Ybp1 and Gpx3 signaling in Candida albicans govern hydrogen peroxide-induced oxidation of the Cap1 transcription factor and macrophage escape

Peer reviewedPublisher PD

'Pre-semantic' cognition in semantic dementia: Six deficits in search of an explanation.

‘‘Oh, sir, you must be well aware that life is full of endless absurdities which do not even have to appear plausible, since they are true.’’ —From Six Characters in Search of an Author, by Luigi Pirandello (1921) & On the basis of a theory about the role of semantic knowl-edge in the recognition and production of familiar words and objects, we predicted that patients with semantic dementia would reveal a specific pattern of impairment on six different tasks typically considered ‘‘pre-’ ’ or ‘‘non-’ ’ semantic: reading aloud, writing to dictation, inflecting verbs, lexical decision, object decision, and delayed copy drawing. The prediction was that all tasks would reveal a frequency-by-typicality interaction, with patients performing especially poorly on lower-frequency items with atypical structure (e.g., words with an atypical spelling-to-sound relationship; objects with an atypical feature for their class, such as the hump on a camel, etc). Of 84 critical observations (14 patients performing 6 tasks), this prediction was correct in 84/84 cases; and a single component in a factor analysis accounted for 87 % of the variance across seven mea-sures: each patient’s degree of impairment on atypical items in the six experimental tasks and a separate composite score re-f lecting his or her degree of semantic impairment. Errors also consistently conformed to the predicted pattern for both ex-pressive and receptive tasks, with responses reflecting residual knowledge about the typical surface structure of each domain. We argue that these results cannot be explained as associated but unrelated deficits but instead are a principled consequence of a primary semantic impairment. &amp

A Core Switching Strategy to Pyrrolo[2,3-b]quinolines and Diazocino[1,2-a]indolinones

Two novel core-switching rearrangements to natural product-like privileged scaffolds that proceed in up to 99% yield have been developed. The deviation away from planarity of the central N-acyl urea carbonyl, caused by the structure of the medium-sized ring, dictates the exclusive reaction outcome. Proposed mechanisms and products for the reaction pathways are supported by small molecule X-ray crystallography and an isolated intermediate. Twenty-four novel rearrangement products are reported

Connectionist perspectives on language learning, representation and processing.

The field of formal linguistics was founded on the premise that language is mentally represented as a deterministic symbolic grammar. While this approach has captured many important characteristics of the world\u27s languages, it has also led to a tendency to focus theoretical questions on the correct formalization of grammatical rules while also de-emphasizing the role of learning and statistics in language development and processing. In this review we present a different approach to language research that has emerged from the parallel distributed processing or \u27connectionist\u27 enterprise. In the connectionist framework, mental operations are studied by simulating learning and processing within networks of artificial neurons. With that in mind, we discuss recent progress in connectionist models of auditory word recognition, reading, morphology, and syntactic processing. We argue that connectionist models can capture many important characteristics of how language is learned, represented, and processed, as well as providing new insights about the source of these behavioral patterns. Just as importantly, the networks naturally capture irregular (non-rule-like) patterns that are common within languages, something that has been difficult to reconcile with rule-based accounts of language without positing separate mechanisms for rules and exceptions

International Veterinary Epilepsy Task Force consensus report on epilepsy definition, classification and terminology in companion animals

Dogs with epilepsy are among the commonest neurological patients in veterinary practice and therefore have historically attracted much attention with regard to definitions, clinical approach and management. A number of classification proposals for canine epilepsy have been published during the years reflecting always in parts the current proposals coming from the human epilepsy organisation the International League Against Epilepsy (ILAE). It has however not been possible to gain agreed consensus, “a common language”, for the classification and terminology used between veterinary and human neurologists and neuroscientists, practitioners, neuropharmacologists and neuropathologists. This has led to an unfortunate situation where different veterinary publications and textbook chapters on epilepsy merely reflect individual author preferences with respect to terminology, which can be confusing to the readers and influence the definition and diagnosis of epilepsy in first line practice and research studies. In this document the International Veterinary Epilepsy Task Force (IVETF) discusses current understanding of canine epilepsy and presents our 2015 proposal for terminology and classification of epilepsy and epileptic seizures. We propose a classification system which reflects new thoughts from the human ILAE but also roots in former well accepted terminology. We think that this classification system can be used by all stakeholders

Population-Level Benefits from Providing Effective HIV Prevention Means to Pregnant Women in High Prevalence Settings

