Effects of motion and audio-visual redundancy on upright and inverted face and feature preferences in 4-13-month old pre- and full-term NICU graduates.

NICU infants are reported to have diminished social orientation and increased risk of socio-communicative disorders. In this eye tracking study, we used a preference for upright compared to inverted faces as a gauge of social interest in high medical risk full- and pre-term NICU infants. We examined the effects of facial motion and audio-visual redundancy on face and eye/mouth preferences across the first year. Upright and inverted baby faces were simultaneously presented in a paired-preference paradigm with motion and synchronized vocalization varied. NICU risk factors including birth weight, sex, and degree of CNS injury were examined. Overall, infants preferred the more socially salient upright faces, making this the first report, to our knowledge, of an upright compared to inverted face preference among high medical risk NICU infants. Infants with abnormalities on cranial ultrasound displayed lower social interest, i.e. less of a preferential interest in upright faces, when viewing static faces. However, motion selectively increased their upright face looking time to a level equal that of infants in other CNS injury groups. We also observed an age-related sex effect suggesting higher risk in NICU males. Females increased their attention to the mouth in upright faces across the first year, especially between 7-10 months, but males did not. Although vocalization increased diffuse attention toward the screen, contrary to our predictions, there was no evidence that the audio-visual redundancy embodied in a vocalizing face focused additional attention on upright faces or mouths. This unexpected result may suggest a vulnerability in response to talking faces among NICU infants that could potentially affect later verbal and socio-communicative development.

Genome-wide differential expression of synaptic long noncoding RNAs in autism spectrum disorder.

A genome-wide differential expression of long noncoding RNAs (lncRNAs) was identified in blood specimens of autism spectrum disorder (ASD). A total of 3929 lncRNAs were found to be differentially expressed in ASD peripheral leukocytes, including 2407 that were upregulated and 1522 that were downregulated. Simultaneously, 2591 messenger RNAs (mRNAs), including 1789 upregulated and 821 downregulated, were also identified in ASD leukocytes. Functional pathway analysis of these lncRNAs revealed neurological pathways of the synaptic vesicle cycling, long-term depression and long-term potentiation to be primarily involved. Thirteen synaptic lncRNAs, including nine upregulated and four downregulated, and 19 synaptic mRNAs, including 12 upregulated and seven downregulated, were identified as being differentially expressed in ASD. Our identification of differential expression of synaptic lncRNAs and mRNAs suggested that synaptic vesicle transportation and cycling are important for the delivery of synaptosomal protein(s) between presynaptic and postsynaptic membranes in ASD. Finding of 19 lncRNAs, which are the antisense, bi-directional and intergenic, of HOX genes may lead us to investigate the role of HOX genes involved in the development of ASD. Discovery of the lncRNAs of SHANK2-AS and BDNF-AS, the natural antisense of genes SHANK2 and BDNF, respectively, indicates that in addition to gene mutations, deregulation of lncRNAs on ASD-causing gene loci presents a new approach for exploring possible epigenetic mechanisms underlying ASD. Our study also opened a new avenue for exploring the use of lncRNA(s) as biomarker(s) for the early detection of ASD.

A novel antibody-drug conjugate targeting SAIL for the treatment of hematologic malignancies.

Although several new therapeutic approaches have improved outcomes in the treatment of hematologic malignancies, unmet need persists in acute myeloid leukemia (AML), multiple myeloma (MM) and non-Hodgkin's lymphoma. Here we describe the proteomic identification of a novel cancer target, SAIL (Surface Antigen In Leukemia), whose expression is observed in AML, MM, chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). While SAIL is widely expressed in CLL, AML, MM, DLBCL and FL patient samples, expression in cancer cell lines is mostly limited to cells of AML origin. We evaluated the antitumor activity of anti-SAIL monoclonal antibodies, 7-1C and 67-7A, conjugated to monomethyl auristatin F. Following internalization, anti-SAIL antibody-drug conjugates (ADCs) exhibited subnanomolar IC50 values against AML cell lines in vitro. In pharmacology studies employing AML cell line xenografts, anti-SAIL ADCs resulted in significant tumor growth inhibition. The restricted expression profile of this target in normal tissues, the high prevalence in different types of hematologic cancers and the observed preclinical activity support the clinical development of SAIL-targeted ADCs.

