The cytochrome c gene proximal enhancer drives activity-dependent reporter gene expression in hippocampal neurons

The proximal enhancer of the cytochrome c gene (Cycs) contains binding sites for both cAMP response element binding proteins (CREB) and Nuclear Respiratory Factor 1 (NRF1). To investigate how neuronal activity regulates this enhancer region, a lentivirus was constructed in which a short-lived green fluorescent protein (GFP) was placed under the transcriptional control of the Cycs proximal enhancer linked to a synthetic core promoter. Primary hippocampal neurons were infected, and the synaptic strengths of individual neurons were measured by whole-cell patch clamping. On average the amplitude of miniature postsynaptic currents (mEPSCs) was higher in brighter GFP+ neurons, while the frequency of mEPSCs was not significantly different. Increasing neural activity by applying a GABAA receptor antagonist increased GFP expression in most neurons, which persisted after homeostatic synaptic scaling as evidenced by a decrease in the amplitude and frequency of mEPSCs. Removing the CREB binding sites revealed that calcium influx through L-type channels and NMDA receptors, and ERK1/2 activation played a role in NRF1-mediated transcription. CREB and NRF1, therefore, combine to regulate transcription of Cycs in response to changing neural activity

Being an Early-Career CMS Academic in the Context of Insecurity and ‘Excellence’: The Dialectics of Resistance and Compliance

Drawing on a dialectical approach to resistance, we conceptualise the latter as a multifaceted, pervasive and contradictory phenomenon. This enables us to examine the predicament in which early-career Critical Management Studies academics find themselves in the current times of academic insecurity and ‘excellence’, as gleaned through this group’s understandings of themselves as resisters and participants in the complex and contradictory forces constituting their field. We draw on 24 semi-structured interviews to map our participants’ accounts of themselves as resisters in terms of different approaches to tensions and contradictions between, on the one hand, the interviewees’ Critical Management Studies alignment and, on the other, the ethos of business school neoliberalism. Emerging from this analysis are three contingent and interlinked narratives of resistance and identity – diplomatic, combative and idealistic – each of which encapsulates a particular mode (negotiation, struggle, and laying one’s own path) of engaging with the relationship between Critical Management Studies and the business school ethos. The three narratives show how early-career Critical Management Studies academics not only use existing tensions, contradictions, overlaps and alliances between these positions to resist and comply with selected forces within each, but also contribute to the (re-)making of such overlaps, alliances, tensions and contradictions. Through this reworking of what it means to be both Critical Management Studies scholars and business school academics, we argue, early-career Critical Management Studies academics can be seen as active resisters and re-constituters of their complex field

Nerve-preserving aortoiliac reconstruction surgery: Anatomical study and surgical approach

AbstractObjective: Dysfunctional ejaculation and, to a lesser extent, dysfunctional erection caused by disruption of efferent sympathetic pathways is a common complication after aortoiliac reconstruction surgery. The aim was to give an anatomic motivation for a nerve-preserving approach on the basis of right-sided unilateral disruption of lumbar splanchnic nerves. Methods: Anatomic and microscopic analysis of preaortic and para-aortic retroperitoneal regions in human cadavers was performed. Anatomic analysis was conducted of two aortoiliac reconstruction operations performed on human cadavers; one was performed according to a single-blind procedure, the second with a modified procedure. Results: The lumbar splanchnic nerves supplying the superior hypogastric plexus from the right side were found to be less voluminous than the left-sided ones. The superior hypogastric plexus was found slightly shifted to the left of the midsagittal plane across the abdominal aorta and its bifurcation. Microscopic analysis revealed a thin fascia between the aorta and the subperitoneal tissue compartment. This fascia was used as a plain of dissection to mobilize the preaortic nerve-plexuses without damage from the aortic wall. Analysis of the specimens operated on showed a significant difference in nerve disruption. The standard procedure caused total disruption of the superior hypogastric plexus and extensive disruption of the inferior mesenteric plexus. The modified procedure only caused right-sided unilateral disruption of lumbar splanchnic nerves. Conclusion: The autonomic nerves supplying the bladder neck, the vas deferens, and the prostate are closely related to the abdominal aorta and its bifurcation. Right-sided unilateral disruption of lumbar splanchnic nerves without further damage to nervous structures would ensure at least one functional sympathetic pathway remaining after aortoiliac reconstruction surgery. (J Vasc Surg 2001;33:983-9.

Stime di emissioni di inquinanti provenienti da sorgenti di traffico nell’area veneziana.

