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PubMed1994

A second look at second-order belief attribution in autism.

Compared the performance of autistic and mentally retarded subjects, all of whom had passed a standard first-order test of false belief, on a new second-order belief task. 12 autistic and 12 mentally retarded subjects, matched on verbal mental age (assessed by PPVT and a sentence comprehension subtest of the CELF) and full-scale IQ were given two trials of a second-order reasoning task which was significantly shorter and less complex than the standard task used in all previous research. The majority of subjects in both groups passed the new task, and were able to give appropriate justifications to their responses. No group differences were found in performance on the control or test questions. Findings are interpreted as evidence for the role of information processing factors rather than conceptual factors in performance on higher order theory of mind tasks.

Adolescent↗

PubMed1995

[The role of neurotrophic factors in adaptational processes in the nervous system].

Many of neurotrophic factors (NTF) promote the survival during development, growth and neurite differentiation of neurons. The most known NTF are nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophins-3,4,5. These factors increase the survival of peripheral sensory neurons and some central neurons. The NTF are produced by the target of neuronal proections including brain tissues. So the process of adaptation in the nervous system may be also connected with level of the NTF. Recently it is shown that the NTF level in the brain is changed by central nervous system deseases--epilepsy, Parcinson and Alcgeimer deseases. In this conditions NGF and BDNF mRNC expression and their receptors mRNC are increased. So NTF diffusion in intracellular space can provide the brain function regulation in normal and pathological conditions. Model of chronic epileptogenesis was in vitro. The organotypic coculture was used--the rat newborn hippocampus and chick embryo dorsal root ganglia. Veratridine (30 nM) added in culture media induced neuronal activity in hippocampus explants and the level of NTF in media cosequently rised. It was shown that neurite-stimulating effect was mediated by veratridine. This action was blocked by NGF-antybody treatment and due to NGF activity.

Adaptation, Physiological↗

PubMed1998

Information processing deficits associated with developmental coordination disorder: a meta-analysis of research findings.

A meta-analysis was conducted to identify information processing factors that characterise children with Developmental Coordination Disorder (DCD). A total of 50 studies yielded 374 effect sizes based on 983 DCD and 987 control children. A mild generalised performance deficit was indicated, since motor-impaired children were inferior on almost all measures of information processing. There were, however, several areas where their deficiencies were more pronounced. The greatest deficiency was in visual-spatial processing. This was evident regardless of whether or not the tasks involved a motor component. Most other deficiencies were in the small-to-moderate range and included kinaesthetic and cross-modal processing. The findings support the notion that perceptual problems, particularly in the visual modality, are associated with difficulties in motor coordination.

Child↗

PubMed1991

Complex factors in hydrocarbon/water, soil/water and fish/water partitioning.

Many partitioning and toxicological events that appear to correlate simply with log P (octanol/water) can be resolved into greater detail by a factoring process. Log P can be separated into lipophilic (PL) and hydrophilic (PH) contributions that combine well with polarizability (MR) and hydrogen-bonding (HB) to describe partitioning and non-specific binding in phases that differ greatly from n-octanol. In addition, hydrogen-bonding can be factored into donor groups (HBD) and acceptor groups (HBA) for stronger correlations and greater mechanistic insight. These descriptors are applied to a variety of problems in simple partitioning, soil organic matter binding, bioaccumulation in fish, and aquatic narcosis and toxicity.

Animals↗

PubMed1991

Proper and improper folding of proteins in the cellular environment.

Protein folding in the cellular environment involves an interplay between the intrinsic biophysical properties of a protein, in both its folded and unfolded states, and various accessory proteins that aid the process. Factors such as peptidyl prolyl isomerase, protein disulfide isomerase, thioredoxin, and SecB may interact with the unfolded forms of specific classes of proteins, while members of the hsp70/DnaK and hsp60/GroEL molecular chaperone families may play a more general role in folding. Secretion, proteolysis, and aggregation are other in vivo processes that depend greatly on the folding behavior of a given protein. Intrinsic folding rates, or even translation rates, of nascent proteins may be optimized by natural selection to ensure smooth coordination with all the cellular components required for a successful folding reaction.

