Heat and mass transfer in the process of electrofractionation of secondary milk products

Paper presented at the 6th International Conference on Heat Transfer, Fluid Mechanics and Thermodynamics, South Africa, 30 June - 2 July, 2008.Complete and wasteless processing of milk envisages a complex utilization and recovery of raw products, including secondary resources, taking into account ecological factors due to high indices of biological and chemical oxygen demand of whey. Electrical activation of whey is one of the promising methods of processing of secondary milk raw products that we have studied and used for recovery of protein-mineral concentrate, inversion of lactose into lactulose and their subsequent application. The working regimes of heat and mass transfer, characteristics of the obtained products and advantages of electrophysical treatment are described.vk201

Неинвазивная диагностика заболеваний печени

Department of Pediatrics, Nicolae Testemitanu State Medical and Pharmaceutical University, Congresul III al Medicilor de Familie din Republica Moldova, 17–18 mai, 2012, Chişinău, Republica Moldova, Conferinţa Naţională „Maladii bronhoobstructive la copii”, consacrată profesorului universitar, doctor habilitat Victor Gheţeul, 27 aprilie, Chişinău, Republica MoldovaNoninvasive tests quickly and reliably differentiate patients with advanced fibrosis and those without fibrosis; they can be used as a rapid method of screening patients with infections and with hepatitisviruses B, C, D. Elastography is a method based on ultrasound, a non-invasive concept in assessing the nature of the tissue, which provides information about the elasticity of tissue examined and the degree of fibrosis. Noninvasive tests are an attractive alternative to liver puncture biopsy for staging and monitoring of chronic liver disease. Elastography examination for children is a priority because it is a noninvasive method with high information (data) and can be applied in medical practice in screening, diagnosis and monitoring of patients.Неинвазивные тесты позволяют оперативно и достоверно дифференцировать пациентов с F1-F4 стадиями фиброза печени и могут быть использованы в качестве как скрининга, так и мониторинга за пациентами с вирусными инфекциями B, C, D. Эластография является методом, основанным на ультразвуковой неинвазивной концепции в оценке морфологической структуры ткани, и предоставляет информацию об ее эластичности и степени фиброза. Неинвазивные тесты предстают привлекательной альтернативой пункционной биопсии печени для стадиализации и мониторинга хронических заболеваний печени. Метод эластографии печени у детей является приоритетным, поскольку является неинвазивным с высокой степенью информативности и достоверности и может применяться в медицинской практике в качестве скрининга, диагностики и мониторинга пациентов с патологией печени

