Scalable Electrochemical Decarboxylative Olefination Driven by Alternating Polarity.

A mild, scalable (kg) metal-free electrochemical decarboxylation of alkyl carboxylic acids to olefins is disclosed. Numerous applications are presented wherein this transformation can simplify alkene synthesis and provide alternative synthetic access to valuable olefins from simple carboxylic acid feedstocks. This robust method relies on alternating polarity to maintain the quality of the electrode surface and local pH, providing a deeper understanding of the Hofer-Moest process with unprecedented chemoselectivity.

Room-temperature magnetoresistance in NiFe/C8-BTBT/NiFe nanojunctions fabricated from magnetic thin-film edges using a novel technique.

Molecular spintronic devices are gaining popularity because the organic semiconductors with long spin relaxation times are expected to have long spin diffusion lengths. A typical molecular spintronic device consists of organic molecules sandwiched between two magnetic layers, which exhibits magnetoresistance (MR) effect. Nanosized devices are also expected to have a high spin polarization, leading to a large MR effect owing to effective orbital hybridization.

Highly Potent and Oral Macrocyclic Peptides as a HIV-1 Protease Inhibitor: mRNA Display-Derived Hit-to-Lead Optimization.

Human immunodeficiency virus type-1 (HIV-1) protease is essential for viral propagation, and its inhibitors are key anti-HIV-1 drug candidates. In this study, we discovered a novel HIV-1 protease inhibitor (compound ) with potent antiviral activity and oral bioavailability using a structure-based drug design approach via X-ray crystal structure analysis and improved metabolic stability, starting from hit macrocyclic peptides identified by mRNA display against HIV-1 protease. We found that the improvement of the proteolytic stability of macrocyclic peptides by introducing a methyl group to the α-position of amino acid is crucial to exhibit strong antiviral activity.

Chemoselective (Hetero)Arene Electroreduction Enabled by Rapid Alternating Polarity.

Conventional chemical and even electrochemical Birch-type reductions suffer from a lack of chemoselectivity due to a reliance on alkali metals or harshly reducing conditions. This study reveals that a simpler avenue is available for such reductions by simply altering the waveform of current delivery, namely rapid alternating polarity (rAP). The developed method solves these issues, proceeding in a protic solvent, and can be easily scaled up without any metal additives or stringently anhydrous conditions.

Chemoselective Electrosynthesis Using Rapid Alternating Polarity.

Challenges in the selective manipulation of functional groups (chemoselectivity) in organic synthesis have historically been overcome either by using reagents/catalysts that tunably interact with a substrate or through modification to shield undesired sites of reactivity (protecting groups). Although electrochemistry offers precise redox control to achieve unique chemoselectivity, this approach often becomes challenging in the presence of multiple redox-active functionalities. Historically, electrosynthesis has been performed almost solely by using direct current (DC).

Macrocyclic Peptides as a Novel Class of NNMT Inhibitors: A SAR Study Aimed at Inhibitory Activity in the Cell.

Nicotinamide -methyltransferase (NNMT), which catalyzes the methylation of nicotinamide, is a cytosolic enzyme that has attracted much attention as a therapeutic target for a variety of diseases. However, despite the considerable interest in this target, reports of NNMT inhibitors have still been limited to date. In this work, utilizing translated macrocyclic peptide libraries, we identified peptide as a novel class of NNMT inhibitors.

Discovery of a benzimidazole series as the first highly potent and selective ACSL1 inhibitors.

Long-chain acyl-CoA synthetase-1 (ACSL1), an enzyme that catalyzes the synthesis of long-chain acyl-CoA from the corresponding fatty acids, is believed to play essential roles in lipid metabolism. Structure activity relationship studies based on HTS hit compound 1 delivered the benzimidazole series as the first selective and highly potent ACSL1 inhibitors. Representative compound 13 exhibited not only remarkable inhibitory activity against ACSL1 (IC = 0.

Mechanical properties of temperature-responsive gels containing ethylene glycol in their side chains.

The mechanical properties of temperature-responsive and biocompatible poly(oligo-ethylene glycol methyl ether methacrylate)-based gels were investigated using dynamic viscoelasticity measurements so as to find applications in tissue and biomedical engineering. The gels were copolymerized using two ethylene glycol methacrylate monomers with diethylene glycol side chains: diethylene glycol methacrylate (MeOMA), which contains two ethylene oxide units, and oligo-ethylene glycol methyl ether methacrylate (OEGMA) with either four or five ethylene oxide units. The storage (G') and loss (G'') moduli of these gels exhibit unique temperature-responsive behavior and depend on the copolymerization ratio.

