739 observed NEAs and new 2-4m survey statistics within the EURONEAR network

We report follow-up observations of 477 program Near-Earth Asteroids (NEAs) using nine telescopes of the EURONEAR network having apertures between 0.3 and 4.2 m. Adding these NEAs to our previous results we now count 739 program NEAs followed-up by the EURONEAR network since 2006. The targets were selected using EURONEAR planning tools focusing on high priority objects. Analyzing the resulting orbital improvements suggests astrometric follow-up is most important days to weeks after discovery, with recovery at a new opposition also valuable. Additionally we observed 40 survey fields spanning three nights covering 11 sq. degrees near opposition, using the Wide Field Camera on the 2.5m Isaac Newton Telescope (INT), resulting in 104 discovered main belt asteroids (MBAs) and another 626 unknown one-night objects. These fields, plus program NEA fields from the INT and from the wide field MOSAIC II camera on the Blanco 4m telescope, generated around 12,000 observations of 2,000 minor planets (mostly MBAs) observed in 34 square degrees. We identify Near Earth Object (NEO) candidates among the unknown (single night) objects using three selection criteria. Testing these criteria on the (known) program NEAs shows the best selection methods are our epsilon-miu model which checks solar elongation and sky motion and the MPC's NEO rating tool. Our new data show that on average 0.5 NEO candidates per square degree should be observable in a 2m-class survey (in agreement with past results), while an average of 2.7 NEO candidates per square degree should be observable in a 4m-class survey (although our Blanco statistics were affected by clouds). At opposition just over 100 MBAs (1.6 unknown to every 1 known) per square degree are detectable to R=22 in a 2m survey based on the INT data, while our two best ecliptic Blanco fields away from opposition lead to 135 MBAs (2 unknown to every 1 known) to R=23.Comment: Published in Planetary and Space Sciences (Sep 2013

Эффективность применения препаратов кальция с витамином Д и минералами для коррекции костной плотности у детей с муковисцидозом

Catedra Pediatrie, Facultatea Rezidenţiat şi Secundariat Clinic, USMF „Nicolae Testemiţanu”Bone disease has been described as a common complication that progresses with age, severity of lung damage and nutritional disorders in patients with cystic fibrosis (CF). Glucocorticoid therapy, maldigestion and malabsorption resulting in the deficiency of vitamin D and minerals such as calcium may contribute to secondary loss of bone mass. A group of 42 patients with CF was examined to measure low bone mass density status (osteopenia, osteoporosis) and the effects of therapy. Z-score showed a decrease in both groups: – 2.83 ± 0.44 DS in CF children < 12 years and – 3.61 ± 0.50 DS in CF patients > 12 years. Three months of treatment with minerals and vitamins supplement produced an increase of Z-score to – 2.44 ± 0.47 DS in children < 12 years and to – 2.85 ± 0.49 in older patients.Патология костной системы частое осложнение у пациентов с муковисцидозом, которая прогрессирует с возрастом, со степенью тяжести повреждения легких и нарушения питания. Терапия с глюкокортикоидами, мальдигестия и мальабсорбция в результате недостатка витамина Д и минералов, таких как кальция, может способствовать потере костной массы. Для выявления признаков сниженной костной плотности (остеопении, остеопороза) были обследованы 42 пациента с муковисцидозом. У детей младше 12 лет значение Z-score было снижено до 2,65 ± 0,56 DS, а для пациентов старше 12 лет уровень Z-score был значительно снижен и составил – 3,43 ± 0,37 DS. На фоне применения кальция с витамином Д и других препаратов, содержащих минералы и витамины, показатель Z-score увеличился до 2,25 ± 0,51 DS в группе детей 12 лет

