Cyclic AMP increases the Adhesion of Fibroblasts to Substratum

THE interaction between the cell surface and the substratum is very important in determining several characteristics of cells growing in tissue culture. Transformed cells are less adherent to the substratum than untransformed cells¹ and this reduced interaction with the substratum may be responsible for abnormal properties such as the loss of contact or density dependent inhibition of growth² and the ability to form colonies in agar and to grow in suspension culture.     

Retinol (Vitamin A) Increases α-Synuclein, β-Amyloid Peptide,Tau Phosphorylation and RAGE Content in Human SH-SY5Y Neuronal Cell Line

Retinoids (vitamin A and derivatives) are recognized as essential factors for central nervous system (CNS) development. Retinol (vitamin A) also was postulated to be a major antioxidant component of diet as it modulates reactive species (RS) production and oxidative stress in biological systems. Oxidative stress plays a major role either in pathogenesis or development of neurodegenerative diseases, or even in both. Here we investigate the role of retinol supplementation to human neuron-derived SH-SY5Y cells over RS production and biochemical markers associated to neurodegenerative diseases expressed at neuronal level in Parkinson’s disease and Alzheimer’s disease: α-synuclein, β-amyloid peptide, tau phosphorylation and RAGE. Retinol treatment (24 h) impaired cell viability and increased intracellular RS production at the highest concentrations (7 up to 20 µM). Antioxidant co-treatment (Trolox 100 µM) rescued cell viability and inhibited RS production. Furthermore, retinol (10 µM) increased the levels of α-synuclein, tau phosphorylation at Ser396, β-amyloid peptide and RAGE. Co-treatment with antioxidant Trolox inhibited the increased in RAGE, but not the effect of retinol on α-synuclein, tau phosphorylation and β-amyloid peptide accumulation. These data indicate that increased availability of retinol to neurons at levels above the cellular physiological concentrations may induce deleterious effects through diverse mechanisms, which include oxidative stress but also include RS-independent modulation of proteins associated to progression of neuronal cell death during the course of neurodegenerative diseases.     

Focal adhesion kinase maintains,but not increases the adhesion of dental pulp cells

Focal adhesion kinase (FAK) functions as a key enzyme in the integrin-mediated adhesion-signalling pathway. Here, we aimed to investigate the effects of FAK on adhesion of human dental pulp (HDP) cells. We transfected lentiviral vectors to silence or overexpress FAK in HDP cells ex vivo. Early cell adhesion, cell survival and focal contacts (FCs)-related proteins (FAK and paxillin) were examined. By using immunofluorescence, the formation of FCs and cytoskeleton was detected, respectively. We found that both adhesion and survival of HDP cells were suppressed by FAK inhibition. However, FAK overexpression slightly inhibited cell adhesion and exhibited no change in cell survival compared with the control. A thick rim of cytoskeleton accumulated and smaller dot-shaped FCs appeared in FAK knockdown cells. Phosphorylation of paxillin (p-paxillin) was inhibited in FAK knockdown cells, verifying that the adhesion was inhibited. Less cytoskeleton and elongated FCs were observed in FAK-overexpressed cells. However, p-paxillin had no significant difference compared with the control. In conclusion, the data suggest that FAK maintains cell adhesion, survival and cytoskeleton formation, but excessive FAK has no positive effects on these aspects.     

Celastrol Induces Autophagy by Targeting AR/miR-101 in Prostate Cancer Cells

Autophagy is an evolutionarily conserved process responsible for the degradation and recycling of cytoplasmic components through autolysosomes. Targeting AR axis is a standard strategy for prostate cancer treatment; however, the role of AR in autophagic processes is still not fully understood. In the present study, we found that AR played a negative role in AR degrader celastrol-induced autophagy. Knockdown of AR in AR-positive prostate cancer cells resulted in enhanced autophagy. Ectopic expression of AR in AR-negative prostate cancer cells, or gain of function of the AR signaling in AR-positive cells, led to suppression of autophagy. Since miR-101 is an inhibitor of autophagy and its expression was decreased along with AR in the process of celastrol-induced autophagy, we hypothesize that AR inhibits autophagy through transactivation of miR-101. AR binding site was defined in the upstream of miR-101 gene by luciferase reporter and ChIP assays. MiR-101 expression correlated with AR status in prostate cancer cell lines. The inhibition of celastrol-induced autophagy by AR was compromised by blocking miR-101; while transfection of miR-101 led to inhibition of celastrol-induced autophagy in spite of AR depletion. Furthermore, mutagenesis of the AR binding site in miR-101 gene led to decreased suppression of autophagy by AR. Finally, autophagy inhibition by miR-101 mimic was found to enhance the cytotoxic effect of celastrol in prostate cancer cells. Our results demonstrate that AR inhibits autophagy via transactivation of miR-101, thus combination of miR-101 mimics with celastrol may represent a promising therapeutic approach for treating prostate cancer.     

