Arthroscopic Lower Trapezius Tendon Transfer for a Patient with Axillary Nerve Injury and Concomitant Rotator Cuff Tear: A Case Report and Technical Notes.

: Concomitant nerve injuries with musculoskeletal injuries present a challenging problem. The goals of nerve reconstruction for the shoulder include shoulder abduction and external rotation. When patients fail to achieve acceptable shoulder external rotation and shoulder abduction, tendon transfers such as trapezius transfer offer a reliable option in the subsequent stage.

Respondents of health survey powered by the innovative NURO app exhibit correlations between exercise frequencies and diet habits, and between stress levels and sleep wellness.

Nurosene's NURO app (nurosene.com) is an innovative smartphone application that gathers and analyzes active self-report metrics from users, empowering them with data-driven health machine intelligence. We present the data collected and analyzed from the initial round of participants who responded to a 12-question survey on their life-style and health status.

A Dual Inhibitor of DYRK1A and GSK3β for β-Cell Proliferation: Aminopyrazine Derivative GNF4877.

Loss of β-cell mass and function can lead to insufficient insulin levels and ultimately to hyperglycemia and diabetes mellitus. The mainstream treatment approach involves regulation of insulin levels; however, approaches intended to increase β-cell mass are less developed. Promoting β-cell proliferation with low-molecular-weight inhibitors of dual-specificity tyrosine-regulated kinase 1A (DYRK1A) offers the potential to treat diabetes with oral therapies by restoring β-cell mass, insulin content and glycemic control.

Selective DYRK1A Inhibitor for the Treatment of Type 1 Diabetes: Discovery of 6-Azaindole Derivative GNF2133.

Autoimmune deficiency and destruction in either β-cell mass or function can cause insufficient insulin levels and, as a result, hyperglycemia and diabetes. Thus, promoting β-cell proliferation could be one approach toward diabetes intervention. In this report we describe the discovery of a potent and selective DYRK1A inhibitor GNF2133, which was identified through optimization of a 6-azaindole screening hit.

One-Pot Electrochemical Nickel-Catalyzed Decarboxylative Sp-Sp Cross-Coupling.

A one-pot electrochemical nickel-catalyzed decarboxylative sp-sp cross-coupling reaction has been developed using redox-active esters prepared in situ from alkyl carboxylates and  N-hydroxyphthalimide tetramethyluronium hexafluorophosphate (PITU). This undivided cell one-pot method enables C-C bond formation using inexpensive, benchtop-stable reagents with isolated yields up to 95% with good functional group tolerance, which includes nitrile, ketone, ester, alkene and selectivity over other aromatic halogens.

Generation and Cross-Coupling of Organozinc Reagents in Flow.

A versatile flow synthesis method for in situ formation of organozinc reagents and subsequent cross-coupling with aryl halides and activated carboxylic acids is reported. Formation of organozinc reagents is achieved by pumping organic halides, in the presence of ZnCl and LiCl, through an activated Mg-packed column under flow conditions. This method provides efficient in situ formation of aryl, primary, secondary, and tertiary alkyl organozinc reagents, which are subsequently telescoped downstream to a Negishi or decarboxylative Negishi cross-coupling reaction.

Species Delimitation, Phylogenetic Relationships, and Temporal Divergence Model in the Genus .

The definition of species boundaries constitutes an important challenge in biodiversity studies. In this work we applied the Generalized Mixed Yule Coalescent (GMYC) method, which determines a divergence threshold to delimit species in a phylogenetic tree. Based on the tree branching pattern, the analysis fixes the transition threshold between speciation and the coalescent process associated with the intra-species diversification.

Tuning a Protein-Labeling Reaction to Achieve Highly Site Selective Lysine Conjugation.

Activated esters are widely used to label proteins at lysine side chains and N termini. These reagents are useful for labeling virtually any protein, but robust reactivity toward primary amines generally precludes site-selective modification. In a unique case, fluorophenyl esters are shown to preferentially label human kappa antibodies at a single lysine (Lys188) within the light-chain constant domain.

