Preliminary results of a study of magnetic properties in the Foum-Zguid dyke (Morocco)

This work focuses on the study of flow and propagation of magma using rock magnetic analyses along sections across the thick Jurassic dyke of Foum-Zguid (Southern Morocco). Thermomagnetic data show that Ti-poor titanomagnetite is the main magnetic carrier. Petrographic analysis shows that the main Ti phase (ilmenite) occurs either as lamellae within spinel (center of the dyke) or as isolated grains (dyke margin). Bulk magnetic properties display distinct behavior according to the distance to the dyke margin; grain size of the main magnetic carrier decreases towards the center of the dyke, while the natural remanent magnetization and the bulk magnetic susceptibility increase. Only the magnetic susceptibility ellipsoid close to the dyke margin corresponds to that usually found in thin dykes, with the magnetic foliation sub parallel to dyke margins. Maximum principal axis is in most cases either parallel or perpendicular to the intersection between the planes of magnetic foliation and dyke wall. Moreover, when this axis is perpendicular to the intersection it is associated with a more oblate magnetic susceptibility ellipsoid shape, indicating the presence of complex magnetic fabrics. The studied magnetic properties show that, in this 100 m wide thick dyke, flow structures related with dyke propagation are only preserved close to the quickly cooled dyke margins. (C) 2004 Elsevier Ltd. All rights reserved

Striking Denervation of Neuromuscular Junctions without Lumbar Motoneuron Loss in Geriatric Mouse Muscle

Reasons for the progressive age-related loss of skeletal muscle mass and function, namely sarcopenia, are complex. Few studies describe sarcopenia in mice, although this species is the mammalian model of choice for genetic intervention and development of pharmaceutical interventions for muscle degeneration. One factor, important to sarcopenia-associated neuromuscular change, is myofibre denervation. Here we describe the morphology of the neuromuscular compartment in young (3 month) compared to geriatric (29 month) old female C57Bl/6J mice. There was no significant difference in the size or number of motoneuron cell bodies at the lumbar level (L1–L5) of the spinal cord at 3 and 29 months. However, in geriatric mice, there was a striking increase (by ∼2.5 fold) in the percentage of fully denervated neuromuscular junctions (NMJs) and associated deterioration of Schwann cells in fast extensor digitorum longus (EDL), but not in slow soleus muscles. There were also distinct changes in myofibre composition of lower limb muscles (tibialis anterior (TA) and soleus) with a shift at 29 months to a faster phenotype in fast TA muscle and to a slower phenotype in slow soleus muscle. Overall, we demonstrate complex changes at the NMJ and muscle levels in geriatric mice that occur despite the maintenance of motoneuron cell bodies in the spinal cord. The challenge is to identify which components of the neuromuscular system are primarily responsible for the marked changes within the NMJ and muscle, in order to selectively target future interventions to reduce sarcopenia

Near-infrared Variability of Obscured and Unobscured X-Ray-selected AGNs in the COSMOS Field

We present our statistical study of near infrared (NIR) variability of X-ray selected Active Galactic Nuclei (AGN) in the COSMOS field, using UltraVISTA data. This is the largest sample of AGN light curves in YJHKs bands, making possible to have a global description of the nature of AGN for a large range of redshifts, and for different levels of obscuration. To characterize the variability properties of the sources we computed the Structure Function. Our results show that there is an anti-correlation between the Structure Function $A$ parameter (variability amplitude) and the wavelength of emission, and a weak anti-correlation between $A$ and the bolometric luminosity. We find that Broad Line (BL) AGN have a considerably larger fraction of variable sources than Narrow Line (NL) AGN, and that they have different distributions of the $A$ parameter. We find evidence that suggests that most of the low luminosity variable NL sources correspond to BL AGN, where the host galaxy could be damping the variability signal. For high luminosity variable NL, we propose that they can be examples of "True type II" AGN or BL AGN with limited spectral coverage which results in missing the Broad Line emission. We also find that the fraction of variable sources classified as unobscured in the X-ray is smaller than the fraction of variable sources unobscured in the optical range. We present evidence that this is related to the differences in the origin of the obscuration in the optical and X-ray regimes.Comment: 21 pages, 17 figures, accepted for publication in Ap

