118 research outputs found
Intratumoral functional heterogeneity and chemotherapy
Intratumoral heterogeneity including genetic and nongenetic mechanisms refers to biological differences amongst malignant cells originated within the same tumor. Both, cell differentiation hierarchy and stochasticity in gene expression and signaling pathways may result in phenotypic differences of cancer cells. Since a tumor consists of cancer cell clones that display distinct behaviours, changes in clonal proliferative behavior may also contribute to the phenotypic variability of tumor cells. There is a need to reveal molecular actions driving chemotherapeutic resistance in colon cancer cells. In general, it is widely hypothesized that therapeutic resistance in colorectal cancer is a consequence of the preferential survival of cancer stem cells. However, recent data regarding colorectal cancer suggest that resistance to anticancer therapy and post-therapeutic tumor reappearence could be related to variations of clonal dynamics. Understanding the interaction of genetic and nongenetic determinants influencing the functional diversity and therapy response of tumors should be a future direction for cancer research
Submicron plasticity: yield stress, dislocation avalanches, and velocity distribution
The existence of a well defined yield stress, where a macroscopic piece of
crystal begins to plastically flow, has been one of the basic observations of
materials science. In contrast to macroscopic samples, in micro- and
nanocrystals the strain accumulates in distinct, unpredictable bursts, which
makes controlled plastic forming rather difficult. Here we study by simulation,
in two and three dimensions, plastic deformation of submicron objects under
increasing stress. We show that, while the stress-strain relation of individual
samples exhibits jumps, its average and mean deviation still specify a
well-defined critical stress, which we identify with the jamming-flowing
transition. The statistical background of this phenomenon is analyzed through
the velocity distribution of short dislocation segments, revealing a universal
cubic decay and an appearance of a shoulder due to dislocation avalanches. Our
results can help to understand the jamming-flowing transition exhibited by a
series of various physical systems.Comment: 5 page
Primer immunhiány és autoimmun betegségek
Absztrakt:
A primer immunhiányos betegsĂ©gek a termĂ©szetes Ă©s az adaptĂv immunrendszer
elemeit érintő, genetikailag heterogén immunológiai rendellenességek. A primer
immunhiányban szenvedĹ‘ betegek nemcsak visszatĂ©rĹ‘ fertĹ‘zĂ©sekre, de noninfektĂv
kĂłrállapotokra, Ăgy gyulladásos vagy granulomatosus eltĂ©rĂ©sekre,
lymphoproliferativ és szolid daganatos megbetegedésekre, autoinflammatiós
állapotokra, valamint a legkülönfélébb autoimmun kórformákra is hajlamosabbak.
Az elsődleges immunhiány és az autoimmunitás paradoxonnak tűnő együttes
megjelenĂ©se valĂłdi kihĂvást jelent az immunhiányos betegek autoimmun
szövődményeinek felismerésében. A primer immunhiányos állapotok hátterében
általában egy vagy több, az immunregulációban és/vagy az immuntolerancia
kialakĂtásában kulcsszerepet játszĂł gĂ©n mutáciĂłja áll. A szerteágazĂł
immunológiai rendellenességek, a kompenzatorikus, túlzott mértékű krónikus
gyulladásos válaszreakció és a következményes szövetkárosodás együttese végső
soron szerv-, sejtspecifikus vagy szisztémás autoimmun betegségek kialakulásához
vezet. Számos primer immunhiányos kórképet különböző, sajátos autoimmun
manifesztáció jellemez. A jelen összefoglaló célja a primer immunhiányos
állapotokban megjelenő autoimmun kórképek, valamint az immunrendszeri
rendellenességek alapjául szolgáló molekuláris és celluláris mechanizmusok
áttekintĂ©se. A dolgozat vĂ©gĂ©n ismertetett eset rávilágĂt arra, hogy immunhiányos
állapotokban az autoimmun betegségek felismerése, illetve a dominálóan autoimmun
kĂłrkĂ©p formájában indulĂł fenotĂpusoknál az immunhiány kĂłrismĂ©zĂ©se egyaránt
kihĂvást jelenthet. Orv Hetil. 2018; 159(23): 908–918.
|
Abstract:
Primary immunodeficiencies consist of a group of genetically heterogeneous immune
disorders affecting distinct elements of the innate and adaptive immune system.