Evolutionary Roots and Diversification of the Genus .

Despite the importance of diversification rates in the study of prokaryote evolution, they have not been quantitatively assessed for the majority of microorganism taxa. The investigation of evolutionary patterns in prokaryotes constitutes a challenge due to a very scarce fossil record, limited morphological differentiation and frequently complex taxonomic relationships, which make even species recognition difficult. Although the speciation models and speciation rates in eukaryotes have traditionally been established by analyzing the fossil record data, this is frequently incomplete, and not always available.

Optimization of Platelet-Derived Growth Factor Receptor (PDGFR) Inhibitors for Duration of Action, as an Inhaled Therapy for Lung Remodeling in Pulmonary Arterial Hypertension.

A series of potent PDGFR inhibitors has been identified. The series was optimized for duration of action in the lung. A novel kinase occupancy assay was used to directly measure target occupancy after i.

Direct evidence of recombination in the recA gene of Aeromonas bestiarum.

Two hundred and twenty-one strains representative of all Aeromonas species were characterized using the recA gene sequence, assessing its potential as a molecular marker for the genus Aeromonas. The inter-species distance values obtained demonstrated that recA has a high discriminatory power. Phylogenetic analysis, based on full-length gene nucleotide sequences, revealed a robust topology with clearly separated clusters for each species.

(R)-2-Phenylpyrrolidine Substituted Imidazopyridazines: A New Class of Potent and Selective Pan-TRK Inhibitors.

Deregulated kinase activities of tropomyosin receptor kinase (TRK) family members have been shown to be associated with tumorigenesis and poor prognosis in a variety of cancer types. In particular, several chromosomal rearrangements involving TRKA have been reported in colorectal, papillary thyroid, glioblastoma, melanoma, and lung tissue that are believed to be the key oncogenic driver in these tumors. By screening the Novartis compound collection, a novel imidazopyridazine TRK inhibitor was identified that served as a launching point for drug optimization.

TrkB inhibition by GNF-4256 slows growth and enhances chemotherapeutic efficacy in neuroblastoma xenografts.

Purpose: Neuroblastoma (NB) is one of the most common and deadly pediatric solid tumors. NB is characterized by clinical heterogeneity, from spontaneous regression to relentless progression despite intensive multimodality therapy. There is compelling evidence that members of the tropomyosin receptor kinase (Trk) family play important roles in these disparate clinical behaviors.

Molecular phylogenetics and temporal diversification in the genus Aeromonas based on the sequences of five housekeeping genes.

Several approaches have been developed to estimate both the relative and absolute rates of speciation and extinction within clades based on molecular phylogenetic reconstructions of evolutionary relationships, according to an underlying model of diversification. However, the macroevolutionary models established for eukaryotes have scarcely been used with prokaryotes. We have investigated the rate and pattern of cladogenesis in the genus Aeromonas (γ-Proteobacteria, Proteobacteria, Bacteria) using the sequences of five housekeeping genes and an uncorrelated relaxed-clock approach.

Liver X receptor modulators: a review of recently patented compounds (2009 - 2012).

Introduction: The development of small molecule agonists of the liver X receptors (LXRs) has been an area of interest for over a decade, given the critical role of those receptors in cholesterol metabolism, glucose homeostasis, inflammation, innate immunity and lipogenesis. Many potential indications have been characterized over time including atherosclerosis, diabetes, inflammation, Alzheimer's disease and cancer. However, concerns about the lipogenic effects of full LXRα/β agonists have required extensive efforts aimed at identifying LXRβ agonist with limited activity on the LXRα receptor to increase the safety margins.

Draft Genome Sequence of the Aeromonas diversa Type Strain.

We present here the first genome sequence of the Aeromonas diversa type strain (CECT 4254(T)). This strain was isolated from the leg wound of a patient in New Orleans (Louisiana) and was originally described as enteric group 501 and distinguished from A. schubertii by DNA-DNA hybridization and phenotypical characterization.

Draft Genome Sequence of Aeromonas molluscorum Strain 848TT, Isolated from Bivalve Molluscs.

