Physical anhedonia in the acute phase of schizophrenia

BACKGROUND: The aim of the current study is to investigate the relationship between physical anhedonia and psychopathological parameters, pharmacological parameters or motor side-effects in a sample of inpatients with schizophrenia in an acute episode of their illness. METHOD: Eighty one patients with schizophrenia, consecutively admitted, with an acute episode of their illness, at the Eginition Hospital, Department of Psychiatry, University of Athens, during a one-year period were investigated regarding possible relationships between physical anhedonia, social-demographic data and clinical parameters as well as motor side-effects, induced by antipsychotic agents. All patients were assessed using the Chapman Revised Physical Anhedonia Scale (RPAS), the Positive and Negative Syndrome Scale (PANSS), the Rating Scale for Extrapyramidal Side-Effects (EPSE), the Barnes Akathisia Rating Scale (BARS) and the Abnormal Involuntary Movement Scale (AIMS). Simple cross tabulations were initially employed. Subsequently, multiple regression analysis was performed. RESULTS: Both positive and negative symptoms were associated with physical anhedonia. A positive association between physical anhedonia and the non-paranoid sub-category of schizophrenia was also proved. CONCLUSION: According to these results, it seems that in the acute phase of schizophrenia, physical anhedonia may be a contributing factor to patient's psychopathology

Mitochondrial Homeostasis and Cellular Senescence

Cellular senescence refers to a stress response aiming to preserve cellular and, therefore, organismal homeostasis. Importantly, deregulation of mitochondrial homeostatic mechanisms, manifested as impaired mitochondrial biogenesis, metabolism and dynamics, has emerged as a hallmark of cellular senescence. On the other hand, impaired mitostasis has been suggested to induce cellular senescence. This review aims to provide an overview of homeostatic mechanisms operating within mitochondria and a comprehensive insight into the interplay between cellular senescence and mitochondrial dysfunction

NUCKS overexpression in breast cancer

<p>Abstract</p> <p>Background</p> <p>NUCKS (Nuclear, Casein Kinase and Cyclin-dependent Kinase Substrate) is a nuclear, DNA-binding and highly phosphorylated protein. A number of reports show that <it>NUCKS </it>is highly expressed on the level of mRNA in several human cancers, including breast cancer. In this work, NUCKS expression on both RNA and protein levels was studied in breast tissue biopsies consisted of invasive carcinomas, intraductal proliferative lesions, benign epithelial proliferations and fibroadenomas, as well as in primary cultures derived from the above biopsies. Specifically, in order to evaluate the level of NUCKS protein in correlation with the histopathological features of breast disease, immunohistochemistry was employed on paraffin sections of breast biopsies of the above types. In addition, NUCKS expression was studied by means of Reverse Transcription PCR (RT-PCR), real-time PCR (qRT-PCR) and Western immunoblot analyses in the primary cell cultures developed from the same biopsies.</p> <p>Results</p> <p>The immunohistochemical Results showed intense NUCKS staining mostly in grade I and II breast carcinomas compared to normal tissues. Furthermore, NUCKS was moderate expressed in benign epithelial proliferations, such as adenosis and sclerosing adenosis, and highly expressed in intraductal lesions, specifically in ductal carcinomas <it>in situ </it>(DCIS). It is worth noting that all the fibroadenoma tissues examined were negative for NUCKS staining. RT-PCR and qRT-PCR showed an increase of <it>NUCKS </it>expression in cells derived from primary cultures of proliferative lesions and cancerous tissues compared to the ones derived from normal breast tissues and fibroadenomas. This increase was also confirmed by Western immunoblot analysis. Although NUCKS is a cell cycle related protein, its expression does not correlate with Ki67 expression, neither in tissue sections nor in primary cell cultures.</p> <p>Conclusion</p> <p>The results show overexpression of the NUCKS protein in a number of non malignant breast lesions and cancerous tissues. In particular, the NUCKS overexpression in ADH and DCIS indicates a significant role of this protein in neoplastic progression.</p

Association of TAG-1 with Caspr2 is essential for the molecular organization of juxtaparanodal regions of myelinated fibers

