Subanesthetic ketamine treatment promotes abnormal interactions between neural subsystems and alters the properties of functional brain networks

Acute treatment with subanesthetic ketamine, a non-competitive N-methyl-D-aspartic acid (NMDA) receptor antagonist, is widely utilized as a translational model for schizophrenia. However, how acute NMDA receptor blockade impacts on brain functioning at a systems level, to elicit translationally relevant symptomatology and behavioral deficits, has not yet been determined. Here, for the first time, we apply established and recently validated topological measures from network science to brain imaging data gained from ketamine-treated mice to elucidate how acute NMDA receptor blockade impacts on the properties of functional brain networks. We show that the effects of acute ketamine treatment on the global properties of these networks are divergent from those widely reported in schizophrenia. Where acute NMDA receptor blockade promotes hyperconnectivity in functional brain networks, pronounced dysconnectivity is found in schizophrenia. We also show that acute ketamine treatment increases the connectivity and importance of prefrontal and thalamic brain regions in brain networks, a finding also divergent to alterations seen in schizophrenia. In addition, we characterize how ketamine impacts on bipartite functional interactions between neural subsystems. A key feature includes the enhancement of prefrontal cortex (PFC)-neuromodulatory subsystem connectivity in ketamine-treated animals, a finding consistent with the known effects of ketamine on PFC neurotransmitter levels. Overall, our data suggest that, at a systems level, acute ketamine-induced alterations in brain network connectivity do not parallel those seen in chronic schizophrenia. Hence, the mechanisms through which acute ketamine treatment induces translationally relevant symptomatology may differ from those in chronic schizophrenia. Future effort should therefore be dedicated to resolve the conflicting observations between this putative translational model and schizophrenia

Naturalness Lowers the Upper Bound on the Lightest Higgs Boson Mass in Supersymmetry

We quantify the extent to which naturalness is lost as experimental lower bounds on the Higgs boson mass increase, and we compute the natural upper bound on the lightest supersymmetric Higgs boson mass. We find that it would be unnatural for the mass of the lightest supersymmetric Higgs boson to saturate it's maximal upper bound. In the absence of significant fine-tuning, the lightest Higgs boson mass should lie below $120$ GeV, and in the most natural cases it should be lighter than $108$ GeV. For modest $tan \beta$, these bounds are significantly lower. Our results imply that a failure to observe a light Higgs boson in pre-LHC experiments could provide a serious challenge to the principal motivation for weak-scale supersymmetry.Comment: 11 pages, LaTex, 3 ps.figure

Implementing statically typed object-oriented programming languages

A paraîtreInternational audienceObject-oriented programming languages represent an original implementation issue due to the mechanism known as late binding, aka message sending. The underlying principle is that the address of the actually called procedure is not statically determined, at compile-time, but depends on the dynamic type of a distinguished parameter known as the receiver. In statically typed languages, the point is that the receiver's dynamic type may be a subtype of its static type. A similar issue arises with attributes, because their position in the object layout may depends on the object's dynamic type. Furthermore, subtyping introduces another original feature, i.e. subtype checks. All three mechanisms need specific implementations, data structures and algorithms. In statically typed languages, late binding is generally implemented with tables, called virtual function tables in C++ jargon. These tables reduce method calls to pointers to functions, through a small fixed number of extra indirections. It follows that object-oriented programming yields some overhead, as compared to usual procedural languages. The different techniques and their resulting overhead depend on several parameters. Firstly, inheritance and subtyping may be single or multiple and a mixing is even possible, as in JAVA, which presents single inheritance for classes and multiple subtyping for interfaces. Multiple inheritance is a well known complication. Secondly, the production of executable programs may involve various schemes, from global compilation frameworks, where the whole program is known at compile time, to separate compilation and dynamic loading, where each program unit---usually a class in an object-oriented context---is compiled and loaded independently of any usage. Global compilation is well known to facilitate optimization. In this paper, we review the various implementation schemes available in the context of static typing and in the three cases of single inheritance, multiple inheritance, and single inheritance but with multiple subtyping, e.g. JAVA. The survey focuses on separate compilation and dynamic loading, as it is the most commonly used framework and the most demanding. However, many works have been recently undertaken in the global compilation framework, mostly for dynamically typed languages but also applied to the EIFFEL language in the SMARTEIFFEL compiler. Hence, we examine global techniques and how they can improve implementation efficiency. Finally, a mixed framework is considered, where separate compilation is followed by a global step, similar to linking, which uses global techniques, as well for implementation, with coloring, as for optimization, with type analysis. An application to dynamic loading is sketched

Analysis of age-related left ventricular collagen remodeling in living donors: Implications in arrhythmogenesis

