bluuebunny/crossref_metadata_2025 huggingface dataset:
Does Educational Research Matter?*
Authors: Mortimore Peter
Published: July 2002

ABSTRACT This article endeavours to set British educational research in the context of national and international economic developments and to take account of national educational policy making and educational practice.

It addresses seven questions:

What does the term educational research include?

What are the major tasks of educational research?

What are its successes?

What are its failures?

Why is educational research attacked so frequently?

Would we miss it if it did not exist?

How can we enhance the value of educational research?

It is argued that the scope of educational research is broad, covering different techniques and methodologies and many aspects of the educative process, both formal and informal. Four main tasks emerge: to observe and record systematically; to analyse and draw out implications; to publish findings; and, crucially, to attempt to improve educational processes and outcomes. British educational researchers can point to a substantial corpus of successful work, ranging from large‐scale longitudinal cohort studies to powerful individual case studies; to studies of differential effectiveness, school organisation, curriculum and assessment, inequality and discrimination.

Many such studies have influenced policy and practice. But success should not blind the research community to its shortcomings‐the gaps in knowledge, the inaccessibility of some writing, the mediocrity of some work, and the ways in which researchers relate to those involved in, or affected by, research or those whom it is hoped will be influenced by it. Public perceptions of these shortcomings‐some well founded, others driven by prejudice‐underlie many of the attacks to which researchers and their work are regularly subjected. Whilst educational research might not be missed (even gladly dismissed) by some practitioners and policy makers, this paper argues that the work is essential if independent questioning and impartial evaluations of policy and practice are to take place. We should, however, make every effort to enhance our work. To this end we need to take note of the various BERA Codes of Practice, invest in developing our members' repertoires of research techniques and constantly guard against bias in our work. We must also continue our efforts to relate positively to the elected government of the day. In doing all of these things we must hold fast to our BERA values. We must do what we have been trained to do

ask difficult questions

demand evidence, rather than anecdote, for answers

generate, through our research, new knowledge

formulate new theories

speak up for what we believe is right

A democratic society expects‐and deserves‐nothing less.
Resiliency factors predicting psychological adjustment after political violence among Palestinian children
Authors: Punamäki Raija-Leena , Qouta Samir , El-Sarraj Eyad
Published: July 2002

The effects of cognitive capacity, perceived parenting, traumatic events, and activity, which were ” rst measured in the midst of the political violence of the Intifada in 1993, were examined on post-traumatic stress disorder (PTSD), emotional disorders, school performance, and neuroticism three years later in more peaceful conditions among 86 Palestinian children of 14.04 ± 0.79 years of age. The results showed, ” rst, that PTSD was high among the children who had been exposed to a high level of traumatic events and had responded passively (not actively) to Intifada violence. Discrepant perceived parenting was also decisive for adjustment: Children who perceived their mothers as highly loving and caring but their fathers as not so showed a high level of PTSD. High intellectual but low creative performance was also characteristic of the children suffering from emotional disorders. Second, the hypothesis that cognitive capacity and activity serve a resiliency function if children feel loved and nonrejected at home was confirmed. Third, neuroticism decreased significantly over the three years, especially among the children who had been exposed to a high number of traumatic events.
Out-of-home Child Care Research: A Cultural Perspective
Authors: Rosenthal Miriam K.
Published: July 2002

This paper analyses the cultural context of inquiry and research into the effects of out-of-home child care on children’s development. In particular, it attempts to show how the study of such child care has been shaped by a Western world view in which white, middle class values and social ideology are particularly salient. The effects of this cultural context can be seen in the basic assumptions of studies on out-of-home child care, in the questions these studies pose for investigation, and in the motivation of the investigators engaged in this line of research. These in turn determine the research designs, the units of analysis for the examination of children’s functioning and of the child care environment, the operational definitions of variables, and the statistical procedures employed in many of these studies.

The analysis begins by examining cultural variations in societal attitudes to out-of-home child care as a function of cultural context and basic assumptions concerning childhood, development, and the role ascribed to the family and the community at large in children’s development. The paper then proceeds to examine the relationship between cultural context and its valued developmental goals and the developmental outcomes studied in child care research. The relationships between goals set for child care, cultural beliefs concerning child-rearing practices, the definition of “quality of care” and the study of the relationship of home and child care, in child care research, are also examined. It then explores the major research questions and methodology concerning the effect of child care on development in the Anglo-American child care research tradition. The paper concludes with a discussion of implications for culturally sensitive routes to studying child care.
Barriers to Lone Parents' Employment
Authors: Speak Suzanne
Published: July 2002

In Britain, unemployment amongst lone parents remains persistently high. It does so despite government funded employment and training initiatives, and the tightening of welfare benefits. In October 1998, the Government launched its National Child Care Strategy, aimed partly at getting lone parents back to work. Whilst lack of affordable child care is a crucial barrier to employment for lone parents, without an understanding of the complexity of the transition from benefits to employment, the strategy will have little effect. This article looks at that transition in relation to the neighbourhoods in which many lone parents live.
A process evaluation of the CREDIT (court referral and evaluation for drug intervention and treatment) pilot programme
Authors: HEALE PENNY , LANG ERNIE
Published: July 2002

