Migracja i inwazyjność komórek nowotworowych; rola plastyczności komórek i udział macierzy zewnątrzkomórkowej w tworzeniu przerzutów

Migratory and invasive potential of the cell is determined by the type of a tissue from which the cell derives. However, in case of neoplastic cells they display some plasticity of a phenotype which enables changes in the mode of migration. These transitions may influence the metastatic potential of the tumour. Processes described vitally depend on the tumour microenvironment and may be regulated by the dynamic of the extracellular matrix alterations.Zdolność komórek do migracji jest determinowana przez rodzaj tkanki, z jakiej się wywodzą. W przypadku komórek nowotworowych możliwa jest jednak pewna plastyczność fenotypu, umożliwiająca zmianę typu migracji. Zmiany te mogą mieć wpływ na poziom inwazyjności nowotworu. Opisywane procesy pozostają w ścisłej zależności od mikrośrodowiska, w jakim znajdują się komórki i mogą być regulowane przez zmiany zachodzące w macierzy zewnątrzkomórkowej, która w dynamiczny sposób wpływa na potencjał migracyjny i inwazyjny

The significance of c.690G>T polymorphism (rs34529039) and expression of the CEBPA gene in ovarian cancer outcome

The CEBPA gene is known to be mutated or abnormally expressed in several cancers. This is the first study assessing the clinical impact of CEBPA gene status and expression on the ovarian cancer outcome. The CEBPA gene sequence was analyzed in 118 ovarian cancer patients (44 platinum/cyclophosphamide (PC)-treated and 74 taxane/platinum (TP)-treated), both in tumors and blood samples, and in blood from 236 healthy women, using PCR-Sanger sequencing and Real-Time quantitative PCR (qPCR)-based genotyping methods, respectively. The CEBPA mRNA level was examined with Reverse Transcription quantitative PCR (RT-qPCR). The results were correlated to different clinicopathological parameters. Thirty of 118 (25.4%) tumors harbored the CEBPA synonymous c.690G>T polymorphism (rs34529039), that we showed to be related to up-regulation of CEBPA mRNA levels (p=0.0059). The presence of the polymorphism was significantly associated with poor prognosis (p=0.005) and poor response to the PC chemotherapy regimen (p=0.024). In accordance, elevated CEBPA mRNA levels negatively affected patient survival (pT, p.(Thr230Thr) (rs34529039) polymorphism of the CEBPA gene, together with up-regulation of its mRNA expression, are negative factors worsening ovarian cancer outcome. Their adverse clinical effect depends on a therapeutic regimen used, which might make them potential prognostic and predictive biomarkers for response to DNA-damaging chemotherapy

The RNA-binding landscape of HAX1 protein indicates its involvement in translation and ribosome assembly

HAX1 is a human protein with no known homologues or structural domains. Mutations in the HAX1 gene cause severe congenital neutropenia through mechanisms that are poorly understood. Previous studies reported the RNA-binding capacity of HAX1, but the role of this binding in physiology and pathology remains unexplained. Here, we report the transcriptome-wide characterization of HAX1 RNA targets using RIP-seq and CRAC, indicating that HAX1 binds transcripts involved in translation, ribosome biogenesis, and rRNA processing. Using CRISPR knockouts, we find that HAX1 RNA targets partially overlap with transcripts downregulated in HAX1 KO, implying a role in mRNA stabilization. Gene ontology analysis demonstrated that genes differentially expressed in HAX1 KO (including genes involved in ribosome biogenesis and translation) are also enriched in a subset of genes whose expression correlates with HAX1 expression in four analyzed neoplasms. The functional connection to ribosome biogenesis was also demonstrated by gradient sedimentation ribosome profiles, which revealed differences in the small subunit:monosome ratio in HAX1 WT/KO. We speculate that changes in HAX1 expression may be important for the etiology of HAX1-linked diseases through dysregulation of translation

