Digestive enzymes during development of Ceratitis capitata (Diptera:Tephritidae) and effects of SBTI on its digestive serine proteinase targets

SILVA, Fatima C. B. L. et al. Digestive enzymes during development of Ceratitis capitata (Diptera:Tephritidae) and effects of SBTI on its digestive serine proteinase targets. Insect Biochemistry and Molecular Biology, v. 36, p. 561-569, 2006.ISSN: 0965-1748.DOI: 10.1016/j.ibmb.2006.04.004.

Omega-3 Fatty Acids are Related to Abnormal Emotion Processing in Adolescent Boys with Attention Deficit Hyperactivity Disorder

Background In addition to the core symptoms, attention deficit hyperactivity disorder (ADHD) is associated with poor emotion regulation. There is some evidence that children and young adults with ADHD have lower omega-3 levels and that supplementation with omega-3 can improve both ADHD and affective symptoms. We therefore investigated differences between ADHD and non-ADHD children in omega-3/6 fatty acid plasma levels and the relationship between those indices and emotion-elicited event-related potentials (ERPs). Methods Children/adolescents with (n=31) and without ADHD (n=32) were compared in their plasma omega-3/6 indices and corresponding ERPs during an emotion processing task. Results Children with ADHD had lower mean omega-3/6 and ERP abnormalities in emotion processing, independent of emotional valence relative to control children. ERP abnormalities were significantly associated with lower omega-3 levels in the ADHD group. Conclusions The findings reveal for the first time that lower omega-3 fatty acids are associated with impaired emotion processing in ADHD children.

Omega-3 Fatty Acids are Inversely Related to Callous and Unemotional Traits in Adolescent Boys with Attention Deficit Hyperactivity Disorder

A number of research studies have reported abnormal plasma fatty acid profiles in children with ADHD along with some benefit of n−3 to symptoms of ADHD. However, it is currently unclear whether (lower) long chain-polyunsaturated fatty acids (LC-PUFAs) are related to ADHD pathology or to associated behaviours. The aim of this study was to test whether (1) ADHD children have abnormal plasma LC-PUFA levels and (2) ADHD symptoms and associated behaviours are correlated with LC-PUFA levels. Seventy-two, male children with (n=29) and without a clinical diagnosis of ADHD (n=43) were compared in their plasma levels of LC-PUFA. Plasma DHA was higher in the control group prior to statistical correction. Callous–unemotional (CU) traits were found to be significantly negatively related to both eicosapentaenoic acid (EPA), and total omega-3 in the ADHD group. The findings unveil for the first time that CU and anti-social traits in ADHD are associated with lower omega-3 levels.

Identification of protein targets of nevirapine reactive metabolites using click chemistry and mass spectrometry-based differential proteomics

Abstract : Adverse drug reactions (ADRs) are undesirable effects caused after administration of a single dose or prolonged administration of drug or result from the combination of two or more drugs. Idiosyncratic drug reaction (IDR) is an adverse reaction that does not occur in most patients treated with a drug and does not involve the therapeutic effect of the drug. IDRs are unpredictable and often life-threatening. Idiosyncratic reaction is dependent on drug chemical characteristics or individual immunological response. IDRs are a major problem for drug development because they are usually not detected during clinical trials. In this study we focused on IDRs of Nevirapine (NVP), which is a non-nucleoside reverse transcriptase inhibitor used for the treatment of Human Immunodeficiency Virus (HIV) infections. The use of NVP is limited by a relatively high incidence of skin rash. NVP also causes a rash in female Brown Norway (BN) rats, which we use as animal model for this study. Our hypothesis is that idiosyncratic skin reactions associated with NVP treatment are due to post-translational modifications of proteins (e.g., glutathionylation) detectable by MS. The main objective of this study was to identify the proteins that are targeted by a reactive metabolite of Nevirapine in the skin. The specific objectives derived from the general objective were as follow: 1) To implement the click chemistry approach to detect proteins modified by a reactive NVP-Alkyne (NVP-ALK) metabolite. The purpose of using NVP-ALK was to couple it with Biotin using cycloaddition Click Chemistry reaction. 2) To detect protein modification using Western blotting and Mass Spectrometry techniques, which is important to understand the mechanism of NVP induced toxicity. 3) To identify the proteins using MASCOT search engine for protein identification, by comparing obtained spectrum from Mass Spectrometry with theoretical spectrum to find a matching peptide sequence. 4) To test if the drug or drug metabolites can cause harmful effects, as the induction of oxidative stress in cells (via protein glutathionylation). Oxidative stress causes cell damage that mediates signals, which likely induces the immune response. The results showed that Nevirapine is metabolized to a reactive metabolite, which causes protein modification. The extracted protein from the treated BN rats matched 10% of keratin, which implies that keratin was the protein targeted by the NVP-ALK.

