Breast cancer as a significant social problem

Background: This article is devoted to the topic of breast cancer, which is a very important and overlooked problem by many women. This cancer is the most common malignancy in women in developed countries. It also creates an increasing problem in developing countries and causes high mortality. Early diagnoses of neoplastic lesions and rapid implementation of therapy in most cases allow for successful treatment its prognosis. Self-control is very important, women should examine their breasts by palpation. Further research to diagnose breast cancer are: mammography (MMG), ultrasonography (USG), magnetic resonance (MR), positron emission tomography (PET) and microscopic examination. Material and Methods: In this article, it was analyzed by the latest literature on risk factors, epidemiology, diagnosis and treatment of breast cancer. Articles were searched from PubMed and Google Scholar. Results: Breast cancer risk factors have been shown to be early menstruation, high women's height, high body mass (especially fat content) and hyperinsulinaemia. In addition, genetic factors play an important role. Research also confirms that highly-used cleaners, and at their head, DDP (dichlorodiphenyltrichloroethane) affect the formation of breast cancer. This is the third most common cause of death in women aged 60-85. In treatment, an individual approach to each patient is important. Older women individually discuss the methods of treatment with the doctor, because it gives beneficial results of therapy. Conclusions: Breast cancer has become a very important medical and social problem in older women. Mass media are needed to disseminate knowledge, topics related to treatment and to support the sick. In older women, treatment is more aggressive, and in addition to radiotherapy, a partial mastectomy is performed. Breast cancer is a tought term for woman’s in all age. It is related with fear and loss of self—confidence

Dzieci i młodzież w kręgu oddziaływania mediów i grup rówieśniczych - "w" i "pomimo" czasów ponowoczesnych

Praca recenzowana / peer-reviewed pape

METTL16, Methyltransferase-Like Protein 16: Current Insights into Structure and Function

Methyltransferase-like protein 16 (METTL16) is a human RNA methyltransferase that installs m6A marks on U6 small nuclear RNA (U6 snRNA) and S-adenosylmethionine (SAM) synthetase pre-mRNA. METTL16 also controls a significant portion of m6A epitranscriptome by regulating SAM homeostasis. Multiple molecular structures of the N-terminal methyltransferase domain of METTL16, including apo forms and complexes with S-adenosylhomocysteine (SAH) or RNA, provided the structural basis of METTL16 interaction with the coenzyme and substrates, as well as indicated autoinhibitory mechanism of the enzyme activity regulation. Very recent structural and functional studies of vertebrate-conserved regions (VCRs) indicated their crucial role in the interaction with U6 snRNA. METTL16 remains an object of intense studies, as it has been associated with numerous RNA classes, including mRNA, non-coding RNA, long non-coding RNA (lncRNA), and rRNA. Moreover, the interaction between METTL16 and oncogenic lncRNA MALAT1 indicates the existence of METTL16 features specifically recognizing RNA triple helices. Overall, the number of known human m6A methyltransferases has grown from one to five during the last five years. METTL16, CAPAM, and two rRNA methyltransferases, METTL5/TRMT112 and ZCCHC4, have joined the well-known METTL3/METTL14. This work summarizes current knowledge about METTL16 in the landscape of human m6A RNA methyltransferases

AN ATTEMPTED RECREATION OF THE ORIGINAL CONSTRUCTION OF THE SO-CALLED RETABLE FROM WRÓBLEWO A COMPARATIVE ANALYSIS INVOLVING RETABLES FROM XVth-XVIth-CENTURY EUROPE

