Search results for " development"
showing 10 items of 21333 documents
Expression of p63, p53 and ki-67 in patients with cervical intraepithelial neoplasia
2017
Objective: Cervical intraepithelial neoplasia (CIN) is a dysplastic process in cervical squamous epithelium and carries a risk of progression to cervical cancer. The aim of this study was to compare expression of three biomarkers named p53, p63 and Ki-67 in patients with various grades of cervical intraepithelial neoplasia and in a control group. Material and Method: 58 patients were enrolled in the study. Each patient underwent a colposcopy-guided biopsy of the cervix. Immunostaining for markers (p53, p63 and Ki-67) was performed on tissue samples of normal cases (n=10), CIN I (n=20), CIN II (n=14), and CIN III (n=14). Results: Our study showed a significant increase of the expression of t…
Endoderm development requires centrioles to restrain p53-mediated apoptosis in the absence of ERK activity
2021
Centrioles comprise the heart of centrosomes, microtubule-organizing centers. To study the function of centrioles in lung and gut development, we genetically disrupted centrioles throughout the mouse endoderm. Surprisingly, removing centrioles from the endoderm did not disrupt intestinal growth or development but blocked lung branching. In the lung, acentriolar SOX2-expressing airway epithelial cells apoptosed. Loss of centrioles activated p53, and removing p53 restored survival of SOX2-expressing cells, lung branching, and mouse viability. To investigate how endodermal p53 activation specifically killed acentriolar SOX2-expressing cells, we assessed ERK, a prosurvival cue. ERK was active t…
Plausible Role of Estrogens in Pathogenesis, Progression and Therapy of Lung Cancer
2021
Malignant neoplasms are among the most common diseases and are responsible for the majority of deaths in the developed world. In contrast to men, available data show a clear upward trend in the incidence of lung cancer in women, making it almost as prevalent as breast cancer. Women might be more susceptible to the carcinogenic effect of tobacco smoke than men. Furthermore, available data indicate a much more frequent mutation of the tumor suppressor gene-p53 in non-small cell lung cancer (NSCLC) female patients compared to males. Another important factor, however, might lie in the female sex hormones, whose mitogenic or carcinogenic effect is well known. Epidemiologic data show a correlatio…
Molecular mechanisms of MYCN-dependent apoptosis and the MDM2-p53 pathway: an Achille’s heel to be exploited for the therapy of MYCN amplified neurob…
2012
The p53 oncosuppressor is very seldom mutated in neuroblastoma, but several mecha- nisms cooperate to its functional inactivation in this tumor. Increased MDM2 levels, due to genetic amplification or constitutive inhibition of p14ARF, significantly contribute to this event highlighting p53 reactivation as an attractive perspective for neuroblastoma treat- ment. In addition to its role in tumorigenesis, MYCN sensitizes untransformed and cancer cells to apoptosis. This is associated to a fine modulation of the MDM2-p53 pathway Indeed MYCN induces p53 and MDM2 transcription, and, by evoking a DNA damage response (DDR), it stabilizes p53 and its proapoptotic kinase Homeodomain Interacting Prote…
Factors Enabling and Hindering Value Co-Creation in Continuous Service Development: A Systematic Literature Review
2022
This paper presents a systematic literature review (SLR) investigating the factors that enable and hinder value co-creation in organizations’ continuous service development processes. Employing the lens of service-dominant (S-D) logic, we classify the identified factors into three interrelated dimensions: institutions, resources, and service exchange. Our systematic findings may inform organizations’ efforts to support the emergence of positive rather than negative value outcomes when implementing continuous practices in their service development. In addition, we outline avenues for further research in this emerging topic area. peerReviewed
Attributions and paradoxes of agency in socially sustainable development : perspectives from small-scale NGOs in Jinja, Uganda
2014
During the past decades, sustainable development has become an important phenomenon in the global development discourse. The concept has been widely used by both large international bodies such as the United Nations as well as small grassroots organization. In the beginning, the interest was mainly in questions of environmental and ecological aspects of the concept but especially since the introduction of the Human Development Approach the importance of social and cultural aspects of sustainable development became more important. In the discussions on Human Development and sustainable development, the people are in the center of the discussion. Both concepts emphasize the importance of agen…
Evolutionary Dynamics of Pathoadaptation Revealed by Three Independent Acquisitions of the VirB/D4 Type IV Secretion System in Bartonella
2017
The α-proteobacterial genus Bartonella comprises a group of ubiquitous mammalian pathogens that are studied as a model for the evolution of bacterial pathogenesis. Vast abundance of two particular phylogenetic lineages of Bartonella had been linked to enhanced host adaptability enabled by lineage-specific acquisition of a VirB/D4 type IV secretion system (T4SS) and parallel evolution of complex effector repertoires. However, the limited availability of genome sequences from one of those lineages as well as other, remote branches of Bartonella has so far hampered comprehensive understanding of how the VirB/D4 T4SS and its effectors called Beps have shaped Bartonella evolution. Here, we repor…
Experimental evolution of an RNA virus in cells with innate immunity defects
2015
Experimental evolution studies have shown that RNA viruses respond rapidly to directional selection and thus can adapt efficiently to changes in host cell tropism, antiviral drugs, or other imposed selective pressures. However, the evolution of RNA viruses under relaxed selection has been less extensively explored. Here, we evolved vesicular stomatitis virus in mouse embryonic fibroblasts knocked-out for PKR, a protein with a central role in antiviral innate immunity. Vesicular stomatitis virus adapted to PKR-negative mouse embryonic fibroblasts in a gene-specific manner, since the evolved viruses exhibited little or no fitness improvement in PKR-positive cells. Full-length sequencing revea…
Evidence for Positive Selection in the Capsid Protein-Coding Region of the Foot-and-Mouth Disease Virus (FMDV) Subjected to Experimental Passage Regi…
2001
We present sequence data from two genomic regions of foot-and-mouth disease virus (FMDV) subjected to several experimental passage regimens. Maximum-likelihood estimates of the nonsynonymous-to-synonymous rate ratio parameter (dN/dS) suggested the action of positive selection on some antigenic sites of the FMDV capsid during some experimental passages. These antigenic sites showed an accumulation of convergent amino acid replacements during massive serial cytolytic passages and also in persistent infections of FMDV in cell culture. This accumulation was most significant at the antigenic site A (the G-H loop of capsid VP1), which includes an Arg-Gly-Asp (RGD) cellular recognition motif. Our …
Motor Transitions' Peculiarity of Heterozygous DAT Rats When Offspring of an Unconventional KOxWT Mating.
2020
Abstract Causal factors of psychiatric diseases are unclear, due to gene × environment interactions. Evaluation of consequences, after a dopamine-transporter (DAT) gene knock-out (DAT-KO), has enhanced our understanding into the pathological dynamics of several brain disorders, such as Attention-Deficit/Hyperactivity and Bipolar-Affective disorders. Recently, our attention has shifted to DAT hypo-functional (heterozygous, HET) rodents: HET dams display less maternal care and HET females display marked hypo-locomotion if cared by HET dams (Mariano et al., 2019). We assessed phenotypes of male DAT-heterozygous rats as a function of their parents: we compared “maternal” origin (MAT-HET, obtain…