Conceivability and possibility : some dilemmas for Humeans

This research is published within the Project ‘The Logic of Conceivability’, funded by the European Research Council (ERC CoG), Grant Number 681404.The Humean view that conceivability entails possibility can be criticized via input from cognitive psychology. A mainstream view here has it that there are two candidate codings for mental representations (one of them being, according to some, reducible to the other): the linguistic and the pictorial, the difference between the two consisting in the degree of arbitrariness of the representation relation. If the conceivability of P at issue for Humeans involves the having of a linguistic mental representation, then it is easy to show that we can conceive the impossible, for impossibilities can be represented by meaningful bits of language. If the conceivability of P amounts to the pictorial imaginability of a situation verifying P, then the question is whether the imagination at issue works purely qualitatively, that is, only by phenomenological resemblance with the imagined scenario. If so, the range of situations imaginable in this way is too limited to have a significant role in modal epistemology. If not, imagination will involve some arbitrary labeling component, which turns out to be sufficient for imagining the impossible. And if the relevant imagination is neither linguistic nor pictorial, Humeans will appear to resort to some representational magic, until they come up with a theory of a ‘third code’ for mental representations.Publisher PDFPeer reviewe

Good practices in the creation of the Commune Revitalization Program – cooperation between the University of Adam Mickiewicz and the City of Kalisz

Wejście w życie ustawy o rewitalizacji (Dz.U. z 2015 r. poz. 1777 z późn. zm.) z dniem 18 listopada 2015 r. umożliwiło gminom sprawne planowanie i wdrażanie procesu wyprowadzania obszarów zdegradowanych ze stanu kryzysowego. W ustawie znalazły się kluczowe uregulowania wpływające na programowanie rewitalizacji w Polsce. Jednym z najważniejszych instrumentów jest gminny program rewitalizacji (GPR). Aby móc w pełni wykorzystać potencjał, jaki drzemie w tym dokumencie, należy szukać rozwiązań pozwalających na stworzenie go w jak najbardziej kompleksowej formie. Jednym z przykładów takich działań jest współpraca ośrodka uniwersyteckiego z jednostką samorządu terytorialnego. Można powiedzieć, że dzięki połączeniu wiedzy praktycznej urzędników z wiedzą teoretyczną ekspertów ze środowiska akademickiego uzyskano projekt unikalny w skali kraju. Jest także wyjątkowy dlatego, że w procesie jego tworzenia aktywnie uczestniczyli studenci gospodarki przestrzennej. Celem artykułu jest przedstawienie przebiegu procesu współpracy Uniwersytetu im. Adama Mickiewicza z urzędem podczas sporządzania Gminnego Programu Rewitalizacji dla miasta Kalisza oraz ukazanie roli, jaką odegrali w tym projekcie studenci.The entry of the Revitalization Act on November 18, 2015 enabled municipalities to efficiently plan and conduct the process of moving degraded areas out of the crisis. The Act introduced key regulations affecting the programming of revitalization in Poland. One of the most important instruments is the Municipal Revitalization Program. In order to be able to fully use the potential of this document, we should look for solutions that allow creating the most comprehensive solutions. One of the examples of such activities is cooperation between the university and the local government. Thanks to this combination of practical knowledge of officials with theoretical knowledge of academic experts, we can say that it is a project unique in the country. It is also unique due to the fact that spatial economy students who actively participated in the document creation process were included in the work. The aim of the work is to present the course of the cooperation process of the University of Adam Mickiewicz with the Office during the preparation of the Municipal Revitalization Program for the city of Kalisz and showing the role that the students included in the project played in this project

