Auriculo-condylar syndrome: mapping of a first locus and evidence for genetic heterogeneity

Auriculo-condylar syndrome (ACS), an autosomal dominant disorder of first and second pharyngeal arches, is characterized by malformed ears (`question mark ears`), prominent cheeks, microstomia, abnormal temporomandibular joint, and mandibular condyle hypoplasia. Penetrance seems to be complete, but there is high inter-and intra-familial phenotypic variation, with no evidence of genetic heterogeneity. We herein describe a new multigeneration family with 11 affected individuals (F1), in whom we confirm intra-familial clinical variability. Facial asymmetry, a clinical feature not highlighted in other ACS reports, was highly prevalent among the patients reported here. The gene responsible for ACS is still unknown and its identification will certainly contribute to the understanding of human craniofacial development. No chromosomal rearrangements have been associated with ACS, thus mapping and positional cloning is the best approach to identify this disease gene. To map the ACS gene, we conducted linkage analysis in two large ACS families, F1 and F2 (F2; reported elsewhere). Through segregation analysis, we first excluded three known loci associated with disorders of first and second pharyngeal arches (Treacher Collins syndrome, oculo-auriculo-vertebral spectrum, and Townes-Brocks syndrome). Next, we performed a wide genome search and we observed evidence of linkage to 1p21.1-q23.3 in F2 (LOD max 3.01 at theta = 0). Interestingly, this locus was not linked to the phenotype segregating in F1. Therefore, our results led to the mapping of a first locus of ACS (ACS1) and also showed evidence for genetic heterogeneity, suggesting that there are at least two loci responsible for this phenotype.

Mobius Sequence in a Girl and Arthrogryposis in her Half-Brother: Distinct Phenotypes Caused By Prenatal Injuries

Mobius sequence is a congenital facial and abducens nerve palsy, frequently associated to abnormalities of extremities. Arthrogryposis multiplex congenital is defined as a congenital fixation of multiple joints seldom of neurogenic origin. Both sequences must have a genetic origin, but usually are sporadic cases related to environmental factors such as drugs exposition and maternal trauma. A 5-year-old girl and a 1-year-old boy were born with Mobius sequence and arthrogryposis multiplex congenital, respectively. During pregnancies, the mother had vaginal bleeding at 7 weeks and used crack (free-based cocaine) in the first trimester, respectively. The girl also has equinovarus talipes and autistic behavior. The boy has arthrogryposis with flexion contractures of the feet and knees. A vascular disruption, due to hemorrhage and cocaine exposure, causing a transient ischemic insult to embryos in a critical period of development may be responsible for distinct phenotypes in these cases.

UBE2A Deficiency Syndrome: Mild to Severe Intellectual Disability Accompanied by Seizures, Absent Speech, Urogenital, and Skin Anomalies in Male Patients

We describe three patients with a comparable deletion encompassing SLC25A43, SLC25A5, CXorf56, UBE2A, NKRF, and two non-coding RNA genes, U1 and LOC100303728. Moderate to severe intellectual disability (ID), psychomotor retardation, severely impaired/absent speech, seizures, and urogenital anomalies were present in all three patients. Facial dysmorphisms include ocular hypertelorism, synophrys, and a depressed nasal bridge. These clinical features overlap with those described in two patients from a family with a similar deletion at Xq24 that also includes UBE2A, and in several patients of Brazilian and Polish families with point mutations in UBE2A. Notably, all five patients with an Xq24 deletion have ventricular septal defects that are not present inpatients with a point mutation, which might be attributed to the deletion of SLC25A5. Taken together, the UBE2A deficiency syndrome in male patients with a mutation in or a deletion of UBE2A is characterized by ID, absent speech, seizures, urogenital anomalies, frequently including a small penis, and skin abnormalities, which include generalized hirsutism, low posterior hairline, myxedematous appearance, widely spaced nipples, and hair whorls. Facial dysmorphisms include a wide face, a depressed nasal bridge, a large mouth with downturned corners, thin vermilion, and a short, broad neck. (C) 2010 Wiley-Liss, Inc.

