Apico-basal polarity determinants encoded by crumbs genes affect ciliary shaft protein composition, IFT movement dynamics, and cilia length

One of the most obvious manifestations of polarity in epithelia is the subdivision of the cell surface by cell junctions into apical and basolateral domains. crumbs genes are among key regulators of this form of polarity. Loss of crumbs function disrupts the apical cell junction belt and crumbs overexpression expands the apical membrane size. Crumbs proteins contain a single transmembrane domain and localize to cell junction area at the apical surface of epithelia. In some tissues, they are also found in cilia. To test their role in ciliogenesis, we investigated mutant phenotypes of zebrafish crumbs genes. In zebrafish, mutations of three crumbs genes, oko meduzy/crb2a, crb3a, and crb2b, affect cilia length in a subset of tissues. In oko meduzy (ome), this is accompanied by accumulation of other Crumbs proteins in the ciliary compartment. Moreover, intraflagellar transport (IFT) particle components accumulate in the ciliary shaft of ome;crb3a double mutants. Consistent with the above, Crb3 knockdown in mammalian cells affects the dynamics of IFT particle movement. These findings reveal crumbs-dependent mechanisms that regulate the localization of ciliary proteins, including Crumbs proteins themselves, and show that crumbs genes modulate intraflagellar transport and cilia elongation

Krull Dimension of Tame Generalized Multicoil Algebras

We determine the Krull dimension of the module category of finite dimensional tame generalized multicoil algebras over an algebraically closed field, which are domestic

Cycle-finite module categories

We describe the structure of module categories of finite dimensional algebras over an algebraically closed field for which the cycles of nonzero nonisomorphisms between indecomposable finite dimensional modules are finite (do not belong to the infinite Jacobson radical of the module category). Moreover, geometric and homological properties of these module categories are exhibited

191. Biopsja węzła wartowniczego w operacyjnym raku gruczołu piersiowego – doświadczenia własne

Do chwili obecnej w przypadku raka piersi usunięcie układu chłonnego pachy jest obowiązkowym elementem postępowania chirurgicznego. Zajęcie węzłów chłonnych w przypadku raka piersi jest jednym z czynników rokowniczych jak i wpływa na podjęcie dalszego leczenia uzupełniającego i dlatego usunięcie pachowych węzłów chłonnych jest bardzo ważnym elementem leczenia operacyjnego raka piersi. Technika biopsji węzła wartowniczego (WW) rozwinęła się w przypadkach czerniaka złośliwego skóry i ma na celu precyzyjną ocenę stanu całego dorzecza węzłów chłonnych przy użyciu barwnika Paten Blau V, radioizotopu Tc99 ręcznej sóndy gamma kamery oraz małoinwazyjnej techniki chirurgicznej.Materiał i metodaW okresie od sierpnia 1998 roku do września 2003 roku w I Oddziale Chirurgii Onkologicznej Wielkopolskiego Centrum Onkologii w Poznaniu poddano biopsji WW 400 pacjentek z operacyjnym rakiem piersi. U wszystkich chorych klinicznie nie stwierdzano powiększonych węzłów chłonnych. Wiek pacjentek wahał się od 35 do 70 lat ze średnią wieku 55,2 lat. W przeddzień operacji podawano podskórnie w okolicę guza z czterech wkłuć Nannocoloid znaczony Tc99 w stężeniu 1 mCi zawarty w 4 mililitrach roztworu. Dnia następnego rano wykonywano limfoscyntygrafię celem wykonania mappingu węzła/węzłów wartowniczych. Następnie na sali operacyjnej podawano 1 do 2 mililitrów barwnika Patent Blau V w ten sam sposób, co radiokoloid. Przy użyciu ręcznej sondy gamma kamery identyfikowano miejsce największego wychwytu znacznika w pasze (tzw. Hot, Spot), które zaznaczano. Po odsłonięciu tkanki tłuszczowej pachy uwidaczniano wybarwione drogi chłonne, wzdłuż których dokonywano identyfikację wybarwionego węzła chłonnego. Następnie przy użyciu ręcznej sondy Navigator potwierdzano największy wychwyt promieniowania nad wybarwionym węzłem, w takim przypadku powyższy węzeł chłonny uważany był jako WW i przesyłany do pracowni patologicznej. Po identyfikacji WW chora poddawana była standardowej operacji (mastectomia lub BCT) wraz z limfadenektomią pachową jako nieodłącznym elementem procedury chirurgicznej.WynikiWW udało się zidentyfikować w 97% chorych. W przypadku 7 pacjentek nie udało się odnależć WW. Z pośród chorych z definiowanym WW przerzuty stwierdzono w 20% przypadków, w pozostałej części badanej grupy WW nie zawierał komórek nowotworowych, co stanowi 80% badanej populacji. W badanej grupie chorych stwierdzono 2 przypadki wyniku fałszywie ujemnego. W większoścr przypadków (87,1%) WW występował jako pojedynczy tylko u 2 pacjentów stwierdzono podwójny węzeł chłonny a u jednej chorej WW występował jako potrójny, ogółem mnogie WW wynosiły 2,88% populacji.WnioskiBiopsja WW jest bezpieczną metodą pozwalającą na ocenę dorzecza pachowych węzłów chłonnych w operacyjnym raku piersi. Wyniki nasze potwierdzają w pełni wyniki innych badaczy w Europie i na Świecie

