Coordinated optimization of visual cortical maps (I) Symmetry-based analysis

In the primary visual cortex of primates and carnivores, functional architecture can be characterized by maps of various stimulus features such as orientation preference (OP), ocular dominance (OD), and spatial frequency. It is a long-standing question in theoretical neuroscience whether the observed maps should be interpreted as optima of a specific energy functional that summarizes the design principles of cortical functional architecture. A rigorous evaluation of this optimization hypothesis is particularly demanded by recent evidence that the functional architecture of OP columns precisely follows species invariant quantitative laws. Because it would be desirable to infer the form of such an optimization principle from the biological data, the optimization approach to explain cortical functional architecture raises the following questions: i) What are the genuine ground states of candidate energy functionals and how can they be calculated with precision and rigor? ii) How do differences in candidate optimization principles impact on the predicted map structure and conversely what can be learned about an hypothetical underlying optimization principle from observations on map structure? iii) Is there a way to analyze the coordinated organization of cortical maps predicted by optimization principles in general? To answer these questions we developed a general dynamical systems approach to the combined optimization of visual cortical maps of OP and another scalar feature such as OD or spatial frequency preference.Comment: 90 pages, 16 figure

Familiarization: A theory of repetition suppression predicts interference between overlapping cortical representations

Repetition suppression refers to a reduction in the cortical response to a novel stimulus that results from repeated presentation of the stimulus. We demonstrate repetition suppression in a well established computational model of cortical plasticity, according to which the relative strengths of lateral inhibitory interactions are modified by Hebbian learning. We present the model as an extension to the traditional account of repetition suppression offered by sharpening theory, which emphasises the contribution of afferent plasticity, by instead attributing the effect primarily to plasticity of intra-cortical circuitry. In support, repetition suppression is shown to emerge in simulations with plasticity enabled only in intra-cortical connections. We show in simulation how an extended ‘inhibitory sharpening theory’ can explain the disruption of repetition suppression reported in studies that include an intermediate phase of exposure to additional novel stimuli composed of features similar to those of the original stimulus. The model suggests a re-interpretation of repetition suppression as a manifestation of the process by which an initially distributed representation of a novel object becomes a more localist representation. Thus, inhibitory sharpening may constitute a more general process by which representation emerges from cortical re-organisation

Assessment of pollution risk ascribed to Santa Margarida Military Camp activities (Portugal)

Santa Margarida Military Camp (S.M.M.C.) is the only one Portuguese military training area, including firing ranges for tactical military manoeuvres of mechanised divisions. For this reason, various negative effects on the environment were expected due to the military activities, as the Military Camp’s area is classified as a high vulnerability area to pollution of its multilayer porous aquifers. The aim of this study was to identify and characterise local/regional geochemical impacts caused by the continuing military training activities performed at S.M.M.C. in the course of 52 years. An overview of the geochemical research issues as a basis for risk assessment is presented. A special attention has been put on the quality of local and regional surface waters, shallow groundwaters and groundwaters. Local soils and sediments as well as fragments of shells and bullets were sampled and analysed. The results so far obtained, indicated that none pollution effects were a consequence of the military training activities. Till now, the geochemical signatures such as, high levels of K, Cl and NO3 in waters, detected in particular sites, should be faced as tracers of diffuse pollution ascribed to urban waste disposal and cattle breading

Coordinated optimization of visual cortical maps (II) Numerical studies

It is an attractive hypothesis that the spatial structure of visual cortical architecture can be explained by the coordinated optimization of multiple visual cortical maps representing orientation preference (OP), ocular dominance (OD), spatial frequency, or direction preference. In part (I) of this study we defined a class of analytically tractable coordinated optimization models and solved representative examples in which a spatially complex organization of the orientation preference map is induced by inter-map interactions. We found that attractor solutions near symmetry breaking threshold predict a highly ordered map layout and require a substantial OD bias for OP pinwheel stabilization. Here we examine in numerical simulations whether such models exhibit biologically more realistic spatially irregular solutions at a finite distance from threshold and when transients towards attractor states are considered. We also examine whether model behavior qualitatively changes when the spatial periodicities of the two maps are detuned and when considering more than 2 feature dimensions. Our numerical results support the view that neither minimal energy states nor intermediate transient states of our coordinated optimization models successfully explain the spatially irregular architecture of the visual cortex. We discuss several alternative scenarios and additional factors that may improve the agreement between model solutions and biological observations.Comment: 55 pages, 11 figures. arXiv admin note: substantial text overlap with arXiv:1102.335