Mandibulofacial Dysostosis, Severe Lower Eyelid Coloboma, Cleft Palate, and Alopecia: A New Distinct Form of Mandibulofacial Dysostosis or a Severe Form of Johnson-McMillin Syndrome?

We describe a patient with a phenotype characterized by mandibulofacial dysostosis with severe lower eyelid coloboma, cleft palate, abnormal ears, alopecia, delayed eruption and crowded teeth, and sensorioneural hearing loss. The karyotype and the screening for mutations in the coding region of TCOF1 gene were normal. The clinical signs of our case overlap the new mandibulofacial dysostosis described by Stevenson et al. [2007] and the case with Johnson-McMillin syndrome described by Cushman et al. [2005]. The similar clinical signs, mainly, the severe facial involvement observed in these cases suggest that they can represent a new distinct form of mandibulofacial dysostosis or the end of the spectrum of Johnson McMillin syndrome. (C) 2010 Wiley-Liss, Inc.

Human Stem Cell Cultures from Cleft Lip/Palate Patients Show Enrichment of Transcripts Involved in Extracellular Matrix Modeling By Comparison to Controls

Nonsyndromic cleft lip and palate (NSCL/P) is a complex disease resulting from failure of fusion of facial primordia, a complex developmental process that includes the epithelial-mesenchymal transition (EMT). Detection of differential gene transcription between NSCL/P patients and control individuals offers an interesting alternative for investigating pathways involved in disease manifestation. Here we compared the transcriptome of 6 dental pulp stem cell (DPSC) cultures from NSCL/P patients and 6 controls. Eighty-seven differentially expressed genes (DEGs) were identified. The most significant putative gene network comprised 13 out of 87 DEGs of which 8 encode extracellular proteins: ACAN, COL4A1, COL4A2, GDF15, IGF2, MMP1, MMP3 and PDGFa. Through clustering analyses we also observed that MMP3, ACAN, COL4A1 and COL4A2 exhibit co-regulated expression. Interestingly, it is known that MMP3 cleavages a wide range of extracellular proteins, including the collagens IV, V, IX, X, proteoglycans, fibronectin and laminin. It is also capable of activating other MMPs. Moreover, MMP3 had previously been associated with NSCL/P. The same general pattern was observed in a further sample, confirming involvement of synchronized gene expression patterns which differed between NSCL/P patients and controls. These results show the robustness of our methodology for the detection of differentially expressed genes using the RankProd method. In conclusion, DPSCs from NSCL/P patients exhibit gene expression signatures involving genes associated with mechanisms of extracellular matrix modeling and palate EMT processes which differ from those observed in controls. This comparative approach should lead to a more rapid identification of gene networks predisposing to this complex malformation syndrome than conventional gene mapping technologies.

Clinical and molecular delineation of the 17q21.31 microdeletion syndrome

Background: The chromosome 17q21.31 microdeletion syndrome is a novel genomic disorder that has originally been identified using high resolution genome analyses in patients with unexplained mental retardation. Aim: We report the molecular and/or clinical characterisation of 22 individuals with the 17q21.31 microdeletion syndrome. Results: We estimate the prevalence of the syndrome to be 1 in 16 000 and show that it is highly underdiagnosed. Extensive clinical examination reveals that developmental delay, hypotonia, facial dysmorphisms including a long face, a tubular or pear-shaped nose and a bulbous nasal tip, and a friendly/amiable behaviour are the most characteristic features. Other clinically important features include epilepsy, heart defects and kidney/urologic anomalies. Using high resolution oligonucleotide arrays we narrow the 17q21.31 critical region to a 424 kb genomic segment (chr17: 41046729-41470954, hg17) encompassing at least six genes, among which is the gene encoding microtubule associated protein tau (MAPT). Mutation screening of MAPT in 122 individuals with a phenotype suggestive of 17q21.31 deletion carriers, but who do not carry the recurrent deletion, failed to identify any disease associated variants. In five deletion carriers we identify a <500 bp rearrangement hotspot at the proximal breakpoint contained within an L2 LINE motif and show that in every case examined the parent originating the deletion carries a common 900 kb 17q21.31 inversion polymorphism, indicating that this inversion is a necessary factor for deletion to occur (p< 10(25)). Conclusion: Our data establish the 17q21.31 microdeletion syndrome as a clinically and molecularly well recognisable genomic disorder.