Potential Therapeutic Targets in Triple Negative Breast Cancer

Triple negative breast cancers (TNBC) are often described as biologically aggressive tumors, with poorer survival compared to other breast cancer subtypes. The fact that TNBC lacks an obvious target like estrogen receptor and HER2 represents a major challenge in the management of these patients. Genomic analyses have revealed that TNBC comprises a diverse group of cancers, which have distinct molecular profiles and different prognosis. These studies also highlighted molecular aberrations that could serve as potential treatment targets. On the other hand, a high percentage of TNBCs express some important surface receptors that have been already exploited in the development of promising targeted therapies, which are currently tested in clinical trials. In this review, we will provide an overview on the molecular diversity of TNBC with special emphasis on the evolving role of some potential biomarkers that may be utilized in the near future.

Integrity and public sector governance : a democratic deficit?

The Effect of Dietary Tartrazine on Brain Dopamine and the Behavioral Symptoms of Attention Deficit Hyperactivity Disorder

Attention Deficit Hyperactivity Disorder is a neurodevelopmental disorder correlated with a decrease in brain dopamine and an increase in behavioral symptoms of hyperactivity and impulsivity. This experiment explored how tartrazine (Yellow #5) impacts these symptoms. After tartrazine administration to Spontaneously Hypertensive Rats (SHR), dopamine concentrations in regions of brain tissue were measured using Enzyme-Linked Immunosorbent Assay analysis. Behavioral testing with a T-maze and open field test measured impulsivity and hyperactivity, respectively. Results indicate that dietary tartrazine increases hyperactive behaviors in the SHR. However, results do not indicate a relationship between dietary tartrazine and brain dopamine. No conclusions regarding the relationship between dietary tartrazine and impulsivity were drawn.

Digestive enzymes during development of Ceratitis capitata (Diptera:Tephritidae) and effects of SBTI on its digestive serine proteinase targets

SILVA, Fatima C. B. L. et al. Digestive enzymes during development of Ceratitis capitata (Diptera:Tephritidae) and effects of SBTI on its digestive serine proteinase targets. Insect Biochemistry and Molecular Biology, v. 36, p. 561-569, 2006.ISSN: 0965-1748.DOI: 10.1016/j.ibmb.2006.04.004.

Attention Deficit Hyperactivity Disorder and Executive Function Impairment: An Overview.

As with any cognitive ability, attention is vulnerable to dysfunction. The most common attentional problem is attention deficit hyperactivity disorder (ADHD). This brief overview will highlight the symptoms and deficits associated with ADHD, its prevalence in today’s society, the association between executive function impairment and ADHD using Barkley’s (1997) work, and the personal and societal effects of the disorder.

The relationship of early social, mental, and behavioral experiences with adult obesity and Alcohol Use Disorder

Stressful life events early in life, including symptoms of mental disorders or childhood maltreatment, may increase risk for worse mental and physical health outcomes in adulthood. The purpose of this dissertation was to examine the effects of childhood Attention Deficit Hyperactivity Disorder (ADHD) symptoms and maltreatment experience on two adult outcomes: obesity and alcohol use disorder (AUD). Mediational effects of adolescent characteristics were explored. This dissertation used Waves I, III, and IV of the National Longitudinal Study of Adolescent to Adult Health. In Paper 1 (Chapter 3), we investigated the association between multiple types of child maltreatment and adult objective (body mass index; BMI) and subjective (self-rated) obesity, as well as mediating effects by adolescent characteristics including depressive symptoms and BMI. Results showed that after adjusting for sex, race/ethnicity, and maternal education, physical maltreatment was moderately associated with adulthood obesity as measured by BMI and self-reported obesity, while sexual maltreatment was more strongly associated with the objective measure but not the subjective measure. The indirect effects of mediation of adolescent BMI and depressive symptoms were statistically significant. In Paper 2 (Chapter 4), the objective was to examine mediation by adolescent depressive symptoms, alcohol consumption, peer alcohol consumption, and delinquency in the relationship between ADHD symptoms and adult AUD. The indirect effects of mediation of adolescent delinquency, alcohol consumption, and peer alcohol consumption were statistically significant in single and multiple mediator models. In Paper 3 (Chapter 5), the objective was to assess the joint effects of maltreatment/neglect on adult AUD. After adjusting for sex, race/ethnicity, child maltreatment, and parental AUD, ADHD symptoms were significantly associated with increased odds of AUD. There was no strong evidence of multiplicative interaction by maltreatment. This association was stronger for males than females, although the interaction term was not statistically significant. This dissertation adds to the literature by examining relationships between several major public health problems: ADHD symptoms, childhood maltreatment, AUD, depressive symptoms, and obesity. This project has implications for understanding how early life stress increases risk for later physical and mental health problems, and identifying potential intervention targets for adolescents.