The Court Referral and Evaluation for Drug Intervention and Treatment programme (CREDIT) was developed by a small group of magistrates at the Melbourne Magistrates' Court who wished to address the high rate of re‐offending while on bail noted among illicit drug using offenders. An evaluation was conducted of the first 9 months' operation of the programme. The evaluation involved an analysis of key performance indicators (client uptake of CREDIT, retention in and satisfactory completion of treatment, the extent of re‐offending while on bail) and interviews with 30 key informants and six programme participants. Despite a lack of conclusive evidence regarding the efficacy of the programme according to the identified key performance indicators, key informant interviews revealed a high level of support for the continuation of the programme.
HIV risk behaviour and prevention in prison: a bleach programme for inmates in NSW
Authors: DOLAN KATE , WODAK ALEX , HALL WAYNE
Published: July 2002

One hundred and eighty‐one inmates in AIDS education courses were surveyed about their risk behaviour and access to disinfectants for syringe cleaning in 1993. Overall, 40% of respondents reported HIV risk behaviour in prison. One‐quarter of respondents reported injecting, of whom three‐quarters reported sharing syringes in prison. Most respondents who shared syringes reported cleaning them with disinfectants (96%), even though only one‐third reported having easy access to disinfectants. One‐sixth of respondents reported sharing tattooing equipment, of whom two‐thirds reported using a disinfectant to clean the tattoo needle. Few respondents reported fellatio (8%) or anal intercourse (4%) in prison. Although some respondents faced difficulty in obtaining disinfectants, almost all respondents cleaned syringes with bleach when sharing. High levels of risk behaviour in prison might be reduced by methadone maintenance and condom programmes. A trial of strict one‐for‐one syringe exchange warrants consideration.
The naloxone eye‐drop test for opioid dependence
Authors: DORE GLENYS M. , NIVEN BRIAN E. , HARGREAVES GORDON , CARADOC‐DAVIES GILLIAN
Published: July 2002

The use of topical ophthalmic naloxone to detect physiological opioid dependence was tested in two double‐blind, placebo‐controlled trials a week apart. The subject group consisted of opioid‐dependent patients on methadone maintenance treatment. The control group consisted of medical student volunteers. For trial 1, two drops of naloxone hydrochloride (1 mg/ml) were instilled in one eye of both subjects and controls, while two drops of an inert saline solution were instilled into the opposite eye. For trial 2 the procedure was repeated. However, on this occasion all controls were administered a single subcutaneous injection of morphine sulphate. Pupil diameter following administration of naloxone was measured by photographs taken at 0, 60 and 90 minutes. Complete data for both days were obtained from 15 controls and 13 subjects. A significant difference was found between mean changes in pupil/iris ratio for the control group compared with the opioid group for both trials. However, discriminant analysis revealed that the test is likely to produce significant numbers of false positive and false negative results. In addition, the test precipitated an opiate withdrawal syndrome in many subjects, and bilateral mydriasis was evident in trial 2. The naloxone eye‐drop test does not appear to be a useful tool in determining the presence of neuroadaptation to opioids.
Assessing the Risks and Benefits of Benzodiazepines for Anxiety Disorders in Patients with a History of Substance Abuse or Dependence
Authors: Posternak Michael A. , Mueller Timothy I.
Published: July 2002

In this article, the authors reevaluate the traditional position that benzodiazepines should be avoided in anxiety disorder patients with a history of substance abuse or dependence. The efficacy of benzodiazepines in each of the anxiety disorders is reviewed, as are their side effects and toxicity. The definitions of benzodiazepine abuse and dependence are discussed, and relevant animal, experimental, and clinical data are reviewed and analyzed. A manual and computerized (MEDLINE) search was performed from 1966 to the present to examine the English‐language literature published on benzodiazepines, substance abuse, and each of the anxiety disorders listed in DSM‐IV. The authors found that benzodiazepines have demonstrated efficacy in generalized anxiety disorder, panic disorder, and agoraphobia; they are promising agents in the treatment of social phobia and alcohol‐induced anxiety disorders. They are generally well tolerated. There is much ambiguity over appropriate definitions for benzodiazepine abuse and dependence: although most benzodiazepine abusers concurrently abuse other substances, there is little evidence to indicate that a history of substance abuse is a major risk factor for future benzodiazepine abuse or dependence. Furthermore, benzodiazepines do not appear to induce relapse of substance abuse in these patients. The authors conclude that the position that benzodiazepines are contraindicated in former substance abusers appears to lack empirical justification. Benzodiazepines may be indicated in certain patients with anxiety disorders and a history of substance abuse or dependence.
Effects of age, gender, duration of drug use and infection with viral hepatitis B and C on lymphocyte subsets in a population of HIV‐negative injecting drug users in Italy
Authors: REZZA GIOVANNI , D'EGIDIO PIETRO , COZZI LEPRI ALESSANDRO , COSTANTINI DAMIANO , PETRUCCI ANDREA , PEZZOTTI PATRIZIO
Published: July 2002

