Identification of BPESC1, a Novel Gene Disrupted by a Balanced Chromosomal Translocation, t(3;4)(q23;p15.2), in a Patient with BPES

The blepharophimosis syndrome (BPES) is a rare genetic disorder characterized by blepharophimosis, ptosis, epicanthus inversus, and telecanthus. In type I, BPES is associated with female infertility, while in type II, the eyelid defect occurs by itself. The BPES syndrome has been mapped to 3q23. Previously, we constructed a YAC-, PAC-, and cosmid-based physical map surrounding the 3q23 translocation breakpoint of a t(3;4)(q23;p15.2) BPES patient, containing a 110-kb PAC (169-C 10) and a 43-kb cosmid (11-L 10) spanning the breakpoint. In this report, we present the identification of BPESC1 (BPES candidate 1), a novel candidate gene that is disrupted by the translocation on chromosome 3. Cloning of the cDNA has been performed starting from a testis-specific EST, AI032396, found in cosmid 11-L 10. The cDNA sequence of BPESC1 is 3518 bp in size and contains an open reading frame of 351 bp. No significant similarities with known proteins have been found in the sequence databases. BPESC1 contains three exons and spans a genomic fragment of 17.5 kb. Expression of BPESC1 was observed in adult testis tissue. We performed mutation analysis in 28 unrelated familial and sporadic BPES patients, but, apart from the disruption by the translocation, found no other disease-causing mutations. These data make it unlikely that BPESC1 plays a major role in the pathogenesis of BPES.     

Endothelin, a potent peptide agonist in the liver

Endothelin, a peptide mediator produced by vascular endothelial cells, caused sustained vasoconstriction of the portal vasculature in the perfused rat liver. The vasoactive effect of endothelin was accompanied by increased glycogenolysis and alterations in hepatic oxygen consumption. The endothelin-induced increase in the portal pressure was concentration-dependent with an EC50 of 1 nM. Endothelin-induced hepatic glycogenolysis was dose-dependent but exhibited a different EC50 than for the vasoconstrictive effects of endothelin. Hepatic vasoconstriction and glycogenolysis following endothelin infusion were inhibited when Ca2+ was removed from the perfusion medium. The endothelin-induced responses in the liver were not altered by prior infusion of phenylephrine (alpha-adrenergic agonist), isoproterenol (beta-adrenergic agonist), angiotensin II, glucagon, platelet-activating factor, or the platelet-activating factor antagonist, BN52021. However, repeated infusion of endothelin resulted in desensitization of the glycogenolytic response but was without a significant effect on hepatic vasoconstriction. Endothelin also stimulated metabolism of inositol phospholipids in isolated hepatocytes and Kupffer cells in primary culture. The present experiments demonstrate, for the first time, that endothelin is a very potent agonist in the liver eliciting both a sustained vasoconstriction of the hepatic vasculature and a significant increase in hepatic glucose output.     

Lyotropic Liquid Crystalline Nanoparticles of Amphotericin B: Implication of Phytantriol and Glyceryl Monooleate on Bioavailability Enhancement

Implication of different dietary specific lipids such as phytantriol (PT) and glyceryl monooleate (GMO) on enhancing the oral bioavailability of amphotericin B (AmB) was examined. Liquid crystalline nanoparticles (LCNPs) were prepared using hydrotrope method, followed by in vitro characterization, Caco-2 cell monolayer uptake, and in vivo pharmacokinetic and toxicity evaluation. Optimized AmB-LCNPs displayed small particle size (<?210 nm) with a narrow distribution (~?0.2), sustained drug release and high gastrointestinal stability, and reduced hemolytic toxicity. PLCNPs presented slower release, i.e., ~?80% as compared to ~?90% release in case of GLCNPs after 120 h. Significantly higher uptake in Caco-2 monolayer substantiated the role of LCNPs in increasing the intestinal permeability followed by increased drug titer in plasma. Pharmacokinetic studies demonstrated potential of PT in enhancing the bioavailability (approximately sixfold) w.r.t. of its native counterpart with reduced nephrotoxicity as presented by reduced nephrotoxicity biomarkers and histology studies. These studies established usefulness of PLCNPs over GLCNPs and plain drug. It can be concluded that acid-resistant lipid, PT, can be utilized efficiently as an alternate lipid for the preparation of LCNPs to enhance bioavailability and to reduce nephrotoxicity of the drug as compared to other frequently used lipid, i.e., GMO.     

Pervasiveness of UVC254-resistant Geobacillus strains in extreme environments

Applied Microbiology and Biotechnology - We have characterized a broad collection of extremophilic bacterial isolates from a deep subsurface mine, compost dumping sites, and several hot spring...     

Stable Formamidinium‐Based Perovskite Solar Cells via In Situ Grain Encapsulation

Formamidinium (FA)‐based lead iodide perovskites have emerged as the most promising light‐absorber materials in the prevailing perovskite solar cells (PSCs). However, they suffer from the phase‐instability issue in the ambient atmosphere, which is holding back the realization of the full potential of FA‐based PSCs in the context of high efficiency and stability. Herein, the tetraethylorthosilicate hydrolysis process is integrated with the solution crystallization of FA‐based perovskites, forming a new film structure with individual perovskite grains encapsulated by amorphous silica layers that are in situ formed at the nanoscale. The silica not only protects perovskite grains from the degradation but also enhances the charge‐carrier dynamics of perovskite films. The underlying mechanism is discussed using a joint experiment‐theory approach. Through this in situ grain encapsulation method, PSCs show an efficiency close to 20% with an impressive 97% retention after 1000‐h storage under ambient conditions.     