Millimeter-wave rotational spectroscopy of FeCN (X 4Δi) and FeNC (X 6Δi): determining the lowest energy isomer.

The pure rotational spectrum of FeCN has been recorded in the frequency range 140-500 GHz using millimeter/sub-millimeter direct absorption techniques. The species was created in an ac discharge of Fe(CO)(5) and cyanogen. Spectra of the (13)C, (54)Fe, and (57)Fe isotopologues were also measured, confirming the linear cyanide structure of this free radical. Lines originating from several Renner-Teller components in the ν(2) bending mode were also observed. Based on the observed spin-orbit pattern, the ground state of FeCN is (4)Δ(i), with small lambda-doubling splittings apparent in the Ω = 5/2, 3/2, and 1/2 components. In addition, a much weaker spectrum of the lowest spin-orbit component of FeNC, Ω = 9/2, was recorded; these data are consistent with the rotational parameters of previous optical studies. The data for FeCN were fit with a Hund's case (a) Hamiltonian and rotational, spin-orbit, spin-spin, and lambda-doubling parameters were determined. Rotational constants were also established from a case (c) analysis for the other isotopologues, excited vibronic states, and for FeNC. The r(0) bond lengths of FeCN were determined to be r(Fe-C) = 1.924 Å and r(C-N) = 1.157 Å, in agreement with theoretical predictions for the (4)Δ(i) state. These measurements indicate that FeCN is the lower energy isomer and is more stable than FeNC by ~1.9 kcal/mol.

Placement, relocation and end of life issues in aging adults with and without Down's syndrome: a retrospective study.

BACKGROUND: Aging adults with Down's syndrome (DS) experience more relocations and other life events than adults with intellectual disabilities aged 50 and older without DS. Age-related functional decline and the higher incidence of dementia were implicated as the contributing factors that led to relocation and nursing home placement. METHOD: A retrospective study of adults with intellectual disabilities who were born prior to the year 1946 was conducted to analyse the number of relocations experienced over a 5- and 10-year period. The cohort consisted of 140 individuals (61 with DS between ages 50-71 years, and 79 without DS between ages 57-89 years) who had been referred to a diagnostic and research clinic. RESULTS: Analyses revealed the number of relocations over a 5- and 10-year period were significantly greater in the DS group. Placement in a nursing home for end of life care was significantly higher in the DS group whereas the majority (90%) in the non-DS group remained in a group home setting. Mortality was significantly earlier in the DS group with the mean age at death to be 61.4 years compared with 73.2 years in the non-DS group. CONCLUSIONS: The present results suggest that aging adults with DS encounter more relocations, and are more likely to have their final placement for end of life care in a nursing home. In contrast, the adults without DS were subjected to less relocation and remained in the same group home setting.

The effects of a home-based intervention for young children with intellectual disabilities in Vietnam.

BACKGROUND: This study was conducted to examine the impact of a 1-year intervention for children with intellectual disabilities (ID) in Vietnam. METHOD: Subjects were 30 preschool-aged children with ID (ages 3 to 6 years). Sixteen were assigned to an intervention group and 14 to a control group. Based on the Portage Curriculum (CESA 5 2003), the intervention trained parents to work with their children through modelling and coaching by teachers during weekly home visits. RESULTS: Comparison of pre-, mid- and post-intervention assessments of the children based on the Vineland Adaptive Behavior Scales (Sparrow et al. 1984a) indicated that the intervention was promising: children in the intervention group improved significantly in most domains of adaptive behaviours, and also performed significantly better than the control group in the areas of personal care and motor skills. CONCLUSIONS: The results from the Vietnam programme are discussed in terms of its implications and strategies for developing programmes for children with disabilities in developing countries.

