Phonological Factors Affecting L1 Phonetic Realization of Proficient Polish Users of English

Acoustic phonetic studies examine the L1 of Polish speakers with professional level proficiency in English. The studies include two tasks, a production task carried out entirely in Polish and a phonetic code-switching task in which speakers insert target Polish words or phrases into an English carrier. Additionally, two phonetic parameters are studied: the oft-investigated VOT, as well as glottalization vs. sandhi linking of word-initial vowels. In monolingual Polish mode, L2 interference was observed for the VOT parameter, but not for sandhi linking. It is suggested that this discrepancy may be related to the differing phonological status of the two phonetic parameters. In the code-switching tasks, VOTs were on the whole more English-like than in monolingual mode, but this appeared to be a matter of individual performance. An increase in the rate of sandhi linking in the code-switches, except for the case of one speaker, appeared to be a function of accelerated production of L1 target items

General and Specific Promotion of Flagellar Assembly by a Flagellar Nucleoside Diphosphate Kinase

Nucleoside diphosphate kinases (NDKs) play a central role in diverse cellular processes using the canonical NDK activity or alternative mechanisms that remain poorly defined. Our study of dimeric NDK5 in a flagellar motility control complex, the radial spoke (RS), has revealed new modalities. The flagella in Chlamydomonas ndk5 mutant were paralyzed, albeit only deficient in three RS subunits. RS morphology appeared severely changed in averaged cryo-electron tomograms, suggesting that NDK5 is crucial for the intact spokehead formation as well as RS structural stability. Intriguingly, ndk5’s flagella were also short, resembling those of an allelic spoke-less mutant. All ndk5’s phenotypes were rescued by expressions of NDK5 or a mutated NDK5 lacking the canonical kinase activity. Importantly, the mutated NDK5 that appeared fully functional in ndk5 cells elicited a dominant-negative effect in wild-type cells, causing paralyzed short flagella with hypophosphorylated, less abundant, but intact RSs, and accumulated hypophosphorylated NDK5 in the cell body. We propose that NDK5 dimer is an RS structural subunit with an additional mechanism that uses cross-talk between the two NDK monomers to accelerate phosphorylation-related assembly of RSs and entire flagella

Food and feed safety aspects of cisgenic crop plant varieties

This report presents the results of the discussions that identified food and feed safety aspects of cisgenic plant varieties in comparison to conventional varieties on the one hand and transgenic plant varieties on the other hand. It was concluded that on the basis of the general characteristics of cisgenic plant varieties, there is, from a food and feed safety perspective, no scientific basis for a general reduction of requirements for cisgenic crop plant varieties

Tricho-rhino-phalangeal syndrome type I as a “cis-ruption disorder” caused by a translocation

Tricho-rhino-phalangeal syndrome type I (TRPS I; OMIM 190350) and type II (OMIM 150230) are two forms of the rare autosomal-dominant TRP malformation syndrome localised in 8q23.3–24.1. TRPS I is generally caused by point mutations or deletions of the TRPS1 gene, whereas type II is characterised by the presence of multiple cartilage exostoses (EXT) and deletions comprising the TRPS1 and EXT1 genes. In the present study, we have mapped and sequenced the breakpoints of a balanced familial translocation [t(8;13)(q23.3;q21.32)] segregating with mild TRPS I and analysed the TRPS1 candidate gene. The proband, in addition to features compatible with TRPS I, also presented developmental delay and severe mental retardation. The pathogenic chromosome 8 breakpoint was localised within a transposon type I element at 116.768 Mb, 87 kb from the TRPS1 5′ end. The breakpoint on chromosome 13 was localised within a gene-poor region at 65.101 Mb, and the nearest gene, 1.5 Mb distal from the breakpoint, is protocadherin 9 (PCDH9). Analysis of the three affected relatives by the 33K tiling BAC array and of the proband by 2.7-M high-resolution oligonucleotide array painting did not reveal additional genomic variation. Furthermore, mutation screening of the TRPS1 also did not reveal any alteration. Finally, expression studies of TRPS1 performed from LCLs indicate that inter-individual variation is higher than the expected gene expression changes induced by the translocation. Although the reason underlying the severe mental retardation observed in the proband is unknown, the available data indicate that this is not associated with the translocation. As far as we know, this is the first reported case of position effect or “cis-ruption” causing TRPS I. Finally, further studies are necessary to unveil the molecular pathogenic mechanisms of this “cis-ruption disorder” triggered by chromosometranslocation

A rare case of Beckwith–Wiedemann syndrome caused by a de novo microduplication at 11p15.5 of paternal origin

