Natural humoral immune response to ribosomal P0 protein in colorectal cancer patients

Tumor associated antigens are useful in colorectal cancer (CRC) management. The ribosomal P proteins (P0, P1, P2) play an important role in protein synthesis and tumor formation. The immunogenicity of the ribosomal P0 protein in head and neck, in breast and prostate cancer patients and the overexpression of the carboxyl-terminal P0 epitope (C-22 P0) in some tumors were reported

The Role of Bcl-2 and Beclin-1 Complex in “Switching” between Apoptosis and Autophagy in Human Glioma Cells upon LY294002 and Sorafenib Treatment

Background: Gliomas are the most malignant tumors of the central nervous system. One of the factors in their high drug resistance is avoiding programmed death (PCD) induction. This is related to the overexpression of intracellular survival pathways: PI3K-Akt/PKB-mTOR and Ras-Raf-MEK-ERK. Apoptosis and autophagy are co-existing processes due to the interactions between Bcl-2 and beclin-1 proteins. Their complex may be a molecular “toggle-switch” between PCD types. The aim of this research was to investigate the role of Bcl-2:beclin-1 complex in glioma cell elimination through the combined action of LY294002 and sorafenib. Methods: Drug cytotoxicity was estimated with an MTT test. The type of cell death was evaluated using variant microscopy techniques (fluorochrome staining, immunocytochemistry, and transmission electron microscopy), as well as the Bcl-2:beclin-1 complex formation and protein localization. Molecular analysis of PCD indicators was conducted through immunoblotting, immunoprecipitation, and ELISA testing. SiRNA was used to block Bcl-2 and beclin-1 expression. Results: The results showed the inhibitors used in simultaneous application resulted in Bcl-2:beclin-1 complex formation and apoptosis becoming dominant. This was accompanied by changes in the location of the tested proteins. Conclusions: “Switching” between apoptosis and autophagy using PI3K and Raf inhibitors with Bcl-2:beclin-1 complex formation opens new therapeutic perspectives against gliomas

Charged and Hydrophobic Surfaces on the A Chain of Shiga-Like Toxin 1 Recognize the C-Terminal Domain of Ribosomal Stalk Proteins

Shiga-like toxins are ribosome-inactivating proteins (RIP) produced by pathogenic E. coli strains that are responsible for hemorrhagic colitis and hemolytic uremic syndrome. The catalytic A1 chain of Shiga-like toxin 1 (SLT-1), a representative RIP, first docks onto a conserved peptide SD[D/E]DMGFGLFD located at the C-terminus of all three eukaryotic ribosomal stalk proteins and halts protein synthesis through the depurination of an adenine base in the sarcin-ricin loop of 28S rRNA. Here, we report that the A1 chain of SLT-1 rapidly binds to and dissociates from the C-terminal peptide with a monomeric dissociation constant of 13 µM. An alanine scan performed on the conserved peptide revealed that the SLT-1 A1 chain interacts with the anionic tripeptide DDD and the hydrophobic tetrapeptide motif FGLF within its sequence. Based on these 2 peptide motifs, SLT-1 A1 variants were generated that displayed decreased affinities for the stalk protein C-terminus and also correlated with reduced ribosome-inactivating activities in relation to the wild-type A1 chain. The toxin-peptide interaction and subsequent toxicity were shown to be mediated by cationic and hydrophobic docking surfaces on the SLT-1 catalytic domain. These docking surfaces are located on the opposite face of the catalytic cleft and suggest that the docking of the A1 chain to SDDDMGFGLFD may reorient its catalytic domain to face its RNA substrate. More importantly, both the delineated A1 chain ribosomal docking surfaces and the ribosomal peptide itself represent a target and a scaffold, respectively, for the design of generic inhibitors to block the action of RIPs

The Worker Honeybee Fat Body Proteome Is Extensively Remodeled Preceding a Major Life-History Transition

Honeybee workers are essentially sterile female helpers that make up the majority of individuals in a colony. Workers display a marked change in physiology when they transition from in-nest tasks to foraging. Recent technological advances have made it possible to unravel the metabolic modifications associated with this transition. Previous studies have revealed extensive remodeling of brain, thorax, and hypopharyngeal gland biochemistry. However, data on changes in the abdomen is scarce. To narrow this gap we investigated the proteomic composition of abdominal tissue in the days typically preceding the onset of foraging in honeybee workers

