bluuebunny/crossref_metadata_2025 huggingface dataset:
Biomarkers for ragwort poisoning in horses: identification of protein targets
Authors: Moore Rowan E , Knottenbelt Derek , Matthews Jacqueline B , Beynon Robert J , Whitfield Phillip D
Published: August 2008

Background

Ingestion of the poisonous weed ragwort (Senecio jacobea) by horses leads to irreversible liver damage. The principal toxins of ragwort are the pyrrolizidine alkaloids that are rapidly metabolised to highly reactive and cytotoxic pyrroles, which can escape into the circulation and bind to proteins. In this study a non-invasivein vitromodel system has been developed to investigate whether pyrrole toxins induce specific modifications of equine blood proteins that are detectable by proteomic methods.

Results

One dimensional gel electrophoresis revealed a significant alteration in the equine plasma protein profile following pyrrole exposure and the formation of a high molecular weight protein aggregate. Using mass spectrometry and confirmation by western blotting the major components of this aggregate were identified as fibrinogen, serum albumin and transferrin.

Conclusion

These findings demonstrate that pyrrolic metabolites can modify equine plasma proteins. The high molecular weight aggregate may result from extensive inter- and intra-molecular cross-linking of fibrinogen with the pyrrole. This model has the potential to form the basis of a novel proteomic strategy aimed at identifying surrogate protein biomarkers of ragwort exposure in horses and other livestock.
Adipose-derived mesenchymal stem cells from the sand rat: transforming growth factor beta and 3D co-culture with human disc cells stimulate proteoglycan and collagen type I rich extracellular matrix
Authors: Tapp Hazel , Deepe Ray , Ingram Jane A , Kuremsky Marshall , Hanley Edward N , Gruber Helen E
Published: August 2008

Introduction

Adult mesenchymal stem cell therapy has a potential application in the biological treatment of disc degeneration. Our objectives were: to direct adipose-derived mesenchymal stem cells (AD-MSC) from the sand rat to produce a proteoglycan and collagen type I extracellular matrix (ECM) rich in known ECM components of the annulus fibrosis of disc; and to stimulate proteoglycan production by co-culture of human annulus cells with AD-MSC.

Methods

AD-MSC were isolated and characterised by adherence to plastic, appropriate expression of cluster of differentiation (CD) markers, and differentiation to osteoblasts and chondrocytes in vitro. AD-MSC were grown in three-dimensional (3D) culture and treated with or without transforming growth factor beta (TGFβ) to direct them to produce annulus-like ECM as determined by proteoglycan content and collagen expression. AD-MSC were co-cultured with human annulus cells and grown in 3D culture.

Results

AD-MSC produced a proteoglycan and collagen type I rich ECM after treatment with TGFβ in 3D culture as confirmed by a 48% increase in proteoglycan content assayed by 1,9-dimethylmethylene blue (DMB), and by immunohistochemical identification of ECM components. Co-culture of human annulus and sand rat AD-MSC in 3D culture resulted in a 20% increase in proteoglycan production compared with the predicted value of the sum of the individual cultures.

Conclusion

Results support the hypothesis that AD-MSC have potential in cell-based therapy for disc degeneration.
Preconditioning with high mobility group box 1 (HMGB1) induces lipopolysaccharide (LPS) tolerance
Authors: Aneja Rajesh K , Tsung Allan , Sjodin Hanna , Gefter Julia V , Delude Russell L , Billiar Timothy R , Fink Mitchell P
Published: August 2008

High mobility group box protein 1 (HMGB1) modulates the innate immune response when present in the extracellular compartment. Receptors for HMGB1 include TLR4, TLR2, and the receptor for advanced glycation end products (RAGE). We tested the hypothesis that extracellular HMGB1 can induce LPS tolerance. HMGB1 dose-response experiments were performed on IFN-γ-differentiated human monocyte-like THP-1 cells. Treatment with 1 μg/ml HMGB1 18 h before exposure to LPS (1 μg/ml) decreased TNF release, NF-κB nuclear DNA-binding activity, phosphorylation, and degradation of IκBα. Preconditioning with HMGB1 alone and HMGB1 in the presence of polymyxin B decreased LPS-mediated, NF-κB-dependent luciferase reporter gene expression. The specificity of HMGB1 in tolerance induction was supported further by showing that boiled HMGB1 failed to induce tolerance, and antibodies against HMGB1 blocked the induction of LPS tolerance. Bone marrow-derived macrophages obtained from C57Bl/6 wild-type mice became LPS-tolerant following HMGB1 exposure ex vivo, but macrophages derived from RAGE-deficient mice failed to develop tolerance and responded normally to LPS. Mice preconditioned with HMGB1 (20 μg) 1 h before LPS injection (10 mg/kg) had lower circulating TNF compared with control mice preconditioned with saline vehicle. Similarly, decreased nuclear DNA binding of hepatic NF-κB was observed in mice preconditioned with HMGB1. Taken together, these results suggest that extracellular HMGB1 induces LPS tolerance, and the RAGE receptor is required for this induction.
Trogocytosis and killing of IL-4-polarized monocytes by autologous NK cells
Authors: Poupot Mary , Fournié Jean-Jacques , Poupot Rémy
Published: August 2008

