Experience-Driven Axon Retraction in the Pharmacologically Inactivated Visual Cortex Does Not Require Synaptic Transmission

BACKGROUND: Experience during early postnatal development plays an important role in the refinement of specific neural connections in the brain. In the mammalian visual system, altered visual experiences induce plastic adaptation of visual cortical responses and guide rearrangements of afferent axons from the lateral geniculate nucleus. Previous studies using visual deprivation demonstrated that the afferents serving an open eye significantly retract when cortical neurons are pharmacologically inhibited by applying a gamma-aminobutyric acid type A receptor agonist, muscimol, whereas those serving a deprived eye are rescued from retraction, suggesting that presynaptic activity can lead to the retraction of geniculocortical axons in the absence of postsynaptic activity. Because muscimol application suppresses the spike activity of cortical neurons leaving transmitter release intact at geniculocortical synapses, local synaptic interaction may underlie the retraction of active axons in the inhibited cortex. METHOD AND FINDINGS: New studies reported here determined whether experience-driven axon retraction can occur in the visual cortex inactivated by blocking synaptic inputs. We inactivated the primary visual cortex of kittens by suppressing synaptic transmission with cortical injections of botulinum neurotoxin type E, which cleaves a synaptic protein, SNAP-25, and blocks transmitter release, and examined the geniculocortical axon morphology in the animals with normal vision and those deprived of vision binocularly. We found that afferent axons in the animals with normal vision showed a significant retraction in the inactivated cortex, as similarly observed in the muscimol-treated cortex, whereas the axons in the binocularly deprived animals were preserved. CONCLUSIONS: Therefore, the experience-driven axon retraction in the inactivated cortex can proceed in the absence of synaptic transmission. These results suggest that presynaptic mechanisms play an important role in the experience-driven refinement of geniculocortical axons

Fitness Ranking of Individual Mutants Drives Patterns of Epistatic Interactions in HIV-1

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Diet and serum micronutrients in relation to cervical neoplasia and cancer among low-income Brazilian women

Cervical cancer is a leading cancer among women in developing countries. Infection with oncogenic human papillomavirus (HPV) types has been recognized as a necessary cause of this disease. Serum carotenoids and tocopherols have also been associated with risk for cervical neoplasia, but results from previous studies were not consistent. We evaluated the association of serum total carotene and tocopherols, and dietary intakes with the risk of newly diagnosed, histologically confirmed cervical intraepithelial neoplasia (CIN) grades 1, 2, 3 and invasive cancer in a hospital-based case-control study in São Paulo, Brazil. The investigation included 453 controls and 4 groups of cases (CIN1, n = 140; CIN2, n = 126; CIN3, n = 231; invasive cancer, n =108) recruited from two major public clinics between 2003 and 2005. Increasing concentrations of serum lycopene were negatively associated with CIN1, CIN3 and cancer, with odds ratios (OR) (95% CI) for the highest compared to the lowest tertile of 0.53 (0.27-1.00, p for trend = 0.05), 0.48 (0.22-1.04, p for trend = 0.05) and 0.18 (0.06-0.52, p for trend = 0.002), respectively, after adjusting for confounding variables and HPV status. Increasing concentrations of serum alpha- and gamma-tocopherols, and higher dietary intakes of dark green and deep yellow vegetables/fruit were associated with nearly 50% decreased risk of CIN3. These results support the evidence that a healthy and balanced diet leading to provide high serum levels of antioxidants may reduce cervical neoplasia risk in low-income women.The authors thank Instituto Brasileiro de Controle ao Câncer and HospitalPerola Byington for supporting the BRINCA study. The authors are pro-foundly grateful to all participants, and to our fieldwork research team:Lucila Pereira, Adelisa Isabel da Silva, and Carlos Eduardo Teixeira Fernan-dez. LYT has received PhD scholarships from FAPESP (02/11184-0) andCAPES (BEX3775/05-4)

Variation of the vertical distribution of Nabro volcano aerosol layers in the stratosphere observed by LIDAR

Young Min Noh, Dong Ho Shin, and Detlef Müller, ‘ Variation of the vertical distribution of Nabro volcano aerosol layers in the stratosphere observed by LIDAR’, Atmospheric Environment, Vol. 154, pp 1-8, first published online on 17 January 2017, is available online via doi: http://dx.doi.org/10.1016/j.atmosenv.2017.01.033 © 2017 The Authors. Published by Elsevier Ltd. This is an open access article distributed under the CC BY license (http://creativecommons.org/licenses/by/4.0/).We present results of the vertical distribution variation of volcanic aerosol layers in the upper troposphere and lower stratosphere. The data were taken with our multiwavelength aerosol Raman lidar at Gwangju (35.10 N, 126.53 E), Korea. The volcanic ash particles and gases were released around 12 June 2011 during the eruption of the Nabro volcano (13.37 N, 41.7 E) in Eritrea, east Africa. Forward trajectory computations show that the volcanic aerosols were advected from North Africa to East Asia. The first measurement of the aerosol layer over Korea was on 19 June 2011. The aerosol layers appeared between 15 km and 17 km height asl (above sea level). The maximum value of the aerosol layer of the particle backscatter coefficient (1.5 ± 0.3 Mm1 sr1) and the linear particle depolarization ratio at 532 nm (2.2%) were observed at 16.4 km height asl. We continuously probed the upper troposphere and lower stratosphere for this volcanic aerosol layer during the following 6 months, until December 2011. The volcanic aerosol layer showed a single-peak of the particle backscatter coefficient and a comparably narrow vertical thickness at our observation site at the beginning of our observation period (i.e. comparably soon after the initial eruption period). After that initial period the vertical distribution of the plume changed. Multiple peaks and a comparably broad geometrical thickness developed with progressing observation time. The vertical thickness of the volcanic aerosol layer expanded up to 10 km by 3 August 2011. The linear particle depolarization ratios were larger in the lower part of the aerosol layer than the upper part of the aerosol layer. We observed a strong variation of the AOD (aerosol optical depth) in the first two months of our lidar observations. After these two months the AOD gradually decreased with time from September to December 20111 and the maximum particle backscatter coefficients consistently decreased. The corresponding e-folding decay time of the layer AOD was 117 days.Peer reviewe