3D face computational photography using PCA spaces

In this paper, we present a 3D face photography system based on a facial expression training dataset, composed of both facial range images (3D geometry) and facial texture (2D photography). The proposed system allows one to obtain a 3D geometry representation of a given face provided as a 2D photography, which undergoes a series of transformations through the texture and geometry spaces estimated. In the training phase of the system, the facial landmarks are obtained by an active shape model (ASM) extracted from the 2D gray-level photography. Principal components analysis (PCA) is then used to represent the face dataset, thus defining an orthonormal basis of texture and another of geometry. In the reconstruction phase, an input is given by a face image to which the ASM is matched. The extracted facial landmarks and the face image are fed to the PCA basis transform, and a 3D version of the 2D input image is built. Experimental tests using a new dataset of 70 facial expressions belonging to ten subjects as training set show rapid reconstructed 3D faces which maintain spatial coherence similar to the human perception, thus corroborating the efficiency and the applicability of the proposed system.

Functional and Structural Connectivity Between the Perigenual Anterior Cingulate and Amygdala in Bipolar Disorder

Objective: Abnormalities in the morphology and function of two gray matter structures central to emotional processing, the perigenual anterior cingulate cortex (pACC) and amygdala, have consistently been reported in bipolar disorder (BD). Evidence implicates abnormalities in their connectivity in BD. This study investigates the potential disruptions in pACC-amygdala functional connectivity and associated abnormalities in white matter that provides structural connections between the two brain regions in BD. Methods: Thirty-three individuals with BD and 31 healthy comparison subjects (HC) participated in a scanning session during which functional magnetic resonance imaging (fMRI) during processing of face stimuli and diffusion tensor imaging (DTI) were performed. The strength of pACC-amygdala functional connections was compared between BD and HC groups, and associations between these functional connectivity measures from the fMRI scans and regional fractional anisotropy (FA) from the DTI scans were assessed. Results: Functional connectivity was decreased between the pACC and amygdala in the BD group compared with HC group, during the processing of fearful and happy faces (p < .005). Moreover, a significant positive association between pACC-amygdala functional coupling and FA in ventrofrontal white matter, including the region of the uncinate fasciculus, was identified (p < .005). Conclusion: This study provides evidence for abnormalities in pACC-amygdala functional connectivity during emotional processing in BD. The significant association between pACC-amygdala functional connectivity and the structural integrity of white matter that contains pACC-amygdala connections suggest that disruptions in white matter connectivity may contribute to disturbances in the coordinated responses of the pACC and amygdala during emotional processing in BD.

Amperometric detection of benzoyl peroxide in pharmaceutical preparations using carbon paste electrodes with peroxidases naturally immobilized on coconut fibers

This paper describes the applications of anew carbon paste electrode containing fibers of coconut (Cocus nucifera L) fruit, which are very rich in peroxidase enzymes naturally immobilized on its structure. The new sensor was applied for the amperometric quantification of benzoyl peroxide in facial creams and dermatological shampoos. The amperometric measurements were performed in 0.1 mol L(-1) phosphate buffer (pH 5.2), at 0.0 V (versus Ag/AgCl). On these conditions, benzoyl peroxide was rapidly determined in the 5.0-55 mu mol L(-1), with a detection limit of 2.5 mu mol L(-1) (s/n = 3), response time of 4.1 s (90% of the steady state) and sensitivity limit of 0.33 A mol L(-1) cm(-2). The amperometric results are in good agreement with those obtained by spectrophotometric technique, used as a standard method. (C) 2009 Elsevier B.V. All rights reserved.

