Cooperative Substructure and Energetics of Allosteric Regulation of the Catalytic Core of the E3 Ubiquitin Ligase Parkin by Phosphorylated Ubiquitin.

Mutations in the parkin gene product Parkin give rise to autosomal recessive juvenile parkinsonism. Parkin is an E3 ubiquitin ligase that is a critical participant in the process of mitophagy. Parkin has a complex structure that integrates several allosteric signals to maintain precise control of its catalytic activity.

Switching the proton-coupled electron transfer mechanism for non-canonical tyrosine residues in a protein.

The proton-coupled electron transfer (PCET) reactions of tyrosine (Y) are instrumental to many redox reactions in nature. This study investigates how the local environment and the thermodynamic properties of Y influence its PCET characteristics. Herein, 2- and 4-mercaptophenol (MP) are placed in the well-folded αC protein (forming 2MP-αC and 4MP-αC) and oxidized by external light-generated [Ru(L)] complexes.

Anti-tumor effects of cryptotanshinone (CHO) in human osteosarcoma cell lines.

Osteosarcoma is the most prevalent malignant bone tumor and occurs most commonly in the adolescent and young adult population. Despite the recent advances in surgeries and chemotherapy, the overall survival in patients with resectable metastases is around 20%. This challenge in osteosarcoma is often attributed to the drastic differences in the tumorigenic profiles and mutations among patients.

Targeting oncogenic mutations in colorectal cancer using cryptotanshinone.

Colorectal cancer (CRC) is one of the most prevalent types of cancer in the world and ranks second in cancer deaths in the US. Despite the recent improvements in screening and treatment, the number of deaths associated with CRC is still very significant. The complexities involved in CRC therapy stem from multiple oncogenic mutations and crosstalk between abnormal pathways.

Comprehensive live-cell imaging analysis of cryptotanshinone and synergistic drug-screening effects in various human and canine cancer cell lines.

Background: Several studies have highlighted both the extreme anticancer effects of Cryptotanshinone (CT), a Stat3 crippling component from Salvia miltiorrhiza, as well as other STAT3 inhibitors to fight cancer.

Methods: Data presented in this experiment incorporates 2 years of in vitro studies applying a comprehensive live-cell drug-screening analysis of human and canine cancer cells exposed to CT at 20 μM concentration, as well as to other drug combinations. As previously observed in other studies, dogs are natural cancer models, given to their similarity in cancer genetics, epidemiology and disease progression compared to humans.

In Silico Modeling of the Induction of Apoptosis by Cryptotanshinone in Osteosarcoma Cell Lines.

Osteosarcoma (OS) is the most common primary malignant bone tumor of both children and pet canines. Its characteristic genomic instability and complexity coupled with the dearth of knowledge about its etiology has made improvement in the current treatment difficult. We use the existing literature about the biological pathways active in OS and combine it with the current research involving natural compounds to identify new targets and design more effective drug therapies.

Assessment of folate and cobalamin concentrations in relation to their dependent intracellular metabolites in serum of pigs between 6 and 26 weeks of age.

Folate (vitamin B) and cobalamin (vitamin B) play an important role in amino acid metabolism, nucleic acid synthesis, and methyl group transfer. Two intracellular enzymes, methionine synthase and methylmalonyl-CoA mutase, are folate and/or cobalamin-dependent, respectively. At the cellular level, a lack of folate and cobalamin leads to accumulation of serum homocysteine (HCY) and a lack of cobalamin leads to increased methylmalonic acid (MMA) concentrations.

Cryptotanshinone Induces Cell Death in Lung Cancer by Targeting Aberrant Feedback Loops.

Signaling pathways oversee highly efficient cellular mechanisms such as growth, division, and death. These processes are controlled by robust negative feedback loops that inhibit receptor-mediated growth factor pathways. Specifically, the ERK, the AKT, and the S6K feedback loops attenuate signaling via growth factor receptors and other kinase receptors to regulate cell growth.

Bayesian Inference Identifies Combination Therapeutic Targets in Breast Cancer.

Objective: Breast cancer is the second leading cause of cancer death among US women; hence, identifying potential drug targets is an ever increasing need. In this paper, we integrate existing biological information with graphical models to deduce the significant nodes in the breast cancer signaling pathway.