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

Post-Operative Functional Outcomes in Early Age Onset Rectal Cancer

Background: Impairment of bowel, urogenital and fertility-related function in patients treated for rectal cancer is common. While the rate of rectal cancer in the young (<50 years) is rising, there is little data on functional outcomes in this group. Methods: The REACCT international collaborative database was reviewed and data on eligible patients analysed. Inclusion criteria comprised patients with a histologically confirmed rectal cancer, <50 years of age at time of diagnosis and with documented follow-up including functional outcomes. Results: A total of 1428 (n=1428) patients met the eligibility criteria and were included in the final analysis. Metastatic disease was present at diagnosis in 13%. Of these, 40% received neoadjuvant therapy and 50% adjuvant chemotherapy. The incidence of post-operative major morbidity was 10%. A defunctioning stoma was placed for 621 patients (43%); 534 of these proceeded to elective restoration of bowel continuity. The median follow-up time was 42 months. Of this cohort, a total of 415 (29%) reported persistent impairment of functional outcomes, the most frequent of which was bowel dysfunction (16%), followed by bladder dysfunction (7%), sexual dysfunction (4.5%) and infertility (1%). Conclusion: A substantial proportion of patients with early-onset rectal cancer who undergo surgery report persistent impairment of functional status. Patients should be involved in the discussion regarding their treatment options and potential impact on quality of life. Functional outcomes should be routinely recorded as part of follow up alongside oncological parameters

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

A neuropathologic diagnosis of Alzheimer's disease in an older adult with HIV-associated neurocognitive disorder.

We discuss the challenges associated with diagnosing neurodegenerative disorders in older adults living with HIV, illustrated through a case report where neurologic co-diagnosis of Alzheimer's disease (AD) and HIV-associated Neurocognitive Disorder (HAND) are considered. The patient was followed and evaluated for over 4 years and underwent post-mortem neuropathologic evaluation. Further work is needed to identify diagnostic tests that can adequately distinguish HAND from early stage neurodegenerative disorders among older adults living with HIV and cognitive changes

Divergent outcomes in cognitive-behavioral therapy and pharmacotherapy for adult depression

Objective: Although the average depressed patient benefits moderately from cognitive-behavioral therapy (CBT) or pharmacotherapy, some experience divergent outcomes. The authors tested frequencies, predictors, and moderators of negative and unusually positive outcomes. Method: Sixteen randomized clinical trials comparing CBT and pharmacotherapy for unipolar depression in 1,700 patients provided individual pre- and posttreatment scores on the Hamilton Depression Rating Scale (HAM-D) and/or Beck Depression Inventory (BDI). The authors examined demographic and clinical predictors and treatmentmoderators of any deterioration (increase≥1HAM-Dor BDI point), reliable deterioration (increase ≥8 HAM-D or ≥9 BDI points), extreme nonresponse (posttreatment HAM-D score ≥21 or BDI score ≥31), superior improvement (HAM-D or BDI decrease≥ 95%), and superior response (posttreatmentHAM-D or BDI score of 0) using multilevel models. Results: About5'%of patients showedany deterioration, 1% reliable deterioration, 4%% extreme nonresponse, 6!0% superior improvement, and 4%% superior response. Superior improvement on the HAM-D only (odds ratio=1.67) and attrition (odds ratio=1.67) were more frequent in pharmacotherapy than in CBT. Patients with deterioration or superior response had lower pretreatment symptom levels, whereas patients with extreme nonresponse or superior improvement had higher levels. Conclusions: Deterioration and extreme nonresponse and, similarly, superior improvement and superior response, both occur infrequently in randomized clinical trials comparing CBT and pharmacotherapy for depression. Pretreatment symptom levels help forecast negative and unusually positive outcomes but do not guide selection of CBT versus pharmacotherapy. Pharmacotherapy may produce clinician-rated superior improvement and attrition more frequently than does CBT