scholarly journals Achieving Functionality Through Modular Build-up: Structure and Size Selection of Serine Oligopeptidases

2019 ◽  
Vol 20 (11) ◽  
pp. 1089-1101 ◽  
Author(s):  
Anna J. Kiss-Szemán ◽  
Veronika Harmat ◽  
Dóra K. Menyhárd
Keyword(s):  
Serine Proteases ◽  
System Size ◽  
Catalytic Triad ◽  
Selection Strategy ◽  
Regulation System ◽  
Size Selection ◽  
The Family ◽  
Serine Protease Family ◽  
Selection Of

Enzymes of the prolyl oligopeptidase family (S9 family) recognize their substrates not only by the specificity motif to be cleaved but also by size - they hydrolyze oligopeptides smaller than 30 amino acids. They belong to the serine-protease family, but differ from classical serine-proteases in size (80 kDa), structure (two domains) and regulation system (size selection of substrates). This group of enzymes is an important target for drug design as they are linked to amnesia, schizophrenia, type 2 diabetes, trypanosomiasis, periodontitis and cell growth. By comparing the structure of various members of the family we show that the most important features contributing to selectivity and efficiency are: (i) whether the interactions weaving the two domains together play a role in stabilizing the catalytic triad and thus their absence may provide for its deactivation: these oligopeptidases can screen their substrates by opening up, and (ii) whether the interaction-prone β-edge of the hydrolase domain is accessible and thus can guide a multimerization process that creates shielded entrance or intricate inner channels for the size-based selection of substrates. These cornerstones can be used to estimate the multimeric state and selection strategy of yet undetermined structures.

scholarly journals Targeting Mitochondria in Diabetes

2021 ◽  
Vol 22 (12) ◽  
pp. 6642
Author(s):  
Nina Krako Jakovljevic ◽  
Kasja Pavlovic ◽  
Aleksandra Jotic ◽  
Katarina Lalic ◽  
Milica Stoiljkovic ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Mitochondrial Function ◽  
Whole Body ◽  
Noncommunicable Diseases ◽  
Pharmacological Interventions ◽  
Cellular Energy ◽  
Cellular Energy Metabolism ◽  
Data Comparison ◽  
Selection Of

Type 2 diabetes (T2D), one of the most prevalent noncommunicable diseases, is often preceded by insulin resistance (IR), which underlies the inability of tissues to respond to insulin and leads to disturbed metabolic homeostasis. Mitochondria, as a central player in the cellular energy metabolism, are involved in the mechanisms of IR and T2D. Mitochondrial function is affected by insulin resistance in different tissues, among which skeletal muscle and liver have the highest impact on whole-body glucose homeostasis. This review focuses on human studies that assess mitochondrial function in liver, muscle and blood cells in the context of T2D. Furthermore, different interventions targeting mitochondria in IR and T2D are listed, with a selection of studies using respirometry as a measure of mitochondrial function, for better data comparison. Altogether, mitochondrial respiratory capacity appears to be a metabolic indicator since it decreases as the disease progresses but increases after lifestyle (exercise) and pharmacological interventions, together with the improvement in metabolic health. Finally, novel therapeutics developed to target mitochondria have potential for a more integrative therapeutic approach, treating both causative and secondary defects of diabetes.

scholarly journals Transcriptomic and Proteomic Analyses Reveal the Diversity of Venom Components from the Vaejovid Scorpion Serradigitus gertschi

Toxins ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 359 ◽  
Author(s):  
Maria Romero-Gutiérrez ◽  
Carlos Santibáñez-López ◽  
Juana Jiménez-Vargas ◽  
Cesar Batista ◽  
Ernesto Ortiz ◽  
...  
Keyword(s):  
Serine Proteases ◽  
De Novo ◽  
Sequence Similarity ◽  
Scorpion Venom ◽  
Secretory Proteins ◽  
Host Defense Peptides ◽  
The Family ◽  
Pathogenesis Related ◽  
Molecular Masses