Myelination results in a highly segregated distribution of axonal membrane proteins at nodes of Ranvier. Here, we show the role in this process of TAG-1, a glycosyl-phosphatidyl-inositol–anchored cell adhesion molecule. In the absence of TAG-1, axonal Caspr2 did not accumulate at juxtaparanodes, and the normal enrichment of shaker-type K+ channels in these regions was severely disrupted, in the central and peripheral nervous systems. In contrast, the localization of protein 4.1B, an axoplasmic partner of Caspr2, was only moderately altered. TAG-1, which is expressed in both neurons and glia, was able to associate in cis with Caspr2 and in trans with itself. Thus, a tripartite intercellular protein complex, comprised of these two proteins, appears critical for axo–glial contacts at juxtaparanodes. This complex is analogous to that described previously at paranodes, suggesting that similar molecules are crucial for different types of axo–glial interactions

Altered expression pattern of integrin alphavbeta3 correlates with actin cytoskeleton in primary cultures of human breast cancer

Background: Integrins are transmembrane adhesion receptors that provide the physical link between the actin cytoskeleton and the extracellular matrix. It has been well established that integrins play a major role in various cancer stages, such as tumor growth, progression, invasion and metastasis. In breast cancer, integrin alphavbeta3 has been associated with high malignant potential in cancer cells, signaling the onset of widespread metastasis. Many preclinical breast cancer studies are based on established cell lines, which may not represent the cell behavior and phenotype of the primary tumor of origin, due to undergone genotypic and phenotypic changes. In the present study, short-term primary breast cancer cell cultures were developed. Integrin alphavbeta3 localization was studied in correlation with F-actin cytoskeleton by means of immunofluorescence and immunogold ultrastructural localization. Integrin fluorescence intensities were semi-quantitatively assessed by means of computerized image analysis, while integrin and actin expression was evaluated by Western immunoblotting. Results: In the primary breast cancer epithelial cells integrin alphavbeta3 immunofluorescence was observed in the marginal cytoplasmic area, whereas in the primary normal breast epithelial cells it was observed in the main cell body, i.e. in the ventrally located perinuclear area. In the former, F-actin cytoskeleton appeared well-formed, consisting of numerous and thicker stress fibers, compared to normal epithelial cells. Furthermore, electron microscopy showed increased integrin alphavbeta3 immunogold localization in epithelial breast cancer cells over the area of stress fibers at the basal cell surface. These findings were verified with Western immunoblotting by the higher expression of integrin beta3 subunit and actin in primary breast cancer cells, revealing their reciprocal relation, in response to the higher motility requirements, determined by the malignant potential of the breast cancer cells. Conclusion: A model system of primary breast cancer cell cultures was developed, in an effort to maintain the closest resembling environment to the tumor of origin. Using the above system model as an experimental tool the study of breast tumor cell behavior is possible concerning the adhesion capacity and the migrating potential of these cells, as defined by the integrin alphavbeta3 distribution in correlation with F-actin cytoskeleton

Monitoring Autophagy Immunohistochemically and Ultrastructurally during Human Head and Neck Carcinogenesis. Relationship with the DNA Damage Response Pathway

Autophagy is a catabolic process that preserves cellular homeostasis. Its exact role during carcinogenesis is not completely defined. Specifically in head and neck cancer, such information from clinical settings that comprise the whole spectrum of human carcinogenesis is very limited. Towards this direction, we examined the in situ status of the autophagy-related factors, Beclin-1, microtubule-associated protein 1 light chain 3, member B (LC3B) and sequestosome 1/p62 (p62) in clinical material covering all histopathological stages of human head and neck carcinogenesis. This material is unique as each panel of lesions is derived from the same patient and moreover we have previously assessed it for the DNA damage response (DDR) activation status. Since Beclin-1, LC3B and p62 reflect the nucleation, elongation and degradation stages of autophagy, respectively, their combined immunohistochemical (IHC) expression profiles could grossly mirror the autophagic flux. This experimental approach was further corroborated by ultrastructural analysis, applying transmission electron microscopy (TEM). The observed Beclin-1/LC3B/p62 IHC patterns, obtained from serial sections analysis, along with TEM findings are suggestive of a declined authophagic activity in preneoplastic lesions that was restored in full blown cancers. Correlating these findings with DDR status in the same pathological stages are indicative of: (i) an antitumor function of autophagy in support to that of DDR, possibly through energy deprivation in preneoplastic stages, thus preventing incipient cancer cells from evolving; and (ii) a tumor-supporting role in the cancerous stage

