Reinforcement of bio-apatite by zinc substitution in the incisor tooth of a prawn.

Various material-strengthening strategies have evolved in the cuticle and the feeding tools of arthropods. Of particular interest is the crustacean mandible, which is frequently reinforced with calcium phosphate, giving a minerology similar to that of human bones and teeth. We report here a biological strengthening method of apatite by Zn substitution, found in the incisor teeth of the freshwater prawn Macrobrachium rosenbergii. Nanoindentation measurements show a clear positive correlation between the Zn/Ca ratio and the stiffness and hardness of the composite. In the incisor, Zn-substituted apatite forms an internal vertical axis, extending from the sharp outer edges of the tooth to its basal segment. The substitution level in this zone (up to 40%) is very high compared with the levels achieved in synthetic ceramics (<20%). Finite element simulation suggests that the high-Zn axis acts as a unique internal load transfer element, directing stress from the biting cusps to the more compliant underlying layers. In light of the considerable research being invested in developing synthetic calcium phosphate derivatives for human bone and tooth grafts, the innovative mineralogy of the M. rosenbergii incisor may inspire beneficial biomimetic applications. STATEMENT OF SIGNIFICANCE: The controlled incorporation of impurities into biominerals is a widespread phenomenon in biomineralization that may pave the way to new classes of biomimetic materials. The present study reveals a biogenic mineral of zinc-substituted apatite found in the incisor teeth of a prawn. A clear correlation between zinc substitution level and stiffness and hardness, suggests that zinc substitution serves to mechanically reinforce the bioapatite. The spatial arrangement of the high-zinc apatite unveils a material-level adaptation strategy for tooth fortification, in which the rigid high-Zn structure servs as an internal load-transfer element that transmits the stress directly from the tooth's sharp cusps to the more compliant underlying layers.

Feasibility of investigating differential proteomic expression in depression: implications for biomarker development in mood disorders.

The objective of this study was to determine whether proteomic profiling in serum samples can be utilized in identifying and differentiating mood disorders. A consecutive sample of patients with a confirmed diagnosis of unipolar (UP n=52) or bipolar depression (BP-I n=46, BP-II n=49) and controls (n=141) were recruited. A 7.5-ml blood sample was drawn for proteomic multiplex profiling of 320 proteins utilizing the Myriad RBM Discovery Multi-Analyte Profiling platform. After correcting for multiple testing and adjusting for covariates, growth differentiation factor 15 (GDF-15), hemopexin (HPX), hepsin (HPN), matrix metalloproteinase-7 (MMP-7), retinol-binding protein 4 (RBP-4) and transthyretin (TTR) all showed statistically significant differences among groups. In a series of three post hoc analyses correcting for multiple testing, MMP-7 was significantly different in mood disorder (BP-I+BP-II+UP) vs controls, MMP-7, GDF-15, HPN were significantly different in bipolar cases (BP-I+BP-II) vs controls, and GDF-15, HPX, HPN, RBP-4 and TTR proteins were all significantly different in BP-I vs controls. Good diagnostic accuracy (ROC-AUC⩾0.8) was obtained most notably for GDF-15, RBP-4 and TTR when comparing BP-I vs controls. While based on a small sample not adjusted for medication state, this discovery sample with a conservative method of correction suggests feasibility in using proteomic panels to assist in identifying and distinguishing mood disorders, in particular bipolar I disorder. Replication studies for confirmation, consideration of state vs trait serial assays to delineate proteomic expression of bipolar depression vs previous mania, and utility studies to assess proteomic expression profiling as an advanced decision making tool or companion diagnostic are encouraged.

Psychiatry resident-led tutorials increase medical student knowledge and improve national board of medical examiners shelf exam scores.

