Validation of a Brief Prosody Rating Scale for Children with Autism Spectrum Disorder

Differences in the speech prosody, or melody of speech, of persons with autism spectrum disorder (ASD) have long been noted by researchers. Yet, despite many studies, researchers have not identified a universal description of speech prosody in ASD. It may be flat or monotonous, not different from typical, or overly variable. However, atypical speech prosody can immediately set someone apart from their peers. This distinction could negatively social, academic, and vocational interactions. For those persons with ASD whose speech prosody is different from typical and interferes with daily functioning, valid, reliable, and efficient assessments of speech prosody are needed. Currently, there are only three validated assessments for speech prosody specific to ASD and none of them are simultaneously valid, reliable, and efficient. The purpose of this study was to design, validate, and establish sufficient reliability of a one-item, 7-point continuous rating scale for screening the speech prosody of children with ASD. Additionally, I investigated whether a brief, online training would improve reliability. The rating scale ranged from 1 (monotonous) to 7 (overly variable). Thirty-five 30-second audio clips from previous studies were chosen from children with ASD and neurotypical development. Three expert speech-language pathologists (SLPs) selected clips for the end and mid points of the scale and developed gold standard ratings. A total of 42 ASHA-certified SLPs with experience in treating children with ASD rated 20 of the audio clips at two time points. Twenty of the SLPs participated the online training prior to rating. Analyses were conducted using linear mixed-effects modeling, which were built using a research-question, theory-based modeling approach. Results indicated moderate levels of reliability, except for intra-rater reliability in the trained group, which was good (ICC = 0.76). The results also partially supported the validity of the scale; however, this prosody rating scale requires further study and development before wide use

The peach twig borer, Anarsia lineatella Zell. (Lepidoptera: Gelechiidae), in the Okanagan and Similkameen valleys of British Columbia

n/

Glycosylation of hyperthermostable designer cellulosome components yields enhanced stability and cellulose hydrolysis

Biomass deconstruction remains integral for enabling second‐generation biofuel production at scale. However, several steps necessary to achieve significant solubilization of biomass, notably harsh pretreatment conditions, impose economic barriers to commercialization. By employing hyperthermostable cellulase machinery, biomass deconstruction can be made more efficient, leading to milder pretreatment conditions and ultimately lower production costs. The hyperthermophilic bacterium Caldicellulosiruptor bescii produces extremely active hyperthermostable cellulases, including the hyperactive multifunctional cellulase CbCel9A/Cel48A. Recombinant CbCel9A/Cel48A components have been previously produced in Escherichia coli and integrated into synthetic hyperthermophilic designer cellulosome complexes. Since then, glycosylation has been shown to be vital for the high activity and stability of CbCel9A/Cel48A. Here, we studied the impact of glycosylation on a hyperthermostable designer cellulosome system in which two of the cellulosomal components, the scaffoldin and the GH9 domain of CbCel9A/Cel48A, were glycosylated as a consequence of employing Ca. bescii as an expression host. Inclusion of the glycosylated components yielded an active cellulosome system that exhibited long‐term stability at 75 °C. The resulting glycosylated designer cellulosomes showed significantly greater synergistic activity compared to the enzymatic components alone, as well as higher thermostability than the analogous nonglycosylated designer cellulosomes. These results indicate that glycosylation can be used as an essential engineering tool to improve the properties of designer cellulosomes. Additionally, Ca. bescii was shown to be an attractive candidate for production of glycosylated designer cellulosome components, which may further promote the viability of this bacterium both as a cellulase expression host and as a potential consolidated bioprocessing platform organism

Drug-efflux and target-site gene expression patterns in Haemonchus contortus larvae able to survive increasing concentrations of levamisole in vitro

While there is some evidence that changes in nicotinic acetylcholine receptor (nAChR) subunits confer resistance to levamisole in gastrointestinal helminth parasites, the exact nature of the resistance mechanism(s) is unclear. We utilised the presence of a resistant fraction within the Wallangra 2003 isolate of Haemonchus contortus larvae in order to subdivide the population into three subpopulations of larvae able to survive increasing concentrations of the drug. We then measured gene expression levels in the subpopulations and the larval population as a whole, focusing on genes encoding the subunit components of levamisole-sensitive receptors, genes encoding ancillary proteins involved in receptor assembly, and P-glycoprotein (P-gp) genes. The subpopulation surviving the lowest levamisole concentration showed increases of 1.5- to 3-fold in a number of P-gp genes (Hco-pgp-3, -4, -10, and -14) alongside unchanged receptor genes, compared to the whole Wallangra larval population. On the other hand, the subpopulation surviving the intermediate levamisole concentration showed an increase in only a single P-gp (Hco-pgp-14), alongside decreases in some receptor subunit (Hco-unc-63a) and ancillary protein genes (Hco-unc-50, Hco-ric-3.1 and 3.1). The subpopulation surviving the highest levamisole concentration showed further decreases in receptor subunit genes (Hco-unc-63a and Hco-unc-29 paralogs) as well as genes involved in receptor assembly (Hco-unc-74, Hco-unc-50, Hco-ric-3.1 and 3.1), alongside no increased P-gp gene levels. This suggests a biphasic pattern of drug resistance in the larvae of this worm isolate, in which a non-specific P-gp-mediated mechanism confers low levels of resistance, while higher level resistance is due to altered receptor subunit composition as a result of changes in both subunit composition and in the levels of proteins involved in receptor assembly