Diagnostic possibilities of PID in the Republic of Moldova

Departament of Pediatrics, State Medical and Pharmaceutical University “Nicolae Testimiteanu”, Republic of MoldovaAwareness activities: PID are rather rare disorders but they are more common than it was estimated. The rate of recognition and diagnosis of PID is directly dependent on awareness of medical staff (JMF manuscript 2011). According to V.Modell (2011), founder of the JMF, the awareness of medical staff and patients concerning PID remains low all over the world and the majority of patients with recurrent infections are not diagnosed or underdiagnosed. In fact, PID prevalence levels exceed the official data. The handbook entitled “Primary Immunodeficiencies in children” was elaborated for family practitioners, pediatricians and medical residents, and published in 2012. It covers the following topics: general information about children immune system, 10 warning signs for children with PID, clinical presentation, immunological and genetic features of the most common PID syndromes, diagnostic algorithms, and tables with reference values of immunological tests. New diagnostic possibilities of PID in Moldova (2012). Determination of lymphocyte subpopulations using cytoflowmetric analysis, assessment of the IgG subclasses, IgD, evaluation of the C1-estherase activity, phagocytic burst-test using dihydrorhodamine, phagocyitosis killing activity (E.coli) using cytoflowmetric analysis. Algorithm diagnostic of PID in Moldova: Clinical screening – 10 warning signs of PID JMF(clinical features characteristic for well-defined syndromes of PID are also taken into consideration). At risk of PID patients primary are evaluated:: family history, clinical course of disease (especially infectious syndrome characteristic for different forms of PID), documented presence of other features of PID (autoimmunity, malignancy), documented presence of other conditions which can because of infectious susceptibility (structural abnormalities, cystic fi brosis, etc). Children with major risk of IDP are selected and laboratory screening: WBC manual count is made, total IgA, IgG, IgM, Ig E. Patients with major risk of PID are examined using different diagnostic protocols depending on clinical presentation. Different immunological tests are carried out according to the Practice Parameter for the diagnosis and management of PID (Bonilla F. et al., 2005). ESID criteria for PID are used to establish the possible, probable and definitive diagnosis of PID if appropriate. Current situation: 6 children are diagnosed with PID in Moldova currently: • 5 patients with IgA selective deficiency (6-8 years old) • 1 patient with Di George syndrome (4 years old) Currently more than 150 genetic defects determining severe disorders of the immune system have been described. According to the European Society for Primary Immunodefi ciencies database most of the reported immune deficiencies occur with a frequency of not less than 1:100000. The improvement of the diagnosis PID will help to achieve in 2013-2014 the Project “Complex diagnostic approach for patients with rare forms of primary immunodeficiency” which will be achieved with Belarus Republic. Objective of the Project: To elaborate effective diagnostic approach based on the analysis of retrospective and prospective clinical, immunological and genetic data of patients with rare primary immunodeficiency syndromes in the territory of the Republic of Moldova and the Republic of Belarus. It is aimed to perform an in-depth analysis of the disease history, clinical data and immunological disorders in patients with rare (1:100000 to 1:1000000) primary Immunodeficiencies in Moldova and the Republic of Belarus. At least 50 patients with 20 primary immunodefi ciency syndromes of rare incidence will be included. On the basis of the received data in Moldova and the Republic of Belarus a similar algorithm and check-list for clinical and immunological assessment will be developed for children with rare primary immunodefi ciencies. Therefore, a complex diagnostic approach must be elaborated for rare primary immunodefi ciency syndromes, which will include clinical, immunological and genetic features, and will contribute to the same effective as for common immunodefi - ciency syndromes early diagnosis and appropriate treatment. Activities which will help to improve PID diagnosis in Moldova: Implementation of lectures on childhood PID topics in the curricula of postgraduate training for family doctors and pediatricians. PhD research on PID problems. Organization of the J Project meeting in Moldova in the nearest future

Эпидемиологические и вирусологические аспекты гриппа, острых респираторных вирусных инфекций и тяжелых острых респираторных инфекций в Республике Молдова, сезон 2018/2019