Cross-regulations between innate immune cells have been given more and more emphasis. Here, we address the question of bidirectional interactions between activated monocytes and autologous NK cells. Classically activated monocytes (class-monocytes), obtained by priming with IFN-γ, drive an inflammatory immune response. On the contrary, alternatively activated monocytes (alt-monocytes), obtained by stimulation with IL-4 or IL-13, engage an anti-inflammatory immune response. We show that alt-monocytes inhibit proliferation and production of IFN-γ by autologous, IL-2-activated NK cells, whereas class-monocytes do not inhibit these NK cell functions. Reciprocally, IL-2-activated NK cells interact and undertake intensive synaptic transfer with alt-monocytes, whereas interactions with class-monocytes are weaker. This strong trogocytosis correlates with an efficient killing of alt-monocytes, mediated by natural cytotoxicity receptors and a lowered killing of class-monocytes. These results suggest that interactions between NK cells and autologous-activated monocytes modulate inflammatory responses. This might be extended further in the elimination of tumor-associated macrophages, which actively promote solid tumor progression and metastasis.
Predicting the Productive Research Psychiatrist
Authors: Parker Gordon
Published: August 2008

Data were obtained for some 89 psychiatrists who were responsible for 372 first-author research publications over the period 1978–1984, to define predictors of productivity (rate of publishing in scientific journals). A principal components analysis suggested three key researcher dimensions, comprising ‘track record’, ‘experience’ and ‘resource base’ variables. The ‘track record’ dimension was the only significant predictor and was contributed to principally by the number of publications in the early part of the review period, number of citations to published work, rating by peers, and possessions of a research degree.
Poverty of Speech in Schizophrenia and Depression During In-patient and Post-hospital Periods
Authors: Ragin Ann Barnett , Pogue-Geile Michael , Oltmanns Thomas F.
Published: August 2008

Poverty of speech, a prominent feature of the negative symptom construct in schizophrenia, was assessed longitudinally in 12 schizophrenic and 13 depressed subjects at hospital admission and about seven months after discharge in order to evaluate hypotheses concerning course and diagnostic specificity. Multiple measures of the poverty of speech construct were employed, including both clinical and quantitative indices. During the inpatient period, poverty of speech was more pronounced among depressed than schizophrenic subjects. Examination of this specific negative symptom across inpatient and followup evaluations indicated that poverty of speech increased among schizophrenic subjects, but remained relatively stable or declined among depressed subjects. These results suggest that the processes underlying poverty of speech may differ in schizophrenia and depression.
Severity of Withdrawal in Subjects Exposed to a Combination of Alcohol and Minor Tranquillisers
Authors: Thomas Christopher S. , Spurrell Mark , Hackett Richard D. , Hore Brian D.
Published: August 2008

Fifty patients suffering from the alcohol dependence syndrome were detoxified over a 10-day period using a reducing regime of chlordiazepoxide. Twenty-four had been consuming minor tranquillisers together with alcohol prior to admission. The severity of the withdrawal syndrome was assessed daily but no differences were found between the 26 who had taken alcohol alone and the 24 who had taken a combination of alcohol and drugs. Four from each group had a transient hallucinosis and none had fits.
Opiate Withdrawal Symptoms in Response to 10-Day and 21-Day Methadone Withdrawal Programmes
Authors: Gossop Michael , Griffiths Paul , Bradley Brendan , Strang John
Published: August 2008

This study investigates and compares the responses of 132 opiate addicts to a 10-day or a 21-day in-patient oral methadone withdrawal regime. For both groups, symptom severity (on the Opiate Withdrawal Scale) steadily increased through the methadone withdrawal phase, and peaked near the point of completion of the prescribed drug, declining slowly thereafter. Patients on the 10-day programme reported significantly higher peak withdrawal scores than those on the 21-day programme. Although the proportions who completed detoxification were similar, there was a significantly higher drop-out rate immediately after detoxification for the 10-day group. The possible benefits and handicaps of the two withdrawal schedules are considered and recommendations are proposed for further refinement of the present widely adopted approach.
Sex Differences in the Differentiation of Psychiatric Symptomatology
Authors: Briscoe M. E. , Vázquez-Barquero J. L. , Williams P. , Diez-Manrique J. F. , Peña C.
Published: August 2008

A study was conducted using data obtained from the first stage of a community survey in Spain, in which the 60-item version of the GHQ was administered to 1224 adults. Three hypotheses concerning respondents aged under 55 years were tested. The first was that in the context of a principal-components analysis, a greater proportion of the explained variance would be accounted for by the first (general) factor in women than in men. This was supported. The second hypothesis was that the intercorrelations between the GHQ-28 subscales would be greater for women than for men. This was refuted. The third hypothesis was that the differentiation between anxiety and depression would be greater in men than in women. This was supported. The differences investigated were found not to apply among respondents aged 55 years and over.
The Hormonal Environment of Postnatal Depression
Authors: Harris Brian , Johns Sandra , Fung Hedi , Thomas Roger , Walker Richard , Read Graham , Riad-Fahmy Diana
Published: August 2008

