bluuebunny/crossref_metadata_2025 huggingface dataset:
Further Change in the Pattern of Mental Illness in the Elderly
Authors: Christie Alex B. , Wood Eric R. M.
Published: August 2008

The methods of Roth's 1948–49 Graylingwell study, previously applied to a Crichton cohort of elderly patients of the years 1974–76, were repeated in 1984–86. The results support the continuing validity of Roth's classification of mental illness in the elderly, but changes in the diagnostic distribution of the cohort, previously observed in the 1970s study, are further in evidence in the 1980s one. Admissions of dementia cases continued to increase both relatively and absolutely, while the trend of increasing survival in dementia also continued.
Accounting for Delusional Misidentifications
Authors: Ellis Hadyn D. , Young Andrew W.
Published: August 2008

Accounts of the major DMSs are given using theoretical models of the functional components underlying recognition of familiar people. Thus, Capgras' syndrome is suggested to involve impairment of processes that can support ‘covert’ recognition of familiar faces in prosopagnosia. It therefore forms a potential ‘mirror image’ of the impairments underlying prosopagnosia, and earlier attempts to link the two conditions directly are questioned. Frégoli syndrome and intermetamorphosis are explained as defects at different stages of an information-processing chain. Not only are these accounts consistent with the association of different DMSs with different brain injuries, but they also offer both suggestions for new inquiries and predictions about possible preserved and impaired abilities.
Treatment of Alzheimer's Disease
Authors: Bowen David M.
Published: August 2008

Cortical inhibitory neurotransmitters, neuropeptides, dopamine and noradrenaline are probably either not selectively or not critically affected in AD. It is, however, likely that a key change is shrinkage or loss of corticocortical pyramidal neurones, which probably use glutamate as their transmitter. This depletion appears to be circumscribed and clinically relevant.
Stress and Puerperal Psychosis
Authors: Brockington I. F. , Martin C. , Brown G. W. , Goldberg D. , Margison F.
Published: August 2008

Eighty-eight in-patients admitted to a psychiatric mother-and-baby unit and 80 randomly selected recently delivered women in the general population were interviewed using the LEDS. Only five of 33 patients (15%) with puerperal psychosis had provoking agents, which is less than the figure for women in the community (36%). Provoking agents were present in only 8 of 25 patients with post-natal depression, but they were present in seven of nine patients with pre-natal depression and eight of nine women in the community with pre-natal depression.
Are British Psychiatrists Racist?
Authors: Lewis Glyn , Croft-Jeffreys Caroline , David Anthony
Published: August 2008

Out of a sample of 220 British psychiatrists, 139 completed a questionnaire regarding a case vignette of a psychotic illness. The sex and ‘race’ of the vignette were varied and the responses compared. The Afro-Caribbean case was regarded as that of an illness of shorter duration, and requiring less neuroleptics than the white case. Respondents judged the Afro-Caribbean case as potentially more violent and thought criminal proceedings were more appropriate. The female vignette was perceived as less violent, less criminal, and less likely to need neuroleptics. Cannabis psychosis and acute reactive psychosis tended to be diagnosed more often and schizophrenia less often in Afro-Caribbean cases, refuting the claim that psychiatrists tend to overdiagnose schizophrenia in this group. Such ‘race thinking’ (a form of stereotyping which is distinct from ideological racism) could lead to inappropriate management.
Schizophrenia and Marfan Syndrome
Authors: Sirota Pinkhas , Frydman Moshe , Sirota Lea
Published: August 2008

Five index patients and three of their first-degree relatives were affected both by schizophrenia and Marfan syndrome. Since the association appears statistically significant, the possibility of linkage disequilibrium between adjacent genes or a cytogenetic abnormality causing both disorders is suggested. These hypotheses are testable and hold promise in attempting to map the ‘schizophrenia susceptibility gene’ by the candidate-gene approach.
Psychological Sequelae of Torture
Authors: Turner Stuart , Gorst-Unsworth Caroline
Published: August 2008

Torture is one of the most important preventable causes of psychological morbidity. Amnesty International (1987) has reported the use of “brutal torture and ill-treatment” in over 90 countries in the 1980s. In some countries torture has been applied on such a widespread scale and in such an arbitrary manner that whole populations are affected. In Kampuchea under the Pol Pot regime, for example, genocide and torture took place on a massive scale; indeed, merely wearing spectacles became for many a capital offence (Amnesty International, 1983). Similar reports abound from many other countries and regions.
Overexcitement and Disinhibition
Authors: Glue Paul , Nutt David
Published: August 2008

In alcohol withdrawal, abnormalities occur in a number of neurotransmitter systems: there is reduced inhibitory function, and increased activity of excitatory systems. The former, indicated by reduced GABA and alpha-2-adrenoceptor activity, acts in conjunction with, and is exacerbated by, the latter, which itself may be due to the potentiation of NMDA activity by depletion of magnesium, and overactivity of catecholaminergic and CRF neurones. These dysfunctions produce immediate effects and may also contribute to the long-term changes in brain excitability by a kindling-like process. It is possible that early and active treatment may oppose this process. Present strategies for treatment of alcohol withdrawal enhance GABA and alpha-2 inhibitory, or reduce excitatory, mechanisms. Future possibilities include the use of CRF and/or NMDA antagonists.
Towards a System of Outcome Indicators for Mental Health Care
Authors: Jenkins Rachel
Published: August 2008