Studies on chemo- and diastereo-selectivity of the Diels-Alder reactions of sulfinyltoluquinones with cyclopentadiene

Sulfinyltoluquinones (2a-2c) were submitted to thermal or catalyzed [4+2] cycloaddition reactions with cyclopentadiene. For p-tolylsulfinyltoluquinones (2b) and (2c), almost complete C2-C3-chemo- and unlike-diastereoselectivity was achieved by catalysis with ZnBr(2), yielding adducts 6. Under thermal conditions, Diels-Alder reaction took place at the C5-C6 double bonds of quinones 2a-2c, generating mixtures of diastereoisomeric like- and unlike-adducts 4.

Students’ Role in Distance Learning

1. IntroductionMuch of the support that students have in a traditional classroom is absent in a distance learning course. In the traditional classroom, the learner is together with his or her classmates and the teacher; learning is socially embedded. Students can talk to each other and may learn from each other as they go through the learning process together. They also witness the teacher’s expression of the knowledge firsthand. The class participants communicate to each other not only through their words, but also through their gestures, facial expressions and tone of voice, and the teacher can observe the students’ progress and provide guidance and feedback in an as-needed basis. Further, through the habit of meeting in a regular place at a regular time, the participants reinforce their own and each other’s commitment to the course. A distance course must somehow provide learners other kinds of supports so that the distance learner also has a sense of connection with a learning community; can benefit from interaction with peers who are going through a similar learning process; receives feedback that allows him or her to know how he or she is progressing; and is guided enough so that he or she continues to progress towards the learning objectives. This cannot be accomplished if the distance course does not simultaneously promote student autonomy, for the distance course format requires students to take greater responsibility for their own learning. This chapter presents one distance learning course that was able to address all of these goals. The English Department at Högskolan Dalarna, Sweden, participates in a distance learning program with Vietnam National University. Students enrolled in this program study half-time for two years to complete a Master’s degree in English Linguistics. The distance courses in this program all contain two types of regular class meetings: one type is student-only seminars conducted through text chat, during which students discuss and complete assignments that prepare them for the other type of class meeting, also conducted through text chat, where the teacher is present and is the one to lead the discussion of seminar issues and assignments. The inclusion of student-only seminars in the course design allows for student independence while at the same time it encourages co-operation and solidarity. The teacher-led seminars offer the advantages of a class led by an expert.In this chapter, we present chatlog data from Vietnamese students in one distance course in English linguistics, comparing the role of the student in both student-only and teacher-led seminars. We discuss how students navigate their participation roles, through computer-mediated communication (CMC), according to seminar type, and we consider the emerging role of the autonomous student in the foreign-language medium, distance learning environment. We close by considering aspects of effective design of distance learning courses from the perspective of a foreign language (FL) environment.

La risa en los Chistes de Facebook

People tell jokes in order to amuse and produce laughter. It is possible to represent laughter in the cyberspace discourse by writing how it sounds or by using a representation of a facial expression formed by various combinations of keyboard characters called emoticon. Jokes are appreciated by both men and women in our society but is there any difference between the way they represent laughter in the cyberspace discourse? In this research, we use the qualitative and quantitative method. First, we analyze the mechanism of linguistic construction of five jokes and their types and techniques based on Freud’s theory about this subject. Then we present the reactions produced by the jokes found in a social network and focus in the written representation of the laughter. The results show us that more women than men react to the jokes by writing a comment. The most popular laughter used by both men and women in a Spanish social network is "jajajaja" and the emoticon "XD". We have also found that people use the international laughter "hahahaha" and more women than men use "jejeje" to represent laughter in the same network. Although each individual has a laughter style, the way people represent the laughter graphically in the cyberspace discourse is almost the same between men and women but it differs in the way they use them as a reaction to the type and technique of the joke.