The incidence of postnatal depression is high, and dramatic changes in steroid hormones and prolactin occur in the postpartum period. In an attempt to correlate these events, 147 mothers, six to eight weeks after delivery of a healthy infant, completed standard psychological tests, including the Edinburgh, Montgomery-åsberg, and Raskin scales. They also provided matched samples of plasma for assay of cortisol, oestradiol, progesterone and prolactin, and saliva for assay of cortisol and progesterone. All steroid concentrations were within the appropriate normal ranges. Of the mothers, 14.9% were depressed on all three scales. Significant correlations were seen between depression ratings and salivary progesterone and prolactin. In bottle-feeders, salivary progesterone was positively associated with depression, whereas in breast-feeders it was negatively associated. Plasma prolactin levels were inappropriately low in depressed breast-feeders. These data indicate that differing therapies may be appropriate for depression in breast- and bottle-feeders.
The Occurrence of Depression Following Mania
Authors: Lucas C. P. , Rigby J. C. , Lucas S. B.
Published: August 2008

In a retrospective analysis of 100 cases of mania (1981–1985), the incidence of subsequent depression was found to be 30%. Its occurrence was significantly associated with three factors: cyclothymic premorbid personality, family history of affective disorder, and past history of depression. By discriminant analysis, outcome could be predicted successfully in 81% of cases.
Self-Cathexis and Other-Cathexis
Authors: Macdiarmid D.
Published: August 2008

The history is traced of observations made of the phenomena associated with self-cathexis and other-cathexis. Owing to personal and other conflicts in the history of psychiatry and psychotherapy, the development of these observations was disturbed, and they were re-observed and re-described using different terminologies in accounts which have not hitherto been collected and compared. When this is done, a consensus appears which can be stated in a common language to facilitate further accretion of observation, and further research and debate.
Transient Recurrence of Auditory Hallucinations During Acute Dystonia
Authors: Chiu Leo P. W.
Published: August 2008

Three schizophrenic patients who had transient recurrence of auditory hallucinations during acute dystonia precipitated by neuroleptic medication are reported. If it is accepted that psychotic symptoms result from dopaminergic overactivity, such phenomena suggest that acute dystonia might also have been caused by increased dopaminergic neurotransmission in these cases.
Obsessive-Compulsive Disorder in a Mentally Retarded Woman
Authors: McNally Richard J. , Calamari John E.
Published: August 2008

Obsessive-compulsive disorder is extremely rare among mentally retarded people. We report here a case of a mildly mentally retarded woman who exhibits contamination obsessions, compulsive hand-washing rituals, and avoidance.
The Evaluation of Mental Health Care Systems
Authors: Häfner Heinz , an der Heiden Wolfram
Published: August 2008

While the demand for deinstitutionalisation, strongly supported by the economic aspect of the issue, has resulted in a steep decline in the number of psychiatric beds in many Western countries, the evaluation of extramural psychiatric care has several difficulties, including that of proving effectiveness without experimental control of confounding influences. For a cohort of schizophrenic patients we investigated the impact of outpatient psychiatric treatment on length of stay in hospital and length of stay in the community. Outpatient care had a significant influence on read mission, but no effect on the length of inpatient treatment. While the average cost of community care was less than half that of traditional hospital care, in 6% of the patients this threshold value of continued inpatient care was exceeded. There also seems to be a non-monetary threshold, above which community care is no longer appropriate.
Benefits and Problems of Routine Laboratory Investigations in Adult Psychiatric Admissions
Authors: White Anthony J. , Barraclough Brian
Published: August 2008

A survey of laboratory investigations in the management of 1007 non-geriatric admissions to a district general hospital adult psychiatric unit showed a wide variation in the number of tests performed, and in the abnormal proportion between test types. Despite a policy of screening on admission, 40% of admissions had no tests. Physical illness attributable to mental illness was common, but rarely serious and usually apparent clinically. Mental illness attributable to physical illness detected by laboratory tests was rare: five cases of thyroid disease in women with affective disorder, and two cases of chest infection with raised white cell count in sustained mania. The findings show that tests are frequently used in circumstances where the result is of no apparent value. Test use might be improved by restricting screening to thyroid function and laboratory urine analysis, each in women. There are particular indications for white cell count in sustained or unexplained relapse of mental illness, and for syphilis serology when disinhibition may have exposed the patient to infection.
Chronic Psychiatric Complaints and the General Health Questionnaire
Authors: Koeter M. W. J. , van den Brink W. , Ormel J.
Published: August 2008

The sensitivity of the GHQ and a revised scoring procedure (CGHQ) for chronic psychiatric complaints was investigated on 175 outpatients. The mean level of severity of symptoms of the groups with and without chronic complaints was not significantly different. However, patients with chronic complaints showed a significantly lower mean GHQ score than patients without chronic complaints. The mean CGHQ scores of the two groups did not differ, suggesting that the CGHQ is a better indicator of the severity of the chronic psychiatric state than the GHQ. The revised scoring procedure resulted in a decrease in the number of false negatives. The strongest reduction in false negatives, however, was induced by a combination of the original and the revised scoring procedures. This reduction was achieved at the expense of only a small increase in the number of false positives. Altogether, the revised scoring procedure proved to be only marginally better.
Mania in the elderly
Authors: Stone Kit
Published: August 2008

A retrospective study of 92 patients admitted with mania, aged over 65 years of age, found that 26% had no prior history of affective illness; 30% had previously only experienced depression, and half of these had at least three episodes of depression before the first manic illness. Patients with a family history of affective disorders had a significantly earlier age of onset of illness. There was evidence of cerebral organic impairment in 24% of the patients, and this group had a significantly later age of onset of illness. Prognosis was good, with only 8% still in hospital at six months. Half of the patients were started on lithium prophylaxis, but this did not significantly alter the number of readmissions. A quarter of those started on lithium developed evidence of lithium toxicity.
Schizophrenia and the Perception of Emotions
Authors: Cramer Philip , Weegman Martin , O'Neill Mike
Published: August 2008