The article discusses assorted probable variants of the appearance of the so-called altar from Wróblewo, and outlines brief schemes of the structures and forms of European altars from the period. The so-called altar from Wróblewo, executed in about 1500, was in all likelihood intended for one of the churches in Gdańsk. The founder of the retable was a representative of the patrician Scheweke family (probably Johan Scheweke). In 1591, a second foundation encompassed already four painted wings of the altar structure. The middle part and the remaining elements were either destroyed or lost prior to this date. The wings were subsequently transferred to a private chapel of the Scheweke family in Wróblewo near Gdańsk, and remained there to the destruction of the chapel in approx. 1945. The preserved three wings are at present featured in the National Museum in Gdańsk. The extant fragments, i.e. the three wings as well as source data about the fourth wing make it possible to deduce information about links with the non-extant corpse, as well as the altar as a whole. This task is assisted by the preserved frame and an opportunity of recreating the sequence of the depicted events. The wing obverses, showing scenes from an apocryphainspired of the Virgin Mary, indicate the Marian character of the whole retable. The series starts with The Offering of Mary in the Temple, followed by The Miracle with the Rod. The central part of the altar would have contained consecutive depictions supplementing the story of the Holy Virgin Mary, closed by the last wings, i.e. The Slaughter of the Innocents and Respite While Fleeing to Egypt. Comparative analyses with the forms of other European altar structures make it feasible to determine the existence of a number of other presumable combinations of the retable’s appearance. The absence of information concerning other fragments of the retable and the technique of their execution, as well as the central part (carved or painted), also decidedly reduces the possibility of explaining the original appearance of the altar and multiplies assorted variants. Apparently, there is no doubt as regards the appearance of the altar with a closed middle part, which showed likenesses of saints standing against the backdrop of walls. The style of the execution of the wings, the original polychrome, and the selection of the topics, together with a comparative analysis involving other European retables from a similar period provide only a partial solution to the original appearance of the altar from Wróblewo, which reflected, e. g. Low Countries and German impact. Due to the absence of more numerous data, the selection of one of the solutions proposed in the article, or elsewhere, continues to remain an open issue

Chloroplastic Serine Hydroxymethyltransferase From Medicago truncatula: A Structural Characterization

Serine hydroxymethyltransferase (SHMT, EC 2.1.2.1) is a pyridoxal 5′-phosphate (PLP)-dependent enzyme which catalyzes the reversible serine-to-glycine conversion in either a tetrahydrofolate-dependent or -independent manner. The enzyme is also responsible for the tetrahydrofolate-independent cleavage of other β-hydroxy amino acids. In addition to being an essential player in the serine homeostasis, SHMT action is the main source of activated one-carbon units, which links SHMT activity with the control of cell proliferation. In plants, studies of SHMT enzymes are more complicated than of those of, e.g., bacterial or mammalian origins because plant genomes encode multiple SHMT isozymes that are targeted to different subcellular compartments: cytosol, mitochondria, plastids, and nucleus. Here we report crystal structures of chloroplast-targeted SHMT from Medicago truncatula (MtSHMT3). MtSHMT3 is a tetramer in solution, composed of two tight and obligate dimers. Our complexes with PLP internal aldimine, PLP-serine and PLP-glycine external aldimines, and PLP internal aldimine with a free glycine reveal structural details of the MtSHMT3-catalyzed reaction. Capturing the enzyme in different stages along the course of the slow tetrahydrofolate-independent serine-to-glycine conversion allowed to observe a unique conformation of the PLP-serine γ-hydroxyl group, and a concerted movement of two tyrosine residues in the active site