A system of outcome indicators for mental health care is urgently needed in order to ensure that clinicians, district health authorities, and directors of public health can monitor and evaluate mental health care. Theoretical aspects of health care indicators and the various classes of outcome measures available can be used to draw up a preliminary system of indicators of health care input, process and outcome for the major categories of mental illness, including schizophrenia, affective psychosis, neurosis, dementia, mental handicap, child psychiatry, forensic psychiatry, alcohol and drugs. Such a system is not intended to be definitive or exhaustive but rather to form a basis for development by clinicians, researchers and planners for their own requirements.
Suicide in Cork and Ireland
Authors: Kelleher Michael J. , Daly Maura
Published: August 2008

The official suicide rate in Ireland increased markedly between 1970 and 1985. This is a genuine increase in suicide and not an apparent one due to previous deficiencies in recording practices. Possible reasons for this change include an increase in‘anomie’shown by a rise in the rates of crime, illegitimacy and admissions to hospital for alcoholism, a decline in social cohesion revealed by a fall in the marriage rate and a rise in the number of separated couples, and an increase in unemployment.
Regional Brain Metabolism During Auditory Hallucinations in Chronic Schizophrenia
Authors: Cleghorn J. M. , Garnett E. S. , Nahmias C. , Brown G. M. , Kaplan R. D. , Szechtman H. , Szechtman B. , Franco S. , Dermer S. W. , Cook P.
Published: August 2008

Regions of the brain involved in language and attention were studied using [18F]-fluorodeoxyglucose in PET. In nine chronic DSM–III schizophrenic patients who had persistent auditory hallucinations, ten who had recovered from hallucinations and ten normal controls. In none of the regions examined was metabolic activity significantly different in hallucinating patients compared with that in other groups. However, a pattern of seven significant correlations of metabolic activity between language regions and between frontal and parietal cortex characterised the hallucinating but not the other groups. Three of the seven correlations were significantly greater in hallucinating patients than in the two other groups, and six were greater in hallucinating patients than controls. Metabolism in Broca's region and its right-hemisphere homologue correlated positively and significantly in the hallucinating group, as it did in anterior cingulate and left superior temporal areas, and in right frontal and parietal areas. Hallucination ratings correlated with metabolism in the anterior cingulate region.
Obstetric Complications, the Putative Familial-Sporadic Distinction, and Tardive Dyskinesia in Schizophrenia
Authors: O'Callaghan Eadbhard , Larkin Conall , Kinsella Anthony , Waddington John L.
Published: August 2008

Obstetric complications were more common in the histories of those schizophrenic outpatients without a family history of psychiatric disorder, and were associated with an earlier onset of their illness. Those patients with tardive dyskinesia were more likely to have a family history of psychiatric disorder, less likely to have experienced obstetric complications, and showed greater cognitive deficit. Obstetric complications should be considered in juxtaposition with genetic factors in evaluating the putative familial-sporadic distinction in schizophrenia. Additionally, familial/genetic factors appear to contribute to vulnerability to tardive dyskinesia.
Genetic Linkage in Mental Illness
Authors: Baron Miron , Endicott Jean , Ott Jurg
Published: August 2008

Advances in genetic linkage strategies, including techniques of molecular genetics, augur well for the discovery of disease-related genes in mental disorders. Recent studies showing linkage of chromosomal loci to bipolar affective illness and schizophrenia attest to the potential in the ‘new genetics'. However, the failure to replicate some of the early findings has led to calls for re-evaluation of the methodology in psychiatric research. Problems in studying complex (psychiatric) disorders include diagnostic uncertainties, unclear mode of transmission, aetiological heterogeneity, cohort effects, and assortative mating. Knowing the potential pitfalls in linkage analysis of mental illness should avert spurious findings and will increase the prospects of success.
Monoamines and Abnormal Behaviour a Multi-Aminergic Perspective
Authors: Van Praag H. M. , Asnis G. M. , Kahn R. S. , Brown S. L. , Korn M. , Friedman J. M. Harkavy , Wetzler S.
Published: August 2008

Classical nosology has been the cornerstone of biological psychiatric research; finding biological markers and eventually causes of disease entities has been the major goal. Another approach, designated as ‘functional’, is advanced here, attempting to correlate biological variables with psychological dysfunctions, the latter being considered to be the basic units of classification in psychopathology. Signs of diminished DA, 5–HT and NA metabolism, as have been found in psychiatric disorders, are not disorder-specific, but rather are related to psychopathological dimensions (hypoactivity/inertia, increased aggression/anxiety, and anhedonia) independent of the nosological framework in which these dysfunctions occur. Implications of the functional approach for psychiatry include a shift from nosological to functional application of psychotropic drugs. Functional psychopharmacology will be dysfunction-orientated and therefore geared towards utilising drug combinations. This prospect is hailed as progress, both practically and scientifically.
The Systematic Collection of Patient Data in a Centre for Child and Adolescent Psychiatry
Authors: Treffers Philip D. A. , Goedhart Arnold W. , Waltz Jan W. , Koudijs Els
Published: August 2008

Computerisation of case records has been slow to take place in child psychiatry, partly because of the amount of detailed and sometimes complex information required. A program for storing case records has been developed and it has proved of great value in epidemiological work, for example, regarding patient age structures and family compositions.
To Weigh or Not to Weigh?
Authors: Touyz S. W. , Lennerts W. , Freeman R. J. , Beumont P. J. V.
Published: August 2008