Patients with primary immunodeficiency are more prone to develop not only
recurrent infections, but non-infectious complications, like inflammatory or
granulomatous conditions, lymphoproliferative and solid malignancies,
autoinflammatory disorders, and a broad spectrum of autoimmune diseases. The
concomitant appearance of primary immunodeficiency and autoimmunity appears to
be rather paradoxical, therefore making the diagnosis of immunodeficiency
patients with autoimmune complications challenging. Mutations of one or more
genes playing a fundamental role in immunoregulation and/or immune tolerance
network are thought to be responsible for primary immunodeficiencies. The
diverse immunological abnomalities along with the compensatory and excessive
sustained inflammatory response result in tissue damage and finally in
manifestation of organ-, cell-specific or systemic autoimmune diseases. Several
forms of primary immunodeficiency disorders are characterized by a variety of
specific autoimmune phenomena. This overview addresses the spectrum of
autoimmune diseases associated with primary immunodeficiencies, and explores the
molecular and cellular mechanisms underlying abnormalities of the immune system.
The case presented finally highlights that both the recognition of autoimmune
diseases in association with immunodeficiencies and the diagnosis of
immunodefiency in those phenotypes with predominant autoimmunity could be
challenging. Orv Hetil. 2018; 159(23): 908–918
Migráció, helyi társadalom, identitás = Migration, local society, identity
A vizsgált telepĂĽlĂ©seken az elmĂşlt másfĂ©l Ă©vtizedben a migráciĂłs folyamatok polarizálĂłdásának lehetĂĽnk tanĂşi. A falvak egy rĂ©sze a nĂ©pessĂ©g tartĂłs csökkenĂ©sĂ©nek következmĂ©nyeivel, az elöregedĂ©ssel, a fiatal, kĂ©pzett generáciĂłk eltűnĂ©sĂ©vel kĂĽszködik, mĂg a szuburb falvak Ă©ppen a nĂ©pessĂ©g gyors növekedĂ©sĂ©bĹ‘l fakadĂł problĂ©mákat igyekeznek kezelni. A nĂ©met kisebbsĂ©g, a kisebbsĂ©gi politizálás esĂ©lyei felĹ‘l nĂ©zve mindkĂ©t irányĂş migráciĂłs folyamat kedvezĹ‘tlen: egyrĂ©szt kiĂĽrĂĽlnek a kisebbsĂ©gi kultĂşra, Ă©rdekkĂ©pviselet intĂ©zmĂ©nyesĂĽlt formái, másrĂ©szt a helyi hatalomban mind nagyobb mĂ©rtĂ©kű a svábok tĂ©rvesztĂ©se. Ha a nĂ©met kisebbsĂ©g asszimiláciĂłrĂłl beszĂ©lĂĽnk, akkor egyĂşttal a kisebbsĂ©gi identitás alakváltozásairĂłl beszĂ©lĂĽnk. A vegyes házasságok - köttessenek bár kisebbsĂ©gek, kisebbsĂ©g Ă©s többsĂ©g között -, valamint a nĂ©metek magyar hazával szembeni mindenkori lojalitása, a többes etnikai, kulturális identitás lehetĹ‘sĂ©gĂ©t teremtik meg s táplálják. A kisebbsĂ©gi identitás elszakadása a családon belĂĽl áthagyományozott tradicionális lokális kultĂşrátĂłl Ă©s dialektustĂłl, nem csak azt eredmĂ©nyezi, hogy a magyarországi nĂ©metek számára a kultĂşra, a (nĂ©met irodalmi) nyelv az iskolában elsajátĂtandĂł tartalommá vált (amely egyĂ©bkĂ©nt bárki más számára is hozzáfĂ©rhetĹ‘), hanem azt is, hogy a nemzetisĂ©gi identitás, kötĹ‘dĂ©s (kĂĽlönösebb kockázat nĂ©lkĂĽli) választás kĂ©rdĂ©se lett. Ez viszont azt is jelenti, hogy közössĂ©gi identitáskĂ©nt valĂł megmaradása, fenntartása csak tudatos, intĂ©zmĂ©nyĂ©pĂtĹ‘ politikával biztosĂthatĂł. | In the settlements under survey in the past fifteen years the polarisation of migration tendencies could be observed. A part of the villages struggles with a steady decrease of population , with ageing population and the lack of the young qualified inhabitants, whereas suburban villages try to cope with the problems deriving from the quick increase in population number. In general, for the chances of political representation of ethnic and national minorities both types of migration tendency have proved