Audiovisual tapes of emotional situations were shown to 34 schizophrenics and 15 controls who were asked to rate the emotional content of the scenes using an adjective check-list. The schizophrenic patients failed to detect the dominant character of the scenes, and perceived the opposite emotions to those perceived by the controls. Such deviant responses were not related to paranoid symptoms, flattened affect, formal thought disorder, general level of morbidity, or duration of in-patient stay.
Unresolved Grief Presenting with Features of a Negative Therapeutic Reaction
Authors: Nightingale Anne M.
Published: August 2008

A 44-year-old depressed widow in psychodynamic psychotherapy suffered repeated relapses of symptoms following improvement. This was seen as a negative therapeutic reaction.
“Not Worth Powder and Shot”
Authors: Harding T.-W.
Published: August 2008

Dr Montagu Lomax worked as an assistant medical officer at Prestwich Asylum for two years from 1917. His book, The Experiences of an Asylum Doctor, was published in 1921. He was condemned by the psychiatric establishment for his description of inhuman, custodial, and antitherapeutic conditions. Access to previously confidential official papers, to the archives of Prestwich Hospital, and to Professor George Robertson's correspondence has permitted a reconstruction of the Lomax affair. Lomax was a dedicated and sincere clinician. Senior Ministry of Health officials regarded Lomax's book as “temperate”, “well founded”, and an opportunity to secure public support for long needed legal and administrative reforms. Through his book, Lomax made a lasting contribution to the cause of mental health reform.
Handedness and Epileptic Schizophrenia
Authors: Oyebode Femi , Davison Kenneth
Published: August 2008

Thirty-two epileptic patients with RDC diagnoses of schizophrenia were tested for handedness on the Annett Handedness Schedule, and handedness was assigned on the basis of Annett–Maudsley criteria. They were compared with three other groups of patients. Five (15.6%) of the epileptic schizophrenic patients were mixed or left handed. The prevalence of mixed and left handedness did not differ between the samples studied. However, there was a significant reduction of mixed and left handedness in male epileptics with schizophrenia. Mixed or left handedness in male epileptics appears to be protective against the development of psychiatric illness in general.
Life Events and the Onset of Mania
Authors: Sclare Paul , Creed Francis
Published: August 2008

Thirty manic in-patients were interviewed in hospital using the LEDS, and 24 were re-interviewed 6–12 months after discharge. Data for life events were analysed by: comparing events before onset of mania and before re-interview; and comparing these manic patients with patients in other studies which examined life events and the onset of schizophrenia and depression. No relationship was found between life events and the onset of mania in this preliminary study. Previous studies reporting a link between events and the onset of mania have serious methodological flaws, and definitive data have yet to be produced.
The Social Psychiatry of Later Life
Authors: Henderson A. S.
Published: August 2008

Throughout the two million years of human existence, it is without precedent that the elderly should now constitute such a large proportion of the world's population. Although it is already trite to emphasise this remarkable change in the global population structure, the increase is nothing less than an awesome imperative for public health as a socially responsible science. By the year 2025 AD, the United Kingdom will have 14 million persons aged over 60, which would be 26% of the population. Just under two million of them will be over 80 years old (United Nations, 1985). In Australia and New Zealand, 24.8% of the population will be aged 60 years or more. About one million Australians will be 80 years or over. West Germany will have 2.4 million aged over 80, the USA 7.7 million. The People's Republic of China will have 19.3% of its 1.5 billion people who will be aged over 60, and over 25 million will be over 80 years.
Violent Death and Mental Illness
Authors: King Elizabeth , Barraclough Brian
Published: August 2008

The names of 412 residents of the catchment population of a district general hospital unit who died potentially self-inflicted deaths in the eight years 1974–81 were identified. They were classified as suicide (245), accidental death (126), and undetermined (41). In each group, over half had a lifetime history of psychiatric treatment and over a third were psychiatric patients at the time of their death. The relative risk of a violent death for those who died within a year of their last psychiatric contact was 27 times greater than that of residents with no recent psychiatric contact. The relative risk was highest for those aged 35–44 and lowest for those of 75 years and over.
Problems Reported by Relatives in a Community Study of Dementia
Authors: O'Connor D. W. , Pollitt P. A. , Roth M. , Brook C. P. B. , Reiss B. B.
Published: August 2008

The supporters of 120 demented elderly people completed rating scales of the frequency and severity of the problems they faced, the amount of strain they experienced and their psychological well-being. Problems and strain increased with the degree of dementia. Problems relating to physical dependency, forgetfulness and inertia were relatively common, while disturbed behaviours were relatively uncommon. Physical dependency and disturbed behaviour were less well tolerated than forgetfulness and inertia, but all problem categories were positively associated with measures of strain. Wives reported more problems and strain than husbands, and co-resident children were under greater strain than children who lived independently.
Sex Differences in the Age of Onset of Bipolar Affective Illness
Authors: Sibisi Charles D. T.
Published: August 2008

