Protease inhibitors from marine venomous animals and their counterparts in terrestrial venomous animals

The Kunitz-type protease inhibitors are the best-characterized family of serine protease inhibitors, probably due to their abundance in several organisms. These inhibitors consist of a chain of ~60 amino acid residues stabilized by three disulfide bridges, and was first observed in the bovine pancreatic trypsin inhibitor (BPTI)-like protease inhibitors, which strongly inhibit trypsin and chymotrypsin. In this review we present the protease inhibitors (PIs) described to date from marine venomous animals, such as from sea anemone extracts and Conus venom, as well as their counterparts in terrestrial venomous animals, such as snakes, scorpions, spiders, Anurans, and Hymenopterans. More emphasis was given to the Kunitz-type inhibitors, once they are found in all these organisms. Their biological sources, specificity against different proteases, and other molecular blanks (being also K+ channel blockers) are presented, followed by their molecular diversity. Whereas sea anemone, snakes and other venomous animals present mainly Kunitz-type inhibitors, PIs from Anurans present the major variety in structure length and number of Cys residues, with at least six distinguishable classes. A representative alignment of PIs from these venomous animals shows that, despite eventual differences in Cys assignment, the key-residues for the protease inhibitory activity in all of them occupy similar positions in primary sequence. The key-residues for the K+ channel blocking activity was also compared

Einfluss von Stereotypen und nonverbalem Verhalten auf die Eindrucksbildung: Besonderheiten bei hochfunktionalem Autismus

Hintergrund: Hochfunktionaler Autismus (HFA) ist durch normale kognitive Entwicklung bei gleichzeitigen sozial-kognitiven Besonderheiten gekennzeichnet. Bislang liegen kaum Erkenntnisse über die Verwendung verschiedener Informationsquellen für die Eindrucksbildung bei HFA vor. Vor dem Hintergrund bestehender Theorien (insbesondere Theorie der mangelnden zentralen Kohärenz) und der aktuellen Studienlage ist zu vermuten, dass Probleme bei Datensteuerung auftreten, konzeptgesteuert zu verarbeitende Informationen von Personen mit HFA jedoch gut angewendet werden können. Diese Arbeit untersucht, wie sich Stereotype und nonverbales Verhalten auf die Eindrucksbildung bei Personen mit HFA im Vergleich zu Kontrollpersonen auswirken. Methode: In zwei Studien wurde der Einfluss von Berufsstereotypen und nonverbalem Bewegungsverhalten auf die Eindrucksbildung bei einer Stichprobe von Personen mit HFA und einer nach Alter, Geschlecht und IQ parallelisierten Kontrollgruppe untersucht. In Studie 1 wurde zunächst eine kategoriale Vorinformation über den Beruf der Zielperson gegeben. Danach sahen die Versuchspersonen Filme mit Ausschnitten aus Bewerbungsgesprächen. In diesen Filmen waren Aussehen und Geschlecht der Zielpersonen durch Computeranimationen neutralisiert und somit nur die nonverbale Bewegungsinformation als Informationsquelle vorhanden. In Studie 2 wurde bei ansonsten ähnlichem Ablauf das Berufsstereotyp nicht kategorial, sondern in Form eines Lebenslaufes aktiviert. Die abhängige Variable (Eindruck) wurde in beiden Studien mit einem semantischen Differential erhoben. Ergebnisse: Bei HFA zeigte sich in Studie 1 eine bevorzugte Nutzung der kategorialen stereotypen Vorinformation. In der Kombination mit der kategorialen Vorinformation erwies sich auch das nonverbale Verhalten bei Personen mit HFA als einflussreich, wobei die Wirkung des nonverbalen Verhaltens weniger umfassend war als bei Kontrollpersonen. In Studie 2 hatte die Lebenslauf-Vorinformation bei Personen mit HFA deutlich weniger Einfluss auf den Eindruck als in der Kontrollgruppe. Auch das nonverbale Verhalten wurde in Studie 2 von Personen mit HFA kaum genutzt. Fazit: Personen mit HFA nutzen Stereotype für die Eindrucksbildung, jedoch vor allem dann, wenn wie bei kategorialer Stereotypaktivierung (Studie 1) reine Konzeptsteuerung erfolgen kann. In diesem Fall gelingt auch die nachfolgende Verarbeitung des nonverbalen Verhaltens, allerdings in einer reduzierteren Form als bei Kontrollpersonen. Bei sowohl daten- als auch konzeptgesteuert zu verarbeitender Information (Lebenslauf-Vorinformation, Studie 2) haben Personen mit HFA hingegen Defizite. Dies wirkt sich auch auf nachfolgend präsentiertes nonverbales Verhalten aus, das dann deutlich weniger als von Kontrollpersonen genutzt werden kann. Hieraus können sozial-kognitive Trainingsmaßnahmen abgeleitet werden, die auf der Vermittlung von sozial relevanten Kategorien und deren flexiblem Einsatz basieren

