Linguistic and perceptual processing of communicative cues in Asperger Syndrome

Asperger Syndrome (AS) belongs to autism spectrum disorders where both verbal and non-verbal communication difficulties are at the core of the impairment. Social communication requires a complex use of affective, linguistic-cognitive and perceptual processes. In the four studies included in the current thesis, some of the linguistic and perceptual factors that are important for face-to-face communication were studied using behavioural methods. In all four studies the results obtained from individuals with AS were compared with typically developed age, gender and IQ matched controls. First, the language skills of school-aged children were characterized in detail with standardized tests that measured different aspects of receptive and expressive language (Study I). The children with AS were found to be worse than the controls in following complex verbal instructions. Next, the visual perception of facial expressions of emotion with varying degrees of visual detail was examined (Study II). Adults with AS were found to have impaired recognition of facial expressions on the basis of very low spatial frequencies which are important for processing global information. Following that, multisensory perception was investigated by looking at audiovisual speech perception (Studies III and IV). Adults with AS were found to perceive audiovisual speech qualitatively differently from typically developed adults, although both groups were equally accurate in recognizing auditory and visual speech presented alone. Finally, the effect of attention on audiovisual speech perception was studied by registering eye gaze behaviour (Study III) and by studying the voluntary control of visual attention (Study IV). The groups did not differ in eye gaze behaviour or in the voluntary control of visual attention. The results of the study series demonstrate that many factors underpinning face-to-face social communication are atypical in AS. In contrast with previous assumptions about intact language abilities, the current results show that children with AS have difficulties in understanding complex verbal instructions. Furthermore, the study makes clear that deviations in the perception of global features in faces expressing emotions as well as in the multisensory perception of speech are likely to harm face-to-face social communication.

Two beam photoluminescence of PbS quantum dots in polyvinyl alcohol

We report the effect of dual beam excitation on the photoluminescence (PL) from PbS quantum dots in polyvinyl alcohol by using two excitation lasers, namely Ar+ (514.5 nm) and He-Ne laser (670 nm). Both sources of excitation gave similar PL spectra around 1.67 eV (related to shallow traps) and 1.1 eV (related to deep traps). When both lasers were used at the same time, we found that the PL induced by each of the lasers was partly quenched by the illumination of the other laser. The proposed mechanism of this quenching effect involves traps that are populated by one specific laser excitation, being photo-ionized by the presence of the other laser. Temperature, laser intensity and modulation frequency dependent quenching efficiencies are presented in this paper. This reversible modulation has potential for optical switching and memory device applications. (C) 2010 Elsevier B.V. All rights reserved.

Angelman Syndrome Protein UBE3A Interacts with Primary Microcephaly Protein ASPM, Localizes to Centrosomes and Regulates Chromosome Segregation

Many proteins associated with the phenotype microcephaly have been localized to the centrosome or linked to it functionally. All the seven autosomal recessive primary microcephaly (MCPH) proteins localize at the centrosome. Microcephalic osteodysplastic primordial dwarfism type II protein PCNT and Seckel syndrome (also characterized by severe microcephaly) protein ATR are also centrosomal proteins. All of the above findings show the importance of centrosomal proteins as the key players in neurogenesis and brain development. However, the exact mechanism as to how the loss-of-function of these proteins leads to microcephaly remains to be elucidated. To gain insight into the function of the most commonly mutated MCPH gene ASPM, we used the yeast two-hybrid technique to screen a human fetal brain cDNA library with an ASPM bait. The analysis identified Angelman syndrome gene product UBE3A as an ASPM interactor. Like ASPM, UBE3A also localizes to the centrosome. The identification of UBE3A as an ASPM interactor is not surprising as more than 80% of Angelman syndrome patients have microcephaly. However, unlike in MCPH, microcephaly is postnatal in Angelman syndrome patients. Our results show that UBE3A is a cell cycle regulated protein and its level peaks in mitosis. The shRNA knockdown of UBE3A in HEK293 cells led to many mitotic abnormalities including chromosome missegregation, abnormal cytokinesis and apoptosis. Thus our study links Angelman syndrome protein UBE3A to ASPM, centrosome and mitosis for the first time. We suggest that a defective chromosome segregation mechanism is responsible for the development of microcephaly in Angelman syndrome.

Synthesis based on cyclohexadienes .22. Formal syntheses of patchouli alcohol and norpatchoulenol

The preparation of 6-endo-formyl-1,3,3-trimethylbicyclo[2.2.2]octan-2-one 7 and 6-endo-acetyl-1,3,3-trimethylbicyclo[2.2.2]octan-2-one 8, the two key intermediates for the synthesis of patchouli alcohol 1 and norpatchoulenol 2, is reported by a simple and short method from 2-methylbenzoic acid.

