Effects of Repeated Central Administration of Endothelin Type A Receptor Antagonist on the Development of Neuropathic Pain in Rats

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The imperialist claws of MetaCapitalism

The information and industrial revolutions are so different and yet similar. Both enjoyed the emergence of accounting measurement and management techniques which privileged the efficient allocation of resources as the principal imperative to a firm\u27s participation in a free market economy. MetaCapitalism is one such corporate change strategy which promised untold wealth and unprecedented growth, and under that guise a predatory Darwinistic corporate strategy was implemented. Fundamentally, it promotes extreme outsourcing and downsizing of human capital, de-capitalisation of all non-core capital assets and the diminished role of the State in the global free market economy. Yet the most disturbing aspect is its complete and total disregard for even the slightest social or public policy implications. Essentially then, its most salient danger is an unmistakable endorsement of a fundamentalist brand of value free, reckless capitalism that is ultimately detrimental not only to the long-term business interest, but human as well. One of the main findings of evaluating the Fortune 100 companies\u27 performance in implementing MetaCapitalism was the resulting monopolies. Lenin described monopolies as essential to imperialism which is the highest stage of capitalism. The parallels between the resulting monopolies under MetaCapitalism, and what Lenin described as the final stage of Capitalism are poignant. I would like to draw upon those parallels in the hope that earlier work might enlighten our understanding and inform our critique of MetaCapiatlism

Influence of Maternal Infection and Pregnancy Complications on Cord Blood Telomere Length

BACKGROUND: Exposure to suboptimal intrauterine environment might induce structural and functional changes that can affect neonatal health. Telomere length as an important indicator of cellular health has been associated with increased risk for disease development. OBJECTIVES: This study was aimed to examine the independent and combined effects of maternal, obstetric, and foetal factors on cord blood telomere length (TL). METHODS: Pregnant women at the gestational age of 20th to 24th week who attended the antenatal clinic of a major local hospital in Hong Kong were recruited. Participants were asked to complete a questionnaire on demographics, health-related quality of life, and history of risk behaviors. Medical history including pregnancy complications and neonatal outcomes was obtained from electronic medical records of both mother and neonate. Umbilical cord blood was collected at delivery for TL determination. RESULTS: A total of 753 pregnant women (average age: 32:18 ± 4:51 years) were recruited. The prevalence of maternal infection, anaemia, and hypertension during pregnancy was 30.8%, 30.0%, and 6.0%, respectively. The adjusted regression model displayed that maternal infection was negatively associated with cord blood TL (β = −0:18, p = 0:026). This association became even stronger in the presence of antenatal anaemia, hypertension, delivery complications, or neonatal jaundice (β = −0:25 to −0.45). Conclusions. This study consolidates evidence on the impact of adverse intrauterine environment at the cellular level. Maternal infection was significantly associated with shorter cord blood TL in a unique manner such that its presence may critically determine the susceptibility of telomere to other factors

Diagnostic yield of array CGH in patients with autism spectrum disorder in Hong Kong

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Emotion based attentional priority for storage in visual short-term memory

A plethora of research demonstrates that the processing of emotional faces is prioritised over non-emotive stimuli when cognitive resources are limited (this is known as ‘emotional superiority’). However, there is debate as to whether competition for processing resources results in emotional superiority per se, or more specifically, threat superiority. Therefore, to investigate prioritisation of emotional stimuli for storage in visual short-term memory (VSTM), we devised an original VSTM report procedure using schematic (angry, happy, neutral) faces in which processing competition was manipulated. In Experiment 1, display exposure time was manipulated to create competition between stimuli. Participants (n = 20) had to recall a probed stimulus from a set size of four under high (150 ms array exposure duration) and low (400 ms array exposure duration) perceptual processing competition. For the high competition condition (i.e. 150 ms exposure), results revealed an emotional superiority effect per se. In Experiment 2 (n = 20), we increased competition by manipulating set size (three versus five stimuli), whilst maintaining a constrained array exposure duration of 150 ms. Here, for the five-stimulus set size (i.e. maximal competition) only threat superiority emerged. These findings demonstrate attentional prioritisation for storage in VSTM for emotional faces. We argue that task demands modulated the availability of processing resources and consequently the relative magnitude of the emotional/threat superiority effect, with only threatening stimuli prioritised for storage in VSTM under more demanding processing conditions. Our results are discussed in light of models and theories of visual selection, and not only combine the two strands of research (i.e. visual selection and emotion), but highlight a critical factor in the processing of emotional stimuli is availability of processing resources, which is further constrained by task demands

