53BP1‐mediated recruitment of RASSF1A to ribosomal DNA breaks promotes local ATM signaling

DNA lesions occur across the genome and constitute a threat to cell viability; however, damage at specific genomic loci has a relatively greater impact on overall genome stability. The ribosomal RNA gene repeats (rDNA) are emerging fragile sites. Recent progress in understanding how the rDNA damage response is organized has highlighted a key role of adaptor proteins. Here, we show that the scaffold tumor suppressor RASSF1A is recruited to rDNA breaks. RASSF1A recruitment to double‐strand breaks is mediated by 53BP1 and depends on RASSF1A phosphorylation at Serine 131 by ATM kinase. Employing targeted rDNA damage, we uncover that RASSF1A recruitment promotes local ATM signaling. RASSF1A silencing, a common epigenetic event during malignant transformation, results in persistent breaks, rDNA copy number alterations and decreased cell viability. Overall, we identify a novel role for RASSF1A at rDNA break sites, provide mechanistic insight into how the DNA damage response is organized in a chromatin context, and provide further evidence for how silencing of the RASSF1A tumor suppressor contributes to genome instability.     

L’insight et les schizophrénies: un paradoxe?

The aim of this paper is to focus on the concept of “insight” in schizophrenia. Insight corresponds to an interior view of oneself and its relationships to the world, and is directed from the exterior to the interior world. This view is linked with the concepts of truth, discovery and clarity. The study of the insight concept in regards to schizophrenia is paradoxical. Psychoanalytical, phenomenological and empirical models show that there are three different levels of analysis: (a) the patient, with his or her troubled mind and the individual factors of expression, (b) the physician, with his or her own beliefs, knowledge about the disease, personal emotions, experience and attitudes, (c) the interaction between physician and patient. In most recent psychometric studies, insight is restricted to the evaluation of the degree of the patient’s acceptance of his or her disease. This restriction shows a multidimensional phenomenon, which varies according to time and is disturbed by schizophrenia. Insight is correlated with the symptoms of the disease, with IQ, with the acute stages of the schizophrenia disease, with acting out, and with the frequency of hospitalisation, especially when nonvoluntary. However, results differ concerning the correlation of insight with suicide, cognitive functions and cerebral anatomy. From the point of view of clinical practice, it is the psychiatrist’s insight which plays an important role in the process of the emergence of the patient’s insight. To objectively study this process, more complex models are necessary, which would imply further developments in the theory of psychiatric practice.     

Synthesis of derivatives of the keto-pyrrolyl-difluorophenol scaffold: Some structural aspects for aldose reductase inhibitory activity and selectivity

Seven novel ARIs (3a–c, 4a–c and 5) were synthesized with the implementation of an optimized and, partially, selective synthetic procedure, via a Friedel–Crafts acylation reaction. The synthesized ARIs have values of IC₅₀^ALR2 ranging from 0.19 μM (in case of compound 3b) to 2.3 μM (in case of compound 4a), while the values of selectivity index towards ALR1 range from 1 (in case of compound 3b) to 238 (in case of compound 3a). Finally, we found out that the presence of an additional (secondary) aromatic area is not a prerequisite feature for ARI activity.     

Glycosylation and adhesiveness differentiate larval Ceratitis capitata tyrosinases

Larval Ceratitis capitata phenoloxidases (POs) from hemocytes, serum, integument, and fat body were analyzed. Two types of PO were recorded: the tyrosinase type found in hemocytes, serum, integument, and fat body and the laccase type found in integument. Tyrosinase from all larval tissues and integumental laccase as well, showed similarity in molecular weight (93 KDa), activation by Escherichia coli at 5 mM Ca²⁺, and reactivity to antibodies raised against serum tyrosinase. However, the enzymes differed with respect to their glycosylation and adhesiveness. The serum and integumental enzyme forms contain concanavalin A reacting material, whereas hemocyte and integumental tyrosinase(s) are adhesive. These differences in enzyme forms, although not influencing their substrate specificity, seem to give advantages to performing their function, i.e., the adhesive enzyme form facilitates the adherence to E. coli cell wall and hemocyte surface (unpublished data) while the glycosylated form facilitated the secretion into serum. © 1994 Wiley-Liss, Inc.     

Atx regulates skeletal muscle regeneration via LPAR1 and promotes hypertrophy

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Polarization‐dependent second‐harmonic generation for collagen‐based differentiation of breast cancer samples

Nonlinear optical imaging techniques have been widely used to reveal biological structures for accurate diagnosis at the cellular as well as the tissue level. In the present study, polarization‐dependent second‐harmonic generation (PSHG) was used to determine collagen orientation in breast cancer biopsy tissues (grades 0, I, II and III). The obtained data were processed using fast Fourier transform (FFT) analysis, while second‐harmonic generation (SHG) anisotropy and the “ratio parameter” values were also calculated. Such measurements were shown to be able to distinguish collagen structure modifications in different cancer grades tested. The analysis presented herein suggests that PSHG imaging could provide a quantitative evaluation of the tumor state and the distinction of malignant from benign breast tissues. The obtained results also allowed the development of a biophysical model, which can explain the aforementioned differentiations and is in agreement with the simulations relating the SHG anisotropy values with the mechanical tension applied to the collagen during cancer progression. The current approach could be a step forward for the development of new, nondestructive, label free optical diagnostic tools for cancer reducing the need of recalls and unnecessary biopsies, while potentially improving cancer detection rates.     

Monitoring aging-associated structural alterations in Caenorhabditis elegans striated muscles via polarization-dependent second-harmonic generation measurements

The in-vivo elucidation of the molecular mechanisms underlying muscles dysfunction due to aging via non-invasive label free imaging techniques is an important issue with high biological significance. In this study, polarization-dependent second-harmonic generation (PSHG) was used to evaluate structural alterations in the striated muscles during Caenorhabditis elegans lifespan. Young and old wild-type animals were irradiated. The obtained results showed that it was not feasible to detect differences in the structure of myosin that could be correlated with the aging of the worms, via the implementation of the classical, widely used, cylindrical symmetry model and the calculation of the SHG anisotropy values. A trigonal symmetry model improved the extracted results; however, the best outcome was originated from the application of a general model. Myosin structural modifications were monitored via the estimation of the difference in spectral phases derived from discrete Fourier transform analysis. Age classification of the nematodes was achieved by employing both models, proving the usefulness of the usage of PSHG microscopy as a potential diagnostic tool for the investigation of muscle diseases.