Surface chemical studies on the competitive adsorption of poly(acrylic acid) and poly(vinyl alcohol) onto alumina

The adsorption of poly(acrylic acid) (PAA) and poly(vinyl alcohol) (PVA) onto alumina has been studied as a function of pH, both individually and in the presence of each other. The adsorption density of PAA is found to decrease with an increase of pH while that of PVA shows the opposite trend. In a binary system containing PAA and PVA, the presence of PVA does not affect the adsorption of PAA onto alumina, but the addition of PAA diminishes the adsorption of PVA in the pH range investigated. The adsorption isotherm of PAA at acidic pH exhibits high-affinity Langmuirian behavior. The isotherms for PVA appear rounded and are of the low-affinity type, Once again the adsorption isotherms of PAA remain unaltered in the presence of PVA whereas those of PVA are significantly affected resulting in a lowering of the adsorption density consequent to PAA addition. A variation in the sequence of addition of PAA and PVA does not affect the adsorption behavior of either of the polymers, The electrokinetic behavior of alumina with PAA is hardly influenced by the addition of PVA, On the other hand, the electrophoretic mobility of alumina in the presence of PVA is significantly altered in the presence of PAA and closely resembles the trend observed with PAA alone. Desorption studies reveal that over 80% of PVA could be desorbed in the pH range 3-9 whereas in the case of PAA, the percent desorption increases from 20 to about 70% as the pH is increased from about 3 to 8. Solution conductivity tests confirm interaction of aluminum species and PAA in the bulk solution. FTIR spectroscopic data provide evidence in support of hydrogen bonding and chemical interaction in the case of the PAA-alumina system and hydrogen bonding with respect to the PVA-alumina interaction. (C) 1999 Academic Press.

Unique Utilization of a Phosphoprotein Phosphatase Fold by a Mammalian Phosphodiesterase Associated with WAGR Syndrome

Metallophosphoesterase-domain-containing protein 2 (MPPED2) is a highly evolutionarily conserved protein with orthologs found from worms to humans. The human MPPED2 gene is found in a region of chromosome 11 that is deleted in patients with WAGR (Wilms tumor, aniridia, genitourinary anomalies, and mental retardation) syndrome, and MPPED2 may function as a tumor suppressor. However, the precise cellular roles of MPPED2 are unknown, and its low phosphodiesterase activity suggests that substrate hydrolysis may not be its prime function. We present here the structures of MPPED2 and two mutants, which show that the poor activity of MPPED2 is not only a consequence of the substitution of an active-site histidine residue by glycine but also due to binding of AMP or GMP to the active site. This feature, enhanced by structural elements of the protein, allows MPPED2 to utilize the conserved phosphoprotein-phosphatase-like fold in a unique manner, ensuring that its enzymatic activity can be combined with a possible role as a scaffolding or adaptor protein. (C) 2011 Elsevier Ltd. All rights reserved.

Chitosan-polyvinyl alcohol-sulfonated polyethersulfone mixed-matrix membranes as methanol-barrier electrolytes for DMFCs

Chitosan (CS)-polyvinyl alcohol (PVA) cross-linked with sulfosuccinic acid (SSA) and modified with sulfonated polyethersulfone (SPES) mixed-matrix membranes are reported for their application in direct methanol fuel cells (DMFCs). Polyethersulfone (PES) is sulfonated by chlorosulfonic acid and factors affecting the sulfonation reaction, such as time and temperature, are studied. The ion-exchange capacity, degree of sulfonation, sorption, and proton conductivity for the mixed-matrix membranes are investigated. The mixed-matrix membranes are also characterised for their mechanical and thermal properties. The methanol-crossover flux across the mixed-matrix membranes is studied by measuring the mass balance of methanol using the density meter. The methanol cross-over for these membranes is found to be about 33% lower in relation to Nafion-117 membrane. The DMFC employing CS-PVA-SPES mixed-matrix membrane with an optimum content of 25 wt % SPES delivers a peak power-density of 5.5 mW cm-2 at a load current-density of 25 mA cm-2 while operating at 70 degrees C. (C) 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012