Influence of elevated-CRP level-related polymorphisms in non-rheumatic Caucasians on the risk of subclinical atherosclerosis and cardiovascular disease in rheumatoid arthritis

Association between elevated C-reactive protein (CRP) serum levels and subclinical atherosclerosis and cardiovascular (CV) events was described in rheumatoid arthritis (RA). CRP, HNF1A, LEPR, GCKR, NLRP3, IL1F10, PPP1R3B, ASCL1, HNF4A and SALL1 exert an influence on elevated CRP serum levels in non-rheumatic Caucasians. Consequently, we evaluated the potential role of these genes in the development of CV events and subclinical atherosclerosis in RA patients. Three tag CRP polymorphisms and HNF1A, LEPR, GCKR, NLRP3, IL1F10, PPP1R3B, ASCL1, HNF4A and SALL1 were genotyped in 2,313 Spanish patients by TaqMan. Subclinical atherosclerosis was determined in 1,298 of them by carotid ultrasonography (by assessment of carotid intima-media thickness-cIMT-and presence/absence of carotid plaques). CRP serum levels at diagnosis and at the time of carotid ultrasonography were measured in 1,662 and 1,193 patients, respectively, by immunoturbidimetry. Interestingly, a relationship between CRP and CRP serum levels at diagnosis and at the time of the carotid ultrasonography was disclosed. However, no statistically significant differences were found when CRP, HNF1A, LEPR, GCKR, NLRP3, IL1F10, PPP1R3B, ASCL1, HNF4A and SALL1 were evaluated according to the presence/absence of CV events, carotid plaques and cIMT after adjustment. Our results do not confirm an association between these genes and CV disease in RA

Efficacy of Anakinra in Refractory Adult-Onset Still's Disease: Multicenter Study of 41 Patients and Literature Review

Adult-onset Still's disease (AOSD) is often refractory to standard therapy. Anakinra (ANK), an interleukin-1 receptor antagonist, has demonstrated efficacy in single cases and small series of AOSD. We assessed the efficacy of ANK in a series of AOSD patients. Multicenter retrospective open-label study. ANK was used due to lack of efficacy to standard synthetic immunosuppressive drugs and in some cases also to at least 1 biologic agent. Forty-one patients (26 women/15 men) were recruited. They had a mean age of 34.4 ± 14 years and a median [interquartile range (IQR)] AOSD duration of 3.5 [2-6] years before ANK onset. At that time the most common clinical features were joint manifestations 87.8%, fever 78%, and cutaneous rash 58.5%. ANK yielded rapid and maintained clinical and laboratory improvement. After 1 year of therapy, the frequency of joint and cutaneous manifestations had decreased to 41.5% and to 7.3% respectively, fever from 78% to 14.6%, anemia from 56.1% to 9.8%, and lymphadenopathy from 26.8% to 4.9%. A dramatic improvement of laboratory parameters was also achieved. The median [IQR] prednisone dose was also reduced from 20 [11.3-47.5] mg/day at ANK onset to 5 [0-10] at 12 months. After a median [IQR] follow-up of 16 [5-50] months, the most important side effects were cutaneous manifestations (n = 8), mild leukopenia (n = 3), myopathy (n = 1), and infections (n = 5). ANK is associated with rapid and maintained clinical and laboratory improvement, even in nonresponders to other biologic agents. However, joint manifestations are more refractory than the systemic manifestations

A voting approach to identify a small number of highly predictive genes using multiple classifiers