Bacterial Proteins↗

PubMed1996

Improving pain management in critical care.

BACKGROUND: In April 1994 at the University of California at Los Angeles Medical Center the Surgical Intensive Care Unit's (SICU's) Quality Improvement Council unanimously agreed on pain management as one of the major factors that negatively affect outcomes for their patient population. Using the FOCUS-PDCA (plan-do-check-act) model for quality improvement (QI), the council chartered a subcommittee to improve the pain management in their ICUs. METHODOLOGY: The subcommittee first measured the pain assessment scores of patients at transfer from the ICU. After ascertaining that these scores were greater than the goal of 2, the process of providing pain relief was examined with the assistance of process control statistics, which showed a process barely capable of meeting the goal of pain score of 2 or less on a 0-5 scale. The process factors that affected this outcome were examined and changes were made where appropriate. One of these changes was development of a guideline for acute pain management based on the Agency for Health Care Policy Research's Acute Pain Management Clinical Practice Guideline. Reassessment of the pain scores and the process was then conducted. RESULTS: The pain assessment scores at transfer from the ICU decreased significantly. Thirty-five percent of patients in the preguideline survey rated their scores as greater than 2, compared with only 21% at the postguideline survey. Pain assessment and documentation also improved significantly. CONCLUSION: The Quality Improvement Council felt that improvements in pain management were due largely to their having provided staff with the right tools to use in assessing, documenting, and controlling pain. Gains in pain management continue to be made.

Hospitals, University↗

PubMed1988

[Effect of nerve growth factor on synaptic processes in the sympathetic ganglion].

The nerves growth factor (7S NGF) from salivary glands of male mice activated the interneuronal relations in the inferior mesenteric plexus of 6-14-day old guinea-pigs. Superfusion of the ganglia with 7S NGF diluted to 1 X 10(-8) M (135 ng/ml) inhibited suppression of the acetylcholine release with hemicholinum or modified solutions. Atropine (1 X 10(-6) M) did not alter, and benzohexonium (1 X 10(-6) M) eliminated the excitatory effect of the 7S NGF Under d-tubocurarine (1 X 10(-6) M) blockade of H-cholinoreceptors, the 7S NGF decreased the MP and increased the duration blockade of synaptic transmission. Reduction of the tested protein effects in presence of potassium (K+ - 0.24 mM) and ouabain (1 X 10(-7) M) suggested the effect of the 7S NGF on processes of active and passive movements of electrogenic cations.

Action Potentials↗

PubMed1999

Cellular transcription factors recruit viral replication proteins to activate the Epstein-Barr virus origin of lytic DNA replication, oriLyt.

DNA replication of Epstein-Barr virus (EBV) during the productive phase of the life cycle of this herpesvirus depends on the cis-acting element oriLyt. It consists of two essential domains, the upstream and the downstream component. Whereas the upstream component contains several DNA-binding motifs for the viral activator protein BZLF1, the downstream component is known to be the binding site of several cellular proteins. We identified cellular transcription factors that bind synergistically to a functionally relevant subsequence of the downstream component, the TD element. Two of these transcription factors, ZBP-89 and Sp1, stimulate replication as shown by protein fusions with the GAL4 DNA-binding domain and a single GAL4 DNA-binding motif inserted into the TD element. In protein binding assays, we observed an interaction of Sp1 and ZBP-89 with the viral DNA polymerase and its processivity factor. Our data indicate that cellular transcriptional activators tether viral replication proteins to the lytic origin via direct protein-protein interactions to assemble the viral replication complex at oriLyt.

Base Sequence↗

PubMed2000

The carboxyl terminus of vertebrate poly(A) polymerase interacts with U2AF 65 to couple 3'-end processing and splicing.