The present study compares the rate of weight gain during refeeding in 15 anorectic patients who were weighed daily with that of 15 who were weighed three times per week. There was no significant difference between the two groups.
The Effect of Neuroleptics on Cognitive and Psychomotor Function
Authors: King David J.
Published: August 2008

There has been great variability and inconsistency in the reported effects of neuroleptic drugs on cognitive and psychomotor function in both patients and normal controls. Experimental design rather than any particular cognitive or psychomotor test appears to have determined the sensitivity of detection of neuroleptic drug effects. In general, sedative phenothiazines have been found to depress psychomotor function and sustained attention, but higher cognitive functions are relatively unaffected. In the majority of studies of schizophrenic patients, both cognitive function and attention improve with neuroleptic treatment, in parallel with clinical recovery. Negative symptoms are not increased and usually show slight improvement with neuroleptic treatment. Controls are more sensitive than schizophrenic patients to neuroleptic drug-induced impairments. Tolerance has been seen in patients but has not been demonstrated in normal volunteers. The way in which neuroleptics produce their beneficial effects in patients remains unknown. Three main hypotheses to replace early arousal theories are proposed: normalisation of attention, facilitated indirectly by suppression of ‘released’ limbic dopamine hyperactivity; normalisation of asymmetrical temporohippocampal function; or direct improvement of attentional processing. Studies of the effects of new antipsychotic drugs with selective actions and the development of more reliable and selective tests of psychomotor and cognitive functions are required.
The TAPS Project. 5: the Structure of Social-Network Data Obtained from Long-Stay Patients
Authors: Leff J. , O'Driscoll C. , Dayson D. , Wills W. , Anderson J.
Published: August 2008

The Social Network Schedule was successfully completed on 489 (64%) of 770 long-stay patients in Friern and Claybury Hospitals and the data on 3774 social contacts of the patients subjected to log-linear modelling. This showed that the category ‘confidant’ was salient in understanding the data. Latent-class analysis highlighted the importance of the nature of the social interaction between patients and their contacts. In particular, non-verbal exchanges of goods and services emerged as important in creating social bonds.
Three Thousand Days of Pregnancy
Authors: De Pauw Karel W.
Published: August 2008

An unusual case of pseudocyesis of almost ten-year duration, characterised by a monosymptomatic hypochondriacal delusion and a selective response to pimozide is reported. The nosological status of the diagnosis, delusional (paranoid) disorder, is suggested to be a variety of the Kraepelinian concept of paranoia. The therapeutic pitfalls of relying on a phenomenological distinction between overvalued ideas and delusional beliefs are discussed.
Multiple functions encoded by the N-terminal PAT domain of adipophilin
Authors: Orlicky David J. , DeGala Greg , Greenwood Carrie , Bales Elise S. , Russell Tanya D. , McManaman James L.
Published: August 2008

Adipophilin (ADPH), a member of the perilipin family of cytoplasmic lipid droplet (CLD)-binding proteins, is crucially dependent on triglyceride synthesis for stability. We have used cell lines expressing full-length or N-terminally modified forms of ADPH to investigate the role of the N-terminus in regulating ADPH stability and interactions with CLD. Full-length ADPH was unstable and could not be detected on CLDs unless cultures were incubated with oleic acid (OA) to stimulate triglyceride synthesis, or were treated with MG132 to block proteasomal degradation. By contrast, ADPH lacking amino acids 1-89 (Δ 2,3 ADPH), or N-terminally GFP-tagged full-length ADPH, was stable in the absence of OA or MG132, as was the closely related protein TIP47. However, none of these proteins localized to CLDs unless OA was added to the culture medium. Furthermore, immunofluorescence analysis showed that TIP47 localization to CLDs was prevented by full-length ADPH, but not by Δ 2,3 ADPH. These results suggest that the N-terminal region of ADPH mediates proteasomal degradation and access of TIP47 to the CLD surface and possibly contributes to CLD stability. Chimeras of ADPH and TIP47, generated by swapping their N- and C-terminal halves, showed that these properties are specific to ADPH.
Canonical Wnt signalling induces satellite-cell proliferation during adult skeletal muscle regeneration
Authors: Otto Anthony , Schmidt Corina , Luke Graham , Allen Steve , Valasek Petr , Muntoni Francesco , Lawrence-Watt Diana , Patel Ketan
Published: August 2008

Satellite cells represent the stem cell population of adult skeletal muscle. The molecular mechanisms that control the proliferation of satellite cells are not well understood. In this study, we show that in response to injury, myofibres activate Wnt ligand transcription and activate a reporter cell line that is sensitive to the canonical Wnt-signalling pathway. Activated satellite cells on isolated cultured myofibres show robust expression of activated-β-catenin (Act-β-Cat), a key downstream transcriptional coactivator of canonical Wnt signalling. We provide evidence that the Wnt family of secreted glycoproteins act on satellite cells in a ligand-specific manner. Overexpression of Wnt1, Wnt3a or Wnt5a protein causes a dramatic increase in satellite-cell proliferation. By contrast, exposure of satellite cells to Wnt4 or Wnt6 diminishes this process. Moreover, we show that the prolonged satellite-cell quiescence induced by inhibitory Wnt is reversible and exposing inhibited satellite cells to stimulatory Wnt signalling restores their proliferation rate. Stimulatory Wnt proteins induce premature satellite cell BrdU incorporation as well as nuclear translocation of Act-β-Cat. Finally, we provide evidence that the Act-β-Cat translocation observed in single fibres during in vitro culture also occurs in cases of acute and chronic skeletal muscle regeneration in rodents and humans. We propose that Wnt proteins may be key factors that regulate the rate of satellite-cell proliferation on adult muscle fibres during the wound-healing response.
Arginine deiminase has multiple regulatory roles in the biology ofGiardia lamblia
Authors: Touz Maria Carolina , Rópolo Andrea Silvana , Rivero Maria Romina , Vranych Cecilia Veronica , Conrad John Thomas , Svard Staffan Gunnar , Nash Theodore Elliott
Published: August 2008

