Multi-level evidence of an allelic hierarchy of USH2A variants in hearing, auditory processing and speech/language outcomes.

Language development builds upon a complex network of interacting subservient systems. It therefore follows that variations in, and subclinical disruptions of, these systems may have secondary effects on emergent language. In this paper, we consider the relationship between genetic variants, hearing, auditory processing and language development. We employ whole genome sequencing in a discovery family to target association and gene x environment interaction analyses in two large population cohorts; the Avon Longitudinal Study of Parents and Children (ALSPAC) and UK10K. These investigations indicate that USH2A variants are associated with altered low-frequency sound perception which, in turn, increases the risk of developmental language disorder. We further show that Ush2a heterozygote mice have low-level hearing impairments, persistent higher-order acoustic processing deficits and altered vocalizations. These findings provide new insights into the complexity of genetic mechanisms serving language development and disorders and the relationships between developmental auditory and neural systems

Anomaly Cancelation in Field Theory and F-theory on a Circle

We study the manifestation of local gauge anomalies of four- and six-dimensional field theories in the lower-dimensional Kaluza-Klein theory obtained after circle compactification. We identify a convenient set of transformations acting on the whole tower of massless and massive states and investigate their action on the low-energy effective theories in the Coulomb branch. The maps employ higher-dimensional large gauge transformations and precisely yield the anomaly cancelation conditions when acting on the one-loop induced Chern-Simons terms in the three- and five-dimensional effective theory. The arising symmetries are argued to play a key role in the study of the M-theory to F-theory limit on Calabi-Yau manifolds. For example, using the fact that all fully resolved F-theory geometries inducing multiple Abelian gauge groups or non-Abelian groups admit a certain set of symmetries, we are able to generally show the cancelation of pure Abelian or pure non-Abelian anomalies in these models.Comment: 48 pages, 2 figures; v2: typos corrected, comments on circle fluxes adde

Refined Checks and Exact Dualities in Three Dimensions

We discuss and provide nontrivial evidence for a large class of dualities in three-dimensional field theories with different gauge groups. We match the full partition functions of the dual phases for any value of the couplings to underpin our proposals. We focus on two classes of models. The first class, motivated by the AdS/CFT conjecture, consists of necklace U(N) quiver gauge theories with non chiral matter fields. We also consider orientifold projections and establish dualities among necklace quivers with alternating orthogonal and symplectic groups. The second class consists of theories with tensor matter fields with free theory duals. In most of these cases the R-symmetry mixes with IR accidental symmetries and we develop the prescription to include their contribution into the partition function and the extremization problem accordingly.Comment: 38 pages, 3 figure, using jheppu

PlatoSim: an end-to-end PLATO camera simulator for modelling high-precision space-based photometry

Context. PLAnetary Transits and Oscillations of stars (PLATO) is the ESA M3 space mission dedicated to detect and characterise transiting exoplanets including information from the asteroseismic properties of their stellar hosts. The uninterrupted and high-precision photometry provided by space-borne instruments such as PLATO require long preparatory phases. An exhaustive list of tests are paramount to design a mission that meets the performance requirements and, as such, simulations are an indispensable tool in the mission preparation. Aims. To accommodate PLATO’s need of versatile simulations prior to mission launch that at the same time describe innovative yet complex multi-telescope design accurately, in this work we present the end-to-end PLATO simulator specifically developed for that purpose, namely PlatoSim. We show, step-by-step, the algorithms embedded into the software architecture of PlatoSim that allow the user to simulate photometric time series of charge-coupled device (CCD) images and light curves in accordance to the expected observations of PLATO. Methods. In the context of the PLATO payload, a general formalism of modelling, end-to-end, incoming photons from the sky to the final measurement in digital units is discussed. According to the light path through the instrument, we present an overview of the stellar field and sky background, the short- and long-term barycentric pixel displacement of the stellar sources, the cameras and their optics, the modelling of the CCDs and their electronics, and all main random and systematic noise sources. Results. We show the strong predictive power of PlatoSim through its diverse applicability and contribution to numerous working groups within the PLATO mission consortium. This involves the ongoing mechanical integration and alignment, performance studies of the payload, the pipeline development, and assessments of the scientific goals. Conclusions. PlatoSim is a state-of-the-art simulator that is able to produce the expected photometric observations of PLATO to a high level of accuracy. We demonstrate that PlatoSim is a key software tool for the PLATO mission in the preparatory phases until mission launch and prospectively beyond

