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1.
Sci Rep ; 6: 26189, 2016 05 18.
Article in English | MEDLINE | ID: mdl-27189430

ABSTRACT

Although most models suggest continental Antarctica was covered by ice during the Last Glacial Maximum (LGM) it has been speculated that endemic species of soil invertebrates could have survived the Pleistocene at high elevation habitats protruding above the ice sheets. We analyzed a series of soil samples from different elevations at three locations along the Beardmore Glacier in the Transantarctic Mountains (in order of increasing elevation): Ebony Ridge (ER), Cloudmaker (CM), and Meyer Desert (MD). Geochemical analyses show the MD soils, which were exposed during the LGM, were the least weathered compared to lower elevations, and also had the highest total dissolved solids (TDS). MD soils are dominated by nitrate salts (NO3/Cl ratios >10) that can be observed in SEM images. High δ(17)O and δ(18)O values of the nitrate indicate that its source is solely of atmospheric origin. It is suggested that nitrate concentrations in the soil may be utilized to determine a relative "wetting age" to better assess invertebrate habitat suitability. The highest elevation sites at MD have been exposed and accumulating salts for the longest times, and because of the salt accumulations, they were not suitable as invertebrate refugia during the LGM.


Subject(s)
Ecosystem , Soil/chemistry , Antarctic Regions , Geological Phenomena , Ice Cover , Nitrates/analysis
2.
Psychol Med ; 43(10): 2087-96, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23190458

ABSTRACT

BACKGROUND: Schizophrenia is associated with various brain structural abnormalities, including reduced volume of the hippocampi, prefrontal lobes and thalami. Cannabis use increases the risk of schizophrenia but reports of brain structural abnormalities in the cannabis-using population have not been consistent. We used automated image analysis to compare brain structural changes over time in people at elevated risk of schizophrenia for familial reasons who did and did not use cannabis. METHOD: Magnetic resonance imaging (MRI) scans were obtained from subjects at high familial risk of schizophrenia at entry to the Edinburgh High Risk Study (EHRS) and approximately 2 years later. Differential grey matter (GM) loss in those exposed (n=23) and not exposed to cannabis (n=32) in the intervening period was compared using tensor-based morphometry (TBM). RESULTS: Cannabis exposure was associated with significantly greater loss of right anterior hippocampal (pcorrected=0.029, t=3.88) and left superior frontal lobe GM (pcorrected=0.026, t=4.68). The former finding remained significant even after the exclusion of individuals who had used other drugs during the inter-scan interval. CONCLUSIONS: Using an automated analysis of longitudinal data, we demonstrate an association between cannabis use and GM loss in currently well people at familial risk of developing schizophrenia. This observation may be important in understanding the link between cannabis exposure and the subsequent development of schizophrenia.


Subject(s)
Cannabis/adverse effects , Cerebral Cortex/drug effects , Magnetic Resonance Imaging/methods , Schizophrenia/pathology , Adolescent , Adult , Cerebral Cortex/pathology , Female , Follow-Up Studies , Genetic Predisposition to Disease , Hippocampus/drug effects , Hippocampus/pathology , Humans , Magnetic Resonance Imaging/instrumentation , Male , Prefrontal Cortex/drug effects , Prefrontal Cortex/pathology , Schizophrenia/genetics , Scotland , Young Adult
3.
Eur Psychiatry ; 25(6): 366-72, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20542665

ABSTRACT

BACKGROUND: Abnormalities of orbitofrontal cortex (OFC) sulcogyral patterns have been reported in schizophrenia, but it is not known if these predate psychosis. METHODS: Hundred and forty-six subjects at high genetic risk of schizophrenia, 34 first episode of schizophrenia patients (SZ) and 36 healthy controls were scanned and clinically assessed. Utilising the classification system proposed by Chiavaras, we categorised OFC patterns and compared their distribution between the groups, as well as between those high risk subjects who did, and did not develop schizophrenia. The relationship between OFC pattern and schizotypy was explored in high risk subjects. RESULTS: We refined Chiavaras' classification system, with the identification of a previously unreported variant of OFC surface structure. There were significant differences in distribution of OFC patterns between high risk subjects who did or did not develop schizophrenia as well as between the first episode of schizophrenia group and healthy controls. Within the high risk group, possession of OFC Type III was associated with higher ratings on the Structured Inventory for Schizotypy (SIS) psychotic factor. CONCLUSIONS: Our results suggest that OFC Type III is associated with psychotic features before the development of schizophrenia. Characterisation of OFC morphology may have a role in the identification of those at greatest risk of developing schizophrenia.


