Allelic polymorphism of Ovar-DRB1 exon2 gene and parasite resistance in two dairy sheep breeds

The Ovar-DRB1 gene locus is one of the most polymorphic genes of the Major Histocompatibility Complex (Ovar-MHC) and holds a functional role to antigen presentation. The aim of this study was: a) to describe the Ovar-DRB1 locus variability in two dairy Greek sheep breeds and b) to investigate associations between this variability with resistance to gastrointestinal parasitosis. Blood and faecal samples were collected from 231 and 201 animals of Arta and Kalarrytiko breeds, respectively. The identification of alleles was performed using the sequence–base method. Faecal egg counting (FEC) of the gastrointestinal parasites and measures of blood plasma pepsinogen levels were performed in order to evaluate parasitological parameters. From this study in the overall examined animals, thirty-nine Ovar-DRB1 alleles were identified, among them, ten new alleles, reported for the first time in the literature. In Arta breed a total of twenty-four alleles were found. Among the detected alleles, ten were breed specific and five were new. Regarding the Kalarrytiko breed, twenty-nine alleles were found, fifteen of them were unique and nine were new. The studied breeds differed in their allelic profile, with only 12 common from the total of 134 different recorded genotypes. A higher number of animals with high parasitic load and high plasma pepsinogen values were found in Kalarrytiko. Associations between Ovar-DRB1 alleles with FEC values were found with certain heterozygous genotypes to present significantly reduced FEC values. The large number of detected alleles with low frequencies and the fact that the majority of animals were heterozygous, make hard to find strong association

Enhancement of endogenous midbrain neurogenesis by microneurotrophin BNN-20 after neural progenitor grafting in a mouse model of nigral degeneration

We have previously shown the neuroprotective and pro-neurogenic activity of microneurotrophin BNN-20 in the substantia nigra of the “weaver” mouse, a model of progressive nigrostriatal degeneration. Here, we extended our investigation in two clinically-relevant ways. First, we assessed the effects of BNN-20 on human induced pluripotent stem cell-derived neural progenitor cells and neurons derived from healthy and parkinsonian donors. Second, we assessed if BNN-20 can boost the outcome of mouse neural progenitor cell intranigral transplantations in weaver mice, at late stages of degeneration. We found that BNN-20 has limited direct effects on cultured human induced pluripotent stem cell-derived neural progenitor cells, marginally enhancing their differentiation towards neurons and partially reversing the pathological phenotype of dopaminergic neurons generated from parkinsonian donors. In agreement, we found no effects of BNN-20 on the mouse neural progenitor cells grafted in the substantia nigra of weaver mice. However, the graft strongly induced an endogenous neurogenic response throughout the midbrain, which was significantly enhanced by the administration of microneurotrophin BNN-20. Our results provide straightforward evidence of the existence of an endogenous midbrain neurogenic system that can be specifically strengthened by BNN-20. Interestingly, the lack of major similar activity on cultured human induced pluripotent stem cell-derived neural progenitors and their progeny reveals the in vivo specificity of the aforementioned pro-neurogenic effect

Examination of pathway crosstalk and functional modules in papillary thyroid cancer dedifferentiation to anaplastic thyroid cancer

Thyroid cancer, comprising well-differentiated follicular and papillary types, alongside less common medullary and anaplastic subtypes with poor prognoses, exhibits specific anaplastic cases resulting from papillary dedifferentiation, lacking precise molecular evidence. Utilizing Metascape, CTpathway and PathwAX II, the study integrates functional modules and pathway crosstalk for dedifferentiation analysis, conducting a comprehensive two-dimensional assessment of toolset’s functionality, compatibility, and interoperability. Results suggest that transitions between the cancer subtypes involve pathways related to cellular processes, extracellular matrix interactions, and genetic alterations. Metascape enriched crosstalk tool findings, providing extended lists of specific pathways, while CTpathway exhibited better sensitivity and specificity, offering more result customization options and database selection than PathwAX II. PathwAX II, with unique interactive features for network display and identifying depleted pathways, emerges a valuable component in a comprehensive pipeline integrating these three tools. Additional validation against previous clinical studies affirms the reliability of the results, reinforcing PathwAX II’s role as a key reference point in the creation of such a pipeline. The study also suggests future tool development directions, highlighting strengths and limitations across the platforms. The detailed pathway and gene analysis contributes concrete knowledge to the scientific community, serving as a hallmark for future studies

Factors and mechanisms associating the mobilisation of Ca2+ with the activation of the NLRP3 inflammasome : A systematic review

