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Three-stranded coiled coils are peptide structures constructed from amphipathic heptad repeats. Here we show that it is possible to form pure heterotrimeric three-stranded coiled coils by combining three distinct characteristics: (1) a cysteine sulfur layer for metal coordination, (2) a thiophilic, trigonal pyramidal metalloid (Pb(ii)) that binds to these sulfurs and (3) an adjacent layer of reduced steric bulk generating a cavity where water can hydrogen bond to the cysteine sulfur atoms. Cysteine substitution in an a site yields Pb(ii)A2B heterotrimers, while d sites provide pure Pb(ii)C2D or Pb(ii)CD2 scaffolds. Altering the metal from Pb(ii) to Hg(ii) or shifting the relative position of the sterically less demanding layer removes heterotrimer specificity. Because only two of the eight or ten hydrophobic layers are perturbed, catalytic sites can be introduced at other regions of the scaffold. A Zn(ii)(histidine)3(H2O) centre can be incorporated at a remote location without perturbing the heterotrimer selectivity, suggesting a unique strategy to prepare dissymmetric catalytic sites within self-assembling de novo-designed proteins.A method to fabricate heterotrimeric three-stranded coiled-coil peptide structures has now been developed using coordination around a Pb(ii) centre. The heterotrimeric structures require only three cysteines that bind to Pb(ii) to form a trigonal pyramidal structure, and the formation of an adjacent cavity in which water can hydrogen bond to the cysteine sulfur atoms.

We have rationally designed a peptide that assembles into a redox-responsive, antimicrobial metallohydrogel. The resulting self-healing material can be rapidly reduced by ascorbate under physiological conditions and demonstrates a remarkable 160-fold change in hydrogel stiffness upon reduction. We provide a computational model of the hydrogel, explaining why position of nitrogen in non-natural amino acid pyridyl-alanine results in drastically different gelation properties of peptides with metal ions. Given its antimicrobial and rheological properties, the newly designed hydrogel can be used for removable wound dressing application, addressing a major unmet need in clinical care.

Distilled propargyltrichlorosilane with >99% isomeric purity was prepared for the first time, and its asymmetric catalytic regiospecific addition reaction to aldehydes was developed through a systematic catalyst structure–reactivity and selectivity relationship study. The observed catalyst structure–enantioselectivity relationship of the present allenylation reaction was found exactly opposite to that of the analogous allylation reaction. The method provided eleven α-allenic alcohols in 22–99% yield with 61:39–92:8 enantiomeric ratios. Furthermore, possible mechanisms of propargyl–allenyl isomerization of propargyltrichlorosilane were computationally investigated.

Amyloid fibrils are β-sheet-rich protein aggregates commonly found in the organs and tissues of patients with various amyloid-associated diseases. Understanding the structural organization of amyloid fibrils can be beneficial for the search of drugs to successfully treat diseases associated with protein misfolding. The structure of insulin fibrils was characterized by deep ultraviolet resonance Raman (DUVRR) and Nuclear Magnetic Resonance (NMR) spectroscopy combined with hydrogen-deuterium exchange. The compositions of the fibril core and unordered parts were determined at single amino acid residue resolution. All three disulfide bonds of native insulin remained intact during the aggregation process, withstanding scrambling. Three out of four tyrosine residues were packed into the fibril core, and another aromatic amino acid, phenylalanine, was located in the unordered parts of insulin fibrils. In addition, using all-atom MD simulations, the disulfide bonds were confirmed to remain intact in the insulin dimer, which mimics the fibrillar form of insulin.

Insulin degrading enzyme (IDE) is believed to be the major enzyme that metabolizes insulin and has been implicated in the degradation of a number of other bioactive peptides, including amyloid beta peptide (Aβ), glucagon, amylin, and atrial natriuretic peptide. IDE is activated toward some substrates by both peptides and polyanions/anions, possibly representing an important control mechanism and a potential therapeutic target. A binding site for the polyanion ATP has previously been defined crystallographically, but mutagenesis studies suggest that other polyanion binding modes likely exist on the same extended surface that forms one wall of the substrate-binding chamber. Here we use a computational approach to define three potential ATP binding sites and mutagenesis and kinetic studies to confirm the relevance of these sites. Mutations were made at four positively charged residues (Arg 429, Arg 431, Arg 847, Lys 898) within the polyanion-binding region, converting them to polar or hydrophobic residues. We find that mutations in all three ATP binding sites strongly decrease the degree of activation by ATP and can lower basal activity and cooperativity. Computational analysis suggests conformational changes that result from polyanion binding as well as from mutating residues involved in polyanion binding. These findings indicate the presence of multiple polyanion binding modes and suggest the anion-binding surface plays an important conformational role in controlling IDE activity.

Genetic variations in the ITGAM gene (encoding CD11b) strongly associate with risk for systemic lupus erythematosus (SLE). Here we have shown that 3 nonsynonymous ITGAM variants that produce defective CD11b associate with elevated levels of type I interferon (IFN-I) in lupus, suggesting a direct link between reduced CD11b activity and the chronically increased inflammatory status in patients. Treatment with the small-molecule CD11b agonist LA1 led to partial integrin activation, reduced IFN-I responses in WT but not CD11b-deficient mice, and protected lupus-prone MRL/Lpr mice from end-organ injury. CD11b activation reduced TLR-dependent proinflammatory signaling in leukocytes and suppressed IFN-I signaling via an AKT/FOXO3/IFN regulatory factor 3/7 pathway. TLR-stimulated macrophages from CD11B SNP carriers showed increased basal expression of IFN regulatory factor 7 (IRF7) and IFN-β, as well as increased nuclear exclusion of FOXO3, which was suppressed by LA1-dependent activation of CD11b. This suggests that pharmacologic activation of CD11b could be a potential mechanism for developing SLE therapeutics.

