The Promoter Regions of Intellectual Disability-Associated Genes Are Uniquely Enriched in LTR Sequences of the MER41 Primate-Specific Endogenous Retrovirus: An Evolutionary Connection Between Immunity and Cognition

Social behavior and neuronal connectivity in rodents have been shown to be shaped by the prototypical T lymphocyte-derived pro-inflammatory cytokine Interferon-gamma (IFNγ). It has also been demonstrated that STAT1 (Signal Transducer And Activator Of Transcription 1), a transcription factor (TF) crucially involved in the IFNγ pathway, binds consensus sequences that, in humans, are located with a high frequency in the LTRs (Long Terminal Repeats) of the MER41 family of primate-specific HERVs (Human Endogenous Retroviruses). However, the putative role of an IFNγ/STAT1/MER41 pathway in human cognition and/or behavior is still poorly documented. Here, we present evidence that the promoter regions of intellectual disability-associated genes are uniquely enriched in LTR sequences of the MER41 HERVs. This observation is specific to MER41 among more than 130 HERVs examined. Moreover, we have not found such a significant enrichment in the promoter regions of genes that associate with autism spectrum disorder (ASD) or schizophrenia. Interestingly, ID-associated genes exhibit promoter-localized MER41 LTRs that harbor TF binding sites (TFBSs) for not only STAT1 but also other immune TFs such as, in particular, NFKB1 (Nuclear Factor Kappa B Subunit 1) and STAT3 (Signal Transducer And Activator Of Transcription 3). Moreover, IL-6 (Interleukin 6) rather than IFNγ, is identified as the main candidate cytokine regulating such an immune/MER41/cognition pathway. Of note, differences between humans and chimpanzees are observed regarding the insertion sites of MER41 LTRs in the promoter regions of ID-associated genes. Finally, a survey of the human proteome has allowed us to map a protein-protein network which links the identified immune/MER41/cognition pathway to FOXP2 (Forkhead Box P2), a key TF involved in the emergence of human speech. Our work suggests that together with the evolution of immune genes, the stepped self-domestication of MER41 in the genomes of primates could have contributed to cognitive evolution. We further propose that non-inherited forms of ID might result from the untimely or quantitatively inappropriate expression of immune signals, notably IL-6, that putatively regulate cognition-associated genes via promoter-localized MER41 LTRs

Józef Barnn: Humanismo y poesía

Traditionally regarded as apolitical, the poetical work by Józef Baran actually represents a lucid and coherent attempt to vindicate human dignity. Consequently, an ultimate concern of this poetry is the reason of suffering, while a recurrent topic is a self-restrained sense of carpe diem, which often leads to an enlightening inquiry into perennial metaphysical questions (life, death, eternity, God). Baran's Poetics rather reflects his main concerns and his personal ethics: his distinctive, personal style (plain, direct, sometimes ironic, sometimes lyric) resembles a dialogic resort, which consciously urges his reader to jointly discuss those philosophical questions raised by the author in his poems.Tildada tradicionalmente de apolítica, la poesía de Józef Baran representa, no obstante, un lúcido, sentido y coherente intento por defender la dignidad del ser humano a través de la literatura. Nacida de la compasión por el sufrimiento del otro, la poesía de Baran supone una vindicación permanente del valor de la vida y de la importancia de que revisten los pequeños placeres que ésta nos ofrece, llegando en último término a plantearse el sentido de la existencia y el valor que para el hombre posee lo trascendente. La Poética de Baran se halla en consonancia con los presupuestos éticos que defiende a través de sus versos: con su estilo sencillo, directo, tenido de lirismo y de una amable ironía; esta poesía busca ante todo entablar un diálogo con el lector, a quien invita a discutir las grandes cuestiones filosóficas que el poeta ha querido plantear en su obra