Agenția Națională pentru Sănătate Publică, Congresul al VIII-lea al specialiștilor din domeniul sănătății publice și managementului sanitar 24-25 octombrie 2019 Chișinău, Republica MoldovaSezonul de gripă 2018/2019 a debutat mai devreme în comparație cu sezoanele precedente. Perioada epidemică a debutat în săptămâna 03/2019, atingând apogeul în săptămâna 06/2019 și s-a terminat în săptămâna 11/2019. Virusul gripal A(H1)pdm09 a fost predominant, fi ind detectat în 79,8% din cazurile de gripă confi rmate de laborator. Virusul gripal A(H3) a fost detectat în 20,2% cazuri. Virusurile gripale de tip B nu au fost detectate în acest sezon. Toate (4) virusurile gripale A(H1)pdm09 caracterizate genetic aparțin subgrupei 6B.1 (reprezentată prin A/Michigan/45/2015). Principalele caracteristici ale virusurilor din grupa 6B.1 sunt prezența substituțiilor aminoacizilor S84N, S162N (cu apariția unui nou loc potențial de glicozilare) și I216T în HA1. Virusurile gripale A/H3 detectate aparțin subclaselor 3C.2a1b și 3C.2a2. În ceea ce privește virusurile H3N2 circulante în prezent, caracterizarea lor antigenică prin reacția de hemaglutinoinhibare rămâne dificilă din cauza aglutinării instabile a globulelor roșii de cobai, curcan și umane. Nivelul morbidității prin gripă a sporit de 2,2 ori față de sezonul 2017/2018. Nivelul morbidității prin IACRS în sezonul 2018/2019 s-a majorat de 1,07 ori, iar prin SARI – de 1,17 ori față de sezonul precedent. Începând cu săptămâna 40/2018, virusurile respiratorii negripale au fost detectate în 37,7% (130/345) din probe colectate în timpul monitoringului în sistemul de tip santinelă. Au predominat rinovirusurile, adenovirusurile și virusul respirator sincițial.The influenza season started earlier that previous seasons. The epidemic period started at week 03/2019, peaked in week 06/2019 and ended in week 11/2019. Influenza A(H1)pdm09 was the predominant virus detected in 79,8% of ILI cases. Influenza A(H3) was detected in 20,2%. Influenza B viruses were not detected this season. All (4) of the A(H1)pdm09 viruses genetically characterized, belonged to the subgroup 6B.1 (represented by A/Michigan/45/2015). The main characteristics of viruses in the 6B.1 group are that the viruses carry the amino acid substitutions S84N, S162N (introducing a new potential glycosylation site) and I216T in HA1. Detected influenza A/ H3 viruses belonged to subclades 3C.2a1b and 3C.2a2. In the case of currently circulating H3N2 virus’s antigenic characterization continues to be difficult by HI assay due to variable agglutination of red blood cells from guinea pig, turkey and humans. The level of influenza morbidity increased 2,2 times compared to 2017/2018 season. The level of ARI morbidity in this season increased 1,07 times and the SARI recorded increased 1,17 times compared to the previous season. Since week 40/2018 other respiratory viruses were detected in 37,7% (130/345) of samples in sentinel surveillance. Rhinovirus, adenovirus and respiratory syncytial virus was detected in higher level during this season.Сезон гриппа 2018/2019 начался раньше, чем в предыдущие сезоны. Эпидемический период начался на неделе 03/2019, достигнув максимума на неделе 06/2019, и завершился на неделе 11/2019. Вирус гриппа A(H1)pdm09 был доминирующим и выявлен в 79,8% случаев гриппа. Вирус гриппа A(H3) был обнаружен в 20,2% случаев. Вирусы гриппа B не были выявлены в этом сезоне. Все (4) вирусы гриппа A(H1)pdm09б охарактеризованные генетически, относятся к подгруппе 6B.1 (представленную вирусом A/Michigan/45/2015). Основные характеристики вирусов из подгруппы 6B.1 – это наличие аминокислотных замен S84N, S162N (с появлением нового потенциального места гликозилирования) и I216T в HA1. Выявленные вирусы гриппа A/H3 относятся к подклассам 3C.2a1b и 3C.2a2. В случае циркулирующих в настоящее время H3N2, их антигенная характеристика с помощью реакции торможения гемаглютинации по-прежнему затруднена из за нестабильной агглютинации эритроцитов морской свинки, индейки и человека. Уровень заболеваемости гриппом повысился в 2,2 раза по сравнению с сезоном 2017/2018. Заболеваемость ОРВИ в сезоне 2018/2019 увеличилась в 1,07 раз по сравнению с предыдущим сезоном, а количество случаев ТОРИ увеличилось в 1,17 раз. Начиная с недели 40/2018 другие респираторные вирусы были выявлены в 37,7% (130/345) образцов, собранных во время дозорного надзора. Риновирусы, аденовирусы и респираторно-синцитиальные вирусы выявлялись в большом количестве в течении этого сезона

A Potent and Selective Inhibitor of Cdc42 GTPase

Cdc42, a member of the Rho family of GTPases, has been shown to play a role in cell adhesion, cytoskeletal arrangement, phagocytosis and cell motility and migration, in addition to a host of other diverse biological processes. The function of Rho-family GTPases in disease pathogenesis has been well established and identification of small, cell permeable molecules that selectively and reversibly regulate Rho GTPases is of high scientific and potentially therapeutic interest. There has been limited success in identifying inhibitors that specifically interact with small Rho family GTPases. The identified probe, ML141 (CID-2950007), is demonstrated to be a potent, selective and reversible non-competitive inhibitor of Cdc42 GTPase suitable for in vitro assays, with low micromolar potency and selectivity against other members of the Rho family of GTPases (Rac1, Rab2, Rab7). Given the highly complementary nature of the function of the Rho family GTPases, Cdc42 selective inhibitors such as those reported here should help untangle the roles of the proteins in this family

Importance of Extranuclear Estrogen Receptor-α and Membrane G Protein–Coupled Estrogen Receptor in Pancreatic Islet Survival

International audienc

Identification of a small molecule yeast TORC1 inhibitor with a flow cytometry-based multiplex screen