India is a developing economy; here Corporate Social Responsibility (CSR) plays an important role in organizations. In Indian industry one can easily notice a paradigm shift from corporate philanthropist to being socially responsible. The importance of CSR is increasing in Indian corporate scenario because organizations have realized that the ultimate goal is not profit making; besides, this trust building is viable and assists in a functional societal relationship. The compulsion of CSR has emerged in last two decades when Indian organization realized the importance of sustaining in this cut-throat competition era. Before this Indian industries had a materialistic culture. In the hue and cry of LPG (Liberalization, Privatization and Globalization) companies were only focused towards profit maximization which led to social backwash. To overcome this fashion CSR play an important role in sustainable development which is only possible when there is a balance between profit and lowering social backwash or eradicating it. The problem with CSR is that nobody is very clear about what exactly it encompasses. The Indian government has been trying to make it mandatory for companies to spend at least 2% net profits on CSR. Today CSR to some companies means providing lunch to their employees or tackling global warning issues. Nowadays companies have become more transparent in their balance sheets. They are displaying public reporting in their accounting. Companies are incorporating their CSR initiatives in their annual report. This research paper tries to analyse the study of CSR status in India; this can give insight in to what extent companies can follow CSR. I would like to throw light on CSR for Indian organizations which would be helpful for both economic and social interests which would be a futuristic measure as it provides valuable information as well as suggests CSR practices and performance. thoughts.

High-grade gliomas are devastating cancers with dismal prognosis, largely because current chemotherapeutics fail to cross the blood-brain barrier and lack tumor-cell specificity. Nanotechnology aims to overcome these limitations through targeted drug delivery. Here, a quadruple-conjugated nanomodel was synthesized using carbon dots (C-dots) as biocompatible nanocarriers via a one-pot reaction that covalently links two targeting peptides and two anticancer agents. The short peptide (shPep-1) targets the tumor-restricted receptor IL13Rα2, whereas the long peptide (lnPep-1) contains a nuclear localization signal for enhanced intracellular trafficking. Therapeutic cargo consists of epirubicin and the temozolomide metabolite 5-aminoimidazole-4-carboxamide. This nanomodel displays potent cytotoxicity in multiple high-grade glioma cell lines at 50 nM while remaining relatively non-toxic to normal cells (IC₅₀ > 2 µM). Despite a lower drug-loading capacity than single-peptide formulations, it induced greater glioma cell death, underscoring the enhanced therapeutic synergy of its dual-peptide, dual-drug design. Fluorescence studies confirm superior uptake and nuclear delivery, establishing C-dots as a stable, cost-effective, modular platform for next-generation personalized cancer nanotherapies.

Current or Recent trends in management took place as today, organizations face rapid change due to globalization or change in the market conditions. In this paper latest/current/recent trends in organizational change would be addressed effectively in order to achieve overall objective. These trends came in focus due to certain changes in organizations, which some time took place to maximize the benefit and minimize the loss of organization. In today's corporate business environment there are several latest trends. Few are discussed in this paper. Such as 5'S' of Japanese management system and Kaizen. 5'S': Japanese factories and service organizations are well known for their cleanliness and orderliness. Suggests that this results from their ability to instil a sense of responsibility and discipline into their workers, particularly at plant level. Describes the Japanese 5-S practice, the logic behind which is that organization, neatness, cleanliness, standardization and discipline at the workplace are basic requirements for producing high-quality products and services, with little or no waste, while maintaining high levels of productivity. Aims to promote the 5-S technique and explore the reasons why it has been widely used in Japan as the first step towards TQM in both the manufacturing and services industries. Kaizen: Kaizen is a general approach to improvement, 5S is a way to lay the groundwork for improvement. The two go hand in hand with 5S being part of the Kaizen system and lean manufacturing. When we have a Kaizen 5S workplace we reflect an organization that values and implements continuous improvement. We can get great business results with this kind of Kaizen 5S approach. 5S can become an important means of business and a driver for an effective Kaizen continuous improvement environment. Employees in a 5S environment feel responsibility, ownership, and involvement. We also get a reduction in waste and improved quality and productivity. Morale is high and profitability increases. That is the idea behind the principles. In this study, we will discuss on 5S and Kaizen Japanese Techniques to improve growth in Business.

Employees are the essential part of any institution in the growth and existences of any organization so the welfare of employee is an important criterion that cannot be overlooked. Public sector and private sector banks are contributing in the welfare of employees. These welfare measures include housing facilities, medical benefit, retirement benefit, welfare measures for family member and loan facilities. Employee welfare is also important because if the organization only expecting high performance then its mere waste because it also provide motivational rip to the employees. The Banking Industry has a vital role in the economy of the country. State Bank of India is the nationalised owned bank where as HDFC is private sector bank. This paper will explain the clear depiction and comparative analysis on welfare measures in both the sectors bank. For this purpose a study of 200 respondents was conducted from employees of both the banks in Gorakhpur region.