Data from a UK national sample showed differences between the sexes in age-specific inception rates for mania. Women had a higher inception rate than men during the middle years. The cumulative admission rates were nearly equal between the sexes.
Mass Sociogenic Illness by Proxy: Parentally Reported Epidemic in an Elementary School
Authors: Wessely Simon , Wardle Christopher J.
Published: August 2008

“In a cluster of illness reported among students at an elementary school parents mentioned many signs and symptoms including headache, pallor, dark circles under the eyes, nausea, and vomiting – which they attributed to exposure to recurrent leaks of natural gas at the school. It is likely that the parents spread among themselves the notion of toxic exposure at the school. A questionnaire revealed no spatial clustering, but increased reports of symptoms were related to intense media coverage. A thorough environmental and epidemiological investigation was negative, there being no evidence of a continuing gas leak or other potential causes. At a strictly biological level, the complaints in this reported ‘cluster’ apparently represented the sporadic occurrence of common childhood illnesses. The possibility of an epidemic from toxic exposure at the school caused intense parental concern and led to a major public health problem. The established term ‘mass sociogenic illness' seems inapplicable here because complaints did not come principally from the students and the apparent epidemic illness was not transmitted among them. The term ‘mass sociogenic illness by proxy’ is proposed to describe this incident, in which transmission in one group (the parents) resulted in reports of an epidemic in another group (students).”
Delusional Misidentification, AIDS and the Right Hemisphere
Authors: Crichton Paul , Lewis Shôn
Published: August 2008

A patient with AIDS developed the Capgras' syndrome as part of an acute confusional state resulting from an opportunistic infection. Neuropsychological testing suggested non-dominant hemisphere dysfunction with impaired facial recognition. Serial CT scanning showed a right parietal lesion which resolved after the psychosis improved. These findings provide further evidence for the hypothesis that selective visuospatial deficits underlie the development of Capgras' syndrome.
Rapid-Cycling Disorder in Association with Cerebral Sarcoidosis
Authors: Walbridge D. G.
Published: August 2008

A 48-hour rapid-cycling disorder in a patient with pre-existing cerebral sarcoidosis, not described previously, was similar to that of others in the literature in that the mood switching occurred during sleep. Although the condition is rare, its existence raises important questions regarding the neurophysiology of affective disorders in general.
The Interval General Health Questionnaire
Authors: Surtees P. G. , Miller P. Mcc.
Published: August 2008

An adaptation of the LIFE procedure was used with a self-report questionnaire to assess 173 medical students, close to their enrolment and again about six months later. The assessment procedure enabled changes in symptoms of anxiety and depression over the interval between interviews to be recorded and the subsequent classification of the symptom patterns into course categories. While women scored markedly higher than men at initial assessment, this was not so at follow-up. Almost 25% of students reported the co-occurrence of at least five psychological symptoms at some time during the six months. For many students these were of a persistent nature. The adapted GHQ meets the dual demands of restricted interview time and the need to assess the more minor psychological conditions.
Prenatal Nicotine Exposure Alters Early Pancreatic Islet and Adipose Tissue Development with Consequences on the Control of Body Weight and Glucose Metabolism Later in Life
Authors: Somm Emmanuel , Schwitzgebel Valérie M. , Vauthay Delphine M. , Camm Emily J. , Chen Chang Y. , Giacobino Jean-Paul , Sizonenko Stéphane V. , Aubert Michel L. , Hüppi Petra S.
Published: August 2008

Despite medical advice, 20–30% of female smokers continue to smoke during pregnancy. Epidemiological studies have associated maternal smoking with increased risk of obesity and type-2 diabetes in the offspring. In the present study, we investigated the impact of prenatal nicotine exposure (3 mg/kg in Sprague Dawley rats via osmotic Alzet minipumps) on the early endocrine pancreas and adipose tissue development in rat pups before weaning. Body weight, fat deposition, food intake and food efficiency, cold tolerance, spontaneous physical activity, glucose utilization, and insulin sensitivity were also examined at adulthood. Prenatal nicotine exposure led to a decrease in endocrine pancreatic islet size and number at 7 d of life (postnatal d 7), which corroborates with a decrease in gene expression of specific transcription factors such as pancreatic and duodenal homeobox 1, Pax-6, Nkx6.1, and of hormones such as insulin and glucagon. The prenatal nicotine exposure also led to an increase in epididymal white adipose tissue weight at weaning (postnatal d 21), and marked hypertrophy of adipocytes, with increased gene expression of proadipogenic transcription factors such as CAAT-enhancer-binding protein-α, peroxisome proliferator activated receptor-γ, and sterol regulatory element binding protein-1C. These early tissue alterations led to significant metabolic consequences, as shown by increased body weight and fat deposition, increased food efficiency on high-fat diet, cold intolerance, reduced physical activity, and glucose intolerance combined with insulin resistance observed at adulthood. These results prove a direct association between fetal nicotine exposure and offspring metabolic syndrome with early signs of dysregulations of adipose tissue and pancreatic development.
Regulation of Bovine Tumor Necrosis Factor-α-Induced Protein 6 in Ovarian Follicles during the Ovulatory Process and Promoter Activation in Granulosa Cells
Authors: Sayasith Khampoune , Bouchard Nadine , Doré Monique , Sirois Jean
Published: August 2008