Beckwith–Wiedemann syndrome (BWS) is a disorder of growth regulation exhibiting somatic overgrowth and predisposition to paediatric tumours. With an incidence estimated at 1 in 13,700, it is caused by various epigenetic and/or genetic alterations associated with disturbances within two different 11p15 domains that are controlled by distinct imprinting control regions (ICR), ICR1 and ICR2. The majority of patients have abnormalities within ICR2 presenting hypomethylation, while less frequent aetiologies include mosaic paternal 11p uniparental disomy (11patUPD), maternally inherited mutations of the CDKN1C gene, and hypermethylation of ICR1. A few patients have cytogenetic abnormalities involving 11p15.5. Since the subgroups are associated with different recurrence risks, the identification of the molecular cause of BWS is particularly important for the follow-up of the patient and the genetic counselling of both the patient and the family. Here, we report a 13-year-old girl with clinical diagnosis of BWS presenting macrosomia, umbilical hernia, kidney abnormalities, hydramnius, prematurity, typical face, advanced bone age, moderate developmental delay, prominent occiput and forehead, round face, epicanthus, short nasal bridge, and microretrognathia. Cytogenetic analysis with highresolution banding showed an apparently normal karyotype. Microsatellite analysis and methylationspecific multiplex ligation-dependent probe amplification revealed a de novo microduplication at 11p15.5 of paternal origin. Duplication has a minimum size of 600 kb, covering only ICR1, not affecting ICR2. This sporadic case with a de novo duplication without other chromosomal abnormalities makes genotype–phenotype correlation difficult. As far as we know, this is one of the smallest duplications associated with BWS and is consistent with the independent regulation of ICR1 and ICR2. Our patient presented moderate developmental delay and craniofacial features typical of 11p15 duplication. Future studies exploiting this subtle 11p15.5 rearrangement will provide an important tool to further dissecting the genomics of BWS region and the pathogenesis of this imprinting disorder

Circumventing embryonic lethality with Lcmt1 deficiency: generation of hypomorphic Lcmt1 mice with reduced protein phosphatase 2A methyltransferase expression and defects in insulin signaling.

Protein phosphatase 2A (PP2A), the major serine/threonine phosphatase in eukaryotic cells, is a heterotrimeric protein composed of structural, catalytic, and targeting subunits. PP2A assembly is governed by a variety of mechanisms, one of which is carboxyl-terminal methylation of the catalytic subunit by the leucine carboxyl methyltransferase LCMT1. PP2A is nearly stoichiometrically methylated in the cytosol, and although some PP2A targeting subunits bind independently of methylation, this modification is required for the binding of others. To examine the role of this methylation reaction in mammalian tissues, we generated a mouse harboring a gene-trap cassette within intron 1 of Lcmt1. Due to splicing around the insertion, Lcmt1 transcript and LCMT1 protein levels were reduced but not eliminated. LCMT1 activity and methylation of PP2A were reduced in a coordinate fashion, suggesting that LCMT1 is the only PP2A methyltransferase. These mice exhibited an insulin-resistance phenotype, indicating a role for this methyltransferase in signaling in insulin-sensitive tissues. Tissues from these animals will be vital for the in vivo identification of methylation-sensitive substrates of PP2A and how they respond to differing physiological conditions

The Toxoplasma gondii active serine hydrolase 4 regulates parasite division and intravacuolar parasite architecture

ABSTRACT Hydrolase are enzymes that regulate diverse biological processes, including posttranslational protein modifications. Recent work identified four active serine hydrolases (ASHs) in Toxoplasma gondii as candidate depalmitoylases. However, only TgPPT1 (ASH1) has been confirmed to remove palmitate from proteins. ASH4 (TgME49_264290) was reported to be refractory to genetic disruption. We demonstrate that recombinant ASH4 is an esterase that processes short acyl esters but not palmitoyl thioesters. Genetic disruption of ASH4 causes defects in cell division and premature scission of parasites from residual bodies. These defects lead to the presence of vacuoles with a disordered intravacuolar architecture, with parasites arranged in pairs around multiple residual bodies. Importantly, we found that the deletion of ASH4 correlates with a defect in radial dispersion from host cells after egress. This defect in dispersion of parasites is a general phenomenon that is observed for disordered vacuoles that occur at low frequency in wild-type parasites, suggesting a possible general link between intravacuolar organization and dispersion after egress. IMPORTANCE This work defines the function of an enzyme in the obligate intracellular parasite Toxoplasma gondii. We show that this previously uncharacterized enzyme is critical for aspects of cellular division by the parasite and that loss of this enzyme leads to parasites with cell division defects and which also are disorganized inside their vacuoles. This leads to defects in the ability of the parasite to disseminate from the site of an infection and may have a significant impact on the parasite's overall infectivity of a host organism

Familial imbalance in 16p13.11 leads to a dosage compensation rearrangement in an unaffected carrier

Background: We and others have previously reported that familial cytogenetic studies in apparently de novo genomic imbalances may reveal complex or uncommon inheritance mechanisms. Methods: A familial, combined genomic and cytogenetic approach was systematically applied to the parents of all patients with unbalanced genome copy number changes. Results: Discordant array-CGH and FISH results in the mother of a child with a prenatally detected 16p13.11 interstitial microduplication disclosed a balanced uncommon rearrangement in this chromosomal region. Further dosage and haplotype familial studies revealed that both the maternal grandfather and uncle had also the same 16p duplication as the proband. Genomic compensation observed in the mother probably occurred as a consequence of interchromosomal postzygotic nonallelic homologous recombination. Conclusions: We emphasize that such a dualistic strategy is essential for the full characterization of genomic rearrangements as well as for appropriate genetic counselingFISH and aCGH materials were supported by grant 08/PI1207 from Fondo de Investigaciones Sanitarias (FIS) and research project ENDOSCREEN (S2011/BMD-2396) from Comunidad de Madri