To understand the diversity of scorpion venom, RNA from venomous glands from a sawfinger scorpion, Serradigitus gertschi, of the family Vaejovidae, was extracted and used for transcriptomic analysis. A total of 84,835 transcripts were assembled after Illumina sequencing. From those, 119 transcripts were annotated and found to putatively code for peptides or proteins that share sequence similarities with the previously reported venom components of other species. In accordance with sequence similarity, the transcripts were classified as potentially coding for 37 ion channel toxins; 17 host defense peptides; 28 enzymes, including phospholipases, hyaluronidases, metalloproteases, and serine proteases; nine protease inhibitor-like peptides; 10 peptides of the cysteine-rich secretory proteins, antigen 5, and pathogenesis-related 1 protein superfamily; seven La1-like peptides; and 11 sequences classified as “other venom components”. A mass fingerprint performed by mass spectrometry identified 204 components with molecular masses varying from 444.26 Da to 12,432.80 Da, plus several higher molecular weight proteins whose precise masses were not determined. The LC-MS/MS analysis of a tryptic digestion of the soluble venom resulted in the de novo determination of 16,840 peptide sequences, 24 of which matched sequences predicted from the translated transcriptome. The database presented here increases our general knowledge of the biodiversity of venom components from neglected non-buthid scorpions.

scholarly journals Predictive framework for codend size selection of brown shrimp (Crangon crangon) in the North Sea beam-trawl fishery

PLoS ONE ◽  
2018 ◽  
Vol 13 (7) ◽  
pp. e0200464 ◽  
Author(s):  
Juan Santos ◽  
Bent Herrmann ◽  
Daniel Stepputtis ◽  
Claudia Günther ◽  
Bente Limmer ◽  
...  
Keyword(s):  
North Sea ◽  
Brown Shrimp ◽  
Beam Trawl ◽  
Crangon Crangon ◽  
Size Selection ◽  
Trawl Fishery ◽  
The North ◽  
Sea Beam ◽  
The North Sea ◽  
Selection Of

N-Terminal amino acid sequence of rat tonin: homology with serine proteases

1978 ◽  
Vol 56 (9) ◽  
pp. 920-925 ◽  
Author(s):  
N. G. Seidah ◽  
R. Routhier ◽  
M. Caron ◽  
M. Chrétien ◽  
S. Demassieux ◽  
...  
Keyword(s):  
Serine Proteases ◽  
Terminal Sequence ◽  
Renin Substrate ◽  
Amino Terminal ◽  
Single Polypeptide Chain ◽  
Serine Protease Family ◽  
Terminal Amino ◽  
Single Polypeptide ◽  
Carboxy Terminal ◽  
Amino Terminal Sequence

In this paper, we present the amino-terminal sequence of rat tonin, an endopeptidase responsible for the conversion of angiotensinogen, the tetradecapeptide renin substrate, or angiotensin I to angiotensin II. It is shown that isoleucine and proline occupy the amino- and carboxy-terminal residues respectively. The N-terminal sequence analysis permitted the identification of 34 out of the first 40 residue s of the single polypeptide chain composed of 272 amino acids. The se results showed an extensive homology with the sequence of many serine proteases of the trypsin–chymotrypsin family. This information, coupled with the slow inhibition of tonin by diisopropylfluorophosphate, classified this enzyme as a selective endopeptidase of the active serine protease family.

FAMILY DIABETES AND MAIN NONCOMMUNICABLE DISEASES: THE DESCRIBED AND POTENTIAL EFFECT OF METFORMIN (remembering Vladimir Dilman)

2020 ◽  
pp. 713-720
Author(s):  
Л. М. Берштейн
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Potential Effect ◽  
Noncommunicable Diseases ◽  
The Family ◽  
Whole Number ◽  
Long Time ◽  
Relationship Of ◽  
Antidiabetic Biguanides