The rotational spectrum of CoF in all three spin-orbit components of the X3Phi i state.

The pure rotational spectrum of cobalt monofluoride in its X (3)Phi(i) electronic state has been measured in the frequency range of 256-651 GHz using direct absorption techniques. CoF was created by reacting cobalt vapor with F(2) in helium at low pressure (25-30 mTorr). All three spin components were identified in the spectrum of this species, two of which exhibited lambda doubling. Each spin component showed hyperfine splittings from both nuclei: an octet pattern arising from the (59)Co spin of I=72, which is further split into doublets due to the (19)F nucleus (I=12). The data were fitted close to experimental precision using an effective Hamiltonian expressed in Hund's case (a) form, and rotational, fine structure, hyperfine, and lambda-doubling parameters were determined. There is evidence that the rotational levels of the highest spin component (3)Phi(2) are perturbed. The r(0) bond length of CoF was estimated from the rotational constant to be 1.738 014(1) A. This value is in good agreement with previous studies but much more accurate. The matrix elements necessary for the complete treatment of Lambda doubling in a Phi state have been derived and are presented for the first time.

Completing the 3d metal fluoride series: the pure rotational spectrum of ZnF (X2Sigma+).

The pure rotational spectrum of the ZnF radical has been recorded in the range of 176-527 GHz using millimeter/submillimeter direct absorption techniques. This study is the first gas-phase spectroscopic investigation of this species. Between 5 and 11 transitions were measured for each of five isotopologues of this radical (64ZnF, 66ZnF, 67ZnF, 68ZnF, and 70ZnF) in the ground and several excited vibrational (v=1, 2, and 3) states. Each transition consists of spin-rotation doublets with a splitting of approximately 150 MHz, indicating that the electronic ground state of ZnF is 2Sigma+, as predicted by theory. Fluorine hyperfine splitting was observed in three isotopologues (64ZnF, 66ZnF, and 67ZnF), and hyperfine structure from the zinc-67 nucleus (I=52) was additionally resolved in 67ZnF. Rotational, fine structure, and 19F and 67Zn hyperfine constants were determined for ZnF, as well as equilibrium parameters. The bond length of the main isotopologue 64ZnF was calculated to be re=1.7677 A. Evaluation of the hyperfine constants indicates that the sigma orbital containing the unpaired electron is approximately 80% 4s(Zn) in character with approximately 10% contributions from each of the 2p(F) and 4p(Zn) orbitals. These results imply that ZnF is somewhat less ionic than CaF, as suggested by theory.

Parenting stress of mothers and fathers of young children with cognitive delays in Vietnam.

BACKGROUND: This research examined the effects of child and family variables on stress experienced by mothers and fathers of young children with cognitive delays in Vietnam. METHODS: The mothers (n = 106) and fathers (n = 93) whose children (age range = 3-6 years) were identified as having cognitive delays participated in the interview survey. The survey consisted of a set of the standardized questionnaires that were translated into Vietnamese and assessed for the content validity in the Vietnamese context. RESULTS: Mothers experienced more stress than fathers. Path analyses were conducted for mothers and fathers separately. Mothers with female children, those with children of lower intellectual functioning, and those whose husbands had health conditions experienced more stress than the other mothers. Fathers with lower economic status and a smaller social support network were more stressed than the other fathers. Both mothers and fathers were more stressed when they experienced stronger stigma, although the effects were not significant when other variables were considered together in path analyses. CONCLUSIONS: The findings revealed traditional gender roles. Mothers were more affected by the child's characteristics and the spouse's functioning; they anticipated future problems related to the child's functioning more than fathers did. Fathers were more affected by concerns about the family's connection to the wider world such as economic issues and the social support network. Longitudinal studies of how social support and stigma affect families would be valuable.

Amyloid-beta impairs development of neuronal progenitor cells by oxidative mechanisms.