Cell Death by Entosis: Triggers, Molecular Mechanisms and Clinical Significance

Entosis—a homotypic insertion of one cell into another, resulting in a death of the invading cell—has been described in many reports, but crucial aspects of its molecular mechanisms and clinical significance still remain controversial. While actomyosin contractility of the invading cell is very well established as a driving force in the initial phase, and autophagy induced in the outer cell is determined as the main mechanism of degradation of the inner cell, many details remain unresolved. The multitude of triggering factors and crisscrossing molecular pathways described in entosis regulation make interpretations difficult. The question of the physiological role of entosis also remains unanswered. In this review, we summarize the knowledge of molecular mechanisms and clinical data concerning entosis accumulated so far, highlighting both coherent explanations and controversies

Wpływ płci na wyniki analizy rzeźnej kuropatwy polnej Perdix perdix

The experimental material included grey partridges Perdix perdix planned for re-introduction into the natural habitat, reared at the Center of Game Breeding on the area of Mazovia Province. 10 hens and 10 roosters were selected for slaughter. After exsanguination, plucking and evisceration, the birds were cooled for 24 h to a temperature of 4°C. The carcasses were subjected to dissection to enable determination of dressing percentage and calculation in the carcass contents of: breast muscles, leg muscles, adipose fat and giblets. The study showed no effect of sex on results of slaughter analysis of grey partridge.Wpływ płci na wyniki analizy rzeźnej kuropatwy polnej Perdix perdix. Materiał badawczy stanowiły kuropatwy polne Perdix perdix przeznaczone do wsiedlenia do środowiska naturalnego, odchowywane w Ośrodku Hodowli Zwierzyny na terenie województwa mazowieckiego. Do uboju wybrano po 10 kur i 10 kogutów. Ptaki po skrwawieniu, oskubaniu i wypatroszeniu schłodzono w ciągu 24 h do temperatury 4°C, przeprowadzono dysekcję, na podstawie której określono wydajność rzeźną oraz obliczono udział w tuszce: mięśni piersiowych, mięśni nóg, tłuszczu sadełkowego i podrobów. Nie wykazano wpływu płci na wyniki analizy rzeźnej kuropatwy polnej

Charakterystyka włókien mięśniowych mięśni piersiowych i nóg kuropatwy polnej Perdix perdix

Characteristics of muscle fibers of breast and leg muscles of grey partridges Perdix perdix. The experimental material included grey partridges Perdix perdix L. planned for reintroduction into the natural habitat, reared at the Game Breeding Center on the area of Mazovia Province. 10 females and 10 males were selected for slaughter. The birds were slaughtered in poultry abattoir and specimens of their pectoral superficial muscle (pectoralis superfi cialis) and biceps femoris muscle (biceps femoris) were sampled. A greater diameter of fibers was determined for breast muscles. The study did not show any effect of sex on muscle fiber diameter of breast and leg muscles of grey partridges Perdix perdix.Charakterystyka włókien mięśniowych mięśni piersiowych i nóg kuropatwy polnej Perdix perdix. Materiał badawczy stanowiły kuropatwy polne Perdix perdix L. przeznaczone do wsiedlenia do środowiska naturalnego, odchowywane w Ośrodku Hodowli Zwierzyny na terenie województwa mazowieckiego. Do uboju wybrano po 10 kur i 10 kogutów. Ptaki ubito, a następnie pobrano próbki mięśni piersiowych (pectoralis superfi cialis) oraz mięśni nóg (biceps femoris). Większą średnicą włókien charakteryzowały się mięśnie piersiowe. Nie wykazano wpływu płci na średnicę włókien mięśni piersiowych i mięśni nóg kuropatwy polnej Perdix perdix

Wpływ płci na jakość mięsa dzika europejskiego (Sus scrofa scrofa)