Abstract A series of 716 HIV‐negative IDUs entering a large drug treatment centre in central Italy was studied to evaluate the pattern of T‐lymphocyte subsets among IDUs and to determine the effects of individual variables such as age, gender, duration of drug use and infection with viral hepatitis B and C. To this end, white cell count, total lymphocyte count and absolute number of lymphocyte subsets (i.e. CD3+, CD4+ and CD8+), HBV markers and HCV serology, were determined. For each individual, information on age, gender and duration of drug use was collected. To evaluate the association between level of lymphocyte subsets and phases of HBV infection, participants were stratified into three groups: (A) negative for all markers; (B) HBsAg‐positive, with or without HBeAg, and HBsAb‐negative; and (C) HBsAg and HBeAg‐negative, positive for any other serological marker. The median absolute number of CD3+, CD4+ and CD8+ was 1909, 1080 and 770 cells/mm3, respectively, and did not vary across age bands. The CD8+ count was higher in males than in females. There was a tendency for CD3+ lymphocyte counts (mainly due to CD8+ counts) to be higher in individuals with 6‐8 years of drug use compared to those who started injecting 4 years before or less. There was no evidence of increasing counts for a duration of drug use of more than 8 years. With regard to HBV, there was a general tendency for individuals in group “C” to have higher CD3+ and CD8+ counts than those in group “A”. Finally, there was no difference in absolute lymphocyte count subsets between HCV‐positive and HCV‐negative IDUs. In conclusion, demographic and behavioural factors such as long‐term heroin use or infection with HCV do not seem to influence the level of lymphocyte subsets among HIV‐negative IDUs, nor does the infection with HBV seem to determine dramatic changes in CD4+ counts.
Effects of acute ethanol on ventricular myofibrillary protein synthesis in vivo in normotensive and hypertensive rats
Authors: SIDDIQ TAHIR , SANDHU GURJINDER , RICHARDSON PETER J. , PREEDY VICTOR R.
Published: July 2002

Abstract The acute inhibitory effects of ethanol (75 mmol/kg body weight; i.p.; 2.5 hour) on the synthesis of the myofibrillary and other protein fractions in normotensive and hypertensive rats were investigated. Male Wistar rats were subjected to 30 days aortic constriction to induce hypertension. Controls were sham‐operated and subjected to controlled feeding so that both groups of rats received identical food intakes. At the end of the study the left ventricles were analysed. Hypertension was associated with a significant increase in the content of myofibrillary and non‐contractile proteins with slightly reduced protein synthesis. A marked decrease in the rates of contractile and non‐contractile protein synthesis occurred in response to ethanol dosage in sham‐operated control rats. The decline in myofibrillary protein synthesis was greater in the hypertensive animals. A reduction in the synthesis of contractile proteins will compromise the formation of new contractile elements and contribute to the impaired contractility of hypertensive ethanol misusers.
Alcohol and injuries in elderly people
Authors: ADAMS WENDY L. , JONES THOMAS V.
Published: July 2002

Injuries are a common cause of morbidity and mortality among elderly people. Falls are the most common type of accident, accounting for around 40% of injuries. There is substantial evidence that heavy alcohol use is an important risk factor for injuries in younger people, but results of the few studies of alcohol and injuries among elderly people have been inconsistent. In this paper, we review the literature on the effects of alcohol on gait and balance and present reasons that a causal relationship between alcohol and injuries is biologically plausible. We review the epidemiological studies of the relationship between alcohol and falls, hip fractures and other injuries in the elderly population and discuss sources of error in these studies. Selection bias, small sample sizes, measurement error and potential confounders such as age, gender, health status and medications may have played a substantial role in negative results from several studies. Further research that will help clarify the relationship between alcohol and injuries in elderly people is sorely needed.
Association of polymorphism in the alcohol dehydrogenase 2 gene with alcohol‐related organ injuries, especially liver cirrhosis
Authors: YAMAUCHI MASAYOSHI
Published: July 2002

The class I hepatic alcohol dehydrogenases (ADHs) are primarily responsible for ethanol metabolism in humans. Genetic polymorphism at the ADH2 locus results in the inheritance of isozymes of strikingly different catalytic properties. In European and Caucasian American populations, β1, which is encoded by ADH21, is the most common form of the enzyme, while β2, encoded by the ADH22 allele, is found primarily in Orientals. The β2β2 enzyme encoded by ADH22/ADH22 is approximately 20 times more active in ethanol oxidation than the β1β1 enzyme. In vivo the kinetic differences of ADH2 isozymes may influence individual risk for the effects of ethanol. This article will review the role of polymorphisms at the ADH2 loci in genetic predisposition to alcoholism and alcohol‐related organ injury, especially alcoholic cirrhosis.
Neonatal withdrawal syndrome and behavioral effects produced by maternal drug use
Authors: WEINTRAUB ZALMAN , BENTAL YORAM , OLIVAN ANITA , ROTSCHILD AVI
Published: July 2002