Development of an anti-hepatitis B virus (HBV) agent through the structure-activity relationship of the interferon-like small compound CDM-3008.

Hepatitis B, a viral infectious disease caused by hepatitis B virus (HBV), is a life-threatening disease that leads liver cirrhosis and liver cancer. Because the current treatments for HBV, such as an interferon (IFN) formulation or nucleoside/nucleotide analogues, are not sufficient, the development of a more effective agent for HBV is urgent required. CDM-3008 (1, 2-(2,4-bis(trifluoromethyl)imidazo[1,2-a][1,8]naphthyridin-8-yl)-1,3,4-oxadiazole) (RO8191)) is a small molecule with an imidazo[1,2-a][1,8]naphthyridine scaffold that shows anti-HCV activity with an IFN-like effect.

Aggravation of diabetes, and incompletely deficient insulin secretion in a case with type 1 diabetes-resistant human leukocyte antigen DRB1*15:02 treated with nivolumab.

Anti-programmed cell death-1 (PD-1) antibody therapy induces various adverse effects, especially in the endocrine system. Several cases of acute-onset insulin-dependent diabetes after anti-PD-1 antibody therapy have been reported. Many of these cases have a susceptible human leukocyte antigen (HLA) genotype for type 1 diabetes, possibly suggesting that HLA might be involved in the onset of diabetes with anti-PD-1 therapy.

The USP8 mutational status may predict drug susceptibility in corticotroph adenomas of Cushing's disease.

Context: Somatic mutations in the ubiquitin-specific peptidase USP8 gene were recently detected in one- to two-third(s) of corticotroph adenomas of Cushing's disease (CD). These mutations may lead to the deubiquitination of EGFR, thereby increasing EGFR signaling, which has been implicated in ACTH hypersecretion.

Objective: Our objective was to determine the impact of USP8 mutations on the clinicopathological features of CD.

The Complementary Role of Transcription Factors in the Accurate Diagnosis of Clinically Nonfunctioning Pituitary Adenomas.

Clinically nonfunctioning pituitary adenomas (NFAs) may be hormonally inactive tumors of differentiated cells, mainly not only gonadotroph adenomas (GAs) but also silent corticotroph adenomas (SCAs) and other differentiated silent adenomas. Recently, the use of transcription factors has been recommended to confirm cytodiffererentiation of these neoplasms. Our objective was to assess the clinical significance of the new classification system using transcription factors.

Molecular identification and characterization of clustered regularly interspaced short palindromic repeat (CRISPR) gene cluster in Taylorella equigenitalis.

Clustered regularly interspaced short palindromic repeats (CRISPRs), of approximately 10,000 base pairs (bp) in length, were shown to occur in the Japanese Taylorella equigenitalis strain, EQ59. The locus was composed of the putative CRISPRs-associated with 5 (cas5), RAMP csd1, csd2, recB, cas1, a leader region, 13 CRISPR consensus sequence repeats (each 32 bp; 5'-TCAGCCACGTTCGCGTGGCTGTGTGTTTAAAG-3'). These were in turn separated by 12 non repetitive unique spacer regions of similar length.

Purification and characterization of oxygen-inducible haem catalase from oxygen-tolerant Bifidobacterium asteroides.

Bifidobacterium asteroides, originally isolated from honeybee intestine, was found to grow under 20% O(2) conditions in liquid shaking culture using MRS broth. Catalase activity was detected only in cells that were exposed to O(2) and grown in medium containing a haem source, and these cells showed higher viability on exposure to H(2)O(2). Passage through multiple column chromatography steps enabled purification of the active protein, which was identified as a homologue of haem catalase on the basis of its N-terminal sequence.

Efficient synthesis of α,β-unsaturated alkylimines performed with allyl cations and azides: application to the synthesis of an ant venom alkaloid.

An efficient synthesis of α,β-unsaturated alkylimines at low temperature using azides has been developed. Carbocations generated from allyl alcohols helped achieve a rapid conversion under mild conditions with azides to afford reactive α,β-unsaturated imines. Hydroxy or alkoxy groups are essential for these transformations, and utilizing readily accessible allyl alcohols gave a wide extension of substrates.

Phylogenetic analysis of urease-positive thermophilic Campylobacter (UPTC) strains based on the molecular characterization of the flaA gene.

Molecular cloning, nucleotide sequencing, and characterization of the flaA gene from additional isolates of urease-positive thermophilic Campylobacter (UPTC) were performed. These isolates were obtained from the natural environment in Northern Ireland (n = 9 from mussels) and in England (n = 1 from sea water). All isolates carried the shorter flaA gene, [open reading frames (ORFs), 1,461 to 1,503 base pairs], without any internal termination codons, and did not carry any flaA pseudogenes.