Purpose: Wnt signalling has been implicated in breast cancer, and in particular aberrant β-catenin-independent Wnt signalling has been associated with breast cancer metastasis and Tamoxifen resistance. Despite Wnt pathway involvement in many human cancers, attempts to target the pathway therapeutically have been disappointing. The recent discovery that the receptor tyrosine kinase-like orphan receptor 2 (ROR2) is a novel Wnt receptor provides a potential new therapeutic and diagnostic target

Diversity, elevational variation, and phylogeographic origin of stump-toed frogs (Microhylidae: Cophylinae: Stumpffia) on the Marojejy massif, northern Madagascar

Stump-toed frogs (genus Stumpffia Boettger, 1881) are a diverse group of small-bodied frogs endemic to Madagascar. Seven species of this genus occur on Marojejy, a steep massif in northeastern Madagascar. Here we examine the elevational distribution, phylogenetic position, biogeographic origin, and genetic differentiation of this Stumpffia assemblage. We show that none of these species is another’s closest relative, but rather they are all independent lineages that probably colonised the Marojejy Massif through repeated immigration events. All of the lineages on Marojejy are most closely related to species south and southwest of the massif, except one lineage, formerly known as Stumpffia sp. Ca07, but here assigned to S. sorata as a deep conspecific lineage (and referred to as S. cf. sorata), which occurs also in Sorata, 90 km north of Marojejy. The species on Marojejy are typically restricted to narrow elevational ranges, but at least two species, S. cf. sorata and S. tridactyla, occur over elevations spanning 1000 metres. We assessed the genetic variability of these populations, and found considerable haplotype separation in fragments of the mitochondrial 16S rRNA and nuclear Rag-1 genes, suggesting some disruption of gene flow associated with elevation. We discuss the biogeographic implications of our findings and, based on previously published data, the evolution of non-overlapping bioacoustic parameters among the diverse assemblage of Stumpffia species on the Marojejy massif

Development of the corpus callosum and cognition after neonatal encephalopathy

Objective: Neonatal imaging studies report corpus callosum abnormalities after neonatal hypoxic–ischaemic encephalopathy (HIE), but corpus callosum development and relation to cognition in childhood are unknown. Using magnetic resonance imaging (MRI), we examined the relationship between corpus callosum size, microstructure and cognitive and motor outcomes at early school-age children cooled for HIE (cases) without cerebral palsy compared to healthy, matched controls. A secondary aim was to examine the impact of HIE-related neonatal brain injury on corpus callosum size, microstructure and growth. Methods: Participants aged 6–8 years underwent MRI, the Movement Assessment Battery for Children Second Edition and Wechsler Intelligence Scale for Children Fourth Edition. Cross-sectional area, volume, fractional anisotropy and radial diffusivity of the corpus callosum and five subdivisions were measured. Multivariable regression was used to assess associations between total motor score, full-scale IQ (FSIQ) and imaging metrics. Results: Adjusting for age, sex and intracranial volume, cases (N = 40) compared to controls (N = 39) demonstrated reduced whole corpus callosum area (β = −26.9, 95% confidence interval [CI] = −53.17, −0.58), volume (β = −138.5, 95% CI = −267.54, −9.56), fractional anisotropy and increased radial diffusivity (P < 0.05) within segments II–V. In cases, segment V area (β = 0.18, 95% CI = 0.004, 0.35), volume (β = 0.04, 95% CI = 0.001, 0.079), whole corpus callosum fractional anisotropy (β = 13.8 95% CI = 0.6, 27.1) and radial diffusivity (β = −11.3, 95% CI = −22.22, −0.42) were associated with FSIQ. Growth of the corpus callosum was restricted in cases with a FSIQ ≤85, and volume was reduced in cases with mild neonatal multifocal injury compared to white matter injury alone. Interpretation: Following neonatal HIE, morphological and microstructural changes in the corpus callosum are associated with reduced cognitive function at early school age

Rendering an Account: An Open-State Archive in Postgraduate Supervision

The paper begins with a brief account of the transformation of research degree studies under the pressures of global capitalism and neo-liberal governmentality. A parallel transformation is occurring in the conduct of research through the use of information and communication technologies. Yet the potential of ICTs to shape practices of surveillance or to produce new student-supervisor relations and enhance the processes of developing the dissertation has received almost no critical attention. As doctoral supervisor and student, we then describe the features and uses of a web-based open state archive of the student's work-in-progress, developed by the student and accessible to his supervisor. Our intention was to encourage more open conversations between data and theorising, student and supervisor, and ultimately between the student and professional community. However, we recognise that relations of accountability, as these have developed within a contemporary "audit revolution" (Power, 1994, 1997) in universities, create particular "lines of visibility" (Munro, 1996). Thus while the open-state archive may help to redefine in less managerial terms notions of quality, transparency, flexibility and accountability, it might also make possible greater supervisory surveillance. How should we think about the panoptical potential of this archive? We argue that the diverse kinds of interactional patterns and pedagogical intervention it encourages help to create shifting subjectivities. Moreover, the archive itself is multiple, in bringing together an array of diverse materials that can be read in various ways, by following multiple paths. It therefore constitutes a collage, which we identify as a mode of cognition and of accounting distinct from but related to argument and narrative. As a more "open" text (Iser, 1978) it has an indeterminacy which may render it less open to abuse for the technologies of managerial accountability