Although it has been established that the processing factors involved in pre-mRNA splicing and 3'-end formation can influence each other positively, the molecular basis of this coupling interaction was not known. Stimulation of pre-mRNA splicing by an adjacent cis-linked cleavage and polyadenylation site in HeLa cell nuclear extract is shown to occur at an early step in splicing, the binding of U2AF 65 to the pyrimidine tract of the intron 3' splice site. The carboxyl terminus of poly(A) polymerase (PAP) previously has been implicated indirectly in the coupling process. We demonstrate that a fusion protein containing the 20 carboxy-terminal amino acids of PAP, when tethered downstream of an intron, increases splicing efficiency and, like the entire 3'-end formation machinery, stimulates U2AF 65 binding to the intron. The carboxy-terminal domain of PAP makes a direct and specific interaction with residues 17-47 of U2AF 65, implicating this interaction in the coupling of splicing and 3'-end formation.

3' Untranslated Regions↗

PubMed2025

The RNA splicing factor PRPF8 is required for left-right organiser cilia differentiation and determination of cardiac left-right asymmetry via regulation of Arl13b splicing.

Cilia function in the left-right organizer (LRO) is critical for determining internal organ asymmetry in vertebrates. To further understand the genetics of left-right asymmetry, we isolated a mouse mutant with laterality defects, l11Jus27, from a random mutagenesis screen. l11Jus27 mutants carry a missense mutation in the pre-mRNA processing factor, Prpf8. cephalophŏnus (cph) mutant zebrafish, carrying a protein truncating mutation in prpf8, phenocopy the laterality defects of l11Jus27 mutants. Prpf8 mutant mouse and fish embryos have increased expression of an alternative transcript encoding the cilium-associated protein, ARL13B, that lacks exon 9. In zebrafish, over-expression of the arl13b transcript lacking exon 9 perturbed cilium formation and caused laterality defects. The shorter ARL13B protein isoform lacked interactions with intraflagellar transport proteins. Our data suggest that PRPF8 plays a prominent role in LRO cilia by through the regulation of alternative splicing of ARL13B, thus uncovering a new mechanism for cilia-linked developmental defects.

ARL13B↗

PubMed1997

Novel genes involved in endosomal traffic in yeast revealed by suppression of a targeting-defective plasma membrane ATPase mutant.

A novel genetic selection was used to identify genes regulating traffic in the yeast endosomal system. We took advantage of a temperature-sensitive mutant in PMA1, encoding the plasma membrane ATPase, in which newly synthesized Pma1 is mislocalized to the vacuole via the endosome. Diversion of mutant Pma1 from vacuolar delivery and rerouting to the plasma membrane is a major mechanism of suppression of pma1(ts). 16 independent suppressor of pma1 (sop) mutants were isolated. Identification of the corresponding genes reveals eight that are identical with VPS genes required for delivery of newly synthesized vacuolar proteins. A second group of SOP genes participates in vacuolar delivery of mutant Pma1 but is not essential for delivery of the vacuolar protease carboxypeptidase Y. Because the biosynthetic pathway to the vacuole intersects with the endocytic pathway, internalization of a bulk membrane endocytic marker FM 4-64 was assayed in the sop mutants. By this means, defective endosome-to-vacuole trafficking was revealed in a subset of sop mutants. Another subset of sop mutants displays perturbed trafficking between endosome and Golgi: impaired pro-alpha factor processing in these strains was found to be due to defective recycling of the trans-Golgi protease Kex2. One of these strains defective in Kex2 trafficking carries a mutation in SOP2, encoding a homologue of mammalian synaptojanin (implicated in synaptic vesicle endocytosis and recycling). Thus, cell surface delivery of mutant Pma1 can occur as a consequence of disturbances at several different sites in the endosomal system.

Biological Transport↗

PubMed1996

Requirement of proliferating cell nuclear antigen in RAD6-dependent postreplicational DNA repair.

The proliferating cell nuclear antigen (PCNA) acts as a processivity factor for replicative DNA polymerases and is essential for DNA replication. In vitro studies have suggested a role for PCNA-in the repair synthesis step of nucleotide excision repair, and PCNA interacts with the cyclin-dependent kinase inhibitor p21. However, because of the lack of genetic evidence, it is not clear which of the DNA repair processes are in fact affected by PCNA in vivo. Here, we describe a PCNA mutation, pol30-46, that confers ultraviolet (UV) sensitivity but has no effect on growth or cell cycle progression, and the mutant pcna interacts normally with DNA polymerase delta and epsilon. Genetic studies indicate that the pol30-46 mutation is specifically defective in RAD6-dependent postreplicational repair of UV damaged DNA, and this mutation impairs the error-free mode of bypass repair. These results implicate a role for PCNA as an intermediary between DNA replication and postreplicational DNA repair.