Doses in critical organs as limits of the total dose in the treatment of women with inoperable endometrial carcinoma

Surgery is the cornerstone of the treatments for endometrial carcinoma. However, about 20% of women must be treated with radiotherapy alone. They are patients in III FIGO stage and women in stage I and II with coexisting medical problems. The primary treatment of endometrial carcinoma is a combination of brachy-and teletherapy. During teletherapy the patients receive the total dose of 40–44 Gy to the treatment volume in pelvis with the use of the 4 beams-box technique. The second part of the treatment is intracavitary brachytherapy using two curved intrauterine applicators. The placing of the applicators in both corners of the uterus and individualized distribution of active sources in catheters make it possible to approximate the shape of isodoses to the size and shape of the uterus. On the basis of the AP and lateral radiographs with the parameters of the uterus we are able to plan the treatment according to the ICRU 38. The 50–55 Gy dose is distributed in two series with weekly intervals. We do not have much influence on the doses in the limiting organs (rectum, bladder) achived during teletherapy. Only the doses from brachytherapy can be modifed during treatment planning.Doses in critical organs are limiting factors for the administred total dose from brachy and teletherapy. Using the Target 2 Plus system enables to obtain combined isodoses from two parts of the treatment. This approach makes it possible to determine the dose in the points in the limiting organs. The doses at points of maximum exposure, as well as the modification of that dose allow us to avoid the possible complications

Genetic defects of GDF6 in the zebrafish out of sight mutant and in human eye developmental anomalies

Contains fulltext : 88522.pdf (publisher's version ) (Open Access)BACKGROUND: The size of the vertebrate eye and the retina is likely to be controlled at several stages of embryogenesis by mechanisms that affect cell cycle length as well as cell survival. A mutation in the zebrafish out of sight (out) locus results in a particularly severe reduction of eye size. The goal of this study is to characterize the outm233 mutant, and to determine whether mutations in the out gene cause microphthalmia in humans. RESULTS: In this study, we show that the severe reduction of eye size in the outm233 mutant is caused by a mutation in the zebrafish gdf6a gene. Despite the small eye size, the overall retinal architecture appears largely intact, and immunohistochemical studies confirm that all major cell types are present in outm233 retinae. Subtle cell fate and patterning changes are present predominantly in amacrine interneurons. Acridine orange and TUNEL staining reveal that the levels of apoptosis are abnormally high in outm233 mutant eyes during early neurogenesis. Mutation analysis of the GDF6 gene in 200 patients with microphthalmia revealed amino acid substitutions in four of them. In two patients additional skeletal defects were observed. CONCLUSIONS: This study confirms the essential role of GDF6 in the regulation of vertebrate eye size. The reduced eye size in the zebrafish outm233 mutant is likely to be caused by a transient wave of apoptosis at the onset of neurogenesis. Amino acid substitutions in GDF6 were detected in 4 (2%) of 200 patients with microphthalmia. In two patients different skeletal defects were also observed, suggesting pleitrophic effects of GDF6 variants. Parents carrying these variants are asymptomatic, suggesting that GDF6 sequence alterations are likely to contribute to the phenotype, but are not the sole cause of the disease. Variable expressivity and penetrance suggest a complex non-Mendelian inheritance pattern where other genetic factors may influence the outcome of the phenotype