Forty carcasses (38.6-45.9 kg) from male and female (1:1) wild boar, which were shot in one hunting area during the 2014/2015 season, were studied. Samples of MLD were analysed for proximate chemical composition and fatty acid content of IMF as well as shear force and WHC. AI and TI index were calculated. Statistical analysis confirmed a significant (P≤0.05) effect of sex on the water content of MLD, which was higher in males than in females. Protein content of MLD was high and averaged 24%. Meat was lean with IMF below 2.0%. The PUFA/SFA ratio was similar in both groups of sex, and the dietetically beneficial n-6/n-3 PUFA ratio was less than 4:1 because the proportion of n-3 PUFA was high at 4.7-5.1 g/100 g fat. The effect of sex of wild boar on AI was significantly (P≤0.05) higher in males than in females. The results obtained show that the meat of wild boar of both groups of sex would be a rich source of protein in the human diet as well as a source of long-chain n-3 PUFA. The high level of long-chain n-3 PUFA is in line with dietary recommendations for the low n-6/n-3 PUFA. Due to its health-promoting benefits, wild boar meat may provide an alternative to the meat of farm animals.Wpływ płci na jakość mięsa dzika europejskiego (Sus scrofa scrofa). Badania przeprowadzono na 40 tuszach (38.6-45.9kg) pozyskanych od dzików obu płci (1:1) odstrzelonych w jednym rejonie łowieckim centralnej Polski, w sezonie 2014/2015. W próbkach MLD określono podstawowy skład chemiczny i zawartość kwasów tłuszczowych w IMF oraz siłę cięcia i WHC, a także obliczono wartość indeksów AI i TI. Analiza statystyczna potwierdziła istotny (P≤0.05) wpływ płci na zawartość wody w MLD, która była większa u samców niż u samic. Zawartość białka w MLD była duża i wynosiła średnio 24%. Mięso było chude - poziom IMF wynosił poniżej 2.0%. Stosunek PUFA/SFA był zbliżony u obu płci. Korzystna ze względów dietetycznych relacja PUFA n-6/PUFA n-3 wynosiła mniej niż 4:1, ponieważ udział kwasów PUFA n-3 w IMF był wysoki i wynosił 4.7-5.1g/100g tłuszczu. Potwierdzono wpływ płci dzików na wartość indeksu AI, który był istotnie (P≤0.05) większy u samców niż u samic. Uzyskane wyniki wskazują, że mięso dzików obu płci może być bogatym źródłem białka w diecie człowieka, a także źródłem długołańcuchowych kwasów PUFA n-3. Wysoki poziom długołańcuchowych PUFA n-3 koresponduje z zaleceniami dietetyków odnośnie niskiego stosunku PUFA n-6/n-3. Ze względu na swoje walory prozdrowotne mięso dzika może stanowić alternatywę w porównaniu dla mięsa zwierząt gospodarskich

Impact of Delta SARS-CoV-2 Infection on Glucose Metabolism: Insights on Host Metabolism and Virus Crosstalk in a Feline Model

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes enhanced mortality in people with metabolic and cardiovascular diseases. Other highly infectious RNA viruses have demonstrated dependence on glucose transport and utilization, so we hypothesized that SARS-CoV-2 infection could lead to alterations in cellular and whole-body glucose metabolism. Twenty-four healthy domestic cats were intratracheally inoculated with B.1.617.2 (delta) SARS-CoV-2 and samples were collected at 4- and 12-days post-inoculation (dpi). Blood glucose and circulating cortisol concentrations were elevated at 4 and 12 dpi. Serum insulin concentration was statistically significantly decreased, while angiotensin 2 concentration was elevated at 12 dpi. SARS-CoV-2 RNA was detected in the pancreas and skeletal muscle at low levels; however, no change in the number of insulin-producing cells or proinflammatory cytokines was observed in the pancreas of infected cats through 12 dpi. SARS-CoV-2 infection statistically significantly increased GLUT protein expression in both the heart and lungs, correlating with increased AMPK expression. In brief, SARS-CoV-2 increased blood glucose concentration and cardio-pulmonary GLUT expression through an AMPK-dependent mechanism, without affecting the pancreas, suggesting that SARS-CoV-2 induces the reprogramming of host glucose metabolism. A better understanding of host cell metabolism and virus crosstalk could lead to the discovery of novel metabolic therapeutic targets for patients affected by COVID-19