Over the last two decades, drug and alcohol abuse by pregnant women has spread to epidemic proportions. Maternal drug abuse has neurobehavioral and somatic effects which may be long‐lasting and devastating to the offspring. Opiates, such as heroin and pain killers that contain a narcotic component, are widely abused today. A prominent manifestation of fetal exposure to these drugs is the neonatal withdrawal syndrome, which typically includes wakefulness, jitteriness and other symptoms of cerebral irritability. These, in turn, may interrupt early mother‐infant interaction, affecting the infant's long‐term emotional and cognitive development. Fetal cocaine exposure may cause neonatal cerebral irritability, changes in habituation responses, reduced head circumference, poor mental development and long‐lasting impairment of the brain. Benzodiazepines can cause fetal dysmorphism (including microcephaly), neurological and behavioral impairments and neonatal withdrawal symptoms. Maternal use of amphetamines may cause neonatal dysphoria and agitation, as well as long‐term lassitude and drowsiness that may result in poor feeding. Fetal exposure to alcohol may cause neonatal withdrawal symptoms, maladaptive behavior in childhood and the fetal alcohol syndrome (including microcephaly). Maternal alcohol consumption is also a common cause of mental retardation. Fetal exposure to marijuana may delay maturation of the visual system and impair memory and verbal performance at 2 years of age. The inevitable conclusion is that society must seek ways not only to treat, but also to prevent this epidemic. To this end, a key factor would be to identify potential drug abusing mothers before they reach the stage of prenatal care and educate them regarding the fatal consequences of drug abuse.
Substance misuse in Aboriginal Australians
Authors: GRACEY MICHAEL
Published: July 2002

Australia's Aborigines lived in isolation from the rest of humanity as successful hunter‐gatherers for tens of thousands of years. That isolation ended abruptly with British colonization in the late 18th century and was followed by a traumatic 200 years for Aborigines who are now seriously disadvantaged, socio‐economically and in terms of their health standards. It has often been assumed that the Aborigines had no access to psychotropic substances before permanent European contact but several pieces of evidence dispute this view. The history of Aboriginal contact with and usage of intoxicating substances, including alcohol, is extremely complex and affected by a maze of restrictive government policies. These interact with a wide range of other Federal and State policies which have changed rapidly since the late 1960s when Aborigines were first granted the franchise; access to unrestricted drinking followed soon afterwards. Today Aborigines suffer disproportionately to other Australians from the physical and social consequences of excess alcohol consumption, tobacco usage, petrol and other solvent sniffing, usage of marijuana, amphetamines, cocaine and heroin, as well as other drugs. The Aboriginal population is dispersed in cities, towns, fringe settlements, rural and remote areas over this vast continent and there are different patterns of drug usage from place to place. This review attempts to synthesize some of this information in order to give an overview to the history, background, current status of substance misuse by Aborigines as well as some strategies being used to try to overcome this serious problem.
Liver disease due to illicit substance use
Authors: RIORDAN STEPHEN M. , WILLIAMS ROGER
Published: July 2002

While the adverse neurological, cardiovascular, renal, haematologic and musculoskeletal consequences of the use of various illicit substances are widely appreciated, less attention has been directed to possible hepatotoxic effects. This is an important issue in view of increasing evidence in both experimental animals and humans that the use of some illicit substances may be associated with substantial liver damage, leading on occasion to acute liver failure. This manuscript reviews the effects on the liver of some of the most commonly used illicit substances, including ecstasy (3,4‐methylenedioxymethamphetamine), other amphetamines, cocaine, heroin, angel dust (phencyclidine), lysergic acid diethylamide and marijuana. Additional causes of liver damage in those using illicit substances are discussed.
Alcohol problems in a general hospital
Authors: FOY AIDAN
Published: July 2002

Alcohol is a ubiquitous drug which is responsible for a substantial amount of ill health and approximately 20% of patients in a general hospital will have alcohol‐related problems, although only 4% will be admitted with alcohol‐caused conditions. Eight per cent of patients, however, can be expected to have sufficient neuroadaptation to be at risk of withdrawal. This level of prevalence of alcoholism in general hospital patients requires that hospitals must become expert at providing good quality care for alcohol‐related problems in all areas including obstetrics, but particularly in the management of intoxication, withdrawal and the various alcoholrelated diseases. This paper provides some suggested benchmarks for acceptable standards of care for alcohol problems in the acute hospital.
Perceptions of psychosocial adjustment to acquired communication disorders: applications of the Code‐Muller Protocols
Authors: Code Chris , Muller Dave J. , Hogan Anthony , Herrmann Manfred
Published: July 2002

The ‘Code‐Muller protocols’ (CMP) were introduced in 1983 and originally aimed to compare perceptions of psychosocial adjustment to aphasia and related disorders from the separate perspectives of patients, relatives and speech and language therapists as a basis for counselling. In later studies the items of the CMP were also used to examine perceptions of their importance as possible therapy targets in the rehabilitation of people with communication disorders. This paper describes the development of the CMP and presents an overview of their application in aphasia, laryngectomy and acquired deafness and discusses some clinical implications. Studies published in the past 15 years show that aphasic people and their relatives or significant others are significantly more optimistic concerning psychosocial adjustment than their therapists. Furthermore, optimism changes during the course of illness. The relative weightings given for therapy or rehabilitation targets significantly differ between different professional groups concerned with aphasia rehabilitation (speech and language therapists/pathologists, physiotherapists, occupational therapists, psychologists and physicians) and are influenced by clinical experience.
Instrumental assessment and treatment of hypernasality, following maxillofacial surgery, using SNORS: a single case study
Authors: Main Alison , Kelly Steve , Manley Graham
Published: July 2002