Flux balance analysis reveals acetate metabolism modulates cyclic electron flow and alternative glycolytic pathways in Chlamydomonas reinhardtii

Cells of the green alga Chlamydomonas reinhardtii cultured in the presence of acetate perform mixotrophic growth, involving both photosynthesis and organic carbon assimilation. Under such conditions, cells exhibit a reduced capacity for photosynthesis but a higher growth rate, compared to phototrophic cultures. Better understanding of the downregulation of photosynthesis would enable more efficient conversion of carbon into valuable products like biofuels. In this study, Flux Balance Analysis (FBA) and Flux Variability Analysis (FVA) have been used with a genome scale model of C. reinhardtii to examine changes in intracellular flux distribution in order to explain their changing physiology. Additionally, a reaction essentiality analysis was performed to identify which reaction subsets are essential for a given growth condition. Our results suggest that exogenous acetate feeds into a modified tricarboxylic acid cycle, which bypasses the CO2 evolution steps, explaining increases in biomass, consistent with experimental data. In addition, reactions of the oxidative pentose phosphate and glycolysis pathways, inactive under phototrophic conditions, show substantial flux under mixotrophic conditions. Importantly, acetate addition leads to an increased flux through cyclic electron flow (CEF), but results in a repression of CO2 fixation via Rubisco, explaining the down regulation of photosynthesis. However, although CEF enhances growth on acetate, it is not essential – impairment of CEF results in alternative metabolic pathways being increased. We have demonstrated how the reactions of photosynthesis interconnect with carbon metabolism on a global scale, and how systems approaches play a viable tool in understanding complex relationships at the scale of the organism

Hipertensão arterial : enfrentamento da doença na Atenção Básica

Orientadora : Ma. Amanda de Cassia Azevedo da SilvaMonografia (especialização) - Universidade Federal do Paraná, Setor de Ciências da Saúde, Curso de Especialização em Atenção BásicaInclui referênciasResumo: Este plano de intervenção aborda as ações educativas no manejo da hipertensão arterial em uma Unidade Básica de Saúde, no município de Palmas, no estado do Paraná e trata-se da conclusão do Curso de Especialização em Atenção Básica, da Universidade Federal do Paraná, financiado pela Universidade Aberta do Sistema Único de Saúde. A área de abrangência da Unidade Básica de Saúde em foco apresenta um grande número de óbitos por doenças cardiovasculares que tem a hipertensão como principal fator de propensão. Para gerir essa complicação, foram delineados como objetivos o controle dos níveis pressóricos dos usuários hipertensos da Unidade Básica de Saúde Eldorado, do município, através da realização de ações educativas junto aos pacientes com hipertensão arterial sistêmica, assim como de educação continuada para a equipe de saúde. visando o enfrentamento da doença. A realização de ações de prevenção da hipertensão arterial sistêmica e das comorbidades, na população atendida pela equipe da Unidade Básica de Saúde, assim como a capacitação dos profissionais de saúde dessa unidade foram realizadas através ações educativas e palestras. Devido o estado atual da pandemia de COVID- 19, as ações foram executadas em consulta médica, sendo que em fevereiro de 2021 foram realizadas 1189 consultas médicas, das quais 90 eram hipertensos já diagnosticados e 370 solicitações de controle dos níveis pressóricos para reduzir o número de pacientes assintomáticos que vivem com a doença sem conhecimento.Abstract: This intervention plan adresses the educational actions in the management of arterial hypertension in a Basic Health Unit, in the city of Palmas, in the state of Paraná and is the conclusion of the Specialization Course in Primary Care, from the Federal University of Paraná, financed by the Open University of The Unified Health System. The coverage area of the Basic Health Unit in focus has a large number of deaths from cardiovascular diseases, with hypertension as the main propensity factor. In order to manage this complication, the control of blood pressure levels of hypertensive users at the Eldorado Basic Health Unit, in the municipality, was outlined by means of educational activities with patients with systemic arterial hypertension, as well as continuing education on the disease for the health team and the creation of operative groups with users that favor the exchange of experiences, aiming at coping with the disease. Actions to prevent systemic arterial hypertension and comorbidities in the population served by the Basic Health Unit team, as well as the training of health professionals in this unit, were carried out through educational actions and lectures. Due to the current state of the COVID-19 pandemic, the actions were carried out in medical consultation, and in February 2021, 1189 medical consultations were carried out, of which 90 were already diagnosed hypertensive and 370 requested actions to control blood pressure levels and thus reduce the number of asymptomatic patients living with the disease without knowledge. The rest of the 729 consultations were about patients with a previous diagnosis of diabetes, low back pain, mental health and renewal of prescriptions