Time interval integration with a chromosomal translocation affecting 7q31

How exactly auditory stimulation initiates language comprehension is still unknown. Some lines of research point to the possible involvement of sub-cortical and cortical circuits, particularly through a functional network comprising the striatum-thalamus-cortex and cerebellum, in which FOXP2 is expressed. This network is thought to support the production and perception of time intervals. In order to evaluate if deficient perception and timing of short time interval words (SIW) in the range of 20 to 200 ms - crucial for timing correctly the integration of long time interval words (LIW) above 200ms - can increase the degree of difficulty in comprehension, we study here a 11 year old subject, A, with a break at some point in the 7q31 region, where FOXP2 is located. Using an audio-visual test with linguistically relevant SIWs contained in basic grammatical constructions and comparing A’s difficulty score with that of a 4-11 year old normal population (NP) and that of a control matched in age, sex, schooling, language and socioeconomic background, it was found that A scored higher than a 6 year old but lower than a 7 year old. Subject A’s anomalous degree of difficulty for specific constructions with SIWs is not consistent with these ages’ performance, but rather suggests an anomalous impairment in perceiving and timing SIWs without which timing correctly the integration of LIWs might be disrupted

Specific language impairment, autisms spectrum disorders and social (pragmatic) communication disorders: is there overlap in language deficits? A review

Analysing language characteristics and understanding their dynamics is the key for a successful intervention by speech and language therapists (SLT). Thus, this review aims to investigate a possible overlap in language development shared by autism spectrum disorders (ASD), specific language impairment (SLI) and social (pragmatic) communication disorder (SPCD). The sources of this work were the PubMed, PsycInfo and SciELO databases, as well as the Scientific Open Access Repositories of Portugal. The final selection included 18 studies, focused on several linguistic areas. Results suggest that when individuals are matched according to some language or cognitive skills, they will also show similar characteristics in other language domains. Future work should be done based on spontaneous speech.info:eu-repo/semantics/publishedVersio

Language Impairment Resulting from a de novo Deletion of 7q32.1q33

We report on a girl who presents with hearing loss, behavioral disturbances (according to the Inventory for Client and Agency Planning) as well as motor and cognitive delay (according to Battelle Developmental Inventories) which have a significant impact on her speech and language abilities [ according to the Peabody Picture Vocabulary Test (ed 3), and the Prueba de Lenguaje Oral de Navarra-Revisada (Navarra Oral Language Test, Revised)]. Five copy number variations (CNVs) were identified in the child: arr[ hg18] 7q32.1q33(127109685-132492196)x1, 8p23.1(7156900-7359099) x1, 15q13.1(26215673-26884937) x1,Xp22.33(17245-102434)x3, and Xp22.33(964441-965024) x3. The pathogenicity of similar CNVs is mostly reported as unknown. The largest deletion is found in a hot spot for cognitive disease and language impairment and contains several genes involved in brain development and function, many of which have been related to developmental disorders encompassing language deficits (dyslexia, speech-sound disorder, and autism). Some of these genes interact with FOXP2. The proband's phenotype may result from a reduced expression of some of these genes. (C) 2016 S. Karger AG, Base

Globularization and Domestication

This paper aims to explore a potential connection between two hypotheses recently put forward in the context of language evolution. One hypothesis argues that some human-specific change(s) in the hominin brain developmental program habilitated the neuronal workspace that enabled “cognitive modernity” to unfold, also resulting in our globularized braincase. The other argues that the cultural niche resulting from our self-domestication favored the emergence of natural languages. In this article we document numerous links between the genetic changes we have claimed may have brought about globularization and neural crest cells, which have been claimed to explain the constellation of distinctive traits (physical, cognitive, and behavioral) found in all domesticated mammals. If these links turn out to be as robust as we think they are, globularization and self-domestication may well be closely related phenomena in the context of human evolution.Preparation of this work was supported by funds from the Spanish Ministry of Economy and Competitiveness (Grants FFI2013-43823-P and FFI2014-61888-EXP), as well as funds from a Marie Curie International Reintegration Grant from the European Union (PIRG-GA-2009-256413), research funds from the Fundacio Bosch i Gimpera, and from the Generalitat de Catalunya (2014-SGR-200, and FI-grant)