Работа посвящена двум медико-биологическим проблемам - семейному диабету (имея в виду наличие случаев сахарного диабета 2-го типа в семье, в том числе в разных поколениях), а также особенностям его связей с основными неинфекционными заболеваниями человека и приурочена к юбилею известнейшего отечественного специалиста (теоретика и врача) в области геронтологии и эндокринологии профессора В. М. Дильмана. Широко признанные труды Владимира Михайловича, основанные на оригинальных идеях и породившие важные практические следствия (включая применение антидиабетических бигуанидов в не использовавшихся до него областях, необходимость устранения метаболической иммунодепрессии, учета изменений с возрастом на уровне гипоталамического порога в различных гомеостатических системах и целого ряда других предложений), как представляется, в течение долгого времени будут питать интеллектуальным материалом и стимулировать к дальнейшему поиску его последователей и специалистов, которым еще предстоит окунуться в область, очерченную В. М. Дильманом и интересовавшую его в течение многих лет. The work discusses the two biomedical problems: family diabetes (bearing in mind the presence of cases of type 2 diabetes mellitus in the family, including its different generations) and the features of relationship of family diabetes with major non-communicable human diseases (NCDs). The paper is timed to the anniversary of the famous - in our country and abroad - expert in the field of gerontology and endocrinology, Professor V. M. Dilman. The widely recognized works of V. M. Dilman, based on original ideas and giving rise to important practical consequences (including the use of antidiabetic biguanides in areas not studied before him, the need to eliminate metabolic immunodepression, to take into account the changes with age at the level of the hypothalamic threshold in various homeostatic systems and a whole number of other essential proposals), which for a long time, as it seems, will stimulate the further scientific search of his followers and specialists, who have yet to get acquainted with the area that attracted Prof. Dilman and interested him for many years.

The Use of SGLT2i and GLP-1 RA in Patients with Type 2 Diabetes in Thailand: Evidence Review and Recommendations

2021 ◽  
Vol 104 (11) ◽  
pp. 1850-1865
Keyword(s):  
Type 2 Diabetes ◽  
Glucose Lowering ◽  
Sodium Glucose Cotransporter ◽  
Evidence Review ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Glucose Lowering Therapy ◽  
The Cost ◽  
Selection Of

Background: Cardiovascular (CV) and renal comorbidities are common among type 2 diabetes (T2D) patients, and significantly increase the cost and burden of care. Both sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) improve key outcomes including major CV events, hospitalization for heart failure, and renal outcomes, albeit to varying degrees in different T2D populations. Materials and Methods: The authors reviewed evidence from GLP-1 RA and SGLT2i CV outcomes trials and real-world studies in Thailand and elsewhere. Results: The authors formulated recommendations to guide selection of anti-diabetes medication based on patients’ clinical characteristics and CV or renal risk profile. Conclusion: These recommendations could help guide management of CV/renal comorbidities and risk alongside glucose-lowering therapy for individual patients. Keywords: Type 2 diabetes mellitus; Cardiovascular diseases; Chronic kidney disease; Clinical outcomes; SGLT2i; GLP-1 RA

Counseling Parents of Children With Behavior Problems: The Use of Extinction and Time-Out Techniques

PEDIATRICS ◽  
1977 ◽  
Vol 59 (1) ◽  
pp. 78-85
Author(s):  
Ronald S. Drabman ◽  
Greg Jarvie
Keyword(s):  
Problem Behaviors ◽  
Inappropriate Behavior ◽  
Time Intervals ◽  
Alternative Behavior ◽  
Home Setting ◽  
Time Out ◽  
Behavior Response ◽  
Disciplinary Problems ◽  
The Family ◽  
Selection Of

The pediatrician is the professional most frequently sought out for advice concerning disciplinary problems with children in the home. Behavioral psychologists have advocated the use of contingent ignoring and time-out procedures to help reduce problem behaviors; however, practicing pediatricians have found that these two procedures are often not successful. In fact, sometimes the two procedures seem to exacerbate inappropriate behavior. This paper documents the difficulties found in using the ignoring and/or time-out procedures in the home setting. Potential pitfalls in the use of ignoring, including not specifying the target behavior, not taking a baseline, inadvertently, intermittently reinforcing the inappropriate behavior, response bursts, spontaneous recovery, and not reinforcing an appropriate alternative behavior, are described. In addition, several pitfalls in the use of the time-out procedure, including selection of isolation area, inappropriate selection of time intervals, interference from others in the family, and escape attempts on the part of the child are discussed. For each potential problem a remedy is suggested.