Subject(s)
Frontal Lobe/pathology , Magnetic Resonance Imaging , Schizophrenia/pathology , Schizophrenic Psychology , Social Behavior , Adolescent , Adult , Case-Control Studies , Female , Follow-Up Studies , Humans , Male , Psychiatric Status Rating Scales , Risk Factors , Schizophrenia/classification , Schizophrenia/diagnosis , Young Adult
4.
Psychol Med ; 40(6): 945-54, 2010 Jun.
Article in English | MEDLINE | ID: mdl-19732477

ABSTRACT

BACKGROUND: The mildly learning disabled population has a three-fold elevated risk for schizophrenia. It has been proposed that in some individuals this cognitive limitation is a pre-psychotic manifestation of early onset schizophrenia. We examined clinical and neuroanatomical measures of a putative extended phenotype of schizophrenia in an adolescent population receiving special educational assistance. We predicted that people with intellectual impairment and schizotypal features would exhibit amygdala volume reduction as one of the neuroanatomical abnormalities associated with schizophrenia. METHOD: Assessment by clinical interview, neuropsychological assessment and magnetic resonance imaging scanning was carried out in 28 intellectually impaired individuals identified as being at elevated risk of schizophrenia due to the presence of schizotypal traits, 39 intellectually impaired controls and 29 non-intellectually impaired controls. Amygdala volume was compared in these three groups and the relationship between symptomatology and amygdala volume investigated. RESULTS: Right amygdala volume was significantly increased in the elevated risk group compared with the intellectually impaired controls (p=0.05). A significant negative correlation was seen between left amygdala volume and severity of negative symptoms within this group (p<0.05), but not in either control group. CONCLUSIONS: Intellectually impaired subjects judged to be at elevated risk of schizophrenia on the basis of clinical assessment exhibit structural imaging findings which distinguish them from the generality of learning disabled subjects. Within this population reduced amygdala volume may be associated with negative-type symptoms and be part of an extended phenotype that reflects particularly elevated risk and/or early manifestations of the development of psychosis.


Subject(s)
Amygdala/pathology , Education, Special , Image Processing, Computer-Assisted , Learning Disabilities/diagnosis , Magnetic Resonance Imaging , Schizophrenia/diagnosis , Schizophrenic Psychology , Schizotypal Personality Disorder/diagnosis , Adolescent , Analysis of Variance , Dominance, Cerebral/physiology , Female , Humans , Intellectual Disability/diagnosis , Intellectual Disability/pathology , Intellectual Disability/psychology , Intelligence/physiology , Interview, Psychological , Learning Disabilities/pathology , Learning Disabilities/psychology , Male , Neuropsychological Tests/statistics & numerical data , Organ Size/physiology , Phenotype , Psychiatric Status Rating Scales/statistics & numerical data , Psychometrics , Risk Factors , Schizophrenia/pathology , Schizotypal Personality Disorder/pathology , Schizotypal Personality Disorder/psychology , Sex Factors
5.
Nat Immunol ; 2(12): 1126-32, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11702067

ABSTRACT

Using gene expression profiling, we show here that activation of B cells and professional antigen-presenting cells (APCs) induces the expression of common chemokines. Among these, CCL4 was the most potent chemoattractant of a CD4+CD25+ T cell population, which is a characteristic phenotype of regulatory T cells. Depletion of either regulatory T cells or CCL4 resulted in a deregulated humoral response, which culminated in the production of autoantibodies. This suggested that the recruitment of regulatory T cells to B cells and APCs by CCL4 plays a central role in the normal initiation of T cell and humoral responses, and failure to do this leads to autoimmune activation.


Subject(s)
Antigen-Presenting Cells/immunology , Autoimmunity , B-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/immunology , Chemotaxis, Leukocyte , Macrophage Inflammatory Proteins/physiology , Animals , Antigen-Presenting Cells/drug effects , Autoantibodies/biosynthesis , CD4-Positive T-Lymphocytes/drug effects , Cells, Cultured , Chemokine CCL4 , Chemokines/biosynthesis , Gene Expression Profiling , Germinal Center/cytology , Immunophenotyping , Lymphocyte Activation , Lymphocyte Depletion , Macrophage Inflammatory Proteins/pharmacology , Mice , RNA, Messenger/biosynthesis , Receptors, Interleukin-2/physiology , T-Lymphocyte Subsets/classification , Up-Regulation
6.
Science ; 286(5447): 2141-4, 1999 Dec 10.
Article in English | MEDLINE | ID: mdl-10591642

ABSTRACT

Data from ice 3590 meters below Vostok Station indicate that the ice was accreted from liquid water associated with Lake Vostok. Microbes were observed at concentrations ranging from 2.8 x 10(3) to 3.6 x 10(4) cells per milliliter; no biological incorporation of selected organic substrates or bicarbonate was detected. Bacterial 16S ribosomal DNA genes revealed low diversity in the gene population. The phylotypes were closely related to extant members of the alpha- and beta-Proteobacteria and the Actinomycetes. Extrapolation of the data from accretion ice to Lake Vostok implies that Lake Vostok may support a microbial population, despite more than 10(6) years of isolation from the atmosphere.


