The Effects of Charged Amino Acid Side-Chain Length on Diagonal Cross-Strand Interactions between Carboxylate- and Ammonium-Containing Residues in a ß-Hairpin.

The ß-sheet is one of the common protein secondary structures, and the aberrant aggregation of ß-sheets is implicated in various neurodegenerative diseases. Cross-strand interactions are an important determinant of ß-sheet stability. Accordingly, both diagonal and lateral cross-strand interactions have been studied. Surprisingly, diagonal cross-strand ion-pairing interactions have yet to be investigated. Herein, we present a systematic study on the effects of charged amino acid side-chain length on a diagonal ion-pairing interaction between carboxylate- and ammonium-containing residues in a ß-hairpin. To this end, 2D-NMR was used to investigate the conformation of the peptides. The fraction folded population and the folding free energy were derived from the chemical shift data. The fraction folded population for these peptides with potential diagonal ion pairs was mostly lower compared to the corresponding peptide with a potential lateral ion pair. The diagonal ion-pairing interaction energy was derived using double mutant cycle analysis. The Asp2-Dab9 (Asp: one methylene; Dab: two methylenes) interaction was the most stabilizing (-0.79 ± 0.14 kcal/mol), most likely representing an optimal balance between the entropic penalty to enable the ion-pairing interaction and the number of side-chain conformations that can accommodate the interaction. These results should be useful for designing ß-sheet containing molecular entities for various applications.

Crystal structure of dihydropyrimidinase in complex with anticancer drug 5-fluorouracil.

Dihydropyrimidinase (DHPase) catalyzes the reversible cyclization of dihydrouracil to N-carbamoyl-ß-alanine in the second step of the pyrimidine degradation pathway. Whether 5-fluorouracil (5-FU), the best-known fluoropyrimidine that is used to target the enzyme thymidylate synthase for anticancer therapy, can bind to DHPase remains unknown. In this study, we found that 5-FU can form a stable complex with Pseudomonas aeruginosa DHPase (PaDHPase). The crystal structure of PaDHPase complexed with 5-FU was determined at 1.76 Šresolution (PDB entry 6KLK). Various interactions between 5-FU and PaDHPase were examined. Six residues, namely, His61, Tyr155, Asp316, Cys318, Ser289 and Asn337, of PaDHPase were involved in 5-FU binding. Except for Cys318, these residues are also known as the substrate-binding sites of DHPase. 5-FU interacts with the main chains of residues Ser289 (3.0 Å) and Asn337 (3.2 Å) and the side chains of residues Tyr155 (2.8 Å) and Cys318 (2.9 Å). Mutation at either Tyr155 or Cys318 of PaDHPase caused a low 5-FU binding activity of PaDHPase. This structure and the binding mode provided molecular insights into how the dimetal center in DHPase undergoes a conformational change during 5-FU binding. Further research can directly focus on revisiting the role of DHPase in anticancer therapy.

Plasmon resonance scattering at perovskite CH3NH3PbI3 coated single gold nanoparticles: evidence for electron transfer.

We demonstrate the electron transfer between gold nanoparticles and perovskite CH3NH3PbI3 at a single nanoparticle level by plasmon resonance Rayleigh scattering spectroscopy. Different mass concentrations of CH3NH3PbI3 show different formations of crystal grains on the gold nanoparticles, which led to different degrees of red-shift.

[Emotional problems and parenting locus of control in children with anxiety disorders].

OBJECTIVE: To carry out a preliminary study on the emotional problems and parenting locus of control among children with anxiety disorders. METHODS: A total of 110 children with simple anxiety disorders (AD group) and 113 normal children (control group) from September to December 2005 were enrolled. Children were asked to complete the Depression Self-Rating Scale for Children (DSRSC), the Screen for Child Anxiety Related Emotional Disorders (SCARED), and the Parenting Locus of Control Scale (PLOC).A total of 197 valid scales were returned. RESULTS: The scores of somatic, generalized anxiety, separation anxiety, social phobia anxiety, school phobia anxiety, total anxiety, and total depression were all higher in the AD group than in the control group (P<0.01). The score of "education effects" for parents was significantly higher in the AD group than that in the control group (P<0.01). CONCLUSIONS: Children with anxiety disorders tend to have more emotional problems and poorer parental education effects.

[Prevalence of psychiatric disorders in primary and middle school students in Hunan Province].

OBJECTIVE: To investigate the prevalence of psychiatric disorders in a representative sample of primary and middle school students in Hunan Province. METHODS: A total of 9 495 children aged 5-17 years from Hunan urban and rural schools were enrolled by a cluster sampling and a two-phase design. The students' psychiatric status was assessed using the Investigation Screening Inventory for Child Mental Disorder and a semi-structured interview designed based on the DSM-IV criteria. RESULTS: The overall prevalence of psychiatric disorders was 16.22%. Attention-deficit and disruptive behavior disorders were the commonest in the diagnostic categories of psychiatric disorders (10.69%). Regarding specific disorders, the most prevalent was attention-deficit/hyperactivity disorder (5.95%). Psychiatric disorders were more prevalent in boys than in girls (20.49% vs 11.16%; p<0.01). The prevalence of attention-deficit and disruptive behavior disorders in boys was higher than in girls (14.76% vs 5.87%; p<0.01). The prevalence of psychiatric disorders in middle school students (12-17 years) was significantly higher than in primary students (5-11 years) (18.38% vs 14.64%; p<0.01). There were no significant differences in the prevalence of psychiatric disorders between urban and rural students. CONCLUSIONS: Psychiatric disorders are common among primary and middle school students in Hunan Province. The prevalence of this disorder in boys is higher than in girls. The middle school students have higher prevalence than primary students.

[A case-control study on family environment related factors in attention deficit hyperactivity disorder with anxiety disorder].

OBJECTIVE: To study the family rearing pattern of attention deficit hyperactivity disorder (ADHD) with or without anxiety disorder and to explore its risk factors. METHODS: 9495 children and their parents were sampled at random in Hunan province, using two-stage investigation. Those who were diagnosed ADHD and the normal control filled out Egna Minnen av Barndoms Uppfostran and family adaptability and cohesion scale by themselves. RESULTS: The comparison of factors as: actual family cohesion, parents' punishments, rejection, mother's excessive protection, intervention and father's excessive protection were significantly different between ADHD with or without anxiety disorder and normal children (P < 0.05). The comparison of parents' punishments, rejection, excessive protection and intervention were obviously different between ADHD with anxiety disorder and simple ADHD (P < 0.05). Mother's rejection was the influencing factor of simple ADHD, with OR as 1.122. Ideal family cohesion, mother's rejection and father's punishments were the influencing factors of ADHD with anxiety disorder, with OR as 0.966, 1.215 and 1.089 respectively. CONCLUSION: There were some problems in the parental rearing pattern of ADHD with or without anxiety disorder. Mother's rejection, father's punishments and ideal family cohesion were suggested to be correlated with ADHD and anxiety disorder.