Chest imaging findings in children with cystic fibrosis

Department of Pediatrics, NicolaeTestemitanu State Medical and Pharmaceutical University, Department of Imagistic, Research Institute for Maternal and Child Health Care, 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 MoldovaCystic fibrosis (CF) is an inherited chronic life-threatening disease that most critically affects the lungs. It causes the production ofsticky mucus that clogs the lungs and leads to inflammation. The severity of lung damage determines the evolution of the disease and requires instrumental confirmation. Research was performed to determinate the structural changes of the lung tissue in children with CF by the conventional chest X-ray and thorax spiral computed tomography (CT). In this study we evaluated the chest X-raysof 55 patients (32 girls and 23 boys) and the CT scans of 36 patients with CF (21 girls and 15 boys), from 2 to 18 years. Four patients had a mild evolution of CF, 10 children had moderate, and 21 suffered from the severe form of the disease. The most common chest radiographic findings in CF patients were hyperinflation (87.3%), bronchial thickening (94.5%) and dilatation (41.8%), an increase in interstitial markings (76.3%), and pneumofibrosis (85.4%). Abnormal findings were detected in 94.4% patients examined by CT. Bronchiectasis developed in 77.7% CF patients, including 28.6% cases in the upper or mid lobes and 71.4% children with generalized bronchiectasis. Cysticbronchus deformations withliquid levels were identified in 2 of the patients with severe evolution of CF. Sectors of fibrosis were revealed in 6 spiral CT images. In two of the CF children CT findings of chronic obstructive bronchitis were detected, and in other two patients no structural bronchial changes were founded. The method of spiral tomography offeredmore complete and detailed information about the anatomo-morphological substrate of pulmonary modifications in children with cystic fibrosis. In children with CF structural bronchopulmonaryspiral CTsreveals modifications such as focal fibrosis, and sometimes widespread bronchial deformations with saccate bronchiectasis

Anterograde trafficking of KCa3.1 in polarized epithelia is Rab1- And Rab8-Dependent and recycling endosome-independent

The intermediate conductance, Ca2+-activated K+ channel (KCa3.1) targets to the basolateral (BL) membrane in polarized epithelia where it plays a key role in transepithelial ion transport. However, there are no studies defining the anterograde and retrograde trafficking of KCa3.1 in polarized epithelia. Herein, we utilize Biotin Ligase Acceptor Peptide (BLAP)-tagged KCa3.1 to address these trafficking steps in polarized epithelia, using MDCK, Caco-2 and FRT cells. We demonstrate that KCa3.1 is exclusively targeted to the BL membrane in these cells when grown on filter supports. Following endocytosis, KCa3.1 degradation is prevented by inhibition of lysosomal/proteosomal pathways. Further, the ubiquitylation of KCa3.1 is increased following endocytosis from the BL membrane and PR-619, a deubiquitylase inhibitor, prevents degradation, indicating KCa3.1 is targeted for degradation by ubiquitylation. We demonstrate that KCa3.1 is targeted to the BL membrane in polarized LLC-PK1 cells which lack the m1B subunit of the AP-1 complex, indicating BL targeting of KCa3.1 is independent of μ1B. As Rabs 1, 2, 6 and 8 play roles in ER/Golgi exit and trafficking of proteins to the BL membrane, we evaluated the role of these Rabs in the trafficking of KCa3.1. In the presence of dominant negative Rab1 or Rab8, KCa3.1 cell surface expression was significantly reduced, whereas Rabs 2 and 6 had no effect. We also co-immunoprecipitated KCa3.1 with both Rab1 and Rab8. These results suggest these Rabs are necessary for the anterograde trafficking of KCa3.1. Finally, we determined whether KCa3.1 traffics directly to the BL membrane or through recycling endosomes in MDCK cells. For these studies, we used either recycling endosome ablation or dominant negative RME-1 constructs and determined that KCa3.1 is trafficked directly to the BL membrane rather than via recycling endosomes. These results are the first to describe the anterograde and retrograde trafficking of KCa3.1 in polarized epithelia cells. © 2014 Bertuccio et al

Респираторная функция у детей с муковисцидозом, с сопутствующей бронхиальной астмой и оториноларингической патологией

