Early and late mechanisms of surround suppression in striate cortex of macaque

The response of a neuron in striate cortex to an optimally configured visual stimulus is generally reduced when the stimulus is enlarged to encroach on a suppressive region that surrounds its classical receptive field (CRF). To characterize the mechanism that gives rise to this suppression, we measured its spatiotemporal tuning, its susceptibility to contrast adaptation, and its capacity for interocular transfer. Responses to an optimally configured grating confined to the CRF were strongly suppressed by annular surrounding gratings drifting at a wide range of temporal and spatial frequencies (including spatially uniform fields) that extended from well below to well above the range that drives most cortical neurons. Suppression from gratings capable of driving cortical CRFs was profoundly reduced by contrast adaptation and showed substantial interocular transfer. Suppression from stimuli that lay outside the spatiotemporal passband of most cortical CRFs was relatively stronger when the stimulus on the CRF was of low contrast, was generally insusceptible to contrast adaptation, and showed little interocular transfer. Our findings point to the existence of two mechanisms of surround suppression: one that is prominent when high-contrast stimuli drive the CRF, is orientation selective, has relatively sharp spatiotemporal tuning, is binocularly driven, and can be substantially desensitized by adaptation; the other is relatively more prominent when low-contrast stimuli drive the CRF, has very broad spatiotemporal tuning, is monocularly driven, and is insusceptible to adaptation. Its character suggests an origin in the input layers of primary visual cortex, or earlier

The prognostic role of intragenic copy number breakpoints and identification of novel fusion genes in paediatric high grade glioma

BACKGROUND: Paediatric high grade glioma (pHGG) is a distinct biological entity to histologically similar tumours arising in older adults, and has differing copy number profiles and driver genetic alterations. As functionally important intragenic copy number aberrations (iCNA) and fusion genes begin to be identified in adult HGG, the same has not yet been done in the childhood setting. We applied an iCNA algorithm to our previously published dataset of DNA copy number profiling in pHGG with a view to identify novel intragenic breakpoints. RESULTS: We report a series of 288 iCNA events in pHGG, with the presence of intragenic breakpoints itself a negative prognostic factor. We identified an increased number of iCNA in older children compared to infants, and increased iCNA in H3F3A K27M mutant tumours compared to G34R/V and wild-type. We observed numerous gene disruptions by iCNA due to both deletions and amplifications, targeting known HGG-associated genes such as RB1 and NF1, putative tumour suppressors such as FAF1 and KIDINS220, and novel candidates such as PTPRE and KCND2. We further identified two novel fusion genes in pHGG - CSGALNACT2:RET and the complex fusion DHX57:TMEM178:MAP4K3. The latter was sequence-validated and appears to be an activating event in pHGG. CONCLUSIONS: These data expand upon our understanding of the genomic events driving these tumours and represent novel targets for therapeutic intervention in these poor prognosis cancers of childhood.We are grateful for support from the Rosetrees Trust, the Brain Tumour Charity and Fundacao para a Ciencia e Tecnologia, Portugal (PhD Studentship SFRH/BD/33473/2008). DC, AM, LB and CJ acknowledge NHS funding to the Biomedical Research Centre

Building Babies - Chapter 16

In contrast to birds, male mammals rarely help to raise the offspring. Of all mammals, only among rodents, carnivores, and primates, males are sometimes intensively engaged in providing infant care (Kleiman and Malcolm 1981). Male caretaking of infants has long been recognized in nonhuman primates (Itani 1959). Given that infant care behavior can have a positive effect on the infant’s development, growth, well-being, or survival, why are male mammals not more frequently involved in “building babies”? We begin the chapter defining a few relevant terms and introducing the theory and hypotheses that have historically addressed the evolution of paternal care. We then review empirical findings on male care among primate taxa, before focusing, in the final section, on our own work on paternal care in South American owl monkeys (Aotus spp.). We conclude the chapter with some suggestions for future studies.Deutsche Forschungsgemeinschaft (HU 1746/2-1) Wenner-Gren Foundation, the L.S.B. Leakey Foundation, the National Geographic Society, the National Science Foundation (BCS-0621020), the University of Pennsylvania Research Foundation, the Zoological Society of San Dieg

Characterization of deposits formed on diesel injectors in field test and from thermal oxidative degradation of n-hexadecane in a laboratory reactor