to be unfavourable. The institutionalised forms of the representation of minority culture and the enforcement of minority rights have become emptied; on the other hand Germans have lost considerable positions and functions in shaping local politics. In case the assimilation of the German minority is taken into consideration, then, at the same time, it should be understood as a transformation of the forms of minority identity. Mixed marriages and the persisting loyalty of Germans to Hungary as homeland establish and promote the possibility of multiple ethnic and cultural identity. The secession of minority identity from the traditional local culture and dialect formerly transmitted within the families results not only in that for Germans in Hungary German culture and standard German language has become a subject to be acquired at educational institutions, but also in that national identity and attachment has become a matter of choice. This means that the maintenance of communal minority identity can only be ensured with conscious institution-constructing policy
Arabidopsis NAP-related proteins (NRPs) are soluble nuclear proteins immobilized by heat
Nucleosome assembly protein-related proteins (NRPs) are multifunctional proteins having histone chaperone and phosphatase inhibitor properties. Although it is believed that these proteins are nuclear and bind the chromatin, they can be detected in the cytoplasmic but not in the nuclear protein fraction by immunoblotting analysis. It is shown here that under normal conditions, NRPs are nuclear but soluble and leak out of the nuclei during their purification. However, under elevated temperatures (above 42 degrees C), NRPs display significantly reduced mobility and are retained in the nuclei during purification probably due to binding other immobile macromolecules in the nucleus. Our observations highlight the necessity to use different techniques in parallel to unambiguously determine the intracellular localization of proteins. As heat adapted (38 degrees C, 2 h followed by 2 h recovery) and heat shocked (45 degrees C, 1 h), Arabidopsis seedlings were found to have phenotypes similar to those observed in the NRP loss-offunction mutants nrp1-1 nrp2-1 (short, branching roots, increased bleomycin sensitivity), it was also investigated whether the immobilization of NRPs by heat results in disturbed NRP functions. The results indicated, however, that heat affected the investigated traits independent on the presence of NRPs
NagyfelbontásĂş elválasztástechnikai mĂłdszerek (MEKC, CZE) fejlesztĂ©se. Gyakorlati alkalmazások biolĂłgiailag aktĂv molekulák fizikai-kĂ©miai Ă©s biolĂłgiai tulajdonságainak jellemzĂ©sĂ©re = Development of high performance separation techniques (MEKC, CZE). Practical applications for physico-chemical and biological characterisation of biologically active molecules
Az elválasztási mĂłdszerek fejlesztĂ©se során vizsgáltuk a CZE-ben puffer mĂłdosĂtĂłkĂ©nt alkalmazott szerves oldĂłszereknek az elválasztási mechanizmusra, az analizált molekula konformáciĂłjára/szolvatáciĂłjára gyakorolt hatását. MegkezdtĂĽk a biokompatiblis CZE mĂłdszerek kifejlesztĂ©se során alkalmazhatĂł polimer bevonatok tulajdonságainak, alkalmazhatĂłságának vizsgálatát.BizonyĂtottuk, hogy a MEKC-ben bevezetett relatĂv micelláris fázistartĂłzkodási idĹ‘ alkalmas egyrĂ©szt az analizált molekulák lipofilitásának kĂsĂ©rleti meghatározására, másrĂ©szt alkalmas a MEKC-ben alkalmazandĂł micelláris fázisok lipofilitásának számszerű jellemzĂ©sĂ©re. BevezettĂĽk a CLOGP50 fogalmát, amely az a lipofilitási Ă©rtĂ©k, amellyel rendelkezĹ‘ molekula teljes analĂzis idejĂ©nek Ă©ppen a felĂ©t tölti a micelláris