Inflammasomes are multiprotein complexes that play a critical role in the regulation of inflammation and the inflammatory responses against pathogens. NLRP3 (NOD-, LRR-and pyrin domain-containing protein 3) is among the molecules involved in the homonymous and well-studied NLRP3 inflammasome that accounts for the release of the pro-inflammatory cytokines interleukin (IL) 1-β and 18. Two signals (priming and activation) that include molecular and cellular events lead to the activation of the complex; the main events involved during the activation phase are ionic fluxes, mitochondrial dysfunction, and lysosomal damage. Calcium mobilisation belongs to the signalling events of ionic fluxes associated with the complex assembly initiation. Although no consensus has been established regarding the ionic Ca2+ fluxes and the exact mechanisms contributing to NLRP3 activation, several sources agree that Ca2+ mobilisation homeostasis is essential for the canonical function of the NLRP3 inflammasome, and other cellular processes associated with it. This systematic review aimed to determine the factors and mechanisms related to Ca2+ mobilisation contributing to inflammasome activation, examine NLRP3-associated pathologies, and propose potential therapeutic targets. The literature sources found were evaluated using the CASP tool. The obtained information revealed an intertwined relation of Ca2+ flux with the calcium-sensing receptor, reactive oxygen species (ROS) generation, lysosome rupture, Ca2+-permeable channels and K+ efflux contributing to NLRP3 inflammasome activation. The summarised knowledge in this review has led to the proposal of future studies through references to different NLRP3-related diseases such as Alzheimer’s and diabetes type II, while potential therapeutic targets were also discussed

Factors and mechanisms associating the mobilisation of Ca2+ with the activation of the NLRP3 inflammasome : A systematic review

Inflammasomes are multiprotein complexes that play a critical role in the regulation of inflammation and the inflammatory responses against pathogens. NLRP3 (NOD-, LRR-and pyrin domain-containing protein 3) is among the molecules involved in the homonymous and well-studied NLRP3 inflammasome that accounts for the release of the pro-inflammatory cytokines interleukin (IL) 1-β and 18. Two signals (priming and activation) that include molecular and cellular events lead to the activation of the complex; the main events involved during the activation phase are ionic fluxes, mitochondrial dysfunction, and lysosomal damage. Calcium mobilisation belongs to the signalling events of ionic fluxes associated with the complex assembly initiation. Although no consensus has been established regarding the ionic Ca2+ fluxes and the exact mechanisms contributing to NLRP3 activation, several sources agree that Ca2+ mobilisation homeostasis is essential for the canonical function of the NLRP3 inflammasome, and other cellular processes associated with it. This systematic review aimed to determine the factors and mechanisms related to Ca2+ mobilisation contributing to inflammasome activation, examine NLRP3-associated pathologies, and propose potential therapeutic targets. The literature sources found were evaluated using the CASP tool. The obtained information revealed an intertwined relation of Ca2+ flux with the calcium-sensing receptor, reactive oxygen species (ROS) generation, lysosome rupture, Ca2+-permeable channels and K+ efflux contributing to NLRP3 inflammasome activation. The summarised knowledge in this review has led to the proposal of future studies through references to different NLRP3-related diseases such as Alzheimer’s and diabetes type II, while potential therapeutic targets were also discussed

In Vitro Propagation of the Mount Parnitha Endangered Species <i>Sideritis raeseri</i> subsp. <i>Attica</i>

Over the past few decades, both wildfires and human-sparked fires have ravaged Mount Parnitha, destroying the mountain’s unique natural ecosystem, applying pressure to its flora, and subjecting the vulnerable populations of Sideritis raeseri subsp. attica to excessive stress. The present study aims to establish an efficient micropropagation method starting from in vitro-grown seedlings. The in vitro germination study carried out during the production of seedlings revealed a higher germination rate (34.0% and 37.0%, respectively) at 20.0 °C and 25.0 °C. The in vitro-derived seedlings studied were used as the starting material for the establishment of various media. Murashige and Skoog (MS) media, hormone-free and containing 0.5 mg L−1 6-benzyladenine (BA), led to the satisfactory (84.0–89.0%) establishment of plantlets. During the multiplication phase, the study used BA in conjunction with α-naphthaleneacetic acetic acid and four different cytocinins (BA; kinetin (KIN); 6-(γ-γ-dimethylallylamino) purine; zeatin) at low concentrations (0.5 mg L−1). During the second subculture, a high multiplication index (7.3 and 6.4, respectively) was found for the hormone-free MS medium and the MS medium containing KIN at 0.5 mg L−1. Hyperhydricity took place on the media supplemented with hormones. Rooting occurred on the half-strength MS medium (51.0%). After two months, the plants’ survival rate stood at 100.0%, as did their ex vitro acclimatisation rate, which also registered at 100.0%. The present results could encourage not only the introduction of S. raeseri subsp. attica into the industry of floriculture as a new ornamental plant but also its ex vitro conservation

Optimization of the production of extracellular α-amylase by Kluyveromyces marxianus IF0 0288 by response surface methodology

The aim of this work was to study the production of extracellular α-amylase by Kluyveromyces marxianus IF0 0288 using optimized nutritional and cultural conditions in a complex yeast medium under aerobic batch fermentation. By applying the conventional "one-variable-at-a-time" approach and the response surface methodology, the effect of four fermentation parameters (type of carbon source, initial culture pH, temperature, and incubation time) on the growth and α-amylase production was evaluated. The production of α-amylase during 60 h of fermentation increased 13-fold under optimized conditions (1% starch, pH 6.0, 30ºC) in comparison to the conventional optimization method. The initial pH value of 6.13 and temperature of 30.3ºC were optimal conditions by the response surface methodology, leading to further improvement (up to 13-fold) in the production of extracellular α-amylase. These results constituted first evidence that K. marxianus could be potentially used as an effective source of extracellular α-amylase