Neuronal progenitor cells (NPCs) are being considered for treatment of neurodegenerative diseases associated with beta-amyloidosis: Alzheimer's disease (AD) and Down syndrome (DS). However, the neurotoxic properties of amyloid-beta peptide (Abeta) may impair survival and differentiation of transplanted NPCs. Hence, we studied the influence of Abeta on development of human NPCs--proliferation, migration, formation of colonies of neurons, formation processes--in culture. Pre-fibrillized human Abeta1-40 blocked development of neuronal colonies. NPC development was impaired in the presence of soluble Abeta1-40 (1.75-7 microM), and NPC differentiation into large and small neurons was altered, as demonstrated by morphometry. Antioxidant vitamin E partially abolished these effects, but not the reduced formation of neuronal processes. NPCs cultured with 7 microM Abeta1-40 accumulated Abeta monomers and oligomers and contained higher levels of protein carbonyls and lipid peroxidation products HNE and MDA. We suggest that Abeta1-40 impairs development of NPCs by oxidative damage. Hence, a prerequisite of successful neuroreplacement therapy using NPCs in AD and DS/AD may be removal of amyloid-beta and antioxidative treatment.

High-resolution spectroscopy of CoS (X4Deltai): examining 3d transition-metal sulfide bonds.

The pure rotational spectrum of CoS, the cobalt sulfide radical, has been measured using direct absorption techniques in the frequency range of 180-540 GHz. This study is the first spectroscopic investigation of any kind of this molecule. CoS was created by reacting cobalt vapor with H2S. Four spin components were identified in the spectra of this species, one of which exhibited lambda doubling, identifying the ground state as 4Deltai. Transitions arising from the lowest spin component of the less abundant Co 35S isotopomer have also been detected, as well as from v=1 and v=2 of the main species. The spectra were readily identified because each spin component exhibited an octet pattern arising from the 59Co spin of I=72. The data were fit using Hund's case (a) Hamiltonian, and rotational, fine-structure, hyperfine, and lambda-doubling constants were determined. The hyperfine parameters support a delta3pi2 electron configuration and are consistent with some orbital overlap between the metal and sulfur atoms. From the rotational constant, the bond length of CoS was calculated to be r0=1.977 985 06(10) A. This bond length is significantly shorter than that of MnS or FeS, in contrast to the bond distances found in the oxide analogs which are all similar in value. These results indicate that the 3d metal sulfides differ somewhat from their oxide counterparts, probably due to the availability of sulfur p orbitals for bonding.

Characterizing the later 3d cyanides: the submillimeter spectrum of CoCN(X 3Phi i).

The pure rotational spectrum of the CoCN radical has been recorded in the frequency range 350-500 GHz using direct absorption techniques. This study is the first spectroscopic observation of this molecule by any experimental technique. Spectra of Co (13)CN have been measured as well. These data indicate that this species is linear in its ground electronic state and has the cyanide, as opposed to the isocyanide, geometry. The ground state term has been assigned as (3)Phi(i), based on the measurement of three spin components (Omega=4, 3, and 2) and in analogy to other isovalent cobalt-bearing species. Hyperfine splittings resulting from the (59)Co nuclear spin of I=7/2 were observed in every transition, each of which exhibited an octet pattern. For the lowest energy spin component, Omega=4, vibrational satellite features were also identified arising from the first quantum of the Co-C (v(1)=1) stretch and the v(2)=1 and v(2)=2 quanta of the bending mode, which were split by Renner-Teller interactions. The ground state measurements of CoCN were analyzed with a case a(beta) Hamiltonian, establishing rotational, fine structure, and hyperfine parameters. The vibrational and Co (13)CN spectra for the Omega=4 component were fit as well. An r(0) structure was also calculated, providing estimates of the Co-C and C-N bond distances, based on the Omega=4 transitions. CoCN is the fourth molecule in the 3d transition metal series to exhibit the linear cyanide structure, along with the Zn, Cu, and Ni analogs. The preference for this geometry, as opposed to the isocyanide form, may indicate a greater degree of covalent bonding in these species.