OBJECTIVES: Psychiatry residents have tremendous potential as educators. The authors envisioned residents as small-group tutors, efficiently assessing and correcting knowledge deficits using cases with discussion prompts and teaching points. They empirically tested whether this improves knowledge acquisition. METHODS: Senior residents delivered eight tutorials during clerkship, which covered child and adolescent psychiatry, anxiety, mood, psychotic, cognitive, and substance use disorders. A 50-item multiple-choice quiz was administered at the beginning and end of clerkship. National Board of Medical Examiners (NBME) shelf exam scores from intervention year were compared to the 4 years prior to resident involvement. RESULTS: Mean score on the initial quiz was 34.5 ± 3.7 and 41.8 ± 3.5 on second attempt (p < 0.001). Mean score for NBME psychiatry subject exam during intervention year was 83.2 ± 8.9 and for the four prior years was 78.0 ± 9.3, which was significant (p = 0.002). CONCLUSIONS: Resident-led tutorials provide an effective means of increasing psychiatric knowledge and improving performance on NBME subject exams.

A 1q44 deletion, paternal UPD of chromosome 2 and a deletion due to a complex translocation detected in children with abnormal phenotypes using new SNP array technology.

Children with intellectual disability, dysmorphic features, malformations and/or growth abnormalities frequently display normal karyotypes. Recent studies have shown that genome-wide single nucleotide polymorphism (SNP) arrays can be effective in detecting abnormalities involving copy number variation (CNV), deletions, duplications and loss of heterozygosity (LOH) that routine cytogenetic tests fail to identify. Five patients with various degrees of intellectual disability and/or dysmorphic features and other malformations were whole-genome genotyped using the Human-1 Genotyping BeadChip--Exon-Centrix 100K SNP arrays (Illumina). All patients had undergone routine cytogenetic testing; four patients had normal karyotypes, while one patient had an apparently balanced complex translocation involving chromosomes 1q25, 1q32, 2q23, 7q22 and 16q24. We detected deletions on chromosome 1q44 and 13q31.1 in one patient, and LOH of the entire chromosome 2 in another patient, both with cytogenetically normal karyotypes. The patient with the complex translocation had a deletion on chromosome 7q22.2-22.3, which is in conjunction with one of the translocation breakpoints. Our findings provide further evidence of there being a critical region for the development of microcephaly and corpus callosum abnormalities in children with distal 1q deletions. We have also shown that apparently balanced complex translocations might not be balanced at the DNA level, and we report the fourth case of paternal uniparental disomy of chromosome 2. The results of this study suggest that it may be desirable to investigate idiopathic mental retardation using genome-wide SNP arrays, in conjunction with other cytogenetic and molecular techniques.

Gamma interferon production in response to homologous and heterologous strain antigens in mice chronically infected with Rickettsia tsutsugamushi.

The ability of antigen-responsive, thymus-derived lymphocytes to produce immune (gamma) interferon was investigated during the development and expression of cellular immunity to Rickettsia tsutsugamushi. C3H/HeDub mice infected subcutaneously with the Gilliam strain developed the ability to produce serum interferon in response to intravenously inoculated antigen which correlated with the development of resistance to intraperitoneal rechallenge. Antigen-responsive lymphocytes, measured by interferon production and proliferation, were first apparent in draining lymph node cells, but spleen cell responses were detectable relatively soon after the appearance of reactive lymph node cells. The peak spleen cell response was of a greater magnitude and was found to be relatively long-lived. Reactivity to heterologous strains of R. tsutsugamushi also developed after immunization and paralleled the homologous responses, although reactivity was greatest to homologous antigens. Responses to heterologous strains differed in magnitude and time of appearances; however, immune mice resisted challenge with all strains of R. tsutsugamushi tested.

Production of gamma interferon in mice immune to Rickettsia tsutsugamushi.