Demonstration of the absence of intervening sequences (IVSs) within 16S rRNA genes of Taylorella equigenitalis and Taylorella asinigenitalis isolates.

A total of 57 Taylorella equigenitalis (n=22) and Taylorella asinigenitalis (n=35) isolates was shown not to carry any intervening sequences (IVSs) within 16S rRNA gene sequences. By contrast, we have already shown the genus Taylorella group to carry several kinds of IVSs within the 23S rRNA gene sequences.

Critical factors in the limited occurrence of the Japanese tree sap mite Hericia sanukiensis (Acari: Astigmata: Algophagidae) inhabiting the sap of the oak Quercus acutissima.

Hericia sanukiensis (Astigmata: Algophagidae) is a semi-aquatic mite inhabiting fermented sap flux of the Japanese sawtooth oak (Quercus acutissima) and utilizes Nitidulidae (Coleoptera) as the dispersal (phoretic) carrier. Although nitidulid beetles are commonly found in sap flux, the occurrence of H. sanukiensis has been extremely limited to a few trees in Shikoku Island, Kagawa Prefecture, Japan.

A phylogenetic comparison of urease-positive thermophilic Campylobacter (UPTC) and urease-negative (UN) C. lari.

In the present study, the reliability of full-length gene sequence information for several genes including 16S rRNA was examined, for the discrimination of the two representative Campylobacter lari taxa, namely urease-negative (UN) C. lari and urease-positive thermophilic Campylobacter (UPTC). As previously described, 16S rRNA gene sequence are not reliable for the molecular discrimination of UN C.

Development of a new molecular detection method for Taylorella equigenitalis.

On PCR amplification of the intervening sequences (IVSs) in the central (helix 45) region within 23S rRNA gene sequences with T. equigenitalis (n = 34), as well as T. asinigenitalis (n = 35) and Bordetella (n = 11) isolates by using the primer pair of f-/r-23STis2, approximately 0.

Molecular identification and characterization of the intervening sequences (IVSs) within 23S ribosomal RNA (rRNA) genes of Taylorella asinigenitalis isolated in France.

In the helix 25 region, 32 French Taylorella asinigenitalis isolates carried at least one 23S rRNA gene not containing intervening sequences (IVSs). No IVSs in the region were identified in three isolates and the other remaining 29 isolates carried one or more IVSs (UCD-1(T)IVS1A, UCD-1(T)IVS1B and UK-1IVS1B) described already and two new kinds of IVS (TaIVS1C and TaIVS1D). In the helix 45 region, no T.

Prostate cancer risk in relation to insulin-like growth factor (IGF)-I and IGF-binding protein-3: A nested case-control study in large scale cohort study in Japan.

High levels of insulin-like growth factor (IGF)-I are reported to be associated with an increased risk of prostate cancer. On the other hand, the insulin-like growth factor binding protein-3 (IGFBP-3) may decrease the risk. We therefore investigated the influence of serum IGF-I and IGFBP-3 on prostate cancer risk in a case-control study nested within a large-scale cohort in Japan (the Japan Collaborative Cohort Study).

Life history of the newly discovered Japanese tree sap mite, Hericia sanukiensis (Acari, Astigmata, Algophagidae).

Hericia sanukiensis (Acari, Algophagidae) is a species of tree sap mite which has been newly discovered in the sap flux of oak trees (Quercus acutissima). In this study, we have clarified the life history of H. sanukiensis at the onset of sap exudation in spring, overwintering deutonymphs molt to tritonymphs as their molting is exacerbated by the sugar contained in the tree sap, and develop to adulthood and reproduce.

Stroke subtypes and lesion sites in Akita, Japan.

Stroke patients who underwent computed tomography (CT) were enrolled in a stroke registry in Akita, Japan, which comprised 7288 first-ever stroke cases during 1999 to 2001. Differences in age and sex were evaluated with respect to type-specific incidences and lesion sites. The incidence increased with age, except for subarachnoid hemorrhage (SAH) in men after age 40.

Diabetes mellitus and kidney cancer risk: the results of Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC Study).

Background: Diabetes mellitus (DM) is reported as being a risk factor associated with kidney cancer in Western countries. The incidence of both kidney cancer and DM is lower in Japan than the other developed countries, albeit on the rise.

Methods: We evaluated the risk factors for kidney cancer mortality using the database of the Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC) study.