Background:HIV prevalence among pregnant women in Southern Africa is extremely high. Epidemiological studies suggest that pregnancy increases the risk of HIV sexual acquisition and that HIV infections acquired during pregnancy carry higher risk of mother-to-child transmission (MTCT). We analyze the potential benefits from extending the availability of effective microbicide to pregnant women (in addition to non-pregnant women) in a wide-scale intervention.Methods and Findings:A transmission dynamic model was designed to assess the impact of microbicide use in high HIV prevalence settings and to estimate proportions of new HIV infections, infections acquired during pregnancy, and MTCT prevented over 10 years. Our analysis suggests that consistent use of microbicide with 70% efficacy by 60% of non-pregnant women may prevent approximately 40% and 15% of new infections in women and men respectively over 10 years, assuming no additional increase in HIV risk to either partner during pregnancy (RRHIV/preg = 1). It may also prevent 8-15% MTCT depending on the increase in MTCT risk when HIV is acquired during pregnancy compared to before pregnancy (RRMTCT/preg). Extending the microbicides use during pregnancy may improve the effectiveness of the intervention by 10% (RRHIV/preg = 1) to 25% (RRHIV/preg = 2) and reduce the number of HIV infections acquired during pregnancy by 40% to 70% in different scenarios. It may add between 6% (RRHIV/preg = 1, RRMTCT/preg = 1) and 25% (RRHIV/preg = 2, RRMTCT/preg = 4) to the reduction in the residual MTCT.Conclusion:Providing safe and effective microbicide to pregnant women in the context of wide-scale interventions would be desirable as it would increase the effectiveness of the intervention and significantly reduce the number of HIV infections acquired during pregnancy. The projected benefits from covering pregnant women by the HIV prevention programs is more substantial in communities in which the sexual risk during pregnancy is elevated. © 2013 Dimitrov et al

The geography of recent genetic ancestry across Europe

The recent genealogical history of human populations is a complex mosaic formed by individual migration, large-scale population movements, and other demographic events. Population genomics datasets can provide a window into this recent history, as rare traces of recent shared genetic ancestry are detectable due to long segments of shared genomic material. We make use of genomic data for 2,257 Europeans (the POPRES dataset) to conduct one of the first surveys of recent genealogical ancestry over the past three thousand years at a continental scale. We detected 1.9 million shared genomic segments, and used the lengths of these to infer the distribution of shared ancestors across time and geography. We find that a pair of modern Europeans living in neighboring populations share around 10-50 genetic common ancestors from the last 1500 years, and upwards of 500 genetic ancestors from the previous 1000 years. These numbers drop off exponentially with geographic distance, but since genetic ancestry is rare, individuals from opposite ends of Europe are still expected to share millions of common genealogical ancestors over the last 1000 years. There is substantial regional variation in the number of shared genetic ancestors: especially high numbers of common ancestors between many eastern populations likely date to the Slavic and/or Hunnic expansions, while much lower levels of common ancestry in the Italian and Iberian peninsulas may indicate weaker demographic effects of Germanic expansions into these areas and/or more stably structured populations. Recent shared ancestry in modern Europeans is ubiquitous, and clearly shows the impact of both small-scale migration and large historical events. Population genomic datasets have considerable power to uncover recent demographic history, and will allow a much fuller picture of the close genealogical kinship of individuals across the world.Comment: Full size figures available from http://www.eve.ucdavis.edu/~plralph/research.html; or html version at http://ralphlab.usc.edu/ibd/ibd-paper/ibd-writeup.xhtm

How to find an attractive solution to the liar paradox

The general thesis of this paper is that metasemantic theories can play a central role in determining the correct solution to the liar paradox. I argue for the thesis by providing a specific example. I show how Lewis’s reference-magnetic metasemantic theory may decide between two of the most influential solutions to the liar paradox: Kripke’s minimal fixed point theory of truth and Gupta and Belnap’s revision theory of truth. In particular, I suggest that Lewis’s metasemantic theory favours Kripke’s solution to the paradox over Gupta and Belnap’s. I then sketch how other standard criteria for assessing solutions to the liar paradox, such as whether a solution faces a so-called revenge paradox, fit into this picture. While the discussion of the specific example is itself important, the underlying lesson is that we have an unused strategy for resolving one of the hardest problems in philosophy

The plight of the sense-making ape

This is a selective review of the published literature on object-choice tasks, where participants use directional cues to find hidden objects. This literature comprises the efforts of researchers to make sense of the sense-making capacities of our nearest living relatives. This chapter is written to highlight some nonsensical conclusions that frequently emerge from this research. The data suggest that when apes are given approximately the same sense-making opportunities as we provide our children, then they will easily make sense of our social signals. The ubiquity of nonsensical contemporary scientific claims to the effect that humans are essentially--or inherently--more capable than other great apes in the understanding of simple directional cues is, itself, a testament to the power of preconceived ideas on human perception