The super nasal oral ratiometry system (SNORS) is a commercially available system which measures both nasal and oral airflow during speech, allowing the very rapid movement of the velum to be measured. SNORS uses a modified oxygen mask, which houses the airflow sensors and microphones, and a standard personal computer. By calculating nasalance (the percentage of airflow that is nasal), an estimation of velopharyngeal closure, which is independent of speech intensity, is achieved. SNORS can be used for objective assessment, where the subject is required to speak a number of words selected to demonstrate velopharyngeal function. SNORS also provides biofeedback, using a simple realtime display of nasal and oral airflow. Velopharyngeal insufficiency (VPI) is the inability to make adequate velpharyngeal closure, and may be the result of either neurological or, as in this case, structural abnormalities. It results in abnormal speech characteristics, such as omissions, substitutions or weak articulation of consonants, and hypernasality. T.W., a 52 year old male, had very hypernasal speech following extensive maxillofacial surgery, for the removal of a tonsillar carcinoma. SNORS was successfully used as both an assessment and a therapy tool in the treatment of this patient. The effectiveness of conventional speech and language therapy vs. SNORS biofeedback therapy was compared. Initially, while there was some movement of the velum, the patient could not achieve velopharyngeal closure. Conventional therapy aimed to strengthen and improve the function of the velum and following this there was some minimal improvement: the patient could now achieve, but not maintain, closure. Reassessment, following a non‐treatment period, showed little further change. SNORS biofeedback therapy was then given. This raised the patient's awareness of his velopharyngeal function, thus helping him to maintain closure, thereby reducing hypernasality. SNORS therapy proved significantly more effective than conventional speech and language therapy, in this case. Further intervention is outlined, and the benefits of multiparameter assessment of speech are discussed.
Inappropriate sexual behaviour experienced by speech‐language therapists
Authors: Williams Timothy H. , de Seriere Jo , Boddington Lyn
Published: July 2002

Inappropriate sexual behaviour by clients or patients of health professionals has been noted as a considerable problem in a number of professions. Similarly, sexual harassment by colleagues or employers has been identified as causing stress and harm. The primary objective of this study was to investigate the experience of speech‐language therapists in New Zealand of inappropriate sexual behaviour (ISB) by colleagues, clients, and care givers of clients. A questionnaire developed by McComas and colleagues to investigate ISB directed by patients at physical therapists in Canada was adapted to meet the broader requirements of this study. This questionnaire was sent to all members of the New Zealand Speech‐Language Therapists' Association and to current third‐ and fourth‐year students in the Bachelor of Speech and Language Therapy degree programme in 1994. The overall return rate was 70%. A large number of respondents (81%) reported experiencing some level of ISB. The number of incidents of ISB from clients and colleagues was identified with equal frequency; care givers less frequently. Fewer students than qualified therapists reported ISB as sexual harassment. ISB affects work performance (e.g. absenteeism) and causes psychological reactions (e.g. stress). A majority of respondents reported being satisfied with how they handled ISB but considered there would be value in having training for both qualified and student therapists in managing such behaviour. Conclusions drawn from the study are that colleagues as well as clients are a serious source of ISB for qualified and student speech‐language therapists; that negative effects in this group are similar to those in other professions; that speech‐language therapists experience less ISB from clients than some other professions; and that, despite legal steps to curb sexual harassment, it continues to be an issue that requires local administrative and educative attention.
Protein Kinase C Activation Upregulates Intercellular Adhesion of α-Catenin–negative Human Colon Cancer Cell Variants via Induction of Desmosomes
Authors: Hengel Jolanda van , Gohon Lionel , Bruyneel Erik , Vermeulen Stefan , Cornelissen Maria , Mareel Marc , Roy Frans van
Published: July 2002

The α-catenin molecule links E-cadherin/ β-catenin or E-cadherin/plakoglobin complexes to the actin cytoskeleton. We studied several invasive human colon carcinoma cell lines lacking α-catenin. They showed a solitary and rounded morphotype that correlated with increased invasiveness. These round cell variants acquired a more normal epithelial phenotype upon transfection with an α-catenin expression plasmid, but also upon treatment with the protein kinase C (PKC) activator 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Video registrations showed that the cells started to establish elaborated intercellular junctions within 30 min after addition of TPA. Interestingly, this normalizing TPA effect was not associated with α-catenin induction. Classical and confocal immunofluorescence showed only minor TPA-induced changes in E-cadherin staining. In contrast, desmosomal and tight junctional proteins were dramatically rearranged, with a conversion from cytoplasmic clusters to obvious concentration at cell–cell contacts and exposition at the exterior cell surface. Electron microscopical observations revealed the TPA-induced appearance of typical desmosomal plaques. TPA-restored cell–cell adhesion was E-cadherin dependent as demonstrated by a blocking antibody in a cell aggregation assay. Addition of an antibody against the extracellular part of desmoglein-2 blocked the TPA effect, too. Remarkably, the combination of anti–E-cadherin and anti-desmoglein antibodies synergistically inhibited the TPA effect.