Methods: We make use of biological information from the literature to develop a Bayesian network.

In Silico Design and Experimental Validation of Combination Therapy for Pancreatic Cancer.

The number of deaths associated with Pancreatic Cancer has been on the rise in the United States making it an especially dreaded disease. The overall prognosis for pancreatic cancer patients continues to be grim because of the complexity of the disease at the molecular level involving the potential activation/inactivation of several diverse signaling pathways. In this paper, we first model the aberrant signaling in pancreatic cancer using a multi-fault Boolean Network.

A Gaussian Mixture-Model Exploiting Pathway Knowledge for Dissecting Cancer Heterogeneity.

In this work, we develop a systematic approach for applying pathway knowledge to a multivariate Gaussian mixture model for dissecting a heterogeneous cancer tissue. The downstream transcription factors are selected as observables from available partial pathway knowledge in such a way that the subpopulations produce some differential behavior in response to the drugs selected in the upstream. For each subpopulation, each unique (drug, observable) pair is considered as a unique dimension of a multivariate Gaussian distribution.

An in-silico study examining the induction of apoptosis by Cryptotanshinone in metastatic melanoma cell lines.

Background: Metastatic melanoma is an aggressive form of skin cancer that evades various anti-cancer treatments including surgery, radio-,immuno- and chemo-therapy. TRAIL-induced apoptosis is a desirable method to treat melanoma since, unlike other treatments, it does not harm non-cancerous cells. The pro-inflammatory response to melanoma by nF κB and STAT3 pathways makes the cancer cells resist TRAIL-induced apoptosis.

A Bayesian approach to determine the composition of heterogeneous cancer tissue.

Background: Cancer Tissue Heterogeneity is an important consideration in cancer research as it can give insights into the causes and progression of cancer. It is known to play a significant role in cancer cell survival, growth and metastasis. Determining the compositional breakup of a heterogeneous cancer tissue can also help address the therapeutic challenges posed by heterogeneity.

Comparative Therapeutic Effects of Minocycline Treatment and Bone Marrow Mononuclear Cell Transplantation following Striatal Stroke.

We explored the comparative effects of minocycline treatment and intrastriatal BMMC transplantation after experimental striatal stroke in adult rats. Male Wistar adult rats were divided as follows: saline-treated ( = 5), minocycline-treated ( = 5), and BMMC-transplanted ( = 5) animals. Animals received intrastriatal microinjections of 80 pmol of endothelin-1 (ET-1).

Cytotoxicity and anti-Leishmania amazonensis activity of Citrus sinensis leaf extracts.

Context: Leishmania amazonensis is the main agent of diffuse cutaneous leishmaniasis, a disease characterized by lesional polymorphism and the commitment of skin surface. Previous reports demonstrated that the Citrus genus possess antimicrobial activity.

Objective: This study evaluated the anti-L.

Indomethacin treatment reduces microglia activation and increases numbers of neuroblasts in the subventricular zone and ischaemic striatum after focal ischaemia.

Neuroblasts from the subventricular zone (SVZ) migrate to striatum following stroke, but most of them die in the ischaemic milieu and this can be related to exacerbated microglial activation. Here, we explored the effects of the non-steroidal anti-inflammatory indomethacin on microglial activation, neuronal preservation and neuroblast migration following experimental striatal stroke in adult rats. Animals were submitted to endothelin-1 (ET-1)-induced focal striatal ischaemia and were treated with indomethacin or sterile saline (i.

Rubiaceae in Brazilian Atlantic Forest remnants: floristic similarity and implications for conservation.

Brazil holds most of the Atlantic Forest Domain and is also one of the Rubiaceae diversity centers in the Neotropics. Despite the urban expansion in the state of Rio de Janeiro, large areas of continuous vegetation with high connectivity degree can still be found. Recently, new Rubiaceae species have been described in the Rio de Janeiro flora, which present small populations and very particular distribution.

Analytic validation of a gas chromatography-mass spectrometry method for quantification of six amino acids in canine serum samples.

Objective: To analytically validate a gas concentration of chromatography-mass spectrometry (GC-MS) method for measurement of 6 amino acids in canine serum samples and to assess the stability of each amino acid after sample storage.