Starość jako wartość i fenomen pedagogiczny

Starość ma niejedno oblicze. Różne dyscypliny naukowe definiują ją na różne sposoby. Niemniej jest ona powiązana z określonym etapem życia i osobistym doświadczaniem jej przez konkretnego człowieka. Żadna z form starzenia się nie może wykluczać człowieka ze społeczności. Każdy stary człowiek ma pełne prawo do zachowania godności i okazywania mu szacunku, a jeśli zachodzi konieczność, do wsparcia i opieki. Wraz z kolejnymi latami życia przestrzeń życiowa i społeczna seniorów zawęża się. Narasta w nich poczucie samotności i osamotnienia. Okres starości nie wyklucza automatycznie ze świadomości seniorów poczucia własnej podmiotowości i tożsamości. Przeprowadzanie„bilansu życia” w okresie starości pozwala, chociaż niekoniecznie prowadzić musi do wnikliwej oceny moralnej swojej osoby. Rzetelny bilans życia polega na indywidualnym odniesieniu się do pytania stawianego samemu sobie o jego ocenę. Upowszechnianie się typu rodziny nuklearnej, w skład której wchodzą jedynie rodzice i dzieci, narastające zjawisko dysfunkcjonalności rodzin, spowodowało zmianę pozycji i roli człowieka starego w rodzinie. Pogarszające się sukcesywnie stan zdrowia i kondycja psychiczna człowieka starego powodują, że jest on marginalizowany przez najbliższe otoczenie, często pozostawiony sam sobie. Nie zawsze rodziny są przygotowane i dojrzałe do współbycia z osobami starszymi. Wejście w wiek senioralny każdego człowieka w różny sposób wieńczy przebytą drogę, która wiodła ku wszelkim potencjalnym możliwościom i prowadziła go na szczyt indywidualnych osiągnięć życiowych. Nie jest i nie musi być ona jego kresem. Ważne jest, aby senior zdawał sobie sprawę z tego, że może być nadal potrzebny innym, powinien wykazywać otwartość i gotowość zdobywania wiedzy i pracy nad samym sobą oraz w miarę sił i możliwości świadczyć dobro na rzecz wspólnoty, do której przynależy. Gerontologia pedagogiczna staje przed zadaniem upowszechniania pewnych norm etosu starości. Do nich zapewne można zaliczyć te, które przyczyniają się do uznania wieku senioralnego jako wartościowego czasu życia..

An Ann-Based Scalable Hashing Algorithm for Computational Clouds with Schedulers

The significant benefits of cloud computing (CC) resulted in an explosion of their usage in the last several years. From the security perspective, CC systems have to offer solutions that fulfil international standards and regulations. In this paper, we propose a model for a hash function having a scalable output. The model is based on an artificial neural network trained to mimic the chaotic behaviour of the Mackey-Glass time series. This hashing method can be used for data integrity checking and digital signature generation. It enables constructing cryptographic services according to the user requirements and time constraints due to scalable output. Extensive simulation experiments are conduced to prove its cryptographic strength, including three tests: a bit prediction test, a series test, and a Hamming distance test. Additionally, flexible hashing function performance tests are run using the CloudSim simulator mimicking a cloud with a global scheduler to investigate the possibility of idle time consumption of virtual machines that may be spent on the scalable hashing protocol. The results obtained show that the proposed hashing method can be used for building light cryptographic protocols. It also enables incorporating the integrity checking algorithm that lowers the idle time of virtual machines during batch task processing

Phosphorylation of the N-terminal domain of ribosomal P-stalk protein uL10 governs its association with the ribosome

The uL10 protein is the main constituent of the ribosomal P-stalk, anchoring the whole stalk to the ribosome through interactions with rRNA. The P-stalk is the core of the GTPase-associated center (GAC), a critical element for ribosome biogenesis and ribosome translational activity. All P-stalk proteins (uL10, P1, and P2) undergo phosphorylation within their C termini. Here, we show that uL10 has multiple phosphorylation sites, mapped also within the N-terminal rRNA-binding domain. Our results reveal that the introduction of a negative charge within the N terminus of uL10 impairs its association with the ribosome. These findings demonstrate that uL10 N-terminal phosphorylation has regulatory potential governing the uL10 interaction with the ribosome and may control the activity of GAC