Nonmotor symptoms in Parkinson's disease: Investigating early-phase onset of behavioral dysfunction in the 6-hydroxydopamine-lesioned rat model

To investigate the psychiatric symptoms accompanying the early phases of Parkinson's disease (PD), we injected adult rats with 10.5 μg 6-hydroxydopamine (6-OHDA) bilaterally into the dorsal striatum. The resulting neurodegeneration led, 12 weeks after injection, to a mild (36%) reduction of striatal dopamine. We tested the behavioral response of sham and 6-OHDA-lesioned animals at different time points after injection to evaluate the onset and progression of behavioral abnormalities. The results showed that such a mild reduction of dopamine levels was associated with a decrease in anxiety-like behavior, an increase in "depression"-like behavior, and a marked change in social behavior. Learning and memory abilities were not affected. Overall, the PD rat model used here displays behavioral alterations having face validity with psychiatric symptoms of the pathology and thus appears to be a valuable tool for investigating the neural bases of the early phases of PD. © 2008 Wiley-Liss, Inc

Uso de conectores para mejorar la producción de textos narrativos en estudiantes de educación primaria de la Institución Educativa Rurin-Pillao, Huánuco 2020

La presente investigación, titulada Uso de conectores para mejorar la producción de textos narrativos en estudiantes de educación primaria de la Institución Educativa Rurin- Pillao, Huánuco 2020, tiene como propósito principal determinar de qué manera influye el uso de conectores en la producción de textos narrativos en estudiantes de educación primaria. El tipo de investigación que se ha considerado es de tipo aplicado con un diseño cuasi experimental con dos grupos de trabajo. La muestra fue seleccionada mediante el muestreo no probabilístico intencionado, para ello, se utilizó la ficha de observación como instrumento de recolección de datos, los mismos que fueron corroborados en su puntuación de acuerdo con la variable que nos permitió obtener los resultados esperados. Una vez ejecutada la investigación a través del análisis de resultados estadísticos se demostró que el uso de conectores tiene una influencia significativa en la producción de textos en los estudiantes de educación primaria, ratificado por los valores t calculada y crítica donde se observa que: 7,97 es mayor que 1,69; en consecuencia, se rechaza la hipótesis nula y se evidencia que el promedio de los puntajes obtenidos en el postest del grupo experimental es mayor que del grupo de control. Por tanto, se afirma que el uso de conectores influye significativamente en la mejora de la producción de textos narrativos en estudiantes de educación primaria de la Institución Educativa Rurin – Pillao, Huánuco 2020

IT\u2019S ALL ABOUT THE SURFACE! VIBRATIONAL SPECTROSCOPY APPLIED TO THE STUDY OF BIOMIMETIC SURFACES FOR TISSUE ENGINEERING.

Tissue engineering is a multidisciplinary field aimed at the creation of biological substitutes that restore and maintain the biological function of a damaged tissue. The key of the success of these biomedical devices lies into surface interactions with living tissues, therefore a common strategy is to create biomimetic surfaces that help cells to colonize the biomaterial, leading to tissue healing. Raman and FT-IR vibrational spectroscopies, apart from being mainly surface and non-destructive techniques, are extremely sensitive to changes in structure and molecular interactions; thus, they have been increasingly used to investigate biomimetic devices. In particular, we have used vibrational spectroscopies to investigate different biomimetic materials and to test some of their proprieties: \u2022 self-assembling peptides adsorbed on titanium surfaces for bone implants, analyzed before and after attack from free radicals (obtained by gamma-radiolysis and mimicking inflammation processes), with the aim to evaluate their capability in resisting to oxidative stress; \u2022 composite (ceramic-polymer, polymer-polymer) bioresorbable biomaterials; \u2022 hydroxyapatite nanomaterials functionalized with proteins to increase biocompatibility

Surface enhanced Raman scattering and quantum-mechanical calculations on self-assembling oligopeptides

Five alternating polar/non-polar peptides derived from the self-assembling peptide EAK-16 (AEAEAKAK)2 were examined in comparison with the EAK-16 parent form (pept1). The peptides were studied for their possible use as biomimetic materials due to their auto-assembling properties and to the presence, in two of them, of the RGD sequence, an active modulator of cell adhesion. The use of SERS allows the detection of peptides at very low concentrations (10-5-10-6 M), a feature of extreme interest to check their presence in the aqueous environment surrounding a metal implant and to study the effects of systematic amino acid substitution along the peptide chain on the corresponding interaction with the Ag colloidal nanoparticles. Quantum-mechanical data on two of the examined peptides were carried out and were very useful for clarifying the bands assignment debated in the literature. The results indicate that, in general, the peptide-nanoparticle interaction takes place through the carboxylate groups. The SERS spectrum displays an enhancement of the bands attributed to carboxylate vibrations, indicating that these groups directly interact with the nanoparticles. The most prominent band of carboxylate groups appears at 1393 cm-1 (symmetrical COO- stretching), intensified and red shifted of about 10 cm-1, as compared to the FT-Raman spectrum. This effect can be attributed to the proximity of the COO- group to the surface and to a charge transfer mechanism. Moreover, other bands can be attributed to COO- vibrations: 909 cm-1 (C-COO- stretching), 655 cm-1 (COO- bending) and 563 cm-1 (COO- wagging). The theoretical calculations pointed out that the last two bands are mixed with amide motions. As regards the other examined peptides, the spacer substitution in the sequence is a factor able to affect the peptide-Ag particles interaction: the increase in the hydrophobic chain length (Ala substituted by 2-aminobutanoic acid) favors the interaction by NH3+ groups, although the charge transfer interaction with the COO- ions is still the main interaction with the colloid. In fact, the presence of many SERS bands attributable to the NH3+ moieties of the Lys amino acid side chains, indicates the existence of interactions between the NH3+ groups and the nanoparticles, mediated by the Cl- anions present in the colloidal solution. The substitution of Ala with an aromatic Tyr residue strongly affects the interaction mechanism: the Tyr residue lies in a position close to perpendicular to the silver surface, partly as tyrosinate ion