Lewis‐Adduct Mediated Grain‐Boundary Functionalization for Efficient Ideal‐Bandgap Perovskite Solar Cells with Superior Stability

State‐of‐the‐art perovskite solar cells (PSCs) have bandgaps that are invariably larger than 1.45 eV, which limits their theoretically attainable power conversion efficiency. The emergent mixed‐(Pb, Sn) perovskites with bandgaps of 1.2–1.3 eV are ideal for single‐junction solar cells according to the Shockley–Queisser limit, and they have the potential to deliver higher efficiency. Nevertheless, the high chemical activity of Sn(II) in these perovskites makes it extremely challenging to control their physical properties and chemical stability, thereby leading to PSCs with relatively low PCE and stability. In this work, the authors employ the Lewis‐adduct SnF₂·3FACl additive in the solution‐processing of ideal‐bandgap halide perovskites (IBHPs), and prepare uniform large‐grain perovskite thin films containing continuously functionalized grain boundaries with the stable SnF₂ phase. Such Sn(II)‐rich grain‐boundary networks significantly enhance the physical properties and chemical stability of the IBHP thin films. Based on this approach, PSCs with an ideal bandgap of 1.3 eV are fabricated with a promising efficiency of 15.8%, as well as enhanced stability. The concept of Lewis‐adduct‐mediated grain‐boundary functionalization in IBHPs presented here points to a new chemical route for approaching the Shockley–Queisser limit in future stable PSCs.     

Biotic and Abiotic Drivers of Peatland Growth and Microtopography: A Model Demonstration

Peatlands are important carbon reserves in terrestrial ecosystems. The microtopography of a peatland area has a strong influence on its carbon balance, determining carbon fluxes at a range of spatial scales. These patterned surfaces are very sensitive to changing climatic conditions. There are open research questions concerning the stability, behaviour and transformation of these microstructures, and the implications of these changes for the long-term accumulation of organic matter in peatlands. A simple two-dimensional peat microtopographical model was developed, which accounts for the effects of microtopographical variations and a dynamic water table on competitive interactions between peat-forming plants. In a case study of a subarctic mire in northern Sweden, we examined the consequences of such interactions on peat accumulation patterns and the transformation of microtopographical structure. The simulations demonstrate plausible interactions between peatland growth, water table position and microtopography, consistent with many observational studies, including an observed peat age profile from the study area. Our model also suggests that peatlands could exhibit alternative compositional and structural dynamics depending on the initial topographical and climatic conditions, and plant characteristics. Our model approach represents a step towards improved representation of peatland vegetation dynamics and net carbon balance in Earth system models, allowing their potentially important implications for regional and global carbon balances and biogeochemical and biophysical feedbacks to the atmosphere to be explored and quantified.     

Evaluation of potential flavonoid inhibitors of glyoxalase-I based on virtual screening and in vitro studies

Glyoxalase-I (GLO-I) is a component of the ubiquitous detoxification system involved in the conversion of methylglyoxal (MG) to d-lactate in the glycolytic pathway. MG toxicity arises from its ability to form advanced glycation end products. GLO-I has been reported to be frequently overexpressed in various types of cancer cells. In this study, we performed structure-based virtual screening of focused flavonoids commercial library to identify potential and specific inhibitors of GLO-I. The compounds were ranked based on Glide extra precision docking score and five hits (curcumin, quercetin, morin, naringin and silibinin) were selected on the basis of their interaction with active site amino acid residues of GLO-I. Mixed mode QM/MM calculation was performed on the top-scoring hit to ascertain the role of zinc ion in ligand binding. In addition, the identified hits were subjected to MM/GBSA binding energy prediction, ADME prediction and similarity studies. The hits were tested in vitro for cell viability, and GLO-I inhibition. Naringin (ST072162) was found to be most potent inhibitor of GLO-I among the identified hits with highest glide XP dock score of ?14.906. These findings suggest that naringin could be a new scaffold for designing inhibitors against GLO-I with potential application as anticancer agents.     

Green synthesis of isoamyl acetate via silica immobilized novel thermophilic lipase from <Emphasis Type="Italic">Bacillus aerius</Emphasis>

Isoamyl acetate, a pear or banana flavor, is widely used in food, beverage, cosmetic, and pharmaceutical industries. In the present work, lipase from Bacillus aerius was immobilized on silica gel matrix in the presence of a cross-linking agent, glutaraldehyde, and its efficiency in synthesizing isoamyl acetate using esterification reaction was studied. The esterification of acetic acid and isoamyl alcohol by silica-bound lipase was studied as a function of time and temperatures. The incubation time of 10 h, temperature of 55°C, substrate molar ratio 1: 1, and the amount of lipase as 1% were found to be optimal for the esterification reaction. The bound lipase catalyzed the esterification of acetic acid by isoamyl alcohol with the yield of about 68% under the optimized reaction conditions. The product was identified as isoamyl acetate using gas-liquid chromatography, nuclear magnetic resonance, and Fourier transform IR spectroscopy analysis by the presence of an ester group at the wavenumber of 1720.5 cm^–1.