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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↗

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↗

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↗

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↗

PubMed1994

Cancer survival and the duration of symptoms. An analysis of possible forms of the risk function. ISDS II Project Investigators.

The time interval between onset of symptoms and the diagnosis of cancer [symptom to diagnosis interval (SDI), or duration of symptoms] is a highly complex variable reflecting patient behaviour, the clinical course, the functioning of the health system and tumour biology. In order to assess possible forms of the risk function of SDI upon cancer survival whilst taking into account the effects of age, sex, tumour site and stage at diagnosis, 1887 symptomatic cases of lung, breast, stomach, colon, rectal, bladder cancer and lymphomas registered in the Tumour Registry of the Hospital del Mar (Barcelona) were analysed by means of survival curves and Cox proportional hazards regression. Subjects (mean age 64 years) were followed for a median length of 15 months after diagnosis (follow-up rate 93.5%). SDI showed a weak relationship with tumour stage at diagnosis and with survival: out of the seven sites studied, only in breast cancer was tumour extension at diagnosis significantly influenced by duration of symptoms, and only lung and rectal cancers showed a detectable form of the risk function of SDI upon survival; neither was linear, and for rectal cancer the relationship was complexly related with tumour stage. Hence, results show that forms of the risk function of duration of symptoms on cancer survival are specific to tumour sites, and that the interval should not be represented as a linear, continuous term. Studies analysing more complex sets of factors, processes and forms of the SDI function are needed.

Age Distribution↗

PubMed1992

Arginine specific endopeptidases modify the aggregation properties of a synthetic peptide derived from Alzheimer beta/A4 amyloid.

A synthetic peptide corresponding to the first 28 amino acids of the Alzheimer disease amyloid beta/A4 peptide (3.2 kDa) aggregated to a high molecular weight (15 kDa) on SDS/urea polyacrylamide gels. Proteinase K, V8 protease, trypsin, and endopeptidase Lys-C readily degraded the aggregate. By contrast, when digested by endopeptidase Arg-C, a new polypeptide aggregate of higher molecular weight (16 kDa) was observed on denaturing gels without degraded smaller products. The new aggregate was comprised of three peptides: an intact beta/A4(1-28) and partially degraded peptides beta/A4(1-5) plus beta/A4(6-28). The results were confirmed by treatment of beta/A4 with other arginine-specific proteases: the gamma subunit of nerve growth factor and clostripain. The results indicate that arginine-specific proteases, including a growth factor processing enzyme, can nick aggregated beta/A4(1-28) amyloid and alter the configuration to produce a more complex aggregated form. If similar highly specific proteolytic mechanisms occur in the Alzheimer disease brain, the processing may promote the formation of high molecular weight aggregates that contribute to the development of relatively insoluble senile plaque core protein.

Alzheimer Disease↗

PubMed1995

A late Golgi sorting function for Saccharomyces cerevisiae Apm1p, but not for Apm2p, a second yeast clathrin AP medium chain-related protein.

Mammalian clathrin-associated protein (AP) complexes, AP-1 (trans-Golgi network) and AP-2 (plasma membrane), are composed of two large subunits of 91-107 kDa, one medium chain (mu) of 47-50 kDa and one small chain (sigma) of 17-19 kDa. Two yeast genes, APM1 and APM2, have been identified that encode proteins related to AP mu chains. APM1, whose sequence was reported previously, codes for a protein of 54 kDa that has greatest similarity to the mammalian 47-kDa mu 1 chain of AP-1. APM2 encodes an AP medium chain-related protein of 605 amino acids (predicted molecular weight of 70 kDa) that is only 30-33% identical to the other family members. In yeast containing a normal clathrin heavy chain gene (CHC1), disruptions of the APM genes, singly or in combination, had no detectable phenotypic consequences. However, deletion of APM1 greatly enhanced the temperature-sensitive growth phenotype and the alpha-factor processing defect displayed by cells carrying a temperature-sensitive allele of the clathrin heavy chain gene. In contrast, deletion of APM2 caused no synthetic phenotypes with clathrin mutants. Biochemical analysis indicated that Apm1p and Apm2p are components of distinct high molecular weight complexes. Apm1p, Apm2p, and clathrin cofractionated in a discrete vesicle population, and the association of Apm1p with the vesicles was disrupted in CHC1 deletion strains. These results suggest that Apm1p is a component of an AP-1-like complex that participates with clathrin in sorting at the trans-Golgi in yeast. We propose that Apm2p represents a new class of AP-medium chain-related proteins that may be involved in a nonclathrin-mediated vesicular transport process in eukaryotic cells.