High temperature and vapor pressure deficit aggravate architectural effects but ameliorate non-architectural effects of salinity on dry mass production of tomato

Tomato (Solanum lycopersicum L.) is an important vegetable crop and often cultivated in regions exposed to salinity and high temperatures (HT) which change plant architecture, decrease canopy light interception and disturb physiological functions. However, the long-term effects of salinity and HT combination (S+HT) on plant growth are still unclear. A dynamic functional-structural plant model (FSPM) of tomato was parameterized and evaluated for different levels of S+HT combinations. The evaluated model was used to quantify the contributions of morphological changes (architectural effects) and physiological disturbances (non-architectural effects) on the reduction of shoot dry mass under S+HT. The model predicted architectural variables with high accuracy (>85%), which ensured the reliability of the model analyses. HT enhanced architectural effects but reduced non-architectural effects of salinity on dry mass production. The stronger architectural effects of salinity under HT could not be counterbalanced by the smaller non-architectural effects. Therefore, long-term influences of HT on shoot dry mass under salinity were negative at the whole plant level. Our model analysis highlights the importance of plant architecture at canopy level in studying the plant responses to the environments and shows the merits of dynamic FSPMs as heuristic tools.

A tentative argument for regional quality targets in assimilating schwa

Amerikanenglannin redusoitunut švaa-vokaali tuotetaan puheessa laadultaan huomattavan monimuotoisena. Kirjallisuudessa ei kuitenkaan vallitse selkeää käsitystä siitä, mitkä tekijät ehdollistavat tätä švaan laatuvaihtelua, ja etenkin sen mahdollinen sosiaalinen ulottuvuus on jäänyt aiemmissa tutkimuksissa varsin vähälle huomiolle. Tässä tutkielmassa pyritäänkin selvittämään, millainen vaikutus puhujan alueellisella murteella on hänen tuottamansa švaan akustiikkaan. Tutkimukseen valittiin 21 informanttia muutamista Yhdysvaltain eteläisistä ja läntisistä osavaltioista. Informanttien haastattelunauhoitteista poimittiin analyysiin yhteensä 433 švaan F1- ja F2-formanttiarvot siten kuin ne esiintyivät sanassa the. Analyysissä havaittiin, että eteläisten puhujien švaat keskittyivät vokaalien [u,U] tuntumaan, kun taas läntisten informanttien švaat asettuivat vokaalien [i,u] väliin. Tulokset antoivat aihetta kysyä, onko eteläinen švaa sulautunut takavokaaleihin [u,U]. Kysymystä varten suoritettiin jatkotutkimus, johon valittiin yksi ensimmäisen tutkimuksen eteläisistä puhujista. Puhujalta mitattiin 66 švaan ja 45 [U]:n formantit. Näitä tarkastellessa löydettiin tilastollista viitettä siitä, että puhujan švaa oli saattanut sulautua vokaaliin [U]. Tulostensa pohjalta tutkielma ehdottaa, että the-sanassa esiintyvässä amerikanenglannin švaassa saattaa toteutua puhujan alueellista murretta mukaileva tavoitevaihe siitä huolimatta, että tämä vokaali on samanaikaisesti huomattavasti kontekstiinsa assimiloitunut. Tavoitevaihe näyttäisi lähtökohtaisesti sijoittuvan F2:ssa vokaalialueen keskelle, ollen kuitenkin eteläisten puhujien kohdalla altis siirtymään taaemmas kohti vokaalilaatuja [u,U].

The conformational landscape of RNA translational regulators and their potential as drug discovery targets

RNA is an underutilized target for drug discovery. Once thought to be a passive carrier of genetic information, RNA is now known to play a critical role in essentially all aspects of biology including signaling, gene regulation, catalysis, and retroviral infection. It is now well-established that RNA does not exist as a single static structure, but instead populates an ensemble of energetic minima along a free-energy landscape. Knowledge of this structural landscape has become an important goal for understanding its diverse biological functions. In this case, NMR spectroscopy has emerged as an important player in the characterization of RNA structural ensembles, with solution-state techniques accounting for almost half of deposited RNA structures in the PDB, yet the rate of RNA structure publication has been stagnant over the past decade. Several bottlenecks limit the pace of RNA structure determination by NMR: the high cost of isotopic labeling, tedious and ambiguous resonance assignment methods, and a limited database of RNA optimized pulse programs. We have addressed some of these challenges to NMR characterization of RNA structure with applications to various RNA-drug targets. These approaches will increasingly become integral to designing new therapeutics targeting RNA.