Nogo receptor antagonizes p75NTR-dependent motor neuron death

The Nogo-66 receptor (NgR) plays a critical role in restricting axon regeneration in the central nervous system. This inhibitory action is in part mediated by a neuronal receptor complex containing p75NTR, a multifunctional receptor also well known to trigger cell death upon binding to neurotrophins such as NGF. In the present study, we show that Pep4 and NEP1-40, which are two peptides derived from the Nogo-66 sequence that modulate NgR-mediated neurite outgrowth inhibition, prevent NGF-stimulated p75NTR-dependent death of cultured embryonic motor neurons. They also confer protection on spinal cord motor neurons after neonatal sciatic nerve axotomy. These findings demonstrate an as-yet-unknown function of NgR in maintaining neuronal survival that may be relevant for motor neuron development and degeneration.     

Effects of equid herpesvirus 1 (EHV-1) AR8 and HH1 strains on BALB-c mice

Here, we used a murine model to describe and compare the pathogenic potential of the Argentinean equid herpesvirus 1 (EHV-1) AR8 strain with the Japanese HH1 reference strain. In AR8-inoculated animals, clinical signs began earlier, but the viremic phase was shorter. Virus isolation and DNA detection in the lungs, liver and spleen were positive for both strains at different times postinfection (pi). Infection foci produced by both strains were immunohistochemically detected in lungs from day 1 to day 4 pi. We conclude that whichever EHV-1 strain is selected to experimentally reproduce the disease, it needs appropriate standardization in order to provide valid conclusions.     

Bone Modeling Patterns and Morphometric Craniofacial Variation in Individuals From Two Prehistoric Human Populations From Argentina

Native human populations from South America display high levels of craniofacial variation encompassing gracile and robust skulls. Nevertheless, the processes of bone modeling by which morphological variation among populations were attained, remain poorly understood. Here we analyze the relationship between patterns of bone formation and resorption and morphometric variation in the upper face of adults belonging to farmers and hunter‐gatherers from northwestern and south Argentina. Our analyses reveal a common pattern of bone modeling of the malar bone characterized by the presence of formation areas. Thus, the larger size and greater development of malar bone exhibited by hunter‐gatherers would be linked to a greater magnitude of bone formation activity. Conversely, the glabella and the superciliary arch presented both formation and resorption areas with a variable distribution among individuals. In the extreme corresponding to more robust morphologies, the great development of the glabella is related to the presence of large formation fields, both in the upper region and toward the frontonasal suture. The less robust morphologies show resorption fields at the upper margin of the glabella, which would contribute to the weaker development of this region. The superciliary arch showed a complex relationship between its morphometric and histological variation; the individuals located at both extremes of the shape space presented large resorption areas located on its upper margin. Overall, our results show the existence of intraspecific variation in the patterns of bone modeling in the human upper face. Anat Rec, 297:1829–1838, 2014. © 2014 Wiley Periodicals, Inc.     

Peroxynitrite-induced cytotoxicity in cultured astrocytes is associated with morphological changes and increased nitrotyrosine immunoreactivity

We have established a cell culture model of spinal cord astrocytes to study the cytotoxicity of peroxynitrite. Nitric oxide (NO) has been implicated as a key contributor to neurotoxicity. NO reacts with superoxide to generate peroxynitrite, a strong oxidant and nitrating agent with deleterious cytotoxic and pro-apoptotic effects. Peroxynitrite and nitrotyrosine are formed in damaged motor neurons in amyotrophic lateral sclerosis (ALS), which are surrounded by reactive astrocytes. To determine the effects of extracellular addition of peroxynitrite, purified astrocytes monolayers prepared from neonatal rat spinal cords were exposed to peroxynitrite (0.25–0.75 mM) for 5 min and further incubated in culture medium for 24–72 h. Peroxynitrite exposure did not result in apparent cell loss or damage of the monolayer. However, a substantial number of cells adopted reactive features, with long processes displaying intense immunoreactivity to glial fibrillary acidic protein (GFAP). Western blot analysis performed 24 h after peroxynitrite treatment showed that GFAP levels were not modified by the oxidant. There were no changes in cell viability parameters in astrocyte cultures after peroxynitrite, indicating that astrocytes are more resistant to the oxidant than other cell types. Peroxynitrite reacts with protein-bound tyrosine residues to form nitrotyrosine. We observed a modest to strong nitrotyrosine immunoreactivity in astrocytes 24 h following peroxynitrite exposure. There was a remarkable association between nitrotyrosine and high-intensity GFAP immunoreactivity in astrocytes bearing long processes. These results suggest that peroxynitrite induces a characteristic long-lasting reactive astrocytic phenotype and provide new insight into understanding the origin of reactive astrocytes occurring in ALS.     

