evolvability Dotaz Zobrazit nápovědu
The loss of control of cell proliferation, apoptosis regulation and contact inhibition leads to tumor development. While benign tumors are restricted to their primary space, i.e. where these tumors first originate, the metastatic tumors not only disseminate- facilitated by hypoxia-driven neovascularization- to distant secondary sites but also show substantial changes in metabolism, tissue architectures, gene expression profiles and immune phenotypes. All these alterations result in radio-, chemo- and immune-resistance rendering these metastatic tumor cells refractory to therapy. Since the beginning of the transformation, these factors- which influence each other- are incorporated to the developing and metastasizing tumor. As a result, the complexities in the heterogeneity of tumor progressively increase. This space-time function in the heterogeneity of tumors is generated by various conditions and factors at the genetic as well as microenvironmental levels, for example, endogenous retroviruses, methylation and epigenetic dysregulation that may be etiology-specific, cancer associated inflammation, remodeling of the extracellular matrix and mesenchymal cell shifted functions. On the one hand, these factors may cause de-differentiation of the tumor cells leading to cancer stem cells that contribute to radio-, chemo- and immune-resistance and recurrence of tumors. On the other hand, they may also enhance the heterogeneity under specific microenvironment-driven proliferation. In this editorial, we intend to underline the importance of heterogeneity in cancer progress, its evaluation and its use in correlation with the tumor evolution in a specific patient as a field of research for achieving precise patient-tailored treatments and amelioration of diagnostic (monitoring) tools and prognostic capacity.
- MeSH
- extracelulární matrix MeSH
- lidé MeSH
- nádorové kmenové buňky MeSH
- nádorové mikroprostředí genetika MeSH
- nádory * genetika MeSH
- patologická angiogeneze MeSH
- proliferace buněk genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- úvodníky MeSH
Spermatozoa represent the morphologically most diverse type of animal cells and show remarkable variation in size across and also within species. To understand the evolution of this diversity, it is important to reveal to what degree this variation is genetic or environmental in origin and whether this depends on species' life histories. Here we applied quantitative genetic methods to a pedigreed multigenerational data set of the collared flycatcher Ficedula albicollis, a passerine bird with high levels of extra-pair paternity, to partition genetic and environmental sources of phenotypic variation in sperm dimensions for the first time in a natural population. Narrow-sense heritability (h2 ) of total sperm length amounted to 0.44 ± 0.14 SE, whereas the corresponding figure for evolvability (estimated as coefficient of additive genetic variation, CVa ) was 0.02 ± 0.003 SE. We also found an increase in total sperm length within individual males between the arrival and nestling period. This seasonal variation may reflect constraints in the production of fully elongated spermatozoa shortly after arrival at the breeding grounds. There was no evidence of an effect of male age on sperm dimensions. In many previous studies on laboratory populations of several insect, mammal and avian species, heritabilities of sperm morphology were higher, whereas evolvabilities were similar. Explanations for the differences in heritability may include variation in the environment (laboratory vs. wild), intensity of sexual selection via sperm competition (high vs. low) and genetic architecture that involves unusual linkage disequilibrium coupled with overdominance in one of the studied species.
- MeSH
- biologická evoluce MeSH
- fenotyp * MeSH
- kvantitativní znak dědičný * MeSH
- Passeriformes genetika MeSH
- spermie cytologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The extrinsic PsbU and PsbV proteins are known to play a critical role in stabilizing the Mn4CaO5 cluster of the PSII oxygen-evolving complex (OEC). However, most isolates of the marine cyanobacterium Prochlorococcus naturally miss these proteins, even though they have kept the main OEC protein, PsbO. A structural homology model of the PSII of such a natural deletion mutant strain (P. marinus MED4) did not reveal any obvious compensation mechanism for this lack. To assess the physiological consequences of this unusual OEC, we compared oxygen evolution between Prochlorococcus strains missing psbU and psbV (PCC 9511 and SS120) and two marine strains possessing these genes (Prochlorococcus sp. MIT9313 and Synechococcus sp. WH7803). While the low light-adapted strain SS120 exhibited the lowest maximal O2 evolution rates (Pmax per divinyl-chlorophyll a, per cell or per photosystem II) of all four strains, the high light-adapted strain PCC 9511 displayed even higher PChlmax and PPSIImax at high irradiance than Synechococcus sp. WH7803. Furthermore, thermoluminescence glow curves did not show any alteration in the B-band shape or peak position that could be related to the lack of these extrinsic proteins. This suggests an efficient functional adaptation of the OEC in these natural deletion mutants, in which PsbO alone is seemingly sufficient to ensure proper oxygen evolution. Our study also showed that Prochlorococcus strains exhibit negative net O2 evolution rates at the low irradiances encountered in minimum oxygen zones, possibly explaining the very low O2 concentrations measured in these environments, where Prochlorococcus is the dominant oxyphototroph.