Extent, Awareness and Perception of Dissemination Bias in Qualitative Research: An Explorative Survey

BACKGROUND: Qualitative research findings are increasingly used to inform decision-making. Research has indicated that not all quantitative research on the effects of interventions is disseminated or published. The extent to which qualitative researchers also systematically underreport or fail to publish certain types of research findings, and the impact this may have, has received little attention. METHODS: A survey was delivered online to gather data regarding non-dissemination and dissemination bias in qualitative research. We invited relevant stakeholders through our professional networks, authors of qualitative research identified through a systematic literature search, and further via snowball sampling. RESULTS: 1032 people took part in the survey of whom 859 participants identified as researchers, 133 as editors and 682 as peer reviewers. 68.1% of the researchers said that they had conducted at least one qualitative study that they had not published in a peer-reviewed journal. The main reasons for non-dissemination were that a publication was still intended (35.7%), resource constraints (35.4%), and that the authors gave up after the paper was rejected by one or more journals (32.5%). A majority of the editors and peer reviewers "(strongly) agreed" that the main reasons for rejecting a manuscript of a qualitative study were inadequate study quality (59.5%; 68.5%) and inadequate reporting quality (59.1%; 57.5%). Of 800 respondents, 83.1% "(strongly) agreed" that non-dissemination and possible resulting dissemination bias might undermine the willingness of funders to support qualitative research. 72.6% and 71.2%, respectively, "(strongly) agreed" that non-dissemination might lead to inappropriate health policy and health care. CONCLUSIONS: The proportion of non-dissemination in qualitative research is substantial. Researchers, editors and peer reviewers play an important role in this. Non-dissemination and resulting dissemination bias may impact on health care research, practice and policy. More detailed investigations on patterns and causes of the non-dissemination of qualitative research are needed

Current status of MELCOR 2.2 for fusion safety analyses

MELCOR is an integral code developed by Sandia National Laboratories (SNL) for the US Nuclear Regulatory Commission (USNRC) to perform severe accident analyses of Light Water Reactors (LWR). More recently, MELCOR capabilities are being extended also to analyze non-LWR fission technologies. Within the European MELCOR User Group (EMUG), organized in the framework of USNRC Cooperative Severe Accident Research Program (CSARP), an activity on the evaluation of the applicability of MELCOR 2.2 for fusion safety analyses has been launched and it has been coordinated by ENEA. The aim of the activity was to identify the physical models to be possibly implemented in MELCOR 2.2 necessary for fusion safety analyses, and to check if those models are already available in MELCOR 1.8.6 for fusion version, developed by Idaho National Laboratory (INL). From this activity, a list of modeling needs emerged from the safety analyses of fusion-related installations have been identified and described. Then, the importance of the various needs, intended as the priority for model implementation in the MELCOR 2.2 code, has been evaluated according to the technical expert judgement of the authors. In the present paper, the identified modeling needs are discussed. The ultimate goal would be to propose to have a single integrated MELCOR 2.2 code release capable to cover both fission and fusion applications