Our studies show that it is possible to bypass the need for normal α-catenin expression to establish tight intercellular adhesion by epithelial cells. Apparently, the underlying mechanism comprises upregulation of desmosomes and tight junctions by activation of the PKC signaling pathway, whereas E-cadherin remains essential for basic cell–cell adhesion, even in the absence of α-catenin.
Cellular Localization, Expression, and Structure of the Nuclear Dot Protein 52
Authors: Sternsdorf Thomas , Jensen Kirsten , Züchner Dirk , Will Hans
Published: July 2002

Nuclear dots containing PML and Sp100 proteins (NDs) play a role in the development of acute promyelocytic leukemia, are modified after infection with various viruses, and are autoimmunogenic in patients with primary biliary cirrhosis (PBC). PML and Sp100 gene expression is strongly enhanced by interferons (IFN). Based on immunostaining with a monoclonal antibody (mAb C8A2), a third protein, nuclear dot protein 52 (NDP52), was recently localized in NDs. Here we analyzed the cellular localization, expression, and structure of NDP52 in more detail. Our NDP52-specific sera revealed mainly cytoplasmic staining but no ND pattern, neither in untreated nor in IFN-treated cells. Cells transfected with NDP52 expression vectors showed exclusively cytoplasmic staining. In subcellular fractionation experiments, NDP52 was found in cytoplasmic and nuclear fractions. Unlike as described for Sp100 and PML, NDP52 mRNA and protein levels were only marginally enhanced by IFN γ and not enhanced at all by IFN β. NDP52 homodimerization but no heterodimerization with Sp100 or PML could be demonstrated. None of the 93 PBC sera tested contained autoantibodies against NDP52. Finally, mAb C8A2 reacted not only with NDP52 but also with a conformation-dependent epitope on the Sp100 protein. These data imply that NDP52 forms homodimers but no heterodimers with Sp100 and PML, lacks autoantigenicity in PBC, localizes mainly in the cytoplasm, and is associated with the nucleus, but not with NDs. Finally, unlike Sp100 and PML, NDP52 expression is neither markedly enhanced nor localization detectably altered by type I and II IFNs.
Kinesin-related KIP3 of Saccharomyces cerevisiae Is Required for a Distinct Step in Nuclear Migration
Authors: DeZwaan Todd M. , Ellingson Eric , Pellman David , Roof David M.
Published: July 2002

Spindle orientation and nuclear migration are crucial events in cell growth and differentiation of many eukaryotes. Here we show that KIP3, the sixth and final kinesin-related gene in Saccharomyces cerevisiae, is required for migration of the nucleus to the bud site in preparation for mitosis. The position of the nucleus in the cell and the orientation of the mitotic spindle was examined by microscopy of fixed cells and by time-lapse microscopy of individual live cells. Mutations in KIP3 and in the dynein heavy chain gene defined two distinct phases of nuclear migration: a KIP3-dependent movement of the nucleus toward the incipient bud site and a dynein-dependent translocation of the nucleus through the bud neck during anaphase. Loss of KIP3 function disrupts the unidirectional movement of the nucleus toward the bud and mitotic spindle orientation, causing large oscillations in nuclear position. The oscillatory motions sometimes brought the nucleus in close proximity to the bud neck, possibly accounting for the viability of a kip3 null mutant. The kip3 null mutant exhibits normal translocation of the nucleus through the neck and normal spindle pole separation kinetics during anaphase. Simultaneous loss of KIP3 and kinesin-related KAR3 function, or of KIP3 and dynein function, is lethal but does not block any additional detectable movement. This suggests that the lethality is due to the combination of sequential and possibly overlapping defects. Epitope-tagged Kip3p localizes to astral and central spindle microtubules and is also present throughout the cytoplasm and nucleus.
ATP- and Gap Junction–dependent Intercellular Calcium Signaling in Osteoblastic Cells
Authors: Jørgensen Niklas R. , Geist Steven T. , Civitelli Roberto , Steinberg Thomas H.
Published: July 2002

Many cells coordinate their activities by transmitting rises in intracellular calcium from cell to cell. In nonexcitable cells, there are currently two models for intercellular calcium wave propagation, both of which involve release of inositol trisphosphate (IP3)- sensitive intracellular calcium stores. In one model, IP3 traverses gap junctions and initiates the release of intracellular calcium stores in neighboring cells. Alternatively, calcium waves may be mediated not by gap junctional communication, but rather by autocrine activity of secreted ATP on P2 purinergic receptors. We studied mechanically induced calcium waves in two rat osteosarcoma cell lines that differ in the gap junction proteins they express, in their ability to pass microinjected dye from cell to cell, and in their expression of P2Y2 (P2U) purinergic receptors. ROS 17/2.8 cells, which express the gap junction protein connexin43 (Cx43), are well dye coupled, and lack P2U receptors, transmitted slow gap junction-dependent calcium waves that did not require release of intracellular calcium stores. UMR 106-01 cells predominantly express the gap junction protein connexin 45 (Cx45), are poorly dye coupled, and express P2U receptors; they propagated fast calcium waves that required release of intracellular calcium stores and activation of P2U purinergic receptors, but not gap junctional communication. ROS/P2U transfectants and UMR/Cx43 transfectants expressed both types of calcium waves. Gap junction–independent, ATP-dependent intercellular calcium waves were also seen in hamster tracheal epithelia cells. These studies demonstrate that activation of P2U purinergic receptors can propagate intercellular calcium, and describe a novel Cx43-dependent mechanism for calcium wave propagation that does not require release of intracellular calcium stores by IP3. These studies suggest that gap junction communication mediated by either Cx43 or Cx45 does not allow passage of IP3 well enough to elicit release of intracellular calcium stores in neighboring cells.
Identification of a Preinitiation Step in DNA Replication That Is Independent of Origin Recognition Complex and cdc6, but Dependent on cdk2
Authors: Hua Xuequn Helen , Newport John
Published: July 2002

