The upshot of up states in the neocortex: From slow oscillations to memory formation

Contains fulltext : 201422.pdf (publisher's version ) (Open Access

Onecut-dependent Nkx6.2 transcription factor expression is required for proper formation and activity of spinal locomotor circuits.

In the developing spinal cord, Onecut transcription factors control the diversification of motor neurons into distinct neuronal subsets by ensuring the maintenance of Isl1 expression during differentiation. However, other genes downstream of the Onecut proteins and involved in motor neuron diversification have remained unidentified. In the present study, we generated conditional mutant embryos carrying specific inactivation of Onecut genes in the developing motor neurons, performed RNA-sequencing to identify factors downstream of Onecut proteins in this neuron population, and employed additional transgenic mouse models to assess the role of one specific Onecut-downstream target, the transcription factor Nkx6.2. Nkx6.2 expression was up-regulated in Onecut-deficient motor neurons, but strongly downregulated in Onecut-deficient V2a interneurons, indicating an opposite regulation of Nkx6.2 by Onecut factors in distinct spinal neuron populations. Nkx6.2-null embryos, neonates and adult mice exhibited alterations of locomotor pattern and spinal locomotor network activity, likely resulting from defective survival of a subset of limb-innervating motor neurons and abnormal migration of V2a interneurons. Taken together, our results indicate that Nkx6.2 regulates the development of spinal neuronal populations and the formation of the spinal locomotor circuits downstream of the Onecut transcription factors

Phytoplankton dynamics in relation to seasonal variability and upwelling and relaxation patterns at the mouth of Ria de Aveiro (West Iberian Margin) over a four-year period

From June 2004 to December 2007, samples were weekly collected at a fixed station located at the mouth of Ria de Aveiro (West Iberian Margin). We examined the seasonal and inter-annual fluctuations in composition and community structure of the phytoplankton in relation to the main environmental drivers and assessed the influence of the oceano-graphic regime, namely changes in frequency and intensity of upwelling events, over the dynamics of the phytoplankton assemblage. The samples were consistently handled and a final subset of 136 OTUs (taxa with relative abundance > 0.01%) was subsequently submitted to various multivariate analyses. The phytoplankton assemblage showed significant changes at all temporal scales but with an overriding importance of seasonality over longer-(inter-annual) or shorter-term fluctuations (upwelling-related). Sea-surface temperature, salinity and maximum upwelling index were retrieved as the main driver of seasonal change. Seasonal signal was most evident in the fluctuations of chlorophyll a concentration and in the high turnover from the winter to spring phytoplankton assemblage. The seasonal cycle of production and succession was disturbed by upwelling events known to disrupt thermal stratification and induce changes in the phytoplankton assemblage. Our results indicate that both the frequency and intensity of physical forcing were important drivers of such variability, but the outcome in terms of species composition was highly dependent on the available local pool of species and the timing of those events in relation to the seasonal cycle. We conclude that duration, frequency and intensity of upwelling events, which vary seasonally and inter-annually, are paramount for maintaining long-term phytoplankton diversity likely by allowing unstable coexistence and incorporating species turnover at different scales. Our results contribute to the understanding of the complex mechanisms of coastal phytoplankton dynamics in relation to changing physical forcing which is fundamental to improve predictability of future prospects under climate change.Portuguese Foundation for Science and Technology (FCT, Portugal) [SFRH/BPD/ 94562/2013]; FEDER funds; national funds; CESAM [UID/AMB/50017]; FCT/MEC through national funds; FEDERinfo:eu-repo/semantics/publishedVersio

Multiplexed, High Density Electrophysiology with Nanofabricated Neural Probes

Extracellular electrode arrays can reveal the neuronal network correlates of behavior with single-cell, single-spike, and sub-millisecond resolution. However, implantable electrodes are inherently invasive, and efforts to scale up the number and density of recording sites must compromise on device size in order to connect the electrodes. Here, we report on silicon-based neural probes employing nanofabricated, high-density electrical leads. Furthermore, we address the challenge of reading out multichannel data with an application-specific integrated circuit (ASIC) performing signal amplification, band-pass filtering, and multiplexing functions. We demonstrate high spatial resolution extracellular measurements with a fully integrated, low noise 64-channel system weighing just 330 mg. The on-chip multiplexers make possible recordings with substantially fewer external wires than the number of input channels. By combining nanofabricated probes with ASICs we have implemented a system for performing large-scale, high-density electrophysiology in small, freely behaving animals that is both minimally invasive and highly scalable