- MeSH
- bakteriální proteiny chemie genetika fyziologie MeSH
- chlorofyl metabolismus MeSH
- fotosyntéza fyziologie MeSH
- fotosystém II - proteinový komplex chemie genetika fyziologie MeSH
- genom bakteriální MeSH
- kyslík metabolismus MeSH
- molekulární modely MeSH
- průtoková cytometrie MeSH
- sinice genetika metabolismus MeSH
- světlo MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
Robust photosynthesis in chloroplasts and cyanobacteria requires the participation of accessory proteins to facilitate the assembly and maintenance of the photosynthetic apparatus located within the thylakoid membranes. The highly conserved Ycf48 protein acts early in the biogenesis of the oxygen-evolving photosystem II (PSII) complex by binding to newly synthesized precursor D1 subunit and by promoting efficient association with the D2 protein to form a PSII reaction center (PSII RC) assembly intermediate. Ycf48 is also required for efficient replacement of damaged D1 during the repair of PSII. However, the structural features underpinning Ycf48 function remain unclear. Here we show that Ycf48 proteins encoded by the thermophilic cyanobacterium Thermosynechococcus elongatus and the red alga Cyanidioschyzon merolae form seven-bladed beta-propellers with the 19-aa insertion characteristic of eukaryotic Ycf48 located at the junction of blades 3 and 4. Knowledge of these structures has allowed us to identify a conserved "Arg patch" on the surface of Ycf48 that is important for binding of Ycf48 to PSII RCs but also to larger complexes, including trimeric photosystem I (PSI). Reduced accumulation of chlorophyll in the absence of Ycf48 and the association of Ycf48 with PSI provide evidence of a more wide-ranging role for Ycf48 in the biogenesis of the photosynthetic apparatus than previously thought. Copurification of Ycf48 with the cyanobacterial YidC protein insertase supports the involvement of Ycf48 during the cotranslational insertion of chlorophyll-binding apopolypeptides into the membrane.
- MeSH
- biologická evoluce * MeSH
- chování fyziologie klasifikace MeSH
- fyzika metody trendy MeSH
- kognitivní věda dějiny metody trendy MeSH
- lidé MeSH
- motorické neurony * fyziologie MeSH
- odměna MeSH
- princip potěšení-bolest MeSH
- protézy a implantáty trendy MeSH
- represe (psychologie) MeSH
- ryby fyziologie genetika růst a vývoj MeSH
- vědomí * fyziologie MeSH
- zraková percepce fyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
Differentiation is a central aspect of the parasite life cycle and encompasses adaptation to both host and environment. If we accept that evolution cannot anticipate an organism's needs as it enters a new environment, how do parasite differentiation pathways arise? The transition between vertebrate and insect stage African trypanosomes is probably one of the better studied and involves a cell-cycle arrested or 'stumpy' form that activates metabolic pathways advantageous to the parasite in the insect host. However, a range of stimuli and stress conditions can trigger similar changes, leading to formation of stumpy-like cellular states. We propose that the origin and optimisation of this differentiation program represents repurposing of a generic stress response to gain considerable gain-of-fitness associated with parasite transmission.
Kazuistika popisuje případ pacientky, u které jsem stanovil postupně diagnózu primární hyperparatyreózy. Pacientka byla nakonec indikována k operačnímu řešení choroby.
A case report is presented of a woman diagnosed with primary hyperparathyreosis. The patient was scheduled for surgery.
The p53 tumor suppressor and its key regulator MDM2 play essential roles in development, ageing, cancer, and cellular stress responses in mammals. Following DNA damage, MDM2 interacts with p53 mRNA in an ATM kinase-dependent fashion and stimulates p53 synthesis, whereas under normal conditions, MDM2 targets the p53 protein for degradation. The peptide- and RNA motifs that interact with MDM2 are encoded by the same conserved BOX-I sequence, but how these interactions have evolved is unknown. Here, we show that a temperature-sensitive structure in the invertebrate Ciona intestinalis (Ci) p53 mRNA controls its interaction with MDM2. We also show that a nonconserved flanking region of Ci-BOX-I domain prevents the p53-MDM2 protein-protein interaction. These results indicate that the temperature-regulated p53 mRNA-MDM2 interaction evolved to become kinase regulated in the mammalian DNA damage response. The data also suggest that the negative regulation of p53 by MDM2 via protein-protein interaction evolved in vertebrates following changes in the BOX-I flanking sequence.
- MeSH
- apoptóza genetika MeSH
- Ciona intestinalis MeSH
- DNA primery MeSH
- messenger RNA genetika metabolismus MeSH
- nádorové buněčné linie MeSH
- nádorový supresorový protein p53 genetika metabolismus MeSH
- poškození DNA MeSH
- protoonkogenní proteiny c-mdm2 genetika metabolismus MeSH
- RRM proteiny genetika metabolismus MeSH
- sekvence nukleotidů MeSH
- terciární struktura proteinů MeSH
- vazba proteinů MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The role of cytoreductive nephrectomy in metastatic renal cell carcinoma (RCC) has been studied intensively over the past few decades. Interestingly, the opinion with regard to the importance of this procedure has switched from a recommendation as a standard of care to an almost complete refutation. However, no definitive agreement on cytoreductive nephrectomy, including the pros and cons of the procedure, has been reached, and the topic remains highly controversial. With the advent of immune checkpoint inhibitors, we have experienced a paradigm shift, with immunotherapy playing a crucial role in the treatment algorithm. Nevertheless, obtaining results from prospective clinical trials on the role of cytoreductive nephrectomy requires time, and once some data have been gathered, the standards of systemic therapy may be different, and we stand again at the beginning. This review summarizes current knowledge on the topic in the light of newly evolving treatment strategies. The crucial point is to recognize who could be an appropriate candidate for immediate cytoreductive surgery that may facilitate the effect of systemic therapy through tumor debulking, or who might benefit from deferred cytoreduction in the setting of an objective response of the tumor. The role of prognostic factors in management decisions as well as the technical details associated with performing the procedure from a urological perspective are discussed. Ongoing clinical trials that may bring new evidence for transforming therapeutic paradigms are listed.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