Estudo clínico e bioquímico de 28 pacientes com mucopolissacaridose tipo VI

Realizamos um estudo observacional de pacientes com mucopolissacaridose tipo VI, com o objetivo de determinar o perfil epidemiológico, clínico e bioquímico de um grupo de pacientes sul-americanos a fim de contribuir em estudos futuros de correlação genótipo-fenótipo e de avaliação de protocolos clínicos. Os critérios de inclusão foram: ter 4 anos ou mais e confirmação bioquímica da doença (níveis reduzidos da atividade da ARSB, aumento de GAGs urinários e atividade normal de outra sulfatase). Os critérios de exclusão foram: terapia com reposição enzimática atual ou prévia ou ter realizado transplante de medula óssea. Foram avaliados 28 pacientes por anamnese, exame físico, acocardiograma, eletrocardiograma, avaliação oftalmológica, medidas de glicosaminoglicanos urinários e da atividade da N-acetilgalactosamina-4-sulfatase em leucócitos. A amostra estudada tinha 92,9% de brasileiros, sendo 53,8% da região sudeste. No momento da avaliação, a média de idade foi de 97,1 meses e a média de idade ao diagnóstico foram de 48,4 meses. Em 88% da amostra os sintomas iniciaram com menos de 36 meses e em 27% das famílias houve relato de consangüinidade entre os pais. A média de peso e estatura ao nascimento foi de 3481 gramas e 51,3 centímetros, respectivamente. Da amostra, 57,1% nasceram de parto vaginal. Todos apresentavam alguma alteração ecocardiográfica, bem como opacificação corneana. As manifestações clínicas mais freqüentes foram: baixa estatura, opacificação corneana, facies grosseira, contraturas articulares e mãos em garra. A média da atividade enzimática em leucócitos foi de 5,4 nmoles/h x mg proteína e a excreção urinária de glicosaminoglicanos foi, em média, 7,9 vezes superior ao normal. O número de manifestações clínicas citadas não apresentou correlação significativa com a idade, com a excreção urinária de GAGs ou com a atividade enzimática em leucócitos. Também não houve correlação significativa entre a excreção urinária de GAGS e a atividade enzimática. Concluímos que a MPS VI é uma patologia com alta morbidade e que, comparados com a literatura, os pacientes da nossa amostra têm um diagnóstico tardio e maior freqüência de alterações cardiológicas.

Efeitos fisiológicos e comportamentais de um protocolo de contenção em recém-nascidos pré-termo

Introdução: Programas de posicionamento têm sido propostos a fim de favorecer o desenvolvimento de recém-nascidos pré-termo e a facilitação dos movimentos que já realizava intra-útero, como levar a mão à boca ou à face, por exemplo. O presente estudo tem por objetivo determinar os efeitos de um protocolo de contenção postural sobre a estabilidade fisiológica e comportamental de recém-nascidos pré-termo quando submetidos à troca de fraldas. Método: Ensaio clínico de randomização cruzada com 47 recém-nascidos de peso ao nascer (PN) < 2000g e idade gestacional (IG) < 35 semanas internados no Serviço de Neonatologia do Hospital de Clínicas de Porto Alegre. Alegre. Os bebês foram avaliados com e sem o uso da intervenção proposta, que se trata do posicionamento do bebê em um ninho de forma oval, previamente produzido com toalhas enroladas de forma a dar contenção ao redor de todo o corpo, cabeça, costas, membros e apoio aos pés. Durante a observação como Controle, foi considerado o modelo de cuidado utilizado no serviço, que propõe intervenções específicas quanto ao posicionamento, mantendo o bebê apoiado com rolos de cueiros macios, posicionado em decúbito lateral ou ventral com os membros agrupados junto ao corpo.Uma Planilha de Avaliação foi elaborada para investigar os efeitos deste protocolo de Contenção Postural cinco minutos antes, imediatamente após, cinco minutos após e dez minutos após a realização de troca de fraldas.Resultados: A comparação entre os grupos mostrou maior Frequência Cardíaca (P=0,012), e menor Escore de Retraimento, Mímica Facial e Escore Facial de Dor (P<0,0001) no grupo Intervenção em relação ao grupo Controle. Conclusão: Os resultados desse estudo apontam para um efeito favorável da intervenção proposta sobre a estabilidade fisiológica e comportamental, com redução nos sinais de dor estresse durante a troca de fraldas.