Perturbations in the pure rotational spectrum of CoCl (X 3 Phi i): a submillimeter study.

The millimeter/submillimeter-wave spectrum of the CoCl radical (X (3)Phi(i)) has been recorded using direct absorption techniques in the frequency range 340-510 GHz. This work is the first pure rotational study of this molecule. The radical was created by the reaction of Cl(2) with cobalt vapor. Rotational transitions arising from the Omega=4, 3, and 2 spin-orbit components of Co(35)Cl have been measured, all of which exhibit hyperfine splittings due to the (59)Co nucleus (I=7/2). Transitions arising from the Co(37)Cl species were also recorded, as well as those originating in the v=1, 2, 3, and 4 vibrational states of both isotopomers. The spin-orbit pattern exhibited by the molecule is unusual, with the Omega=3 component significantly shifted relative to the other spin components. In addition, the regular octet hyperfine splittings become distorted above a certain J value for the Omega=3 transitions only. These effects suggest that the molecule is highly perturbed in its ground state, most likely a result of second-order spin-orbit mixing with a nearby isoconfigurational (1)Phi(3) state. The complete data set for Co(35)Cl and Co(37)Cl were fit successfully with a case (a) Hamiltonian but required a large negative spin-spin constant of lambda=-7196 GHz and higher order centrifugal distortion corrections to the rotational, spin-orbit, spin-spin, and hyperfine terms. The value of the spin-spin constant suggests that the Omega=3 component is shifted to higher energy and lies near the Omega=2 sublevel. The hyperfine parameters are consistent with a delta(3)pi(3) electron configuration and indicate that CoCl is more covalent than CoF.

Identification of a human centrosomal calmodulin-binding protein that shares homology with pericentrin.

Eukaryotic chromosome segregation depends on the mitotic spindle apparatus, a bipolar array of microtubules nucleated from centrosomes. Centrosomal microtubule nucleation requires attachment of gamma-tubulin ring complexes to a salt-insoluble centrosomal core, but the factor(s) underlying this attachment remains unknown. In budding yeast, this attachment is provided by the coiled-coil protein Spc110p, which links the yeast gamma-tubulin complex to the core of the yeast centrosome. Here, we show that the large coiled-coil protein kendrin is a human orthologue of Spc110p. We identified kendrin by its C-terminal calmodulin-binding site, which shares homology with the Spc110p calmodulin-binding site. Kendrin localizes specifically to centrosomes throughout the cell cycle. N-terminal regions of kendrin share significant sequence homology with pericentrin, a previously identified murine centrosome component known to interact with gamma-tubulin. In mitotic human breast carcinoma cells containing abundant centrosome-like structures, kendrin is found only at centrosomes associated with spindle microtubules.

Changing HIV infection rates and risk in an African-American community cohort.

This longitudinal study of a homogeneously urban African-American community cohort drawn from the metropolitan New York area (USA) analyzed three-year change in HIV-1 antibody prevalence and self-reported risk practices separately for men and women. Specifically, risk practices reported on personal interviews and results from blood sero-assay in 1989-1990 were compared to similar interview reports of risk practices and HIV assay from saliva samples in 1993. Results showed: (1) women's infection rates increased more than men's, resulting in a male to female infection ratio of 1.5:1; (2) heterosexual transmission accounted for most of women's new infection; (3) in multivariate analysis, multiple partners was a significant heterosexual risk indicator for both men and women, increasing infection odds five-fold; and (4) buying sex also increased heterosexual men's infection odds approximately five-fold. Results document increasing rates of African-American HIV infection linked largely to heterosexual exposure risk, that the African-American male-female infection ratio resembles the global rather than North American one, and also the utility of an expanded classification of heterosexual exposure risk.

Calmodulin localizes to the spindle pole body of Schizosaccharomyces pombe and performs an essential function in chromosome segregation.