Amine-storing Organelles in Soma and Dendrites of Human Locus Coeruleus Neurons

Previous studies have identified in human catecholamine neurons abundant spherical acidophilic protein bodies (PB), which originate from mitochondria retaining the double membrane (Issidorides et al., 1996). In locus coeruleus (LC), PB have somatodendritic distribution and are unequivocal storage vesicles for noradrenaline, as demonstrated by immunolocalization of Dopamine-β-Hydroxylase (Issidorides et al., 2004). This species-specific phenotype in man is the result of important physiological functions, because depletion or missing of PB is accompanied with Parkinson’s disease. The aim of this study was to investigate the composition of PB and their role in normal and pathological conditions. Post mortem brain specimens of LC were collected from 13 control subjects and 12 cases of Parkinson’s disease patients. Human adrenal medulla was used as a model tissue and histochemical and immunohistochemical correlation between PB and chromaffin granules was made. At the ultrastructural level, colloidal gold method was used for the accurate localization of macromolecules, at high resolution. The mitochondrial origin of PB was sealed with their positive immunoreactivity for mitochondrial porin. The next purpose was to reinforce the identity of PB as monoamine storage sites and to assess their potential of somatodendritic release. For this reason we studied the subcellular immunolocalization of Chromogranin A (CgA) and Vesicular Monoamine Transporter 2 (VMAT2), given the fact that their localization defines the vesicles capacity of filling with monoamine and hence exocytotic release (Schafer et al., 2010; Li et al., 2005). The data provided, demonstrate the novel ultrastructural immunolocalization of both CgA and VMAT2 in PB, supporting their involvement in somatodendritic storage and release of noradrenaline in human LC. In Parkinson’s disease, immunolocalization of VMAT2 in the LC revealed the reduction of protein compared to normal controls. Reduced expression of VMAT2 leads to defective sequestration of monoamines into vesicles, their accumulation in the cytoplasm and eventually the emergence of Parkinson’s disease phenotype. Parkinson’s disease is characterized by a progressive cellular deposition of the synaptic protein a-synuclein in diverse brain regions (Schulz, 2007). Along with the impairment of mitochondrial respiration, both mitochondrial fission/fusion have been shown to be altered (Cardoso, 2011). In view of the above, we investigated the mitochondrial ultrastructure in LC from Parkinson’s disease patients along with a-synuclein immunolocalization. The morphological study revealed disrupted mitochondrial ultrastructure indicating dysfunction in normal neurotransmitter-storing organelle production, leading to defective sequestration of monoamine into vesicles. Immunolocalization of a-synuclein in Parkinson’s disease brains revealed the accumulation of this protein in different stages in physiologically appearing neurons, as well as, in mature brainstem Lewy bodies. At the electron microscope the subcellular localization of this protein in PB, as well as, in neuromelanin of LC neurons was revealed. The study of PB, which are responsible for the somatodentritic storage and possible release of noradrenaline in human LC neurons, and their contribution in the formation of Lewy bodies, as indicated by the localization of common components among these two structures may be helpful towards the understanding of Parkinson’s disease

Identification of coronavirus particles by electron microscopy:a complementary tool for deciphering COVID-19

Identification of coronavirus particles by electron microscopy: a complementary tool for deciphering COVID-19 https://bit.ly/3Kk5PT

Scrotal Apocrine Adenocarcinoma with Pagetoid Phenomenon and Inguinal Lymph Node Metastases.

We report a case of scrotal apocrine adenocarcinoma in a 72-year-old Caucasian male which was initially presented as a reddish superficial lesion which in time became an ulcerated nodule. The initial pathological examination showed an apocrine adenocarcinoma with pagetoid phenomenon. The tumor recurred after four months and then excision biopsy showed tumor with pagetoid phenomenon which reached all the surgical margins. Three months later an ulcerated nodule in the scrotum and greatly enlarged ipsilateral inguinal lymph nodes were noticed. The final pathological examination showed multiple separated malignant foci, some with overlying pagetoid phenomenon and inguinal lymph node metastases. Immunohistochemistry showed positivity for Gross Cystic Disease Fluid Protein-15 (GCDFP-15), androgen receptors, and score 3+ for the Human Epidermal growth factor Receptor-2 (HER2). The aggressive behavior of the present tumor goes along with previous reports showing that HER2 high score cases exhibit a worse prognosis