Samples: Surplus serum from 80 canine samples submitted to the Gastrointestinal Laboratory at Texas A&M University and serum samples from 12 healthy dogs.

Procedures: GC-MS was validated to determine precision, reproducibility, limit of detection, and percentage recovery of known added concentrations of 6 amino acids in surplus serum samples.

Stability of 3-bromotyrosine in serum and serum 3-bromotyrosine concentrations in dogs with gastrointestinal diseases.

Background: 3-Bromotyrosine (3-BrY) is a stable product of eosinophil peroxidase and may serve as a marker of eosinophil activation. A gas chromatography/mass spectrometry method to measure 3-BrY concentrations in serum from dogs has recently been established and analytically validated. The aims of this study were to determine the stability of 3-BrY in serum, to determine the association between peripheral eosinophil counts and the presence of an eosinophilic infiltrate in the gastrointestinal tract, and to compare serum 3-BrY concentrations in healthy dogs (n = 52) and dogs with eosinophilic gastroenteritis (EGE; n = 27), lymphocytic-plasmacytic enteritis (LPE; n = 25), exocrine pancreatic insufficiency (EPI; n = 26), or pancreatitis (n = 27).

Concentration of Inorganic Elements Content in Benthic Seaweeds of Fernando de Noronha Archipelago by Synchrotron Radiation Total Reflection X-Ray Fluorescence Analysis (SRTXRF).

SRTXRF WAS USED TO DETERMINE AS, BA, BR, CA, CO, CR, CS, CU, DY, FE, K, MN, MO, NI, PB, RB, SR, TI, V, AND ZN IN ELEVEN SEAWEED SPECIES COMMONLY FOUND IN FERNANDO DE NORONHA: Caulerpa verticillata (J. Agardh) (Chlorophyta), Asparagopsis taxiformis (Delile), Dictyurus occidentalis (J. Agardh), Galaxaura rugosa (J.

Proteomics: clinical applications.

The word proteomics was coined in 1997 to describe the changes in all proteins expressed by a genome. Several sophisticated techniques including two-dimensional electrophoresis, imaging, mass spectrometry, and bioinformatics are used in proteomics to identify, quantify, and characterize proteins. Clinical proteomics is the application ofproteomics techniques to the medical field.

Proteomics technology.

Proteomics techniques are essential tools for protein detection and characterization. Besides several advances in the proteomics field, the two-dimensional electrophoresis (2-DE) technique is the most important method for protein separation. The combination of 2-DE technique, new advances in mass spectrometry and bioinformatics promises to unveil protein function and pathological mechanisms of disease.

Introduction to proteomics.

Technological advances in the field of genomics have given rise to the development of a new area called proteomics. Proteomics involves the analysis of all proteins expressed in a genome and uses a combination of sophisticated technologies such as two-dimensional electrophoresis, mass spectrometry and bioinformatics to identify and characterize proteins. This new area offers the potential to discover new biomarkers, improve diagnosis, and improve the prognosis of disease processes.

Correlation of mitochondrial protein expression in complexes I to V with natural and induced forms of canine idiopathic dilated cardiomyopathy.

Objective: To identify qualitative and quantitative differences in cardiac mitochondrial protein expression in complexes I to V between healthy dogs and dogs with natural or induced dilated cardiomyopathy (DCM).

Sample Population: Left ventricle samples were obtained from 7 healthy dogs, 7 Doberman Pinschers with naturally occurring DCM, and 7 dogs with DCM induced by rapid right ventricular pacing.

Procedures: Fresh and frozen mitochondrial fractions were isolated from the left ventricular free wall and analyzed by 2-dimensional electrophoresis.

Characterization of canine mitochondrial protein expression in natural and induced forms of idiopathic dilated cardiomyopathy.

Objective: To map canine mitochondrial proteins and identify qualitative and quantitative differences in heart mitochondrial protein expression between healthy dogs and dogs with naturally occurring and induced dilated cardiomyopathy (DCM).

Sample Population: Left ventricle samples were obtained from 7 healthy dogs, 7 Doberman Pinschers with naturally occurring DCM, and 7 dogs with induced DCM.

Procedures: Fresh and frozen mitochondrial fractions were isolated from the left ventricular free wall and analyzed by 2-dimensional electrophoresis.