On the authorship and publication dates of Theraphosa and Theraphosidae (Araneae, Mygalomorphae): a clarification

Bionomina ◽  
2021 ◽  
Vol 24 (1) ◽  
Author(s):  
RAINER BREITLING
Keyword(s):  
19Th Century ◽  
Relevant Literature ◽  
Historical Context ◽  
Publication Date ◽  
Diverse Group ◽  
Early 19Th Century ◽  
The Family ◽  
Minority View ◽  
Case Based ◽  
Selection Of

The genus Theraphosa was established by Thorell (1870) as the type genus of the simultaneously published family Theraphosidae, the most diverse group of mygalomorph spiders. This authorship and publication date have long been accepted by the majority of authors. However, there has been a long-standing minority view that the genus name should be attributed to Walckenaer (1805), and the publication date of the family name changed to 1869.             A thought-provoking recent publication has examined this case. Based on a limited selection of the relevant literature, the authors struggled to make sense of their sources and prematurely concluded that the minority opinion might indeed be correct. They overlooked the potentially destabilising implications of this reattribution.             This paper revisits the evidence in the light of a much wider range of relevant publications, places it in its important historical context and, on the basis of the current rules of nomenclature, concludes that the traditional consensus has indeed been correct.                 Thus, Theraphosa Thorell, 1870 is the type genus of Theraphosidae Thorell, 1870 and a nomen protectum, while Theraphosa Schinz, 1823 is a nomen oblitum, mostly limited to the German textbook literature of the early 19th century. Teraphosa Eichwald, 1830 and Teraphosa Gistel, 1848 are junior synonyms of Avicularia Lamarck, 1818 (syn. nov.). Theraphosa Walckenaer, 1805 is a suprageneric name of the class-series (synonymous to Mygalomorphae) and not available at the genus level.

scholarly journals Effect of diabetes self-management education on glycaemic control among type 2 diabetic patients at a family medicine clinic in Kenya: A randomised controlled trial

2018 ◽  
Vol 10 (1) ◽  
Author(s):  
Catherine W. Gathu ◽  
Jacob Shabani ◽  
Nancy Kunyiha ◽  
Riaz Ratansi
Keyword(s):  
Family Medicine ◽  
Usual Care ◽  
Primary Outcome ◽  
Self Management ◽  
Diabetic Patients ◽  
Educational Approach ◽  
Medicine Clinic ◽  
The Family

Background: Diabetes self-management education (DSME) is a key component of diabetes care aimed at delaying complications. Unlike usual care, DSME is a more structured educational approach provided by trained, certified diabetes educators (CDE). In Kenya, many diabetic patients are yet to receive this integral component of care. At the family medicine clinic of the Aga Khan University Hospital (AKUH), Nairobi, the case is no different; most patients lack education by CDE.Aim: This study sought to assess effects of DSME in comparison to usual diabetes care by family physicians.Setting: Family Medicine Clinic, AKUH, Nairobi.Methods: Non-blinded randomised clinical trial among sub-optimally controlled (glycated haemoglobin (HbA1c) ≥ 8%) type 2 diabetes patients. The intervention was DSME by CDE plus usual care versus usual care from family physicians. Primary outcome was mean difference in HbA1c after six months of follow-up. Secondary outcomes included blood pressure and body mass index.Results: A total of 220 diabetes patients were screened out of which 140 met the eligibility criteria and were randomised. Around 96 patients (69%) completed the study; 55 (79%) in the DSME group and 41 (59%) in the usual care group. The baseline mean age and HbA1c of all patients were 48.8 (standard deviation [SD]: 9.8) years and 9.9% (SD: 1.76%), respectively. After a 6-month follow-up, no significant difference was noted in the primary outcome (HbA1c) between the two groups, with a mean difference of 0.37 (95% confidence interval: -0.45 to 1.19; p = 0.37). DSME also made no remarkable change in any of the secondary outcome measures.Conclusion: From this study, short-term biomedical benefits of a structured educational approach seemed to be limited. This suggested that offering a short, intensified education programme might have limited additional benefit above and beyond the family physicians’ comprehensive approach in managing chronic conditions like diabetes.

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