To study the regulation of bovine TNFα-induced protein 6 (TNFAIP6) prior to ovulation, preovulatory follicles obtained after the treatment with human chorionic gonadotropin (hCG) were used. RT-PCR analyses showed that levels of TNFAIP6 mRNA were low before hCG but significantly increased after hCG treatment in follicles. Further analyses and immunohistochemistry indicated that this increase in transcript and protein levels occurred in theca and granulosa cells. To investigate molecular mechanisms involved in TNFAIP6 transactivation, the activity of bovine TNFAIP6 promoter was studied in granulosa cell cultures. Mutant studies identified the minimal region conferring full-length promoter activity, in which activator protein-1 (AP1) and cAMP response element (CRE) elements were required for promoter activity. Overexpression of dominant-negative AP1 and activating transcription factor/cAMP response element-binding protein (CREB) inhibited forskolin-inducible promoter activity. DNA binding assays demonstrated the importance of AP1 and CRE for activity and identified JunD, FosB, Fra2, CREB1, and CREB2 as being part of the AP1 complex, and FosB, Fra2, and CREB1 for the CRE complex. Chromatin immunoprecipitation assays confirmed binding of these proteins with endogenous TNFAIP6 promoter. Treatment with forskolin, prostaglandin E2, and catalytic subunit protein kinase (cPKA) stimulated, but H89, PKA inhibitor peptide, and indomethacin inhibited, TNFAIP6 promoter activity and gene expression in granulosa cells. Collectively, this study is the first to describe that the ovulatory process in cows is associated with a gonadotropin-dependent induction of TNFAIP6 in ovarian follicles and provide the molecular basis through which AP1 and CRE sites and PKA activation played important roles in the regulation of TNFAIP6 in granulosa cells.
Angiotensin Type 1 Receptors in the Subfornical Organ Mediate the Drinking and Hypothalamic-Pituitary-Adrenal Response to Systemic Isoproterenol
Authors: Krause Eric G. , Melhorn Susan J. , Davis Jon F. , Scott Karen A. , Ma Li Y. , de Kloet Annette D. , Benoit Stephen C. , Woods Stephen C. , Sakai Randall R.
Published: August 2008

Circulating angiotensin II (ANGII) elicits water intake and activates the hypothalamic-pituitary-adrenal (HPA) axis by stimulating angiotensin type 1 receptors (AT1Rs) within circumventricular organs. The subfornical organ (SFO) and the organum vasculosum of the lamina terminalis (OVLT) are circumventricular organs that express AT1Rs that bind blood-borne ANGII and stimulate integrative and effector regions of the brain. The goal of these studies was to determine the contribution of AT1Rs within the SFO and OVLT to the water intake and HPA response to increased circulating ANGII. Antisense oligonucleotides directed against the AT1R [AT1R antisense (AT1R AS)] were administered into the OVLT or SFO. Quantitative receptor autoradiography confirmed that AT1R AS decreased ANGII binding in the SFO and OVLT compared with the scrambled sequence control but did not affect AT1R binding in other nuclei. Subsequently, water intake, ACTH, and corticosterone (CORT) were assessed after administration of isoproterenol, a β-adrenergic agonist that decreases blood pressure and elevates circulating ANGII. Delivery of AT1R AS into the SFO attenuated water intake, ACTH, and CORT after isoproterenol, whereas similar treatment in the OVLT had no effect. To determine the specificity of this blunted drinking and HPA response, the same parameters were measured after treatment with hypertonic saline, a stimulus that induces drinking independently of ANGII. Delivery of AT1R AS into the SFO or OVLT had no effect on water intake, ACTH, or CORT after hypertonic saline. The results imply that AT1R within the SFO mediate drinking and HPA responses to stimuli that increase circulating ANGII.
Vascular Endothelial Growth Factor Mediates the Estrogen-Induced Breakdown of Tight Junctions between and Increase in Proliferation of Microvessel Endothelial Cells in the Baboon Endometrium
Authors: Aberdeen Graham W. , Wiegand Stanley J. , Bonagura Thomas W. , Pepe Gerald J. , Albrecht Eugene D.
Published: August 2008

To assess whether there is a link between estrogen, vascular endothelial growth factor (VEGF), and early aspects of uterine angiogenesis, an acute temporal study was conducted in which ovariectomized baboons were pretreated with VEGF Trap, which sequesters endogenous VEGF, and administered estradiol at time 0 h. Serum estradiol levels approximated 500 pg/ml 4–6 h after estradiol administration. VEGF mRNA levels in endometrial glandular epithelial and stromal cells were increased to values 6 h after estradiol that were 3.74 ± 0.99-fold (mean ± se) and 5.70 ± 1.60-fold greater (P < 0.05), respectively, than at 0 h. Microvessel interendothelial cell tight junctions, which control paracellular permeability, were present in the endometrium at time 0 h, but not evident 6 h after estradiol administration. Thus, microvessel paracellular cleft width increased (P < 0.01, ANOVA) from 5.03 ± 0.22 nm at 0 h to 7.27 ± 0.48 nm 6 h after estrogen. In contrast, tight junctions remained intact, and paracellular cleft widths were unaltered in estradiol/VEGF Trap and vehicle-treated animals. Endometrial microvessel endothelial cell mitosis, i.e. percent Ki67+/Ki67− immunolabeled endothelial cells, increased (P < 0.05) from 2.9 ± 0.3% at 0 h to 21.4 ± 7.0% 6 h after estrogen treatment but was unchanged in estradiol/VEGF Trap and vehicle-treated animals. In summary, the estrogen-induced disruption of endometrial microvessel endothelial tight junctions and increase in endothelial cell proliferation were prevented by VEGF Trap. Therefore, we propose that VEGF mediates the estrogen-induced increase in microvessel permeability and endothelial cell proliferation as early steps in angiogenesis in the primate endometrium.
Fibroblast Growth Factor 21 Corrects Obesity in Mice
Authors: Coskun Tamer , Bina Holly A. , Schneider Michael A. , Dunbar James D. , Hu Charlie C. , Chen Yanyun , Moller David E. , Kharitonenkov Alexei
Published: August 2008