Concentric Magnetic Structures for Magnetophoretic Bead Collection,Cell Trapping and Analysis of Cell Morphological Changes Caused by Local Magnetic Forces

Concentric magnetic structures (ring and square) with domain wall (DW) pinning geometry are designed for biological manipulation. Magnetic beads collection was firstly demonstrated to analyse the local magnetic field generated by DWs and the effective regions to capture magnetic targets of size 1 μm. Primary mouse embryonic fibroblasts (MEFs) are magnetically labeled by internalizing poly (styrene sulfonic acid) stabilized magnetic nanoparticles (PSS-MNPs) and then are selectively trapped by head-to-tail DWs (HH DWs) or tail-to-tail DWs (TT DWs) to be arranged into linear shape or cross shape. The morphologies and the nuclear geometry of the cells growing on two kinds of concentric magnetic structures are shown to be distinctive. The intracellular magnetic forces generated by the local magnetic field of DWs are found to influence the behaviour of cells.     

Using variation partitioning techniques to quantify the effects of invasive alien species on native urban bird assemblages

Quantifying the impacts that invasive alien species (IAS) cause on affected systems is not an easy task. Here, we explore the application of variation partitioning techniques to measure and control for the effects of possible confounding factors when studying the impact that feral pigeons, European starlings, and house sparrows cause on native urban bird communities in Mexico. We argue that these IAS are provoking a severe impact on whole assemblages of native passerines only if (a) their marginal effect is statistically significant, (b) it remains so after partialling out other explanatory variables, and (c) is larger than (or similar to) the conditional effect of these covariates. We censused passerine bird assemblages and measured habitat variables in a number of greenspaces in three replicate study areas. Then, by means of partial redundancy analyses, we decomposed the total variability in bird data as a function of IAS, physical variables and vegetation data. In one of the study areas the marginal effect of IAS on native assemblages was significant, but the conditional effect was not. We conclude that this IAS effect was confounded with other explanatory variables. In the other study areas, no (marginal or partial) significant effect was found. Without invoking interspecific competition, our results support the opportunistic hypothesis, according to which IAS can exploit ecological conditions in modern cities that native species cannot even tolerate. Finally, apart from the Precautionary Principle, we found no scientific justification to control the abundance of the three IAS in our study areas.     

A Mucormycosis Case in a Cirrhotic Patient Successfully Treated with Posaconazole and Review of Published Literature

Mucormycosis is an invasive fungal infection associated with a high mortality rate, especially in immunocompromised hosts. Mucormycosis rarely occurs in cirrhotic patients. Here, we report a case of mucormycosis with underlying liver cirrhosis and diabetes mellitus. The patient suffered from maxillary sinusitis and osteomyelitis, and the infection was successfully treated with antifungal agents, surgical debridement, and hyperbaric oxygen therapy. The antifungal treatments used were liposomal amphotericin B, itraconazole, and posaconazole. Although our patient had liver cirrhosis (Child-Pugh classification B), no hepatic decompensation was developed during the treatment course of posaconazole. This is the first report of the safe and effective use of posaconazole for the treatment of mucormycosis in a cirrhotic patient.     

Interrogating the neo-pluralist orthodoxy in American anthropology

For most of the twentieth century the state was not a major part of the anthropological toolkit. Despite significant archaeologically driven work on evolution and state formation, most socio-cultural anthropologists have viewed the state with empiricist scepticism, populist hostility, or ethnographic indifference. Typically, state-theory has been left to other disciplines, such as political science and sociology. Since the end of the cold war there has been a greatly increased interest in the state among anthropologists. Philip Abrams, Michael Herzfeld, and Akhil Gupta, who coined the phrase “ethnography of the state”, have been particularly important to this development. However, there remains no serious engagement with the body of state-theory generated, over the last century, by political activists, scientists, sociologists, and anthropologists. It will be argued that this has allowed for the growth of an unproblematised orthodoxy around an ethnographically informed variant of classic American pluralist state-theory. This orthodoxy has hobbled the understanding and explanation of complex political phenomena, led to confusion between hypotheses and conclusions, and tied parts of the discipline to a partisan political project that remains largely un-interrogated. This essay seeks to provide context and clarification on state-theory as a step towards discussion of anthropology’s contemporary engagement with the state and broader questions of political action and social change.     

Clinical and Treatment Aspects of Brown–Black Fungi

Brown–black (or dematiaceous) fungi are responsible for a wide variety of infectious syndromes in both immunocompetent and immunocompromised patients, including local infections, allergic disease, pneumonia, brain abscess, and disseminated infection. They are distinct from the more common hyaline molds, Aspergillus and Fusarium, that cause human disease. They are often found in soil and generally distributed worldwide. In recent years, these fungi have been increasingly recognized as important pathogens. Dematiaceous fungi may have unique pathogenic mechanisms owing to the presence of melanin in their cell walls, which imparts the characteristic dark color to their spores and hyphae. Diagnosis rests on careful microscopic and pathologic examination, as there are no specific laboratory tests to reliably identify these fungi. Therapy depends upon the clinical syndrome, although disseminated infection often has high mortality. Triazoles such as voriconazole, posaconazole, and itraconazole are the most active antifungal agents available. Further studies are needed to better understand the pathogenesis and optimal treatment of these uncommon infections.