Modern Modal Testing: A Cautionary Tale

Over the past 50 years, great advances have been achieved in both analytical modal analysis (i.e. finite element models and analysis) and experimental modal analysis (i.e. modal testing) in aerospace and other fields. With the advent of more powerful computers, higher performance instrumentation and data acquisition systems, and powerful linear modal extraction tools, analysts and test engineers have a breadth and depth of technical resources only dreamed of by our predecessors. However, some observed recent trends indicate that hard lessons learned are being forgotten or ignored, and possibly fundamental concepts are not being understood. These trends have the potential of leading to the degradation of the quality of and confidence in both analytical and test results. These trends are a making of our own doing, and directly related to having ever more powerful computers, programmatic budgetary pressures to limit analysis and testing, and technical capital loss due to the retirement of the senior component of a bimodal workforce. This paper endeavors to highlight some of the most important lessons learned, common pitfalls to hopefully avoid, and potential steps that may be taken to help reverse this trend

Enhanced virtual microscopy for collaborative education

<p>Abstract</p> <p>Background</p> <p>Curricular reform efforts and a desire to use novel educational strategies that foster student collaboration are challenging the traditional microscope-based teaching of histology. Computer-based histology teaching tools and Virtual Microscopes (VM), computer-based digital slide viewers, have been shown to be effective and efficient educational strategies. We developed an open-source VM system based on the Google Maps engine to transform our histology education and introduce new teaching methods. This VM allows students and faculty to collaboratively create content, annotate slides with markers, and it is enhanced with social networking features to give the community of learners more control over the system.</p> <p>Results</p> <p>We currently have 1,037 slides in our VM system comprised of 39,386,941 individual JPEG files that take up 349 gigabytes of server storage space. Of those slides 682 are for general teaching and available to our students and the public; the remaining 355 slides are used for practical exams and have restricted access. The system has seen extensive use with 289,352 unique slide views to date. Students viewed an average of 56.3 slides per month during the histology course and accessed the system at all hours of the day. Of the 621 annotations added to 126 slides 26.2% were added by faculty and 73.8% by students. The use of the VM system reduced the amount of time faculty spent administering the course by 210 hours, but did not reduce the number of laboratory sessions or the number of required faculty. Laboratory sessions were reduced from three hours to two hours each due to the efficiencies in the workflow of the VM system.</p> <p>Conclusions</p> <p>Our virtual microscope system has been an effective solution to the challenges facing traditional histopathology laboratories and the novel needs of our revised curriculum. The web-based system allowed us to empower learners to have greater control over their content, as well as the ability to work together in collaborative groups. The VM system saved faculty time and there was no significant difference in student performance on an identical practical exam before and after its adoption. We have made the source code of our VM freely available and encourage use of the publically available slides on our website.</p

Task-Dependent Interaction between Parietal and Contralateral Primary Motor Cortex during Explicit versus Implicit Motor Imagery

Both mental rotation (MR) and motor imagery (MI) involve an internalization of movement within motor and parietal cortex. Transcranial magnetic stimulation (TMS) techniques allow for a task-dependent investigation of the interhemispheric interaction between these areas. We used image-guided dual-coil TMS to investigate interactions between right inferior parietal lobe (rIPL) and left primary motor cortex (M1) in 11 healthy participants. They performed MI (right index-thumb pinching in time with a 1 Hz metronome) or hand MR tasks, while motor evoked potentials (MEPs) were recorded from right first dorsal interosseous. At rest, rIPL conditioning 6 ms prior to M1 stimulation facilitated MEPs in all participants, whereas this facilitation was abolished during MR. While rIPL conditioning 12 ms prior to M1 stimulation had no effect on MEPs at rest, it suppressed corticomotor excitability during MI. These results support the idea that rIPL forms part of a distinct inhibitory network that may prevent unwanted movement during imagery tasks

