A novel olfactory pathway is essential for fast and efficient blood-feeding in mosquitoes

In mosquitoes, precise and efficient finding of a host animal is crucial for survival. One of the poorly understood aspects of mosquito blood-feeding behavior is how these insects target an optimal site in order to penetrate the skin and blood vessels without alerting the host animal. Here we provide new findings that a piercing structure of the mouthpart of the mosquitoes, the stylet, is an essential apparatus for the stage in blood feeding. Indeed, the stylet possesses a number of sensory hairs located at the tip of the stylet. These hairs house olfactory receptor neurons that express two conventional olfactory receptors of Aedes aegypti (AaOrs), AaOr8 and AaOr49, together with the odorant co-receptor (AaOrco). In vivo calcium imaging using transfected cell lines demonstrated that AaOr8 and AaOr49 were activated by volatile compounds present in blood. Inhibition of gene expression of these AaOrs delayed blood feeding behaviors of the mosquito. Taken together, we identified olfactory receptor neurons in the stylet involved in mosquito blood feeding behaviors, which in turn indicates that olfactory perception in the stylet is necessary and sufficient for mosquitoes to find host blood in order to rapidly acquire blood meals from a host animal

Mcl-1 is a key regulator of the ovarian reserve

A majority of ovarian follicles are lost to natural death, but the disruption of factors involved in maintenance of the oocyte pool results in a further untimely follicular depletion known as premature ovarian failure. The anti-apoptotic B-cell lymphoma 2 (Bcl-2) family member myeloid cell leukemia-1 (MCL-1) has a pro-survival role in various cell types; however, its contribution to oocyte survival is unconfirmed. We present a phenotypic characterization of oocytes deficient in Mcl-1, and establish its role in maintenance of the primordial follicle (PMF) pool, growing oocyte survival and oocyte quality. Mcl-1 depletion resulted in the premature exhaustion of the ovarian reserve, characterized by early PMF loss because of activation of apoptosis. The increasingly diminished surviving cohort of growing oocytes displayed elevated markers of autophagy and mitochondrial dysfunction. Mcl-1-deficient ovulated oocytes demonstrated an increased susceptibility to cellular fragmentation with activation of the apoptotic cascade. Concomitant deletion of the pro-apoptotic Bcl-2 member Bcl-2-associated X protein (Bax) rescued the PMF phenotype and ovulated oocyte death, but did not prevent the mitochondrial dysfunction associated with Mcl-1 deficiency and could not rescue long-term breeding performance. We thus recognize MCL-1 as the essential survival factor required for conservation of the postnatal PMF pool, growing follicle survival and effective oocyte mitochondrial function

Nanoemulsion and Encapsulation Strategy of Hydrophobic Oregano Essential Oil Increased Human Prostate Cancer Cell Death via Apoptosis by Attenuating Lipid Metabolism

Origanum vulgare essential oil (EO) is traditionally well-known for its aromatic properties and biomedical applications, including anticancer. This was the first report where oregano essential oil-based nano emulsion (OENE) was synthesized for studying its effects on prostate cancer cell lines (PC3). At first, we have synthesized OENE and characterized using various spectroscopic analyses. The toxicity and inhibitory concentration (IC50) of OENE toward prostate cancer by MTT analysis were performed. The lipid biogenesis mediated, molecular target pathway analyses were performed using fluorescence cellular staining techniques, real-time RT-PCR, or western blotting analysis. OENE showed IC50 at 13.82 µg/mL and significantly induced distinct morphological changes, including cell shrinkage, cell density, and cell shape reduction. In addition, OENE could also significantly decreased lipid droplet accumulation which was confirmed by studying mRNA transcripts of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) (0.31-fold), fatty acid synthase (FASN) (0.18-fold), and sterol regulatory element-binding protein (SREPB1) (0.11-fold), respectively. Furthermore, there is a significant upregulation BAX (BCL2 associated X) and caspase 3 expressions. Nevertheless, OENE decreased the transcript level of BCL2 (B-cell lymphoma 2), thus resulting in apoptosis. Overall, our present work demonstrated that OENE could be a therapeutic target for the treatment of prostate cancer and warrants in vivo studies.</jats:p

