Nickel-Catalyzed Dehydrogenation of N-Heterocycles Using Molecular Oxygen.

Herein, an efficient and selective nickel-catalyzed dehydrogenation of five- and six-membered N-heterocycles is presented. The transformation occurs in the presence of alkyl, alkoxy, chloro, free hydroxyl and primary amine, internal and terminal olefin, trifluoromethyl, and ester functional groups. Synthesis of an important ligand and the antimalarial drug quinine is demonstrated.

Side-Chain Proline-Based Polymers as Effective Inhibitors for In Vitro Aggregation of Insulin.

Insulin fibril formation is considered as the hallmark of several debilitating pathological conditions. To develop effective therapeutics that are able to control the amyloidogenesis process and inhibit fibril formation, herein we have designed a side-chain proline (Pro)-based homopolymer and block copolymers through the reversible addition-fragmentation chain transfer (RAFT) polymerization technique and further explored their obligatory role in the in vitro insulin fibrillation process. Using a variety of biophysical tools, including turbidity measurements, thioflavin T (ThT) fluorescence kinetics, tyrosine (Tyr) fluorescence study, Nile red (NR) fluorescence assay, dynamic light scattering (DLS) study, circular dichroism (CD) measurements, and isothermal titration calorimetry (ITC) techniques, we demonstrated that Pro-based polymers can significantly inhibit the insulin fibrillation process.

KRAS Preferentially Signals through MAPK in a RAF Dimer-Dependent Manner in Non-Small Cell Lung Cancer.

Assembly of RAS molecules into complexes at the cell membrane is critical for RAS signaling. We previously showed that oncogenic KRAS codon 61 mutations increase its affinity for RAF, raising the possibility that KRAS, the most common KRAS mutation at codon 61, upregulates RAS signaling through mechanisms at the level of RAS assemblies. We show here that KRAS exhibits preferential binding to RAF relative to PI3K in cells, leading to enhanced MAPK signaling in models and human NSCLC tumors.

Coordination polymers of Ag(i) and Hg(i) ions with 2,2'-azobispyridine: synthesis, characterization and enhancement of conductivity in the presence of Cu(ii) ions.

The cationic coordination polymers (CPs) of the types [Hg(abpy)][PF] (1) and [Ag(abpy)][PF] (2) (abpy = 2,2'-azobispyridine) were synthesized and characterized. Experimentation using the crystals confirmed that 1 and 2 are conductors of electricity. The relative conductivity of 1 is 62 times greater than that of 2.

Evolution of confined ice nano structures at different levels of pore filling: a synchrotron based X-ray diffraction study.

We have thoroughly investigated the crystal structure of ice evolved from super cooled water confined in MCM-41 cylindrical nano pores through a synchrotron-based X-ray diffraction (XRD) technique for two different levels of pore filling. A rigorous analysis of XRD data shows that the nucleation dynamics and the structure of nucleated ice highly depend on the level of pore filling. In the nearly fully hydrated pores, ice crystallites start nucleating inside the pores below 240 K and creep out of the pores to form bulk crystals having crystalline structure of a mixed phase of hexagonal and cubic forms.

Regulation of Epithelial-to-Mesenchymal Transition by Alternative Translation Initiation Mechanisms and Its Implications for Cancer Metastasis.

Translation initiation plays a critical role in the regulation of gene expression for development and disease conditions. During the processes of development and disease, cells select specific mRNAs to be translated by controlling the use of diverse translation initiation mechanisms. Cells often switch translation initiation from a cap-dependent to a cap-independent mechanism during epithelial-to-mesenchymal transition (EMT), a process that plays an important role in both development and disease.

Broodstock development and captive maturation of hilsa (Tenualosa ilisha) in a brackishwater pond-based system.

Successful captive broodstock development of clupeid fish, hilsa, is one of the major challenges for the artificial propagation of this economically valued fish. The present study provides novel insights into the pond-reared captive broodstock development of hilsa using artificial feed. In the present study, wild collected hilsa fry (weight 1.

Structure and Characterization of a Covalent Inhibitor of Src Kinase.