Before initiation of DNA replication, origin recognition complex (ORC) proteins, cdc6, and minichromosome maintenance (MCM) proteins bind to chromatin sequentially and form preinitiation complexes. Using Xenopus laevis egg extracts, we find that after the formation of these complexes and before initiation of DNA replication, cdc6 is rapidly removed from chromatin, possibly degraded by a cdk2-activated, ubiquitin-dependent proteolytic pathway. If this displacement is inhibited, DNA replication fails to initiate. We also find that after assembly of MCM proteins into preinitiation complexes, removal of the ORC from DNA does not block the subsequent initiation of replication. Importantly, under conditions in which both ORC and cdc6 protein are absent from preinitiation complexes, DNA replication is still dependent on cdk2 activity. Therefore, the final steps in the process leading to initiation of DNA replication during S phase of the cell cycle are independent of ORC and cdc6 proteins, but dependent on cdk2 activity.
Bone Morphogenetic Protein Signaling Is Required for Maintenance of Differentiated Phenotype, Control of Proliferation, and Hypertrophy in Chondrocytes
Authors: Enomoto-Iwamoto Motomi , Iwamoto Masahiro , Mukudai Yoshiki , Kawakami Yasuhiko , Nohno Tsutomu , Higuchi Yoshinobu , Takemoto Seiji , Ohuchi Hideyo , Noji Sumihare , Kurisu Kojiro
Published: July 2002

To examine the role of bone morphogenetic protein (BMP) signaling in chondrocytes during endochondral ossification, the dominant negative (DN) forms of BMP receptors were introduced into immature and mature chondrocytes isolated from lower and upper portions of chick embryo sternum, respectively. We found that control sternal chondrocyte populations expressed type IA, IB, and II BMP receptors as well as BMP-4 and -7. Expression of a DN-type II BMP receptor (termed DN-BMPR-II) in immature lower sternal (LS) chondrocytes led to a loss of differentiated functions; compared with control cells, the DN-BMPR- II–expressing LS chondrocytes proliferated more rapidly, acquired a fibroblastic morphology, showed little expression of type II collagen and aggrecan genes, and upregulated type I collagen gene expression. Expression of DN-BMPR-II in mature hypertrophic upper sternal (US) chondrocytes caused similar effects. In addition, the DN-BMPR-II–expressing US cells exhibited little alkaline phosphatase activity and type X collagen gene expression, while the control US cells produced both alkaline phosphatase and type X collagen. Both DN-BMPR-II–expressing US and LS chondrocytes failed to respond to treatment with BMP-2 . When we examined the effects of DN forms of types IA and IB BMP receptors, we found that DN-BMPR-IA had little effect, while DN-BMPR-IB had similar but weaker effects compared with those of DN-BMPR-II. We conclude that BMP signaling, particularly that mediated by the type II BMP receptor, is required for maintenance of the differentiated phenotype, control of cell proliferation, and expression of hypertrophic phenotype.
Retrieval of Resident Late-Golgi Membrane Proteins from the Prevacuolar Compartment of Saccharomyces cerevisiae Is Dependent on the Function of Grd19p
Authors: Voos Wolfgang , Stevens Tom H.
Published: July 2002

The dynamic vesicle transport processes at the late-Golgi compartment of Saccharomyces cerevisiae (TGN) require dedicated mechanisms for correct localization of resident membrane proteins. In this study, we report the identification of a new gene, GRD19, involved in the localization of the model late-Golgi membrane protein A-ALP (consisting of the cytosolic domain of dipeptidyl aminopeptidase A [DPAP A] fused to the transmembrane and lumenal domains of the alkaline phosphatase [ALP]), which localizes to the yeast TGN. A grd19 null mutation causes rapid mislocalization of the late-Golgi membrane proteins A-ALP and Kex2p to the vacuole. In contrast to previously identified genes involved in late-Golgi membrane protein localization, grd19 mutations cause only minor effects on vacuolar protein sorting. The recycling of the carboxypeptidase Y sorting receptor, Vps10p, between the TGN and the prevacuolar compartment is largely unaffected in grd19Δ cells. Kinetic assays of A-ALP trafficking indicate that GRD19 is involved in the process of retrieval of A-ALP from the prevacuolar compartment. GRD19 encodes a small hydrophilic protein with a predominantly cytosolic distribution. In a yeast mutant that accumulates an exaggerated form of the prevacuolar compartment (vps27), Grd19p was observed to localize to this compartment. Using an in vitro binding assay, Grd19p was found to interact physically with the cytosolic domain of DPAP A. We conclude that Grd19p is a component of the retrieval machinery that functions by direct interaction with the cytosolic tails of certain TGN membrane proteins during the sorting/budding process at the prevacuolar compartment.
A Role for Dictyostelium RacE in Cortical Tension and Cleavage Furrow Progression
Authors: Gerald Noel , Dai Jianwu , Ting-Beall H. Ping , De Lozanne Arturo
Published: July 2002