Liquidation of Corporation

Import 22/07/2015Diplomová práce se zabývá procesem likvidace obchodních společností v České republice. Cílem této práce je popsat postup likvidace obchodních společností a upozornit na některé problémy, které proces likvidace s sebou přináší, poukázat na řešení základních organizačních a ekonomických otázek související s likvidací a propojit právní a daňový pohled na likvidaci. Práce je rozdělena do čtyř kapitol. V první kapitole jsou definovány jednotlivé právní formy obchodních společností a možné způsoby jejich zrušení. Druhá kapitola se zabývá popisem likvidačního procesu, kdy jsou popsány jednotlivé kroky likvidátora v průběhu likvidace. Třetí kapitola je věnována osobě likvidátora, podmínky nutné k výkonu likvidátora, povolání likvidátora do funkce. Čtvrtá kapitola je věnována praktickým problémům spojenými s procesem likvidace.Thesis deals with the process of liquidation of corporations in the Czech Republic. The aim of this thesis is to describe the procedure of liquidation and to point out some possible problems that could occur during liquidation. The legal and tax point view of the topic will also be included. Thesis is divided into 4 main chapters. Different legal forms of the corporations and the ways of dissolution of companies are defined in the first chapter. The second chapter pursues the process of liquidation. One part of this chapter is devoted to activities of the liquidator. The person of the liquidator, including his competences and required skills, is described in the third chapter. The last chapter is focused on practical problems concerning the process of liquidation.119 - Katedra právavelmi dobř

GSI-I (Z-LLNle-CHO) inhibits γ-secretase and the proteosome to trigger cell death in precursor-B acute lymphoblastic leukemia

Gamma secretase inhibitors (GSIs) comprise a growing class of compounds that interfere with the membrane-bound Notch signaling protein and its downstream intra-nuclear transcriptional targets. As GSI-I (Z-LLNle-CHO) is also a derivative of a widely used proteosome inhibitor MG-132, we hypothesized that this compound might be active in precursor-B acute lymphoblastic leukemia (ALL) cell lines and patient samples. We found that GSI-I treatment of precursor-B ALL blasts induced apoptotic cell death within 18–24 h. With confirmation using RNA and protein analyses, GSI-I blocked nuclear accumulation of cleaved Notch1 and Notch2, and inhibited Notch targets Hey2 and Myc. Microarray analyses of 207 children with high-risk precursor-B ALL demonstrate that Notch pathway expression is a common feature of these neoplasms. However, microarray studies also implicated additional transcriptional targets in GSI-I-dependent cell death, including genes in the unfolded protein response, nuclear factor-κB and p53 pathways. Z-LLNle-CHO blocks both γ-secretase and proteosome activity, inducing more robust cell death in precursor-B ALL cells than either proteosome-selective or γ-secretase-selective inhibitors alone. Using Z-LLNle-CHO in a nonobese diabetes/severe combined immunodeficiency (NOD/SCID) precursor-B ALL xenograft model, we found that GSI-I alone delayed or prevented engraftment of B-lymphoblasts in 50% of the animals comprising the experimental group, suggesting that this compound is worthy of additional testing

Global, regional, and national burden of colorectal cancer and its risk factors, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Funding: F Carvalho and E Fernandes acknowledge support from Fundação para a Ciência e a Tecnologia, I.P. (FCT), in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences UCIBIO and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy i4HB; FCT/MCTES through the project UIDB/50006/2020. J Conde acknowledges the European Research Council Starting Grant (ERC-StG-2019-848325). V M Costa acknowledges the grant SFRH/BHD/110001/2015, received by Portuguese national funds through Fundação para a Ciência e Tecnologia (FCT), IP, under the Norma Transitória DL57/2016/CP1334/CT0006.proofepub_ahead_of_prin