C3H/He mice immunized by subcutaneous infection with Rickettsia tsutsugamushi Gilliam were examined for the production of immune interferon after intravenous administration of irradiated strain Gilliam antigen, in supernatants of immune lymphocytes stimulated with specific antigen, and after a secondary challenge with viable rickettsiae. Mice administered various doses of irradiated whole-organism antigen 28 days after immunization showed circulating levels of interferon which peaked 4 h after inoculation and were antigen dose dependent. The interferon produced was pH 2 sensitive and stable at 56 degrees C for 1 h and was neutralized by antiserum directed against immune, but not against alpha/beta, interferon. The production of another lymphokine, macrophage migration inhibition factor, paralleled that of interferon. The interferon produced by cultures of spleen cells obtained from immune animals was antigen specific and dose dependent. Peak levels were obtained 48 to 72 h after the addition of antigen. The interferon produced by spleen cell cultures after stimulation with Gilliam antigen was characterized as immune interferon by the same physical and antigenic criteria used for serum interferon. Interferon was produced in vitro by the Thy-1.2+ lymphocyte and required the presence of a spleen-adherent cell population. Immune mice produced high circulating levels of immune interferon after intraperitoneal challenge with viable rickettsiae, which suggested a possible role for interferon in the resistance of immune mice to rechallenge with R. tsutsugamushi.

Gamma-irradiated scrub typhus immunogens: development of cell-mediated immunity after vaccination of inbred mice.

Mice immunized with three injections of gamma-irradiated Karp strain of Rickettsia tsutsugamushi were evaluated for the presence of cell-mediated immunity by using delayed-type hypersensitivity, antigen-induced lymphocyte proliferation, and antigen-induced lymphokine production. These animals also were evaluated for levels of circulating antibody after immunization as well as for the presence of rickettsemia after intraperitoneal challenge with viable Karp rickettsiae. After immunization with irradiated Karp rickettsiae, a demonstrable cell-mediated immunity was present as evidenced by delayed-type hypersensitivity responsiveness, lymphocyte proliferation, and production of migration inhibition factor and interferon by immune spleen lymphocytes. Also, a reduction in circulating rickettsiae was seen in mice immunized with irradiated rickettsiae after challenge with 1,000 50% mouse lethal doses of viable, homologous rickettsiae. All responses except antibody titer and reduction of rickettsemia were similar to the responses noted in mice immunized with viable organisms. Antibody levels were lower in mice immunized with irradiated rickettsiae than in mice immunized with viable rickettsiae. Furthermore, mice that were immunized with viable rickettsiae demonstrated markedly lower levels of rickettsemia after intraperitoneal challenge compared with either mice immunized with irradiated rickettsiae or nonimmunized mice.

Hyperfine structure and isotope shift of the 1.3-microm transition of (129)I.

High resolution Fourier transform spectra of the 1.3-microm emission from (127)I and (129)I electrodeless discharge lamps are presented and analyzed. The hyperfine splitting constants of (129)I are: A = 18.35 +/- 0.01 mK and B = 26.55 +/- 0.07 mK for the J = 3/2 ground state and A = 146.32 +/- 0.02 mK for the J = (1/2) excited state. The validity of the theoretical intensity and isotope relationships is confirmed. The isotope shift between (129)I and (127)I for the 1.3-microm transition was measured to be <1 mK.

Automatic precision measurement of spectrograms.

A fully automatic comparator has been designed and implemented to determine precision wavelengths from high-resolution spectrograms. The accuracy attained is superior to that of an experienced operator using a semiautomatic comparator with a photoelectric setting device. The system consists of a comparator, slightly modified for simultaneous data acquisition from two parallel scans of the spectrogram, interfaced to a minicomputer. The software which controls the system embodies three innovations of special interest. (1) Data acquired from two parallel scans are compared and used to separate unknown from standard lines, to eliminate spurious lines, to identify blends of unknown with standard lines, to improve the accuracy of the measured positions, and to flag lines which require special examination. (2) Two classes of lines are automatically recognized and appropriate line finding methods are applied to each. This provides precision measurement for both simple and complex line profiles. (3) Wavelength determination using a least-squares fitted grating equation is supported in addition to polynomial interpolation. This is most useful in spectral regions with sparsely distributed standards. The principles and implementation of these techniques are fully described.