The small GTPase racE is essential for cytokinesis in Dictyostelium. We found that this requirement is restricted to cells grown in suspension. When attached to a substrate, racE null cells form an actomyosin contractile ring and complete cytokinesis normally. Nonetheless, racE null cells fail completely in cytokinesis when in suspension. To understand this conditional requirement for racE, we developed a method to observe cytokinesis in suspension. Using this approach, we found that racE null cells attempt cytokinesis in suspension by forming a contractile ring and cleavage furrow. However, the cells form multiple blebs and fail in cytokinesis by regression of the cleavage furrow. We believe this phenotype is caused by the extremely low level of cortical tension found in racE null cells compared to wild-type cells. The reduced cortical tension of racE null cells is not caused by a decrease in their content of F-actin. Instead, mitotic racE null cells contain abnormal F-actin aggregates. These results suggest that racE is essential for the organization of the cortical cytoskeleton to maintain proper cortical integrity. This function of racE is independent of attachment to a substrate, but can be bypassed by other signaling pathways induced by adhesion to a substrate.
Control of Neuronal Size Homeostasis by Trophic Factor–mediated Coupling of Protein Degradation to Protein Synthesis
Authors: Franklin James L. , Johnson Eugene M.
Published: July 2002

We demonstrate that NGF couples the rate of degradation of long-lived proteins in sympathetic neurons to the rate of protein synthesis. Inhibiting protein synthesis rate by a specific percentage caused an almost equivalent percentage reduction in the degradation rate of long-lived proteins, indicating nearly 1:1 coupling between the two processes. The rate of degradation of short-lived proteins was unaffected by suppressing protein synthesis. Included in the pool of proteins that had increased half-lives when protein synthesis was inhibited were actin and tubulin. Both of these proteins, which had half-lives of several days, exhibited no degradation over a 3-d period when protein synthesis was completely suppressed. The half-lives of seven other long-lived proteins were quantified and found to increase by 84–225% when protein synthesis was completely blocked.

Degradation–synthesis coupling protected cells from protein loss during periods of decreased synthesis. The rate of protein synthesis greatly decreased and coupling between degradation and synthesis was lost after removal of NGF. Uncoupling resulted in net loss of cellular protein and somatic atrophy. We propose that coupling the rate of protein degradation to that of protein synthesis is a fundamental mechanism by which neurotrophic factors maintain homeostatic control of neuronal size and perhaps growth.
Fibronectin Matrix Regulates Activation of RHO and CDC42 GTPases and Cell Cycle Progression
Authors: Bourdoulous Sandrine , Orend Gertraud , MacKenna Deidre A. , Pasqualini Renata , Ruoslahti Erkki
Published: July 2002

Adherent cells assemble fibronectin into a fibrillar matrix on their apical surface. The fibril formation is initiated by fibronectin binding to the integrins α5β1 and αvβ3, and is completed by a process that includes fibronectin self-assembly. We found that a 76– amino acid fragment of fibronectin (III1-C) that forms one of the self-assembly sites caused disassembly of preformed fibronectin matrix without affecting cell adhesion. Treating attached fibroblasts or endothelial cells with III1-C inhibited cell migration and proliferation. Rho-dependent stress fiber formation and Rho-dependent focal contact protein phosphorylation were also inhibited, whereas Cdc42 was activated, leading to actin polymerization into filopodia. ACK (activated Cdc42-binding kinase) and p38 MAPK (mitogen-activated protein kinase), two downstream effectors of Cdc42, were activated, whereas PAK (p21-activated kinase) and JNK/SAPK (c-Jun NH2-terminal kinase/ stress-activated protein kinase) were inhibited. III1-C treatment also modulated activation of JNK and ERK (extracellular signal-regulated kinases) in response to growth factors, and reduced the activity of the cyclin E–cdk2 complex. These results indicate that the absence of fibronectin matrix causes activation of Cdc42, and that fibronectin matrix is required for Rho activation and cell cycle progression.
Saccharomyces cerevisiae Ndc1p Is a Shared Component of Nuclear Pore Complexes and Spindle Pole Bodies
Authors: Chial Heidi J. , Rout Michael P. , Giddings Thomas H. , Winey Mark
Published: July 2002

We report a novel connection between nuclear pore complexes (NPCs) and spindle pole bodies (SPBs) revealed by our studies of the Saccharomyces cerevisiae NDC1 gene. Although both NPCs and SPBs are embedded in the nuclear envelope (NE) in yeast, their known functions are quite distinct. Previous work demonstrated that NDC1 function is required for proper SPB duplication (Winey, M., M.A. Hoyt, C. Chan, L. Goetsch, D. Botstein, and B. Byers. 1993. J. Cell Biol. 122:743–751). Here, we show that Ndc1p is a membrane protein of the NE that localizes to both NPCs and SPBs. Indirect immunofluorescence microscopy shows that Ndc1p displays punctate, nuclear peripheral localization that colocalizes with a known NPC component, Nup49p. Additionally, distinct spots of Ndc1p localization colocalize with a known SPB component, Spc42p. Immunoelectron microscopy shows that Ndc1p localizes to the regions of NPCs and SPBs that interact with the NE. The NPCs in ndc1-1 mutant cells appear to function normally at the nonpermissive temperature. Finally, we have found that a deletion of POM152, which encodes an abundant but nonessential nucleoporin, suppresses the SPB duplication defect associated with a mutation in the NDC1 gene. We show that Ndc1p is a shared component of NPCs and SPBs and propose a shared function in the assembly of these organelles into the NE.