The protozoan parasite Giardia lamblia uses arginine deiminase (ADI) to produce energy from free L-arginine under anaerobic conditions. In this work, we demonstrate that, in addition to its known role as a metabolic enzyme, it also functions as a peptidylarginine deiminase, converting protein-bound arginine into citrulline. G. lamblia ADI specifically binds to and citrullinates the arginine in the conserved CRGKA tail of variant-specific surface proteins (VSPs), affecting both antigenic switching and antibody-mediated cell death. During encystation, ADI translocates from the cytoplasm to the nuclei and appears to play a regulatory role in the expression of encystation-specific genes. ADI is also sumoylated, which might modulate its activity. Our findings reveal a dual role played by ADI and define novel regulatory pathways used by Giardia for survival.
btn1affects cytokinesis and cell-wall deposition by independent mechanisms, one of which is linked to dysregulation of vacuole pH
Authors: Codlin Sandra , Haines Rebecca L. , Jemima J. , Burden E. , Mole Sara E.
Published: August 2008

btn1, the Schizosaccharomyces pombe orthologue of the human Batten-disease gene CLN3, is involved in vacuole pH homeostasis. We show that loss of btn1 also results in a defective cell wall marked by sensitivity to zymolyase, a β-glucanase. The defect can be rescued by expression of Btn1p or CLN3, and the extent of the defect correlates with disease severity. The vacuole and cell-wall defects are linked by a common pH-dependent mechanism, because they are suppressed by growth in acidic pH and a similar glucan defect is also apparent in the V-type H+ ATPase (v-ATPase) mutants vma1Δ and vma3Δ. Significantly, Btn1p acts as a multicopy suppressor of the cell-wall and other vacuole-related defects of these v-ATPase-null cells. In addition, Btn1p is required in a second, pH-independent, process that affects sites of polarised growth and of cell-wall deposition, particularly at the septum, causing cytokinesis problems under normal growth conditions and eventual cell lysis at 37°C. Thus, Btn1p impacts two independent processes, which suggests that Batten disease is more than a pH-related lysosome disorder.
P-Rex1 – a multidomain protein that regulates neurite differentiation
Authors: Waters JoAnne E. , Astle Megan V. , Ooms Lisa M. , Balamatsias Demis , Gurung Rajendra , Mitchell Christina A.
Published: August 2008

The Rac-GEF P-Rex1 promotes membrane ruffling and cell migration in response to Rac activation, but its role in neuritogenesis is unknown. Rac1 promotes neurite differentiation; Rac3, however, may play an opposing role. Here we report that in nerve growth factor (NGF)-differentiated rat PC12 cells, P-Rex1 localised to the distal tips of developing neurites and to the axonal shaft and growth cone of differentiating hippocampal neurons. P-Rex1 expression inhibited NGF-stimulated PC12 neurite differentiation and this was dependent on the Rac-GEF activity of P-Rex1. P-Rex1 inhibition of neurite outgrowth was rescued by low-dose cytochalasin D treatment, which prevents actin polymerisation. P-Rex1 activated Rac3 GTPase activity when coexpressed in PC12 cells. In the absence of NGF stimulation, targeted depletion of P-Rex1 in PC12 cells by RNA interference induced the spontaneous formation of β-tubulin-enriched projections. Following NGF stimulation, enhanced neurite differentiation, with neurite hyper-elongation correlating with decreased F-actin at the growth cone, was demonstrated in P-Rex1 knockdown cells. Interestingly, P-Rex1-depleted PC12 cells exhibited reduced Rac3 and Rac1 GTPase activity. This study has identified P-Rex1 as a Rac3-GEF in neuronal cells that localises to, and regulates, actin cytoskeletal dynamics at the axonal growth cone to in turn regulate neurite differentiation.
Ral-regulated interaction between Sec5 and paxillin targets Exocyst to focal complexes during cell migration
Authors: Spiczka Krystle S. , Yeaman Charles
Published: August 2008