Unregulated Src activity promotes malignant processes in cancer, but no Src-directed targeted therapies are used clinically, possibly because early Src inhibitors produce off-target effects leading to toxicity. Improved selective Src inhibitors may enable Src-directed therapies. Previously, we reported an irreversible Src inhibitor, DGY-06-116, based on the hybridization of dasatinib and a promiscuous covalent kinase probe SM1-71.

Cellular stress orchestrates the localization of hnRNP H to stress granules.

Heterogeneous nuclear ribonucleoprotein (hnRNP) H is a member of hnRNP H/F protein subfamily of hnRNPs that regulate the maturation and post-transcriptional processing of pre-mRNA. As a component of an mRNA export complex, hnRNP H shuttles mature mRNA from the nucleus to the cytoplasm. Although hnRNP H is primarily a nuclear protein, it can accumulate in the cytoplasm in certain tissues and cell types; however, the physiological relevance of hnRNP H cytoplasmic accumulation is unknown.

Molecular Insight into TdfH-Mediated Zinc Piracy from Human Calprotectin by Neisseria gonorrhoeae.

, responsible for the sexually transmitted infection gonorrhea, is an obligate human pathogen exquisitely adapted for survival on mucosal surfaces of humans. This host-pathogen relationship has resulted in evolution by of pathways that enable the use of host metalloproteins as required nutrients through the deployment of outer membrane-bound TonB-dependent transporters (TdTs). Recently, a TdT called TdfH was implicated in binding to calprotectin (CP) and in removal of the bound zinc (Zn), enabling gonococcal growth.

Modulation of acid-sensing ion channels by hydrogen sulfide.

Acid-sensing ion channels (ASICs) have been implicated in many physiological and patho-physiological processes like synaptic plasticity, inflammation, pain perception, stroke-induced brain damage and, drug-seeking behaviour. Although ASICs have been shown to be modulated by gasotransmitters like nitric oxide (NO), their regulation by hydrogen sulfide (HS) is not known. Here, we present strong evidence that HS potentiates ASICs-mediated currents.

Nickel-catalyzed hydrogen-borrowing strategy: chemo-selective alkylation of nitriles with alcohols.

The first nickel-catalyzed hydrogen-borrowing alkylation of a series of aryl acetonitriles with a variety of aryl, heteroaryl, allylic and alkyl alcohols releasing water as the by-product (>33 examples, up to 90% yield) is reported.

Enhancement of Superconductivity by Amorphizing Molybdenum Silicide Films Using a Focused Ion Beam.

We have used focused ion beam irradiation to progressively cause defects in annealed molybdenum silicide thin films. Without the treatment, the films are superconducting with critical temperature of about 1 K. We observe that both resistivity and critical temperature increase as the ion dose is increased.

In situ-grown organo-lead bromide perovskite-induced electroactive γ-phase in aerogel PVDF films: an efficient photoactive material for piezoelectric energy harvesting and photodetector applications.

The unique combination of piezoelectric energy harvesters and light detectors progressively strengthens their application in the development of modern electronics. Here, for the first time, we fabricated a polyvinylidene fluoride (PVDF) and formamidinium lead bromide nanoparticle (FAPbBr3 NP)-based composite aerogel film (FAPbBr3/PVDF) for harvesting electrical energy and photodetector applications. The uniform distribution of FAPbBr3 NPs in FAPbBr3/PVDF was achieved via the in situ synthesis of FAPbBr3 NPs in the PVDF matrix, which led to the stabilization of the γ-phase.

GTP hydrolysis is modulated by Arg34 in the RASopathy-associated KRAS.

RAS proteins are commonly mutated in cancerous tumors, but germline RAS mutations are also found in RASopathy syndromes such as Noonan syndrome (NS) and cardiofaciocutaneous (CFC) syndrome. Activating RAS mutations can be subclassified based on their activating mechanisms. Understanding the structural basis for these mechanisms may provide clues for how to manage associated health conditions.

Proteomic Analysis of Inflammatory Biomarkers Associated With Breast Cancer Recurrence.

Introduction: Breast cancer is the most frequent cancer detected for women, and while our ability to treat breast cancer has improved substantially over the years, recurrence remains a major obstacle. Standard screening for new and recurrent breast cancer involves clinical breast imaging. However, there is no clinically approved noninvasive body fluid test for the early detection of recurrent breast cancer.