Fibroblast growth factor 21 (FGF21) is a metabolic regulator that provides efficient and durable glycemic and lipid control in various animal models. However, its potential to treat obesity, a major health concern affecting over 30% of the population, has not been fully explored. Here we report that systemic administration of FGF21 for 2 wk in diet-induced obese and ob/ob mice lowered their mean body weight by 20% predominantly via a reduction in adiposity. Although no decrease in total caloric intake or effect on physical activity was observed, FGF21-treated animals exhibited increased energy expenditure, fat utilization, and lipid excretion, reduced hepatosteatosis, and ameliorated glycemia. Transcriptional and blood cytokine profiling studies revealed effects consistent with the ability of FGF21 to ameliorate insulin and leptin resistance, enhance fat oxidation and suppress de novo lipogenesis in liver as well as to activate futile cycling in adipose. Overall, these data suggest that FGF21 exhibits the therapeutic characteristics necessary for an effective treatment of obesity and fatty liver disease and provides novel insights into the metabolic determinants of these activities.
Homeostasis established by coordination of subcellular compartment plasticity improves spike encoding
Authors: Chen Na , Chen Xin , Wang Jin-Hui
Published: August 2008

Homeostasis in cells maintains their survival and functions. The plasticity at neurons and synapses may destabilize their signal encoding. The rapid recovery of cellular homeostasis is needed to secure the precise and reliable encoding of neural signals necessary for well-organized behaviors. We report a homeostatic process that is rapidly established through Ca2+-induced coordination of functional plasticity among subcellular compartments. An elevation of cytoplasmic Ca2+ levels raises the threshold potentials and refractory periods of somatic spikes, and strengthens the signal transmission at glutamatergic and GABAergic synapses, in which synaptic potentiation shortens refractory periods and lowers threshold potentials. Ca2+ signals also induce an inverse change of membrane excitability at the soma versus the axon. The integrative effect of Ca2+-induced plasticity among the subcellular compartments is homeostatic in nature, because it stabilizes neuronal activities and improves spike timing precision. Our study of neuronal homeostasis that is fulfilled by rapidly coordinating subcellular compartments to improve neuronal encoding sheds light on exploring homeostatic mechanisms in other cell types.
Effects of dietary polyunsaturated fatty acids on mitochondrial metabolism in mammalian hibernation
Authors: Gerson Alexander R. , Brown Jason C. L. , Thomas Raymond , Bernards Mark A. , Staples James F.
Published: August 2008

Thirteen-lined ground squirrels (Spermophilus tridecemlineatus)were fed one of four isocaloric, isolipemic diets containing 16, 22, 35 or 55 mg linoleic acid (18:2n-6) per gram. Mitochondrial properties were compared between hibernating and summer active states, and between diet groups. As in other studies, state 3 respiration was significantly reduced in hibernation, but only in animals fed the 22 mg g–1 18:2 diet. In the other diet groups, there was no difference in state 3 respiration between the hibernating and summer active groups. In the 22 mg g–1 18:2 diet group, there was no difference in mitochondrial proton conductance between hibernating and summer active animals, again in agreement with earlier studies. However, for all other diet groups,mitochondrial proton conductance was significantly reduced during hibernation. Mitochondrial phospholipid fatty acids changed significantly with hibernation,including increases in unsaturation indices and n-6/n-3, but no differences were found among diet groups. Mitochondrial proton conductance in hibernation showed a positive correlation with the content of linoleic acid(18:2) and arachidonic acid (20:4) in mitochondrial phospholipids. Lipid peroxidation was higher in mitochondria from hibernating animals, probably due to higher unsaturation, but there was no effect of dietary 18:2 on this pattern. Despite the dietary effects on mitochondrial metabolism, all animals hibernated with no differences in bout durations, body temperatures or whole-animal metabolic rates among the diet groups. The reduced mitochondrial proton leak in the 15, 35 and 55 mg g–1 18:2 diet groups might compensate for the inability to suppress respiration, permitting whole-animal energy savings over the hibernation season.
The `upstream wake' of swimming and flying animals and its correlation with propulsive efficiency
Authors: Peng Jifeng , Dabiri John O.
Published: August 2008