Changes in cellular behavior that cause epithelial cells to lose adhesiveness, acquire a motile invasive phenotype and metastasize to secondary sites are complex and poorly understood. Molecules that normally function to integrate adhesive spatial information with cytoskeleton dynamics and membrane trafficking probably serve important functions in cellular transformation. One such complex is the Exocyst, which is essential for targeted delivery of membrane and secretory proteins to specific plasma membrane sites to maintain epithelial cell polarity. Upon loss of cadherin-mediated adhesion in Dunning R3327-5′A prostate tumor cells, Exocyst localization shifts from lateral membranes to tips of protrusive membrane extensions. Here, it colocalizes and co-purifies with focal complex proteins that regulate membrane trafficking and cytoskeleton dynamics. These sites are the preferred destination of post-Golgi transport vesicles ferrying biosynthetic cargo, such as α5-integrin, which mediates adhesion of cells to the substratum, a process essential to cell motility. Interference with Exocyst activity impairs integrin delivery to plasma membrane and inhibits tumor cell motility and matrix invasiveness. Localization of Exocyst and, by extension, targeting of Exocyst-dependent cargo, is dependent on Ral GTPases, which control association between Sec5 and paxillin. Overexpression of Ral-uncoupled Sec5 mutants inhibited Exocyst interaction with paxillin in 5′A cells, as did RNAi-mediated reduction of either RalA or RalB. Reduction of neither GTPase significantly altered steady-state levels of assembled Exocyst in these cells, but did change the observed localization of Exocyst proteins.
An analysis of railway system gauge proving using trains equipped with polystyrene blocks
Authors: Johnson D M
Published: August 2008

In order to test that clearances between trains and the infrastructure are adequate, it has been a common practice on some railway administrations to perform a proving run on new or refurbished railway systems, using trains equipped with a series of frangible polystyrene blocks attached to it. If, at the end of testing, the blocks either remain intact, or have only minor damage from identifiable strikes, this provides confidence that the system is safe for running. Modern techniques of measurement and simulation are now widely used in gauging. Due to extensive validation, the results of such simulation provide sufficient evidence of safety that this alone may be used, without the need for proving runs. Computer simulation provides analysis of a far greater range of scenarios, such as loading, wear, and failure modes that cannot be tested in physical proving. By analysing the gauging system through simulation, this paper seeks to understand the results of ‘polystyrene block gauging’, and in particular whether it provides adequate evidence of safe clearances, and whether it has a place in the gauging of the modern railway.
Reducing uncertainties in structure gauging
Authors: Bradbury W M S , Westwood T
Published: August 2008

This project investigated uncertainties in the gauging process to permit the development of improved methods. Preliminary studies investigated the potential sources of error in the areas of measurement, track and structure position, and vehicle position (including the effects of wind). A Monte-Carlo and an approximate analytic, method quantified individual and total propagated biases and uncertainties in the clearance. The dominant sources of bias were found to be the track tolerances, measurement error allowances, steering allowances, and conservatism in the swept envelope. The dominant sources of uncertainty were found to be specific measurement uncertainties, surface position variations for irregular or poorly aligned structures, approximations in the swept envelope calculation, and the effects of cant variation or wind on the swept envelope. The present method of applying tolerances (by linear super-position) can be challenged as individual tolerances do not bear a consistent relationship with the potential errors and variations they represent and because the superposition results in a level of safety that will vary according to the relative importance of factors at different locations. An improved method for determining and applying tolerances is recommended. This is based on the probabilistic approach used for the uncertainty analysis.
A gauging strategy for Great Britain
Authors: Wilson B C
Published: August 2008

The paper outlines the historical development and issues which affect railway vehicle gauging on the Great Britain rail network and describes the circumstances which make such a strategy viable now. From this, the potential benefits for passengers and freight operations of a gauging strategy are described. An overview of the work undertaken to develop the strategy is provided, which includes the development of a better understanding of the rail network and its interaction with vehicles. The concepts of analysis of the whole network to define profiles for interoperable and intercity vehicles are described and the issues related to double deck trains are discussed. The development of a core network of intermodal freight cleared routes and the need for an enhanced freight gauge classification system are discussed. Preliminary benefits associated with a strategy are shown, along with a description decision support tool for project evaluation. The strands are brought together to describe the main components of the strategy and, finally, the plans for the implementation of the strategy are outlined.
Firefly luciferase gene contains a cryptic promoter
Authors: Vopálenský Václav , Mašek Tomáš , Horváth Ondřej , Vicenová Blanka , Mokrejš Martin , Pospíšek Martin
Published: August 2008

A firefly luciferase (FLuc) counts among the most popular reporters of present-day molecular and cellular biology. In this study, we report a cryptic promoter activity in the luc+ gene, which is the most frequently used version of the firefly luciferase. The FLuc coding region displays cryptic promoter activity both in mammalian and yeast cells. In human CCL13 and Huh7 cells, cryptic transcription from the luc+ gene is 10–16 times weaker in comparison to the strong immediate-early cytomegalovirus promoter. Additionally, we discuss a possible impact of the FLuc gene cryptic promoter on experimental results especially in some fields of the RNA-oriented research, for example, in analysis of translation initiation or analysis of miRNA/siRNA function. Specifically, we propose how this newly described cryptic promoter activity within the FLuc gene might contribute to the previous determination of the strength of the cryptic promoter found in the cDNA corresponding to the hepatitis C virus internal ribosome entry site. Our findings should appeal to the researchers to be more careful when designing firefly luciferase-based assays as well as open the possibility of performing some experiments with the hepatitis C virus internal ribosome entry site, which could not be considered until now.
Propylene Glycol-Induced Lactic Acidosis in a Patient Receiving Continuous Infusion Pentobarbital
Authors: Miller Melissa A , Forni Allison , Yogaratnam Dinesh
Published: August 2008

Objective:

To report a case of probable propylene glycol (PG) toxicity in a patient receiving continuous infusion of pentobarbital for refractory status epilepticus.