We report here the draft genome sequence of Aeromonas molluscorum 848T, the type strain of this Aeromonas species, which was isolated from wedge shells (Donax trunculus) obtained from a retail market in Barcelona, Spain, in 1997.

Reclassification of Aeromonas hydrophila subspecies anaerogenes.

Technological advances together with the continuous description of new taxa have led to frequent reclassifications in bacterial taxonomy. In this study, an extensive bibliographic revision, as well as a sequence analysis of nine housekeeping genes (cpn60, dnaJ, dnaX, gyrA, gyrB, mdh, recA, rpoB and rpoD) and a phenotypic identification of Aeromonas hydrophila subspecies anaerogenes were performed. All data obtained from previous physiological, phylogenetic, and DNA-DNA hybridization studies together with those presented in this study suggested that A.

Discovery of GNF-5837, a Selective TRK Inhibitor with Efficacy in Rodent Cancer Tumor Models.

Neurotrophins and their receptors (TRKs) play key roles in the development of the nervous system and the maintenance of the neural network. Accumulating evidence points to their role in malignant transformations, chemotaxis, metastasis, and survival signaling and may contribute to the pathogenesis of a variety of tumors of both neural and non-neural origin. By screening the GNF kinase collection, a series of novel oxindole inhibitors of TRKs were identified.

Synthesis of a D3-symmetric "trefoil" knotted cyclophane.

A D(3)-symmetric knotted cyclophane, with a subgraph of trefoil topology, was synthesized by cyclization of a D(3)-symmetric scaffold. Control of configuration at the three metal-based stereocenters arises from a bascule/pivot mechanism.

Malate dehydrogenase: a useful phylogenetic marker for the genus Aeromonas.

The reconstruction of correct genealogies among biological entities, the estimation of the divergence time between organisms or the study of the different events that occur along evolutionary lineages are not always based on suitable genes. For reliable results, it is necessary to look at full-length sequences of genes under stabilizing selection (neutral or purifying) and behaving as good molecular clocks. In bacteria it has been proved that the malate dehydrogenase gene (mdh) can be used to determine the inter- and intraspecies divergence, and hence this gene constitutes a potential marker for phylogeny and bacterial population genetics.

Prediction of whole-genome DNA G+C content within the genus Aeromonas based on housekeeping gene sequences.

Different methods are available to determine the G+C content (e.g. thermal denaturation temperature or high performance liquid chromatography, HPLC), but obtained values may differ significantly between strains, as well as between laboratories.

The reference strain Aeromonas hydrophicla CIP 57.50 should be reclassified as Aeromonas salmonicida CIP 57.50.

The use of reference strains is a critical element for the quality control of different assays, from the development of molecular methods to the evaluation of antimicrobial activities. Most of the strains used in these assays are not type strains and some of them are cited erroneously because of subsequent reclassifications and descriptions of novel species. In this study, we propose that the reference strain Aeromonas hydrophila CIP 57.

Reclassification of Geobacillus pallidus (Scholz et al. 1988) Banat et al. 2004 as Aeribacillus pallidus gen. nov., comb. nov.

Although Anoxybacillus and Geobacillus, two genera of thermophilic bacteria close to the genus Bacillus, have only been described recently, the number of species in these genera has increased rapidly. Four thermophilic, lipolytic strains (DR01, DR02, DR03 and DR04) isolated from a hot spring in Veracruz (Mexico), which could not be identified phenotypically, were subjected to 16S rRNA gene sequence analysis. Three strains were identified as belonging to the genus Anoxybacillus, but strain DR03 was identified as Geobacillus pallidus.

Divergent evolution and purifying selection of the flaA gene sequences in Aeromonas.

Background: The bacterial flagellum is the most important organelle of motility in bacteria and plays a key role in many bacterial lifestyles, including virulence. The flagellum also provides a paradigm of how hierarchical gene regulation, intricate protein-protein interactions and controlled protein secretion can result in the assembly of a complex multi-protein structure tightly orchestrated in time and space. As if to stress its importance, plants and animals produce receptors specifically dedicated to the recognition of flagella.