Program CINDI w Polsce: wizja i rzeczywistość. Historia 25 lat działalności

The CINDI (Countrywide Integrated Noncommunicable Diseases Intervention) programme of the World Health Organization is one of the most famous long-term international intervention and research programmes focused on health promotion and prevention of chronic non-communicable diseases on a population scale. The origins of the CINDI Programme date back to the early 1990s, when on the initiative of the WHO European Office and a group of European countries interested in the prevention of noncommunicable diseases, several countries from the European region and Canada joined the international network. In Poland the CINDI initiatives were coordinated by the Department of Preventive and Social Medicine, Medical University of Lodz, and several other urban centres (among others Kalisz, Ostrów Wielkoposki, Chorzów, Toruń, Pabianice, Cieszyn, Włocławek, Przemyśl, Pleszew, Rawa Mazowiecka) joined the national programme activities. This article presents the most important achievements of the CINDI programme, with particular emphasis on health monitoring activities, training of medical staff, and innovative educational and intervention programmes. The anti-tobacco campaign “Quit and Win”, the National Physical Activity Campaign “Revitalize Your Heart” as well as several representative population health surveys in Łódź and Toruń turned out to be particularly successful. Taking into account the social, medical and economic benefits resulting from the long-term activities of the CINDI programme, the authors emphasized the need to undertake further initiatives and out-lined the prospects for development of the programme on a national and international scale.Program CINDI (Countrywide Integrated Noncommunicable Diseases Intervention Programe) Światowej Organizacji Zdrowia należy do najbardziej znanych wieloletnich międzynarodowych programów interwencyjno-badawczych ukierunkowanych na promocję zdrowia i zapobieganie przewlekłym chorobom niezakaźnym w skali populacyjnej. Początki Programu sięgają początku lat 90. Ubiegłego stulecia, kiedy to z inicjatywy Biura Europejskiego WHO oraz grupy krajów europejskich zainteresowanych profilaktyką chorób cywilizacyjnych stworzono sieć obejmującą kilkadziesiąt krajów z obszaru europejskiego WHO i Kanadę. W Polsce działania programu CINDI koordynowała Katedra Medycyny Społecznej i Zapobiegawczej Uniwersytetu Medycznego w Łodzi, a do sieci ośrodków współpracujących włączały się inne jednostki m.in. z Kalisza, Ostrowa Wielkopolskiego, Chorzowa, Torunia, Pabianic, Cieszyna, Włocławka, Przemyśla, Pleszewa, Rawy Mazowieckiej. W niniejszym artykule przedstawiono najważniejsze osiągnięcia programu CINDI, ze szczególnym uwzględnieniem działań monitorujących stan zdrowia, szkolenia kadr medycznych, innowacyjnych programów edukacyjno-interwencyjnych. Szczególnym sukcesem okazały się m.in. kampania antytytoniowa „Rzuć palenie i wygraj”, Ogólnopolska Kampania Aktywności Fizycznej “Postaw serce na nogi”, a także kilkukrotne populacyjne reprezentatywne badania stanu zdrowia ludności w Łodzi i Toruniu. Mając na uwadze społeczne, medyczne i ekonomiczne korzyści wynikające z wieloletnich działań programu CINDI, autorzy podkreślili potrzebę podejmowania dalszych tego typu inicjatyw oraz zakreślili perspektywy dalszego rozwoju programu w skali krajowej i międzynarodowej

The impact of self–narratives of motherhood for mothers of children with autism

The main goal of this study was to identify the impact of a narrative construction of a life challenge - discovering to have a child with autism - on the meaning of life and on resources for coping depending on the challenge’s novelty, i.e. the number of years from the diagnosis. 364 mothers of children with autism participated in a long–term 3x2 experiment. Half of the mothers had children with autism at the age of 9–12 years. For the remaining half, having children with autism was a new and stressful life situation. Their children were 2–3 years old and just diagnosed by a medical center as having autism spectrum disorder. The mothers were assigned to one of three study conditions: they were either asked to write stories of their motherhood or to describe their children’s behavior on a questionnaire or they did not participate in any tasks. One month and then four months after this task the participants completed measures of meaning of life and several well–being scales. The results indicated that following the narrative writing the participants had the highest scores on the meaning of life and well–being scales. This affect was sustained over 4 months and was significant only for mothers with older children. The mediation analysis showed that the effects of the experimental conditions on different well–being scales were mediated by the changes in perceived meaning of life. The results suggest that construction of self–narratives of difficult ongoing challenges facilitates meaning making and subsequently strengthens resources for coping. However, it seems that a meaning-making construction of such self–story may be blocked by the uncertainty and stress caused by novelty of the challenging situation

New aspects of DNA recognition by group II WRKY transcription factor revealed by structural and functional study of AtWRKY18 DNA binding domain