Centrifugation, Density Gradient↗

PubMed1999

The role of TGF-beta in growth, differentiation, and maturation of B lymphocytes.

Transforming growth factor-beta (TGF-beta) affects B cells at all stages in development. It appears to be involved in lymphopoiesis and is required for the development of plasma cells secreting all secondary isotypes. Its ability to inhibit proliferation and stimulate apoptosis suggest that it may be involved both in germinal center development and regulation of B-cell proliferation at sites of high antigen load such as the gastrointestinal tract. Although TGF-beta appears to be required for the generation of B cells secreting secondary isotypes, it inhibits secretion of IgM and IgA from cells expressing those isotypes. In this regard, TGF-beta may alter the level of RNA processing factors either directly or indirectly by inhibiting progression through the cell cycle. One of the best characterized effects of TGF-beta is its ability to stimulate isotype switching to IgA in both mouse and man. There is some controversy concerning its mechanism of action in this process, but its critical role is without question. The controversy may stem in part from an inability to separate the effects of endogenous and exogenous TGF-beta in the multiple models of isotype switching. The influence of endogenous TGF-beta is perhaps best exemplified by analysis of production of the different classes of IgG in mouse strains producing different levels of TGF-beta.

Animals↗

PubMed1997

Mutational analysis of ectopic factor VIII transcripts from hemophilia A patients: identification of cryptic splice site, exon skipping and novel point mutations.

Mutational analysis of the gene for clotting factor VIII is complicated by its large size, the high frequency of de novo mutations and its tissue-specific expression. In order to facilitate the search for mutations, we have used a combination of reverse transcription-polymerase chain reaction (RT-PCR) of ectopic factor VIII transcripts, PCR of genomic DNA, single-strand conformation polymorphism analysis and direct sequencing. Here we describe the characterization of seven potentially pathogenic mutations: five of them are novel and the reason for the pathogenicity of the sixth could be determined. Here cDNA analysis revealed the absence of the first 47 bp of exon 16 in approximately 80% of the processed factor VIII mRNA, likely due to activation of a cryptic acceptor splice site within exon 16. The other novel mutations reported here include the skipping of exon 19, which predicts the removal of the corresponding 39 amino acids from the A3 domain, and four missense mutations: W14G, Y620C, W1889L, and Q2087R.

DNA Mutational Analysis↗

PubMed1999

Effects of executive function impairment on change processes and substance use outcomes in 12-step treatment.

OBJECTIVE: A strong clinical rationale exists to hypothesize that neuropsychological impairment interferes with treatment-initiated change, thereby leading to poor outcome. This study examined the relationship of executive function impairment, change process factors and substance use outcomes in a sample of substance users in intensive 12-step treatment. METHOD: Participants were 118 individuals entering residential or intensive day treatment at two traditional treatment programs. Participants were assessed at entry into treatment, at discharge from treatment, and at 1 and 6 months following treatment. Participants were administered a battery of measures to assess executive function impairment, processes hypothesized to mediate change in 12-step treatment, negative prognostic indicators and substance use outcomes. RESULTS: More than half the sample showed some form of executive function impairment. Executive function impairment did not directly predict worse substance use outcomes nor difficulty acquiring or maintaining change processes. However, impairment significantly moderated the relationship between change processes and outcome. Change processes were strongly related to outcome for unimpaired individuals but weakly related for impaired individuals. CONCLUSIONS: Executive function impairment is not a significant predictor of poor treatment response in 12-step treatment. However, analyses suggest that impaired and unimpaired individuals traverse different pathways in achieving equivalent outcomes.

Adult↗

PubMed1999

The stem-loop binding protein (SLBP1) is present in coiled bodies of the Xenopus germinal vesicle.