Catedra Pediatrie, Facultatea Rezidenţiat şi Secundariat Clinic, USMF „Nicolae Testemiţanu”, Conferinţa naţională ştiinţifico-practică în domeniul otorinolaringologiei pediatrice, 30 octombrie 2009, Chişinău, Republica MoldovaThis study included 26 children 6-18 years old. The study group consisted of 13 children with associated cystic fibrosis (CF), bronchial asthma and otorhinolaryngological (ORL) diseases. The control group included 13 children with CF without signs of asthma and ORL diseases. The results of the study showed the increased frequency of atopic family history, antecedents of personal allergy (atopic dermatitis, allergic rhinitis), and ORL pathology in children from the study group. The spirographic values were significantly lower (p>0,001) in CF associated with bronchial asthma (FVC 54.38±4.2%, FEV1 54.92±5.45%, FEF25-75 60.84±9.57%) than in that of the children from the control group (FVC 67.89±2.4%, FEV1 72.84±2.8%, FEF25-75 115±5.43%). В настоящую работу были включены 26 детей в возрасте 6-18 лет. Основную группу составили 13 детей с муковисцидозом, с сопутствующей бронхиальной астмой и ЛОР патологией, а контрольную группу – 13 детей с муковисцидозом без признаков бронхиальной астмы и ЛОР патологии. Полученные данные доказали наличие семейной предрасположенности к аллергическим заболеваниям, наличие аллергической и ЛОР патологии в анамнезе, которые преобладали в основной группе. Спирометрическое исследование выявило более выраженную (p>0,001) дисфункцию проходимости бронхов у детей с муковисцидозом и бронхиальной астмой (ЖЕЛ 54,38±4,2%, ОФВ1 54,92±5,45%, сос25-75 60,84±9,57%) в сравнении с детьми контрольной группы (ЖЕЛ 67,89±2,4%, ОФВ1 72,84±2,8%, сос25-75 115±5,43%)

Systematic characterization of deubiquitylating enzymes for roles in maintaining genome integrity.

DNA double-strand breaks (DSBs) are perhaps the most toxic of all DNA lesions, with defects in the DNA-damage response to DSBs being associated with various human diseases. Although it is known that DSB repair pathways are tightly regulated by ubiquitylation, we do not yet have a comprehensive understanding of how deubiquitylating enzymes (DUBs) function in DSB responses. Here, by carrying out a multidimensional screening strategy for human DUBs, we identify several with hitherto unknown links to DSB repair, the G2/M DNA-damage checkpoint and genome-integrity maintenance. Phylogenetic analyses reveal functional clustering within certain DUB subgroups, suggesting evolutionally conserved functions and/or related modes of action. Furthermore, we establish that the DUB UCHL5 regulates DSB resection and repair by homologous recombination through protecting its interactor, NFRKB, from degradation. Collectively, our findings extend the list of DUBs promoting the maintenance of genome integrity, and highlight their potential as therapeutic targets for cancer.This is the author's accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ncb302

Enzymatic Blockade of the Ubiquitin-Proteasome Pathway

Ubiquitin-dependent processes control much of cellular physiology. We show that expression of a highly active, Epstein-Barr virus-derived deubiquitylating enzyme (EBV-DUB) blocks proteasomal degradation of cytosolic and ER-derived proteins by preemptive removal of ubiquitin from proteasome substrates, a treatment less toxic than the use of proteasome inhibitors. Recognition of misfolded proteins in the ER lumen, their dislocation to the cytosol, and degradation are usually tightly coupled but can be uncoupled by the EBV-DUB: a misfolded glycoprotein that originates in the ER accumulates in association with cytosolic chaperones as a deglycosylated intermediate. Our data underscore the necessity of a DUB activity for completion of the dislocation reaction and provide a new means of inhibition of proteasomal proteolysis with reduced cytotoxicity.National Institutes of Health (U.S.)EMBO (long term Fellowship 2008-379)Boehringer Ingelheim Fond

Изменения при лучевом исследовании поджелудочной железы у пациентов с муковисцидозом

The ultrasound assessment of a 60 children with CF and 70 healthy children revealed a significantly (p < 0.001) increased dimensions of the pancreas in children with CF aged up to 10 years in comparison to children from the control group of the same age. The CF progression lead to dramatic reduction (p < 0.001) in the pancreas dimensions in patients with CF older than 10 years. Computed tomography of the pancreas in 14 children with cystic fibrosis identify an advanced pancreatic atrophy, with reduced volume in 81.81% cases, significantly lipid involution, and calcification in the lumen of pancreatic ducts.Ультразвуковое исследование 60 детей с муковисцидозом и 70 здоровых детей показало достоверное (р < 0,001) увеличение размеров поджелудочной железы у детей с муковисцидозом младше 10 лет по сравнению с детьми из контрольной группы того же возраста. Прогрессия муковисцидоза привела к резкому снижению (р < 0,001) размеров поджелудочной железы у пациентов с муковисцидозом старше 10 лет. Компьютерная томография поджелудочной железы у 14 детей с муковисцидозом выявила значительную атрофию поджелудочной железы, с уменьшением объемов 81,81% случаев, с жировой инволюцией и кальцификатами в просвете протоков поджелудочной железы