Benign Orbital Tumors with Bone Destruction in Children

Purpose: To present rare benign orbital tumors with bone destruction in children who could not be diagnosed presurgically and may simulate malignant ones. Methods: A retrospective review of cases. Clinical, operative and pathological records in all children with a diagnosis of benign orbital tumors who showed remarkable bone destruction at a tertiary Ophthalmic Center in China between Jan 1, 2000 and Dec 31, 2009 were reviewed. All patients had definitive histopathologic diagnosis. Results: Eight patients with benign orbital tumors showed obvious bone destruction, including six cases of eosinophilic granuloma, one case of leiomyoma and one case of primary orbital intraosseous hemangioma. Among them, three patients were females and five patients were males. Tumors were unilateral in all cases, with both the right and left side affected equally. Age ranged from 3 to 7 years (mean 4.1 years). Symptom duration ranged from 1 to 5 weeks (mean 4.8 weeks). Eyelid swelling and palpable mass were the most common complaint. There was no evidence for multifocal involvement in cases with eosinophilic granuloma. Among six patients with eosinophilic granuloma, two were treated with low dose radiation (10 Gy), three received systemic corticosteroid and one was periodically observed only after incisional biopsy or subtotal curettage. There was no postoperative therapeutic intervention in the two patients with leiomyoma and intraosseous hemangioma. All eight patients regained normal vision without local recurrence after a mean follow-up time o

Haptoglobin phenotype is not a predictor of recurrence free survival in high-risk primary breast cancer patients

Contains fulltext : 70104tjan-heijnen.pdf (publisher's version ) (Open Access)BACKGROUND: Better breast cancer prognostication may improve selection of patients for adjuvant therapy. We conducted a retrospective follow-up study in which we investigated sera of high-risk primary breast cancer patients, to search for proteins predictive of recurrence free survival. METHODS: Two sample sets of high-risk primary breast cancer patients participating in a randomised national trial investigating the effectiveness of high-dose chemotherapy were analysed. Sera in set I (n = 63) were analysed by surface enhanced laser desorption ionisation time-of-flight mass spectrometry (SELDI-TOF MS) for biomarker finding. Initial results were validated by analysis of sample set II (n = 371), using one-dimensional gel-electrophoresis. RESULTS: In sample set I, the expression of a peak at mass-to-charge ratio 9198 (relative intensity 20), identified as haptoglobin (Hp) alpha-1 chain, was strongly associated with recurrence free survival (global Log-rank test; p = 0.0014). Haptoglobin is present in three distinct phenotypes (Hp 1-1, Hp 2-1, and Hp 2-2), of which only individuals with phenotype Hp 1-1 or Hp 2-1 express the haptoglobin alpha-1 chain. As the expression of the haptoglobin alpha-1 chain, determined by SELDI-TOF MS, corresponds to the phenotype, initial results were validated by haptoglobin phenotyping of the independent sample set II by native one-dimensional gel-electrophoresis. With the Hp 1-1 phenotype as the reference category, the univariate hazard ratio for recurrence was 0.87 (95% CI: 0.56 - 1.34, p = 0.5221) and 1.03 (95% CI: 0.65 - 1.64, p = 0.8966) for the Hp 2-1 and Hp 2-2 phenotypes, respectively, in sample set II. CONCLUSION: In contrast to our initial results, the haptoglobin phenotype was not identified as a predictor of recurrence free survival in high-risk primary breast cancer in our validation set. Our initial observation in the discovery set was probably the result of a type I error (i.e. false positive). This study illustrates the importance of validation in obtaining the true clinical applicability of a potential biomarker

Individuals with Le(a+b−) Blood Group Have Increased Susceptibility to Symptomatic Vibrio cholerae O1 Infection

Cholera remains a severe diarrheal disease, capable of causing extensive outbreaks and high mortality. Blood group is one of the genetic factors determining predisposition to disease, including infectious diseases. Expression of different Lewis or ABO blood group types has been shown to be associated with risk of different enteric infections. For example, individuals of blood group O have a higher risk of severe illness due to V. cholerae compared to those with non-blood group O antigens. In this study, we have determined the relationship of the Lewis blood group antigen phenotypes with the risk of symptomatic cholera as well as the severity of disease and immune responses following infection. We show that individuals expressing the Le(a+b−) phenotype were more susceptible to symptomatic cholera, while Le(a–b+) expressing individuals were less susceptible. Individuals with the Le(a–b−) blood group had a longer duration of diarrhea when infected, required more intravenous fluid replacement, and had lower plasma IgA antibody responses to V. cholerae LPS on day 7 following infection. We conclude that there is an association between the Lewis blood group and the risk of cholera, and that this risk may affect the outcome of infection as well as possibly the efficacy of vaccination