fázisban. BizonyĂtottuk, hogy ez a CLOGP50 Ă©rtĂ©k alkalmas a micelláris fázisok egymással valĂł összehasonlĂtására. Ez támpontot adhat a MEKC mĂłdszerfejlesztĂ©s során az adott elválasztási feladathoz leginkább megfelelĹ‘ megosztĂłfázis kiválasztására.CZE Ă©s HPLC mĂłdszereket dolgoztunk ki a vizsgált molekulák fizikai-kĂ©miai paramĂ©tereinek meghatározására. BizonyĂtottuk a kĂsĂ©rleti lipofilitási adatok Ă©s a molekulák biolĂłgiai aktivitása közötti jĂł összefĂĽggĂ©st. Ezeket a mĂłdszereket kĂĽlönbözĹ‘ kĂ©miai szerkezetű molekulakönyvtárak jellemzĂ©sĂ©ben, lipofilitásuk meghatározásában, valamint a szintetikus tervezĹ‘munka támogatásában az optimalizálni Ă©rdemes szerkezetek kiválasztásában használtuk fel. | Effect of the organic solvents applied as buffer modifiers in capillary zone electrophoresis (CZE) on the separation has been investigated. Development and characterization of biocompatible polymers applicable as coating material in capillary electrophoresis has been started. Application of the normalized micellar phase residence time has been suggested in micellar electrokinetic chromatography (MEKC), its applicability for the characterization of the lipohilicity of the analytes were proved. CLOGP50 value was defined and it has been applied to compare the lipophility of the pseudo-stationary phases applied in MEKC. CZE and HPLC methods has been developed and applied to determine physico-chemical parameters of molecules possessing antiproliferative activity. Good correlation between the experimentally determined physico-chemical parameters of the investigated molecules and the biological activity of the same molecules has been proved. These separation methods developed in our laboratory has been applied in characterization of molecular libraries of different chemical nature, and were applied to support the optimization of the chemical structure of the core molecules
Contribution of TLR signaling to the pathogenesis of colitis-associated cancer in inflammatory bowel disease
In the intestine a balance between proinflammatory and repair signals of the immune system is essential for the maintenance of intestinal homeostasis. The innate immunity ensures a primary host response to microbial invasion, which induces an inflammatory process to localize the infection and prevent systemic dissemination of pathogens. The key elements of this process are the germline encoded pattern recognition receptors including Toll-like receptors (TLRs). If pathogens cannot be eliminated, they may elicit chronic inflammation, which may be partly mediated via TLRs. Additionally, chronic inflammation has long been suggested to trigger tissue tumorous transformation. Inflammation, the seventh hallmark of cancer, may affect all phases of tumor development, and evade the immune system. Inflammation acts as a cellular stressor and may trigger DNA damage or genetic instability. Furthermore, chronic inflammation can provoke genetic mutations and epigenetic mechanisms that promote malignant cell transformation. Colorectal cancers in inflammatory bowel disease patients are considered typical examples of inflammation-related cancers. Although data regarding the role of TLRs in the pathomechanism of cancer-associated colitis are rather conflicting, functionally these molecules can be classified as ”largely antitumorigenic” and ”largely pro-tumorigenic” with the caveat that the underlying signaling pathways are mainly context (i.e., organ-, tissue-, cell-) and ligand-dependent
Cross-infection Experiments Confirm the Host Specificity of Goussia spp. (Eimeriidae: Apicomplexa) Parasitizing Cyprinid Fish
Summary. The host specificity of the coccidian Goussia carpell