The essential calmodulin genes in both Saccharomyces cerevisiae and Schizosaccharomyces pombe were precisely replaced with genes encoding fusions between calmodulin and the green fluorescent protein (GFP). In living budding yeast the GFP-calmodulin fusion protein (GFP-Cmd1p) localized simultaneously to sites of cell growth and to the spindle pole body (SPB), the yeast analog of the centrosome. Having demonstrated proper localization of GFP-calmodulin in budding yeast, we examined the localization of a fusion between GFP and calmodulin (GFP-Camlp) in fission yeast, where calmodulin had not been localized by any method. We find GFP-Camlp also localizes both to sites of polarized cell growth and to the fission yeast SPB. The localization of calmodulin to the SPB by GFP fusion was confirmed by indirect immunofluorescence. Antiserum to S. pombe calmodulin labeled the ends of the mitotic spindle stained with anti-tubulin antiserum. This pattern was identical to that seen using antiserum to Sad1p, a known SPB component. We then characterized the defects in a temperature-sensitive S. pombe calmodulin mutant. Mutant cam1-E14 cells synchronized in S phase completed DNA synthesis, but lost viability during transit of mitosis. Severe defects in chromosome segregation, including hypercondensation, fragmentation, and unequal allocation of chromosomal material were observed. Immunofluorescence analysis of tubulin revealed a population of cells containing either broken or mislocalized mitotic spindles, which were never observed in wild-type cells. Taken together with the subcellular localization of calmodulin, the observed spindle and chromosome segregation defects suggest that calmodulin performs an essential role during mitosis at the fission yeast SPB.

Psychosocial risk factors of child and adolescent completed suicide.

BACKGROUND: Few psychosocial risk factors for completed suicide in children and adolescents have been studied systematically. The present study was designed to examine the environmental, social, and familial characteristics of a large representative sample of child and adolescent suicides. METHODS: A case-control, psychological autopsy of 120 of 170 consecutive suicides younger than 20 years and 147 community age-, sex-, and ethnically matched control participants in the greater New York, NY, area. RESULTS: There was a significant independent impact of the psychosocial factors on increasing suicide risk among children and adolescents, beyond that risk attributable to psychiatric illness. The most notable risks were derived from school problems, a family history of suicidal behavior, poor parent-child communication, and stressful life events. Sex, ethnicity, and age modified the relationships of a few of the psychosocial factors. CONCLUSIONS: Socioenvironmental circumstances add significantly to a teenager's risk of suicide. The overall effect size on increasing suicide risk of the psychosocial factors is comparable with that for diagnostic factors, highlighting the importance of considering socioenvironmental factors when assessing suicide risk.

Psychiatric diagnosis in child and adolescent suicide.

BACKGROUND: The age, sex, and ethnic distribution of adolescents who commit suicide is significantly different from that of the general population. The present study was designed to examine psychiatric risk factors and the relationship between them and demographic variables. METHODS: A case-control, psychologic autopsy study of 120 of 170 consecutive subjects (age, <20 years) who committed suicide and 147 community age-, sex-, and ethnic-matched control subjects who had lived in the Greater New York (NY) area. RESULTS: By using parent informants only, 59% of subjects who committed suicide and 23% of control subjects who met DSM-III criteria for a psychiatric diagnosis, 49% and 26%, respectively, had had symptoms for more than 3 years, and 46% and 29%, respectively, had had previous contact with a mental health professional. Best-estimate rates, based on multiple informants for these parameters, for suicides only, were 91%, 52%, and 46%, respectively. Previous attempts and mood disorder were major risks factors for both sexes; substance and/or alcohol abuse was a risk factor for males only. Mood disorder was more common in females, substance and/or alcohol abuse occurred exclusively in males (62% of 18- to 19-year-old suicides). The prevalence of a psychiatric diagnosis and, in particular, substance and/or alcohol abuse increased with age. CONCLUSION: A limited range of diagnoses--most commonly a mood disorder alone or in combination with conduct disorder and/or substance abuse--characterizes most suicides among teenagers.