TOR (target of rapamycin) is a serine/threonine kinase, evolutionarily conserved from yeast to human, which functions as a fundamental controller of cell growth. The moderate clinical benefit of rapamycin in mTOR-based therapy of many cancers favors the development of new TOR inhibitors. Here we report a high throughput flow cytometry multiplexed screen using five GFPtagged yeast clones that represent the readouts of four branches of the TORC1 signaling pathway in budding yeast. Each GFP-tagged clone was differentially color-coded and the GFP signal of each clone was measured simultaneously by flow cytometry, which allows rapid prioritization of compounds that likely act through direct modulation of TORC1 or proximal signaling components. A total of 255 compounds were confirmed in dose-response analysis to alter GFP expression in one or more clones. To validate the concept of the high throughput screen, we have characterized CID 3528206, a small molecule most likely to act on TORC1 as it alters GFP expression in all five GFP clones in an analogous manner to rapamycin. We have shown that CID 3528206 inhibited yeast cell growth, and that CID 3528206 inhibited TORC1 activity both in vitro and in vivo with EC50s of 150 nM and 3.9 μM, respectively. The results of microarray analysis and yeast GFP collection screen further support the notion that CID 3528206 and rapamycin modulate similar cellular pathways. Together, these results indicate that the HTS has identified a potentially useful small molecule for further development of TOR inhibitors

Advances in GPCR modeling evaluated by the GPCR Dock 2013 assessment: Meeting new challenges

© 2014 Elsevier Ltd All rights reserved. Despite tremendous successes of GPCR crystallography, the receptors with available structures represent only a small fraction of human GPCRs. An important role of the modeling community is to maximize structural insights for the remaining receptors and complexes. The community-wide GPCR Dock assessment was established to stimulate and monitor the progress in molecular modeling and ligand docking for GPCRs. The four targets in the present third assessment round presented new and diverse challenges for modelers, including prediction of allosteric ligand interaction and activation states in 5-hydroxytryptamine receptors 1B and 2B, and modeling by extremely distant homology for smoothened receptor. Forty-four modeling groups participated in the assessment. State-of-the-art modeling approaches achieved close-to-experimental accuracy for small rigid orthosteric ligands and models built by close homology, and they correctly predicted protein fold for distant homology targets. Predictions of long loops and GPCR activation states remain unsolved problems

Analysis of subcellular metabolite levels of potato tubers (Solanum tuberosum) displaying alterations in cellular or extracellular sucrose metabolism

The expression of a heterologous invertase in potato tubers (Solanum tuberosum) in either the cytosol or apoplast leads to a decrease in total sucrose content and to an increase in glucose. Depending on the targeting of the enzyme different changes in phenotype and metabolism of the tubers occur: the cytosolic invertase expressing tubers show an increase in the glycolytic flux, accumulation of amino acids and organic acids, and the appearance of novel disaccharides; however, these changes are not observed when the enzyme is expressed in the apoplast [Roessner et al. (2001). Plant Cell, 13, 11-29]. The analysis of these lines raised several questions concerning the regulation of compartmentation of metabolites in potato tubers. In the current study we addressed these questions by performing comparative subcellular metabolite profiling. We demonstrate that: (i) hexoses accumulate in the vacuole independently of their site of production, but that the cytosolic invertase expression led to a strong increase in the cytosolic glucose concentration and decrease in cytosolic sucrose, whereas these effects were more moderate in the apoplastic expressors; (ii) three out of four of the novel compounds found in the cytosolic overexpressors accumulate in the same compartment; (iii) despite changes in absolute cellular content the subcellular distribution of amino acids was invariant in the invertase overexpressing tubers. These results are discussed in the context of current models of the compartmentation of primary metabolism in heterotrophic plant tissues

CACHE (Critical Assessment of Computational Hit-finding Experiments): A public–private partnership benchmarking initiative to enable the development of computational methods for hit-finding

One aspirational goal of computational chemistry is to predict potent and drug-like binders for any protein, such that only those that bind are synthesized. In this Roadmap, we describe the launch of Critical Assessment of Computational Hit-finding Experiments (CACHE), a public benchmarking project to compare and improve small-molecule hit-finding algorithms through cycles of prediction and experimental testing. Participants will predict small-molecule binders for new and biologically relevant protein targets representing different prediction scenarios. Predicted compounds will be tested rigorously in an experimental hub, and all predicted binders as well as all experimental screening data, including the chemical structures of experimentally tested compounds, will be made publicly available and not subject to any intellectual property restrictions. The ability of a range of computational approaches to find novel binders will be evaluated, compared and openly published. CACHE will launch three new benchmarking exercises every year. The outcomes will be better prediction methods, new small-molecule binders for target proteins of importance for fundamental biology or drug discovery and a major technological step towards achieving the goal of Target 2035, a global initiative to identify pharmacological probes for all human proteins. [Figure not available: see fulltext.