Development of compensatory hepatic hyperplasia in mice carrying the hepatocellular carcinoma ES12a

In a previous paper we reported that the presence of the hepatocellular carcinoma SS1K in host mice resulted in an earlier appearance of the hepatocyte mitotic peak during liver regeneration after a partial hepatectomy as well as in an increase in the amplitude of that mitotic wave. In the present work we analyse the effect of another hepatocellular carcinoma, the ES12a (HCES12a). Adult male mice of the C3H/S strain standardised for circadian-periodicity analysis, were used. One group received a subcutaneous graft of the HCES12a tumor, while another group served as control. Fifteen days later, all animals were submitted to a partial (70%) hepatectomy at 10:00 h and beginning at 16:00 h lots of between 5 and 9 host and control animals each were sacrificed at 4 h intervals until 16:00 h on the third day thereafter. All mice were injected with 2 microg/g colchicine 4 hrs before killing, and samples of livers were processed for hematoxylin-eosin staining. We determined the hepatocyte mitotic index for each animal and the mean value +/- the standard error of the mean for each lot. The peak of mitotic activity in the tumor-bearing animals took place four hours earlier than in control mice but the average values of hepatocytic mitotic activity were similar in both groups     

Bird orientation and the geomagnetic field: A review

The possibility that birds use the geomagnetic field to guide their orientation has been repeatedly suggested over the last century. Early attempts to experimentally verify this hypothesis were largely unsuccessful. Recently, however, this issue has been more thoroughly examined, from a variety of approaches, with positive results. Magnetic fields have been shown to have a biological effect on a variety of animals ranging from unicellular organisms to mammals. Many of these organisms, including birds, show changes in orientation behavior as a result of changes in the ambient magnetic field. Specific data supporting the existence of a “magnetic-compass” in birds include demonstrations that (a) changes in the intensity of the ambient magnetic field disrupt various kinds of orientation behavior and (b) that systematic changes in the direction of the ambient magnetic field are accompanied by systematic changes in the direction of orientation. The biggest obstacle in further study of the “magnetic-compass” is the almost complete ignorance of the biophysical mechanism(s) involved in the biological detection of the geomagnetic field. Some theoretical speculations about possible biomagnetic mechanisms are discussed and suggestions for the direction of future research on the “magnetic-compass” and its relation to other orientation behaviors are provided.     

Popliteal fossa sciatic nerve block for ambulatory hallux valgus surgery: comparison of lateral and posterior approaches

OBJECTIVE: The aim of this study was to assess the efficacy, effectiveness, technical difficulty, and clinical usefulness of the popliteal sciatic peripheral nerve block for unilateral hallus valgux surgery and to compare the posterior and lateral approaches. We also aimed to investigate patient comfort during the procedure. MATERIALS AND METHODS: This prospective, randomized trial enrolled 60 patients scheduled for unilateral hallux valgus surgery. The patients were randomly assigned to groups of 30 patients to receive a nerve block by either a posterior or lateral approach. A nerve stimulator was used to locate the response of the two branches forming the sciatic nerve--the posterior tibial nerve and the common peroneal nerve. Then, 20 mL of 0.5% ropivacaine was injected for each nerve. Variables analyzed were efficacy, complications, quality and duration of postoperative analgesia, degree of comfort while the technique was being performed, and level of satisfaction. RESULTS: The level of comfort was good for 19 patients (70%) in the posterior approach group and for 29 (97%) in the lateral approach group (P<0.05). Level of satisfaction was good or very good for 93% and 96% of the patients in the posterior and lateral approach groups, respectively. Block efficacy was excellent for 48 patients (80%), good for 9 (15%), and poor for 3 (5%), with no significant differences between the groups. CONCLUSION: Both the posterior and lateral approaches provide easy access to the sciatic nerve for performing a block. The rate of success is high and postoperative analgesia is good, with no noteworthy complications. However, the lateral approach is more comfortable for the patient.     

Mitochondria in amyotrophic lateral sclerosis: a trigger and a target

Strong evidence shows that mitochondrial dysfunction is involved in amyotrophic lateral sclerosis (ALS), but despite the fact that mitochondria play a central role in excitotoxicity, oxidative stress and apoptosis, the intimate underlying mechanism linking mitochondrial defects to motor neuron degeneration in ALS still remains elusive. Morphological and functional abnormalities occur in mitochondria in ALS patients and related animal models, although their exact nature and extent are controversial. Recent studies postulate that the mislocalization in mitochondria of mutant forms of copper-zinc superoxide dismutase (SOD1), the only well-documented cause of familial ALS, may account for the toxic gain of function of the enzyme, and hence induce motor neuron death. On the other hand, mitochondrial dysfunction in ALS does not seem to be restricted only to motor neurons as it is also present in other tissues, particularly the skeletal muscle. The presence of this 'systemic' defect in energy metabolism associated with the disease is supported in skeletal muscle tissue by impaired mitochondrial respiration and overexpression of uncoupling protein 3. In addition, the lifespan of transgenic mutant SOD1 mice is increased by a highly energetic diet compensating both the metabolic defect and the motorneuronal function. In this review, we will focus on the mitochondrial dysfunction linked to ALS and the cause-and-effect relationships between mitochondria and the pathological mechanisms thought to be involved in the disease.