Solid deposits from commercially available high-pressure diesel injectors (HPDI) were analyzed to study the solid deposition from diesel fuel during engine operation. The structural and chemical properties of injector deposits were compared to those formed from the thermal oxidative stressing of a diesel fuel range model compound, n-hexadecane at 160°C and 450 psi for 2.5 h in a flow reactor. Both deposits consist of polyaromatic compounds (PAH) with oxygen moieties. The similarities in structure and composition of the injector deposits and n-hexadecane deposits suggest that laboratory experiments can simulate thermal oxidative degradation of diesel in commercial injectors. The formation of PAH from n-hexadecane showed that aromatization of straight chain alkanes and polycondensation of aromatic rings was possible at temperatures as low as 160°C in the presence of oxygen. A mechanism for an oxygen-assisted aromatization of cylcoalkanes is proposed

Human papillomavirus infections in women seeking cervical Papanicolaou cytology of Durango, Mexico: prevalence and genotypes

BACKGROUND: HPV infection in women from developing countries is an important public health problem. Therefore, we sought to determine the prevalences of HPV infection and HPV genotypes in a female population of Durango City, Mexico. Also to determine whether any socio-demographic characteristic from the women associated with HPV infection exists. METHODS: Four hundred and ninety eight women seeking cervical Papanicolaou examination in three public Health Centers were examined for HPV infection. All women were tested for HPV DNA PCR by using HPV universal primers. In addition, all positive HPV DNA PCR samples were further analyzed for genotyping of HPV genotype 16, 18 and 33. Socio-demographic characteristics from each participant were also obtained. RESULTS: Twenty-four out of four hundred and ninety-eight (4.8%) women were found infected by HPV. HPV genotype 16 was found in 18 out of the 24 (75%) infected women. Two of them were also coinfected by HPV genotype 18 (8.3%). In the rest 6 PCR positive women, genotyping for HPV genotypes 16, 18 and 33 were negative. CONCLUSION: The prevalence of HPV in women of Durango City is low; however, most infected women have high risk HPV genotype. The women who were studied showed low frequency of risk factors for HPV infection and this may explain the low prevalence of HPV infection. The high frequency of high risk HPV genotypes observed might explain the high rate of mortality for cervical cancer in our region

RIPCAL: a tool for alignment-based analysis of repeat-induced point mutations in fungal genomic sequences

Background Repeat-induced point mutation (RIP) is a fungal-specific genome defence mechanism that alters the sequences of repetitive DNA, thereby inactivating coding genes. Repeated DNA sequences align between mating and meiosis and both sequences undergo C:G to T:A transitions. In most fungi these transitions preferentially affect CpA di-nucleotides thus altering the frequency of certain di-nucleotides in the affected sequences. The majority of previously published in silico analyses were limited to the comparison of ratios of pre- and post-RIP di-nucleotides in putatively RIP-affected sequences – so-called RIP indices. The analysis of RIP is significantly more informative when comparing sequence alignments of repeated sequences. There is, however, a dearth of bioinformatics tools available to the fungal research community for alignment-based RIP analysis of repeat families. Results We present RIPCAL http://www.sourceforge.net/projects/ripcal, a software tool for the automated analysis of RIP in fungal genomic DNA repeats, which performs both RIP index and alignment-based analyses. We demonstrate the ability of RIPCAL to detect RIP within known RIP-affected sequences of Neurospora crassa and other fungi. We also predict and delineate the presence of RIP in the genome of Stagonospora nodorum – a Dothideomycete pathogen of wheat. We show that RIP has affected different members of the S. nodorum rDNA tandem repeat to different extents depending on their genomic contexts. Conclusion The RIPCAL alignment-based method has considerable advantages over RIP indices for the analysis of whole genomes. We demonstrate its application to the recently published genome assembly of S. nodorum

A Tale of Switched Functions: From Cyclooxygenase Inhibition to M-Channel Modulation in New Diphenylamine Derivatives

Cyclooxygenase (COX) enzymes are molecular targets of nonsteroidal anti-inflammatory drugs (NSAIDs), the most used medication worldwide. However, the COX enzymes are not the sole molecular targets of NSAIDs. Recently, we showed that two NSAIDs, diclofenac and meclofenamate, also act as openers of Kv7.2/3 K+ channels underlying the neuronal M-current. Here we designed new derivatives of diphenylamine carboxylate to dissociate the M-channel opener property from COX inhibition. The carboxylate moiety was derivatized into amides or esters and linked to various alkyl and ether chains. Powerful M-channel openers were generated, provided that the diphenylamine moiety and a terminal hydroxyl group are preserved. In transfected CHO cells, they activated recombinant Kv7.2/3 K+ channels, causing a hyperpolarizing shift of current activation as measured by whole-cell patch-clamp recording. In sensory dorsal root ganglion and hippocampal neurons, the openers hyperpolarized the membrane potential and robustly depressed evoked spike discharges. They also decreased hippocampal glutamate and GABA release by reducing the frequency of spontaneous excitatory and inhibitory post-synaptic currents. In vivo, the openers exhibited anti-convulsant activity, as measured in mice by the maximal electroshock seizure model. Conversion of the carboxylate function into amide abolished COX inhibition but preserved M-channel modulation. Remarkably, the very same template let us generating potent M-channel blockers. Our results reveal a new and crucial determinant of NSAID-mediated COX inhibition. They also provide a structural framework for designing novel M-channel modulators, including openers and blockers