A randomized, phase 1, placebo-controlled trial of APG-157 in oral cancer demonstrates systemic absorption and an inhibitory effect on cytokines and tumor-associated microbes.

Background: Although curcumin's effect on head and neck cancer has been studied in vitro and in vivo, to the authors' knowledge its efficacy is limited by poor systemic absorption from oral administration. APG-157 is a botanical drug containing multiple polyphenols, including curcumin, developed under the US Food and Drug Administration's Botanical Drug Development, that delivers the active components to oromucosal tissues near the tumor target.

Methods: A double-blind, randomized, placebo-controlled, phase 1 clinical trial was conducted with APG-157 in 13 normal subjects and 12 patients with oral cancer.

Gonadal recrudescence and annual reproductive hormone pattern of captive female Spotted Scats (Scatophagus argus).

The Spotted Scat (Scatophagus argus), an important euryhaline fish inhabiting mangrove and coastal regions of Indo-Pacific waters, is both an ornamental and food fish in India. Detailed insight into maturation of Spotted Scat when maintained in aquaculture systems, therefore, needs to be elucidated. Lack of information on annual maturation dynamics of female scat collected from their natural habitat and reared in earthen ponds is the basis of this study.

Publisher Correction: Green Synthesis of Substituted Anilines and Quinazolines from Isatoic Anhydride-8-amide.

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

A Natural Quinazoline Derivative from Marine Sponge Induces Apoptosis of Breast Cancer Cells via ROS Production and Intrinsic or Extrinsic Apoptosis Pathways.

Here, we report the therapeutic potential of a natural quinazoline derivative (2-chloro-6-phenyl-8H-quinazolino[4,3-b]quinazolin-8-one) isolated from marine sponge against human breast cancer. The cytotoxicity of the compound was investigated on a human breast carcinoma cell line (MCF-7). Antiproliferative activity of the compound was estimated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.

Morphological interference of two different cobalt oxides derived from a hydrothermal protocol and a single two-dimensional metal organic framework precursor to stabilize the β-phase of PVDF for flexible piezoelectric nanogenerators.

Here, we have fabricated a piezoelectric nanogenerator (PENG) composed of a Co-oxide (CoO) doped electro active PVDF based nanocomposite for efficient piezoelectric energy harvesting application where the CoO inclusion favours nucleation and polar β-phase stabilization in the nanocomposite. The morphological effect on the nucleation and β-phase stabilisation of PVDF has been explored experimentally. The flake-like morphology of CoO nanoparticles, synthesized by using a MOF, has a more effective surface area to nucleate and stabilise the β-phase of PVDF than that of rod-like (hydrothermal) and spherical (commercial) nanoparticles.

Modeling Data-Driven Dominance Traits for Virtual Characters Using Gait Analysis.

We present a data-driven algorithm for generating gaits of virtual characters with varying dominance traits. Our formulation utilizes a user study to establish a data-driven dominance mapping between gaits and dominance labels. We use our dominance mapping to generate walking gaits for virtual characters that exhibit a variety of dominance traits while interacting with the user.

Is Real-Time PCR Targeting Rep 529 Suitable for Diagnosis of Toxoplasmosis in Patients Infected with Non-Type II Strains in North America?

DNA detection is essential to antenatally diagnose a congenital infection and reactivation of a past infection in an immunocompromised patient. Initially, PCR methods targeted the 35-fold repetitive B1 gene, and more recently, coding sequence Rep 529 has been preferred, as it was reported to be repeated 200- to 300-fold and yielded far better sensitivity than amplification of the B1 sequence. To date, few data are available in regard to the efficacy of Rep 529 for non-type II genotypes.

Natural Compounds with Anti-BACE1 Activity as Promising Therapeutic Drugs for Treating Alzheimer's Disease.

Alzheimer's disease is a neurodegenerative disease that leads to irreversible neuronal damage. Senile plaques, composed of amyloid beta peptide, is the principal abnormal characteristic of the disease. Among the factors involved, the secretase enzymes, namely, secretase, beta-site amyloid precursor protein-cleaving enzyme, secretase, and secretase, hold consequential importance.