Comportamentos agressivos em crianças e adolescentes com risco para esquizofrenia: diferenças entre gêneros

OBJECTIVE: This study aimed to investigate whether differences in aggression-related behavioral problems occur between boys and girls at high risk for schizophrenia living in the city of São Paulo, Brazil. METHOD: Using the Child Behavior Checklist, we compared the prevalence of behavioral problems between genders for the offspring (6-18 years) of mothers with diagnosis of schizophrenia and a comparison group of children born to women with no severe mental disorders recruited at the gynecology outpatient clinic of the same hospital. The Structured Clinical Interview for DSM-IV Axis I Disorders, Patient Edition was applied for the evaluation of diagnostic status of mothers. RESULTS: Male children of women with schizophrenia had a lower prevalence of aggressive behavior compared to females (4% vs. 36%; p = 0.005), whereas no gender differences regarding aggression were detected in the comparison group (24% vs. 32%; p = 0.53). Logistic regression analyses showed that male gender and being a child of women with schizophrenia interacted so as to favor lower prevalence of aggressive behavior (p = 0.03). CONCLUSION: These findings reinforce the notion that behavioral gender differences related to schizophrenia are already detectable in childhood.OBJETIVO: Investigar diferenças da ocorrência de comportamentos agressivos entre crianças e adolescentes do sexo masculino e feminino com risco genético para desenvolver esquizofrenia. MÉTODO: A prevalência de comportamentos agressivos foi medida utilizando o inventário de comportamentos para crianças e adolescentes, Child Behavior Checklist, e comparada entre os gêneros para o grupo de crianças filhas de mulheres com esquizofrenia e para um grupo de crianças filhas de mulheres atendidas no serviço de ginecologia do mesmo hospital. A entrevista clínica estruturada para DSM-IV (The Structured Clinical Interview for DSM-IV Axis I Disorders Patient Edition) foi utilizada para confirmar o diagnóstico materno. RESULTADOS: Os filhos de mulheres com esquizofrenia do sexo masculino apresentaram prevalência menor de comportamentos agressivos quando comparados às meninas (4% x 36%; p = 0,005), o que não ocorreu para o grupo comparativo (24% x 32%; p = 0,53). A análise de regressão logística mostrou que pertencer ao sexo masculino e ser filho de mulher com esquizofrenia interagiram de forma a favorecer menor prevalência de comportamentos agressivos (p = 0,03). CONCLUSÃO: Esses achados corroboram para a noção que as diferenças comportamentais entre os gêneros na esquizofrenia podem ser detectadas precocemente durante a infância

Variation in the Structure of Bird Nests between Northern Manitoba and Southeastern Ontario

Traits that converge in appearance under similar environmental conditions among phylogenetically independent lineages are thought to represent adaptations to local environments. We tested for convergence in nest morphology and composition of birds breeding in two ecologically different locations in Canada: Churchill in northern Manitoba and Elgin in southeastern Ontario. We examined nests from four families of passerine birds (Turdidae: Turdus, Parulidae: Dendroica, Emberizidae: Passerculus and Fringillidae: Carduelis) where closely related populations or species breed in both locations. Nests of American Robins, Yellow Warblers, and Carduelis finches had heavier nest masses, and tended to have thicker nest-walls, in northern Manitoba compared with conspecifics or congenerics breeding in southeastern Ontario. Together, all species showed evidence for wider internal and external nest-cup diameters in northern Manitoba, while individual species showed varying patterns for internal nest-cup and external nest depths. American Robins, Yellow Warblers, and Carduelis finches in northern Manitoba achieved heavier nest masses in different ways. American Robins increased all materials in similar proportions, and Yellow Warblers and Common Redpolls used greater amounts of select materials. While changes in nest composition vary uniquely for each species, the pattern of larger nests in northern Manitoba compared to southeastern Ontario in three of our four phylogenetically-independent comparisons suggests that birds are adapting to similar selective pressures between locations

Telomeric Trans-Silencing in Drosophila melanogaster: Tissue Specificity, Development and Functional Interactions between Non-Homologous Telomeres

