Structure-function analysis of pneumococcal DprA protein reveals that dimerization is crucial for loading RecA recombinase onto DNA during transformation

Transformation promotes genome plasticity in bacteria via RecA-driven homologous recombination. In the Gram-positive human pathogen Streptococcus pneumoniae, the transformasome a multiprotein complex, internalizes, protects, and processes transforming DNA to generate chromosomal recombinants. Double-stranded DNA is internalized as single strands, onto which the transformation-dedicated DNA processing protein A (DprA) ensures the loading of RecA to form presynaptic filaments. We report that the structure of DprA consists of the association of a sterile alpha motif domain and a Rossmann fold and that DprA forms tail-to-tail dimers. The isolation of DprA self-interaction mutants revealed that dimerization is crucial for the formation of nucleocomplexes in vitro and for genetic transformation. Residues important for DprA-RecA interaction also were identified and mutated, establishing this interaction as equally important for transformation. Positioning of key interaction residues on the DprA structure revealed an overlap of DprA-DprA and DprA-RecA interaction surfaces. We propose a model in which RecA interaction promotes rearrangement or disruption of the DprA dimer, enabling the subsequent nucleation of RecA and its polymerization onto ssDNA.     

Comparing the rates of tantrum behavior in children with ASD and ADHD as well as children with comorbid ASD and ADHD diagnoses

The current study investigated the presentation of tantrum behaviors in individuals with an autism spectrum disorder (ASD) diagnosis with and without a comorbid diagnosis of attention deficit hyperactivity disorder (ADHD). Participants included 347 children ranging in age from 2 to 18 years old. Diagnostic categories in the current study were based upon clinical diagnosis. The severity of ASD symptomology was measured by the Autism Spectrum Disorder-Diagnostic Child Version (ASD-DC). The presence and severity of tantrum behaviors were measured by the Tantrum behavior subscale of the Autism Spectrum Disorders-Comorbidity for Children (ASD-CC). The influence of diagnosis and ASD symptomology had upon the expression of tantrum behaviors were examined, controlling for participant age. Initial analysis revealed significant differences in the expression of tantrum behavior between the ASD, ADHD and ASD/ADHD groups. However, age did not have a significant influence on the exhibition of tantrum behaviors. Follow-up analyses demonstrated that those individuals diagnosed with an ASD and a comorbid ADHD diagnosis exhibited significantly greater tantrum behavior. Post hoc analyses identified a significant positive correlation between increases in ASD symptomology and elevations of the severity of tantrum behaviors for each group. The observed correlation for the ADHD group was found to be significantly greater than the ASD group. Correlations for individual item responses of the ASD-CC were also computed and discussed for each diagnostic group.     

Moderating effects of challenging behaviors and communication deficits on social skills in children diagnosed with an autism spectrum disorder

One-hundred nine children 3–16 years of age diagnosed with Autistic Disorder, Pervasive Developmental Disorder Not Otherwise Specified, or Asperger's Syndrome were studied. Children resided in six states in the United States. Using moderation analysis via multiple regression, verbal communication and challenging behaviors and how they interact with social skills were examined. Children and adolescents exhibiting fewer challenging behaviors and presenting with better verbal communication skills had the greatest strengths in social skills. Furthermore, challenging behaviors adversely affected social skills more than verbal communication skills. Thus, regardless of verbal communication level, children with low levels of challenging behaviors exhibited greater social skills. Clinical implications of these findings and directions for future research are discussed.     

A case of severe osteomalacia secondary to phosphate diabetes in a renal transplant recipient

Transient hypophosphatemia is frequently observed during the first months after renal transplantation and is usually asymptomatic. Phosphate diabetes is defined as inadequate tubular phosphorus reabsorption leading to persistent renal phosphorus wasting, which is an important but overlooked cause of osteodystrophy in the post-renal transplantation population. We report the case of a 58-year-old male who presented with severe multiple osteoarticular pains within 3 months after successful first kidney transplantation. Bone disease was attributed initially to mild hyperparathyroidism secondary to vitamin D deficiency. Despite the correction of the hyperparathyroidism, the withdrawal of corticosteroids, and the reduction of immunosuppressive treatment to tacrolimus-based monotherapy, the osteoarticular pains persisted. Skeletal investigations at month 9 post-transplantation demonstrated a significant bone mineral density loss associated with osteomalacia and osteoporosis on the bone biopsy. Laboratory data showed persistent hypophosphatemia, and phosphate diabetes was then diagnosed explaining the post-transplant bone disease. A tacrolimus-induced renal tubular disorder was suspected to contribute to the excessive renal phosphorus wasting. The replacement of tacrolimus by sirolimus, in addition to oral phosphorus and vitamin D supplementations, led to the disappearance of pains, the normalization of urinary and plasma phosphate level, and a significant improvement of bone mineralization.     

The moderating effects of intellectual development on core symptoms of autism and PDD-NOS in toddlers and infants

Little research has been conducted on whether deficits in developmental functioning affect the range of core symptoms for autism spectrum disorders (ASD). This study represents a first attempt to determine whether developmental level has an effect on the expression of ASD symptoms in infants and toddlers. Eight hundred and fifty-three infants were evaluated with respect to the nature and extent of their ASD symptoms and developmental functioning. Young children with autism displayed a higher number of symptoms than those with PDD-NOS on all three domains of impairment (social, communication, repetitive behaviors). As expected, children without an ASD evinced far fewer symptoms than both these groups. Developmental level was not found to be a moderator for expression of ASD symptoms for the entire sample, or individual diagnostic groups. Higher developmental level was associated with lower severity of evinced ASD symptoms in the sample.     

Questions About Behavioral Function (QABF): Adaptation and validation of the Spanish version

People with intellectual disabilities (ID) often engage in problem behaviors, such as verbal or physical aggression, property destruction, or self-injury. These behaviors become a challenge for the families and for professionals. Functional behavioral assessment (FBA) is a method used to identify variables that influence or maintain challenging behaviors (CB) and aid in the development of intervention plans. Two major concerns of FBA are that it is time-consuming and requires specialized professionals to interpret data from the natural or experimental environment. Therefore, indirect FBA methods can be used as an alternative. An instrument with excellent psychometric properties that aims to identify the function of behavior is the Questions About Behavioral Function (QABF). This study presents the adaptation of the QABF in Spain. Data from 300 participants with ID and 328 behavioral problems were obtained. An exploratory factor analysis was conducted to identify the components of the QABF, and the test–retest reliability was assessed to evaluate the stability of the QABF over time.     

Food selectivity in children with and without an autism spectrum disorder: Investigation of diagnosis and age

Feeding problems are common in children with autism spectrum disorders (ASDs), with food selectivity being the most frequently reported. Selectivity based on type and/or texture of food is of concern in those with ASD. Variations in symptom presentation of food selectivity in children with different autism spectrum diagnoses across childhood have not often been investigated. Parent-report of food selectivity was examined in 525 children age 2–18 years diagnosed with autistic disorder, PDD-NOS, Asperger's disorder, atypical development, and typical development using information garnered from the Autism Spectrum Disorder-Comorbidity for Children (ASD-CC), a tool to assess emotional issues and comorbid psychopathology. Individuals with an ASD were reported to have significantly more food selectivity than both the atypically developing group and the typically developing group. In addition, the ASD groups, when looked at together, showed a decrease in food selectivity across childhood with significant decrease in the Asperger's disorder group.