The stem-loop binding protein (SLBP1) binds the 3' stem-loop of histone pre-mRNA and is required for efficient processing of histone transcripts in the nucleus. We examined the localization of SLBP1 in the germinal vesicle of Xenopus laevis oocytes. In spread preparations of germinal vesicle contents, an anti-SLBP1 antibody stained coiled bodies and specific chromosomal loci, including terminal granules, axial granules, and some loops. After injection of myc-tagged SLBP1 transcripts into the oocyte cytoplasm, newly translated myc-SLBP1 protein was detectable in coiled bodies within 4 h and in terminal and axial granules by 8 h. To identify the region(s) of SLBP1 necessary for subnuclear localization, we subcloned various parts of the SLBP1 cDNA and injected transcripts of these into the cytoplasm of oocytes. We determined that 113 amino acids at the carboxy terminus of SLBP1 are sufficient for coiled body localization and that disruption of a previously defined RNA-binding domain did not alter this localization. Coiled bodies also contain the U7 small nuclear ribonucleoprotein particle (snRNP), which participates in cleavage of the 3' end of histone pre-mRNA. The colocalization of SLBP1 and the U7 snRNP in the coiled body suggests coordinated control of their functions, perhaps through a larger histone-processing particle. Some coiled bodies are attached to the lampbrush chromosomes at the histone gene loci, consistent with the view that coiled bodies in the oocyte recruit histone-processing factors to the sites of histone pre-mRNA transcription. The non-histone chromosomal sites at which SLBP1 is found include the genes coding for 5 S rRNA, U1 snRNA, and U2 snRNA, suggesting a wider role for SLBP1 in the biosynthesis of small non-spliced RNAs.

Amino Acid Sequence↗

PubMed1996

Dual role of the 44/62 protein as a matchmaker protein and DNA polymerase chaperone during assembly of the bacteriophage T4 holoenzyme complex.

Processive DNA synthesis in the bacteriophage T4 system requires the formation of a holoenzyme complex composed of the T4 DNA polymerase and the 44/62 and 45 accessory proteins. While ATP hydrolysis by the 44/62 protein is essential for holoenzyme formation, the role of the sliding clamp or processivity factor is attributed to the 45 protein. Beyond the need for ATP hydrolysis, the exact role of the 44/62 protein in complex assembly has not been clearly defined. In this paper, we have investigated the kinetics of complex assembly in the presence of both saturating and substoichiometric concentrations of the 44/62 protein. Under saturating conditions, complex assembly is 100% efficient, with all of the polymerase bound in a processive complex. Under conditions of limiting 44/62 protein, the 44/62 protein can act catalytically to assemble the 45 protein and polymerase into a productive complex. However, kinetic simulations indicate that a significant fraction of polymerase is sequestered in a nonproductive complex with the 45 protein. Thus, a second role for the 44/62 protein during complex assembly is that of a chaperone protein to ensure productive pol.45.DNA complex formation. We have also investigated the stability of the 45 protein on the DNA. The off rate of 0.003 s-1 for the 45 protein closely parallels that of the holoenzyme complex. Therefore, disassembly of the complex appears to involve the coordinated dissociation of both the 45 protein and the polymerase from the DNA.

Bacteriophage T4↗

PubMed1999

Self-help groups for families of persons with mental illness: perceived benefits of helpfulness.

Self-help groups have become important resources for families of persons with mental illness. The present study was an attempt to understand the factors perceived by group members as helpful using Yalom's factors in clarifying the dynamics of groups. Members (N = 202) of the Alliance for the Mentally Ill of Pennsylvania (AMI of PA), an association of self-help groups for families of the mentally ill, were recruited and responded to a self-administered questionnaire. Hierarchical block multiple regression indicated that those AMI members who felt information provision and gaining support and self-understanding from the group process was helpful and were longer term participants in their group were more likely to perceive benefit from belonging to the group. The findings may provide the basis for evaluating and improving self-help group effectiveness and contribute to understanding process factors within a self-help group which members find beneficial. Implications for how these groups can attract and maintain members are discussed.

Adult↗