WRKY transcription factors (TFs) constitute one of the largest families of plant TFs. Based on the organization of domains and motifs, WRKY TFs are divided into three Groups (I-III). The WRKY subgroup IIa includes three representatives in A. thaliana, AtWRKY18, AtWRKY40, and AtWRKY60, that participate in biotic and abiotic stress responses. Here we present crystal structures of the DNA binding domain (DBD) of AtWRKY18 alone and in the complex with a DNA duplex containing the WRKY-recognition sequence, W-box. Subgroup IIa WRKY TFs are known to form homo and heterodimers. Our data suggest that the dimerization interface of the full-length AtWRKY18 involves contacts between the DBD subunits. DNA binding experiments and structural analysis point out novel aspects of DNA recognition by WRKY TFs. In particular, AtWRKY18-DBD preferentially binds an overlapping tandem of W-boxes accompanied by a quasi-W-box motif. The binding of DNA deforms the B-type double helix, which suggests that the DNA fragment must be prone to form a specific structure. This can explain why despite the short W-box consensus, WRKY TFs can precisely control gene expression. Finally, this first experimental structure of a Group II WRKY TF allowed us to compare Group I-III representatives

Image_1_Chloroplastic Serine Hydroxymethyltransferase From Medicago truncatula: A Structural Characterization.PDF

<p>Serine hydroxymethyltransferase (SHMT, EC 2.1.2.1) is a pyridoxal 5′-phosphate (PLP)-dependent enzyme which catalyzes the reversible serine-to-glycine conversion in either a tetrahydrofolate-dependent or -independent manner. The enzyme is also responsible for the tetrahydrofolate-independent cleavage of other β-hydroxy amino acids. In addition to being an essential player in the serine homeostasis, SHMT action is the main source of activated one-carbon units, which links SHMT activity with the control of cell proliferation. In plants, studies of SHMT enzymes are more complicated than of those of, e.g., bacterial or mammalian origins because plant genomes encode multiple SHMT isozymes that are targeted to different subcellular compartments: cytosol, mitochondria, plastids, and nucleus. Here we report crystal structures of chloroplast-targeted SHMT from Medicago truncatula (MtSHMT3). MtSHMT3 is a tetramer in solution, composed of two tight and obligate dimers. Our complexes with PLP internal aldimine, PLP-serine and PLP-glycine external aldimines, and PLP internal aldimine with a free glycine reveal structural details of the MtSHMT3-catalyzed reaction. Capturing the enzyme in different stages along the course of the slow tetrahydrofolate-independent serine-to-glycine conversion allowed to observe a unique conformation of the PLP-serine γ-hydroxyl group, and a concerted movement of two tyrosine residues in the active site.</p

Structural basis of methotrexate and pemetrexed action on serine hydroxymethyltransferases revealed using plant models

Serine hydroxymethyltransferases (SHMTs) reversibly transform serine into glycine in a reaction accompanied with conversion of tetrahydrofolate (THF) into 5,10-methylene-THF (5,10-meTHF). In vivo, 5,10-meTHF is the main carrier of one-carbon (1C) units, which are utilized for nucleotide biosynthesis and other processes crucial for every living cell, but hyperactivated in overproliferating cells (e.g. cancer tissues). SHMTs are emerging as a promising target for development of new drugs because it appears possible to inhibit growth of cancer cells by cutting off the supply of 5,10-meTHF. Methotrexate (MTX) and pemetrexed (PTX) are two examples of antifolates that have cured many patients over the years but target different enzymes from the folate cycle (mainly dihydrofolate reductase and thymidylate synthase, respectively). Here we show crystal structures of MTX and PTX bound to plant SHMT isozymes from cytosol and mitochondria-human isozymes exist in the same subcellular compartments. We verify inhibition of the studied isozymes by a thorough kinetic analysis. We propose to further exploit antifolate scaffold in development of SHMT inhibitors because it seems likely that especially polyglutamylated PTX inhibits SHMTs in vivo. Structure-based optimization is expected to yield novel antifolates that could potentially be used as chemotherapeutics