Fenretinide beneficial effects on amyotrophic lateral sclerosis-associated SOD1G93A mutant protein toxicity: in vitro and In vivo evidences

Amyotrophic lateral sclerosis (ALS) is the most frequent motor neuron disease for which effective treatment options are still lacking. ALS occurs in sporadic and familial forms which are clinically indistinguishable; about 20% of familial ALS cases are linked to mutations of the superoxide dismutase 1 (SOD1) gene. Fenretinide (FEN), a cancer chemopreventive and antiproliferative agent currently used in several clinical trials, is a multi-target drug which also exhibits redox regulation activities. We analyzed the effects of FEN on mutant SOD1 (mSOD1) toxicity in motoneuronal (NSC34) and a muscle (C2C12) cell lines and evaluated the impacts of chronic administration of a new nanomicellar fenretinide formulation (NanoMFen) on ALS disease progression in the SOD1G93A mouse model. The results showed that FEN significantly prevents the toxicity of mSOD1 expression in NSC34 motor neuron; furthermore, FEN is able to partially overcome the toxic effect of mSOD1 on the myogenic program of C2C12 muscle cells. Administration of NanoMFen ameliorates the disease progression and increases median survival of mSOD1G93A ALS mice, even when given after disease onset; beneficial effects in ALS mice, however, is restricted to female sex. Our data support the therapeutic potential of FEN against ALS-associated SOD1G93A mutant protein toxicity and promote further studies to elucidate specific cellular targets of the drug in ALS. Furthermore, the sex-related efficacy of NanoMFen in mSOD1G93A ALS mice strengthens the importance, in the perspective of a precision medicine approach, of gender pharmacology in ALS research

Dog-bite-related attacks: A new forensic approach

Dog attacks today represent a health hazard considering that prevention strategies have not always been successful. The identification of the dog that attacked the victim is necessary, considering the civil or criminal consequences for the animal's owner. An accurate scene analysis must be performed collecting a series of important information.Forensic investigations in dog attacks involve different methods, such as the evaluating of the canine Short Tandem Repeat (STR) typing in saliva traces on wounds or bite mark analysis, however, these techniques cannot always be applied. The effort to find new methods to identify the dog that attacked the victim represents a very interesting field for the forensic community.This study aims to propose an innovative approach, based on the identification of the victim's profile in the dog's mouth, using a buccal swab on the suspected aggressor dog, to find the victim's genetic profile. In addition, a further goal of this study is to determine the persistence time of hexogen DNA in the dog's mouth to define a timeframe for performing this particular technique.For this purpose, ten different dogs were used to aggressively bite a bovine sample (reference sample) to simulate the victim. For each dog two buccal swabs were taken at different time intervals: 30', 45', 60', 90', 120', 150', 180' and 240'. The typing of the swabs provided an interpretable profile after 45' while traces of bovine profile were found until 150' after the dog attack simulation.These results could be improved using the human identification kit, which is more sensitive. In the light of this experimental study, the forensic community should consider using this approach in real casework studies with the aim of collecting new data, validating this technique for forensic use. (C) 2020 Elsevier B.V. All rights reserved

Striatal 6-OHDA lesion in mice: Investigating early neurochemical changes underlying Parkinson's disease

Early phases of Parkinson's disease (PD) are characterized by a mild reduction of dopamine (DA) in striatum and by emergence of psychiatric disturbances that precede overt motor symptoms. in order to characterize the neurochemical re-arrangements induced by such striatal impairment, we used a mouse model in which a low dose of 6-hydroxydopamine (6-OHDA) was bilaterally injected into the dorsal striatum. These mice showed a DA reduction of about 40% that remained stable up to 12 weeks after injection. This reduction was accompanied by changes in DA metabolite levels, such as HVA, transiently reduced at 4 weeks, and DOPAC, decreased at 12 weeks. No change in the 5-hydroxytryptamine (5-HT) levels was found but the 5-hydroxyindoleacetic acid (5-HIAA)/5-HT ratio was increased at 4 weeks. In addition, at the same time-point, the levels of 15-F(2t)-IsoP, an index of oxidative stress, and of PGE2, a major product of cyclooxygenase-2, were decreased in different brain areas while BDNF levels were increased. These neurochemical changes were accompanied by altered behavioral responses concerning the emotional reactivity. Overall, the present findings suggest that a change of 5-HT metabolism and a modification of oxidative stress levels may play a role in the early PD degeneration phases. (C) 2009 Elsevier B.V. All rights reserved