Familial Diarrhea Syndrome Caused by an Activating GUCY2C Mutation

BACKGROUND Familial diarrhea disorders are, in most cases, severe and caused by recessive mutations. We describe the cause of a novel dominant disease in 32 members of a Norwegian family. The affected members have chronic diarrhea that is of early onset, is relatively mild, and is associated with increased susceptibility to inflammatory bowel disease, small-bowel obstruction, and esophagitis. METHODS We used linkage analysis, based on arrays with single-nucleotide polymorphisms, to identify a candidate region on chromosome 12 and then sequenced GUCY2C, encoding guanylate cyclase C (GC-C), an intestinal receptor for bacterial heat-stable enterotoxins. We performed exome sequencing of the entire candidate region from three affected family members, to exclude the possibility that mutations in genes other than GUCY2C could cause or contribute to susceptibility to the disease. We carried out functional studies of mutant GC-C using HEK293T cells. RESULTS We identified a heterozygous missense mutation (c.2519G -> T) in GUCY2C in all affected family members and observed no other rare variants in the exons of genes in the candidate region. Exposure of the mutant receptor to its ligands resulted in markedly increased production of cyclic guanosine monophosphate (cGMP). This may cause hyperactivation of the cystic fibrosis transmembrane regulator (CFTR), leading to increased chloride and water secretion from the enterocytes, and may thus explain the chronic diarrhea in the affected family members. CONCLUSIONS Increased GC-C signaling disturbs normal bowel function and appears to have a proinflammatory effect, either through increased chloride secretion or additional effects of elevated cellular cGMP. Further investigation of the relevance of genetic variants affecting the GC-C-CFTR pathway to conditions such as Crohn's disease is warranted. (Funded by Helse Vest Western Norway Regional Health Authority] and the Department of Science and Technology, Government of India.)

Genetic analysis of an Indian family with members affected with Waardenburg syndrome and Duchenne muscular dystrophy

Purpose: Waardenburg syndrome (WS) is characterized by sensorineural hearing loss and pigmentation defects of the eye, skin, and hair. It is caused by mutations in one of the following genes: PAX3 (paired box 3), MITF (microphthalmia-associated transcription factor), EDNRB (endothelin receptor type B), EDN3 (endothelin 3), SNAI2 (snail homolog 2, Drosophila) and SOX10 (SRY-box containing gene 10). Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder caused by mutations in the DMD gene. The purpose of this study was to identify the genetic causes of WS and DMD in an Indian family with two patients: one affected with WS and DMD, and another one affected with only WS. Methods: Blood samples were collected from individuals for genomic DNA isolation. To determine the linkage of this family to the eight known WS loci, microsatellite markers were selected from the candidate regions and used to genotype the family. Exon-specific intronic primers for EDN3 were used to amplify and sequence DNA samples from affected individuals to detect mutations. A mutation in DMD was identified by multiplex PCR and multiplex ligation-dependent probe amplification method using exon-specific probes. Results: Pedigree analysis suggested segregation of WS as an autosomal recessive trait in the family. Haplotype analysis suggested linkage of the family to the WS4B (EDN3) locus. DNA sequencing identified a novel missense mutation p.T98M in EDN3. A deletion mutation was identified in DMD. Conclusions: This study reports a novel missense mutation in EDN3 and a deletion mutation in DMD in the same Indian family. The present study will be helpful in genetic diagnosis of this family and increases the mutation spectrum of EDN3.

Lacrimal Proline Rich 4 (LPRR4) Protein in the Tear Fluid Is a Potential Biomarker of Dry Eye Syndrome

Dry eye syndrome (DES) is a complex, multifactorial, immune-associated disorder of the tear and ocular surface. DES with a high prevalence world over needs identification of potential biomarkers so as to understand not only the disease mechanism but also to identify drug targets. In this study we looked for differentially expressed proteins in tear samples of DES to arrive at characteristic biomarkers. As part of a prospective case-control study, tear specimen were collected using Schirmer strips from 129 dry eye cases and 73 age matched controls. 2D electrophoresis (2DE) and Differential gel electrophoresis (DIGE) was done to identify differentially expressed proteins. One of the differentially expressed protein in DES is lacrimal proline rich 4 protein (LPRR4). LPRR4 protein expression was quantified by enzyme immune sorbent assay (ELISA). LPRR4 was down regulated significantly in all types of dry eye cases, correlating with the disease severity as measured by clinical investigations. Further characterization of the protein is required to assess its therapeutic potential in DES.

Stiffness- and wettability-dependent myoblast cell compatibility of transparent poly(vinyl alcohol) hydrogels

This study reports the in vitro compatibility of muscle cells (C2C12 mouse myoblast cell line) with the transparent poly(vinyl alcohol) (PVA) hydrogels and the results are explained on the basis of surface wettability, crystallinity, and nanoscale elastic stiffness property. Nanoindentation was carried out with a maximum load of 100 mu N for all the hydrogel compositions and the properties such as elastic stiffness, hardness and total work done during indentation were computed. The difference in cell viability as well as adhesion of cultured myoblast cells on the investigated hydrogel substrates were discussed in reference to the difference in the nanoscale elastic properties, crystallinity, and surface wettability. An important result has been that both elastic stiffness and surface wettability synergistically influence myoblast viability/adhesion on PVA hydrogels. (c) 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.