A Functional Taxonomy of Tumor Suppression in Oncogenic KRAS-Driven Lung Cancer

Cancer genotyping has identified a large number of putative tumor suppressor genes. Carcinogenesis is a multistep process, but the importance and specific roles of many of these genes during tumor initiation, growth, and progression remain unknown. Here we use a multiplexed mouse model of oncogenic KRAS–driven lung cancer to quantify the impact of 48 known and putative tumor suppressor genes on diverse aspects of carcinogenesis at an unprecedented scale and resolution. We uncover many previously understudied functional tumor suppressors that constrain cancer in vivo. Inactivation of some genes substantially increased growth, whereas the inactivation of others increases tumor initiation and/or the emergence of exceptionally large tumors. These functional in vivo analyses revealed an unexpectedly complex landscape of tumor suppression that has implications for understanding cancer evolution, interpreting clinical cancer genome sequencing data, and directing approaches to limit tumor initiation and progression. SIGNIFICANCE: Our high-throughput and high-resolution analysis of tumor suppression uncovered novel genetic determinants of oncogenic KRAS–driven lung cancer initiation, overall growth, and exceptional growth. This taxonomy is consistent with changing constraints during the life history of cancer and highlights the value of quantitative in vivo genetic analyses in autochthonous cancer models

Fumarate Analogs Act as Allosteric Inhibitors of the Human Mitochondrial NAD(P)+-Dependent Malic Enzyme

Human mitochondrial NAD(P)+-dependent malic enzyme (m-NAD(P)-ME) is allosterically activated by the four-carbon trans dicarboxylic acid, fumarate. Previous studies have suggested that the dicarboxylic acid in a trans conformation around the carbon-carbon double bond is required for the allosteric activation of the enzyme. In this paper, the allosteric effects of fumarate analogs on m-NAD(P)-ME are investigated. Two fumarate-insensitive mutants, m-NAD(P)-ME_R67A/R91A and m-NAD(P)-ME_K57S/E59N/K73E/D102S, as well as c-NADP-ME, were used as the negative controls. Among these analogs, mesaconate, trans-aconitate, monomethyl fumarate and monoethyl fumarate were allosteric activators of the enzyme, while oxaloacetate, diethyl oxalacetate, and dimethyl fumarate were found to be allosteric inhibitors of human m-NAD(P)-ME. The IC50 value for diethyl oxalacetate was approximately 2.5 mM. This paper suggests that the allosteric inhibitors may impede the conformational change from open form to closed form and therefore inhibit m-NAD(P)-ME enzyme activity

The evolutionary dynamics of extrachromosomal DNA in human cancers

Oncogene amplification on extrachromosomal DNA (ecDNA) is a common event, driving aggressive tumor growth, drug resistance and shorter survival. Currently, the impact of nonchromosomal oncogene inheritance-random identity by descent-is poorly understood. Also unclear is the impact of ecDNA on somatic variation and selection. Here integrating theoretical models of random segregation, unbiased image analysis, CRISPR-based ecDNA tagging with live-cell imaging and CRISPR-C, we demonstrate that random ecDNA inheritance results in extensive intratumoral ecDNA copy number heterogeneity and rapid adaptation to metabolic stress and targeted treatment. Observed ecDNAs benefit host cell survival or growth and can change within a single cell cycle. ecDNA inheritance can predict, a priori, some of the aggressive features of ecDNA-containing cancers. These properties are facilitated by the ability of ecDNA to rapidly adapt genomes in a way that is not possible through chromosomal oncogene amplification. These results show how the nonchromosomal random inheritance pattern of ecDNA contributes to poor outcomes for patients with cancer

Delayed clearance of viral load and marked cytokine activation in severe cases of pandemic H1N1 2009 influenza virus infection

Background: Infections caused by the pandemic H1N1 2009 influenza virus range from mild upper respiratory tract syndromes to fatal diseases. However, studies comparing virological and immunological profile of different clinical severity are lacking. Methods: We conducted a retrospective cohort study of 74 patients with pandemic H1N1 infection, including 23 patients who either developed acute respiratory distress syndrome (ARDS) or died (ARDS-death group), 14 patients with desaturation requiring oxygen supplementation and who survived without ARDS (survived-withoutARDS group), and 37 patients with mild disease without desaturation (mild-disease group). We compared their pattern of clinical disease, viral load, and immunological profile. Results: Patients with severe disease were older, more likely to be obese or having underlying diseases, and had lower respiratory tract symptoms, especially dyspnea at presentation. The ARDS-death group had a slower decline in nasopharyngeal viral loads, had higher plasma levels of proinflammatory cytokines and chemokines, and were more likely to have bacterial coinfections (30.4%), myocarditis (21.7%), or viremia (13.0%) than patients in the survived-without-ARDS or the mild-disease groups. Reactive hemophagocytosis, thrombotic phenomena, lymphoid atrophy, diffuse alveolar damage, and multiorgan dysfunction similar to fatal avian influenza A H5N1 infection were found at postmortem examinations. Conclusions: The slower control of viral load and immunodysregulation in severe cases mandate the search for more effective antiviral and immunomodulatory regimens to stop the excessive cytokine activation resulting in ARDS and death. © 2010 by the Infectious Diseases Society of America. All rights reserved.published_or_final_versio