The interaction between swimming and flying animals and their fluid environments generates downstream wake structures such as vortices. In most studies, the upstream flow in front of the animal is neglected. In this study,we demonstrate the existence of upstream fluid structures even though the upstream flow is quiescent or possesses a uniform incoming velocity. Using a computational model, the flow generated by a swimmer (an oscillating flexible plate) is simulated and a new fluid mechanical analysis is applied to the flow to identify the upstream fluid structures. These upstream structures show the exact portion of fluid that is going to interact with the swimmer. A mass flow rate is then defined based on the upstream structures, and a metric for propulsive efficiency is established using the mass flow rate and the kinematics of the swimmer. We propose that the unsteady mass flow rate defined by the upstream fluid structures can be used as a metric to measure and objectively compare the efficiency of locomotion in water and air.
Spiny lobsters detect conspecific blood-borne alarm cues exclusively through olfactory sensilla
Authors: Shabani Shkelzen , Kamio Michiya , Derby Charles D.
Published: August 2008

When attacked by predators, diverse animals actively or passively release molecules that evoke alarm and related anti-predatory behavior by nearby conspecifics. The actively released molecules are alarm pheromones, whereas the passively released molecules are alarm cues. For example, many insects have alarm-signaling systems that involve active release of alarm pheromones from specialized glands and detection of these signals using specific sensors. Many crustaceans passively release alarm cues, but the nature of the cues,sensors and responses is poorly characterized. Here we show in laboratory and field experiments that injured Caribbean spiny lobsters, Panulirus argus, passively release alarm cues via blood (hemolymph) that induce alarm responses in the form of avoidance and suppression of feeding. These cues are detected exclusively through specific olfactory chemosensors,the aesthetasc sensilla. The alarm cues for Caribbean spiny lobsters are not unique to the species but do show some phylogenetic specificity: P. argus responds primarily with alarm behavior to conspecific blood, but with mixed alarm and appetitive behaviors to blood from the congener Panulirus interruptus, or with appetitive behaviors to blood from the blue crab Callinectes sapidus. This study lays the foundation for future neuroethological studies of alarm cue systems in this and other decapod crustaceans.
The ontogeny of aerobic and diving capacity in the skeletal muscles of Weddell seals
Authors: Kanatous S. B. , Hawke T. J. , Trumble S. J. , Pearson L. E. , Watson R. R. , Garry D. J. , Williams T. M. , Davis R. W.
Published: August 2008

Our objective was to determine the ontogenetic changes in the skeletal muscles of Weddell seals that transform a non-diving pup into an elite diving adult. Muscle biopsies were collected from pups, juveniles and adults and analyzed for changes in fiber type, mitochondrial density, myoglobin concentrations and aerobic, lipolytic and anaerobic enzyme activities. The fiber type results demonstrated a decrease in slow-twitch oxidative (Type I)fibers and a significant increase in fast-twitch oxidative (Type IIA) fibers as the animals mature. In addition, the volume density of mitochondria and the activity of lipolytic enzymes significantly decreased as the seals matured. To our knowledge, this is the first quantitative account describing a decrease in aerobic fibers shifting towards an increase in fast-twitch oxidative fibers with a significant decrease in mitochondrial density as animals mature. These differences in the muscle physiology of Weddell seals are potentially due to their three very distinct stages of life history: non-diving pup, novice diving juvenile, and elite deep diving adult. During the first few weeks of life, pups are a non-diving terrestrial mammal that must rely on lanugo (natal fur) for thermoregulation in the harsh conditions of Antarctica. The increased aerobic capacity of pups, associated with increased mitochondrial volumes,acts to provide additional thermogenesis. As these future elite divers mature,their skeletal muscles transform to a more sedentary state in order to maintain the low levels of aerobic metabolism associated with long-duration diving.
High mitochondrial densities in the hearts of Antarctic icefishes are maintained by an increase in mitochondrial size rather than mitochondrial biogenesis
Authors: Urschel Matthew R. , O'Brien Kristin M.
Published: August 2008

We investigated the molecular mechanisms regulating differences in mitochondrial volume density between heart ventricles of Antarctic notothenioids that vary in the expression of hemoglobin (Hb) and myoglobin(Mb). In mammals, peroxisome proliferator-activated receptor γcoactivator-1α (PGC-1α) and nuclear respiratory factor 1 (NRF-1)stimulate mitochondrial biogenesis and maintain mitochondrial density in muscle tissues. We hypothesized that these factors would also maintain mitochondrial density in the hearts of Antarctic notothenioids. The percent cell volume occupied by mitochondria is significantly lower in hearts of the red-blooded notothenioid Notothenia coriiceps (18.18±0.69%) in comparison with those of the icefish Chaenocephalus aceratus(36.53±2.07%), which lacks both Hb and cardiac Mb. Mitochondrial densities are not different between hearts of N. coriiceps and Chionodraco rastrospinosus, which lacks Hb, but whose heart expresses Mb. Despite differences in mitochondrial volume density between hearts of N. coriiceps and C. aceratus, the levels of transcripts of the genes encoding PGC-1α, NRF-1 and citrate synthase, and the copy number of mitochondrial DNA do not differ. Our results indicate that the high mitochondrial densities in hearts of C. aceratus may result from an increase in organelle size. The surface-to-volume ratio of mitochondria from N. coriiceps is 1.9-fold greater than that of mitochondria from C. aceratus. In addition, the levels of PGC-1α correlate with mitochondrial density in muscle tissues of notothenioids possessing mitochondria of similar size and morphology. Finally, the levels of PGC-1α are 4.6-fold higher in the aerobic pectoral adductor muscle in comparison with the glycolytic skeletal muscle of N. coriiceps. The potential physiological significance of an increase in mitochondrial size in hearts of Antarctic icefishes is discussed.