Efeitos agudos do biperideno sobre vocalizações ultrassônicas de 50 kHz e atividade lomotora de ratos tratados com cocaína

Orientador: Prof. Dr. Claudio da CunhaCoorientador: Dr. José Augusto PochapskiDissertação (mestrado) - Universidade Federal do Paraná, Setor de Ciências Biológicas, Programa de Pós-Graduação em Farmacologia. Defesa : Curitiba, 27/02/023Inclui referências: p. 44-57Resumo: A dependência de cocaína é um problema de saúde pública mundial, gerando graves impactos psicossociais e econômicos. Atualmente, nenhum tratamento para transtorno do uso de cocaína é aprovado pelas agências estatais de controle de medicamentos brasileira (ANVISA) ou internacionais c (FDA). O biperideno, um antagonista dos receptores muscarínicos M1 e M4, demonstrou em estudos clínicos e pré-clínicos um potencial efeito terapêutico para o tratamento de dependência química de cocaína, diminuindo o reforço e a busca pela droga. Entretanto, os efeitos do biperideno sobre o aumento das vocalizações ultrassônicas (USVs) de 50-kHz e hiperlocomoção induzidas pela cocaína ainda não estão totalmente esclarecidos. Neste estudo testamos os efeitos do biperideno sobre vocalizações ultrassônicas (USVs) de 50 kHz e atividade locomotora induzidos por cocaína em ratos Wistar machos adultos. Os ratos foram divididos em 4 grupos que receberam, respectivamente injeções i.p. de solução salina, biperideno (5 mg/kg), cocaína (10 mg/kg) ou biperideno + cocaína. A administração de cocaína aumentou significativamente o número das USVs de 50 kHz e a atividade locomotora dos animais. A administração de biperideno bloqueou o efeito da cocaína sobre as USVs, mas não bloqueou o efeito de hiperlocomoção induzido pela cocaína. O biperideno per se não afetou o número de USVs de 50 kHz, mas causou um aumento na atividade locomotora quando comparado ao grupo salina. Esses resultados sugerem que o biperideno pode atenuar o efeito gratificante, mas não o efeito hiperlocomotor induzido pela cocaína. Outros estudos pré-clínicos são necessários para melhor determinar a natureza dos efeitos da cocaína e outras drogas estimulantes do sistema nervoso central que podem ser bloqueados por drogas antimuscarínicas e seus mecanismos de ação.Abstract: Cocaine use disorder is a worldwide public health problem, generating serious psychosocial and economic impacts. Currently, no treatment for cocaine use disorder has been approved by controlling agencies including ANVISA and FDA. Biperiden, a M1 and M4 muscarinic receptor antagonist, has been shown in clinical and preclinical studies to decrease the drug seeking and reward effects of cocaine. These results demonstrate the biperiden's potential for the treatment of cocaine use disorder. However, the effects of biperiden over cocaine induced increase of 50-kHz ultrasonic vocalizations (USVs) and hyperlocomotion are still unknown. On this study we tested the effects of biperiden on 50-kHz USVs and locomotor activity induced by cocaine in adult male Wistar rats. Rats were divided into 4 groups that received i.p. injections of saline, biperiden (5 mg/kg), cocaine (10 mg/kg), or biperiden + cocaine. Cocaine administration significantly increased the number of 50 kHz USVs and the animals locomotor activity. Administration of biperiden blocked the effect of cocaine on increasing 50-kHz USVs, but not on locomotor activity. Biperiden per se did not affect the number of 50 kHz USVs but caused an increase in locomotor activity when compared to the saline group. These results suggest that biperiden can attenuate the rewarding, but not the hipercomotor, effect of cocaine. Further preclinical studies are needed to better determine the nature of the effects of cocaine and other central nervous system stimulant drugs that can be blocked by antimuscarinic drugs and their mechanisms of action

