospital mortality rate and major adverse cardiovascular event (MACE) after STEMI were 19.51% (32/164), 23.17% (38/164), respectively. The need of inotropics (Odds ratio [OR] 16.43, 95% confidence interval [CI] 1.99-135.75, P < 0.01), the use of defibrillation due to ventricular arrhythmias (OR 33.58, 95% CI 2.96-380.49, P < 0.01) were independent predictors of increased in-hospital mortality. CONCLUSION: In a rural hospital of Bangladesh, in-hospital mortality rate after STEMI is high in spite of thrombolysis and adherence to published guidelines. The prolonged pain-to-door time and the poor coverage of ambulance services in our study highlight the need of community awareness of acute coronary syndrome and comprehensive emergency medical services in rural Bangladesh.

An integrated microfluidic flow-focusing platform for on-chip fabrication and filtration of cell-laden microgels.

We present the development of a stable continuous, and integrated microfluidic platform for the high-throughput fabrication of monodisperse cell-laden microgel droplets with high and maintained cellular viability. This is through combining onto one chip all the required processes from the droplet generation in a flow focusing microfluidic junction passing through on-chip photocrosslinking to the separation of the droplets from the continuous oil phase. To avoid cellular aggregation during the droplet generation process, cells were treated with bovine serum albumin (BSA) before mixing with gelatin methacrylate (GelMA). And, a magnetic mixer was applied to the GelMA prepolymer-cell suspension syringe to eliminate cell sedimentation. These approaches resulted in having a reasonable distribution of cells among monodisperse microdroplets. The microdroplets were irradiated with a 405 nm wavelength laser beam while passing through the crosslinking chamber of the microfluidic device. The produced microgels enter the filtration unit of the same device where they were gently separated from the oil phase into the washing buffer aqueous solution of Tween 80 using the filter microposts array. The viability of the encapsulated cells was around 85% at day 1 and was maintained throughout 5 days. Using this method of controlling cell encapsulation with on-chip crosslinking and oil filtration, highly efficient cell-laden microgel production is achieved. The presented integrated microfluidic platform can be a candidate for standard cell-encapsulation experiments and other tissue engineering applications.

Human ocular thelaziasis caused by gravid Thelazia callipaeda - A unique and rare case report.

An 80-year-old male reported to the clinic with complaints of diminished vision, foreign body sensation, and occasionally some black object moving in front of the right eye. Detailed ocular examination revealed three slender creamy white live worms in the conjunctival sac of the right eye. Total three worms were retrieved and sent to the pathology department for detailed examination. The worm was identified as gravid Thelazia callipaeda. As per the search results in PubMed and Cochrane search engine, this is the first report of human case of gravid Thelazia infestation with simultaneous existence of embryonated or ensheathed eggs and primary-stage larvae in the same worm.

Mosquito abundance and pig seropositivity as a correlate of Japanese encephalitis in human population in Assam, India.

BACKGROUND & OBJECTIVES: Assam is the most vulnerable state for Japanese encephalitis (JE) in India. The situation warrants characterization of epidemiological patterns of JE in vectors, pigs and human population. This investigation was aimed to determine the relative abundance of mosquito species and seroprevalence of JE in pigs in order to draw an epidemiological association with reported human JE cases in Assam. METHODS: Pig sera and mosquitoes from selected farms in Sivasagar and Kamrup districts of Assam were collected fortnightly for one year during June 2015-May 2016. Pig sera were tested for JE antibodies by haemagglutination and virus neurtralization tests. Mosquito species were identified microscopically following the taxonomic keys. The results were analyzed with data on confirmed human JE cases in the selected districts. RESULTS: Culex gelidus (26.07%) and Cx. tritaeniorhynchus (24.07%) were the most abundant species in collected mosquitoes (n = 997). A total of 22.99% of pigs (n = 335) were JEV seropositive and 45.65% of human acute encephalitis syndrome cases (n = 230) were positive for JE virus (JEV) infection. Relative mosquito abundance, pig positivity and human cases were highest during monsoon (June-September) and least during winter (December-February). Rise in mosquito population was observed during pre-monsoon season (March-May) and concurrently higher number of human cases and pig seropositivity were recorded. A good correlation was observed between mosquito number and JEV positivity in pigs/human, and between pigs and human cases (p < 0.05). Human population in Sivasagar was at higher risk for JE infection (OR: 6.46, p < 0.0001) than in Kamrup rural district. INTERPRETATION & CONCLUSION: This study indicates that a seasonal correlation exists between mosquito abundance and JEV seroconversion in pigs with concurrent human JEV outbreaks under field conditions in Sivasagar and Kamrup rural districts of Assam and that monitoring mosquito abundance/density and pig JEV seropositivity may help in predicting JEV outbreak in human population in the region.

Fibular Graft-Effective Panorama for Prosthetic Rehabilitation of Resected Mandible.

Surgical management of extensive tumors in the mandibular region leads to massive disfigurement of the face. Also the prosthetic outcome of such patients rehabilitated with free soft tissue flaps is very poor. Reconstruction of extensive defects to overcome the disfigurement is a challenging procedure and can be achieved with free fibula flap. Free fibula graft provides sufficient length of bone for the reconstruction of the postsurgical defects. Excellent vascularity of fibula flap allows for easy uptake of the graft and osseointegration of the dental implants. The addition of a skin island allows for absolute tension-free intraoral closure that enhances tongue mobility. Fibula graft allows proper tissue support after mandibular reconstruction. After rehabilitation with free fibula graft we can plan for prosthodontic rehabilitation with implant retained prosthesis leading to improved masticatory function. It also helps to improve speech outcome as a stable prosthesis can be delivered with the help of implants retained in the fibula graft. It is essential to assess the outcome of surgical reconstruction with fibula graft followed by prosthetic rehabilitation with implant retained prosthesis for their recognition as a treatment of preference. This article details the clinical report along with various clinical parameters for implant retained prosthetic rehabilitation of the patient who had undergone mandibular resection and reconstruction with free fibula graft.