Case Summary:

A 59-yoar-old woman with a declining mental status was admitted to the intensive care unit for management of status epilepticus. After failing to achieve the therapeutic endpoint of electroencephalogram burst suppression with a continuous infusion of propofol, the sedative regimen was changed to continuous infusion of pentobarbital. The patient received a loading dose of 450 mg (5 mg/kg), and the maintenance infusion was titrated to a dose of 10 mg/kg/h to achieve burst suppression. Twelve hours after the pentobarbital infusion was started, the patient developed an anion gap metabolic acidosis, elevated serum lactate level, hyperosmolality, and increased osmolal gap. The pentobarbital infusion was discontinued, and the patient's acidosis and hyperosmolality resolved.

Discussion:

Pentobarbital contains 40% v/v of PG, which was thought to be a potential source of the patient's metabolic derangements. Reports of toxicity with drugs containing PG. particularly intravenous lorazepam, have been well described in the literature. What we describe, however, is one of few reports involving intravenous pentobarbital. The Naranjo probability scale supports a probable drug-related adverse event in our patient.

Conclusions:

PG toxicity is a potential complication associated with intravenouspentobarbital. Practitioners should be aware of the PG content of pentobarbital and should be familiar with the signs and symptoms associated with PG toxicity.
Delayed-Onset Neutropenia with Divalproex Sodium
Authors: Stoner Steven C , Deal Eli , Lurk Jason T
Published: August 2008

Objective:

To report the development of neutropenia in a patient after almost 8 years of being stabilized on delayed-release divalproex sodium (DVPX).

Case Summary:

A 45-year-old man had been maintained on DVPX for nearly 8 years, with serum valproic acid concentrations of 85-120 mg/L and normal white blood cell (WBC) counts and absolute neutrophil counts (ANCs). Five months prior to the development of neutropenia (defined as ANC <1800 cells/μL), the patient's DVPX dosage was decreased by 250 mg to 1250 mg every morning and 1500 mg every evening. After 2 months of that regimen, the DVPX dosage was increased back to 1500 mg twice daily. Three months alter that increase, the patient's WBC count dropped to 3.7 × 103/μL and ANC was 1199 cells/μL Although the ANC was below 1800 cells/μL, he showed no physical manifestations consistent with neutropenia. DVPX was discontinued, and 2 weeks later the patient's WBC count was 7.2 x 103/μL and ANC was 2290 cells/μL.

Discussion:

Although a complete blood cell count with differential is a commonly accepted form of therapeutic drug monitoring with DVPX, the monitoring is considered most necessary to identify dose-retated thrombocytopenia. However, neutropenia has been rarely associated with the use of DVPX and could contribute to the development of different types of infection, including those of a bacterial, viral, or fungal origin. Although neutropenia is generally mild in severity, potentially severe DVPX-associated neutropenia can occur any time during the course of therapy, although it is most common within the first few months of treatment. In this case, DVPX was the probable cause of the neutropenia, according to the Naranjo probability scale. However, this case of neutropenia is atypical with respect to the timeframe in which it developed and was identified. Although the documented laboratory findings suggest neutropenia, the patient did not experience any clinical complications as a result. The late onset of the patient's neutropenia is unlike other cases that have been documented in the literature.

Conclusions:

Hematologic therapeutic drug monitoring continues to be clinically important regardless of whether the patient is early in therapy or even years later in the course. In this patient, continued regular therapeutic drug monitoring identified a suspected drug-related complication and the medication was able to be discontinued without the development of clinical complications.
Towards novel wood-based materials: Chemical bonds between lignin-like model molecules and poly(furfuryl alcohol) studied by NMR
Authors: Nordstierna Lars , Lande Stig , Westin Mats , Karlsson Olov , Furó István
Published: August 2008

Wood modification with furfuryl alcohol is a non-toxic alternative to conventional preservation treatments. A process in which furfuryl alcohol polymerises in situ was previously proposed for chemical modification of wood. In the present work, liquid model systems were investigated using compounds that resemble repeating units of lignin to verify whether chemical bonds form between the furfuryl alcohol polymer and wood. Using different NMR spectroscopic techniques we confirmed that these model compounds do form covalent bonds with the polymerising polymer. The results indicate that the furan polymer grafts to lignin, supporting observations in similar studies performed with genuine wood materials.
Loss of PINK1 Function Affects Development and Results in Neurodegeneration in Zebrafish
Authors: Anichtchik Oleg , Diekmann Heike , Fleming Angeleen , Roach Alan , Goldsmith Paul , Rubinsztein David C.
Published: August 2008