“I write my letters at school, so I’m ready right?” Low-income Latino children’s transition from preschool to kindergarten

The transition to kindergarten is a significant period in children’s education that initiates the development of skills that promote future academic success. Studies indicate that Latino children in the United States are disproportionately disadvantaged during this critical period of development, and are most likely to fall below the recommended level of kindergarten readiness. Researchers report that Latina mothers often have different beliefs and perceptions of school readiness and parental involvement, but little is known about the preparatory practices of low- income suburban Latina mothers before children enter kindergarten. This study used qualitative interviews to better understand the factors that influence Latino children’s kindergarten readiness and how low-income Latina mothers (N = 17) engage in their children’s educational development as they transition to kindergarten. Latina mothers reported understanding kindergarten readiness in terms of nominal knowledge and emergent literacy skills. When asked about parental involvement practices, mothers reported home-based involvement focusing on socialization rather than school-based involvement focusing on academics. The mothers in this study also reported being actively involved in their children’s kindergarten preparation, engaging in various activities that promote children’s readiness. Barriers to parental involvement were also noted, and included language barriers and busy work schedules. These findings contribute to our understanding of school readiness practices, and parental involvement within low-income Latino families during the transition from preschool to kindergarten.USDA Institute of Food and Agriculture Hatch Project 793-357 [accession number: 1007545]Ope

A generalized conformational energy function of DNA derived from molecular dynamics simulations

Proteins recognize DNA sequences by two different mechanisms. The first is direct readout, in which recognition is mediated by direct interactions between the protein and the DNA bases. The second is indirect readout, which is caused by the dependence of conformation and the deformability of the DNA structure on the sequence. Various energy functions have been proposed to evaluate the contribution of indirect readout to the free-energy changes in complex formations. We developed a new generalized energy function to estimate the dependence of the deformability of DNA on the sequence. This function was derived from molecular dynamics simulations previously conducted on B-DNA dodecamers, each of which had one possible tetramer sequence embedded at its center. By taking the logarithm of the probability distribution function (PDF) for the base-step parameters of the central base-pair step of the tetramer, its ability to distinguish the native sequence from random ones was superior to that with the previous method that approximated the energy function in harmonic form. From a comparison of the energy profiles calculated with these two methods, we found that the harmonic approximation caused significant errors in the conformational energies of the tetramers that adopted multiple stable conformations

Nitroalkanes as Versatile Nucleophiles for Enzymatic Synthesis of Noncanonical Amino Acids

C–C bond-forming reactions often require nucleophilic carbon species rarely compatible with aqueous reaction media, thus restricting their appearance in biocatalysis. Here we report the use of nitroalkanes as a structurally versatile class of nucleophilic substrates for C–C bond formation catalyzed by variants of the β-subunit of tryptophan synthase (TrpB). The enzymes accept a wide range of nitroalkanes to form noncanonical amino acids, where the nitro group can serve as a handle for further modification. Using nitroalkane nucleophiles greatly expands the scope of compounds made by TrpB variants and establishes nitroalkanes as a valuable substrate class for biocatalytic C–C bond formation

Glycosylation of hyperthermostable designer cellulosome components yields enhanced stability and cellulose hydrolysis

Biomass deconstruction remains integral for enabling second‐generation biofuel production at scale. However, several steps necessary to achieve significant solubilization of biomass, notably harsh pretreatment conditions, impose economic barriers to commercialization. By employing hyperthermostable cellulase machinery, biomass deconstruction can be made more efficient, leading to milder pretreatment conditions and ultimately lower production costs. The hyperthermophilic bacterium Caldicellulosiruptor bescii produces extremely active hyperthermostable cellulases, including the hyperactive multifunctional cellulase CbCel9A/Cel48A. Recombinant CbCel9A/Cel48A components have been previously produced in Escherichia coli and integrated into synthetic hyperthermophilic designer cellulosome complexes. Since then, glycosylation has been shown to be vital for the high activity and stability of CbCel9A/Cel48A. Here, we studied the impact of glycosylation on a hyperthermostable designer cellulosome system in which two of the cellulosomal components, the scaffoldin and the GH9 domain of CbCel9A/Cel48A, were glycosylated as a consequence of employing Ca. bescii as an expression host. Inclusion of the glycosylated components yielded an active cellulosome system that exhibited long‐term stability at 75 °C. The resulting glycosylated designer cellulosomes showed significantly greater synergistic activity compared to the enzymatic components alone, as well as higher thermostability than the analogous nonglycosylated designer cellulosomes. These results indicate that glycosylation can be used as an essential engineering tool to improve the properties of designer cellulosomes. Additionally, Ca. bescii was shown to be an attractive candidate for production of glycosylated designer cellulosome components, which may further promote the viability of this bacterium both as a cellulase expression host and as a potential consolidated bioprocessing platform organism