Synapse-associated protein 102/dlgh3 couples the NMDA receptor to specific plasticity pathways and learning strategies

Understanding the mechanisms whereby information encoded within patterns of action potentials is deciphered by neurons is central to cognitive psychology. The multiprotein complexes formed by NMDA receptors linked to synaptic membrane-associated guanylate kinase (MAGUK) proteins including synapse-associated protein 102 (SAP102) and other associated proteins are instrumental in these processes. Although humans with mutations in SAP102 show mental retardation, the physiological and biochemical mechanisms involved are unknown. Using SAP102 knock-out mice, we found specific impairments in synaptic plasticity induced by selective frequencies of stimulation that also required extracellular signal-regulated kinase signaling. This was paralleled by inflexibility and impairment in spatial learning. Improvement in spatial learning performance occurred with extra training despite continued use of a suboptimal search strategy, and, in a separate nonspatial task, the mutants again deployed a different strategy. Double-mutant analysis of postsynaptic density-95 and SAP102 mutants indicate overlapping and specific functions of the two MAGUKs. These in vivo data support the model that specific MAGUK proteins couple the NMDA receptor to distinct downstream signaling pathways. This provides a mechanism for discriminating patterns of synaptic activity that lead to long-lasting changes in synaptic strength as well as distinct aspects of cognition in the mammalian nervous system

Brain volumes and functional outcomes in children without cerebral palsy after therapeutic hypothermia for neonatal hypoxic-ischaemic encephalopathy

Aim: To investigate whether brain volumes were reduced in children aged 6 to 8 years without cerebral palsy, who underwent therapeutic hypothermia for neonatal hypoxic-ischaemic encephalopathy (patients), and matched controls, and to examine the relation between subcortical volumes and functional outcome.   Method: We measured regional brain volumes in 31 patients and 32 controls (median age 7 years and 7 years 2 months respectively) from T1-weighted magnetic resonance imaging (MRI). We assessed cognition using the Wechsler Intelligence Scales for Children, Fourth Edition and motor ability using the Movement Assessment Battery for Children, Second Edition (MABC-2).  Results: Patients had lower volume of whole-brain grey matter, white matter, pallidi, hippocampi, and thalami than controls (false discovery rate-corrected p < 0.05). Differences in subcortical grey-matter volumes were not independent of total brain volume (TBV). In patients, hippocampal and thalamic volumes correlated with full-scale IQ (hippocampi, r = 0.477, p = 0.010; thalami, r = 0.452, p = 0.016) and MABC-2 total score (hippocampi, r = 0.526, p = 0.004; thalami, r = 0.505, p = 0.006) independent of age, sex, and TBV. No significant correlations were found in controls. In patients, cortical injury on neonatal MRI was associated with reduced volumes of hippocampi (p = 0.001), thalami (p = 0.002), grey matter (p = 0.015), and white matter (p = 0.013).  Interpretation: Children who underwent therapeutic hypothermia have reduced whole-brain grey and white-matter volumes, with associations between hippocampal and thalamic volumes and functional outcomes

A distinctive new frog species (Anura, Mantellidae) supports the biogeographic linkage of two montane rainforest massifs in northern Madagascar

We describe a new species of the genus Gephyromantis, subgenus Vatomantis (Mantellidae, Mantellinae), from moderately high elevation (1164–1394 m a.s.l.) on the Marojejy, Sorata, and Andravory Massifs in northern Madagascar. The new species, Gephyromantis (Vatomantis) lomorina sp. n. is highly distinct from all other species, and was immediately recognisable as an undescribed taxon upon its discovery. It is characterised by a granular, mottled black and green skin, reddish eyes, paired subgular vocal sacs of partly white colour, bulbous femoral glands present only in males and consisting of three large granules, white ventral spotting, and a unique, amplitude-modulated advertisement call consisting of a series of 24–29 rapid, quiet notes at a dominant frequency of 5124–5512 Hz. Genetically the species is also strongly distinct from its congeners, with uncorrected pairwise distances ≥10 % in a fragment of the mitochondrial 16S rRNA gene to all other nominal Gephyromantis species. A molecular phylogeny based on 16S sequences places it in a clade with species of the subgenera Laurentomantis and Vatomantis, and we assign it to the latter subgenus based on its morphological resemblance to members of Vatomantis. We discuss the biogeography of reptiles and amphibians across the massifs of northern Madagascar, the evidence for a strong link between Marojejy and Sorata, and the role of elevation in determining community sharing across this landscape