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder in the Western world. PTEN (phosphatase/tensin homolog on chromosome 10)-induced putative kinase 1 (PINK1), a putative kinase that is mutated in autosomal recessive forms of PD, is also implicated in sporadic cases of the disease. Although the mutations appear to result in a loss of function, the roles of this protein and the pathways involved in PINK1 PD are poorly understood. Here, we generated a vertebrate model of PINK1 insufficiency using morpholino oligonucleotide knockdown in zebrafish (Danio rerio). PINK1 knockdown results in a severe developmental phenotype that is rescued by wild-type human PINK1 mRNA. Morphants display a moderate decrease in the numbers of central dopaminergic neurons and alterations of mitochondrial function, including increases in caspase-3 activity and reactive oxygen species (ROS) levels. When the morphants were exposed to several drugs with antioxidant properties, ROS levels were normalized and the associated phenotype improved. In addition, GSK3β-related mechanisms can account for some of the effects of PINK1 knockdown, as morphant fish show elevated GSK3β activity and their phenotype is partially abrogated by GSK3β inhibitors, such as LiCl and SB216763 [3-(2,4-dichlorophenyl)-4-(1-methyl-1H-indol-3-yl)1H-pyrrole-2,5-dione]. This provides new insights into the biology of PINK1 and a possible therapeutic avenue for further investigation.
Regulation of Axonal Elongation and Pathfinding from the Entorhinal Cortex to the Dentate Gyrus in the Hippocampus by the Chemokine Stromal Cell-Derived Factor 1α
Authors: Ohshima Yoichi , Kubo Takekazu , Koyama Ryuta , Ueno Masaki , Nakagawa Masanori , Yamashita Toshihide
Published: August 2008

During the early developmental stage, a neural circuit is established between the entorhinal cortex (EC) and the hippocampal dentate gyrus (DG) via the perforant pathway. However, the manner in which the perforant fibers are navigated has mostly remained a mystery. Here, we analyzed the functional role of a chemokine, namely, stromal cell-derived factor 1α (SDF-1α), in the navigation of the perforant fibers. SDF-1α was observed to promote neurite growth, which is dependent on mDia1, in cultured entorhinal cortical neurons obtained from rats at postnatal day 0. We then used entorhino-hippocampal cocultures comprising green fluorescence-labeled EC and DG slices to assess the projection of the perforant fibers from the EC. Although the specific laminar termination of the entorhinal axons was observed with this system, the number of appropriately terminating entorhinal axons decreased significantly when the SDF-1α signaling pathway was blocked by a neutralizing antibody against SDF-1α or by the specific SDF-1α receptor antagonist AMD3100 (1,1′-[1,4-phenylenebis(methylene)]bis-1,4,8,11-tetra-azacyclotetradecane octahydrochloride). Furthermore, inhibition of the SDF-1α signaling pathway resulted in a decrease in the immunoreactivity for PSD-95 (postsynaptic density protein-95) in the DG, possibly because of a reduction in the number of projecting perforant fibers. These results demonstrate that SDF-1α plays a critical role in promoting the growth of perforant fibers from the EC to the DG.
Very Slow EEG Fluctuations Predict the Dynamics of Stimulus Detection and Oscillation Amplitudes in Humans
Authors: Monto Simo , Palva Satu , Voipio Juha , Palva J. Matias
Published: August 2008

Our ability to perceive weak signals is correlated among consecutive trials and fluctuates slowly over time. Although this “streaking effect” has been known for decades, the underlying neural network phenomena have remained largely unidentified. We examined the dynamics of human behavioral performance and its correlation with infraslow (0.01–0.1 Hz) fluctuations in ongoing brain activity. Full-band electroencephalography revealed prominent infraslow fluctuations during the execution of a somatosensory detection task. Similar fluctuations were predominant also in the dynamics of behavioral performance. The subjects' ability to detect the sensory stimuli was strongly correlated with the phase, but not with the amplitude of the infraslow EEG fluctuations. These data thus reveal a direct electrophysiological correlate for the slow fluctuations in human psychophysical performance. We then examined the correlation between the phase of infraslow EEG fluctuations and the amplitude of 1–40 Hz neuronal oscillations in six frequency bands. Like the behavioral performance, the amplitudes in these frequency bands were robustly correlated with the phase of the infraslow fluctuations. These data hence suggest that the infraslow fluctuations reflect the excitability dynamics of cortical networks. We conclude that ongoing 0.01–0.1 Hz EEG fluctuations are prominent and functionally significant during execution of cognitive tasks.
Representation of Eye Movements and Stimulus Motion in Topographically Organized Areas of Human Posterior Parietal Cortex
Authors: Konen Christina S. , Kastner Sabine
Published: August 2008

Recent imaging studies have shown that the human posterior parietal cortex (PPC) contains four topographically organized areas along the intraparietal sulcus (IPS1–IPS4). Using a memory-guided saccade paradigm, we confirmed the locations and retinotopic organization of IPS1–IPS4 and identified two additional areas, IPS5 and superior parietal lobule 1 (SPL1). IPS5 is located at the intersection of the intraparietal and postcentral sulcus; SPL1 branches off the IPS and extends into the superior parietal lobule. Both areas, as well as IPS1–IPS4, each contain a representation of the contralateral visual hemifield. We then probed core functions of the dorsal pathway in these areas, that is, the representation of eye movements and visual motion, to compare the functional characteristics of human PPC to physiologically and anatomically defined areas in monkey PPC. First, as in monkey PPC, a gradient representation of eye movements was found along the IPS with decreasing responses for saccades and increasing responses for smooth pursuit eye movements from posterior/medial to anterior/lateral. The greatest preference for saccades was found in SPL1 and for smooth pursuit in IPS5. Second, and again similar to monkey PPC, all topographically organized PPC areas responded to different types of motion including planar, circular, and radial optic flow, as assessed using adaptation paradigms. Areas in posterior IPS preferred radial optic flow over planar motion, whereas areas in anterior PPC did not show preference for a particular motion type. Together, our results indicate strikingly similar characteristics in the general functional organization of human and monkey PPC, but also reveal some notable differences.
Nuclear Factor κB Signaling Either Stimulates or Inhibits Neurite Growth Depending on the Phosphorylation Status of p65/RelA
Authors: Gutierrez Humberto , O'Keeffe Gerard W. , Gavaldà Núria , Gallagher Denis , Davies Alun M.
Published: August 2008