A novel prostate cancer subtyping classifier based on luminal and basal phenotypes

Background: Prostate cancer (PCa) is a clinically heterogeneous disease. The creation of an expression-based subtyping model based on prostate-specific biological processes was sought. Methods: Unsupervised machine learning of gene expression profiles from prospectively collected primary prostate tumors (training, n = 32,000; evaluation, n = 68,547) was used to create a prostate subtyping classifier (PSC) based on basal versus luminal cell expression patterns and other gene signatures relevant to PCa biology. Subtype molecular pathways and clinical characteristics were explored in five other clinical cohorts. Results: Clustering derived four subtypes: luminal differentiated (LD), luminal proliferating (LP), basal immune (BI), and basal neuroendocrine (BN). LP and LD tumors both had higher androgen receptor activity. LP tumors also had a higher expression of cell proliferation genes, MYC activity, and characteristics of homologous recombination deficiency. BI tumors possessed significant interferon γactivity and immune infiltration on immunohistochemistry. BN tumors were characterized by lower androgen receptor activity expression, lower immune infiltration, and enrichment with neuroendocrine expression patterns. Patients with LD tumors had less aggressive tumor characteristics and the longest time to metastasis after surgery. Only patients with BI tumors derived benefit from radiotherapy after surgery in terms of time to metastasis (hazard ratio [HR], 0.09; 95% CI, 0.01–0.71; n = 855). In a phase 3 trial that randomized patients with metastatic PCa to androgen deprivation with or without docetaxel (n = 108), only patients with LP tumors derived survival benefit from docetaxel (HR, 0.21; 95% CI, 0.09–0.51). Conclusions: With the use of expression profiles from over 100,000 tumors, a PSC was developed that identified four subtypes with distinct biological and clinical features. Plain language summary: Prostate cancer can behave in an indolent or aggressive manner and vary in how it responds to certain treatments. To differentiate prostate cancer on the basis of biological features, we developed a novel RNA signature by using data from over 100,000 prostate tumors—the largest data set of its kind. This signature can inform patients and physicians on tumor aggressiveness and susceptibilities to treatments to help personalize cancer management

Scaling of columnar joints in basalt

We describe field work, analysis, and modeling of columnar joints from the Columbia River Basalt Group. This work is focused on the regions around the Grand Coulee, Snake River, and Columbia Gorge, which form parts of this unusually homogeneous and very large sample of columnar basalt. We examine in detail the scaling relationship between the column width and the size of the striae and relate these quantitatively to thermal and fracture models. We found that the column radius and stria size are proportional to each other and inversely proportional to the cooling rate of the lava. Near a flow margin, our results put observational constraints on diffusive thermal models of joint formation. Deeper than a few meters into a colonnade, our measurements are consistent with a simple advection-diffusion model of two-phase convective cooling within the joints, regardless of the direction of cooling. This model allows an accurate comparison of igneous columnar jointing and joints due to desiccation in laboratory analog systems. We also identify a new length scale in which wavy columns can appear in some colonnades. The mechanisms leading to the wavy columns are likely related to those underlying similar wavy cracks in 2-D analog systems

WISC-III Cognitive Profiles in Children with Developmental Dyslexia: Specific Cognitive Disability and Diagnostic Utility

This study analysed the usefulness of the Wechsler Intelligence Scale for Children-Third Edition in identifying specific cognitive impairments that are linked to developmental dyslexia (DD) and the diagnostic utility of the most common profiles in a sample of 100 Portuguese children (50 dyslexic and 50 normal readers) between the ages of 8 and 12 years. Children with DD exhibited significantly lower scores in the Verbal Comprehension Index (except the Vocabulary subtest), Freedom from Distractibility Index (FDI) and Processing Speed Index subtests, with larger effect sizes than normal readers in Information, Arithmetic and Digit Span. The Verbal-Performance IQs discrepancies, Bannatyne pattern and the presence of FDI; Arithmetic, Coding, Information and Digit Span subtests (ACID) and Symbol Search, Coding, Arithmetic and Digit Span subtests (SCAD) profiles (full or partial) in the lowest subtests revealed a low diagnostic utility. However, the receiver operating characteristic curve and the optimal cut-off score analyses of the composite ACID; FDI and SCAD profiles scores showed moderate accuracy in correctly discriminating dyslexic readers from normal ones. These results suggested that in the context of a comprehensive assessment, the Wechsler Intelligence Scale for Children-Third Edition provides some useful information about the presence of specific cognitive disabilities in DD. Practitioner Points. Children with developmental dyslexia revealed significant deficits in the Wechsler Intelligence Scale for Children-Third Edition subtests that rely on verbal abilities, processing speed and working memory. The composite Arithmetic, Coding, Information and Digit Span subtests (ACID); Freedom from Distractibility Index and Symbol Search, Coding, Arithmetic and Digit Span subtests (SCAD) profile scores showed moderate accuracy in correctly discriminating dyslexics from normal readers. Wechsler Intelligence Scale for Children-Third Edition may provide some useful information about the presence of specific cognitive disabilities in developmental dyslexia