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Axonal pathology is a key contributor to long-term disability in multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system (CNS), but the mechanisms that underlie axonal pathology in MS remain elusive. Evidence suggests that axonal pathology is a direct consequence of demyelination, as we and others have shown that the node of Ranvier disassembles following loss of myelin. In contrast to the node of Ranvier, we now show that the axon initial segment (AIS), the axonal domain responsible for action potential initiation, remains intact following cuprizone-induced cortical demyelination. Instead, we find that the AIS is disrupted in the neocortex of mice that develop experimental autoimmune encephalomyelitis (EAE) independent of local demyelination. EAE-induced mice demonstrate profound compromise of AIS integrity with a progressive disruption that corresponds to EAE clinical disease severity and duration, in addition to cortical microglial reactivity. Furthermore, treatment with the drug didox results in attenuation of AIS pathology concomitantly with microglial reversion to a less reactive state. Together, our findings suggest that inflammation, but not demyelination, disrupts AIS integrity and that therapeutic intervention may protect and reverse this pathology. GLIA 2016;64:1190-1209.

Formation of lasting memories is believed to rely on structural alterations at the synaptic level. We had found that increased neuronal activity down-regulates Nogo receptor-1 (NgR1) in brain regions linked to memory formation and storage, and postulated this to be required for formation of lasting memories. We now show that mice with inducible overexpression of NgR1 in forebrain neurons have normal long-term potentiation and normal 24-h memory, but severely impaired month-long memory in both passive avoidance and swim maze tests. Blocking transgene expression normalizes these memory impairments. Nogo, Lingo-1, Troy, endogenous NgR1, and BDNF mRNA expression levels were not altered by transgene expression, suggesting that the impaired ability to form lasting memories is directly coupled to inability to down-regulate NgR1. Regulation of NgR1 may therefore serve as a key regulator of memory consolidation. Understanding the molecular underpinnings of synaptic rearrangements that carry lasting memories may facilitate development of treatments for memory dysfunction.behavior ͉ hippocampus ͉ long-term potentiation ͉ myelin inhibitors ͉ synaptic plasticity

Nogo (reticulon-4) is a myelin-associated protein that is expressed in three different splice variants, Nogo-A, Nogo-B, and Nogo-C. Nogo-A inhibits neurite regeneration in the central nervous system. Messenger RNA encoding Nogo is expressed in oligodendrocytes and central and peripheral neurons, but not in astrocytes or Schwann cells. Nogo is a transmembraneous protein; the extracellular domain is termed Nogo-66, and a Nogo-66-receptor (Nogo-R) has been identified. We performed in situ hybridization in human and mouse nervous tissues to map the cellular distribution of Nogo-R gene activity patterns in fetal and adult human spinal cord and sensory ganglia, adult human brain, and the nervous systems of developing and adult mice. In the human fetus Nogo-R was transcribed in the ventral horn of the spinal cord and in dorsal root ganglia. In adult human tissues Nogo-R gene activity was found in neocortex, hippocampus, amygdala, and a subset of large and medium-sized neurons of the dorsal root ganglia. Nogo-R mRNA was not expressed in the adult human spinal cord at detectable levels. In the fetal mouse, Nogo-R was diffusely expressed in brain, brainstem, trigeminal ganglion, spinal cord, and dorsal root ganglia at all stages. In the adult mouse strong Nogo-R mRNA expression was found in neurons in neocortex, hippocampus, amygdala, habenula, thalamic nuclei, brainstem, the granular cell layer of cerebellum, and the mitral cell layer of the olfactory bulb. Neurons in the adult mouse striatum, the medial septal nucleus, and spinal cord did not express Nogo-R mRNA at detectable levels. In summary, Nogo-66-R mRNA expression in humans and mice was observed in neurons of the developing nervous system Expression was downregulated in the adult spinal cord of both species, and specific expression patterns were seen in the adult brain.

Recent agricultural development policies have begun to shift focus from the promotion of a few staple crops toward encouraging crop diversity. The belief is that crop diversification is an effective strategy for dealing with a variety of issues, including poverty alleviation. However, there is a lack of empirical evidence to justify these positions. We contribute to filling this research gap by providing quantitative evidence on the impact of diversity in crop cultivation on household poverty. Using household panel data from Ethiopia we develop a diversity index to measure the effect of crop diversity on poverty status. To control for endogeneity and selection bias resulting from unobserved heterogeneity we utilize a recently developed parametric method for estimating dynamic binary response models with endogenous contemporaneous regressors. Our results provide evidence that households which grow a diverse set of crops are less likely to be poor than households that specialize in their crop production. Additionally, crop diversity reduces the probability that a non-poor household will fall into poverty and the probability that a poor household will remain in poverty. We conclude that crop diversification is a viable way to deal with the exigencies of being poor.

ObjectivesTo explore evidence concerning gender differences in teaching and learning in surgery to guide future initiatives.MethodsThis systematic review was conducted searching in the following electronic databases: MEDLINE, EMBASE, CINAHL, PsycINFO, ERIC, Web of Science, Scopus and PubMed. All studies related to gender differences in surgical education, teaching or learning of surgery at an undergraduate level were included. Data was extracted and critically appraised. Gender differences in learning, teaching, skills acquisition, perceptions and attitudes, interest on surgery, personality and factors influencing interest in surgical careers were differentiated.ResultsThere is an underrepresentation of women in surgical academia, due to lack of role models and gender awareness. It is not clear whether or not gender itself is a factor that affects the learning of surgical tasks. Female students pursuing a surgical career had experienced sexual harassment and gender discrimination that can have an effect on the professional identity formation and specialty choice. There are differences in personality among female and male students interested in surgery. Gender is a determining factor to choose surgery, with a consistent lower proportion of women compared interested in pursuing a surgical career. Mentoring and personality fit are important in medical student’s specialty selection. Female students are more likely to be discouraged from pursuing a surgical career by a lack of female role models.ConclusionsBias against women in surgery still exists. There is a lack of studies that investigate the role of women in the teaching of surgery.

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