Adaptor Protein Complex mu Subunits↗

PubMed1994

Regulated immunoglobulin (Ig) RNA processing does not require specific cis-acting sequences: non-Ig RNA can be alternatively processed in B cells and plasma cells.

Alternative RNA processing of the heavy-chain immunoglobulin mu gene is regulated during B-cell maturation and requires competition between splice and cleavage-polyadenylation reactions that have balanced efficiencies. Studies with modified mu genes have failed to identify gene-specific sequences required for regulation. Thus, the only important feature for regulation may be the balanced competing splice and cleavage-polyadenylation reactions themselves. If this is so, then alternative RNA processing from any gene with similar competitive RNA processing pathways should also be regulated when expression is compared between B cells and plasma cells. To test this prediction, two nonimmunoglobulin genes engineered to have competing splice and cleavage-polyadenylation reactions were expressed in B cells and plasma cells. The ratios of alternative RNAs produced from both genes are different in the two cell types; like the mu gene, relatively more spliced RNA is produced in B cells than in plasma cells. Also, in a survey of mu gene expression in nine non-B-cell lines, only a T-cell line had an expression pattern similar to that of B cells; the expression patterns of all other lines resembled that of the plasma cells. Therefore, regulated mu RNA processing must be mediated by changes in general processing factors whose activity or abundance is regulated, most likely, in B cells.

Alternative Splicing↗

PubMedDate not supplied

Paths to adolescent parenthood: implications for prevention.

Adolescent pregnancy and parenthood are increasingly common today and pose many problems for both the individual persons involved and society as a whole. For programs to address these issues successfully, factors associated with unintended pregnancy and resulting parenthood must first be identified and understood. This paper is a review of current research on the factors associated with the four steps leading to an adolescent becoming a parent. Being an adolescent parent requires taking a particular path at four crossroads: becoming sexually active, not using or incorrectly using contraceptives, carrying rather than aborting a pregnancy, and parenting rather than placing a child for adoption. Much research in the last 15 years has explored adolescent childbearing, but many studies only compared adolescent parents to nonparents to reach conclusions about differences in these groups. This review focuses on recent studies that explore the four processes, or crossroads, separately and it excludes studies that generalize and overlap these processes. Factors that influence adolescent behavior at multiple points on the path to parenthood indicate areas particularly relevant for preventive intervention. For instance, boyfriends exert influence at all four crossroads. Sexual activity and contraceptive use increase with longevity of relationships, yet closer relationships are less often associated with raising a child. Better general communication skills, and particularly an increased ability to discuss sexuality, increases use of contraceptives, and low educational and occupational aspirations appear to influence each successive turn toward parenthood. This summary of current research serves to highlight those individual, family, dyadic, and social factors that exert great impact on adolescent parenthood by influencing young people at each of the four crossroads. These factors suggest potentially effective points for intervention to reduce the incidence of adolescent parenthood. However, poverty, unemployment, and racism also play central roles in early intercourse and childbearing, and any attempt at fundamental change must take these forces into account.

Abortion, Spontaneous↗

PubMed1985

Point process models in asthma attacks for assessing environmental risk factors.

Point process models are reviewed and discussed for assessing the effects of environmental risk factors on asthma attacks. It is pointed out that the logit model and proportional intensity model are useful for analyzing the data based on the diaries recorded consecutively during several months or during a few years. Some covariates that seems to influence upon asthmatics are explored using these models. Further work on estimating the smoothed base-line intensity function is briefly discussed in terms of the Bayes model.

Asthma↗