Nuclear factor κB (NF-κB) signaling is known to promote neurite growth from developing sensory neurons and to enhance the size and complexity of pyramidal neuron dendritic arbors in the developing cerebral cortex. In marked contrast, here we show that NF-κB signaling can also exert a potent inhibitory influence on neurite growth in certain neurons, and can either promote or inhibit neurite growth in the same neurons depending on the mechanism of NF-κB activation. In neonatal superior cervical ganglion sympathetic neurons, enhancing NF-κB transcriptional activity by overexpressing either the p65 NF-κB subunit or the IκB kinase-β (IKKβ) subunit of the IκB kinase complex, or by tumor necrosis factor α (TNFα) treatment, strongly inhibits neurite growth. Paradoxically in neonatal nodose ganglion sensory neurons, enhancing NF-κB transcriptional activity by p65/p50 overexpression increases neurite growth, whereas enhancing NF-κB transcriptional activity by IKKβ overexpression inhibits neurite growth. In addition to activating NF-κB, IKKβ overexpression leads to phosphorylation of p65 on serine 536. Blockade of serine 536 phosphorylation by a S536A-p65 mutant protein prevents the growth-inhibitory effects of IKKβ overexpression in both sensory and sympathetic neurons and the growth-inhibitory effects of TNFα on sympathetic neurons. Furthermore, expression of a p65 S536D phosphomimetic mutant inhibits neurite growth from sensory neurons. These results demonstrate that NF-κB can either stimulate or inhibit neurite growth in developing neurons depending on the phosphorylation status of p65.
Constitutively Active Rap2 Transgenic Mice Display Fewer Dendritic Spines, Reduced Extracellular Signal-Regulated Kinase Signaling, Enhanced Long-Term Depression, and Impaired Spatial Learning and Fear Extinction
Authors: Ryu Jubin , Futai Kensuke , Feliu Monica , Weinberg Richard , Sheng Morgan
Published: August 2008

Within the Ras superfamily of GTPases, Rap1 and Rap2 are the closest homologs to Ras. In non-neural cells, Rap signaling can antagonize Ras signaling. In neurons, Rap also seems to oppose Ras in terms of synaptic function. Whereas Ras is critical for long-term potentiation (LTP), Rap1 has been shown to be required for long-term depression (LTD), and Rap2 has been implicated in depotentiation. Moreover, active Rap1 and Rap2 cause loss of surface AMPA receptors and reduced miniature EPSC amplitude and frequency in cultured neurons. The role of Rap signalingin vivo, however, remains poorly understood. To study the function of Rap2 in the brain and in behavior, we created transgenic mice expressing either constitutively active (Rap2V12) or dominant-negative (Rap2N17) mutants of Rap2 in postnatal forebrain. Multiple lines of Rap2N17 mice showed only weak expression of the transgenic protein, and no phenotype was observed. Rap2V12 mice displayed fewer and shorter dendritic spines in CA1 hippocampal neurons, and enhanced LTD at CA3–CA1 synapses. Behaviorally, Rap2V12 mice showed impaired spatial learning and defective extinction of contextual fear, which correlated with reduced basal phosphorylation of extracellular signal-regulated kinase (ERK) and blunted activation of ERK during fear extinction training. Our data support the idea that Rap2 opposes Ras–ERK signaling in the brain, thereby inhibiting dendritic spine development/maintenance, promoting synaptic depression rather than LTP, and impairing learning. The findings also implicate Rap2 signaling in fear extinction mechanisms, which are thought to be aberrant in anxiety disorders and posttraumatic stress disorder.
Cortisol Inhibits Neuroplasticity Induction in Human Motor Cortex
Authors: Sale Martin V. , Ridding Michael C. , Nordstrom Michael A.
Published: August 2008

We investigated whether plasticity of human motor cortex (M1) is influenced by time of day, and whether changes in circulating levels of cortisol contribute to this effect. Neuroplasticity was induced using paired associative stimulation (PAS), involving electrical stimulation of left median nerve, paired with transcranial magnetic stimulation over the right M1 25 ms later (90 pairs at 0.05 Hz). Surface EMG was recorded from the left abductor pollicis brevis (APB) and first dorsal interosseous muscle. Cortisol levels were assessed from saliva. Time-of-day modulation of PAS effectiveness was assessed in 25 subjects who were tested twice, at 8:00 A.M. and 8:00 P.M. on separate days. In a second double-blind study, 17 subjects were tested with PAS at 8:00 P.M. on two occasions after administration of oral hydrocortisone (24 mg) or placebo. The motor-evoked potential (MEP) in resting APB increased significantly after PAS in the evening (when endogenous cortisol levels were low), but not in the morning. Oral hydrocortisone prevented facilitation of the APB MEP after PAS, and in the drug study, mean salivary cortisol levels were negatively associated with PAS effectiveness. The GABAB-mediated cortical silent period for APB was longer in the morning than in the evening, and was lengthened by PAS and oral hydrocortisone. We conclude that neuroplasticity in human M1 and GABAB-dependent intracortical inhibitory systems are influenced by time of day and modified by circulating levels of cortisol.