Dinodontosaurus (Synapsida, Dicynodontia) reconstituições morfológicas e aspectos biomecânicos

Dicinodontes possuem um mosaico de características, que incluem, por exemplo, extrema redução dentária, movimento propalinal da mandíbula, e o desenvolvimento de uma postura diferenciada em alguns gêneros. Nesses, enquanto os membros anteriores permanecem abduzidos, em uma postura primitiva, os posteriores se tornam totalmente aduzidos. Para discutir aspectos paleobiológicos, foram efetuadas análises morfofuncionais e biomecânicas em espécimes do gênero Dinodontosaurus Romer, 1943, um dicinodonte de porte médio do Mesotriássico do estado do Rio Grande do Sul, Brasil. É endossada a sinonímia da maioria das espécies do gênero com Dinodontosaurus turpior, excetuando-se Dinodontosaurus platygnathus, cujos materiais apresentam características conflitantes, e é tratado aqui como nomen dubium. É apresentada uma sucinta descrição osteológica para as formas juvenis do gênero, nos quais se observa a presença de seis vértebras sacrais, além de um mínimo de 17 caudais, adicionando informações que permitem novas reconstruções esqueletais. Enfoque é dado na miologia facial e dos membros, com base na comparação de modelos para diferentes taxa, seguindo a abordagem de suporte filogenético de animais viventes. Apenas músculos de presença inequívoca são reconstituídos, a menos quando há argumentos morfológicos convincentes. A partir de observações morfofuncionais, é eliminada a possibilidade de Dinodontosaurus utilizar suas presas com a mandíbula aberta, seja para alimentação ou defesa, e é reforçado seu caráter como ornamentação Na falta de análogos posturais modernos, comparações com preguiças terrícolas extintas levaram alguns autores a propostas de uma postura bípede para os dicinodontes, ao menos facultativa, para se erguerem nas patas traseiras e alcançarem níveis mais elevados de vegetação. Para testar essa hipótese, foram abordados vários aspectos biomecânicos envolvidos na postura bípede, em Dinodontosaurus. Seu centro de massa foi localizado a partir da suspensão de modelos em argila, estando posicionado em um ponto, no plano sagital, aproximadamente na metade da distância entre os estilopódios anteriores e posteriores, um pouco mais próximo dos primeiros; para os indivíduos juvenis, um modelo digital obtido através de scanner 3D a laser também corroborou esse posicionamento, o que sugere que a postura bípede não poderia ser facilmente mantida sem apoio, e um caminhar bípede seria totalmente impraticável. Foram estimados os momentos de resistência da coluna vertebral, a partir de medidas da largura e altura dos centros vertebrais em sua borda posterior, sendo que os resultados foram compatíveis com um animal de postura quadrúpede. Foram também calculados os índices de capacidade atlética para os ossos longos dos membros anteriores e posteriores; para isso, foram estimadas as massas, com os indivíduos juvenis atingindo entre 23 e 32kg, enquanto o adulto não ultrapassaria 300kg. As massas foram obtidas baseando-se em estimativas de volume a partir de silhuetas e de modelos tridimensionais em computação Os valores obtidos para os índices de capacidade atlética são muito superiores aos de outros animais descritos na literatura, embora sejam compatíveis com outros terápsidos não-mamalianos julgados quadrúpedes, e estão na mesma ordem de grandeza entre os ossos dos membros anteriores e posteriores, o que também alude à postura quadrúpede. Através de observações morfológicas gerais, localização do centro de massa, estimativa de momentos de resistência da coluna vertebral e cálculo de índices de capacidade atlética para os membros, conclui-se que, ao menos no que concerne a Dinodontosaurus, não há evidências que suportem as analogias morfofuncionais com as preguiças terrícolas, animais que apresentam diversas adaptações para o bipedalismo. Os resultados para os índices de capacidade atlética também lançam dúvidas sobre sua aplicabilidade generalizada em comparações paleobiológicas.