Age-related fibrosis in the left ventricle (LV) has been mainly studied in animals by assessing collagen content. Using second-harmonic generation microscopy and image processing, we evaluated amount, aggregation and spatial distribution of LV collagen in young to old pigs, and middle-age and elder living donors. All collagen features increased when comparing adult and old pigs with young ones, but not when comparing adult with old pigs or middle-age with elder individuals. Remarkably, all collagen parameters strongly correlated with lipofuscin, a biological age marker, in humans. By building patient-specific models of human ventricular tissue electrophysiology, we confirmed that amount and organization of fibrosis modulated arrhythmia vulnerability, and that distribution should be accounted for arrhythmia risk assessment. In conclusion, we characterize the age-associated changes in LV collagen and its potential implications for ventricular arrhythmia development. Consistency between pig and human results substantiate the pig as a relevant model of age-related LV collagen dynamics. © 2022 The Author(s

Is Homosexuality a Paraphilia? The Evidence For and Against

Whether homosexuality should be described as one among many paraphilic sexual interests or an altogether different dimension of sexual interest has long been discussed in terms of its political and social implications. The present article examined the question instead by comparing the major correlates and other features of homosexuality and of the paraphilias, including prevalence, sex ratio, onset and course, fraternal birth order, physical height, handedness, IQ and cognitive neuropsychological profile, and neuroanatomy. Although those literatures remain underdeveloped, the existing findings thus far suggest that homosexuality has a pattern of correlates largely, but not entirely, distinct from that identified among the paraphilias. At least, if homosexuality were deemed a paraphilia, it would be relatively unique among them, taxonometrically speaking

Topography of the Chimpanzee Corpus Callosum

The corpus callosum (CC) is the largest commissural white matter tract in mammalian brains, connecting homotopic and heterotopic regions of the cerebral cortex. Knowledge of the distribution of callosal fibers projecting into specific cortical regions has important implications for understanding the evolution of lateralized structures and functions of the cerebral cortex. No comparisons of CC topography in humans and great apes have yet been conducted. We investigated the topography of the CC in 21 chimpanzees using high-resolution magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). Tractography was conducted based on fiber assignment by continuous tracking (FACT) algorithm. We expected chimpanzees to display topographical organization similar to humans, especially concerning projections into the frontal cortical regions. Similar to recent studies in humans, tractography identified five clusters of CC fibers projecting into defined cortical regions: prefrontal; premotor and supplementary motor; motor; sensory; parietal, temporal and occipital. Significant differences in fractional anisotropy (FA) were found in callosal regions, with highest FA values in regions projecting to higher-association areas of posterior cortical (including parietal, temporal and occipital cortices) and prefrontal cortical regions (p<0.001). The lowest FA values were seen in regions projecting into motor and sensory cortical areas. Our results indicate chimpanzees display similar topography of the CC as humans, in terms of distribution of callosal projections and microstructure of fibers as determined by anisotropy measures

Law, Environment, and the “Nondismal” Social Sciences

Over the past 30 years, the influence of economics over the study of environmental law and policy has expanded considerably, becoming in the process the predominant framework for analyzing regulations that address pollution, natural resource use, and other environmental issues. This review seeks to complement the expansion of economic reasoning and methodology within the field of environmental law and policy by identifying insights to be gleaned from various “nondismal” social sciences. In particular, three areas of inquiry are highlighted as illustrative of interdisciplinary work that might help to complement law and economics and, in some cases, compensate for it: the study of how human individuals perceive, judge, and decide; the observation and interpretation of how knowledge schemes are created, used, and regulated; and the analysis of how states and other actors coordinate through international and global regulatory regimes. The hope is to provide some examples of how environmental law and policy research can be improved by deeper and more diverse engagement with social science

An Intergenic Region Shared by At4g35985 and At4g35987 in Arabidopsis Thaliana is a Tissue Specific and Stress Inducible Bidirectional Promoter Analyzed in Transgenic Arabidopsis and Tobacco Plants

On chromosome 4 in the Arabidopsis genome, two neighboring genes (calmodulin methyl transferase At4g35987 and senescence associated gene At4g35985) are located in a head-to-head divergent orientation sharing a putative bidirectional promoter. This 1258 bp intergenic region contains a number of environmental stress responsive and tissue specific cis-regulatory elements. Transcript analysis of At4g35985 and At4g35987 genes by quantitative real time PCR showed tissue specific and stress inducible expression profiles. We tested the bidirectional promoter-function of the intergenic region shared by the divergent genes At4g35985 and At4g35987 using two reporter genes (GFP and GUS) in both orientations in transient tobacco protoplast and Agro-infiltration assays, as well as in stably transformed transgenic Arabidopsis and tobacco plants. In transient assays with GFP and GUS reporter genes the At4g35985 promoter (P85) showed stronger expression (about 3.5 fold) compared to the At4g35987 promoter (P87). The tissue specific as well as stress responsive functional nature of the bidirectional promoter was evaluated in independent transgenic Arabidopsis and tobacco lines. Expression of P85 activity was detected in the midrib of leaves, leaf trichomes, apical meristemic regions, throughout the root, lateral roots and flowers. The expression of P87 was observed in leaf-tip, hydathodes, apical meristem, root tips, emerging lateral root tips, root stele region and in floral tissues. The bidirectional promoter in both orientations shows differential up-regulation (2.5 to 3 fold) under salt stress. Use of such regulatory elements of bidirectional promoters showing spatial and stress inducible promoter-functions in heterologous system might be an important tool for plant biotechnology and gene stacking applications