Városi csapadĂ©kvĂzgyűjtĹ‘ tározĂł mĂ©retĂ©nek vizsgálata az 1901-2020 idĹ‘szak napi meteorolĂłgiai adatai alapján = Evaluation of urban rainwater storage sizing based on daily meteorological data for the 1901 – 2020 period
A tanulmány az Ă©pĂĽletek tetĹ‘vizeinek gyűjtĂ©sĂ©re szolgálĂł csapadĂ©kvĂz tározĂłk vizsgálatát mutatja be, egy a magyarországi viszonyok között jellemzĹ‘ tetĹ‘mĂ©rettel Ă©s egy lehetsĂ©ges vĂzhasználattal. A vizsgálat egy egyszerű, napi csapadĂ©k Ă©s hĹ‘mĂ©rsĂ©klet adatokon alapulĂł modell alapján törtĂ©nt. A modell, minthogy 120 Ă©v adatain alapul, alkalmas arra, hogy az idĹ‘közben lezajlott ingadozások Ă©s a bekövetkezett emberi tevĂ©kenysĂ©gre visszavezethetĹ‘ klĂmaváltozás hatásait bemutassa. Emellett vizsgálhatĂł az egyes járatos nĂ©vleges tĂ©rfogatĂş tározĂłk nĂ©hány jellemzĹ‘je is. A tanulmányban az Ă©ves Ă©s a fagymentes idĹ‘szakra kiterjesztett csapadĂ©kgyűjtĂ©s eredmĂ©nyeit mutattuk be. Vizsgálat tárgyát kĂ©pezte egy extrĂ©m nagy tározĂł alkalmazása is, amely során az öntözött terĂĽlet változtatása volt elemezhetĹ‘. A vizsgálatok egyik megállapĂtása az, hogy a tározás optimális mĂ©rettartományának felsĹ‘ határa a felvett bemeneti Ă©s kimenti paramĂ©terek mellett, az adott napi meteorolĂłgiai adatok figyelembevĂ©telĂ©vel a 20 m3 környezetĂ©ben helyezkedik el. A tározĂł kihasználtsága efelett lĂ©nyegĂ©ben alig Ă©rtelmezhetĹ‘ Ă©s az optimális tĂ©rfogat valahol e szint alatt találhatĂł. Vizsgáltuk azt is, hogy az egyes paramĂ©terek aránya mikĂ©nt változott az elmĂşlt Ă©vszázadban. A tanulmány megállapĂtása az, hogy az öntözĂ©si cĂ©lĂş vĂzvisszatartás mindenkĂ©pp pozitĂv hatásĂş. A nagyobb tározĂł kialakĂtása általában jobb mutatĂłkat eredmĂ©nyez, de felvethetĹ‘, hogy egy háztartás esetĂ©ben a beruházási költsĂ©gek megtĂ©rĂĽlĂ©se mikĂ©pp alakul, ez további vizsgálatok tárgya kell legyen. = The study presents the investigation of rainwater reservoirs for collecting roof water from
buildings, with a roof size typical for Hungarian conditions and a possible water use. The study
was based on a simple model based on daily precipitation and temperature data.The model
results, which took into account 120 years of data, are suitable for showing the effects of the
fluctuations that have taken place in the meantime as the spontaneous fluctuations of the climate
and by climate change that can be traced back to human activity. In addition, it was possible
to examine some of the characteristics of each reservoir with a nominal volume. In the study,
we have presented the results of rainwater collection in the case of annual (whole-year) and
seasonal (frost-free) periods. The examination of an extremely large reservoir was also the
subject of the study, during which the change in the irrigated area was analyzed. One of the findings of the tests is that the estimated upper limit of the optimal size of the reservoir. It was
found that with the frame of the recorded input and output parameters, taking into account the
meteorological data, the maximum reasonable size of the tank is around 20 m3
, although the
optimal volume is to be found well below this value. The utilization of greater reservoir cannot
be interpreted. We also examined how the ratio of individual parameters changed over the past
century. The conclusion of the study is that water retention for irrigation purposes is definitely
positive. The design of a larger reservoir usually results in better indicators, but it is possible
to raise the question of how the return on investment costs can be validate in the case of a
household. This question should be the subject of further investigations
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