BACKGROUND: The study of P element repression in Drosophila melanogaster led to the discovery of the telomeric Trans-Silencing Effect (TSE), a homology-dependent repression mechanism by which a P-transgene inserted in subtelomeric heterochromatin (Telomeric Associated Sequences, "TAS") has the capacity to repress in trans, in the female germline, a homologous P-lacZ transgene located in euchromatin. TSE can show variegation in ovaries, displays a maternal effect as well as an epigenetic transmission through meiosis and involves heterochromatin and RNA silencing pathways. PRINCIPAL FINDINGS: Here, we analyze phenotypic and genetic properties of TSE. We report that TSE does not occur in the soma at the adult stage, but appears restricted to the female germline. It is detectable during development at the third instar larvae where it presents the same tissue specificity and maternal effect as in adults. Transgenes located in TAS at the telomeres of the main chromosomes can be silencers which in each case show the maternal effect. Silencers located at non-homologous telomeres functionally interact since they stimulate each other via the maternally-transmitted component. All germinally-expressed euchromatic transgenes tested, located on all major chromosomes, were found to be repressed by a telomeric silencer: thus we detected no TSE escaper. The presence of the euchromatic target transgene is not necessary to establish the maternal inheritance of TSE, responsible for its epigenetic behavior. A single telomeric silencer locus can simultaneously repress two P-lacZ targets located on different chromosomal arms. CONCLUSIONS AND SIGNIFICANCE: Therefore TSE appears to be a widespread phenomenon which can involve different telomeres and work across the genome. It can explain the P cytotype establishment by telomeric P elements in natural Drosophila populations

Theories of schizophrenia: a genetic-inflammatory-vascular synthesis

BACKGROUND: Schizophrenia, a relatively common psychiatric syndrome, affects virtually all brain functions yet has eluded explanation for more than 100 years. Whether by developmental and/or degenerative processes, abnormalities of neurons and their synaptic connections have been the recent focus of attention. However, our inability to fathom the pathophysiology of schizophrenia forces us to challenge our theoretical models and beliefs. A search for a more satisfying model to explain aspects of schizophrenia uncovers clues pointing to genetically mediated CNS microvascular inflammatory disease. DISCUSSION: A vascular component to a theory of schizophrenia posits that the physiologic abnormalities leading to illness involve disruption of the exquisitely precise regulation of the delivery of energy and oxygen required for normal brain function. The theory further proposes that abnormalities of CNS metabolism arise because genetically modulated inflammatory reactions damage the microvascular system of the brain in reaction to environmental agents, including infections, hypoxia, and physical trauma. Damage may accumulate with repeated exposure to triggering agents resulting in exacerbation and deterioration, or healing with their removal. There are clear examples of genetic polymorphisms in inflammatory regulators leading to exaggerated inflammatory responses. There is also ample evidence that inflammatory vascular disease of the brain can lead to psychosis, often waxing and waning, and exhibiting a fluctuating course, as seen in schizophrenia. Disturbances of CNS blood flow have repeatedly been observed in people with schizophrenia using old and new technologies. To account for the myriad of behavioral and other curious findings in schizophrenia such as minor physical anomalies, or reported decreased rates of rheumatoid arthritis and highly visible nail fold capillaries, we would have to evoke a process that is systemic such as the vascular and immune/inflammatory systems. SUMMARY: A vascular-inflammatory theory of schizophrenia brings together environmental and genetic factors in a way that can explain the diversity of symptoms and outcomes observed. If these ideas are confirmed, they would lead in new directions for treatments or preventions by avoiding inducers of inflammation or by way of inflammatory modulating agents, thus preventing exaggerated inflammation and consequent triggering of a psychotic episode in genetically predisposed persons

The COGs (context, object, and goals) in multisensory processing

Our understanding of how perception operates in real-world environments has been substantially advanced by studying both multisensory processes and “top-down” control processes influencing sensory processing via activity from higher-order brain areas, such as attention, memory, and expectations. As the two topics have been traditionally studied separately, the mechanisms orchestrating real-world multisensory processing remain unclear. Past work has revealed that the observer’s goals gate the influence of many multisensory processes on brain and behavioural responses, whereas some other multisensory processes might occur independently of these goals. Consequently, other forms of top-down control beyond goal dependence are necessary to explain the full range of multisensory effects currently reported at the brain and the cognitive level. These forms of control include sensitivity to stimulus context as well as the detection of matches (or lack thereof) between a multisensory stimulus and categorical attributes of naturalistic objects (e.g. tools, animals). In this review we discuss and integrate the existing findings that demonstrate the importance of such goal-, object- and context-based top-down control over multisensory processing. We then put forward a few principles emerging from this literature review with respect to the mechanisms underlying multisensory processing and discuss their possible broader implications