Self‐compassion and emotion regulation difficulties in obsessive–compulsive disorder

Lack of self‐compassion and deficits in emotion regulation are associated with various psychopathological symptoms and may play a role in the development and maintenance of obsessive–compulsive disorder (OCD). However, further empirical research is still needed to better understand these constructs in the context of this disorder. The present study investigated the relation between self‐compassion, emotion regulation difficulties, obsessive beliefs, and obsessive–compulsive symptom severity in 90 patients with OCD using self‐report questionnaires. Symptom severity and obsessive beliefs were negatively correlated to self‐compassion and positively associated with emotion regulation difficulties. Additionally, self‐compassion showed a negative relation to emotion regulation difficulties. Emotion regulation difficulties—but not self‐compassion—predicted symptom severity when controlling for obsessive beliefs and depression in a hierarchical regression analysis. Further analyses showed that emotion regulation deficits mediated the relationship between self‐compassion and OCD symptom severity. Our results provide preliminary evidence that targeting self‐compassion and putting more emphasis on emotion regulation deficits might be promising treatment approaches for patients with OCD. Future studies could investigate which specific interventions that directly address these variables improve treatment outcome

Change in obsessive beliefs as predictor and mediator of symptom change during treatment of obsessive-compulsive disorder - a process-outcome study

Background: Cognitive models of obsessive-compulsive disorder suggest that changes in obsessive beliefs are a key mechanism of treatments for obsessive-compulsive disorder. Thus, in the present process-outcome study, we tested whether changes in obsessive beliefs during a primarily cognitive behavioral inpatient treatment predicted treatment outcome and whether these changes mediated symptom changes over the course of treatment. Methods: Seventy-one consecutively admitted inpatients with obsessive-compulsive disorder were assessed with the Yale-Brown Obsessive-Compulsive Scale and the Obsessive Beliefs Questionnaire at treatment intake, after six weeks of treatment and at discharge, and with the Beck-Depression-Inventory-II at intake and discharge. Results: Changes in obsessive beliefs during the first six weeks of treatment predicted obsessive-compulsive symptoms at discharge when controlling for obsessive-compulsive and depressive symptoms at intake in a hierarchical regression analysis. Multilevel mediation analyses showed that reductions in obsessive beliefs partially mediated improvements in obsessive-compulsive symptoms over time. Conclusions: Our findings indicate that decreasing obsessive beliefs in inpatient cognitive behavioral therapy for obsessive-compulsive disorder might be a promising treatment approach

The Roles and Benefits of Using Undergraduate Student Leaders to Support the Work of SUMMIT-P

The article by Poole, Turner, and Maher-Boulis (2020) describes one way in which undergraduates have been used to support the SUMMIT-P goal of investigating examples of how mathematics and statistics are applied in partner discipline courses. Two other universities in the SUMMIT-P consortium, San Diego State University and Oregon State University, also use undergraduates in different ways to support the work of integrating science applications into math classes. In this article, we compare and contrast these three uses to further highlight this somewhat untapped resource