<p>Abstract</p> <p>Background</p> <p>Microarray gene expression profiling has provided extensive datasets that can describe characteristics of cancer patients. An important challenge for this type of data is the discovery of gene sets which can be used as the basis of developing a clinical predictor for cancer. It is desirable that such gene sets be compact, give accurate predictions across many classifiers, be biologically relevant and have good biological process coverage.</p> <p>Results</p> <p>By using a new type of multiple classifier voting approach, we have identified gene sets that can predict breast cancer prognosis accurately, for a range of classification algorithms. Unlike a wrapper approach, our method is not specialised towards a single classification technique. Experimental analysis demonstrates higher prediction accuracies for our sets of genes compared to previous work in the area. Moreover, our sets of genes are generally more compact than those previously proposed. Taking a biological viewpoint, from the literature, most of the genes in our sets are known to be strongly related to cancer.</p> <p>Conclusion</p> <p>We show that it is possible to obtain superior classification accuracy with our approach and obtain a compact gene set that is also biologically relevant and has good coverage of different biological processes.</p

HIV and HPV infections and ocular surface squamous neoplasia: systematic review and meta-analysis.

BACKGROUND: The frequency of ocular surface squamous neoplasias (OSSNs) has been increasing in populations with a high prevalence of infection with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and infection with human papillomavirus (HPV). We aimed to quantify the association between HIV/AIDS and HPV infection and OSSN, through systematic review and meta-analysis. METHODS: The articles providing data on the association between HIV/AIDS and/or HPV infection and OSSN were identified in MEDLINE, SCOPUS and EMBASE searched up to May 2013, and through backward citation tracking. The DerSimonian and Laird method was used to compute summary relative risk (RR) estimates and 95% confidence intervals (95% CI). Heterogeneity was quantified with the I(2) statistic. RESULTS: HIV/AIDS was strongly associated with an increased risk of OSSN (summary RR=8.06, 95% CI: 5.29-12.30, I(2)=56.0%, 12 studies). The summary RR estimate for the infection with mucosal HPV subtypes was 3.13 (95% CI: 1.72-5.71, I(2)=45.6%, 16 studies). Four studies addressed the association between both cutaneous and mucosal HPV subtypes and OSSN; the summary RR estimates were 3.52 (95% CI: 1.23-10.08, I(2)=21.8%) and 1.08 (95% CI: 0.57-2.05, I(2)=0.0%), respectively. CONCLUSION: Human immunodeficiency virus infection increases the risk of OSSN by nearly eight-fold. Regarding HPV infection, only the cutaneous subtypes seem to be a risk factor

Expanding the knowledge about Leishmania species in wild mammals and dogs in the Brazilian savannah

Background: Wild, synanthropic and domestic mammals act as hosts and/or reservoirs of several Leishmania spp. Studies on possible reservoirs of Leishmania in different areas are fundamental to understand host-parasite interactions and develop strategies for the surveillance and control of leishmaniasis. In the present study, we evaluated the Leishmania spp. occurrence in mammals in two conservation units and their surroundings in Brasília, Federal District (FD), Brazil. Methods: Small mammals were captured in Brasília National Park (BNP) and Contagem Biological Reserve (CBR) and dogs were sampled in residential areas in their vicinity. Skin and blood samples were evaluated by PCR using different molecular markers (D7 24Sα rRNA and rDNA ITS1). Leishmania species were identified by sequencing of PCR products. Dog blood samples were subjected to the rapid immunochromatographic test (DPP) for detection of anti-Leishmania infantum antibodies. Results: 179 wild mammals were studied and 20.1% had Leishmania DNA successfully detected in at least one sample. Six mammal species were considered infected: Clyomys laticeps, Necromys lasiurus, Nectomys rattus, Rhipidomys macrurus, Didelphis albiventris and Gracilinanus agilis. No significant difference, comparing the proportion of individuals with Leishmania spp., was observed between the sampled areas and wild mammal species. Most of the positive samples were collected from the rodent N. lasiurus, infected by L. amazonensis or L. braziliensis. Moreover, infections by Trypanosoma spp. were detected in N. lasiurus and G. agilis. All 19 dog samples were positive by DPP; however, only three (15.8%) were confirmed by PCR assays. DNA sequences of ITS1 dog amplicons showed 100% identity with L. infantum sequence. Conclusions: The results suggest the participation of six species of wild mammals in the enzootic transmission of Leishmania spp. in FD. This is the first report of L. amazonensis in N. lasiurus