Transmission Dynamics of Methicillin-Resistant Staphylococcus aureus in a Medical Intensive Care Unit in India

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a global pathogen and an important but seldom investigated cause of morbidity and mortality in lower and middle-income countries where it can place a major burden on limited resources. Quantifying nosocomial transmission in resource-poor settings is difficult because molecular typing methods are prohibitively expensive. Mechanistic statistical models can overcome this problem with minimal cost. We analyse the transmission dynamics of MRSA in a hospital in south India using one such approach and provide conservative estimates of the organism's economic burden. Methods and Findings: Fifty months of MRSA infection data were collected retrospectively from a Medical Intensive Care Unit (MICU) in a tertiary hospital in Vellore, south India. Data were analysed using a previously described structured hidden Markov model. Seventy-two patients developed MRSA infections and, of these, 49 (68%) died in the MICU. We estimated that 4.2% (95%CI 1.0, 19.0) of patients were MRSA-positive when admitted, that there were 0.39 MRSA infections per colonized patient month (0.06, 0.73), and that the ward-level reproduction number for MRSA was 0.42 (0.08, 2.04). Anti-MRSA antibiotic treatment costs alone averaged $124/patient, over three times the monthly income of more than 40% of the Indian population. Conclusions: Our analysis of routine data provides the first estimate of the nosocomial transmission potential of MRSA in India. The high levels of transmission estimated underline the need for cost-effective interventions to reduce MRSA transmission in hospital settings in low and middle income countries. © 2011 Christopher et al

Experience with an online prospective database on adolescent idiopathic scoliosis: development and implementation

Considerable variability exists in the surgical treatment and outcomes of adolescent idiopathic scoliosis (AIS). This is due to the lack of evidence-based treatment guidelines and outcome measures. Although clinical trials have been extolled as the highest form of evidence for evaluating treatment efficacy, the disadvantage of cost, time, lack of feasibility, and ethical considerations indicate a need for a new paradigm for evidence based research in this spinal deformity. High quality clinical databases offer an alternative approach for evidence-based research in medicine. So, we developed and established Scolisoft, an international, multidimensional and relational database designed to be a repository of surgical cases for AIS, and an active vehicle for standardized surgical information in a format that would permit qualitative and quantitative research and analysis. Here, we describe and discuss the utility of Scolisoft as a new paradigm for evidence-based research on AIS. Scolisoft was developed using dot.net platform and SQL server from Microsoft. All data is deidentified to protect patient privacy. Scolisoft can be accessed at www.scolisoft.org. Collection of high quality data on surgical cases of AIS is a priority and processes continue to improve the database quality. The database currently has 67 registered users from 21 countries. To date, Scolisoft has 200 detailed surgical cases with pre, post, and follow up data. Scolisoft provides a structured process and practical information for surgeons to benchmark their treatment methods against other like treatments. Scolisoft is multifaceted and its use extends to education of health care providers in training, patients, ability to mine important data to stimulate research and quality improvement initiatives of healthcare organizations

Limits on WWZ and WW\gamma couplings from p\bar{p}\to e\nu jj X events at \sqrt{s} = 1.8 TeV

We present limits on anomalous WWZ and WW-gamma couplings from a search for WW and WZ production in p-bar p collisions at sqrt(s)=1.8 TeV. We use p-bar p -> e-nu jjX events recorded with the D0 detector at the Fermilab Tevatron Collider during the 1992-1995 run. The data sample corresponds to an integrated luminosity of 96.0+-5.1 pb^(-1). Assuming identical WWZ and WW-gamma coupling parameters, the 95% CL limits on the CP-conserving couplings are -0.33<lambda<0.36 (Delta-kappa=0) and -0.43<Delta-kappa<0.59 (lambda=0), for a form factor scale Lambda = 2.0 TeV. Limits based on other assumptions are also presented.Comment: 11 pages, 2 figures, 2 table