Subject(s)
Bacteria/isolation & purification , Fresh Water/microbiology , Ice , Antarctic Regions , Bacteria/classification , Bacteria/genetics , Bacterial Physiological Phenomena , DNA, Bacterial/genetics , DNA, Bacterial/isolation & purification , DNA, Ribosomal/genetics , DNA, Ribosomal/isolation & purification , Fresh Water/chemistry , Genes, rRNA , Microscopy, Electron, Scanning , Microscopy, Fluorescence , Minerals/analysis , Pressure , Proteobacteria/classification , Proteobacteria/genetics , Proteobacteria/isolation & purification , Proteobacteria/physiology , RNA, Ribosomal, 16S/genetics , Temperature , Water Microbiology
8.
Biochem Biophys Res Commun ; 220(2): 310-4, 1996 Mar 18.
Article in English | MEDLINE | ID: mdl-8645302

ABSTRACT

15-lipoxygenase (15-LO) expression in artery wall cells has been demonstrated during the development of atherosclerosis in various animal models. We examined whether the expression of 15-LO in aortic endothelial cells affects the gene expression of the adhesion molecule, vascular cell adhesion molecule-1 (VCAM-1). Transient transfection of human 15-LO cDNA into bovine aortic endothelial cells led to the expression of 15-LO protein and enzymatic activity. We studied the induction of VCAM-1 mRNA in these cells. 15-LO expressing cells showed no detectable levels of VCAM-1 message. However, when TNF was added to these cells there was a synergistic increase in VCAM-1 expression relative to cells that were transfected with control plasmid pcDNA I. Our data suggest that 15-LO expression in aortic endothelium may amplify the expression of VCAM-1 induced by inflammatory stimulus during atherogenesis.


Subject(s)
Arachidonate 15-Lipoxygenase/genetics , Endothelium, Vascular/enzymology , Gene Expression Regulation , Gene Expression , Tumor Necrosis Factor-alpha/pharmacology , Vascular Cell Adhesion Molecule-1/genetics , Animals , Antithrombins , Aorta , Cattle , Cells, Cultured , Humans , Linoleic Acids/biosynthesis , RNA, Messenger/metabolism , Transfection
9.
EMBO J ; 13(18): 4329-42, 1994 Sep 15.
Article in English | MEDLINE | ID: mdl-7925277

ABSTRACT

NUF1/SPC110, encoding a nuclear filament-related protein which is a component of the yeast spindle pole body (SPB), has been identified in a screen designed to isolate genes encoding targets of yeast calmodulin. Spc110p interacts with calmodulin by two different criteria and the calmodulin interacting region has been localized within the C-terminus of the protein. Point mutations between residues 898 and 917 further define the calmodulin binding site within this region. Mutations in this domain which abolish calmodulin binding in vitro prevent Spc110p function in vivo, demonstrating that calmodulin binding by Spc110p has important functional consequences. In keeping with a role for calmodulin in Spc110p function, we show that calmodulin localizes to the yeast SPB when cells are prepared under appropriate conditions. Non-functional mutant Spc110 proteins which cannot bind calmodulin are present at lowered steady-state levels in the cell; when their level is increased by elevated gene dosage, partial recovery of Spc110p function is seen. Overexpression of calmodulin suppresses the defect(s) associated with the mutant Spc110 proteins, supporting the notion that Spc110p stability is a consequence of its ability to bind calmodulin and pointing to a direct role for calmodulin in Spc110p function.


Subject(s)
Calmodulin/metabolism , Fungal Proteins/metabolism , Genes, Fungal/genetics , Nuclear Proteins/metabolism , Saccharomyces cerevisiae Proteins , Saccharomyces cerevisiae/physiology , Spindle Apparatus/physiology , Alleles , Amino Acid Sequence , Binding Sites/genetics , Calcium/pharmacology , Calmodulin/genetics , Calmodulin/isolation & purification , Calmodulin-Binding Proteins , Cell Compartmentation , Cell Cycle/physiology , Cytoskeletal Proteins , DNA Mutational Analysis , Fluorescent Antibody Technique , Fungal Proteins/genetics , Gene Expression Regulation, Fungal , Genomic Library , Molecular Sequence Data , Mutagenesis, Insertional , Nuclear Proteins/genetics , Protein Binding/drug effects , Protein Binding/genetics , Protein Structure, Secondary , Recombinant Proteins/metabolism , Restriction Mapping , Saccharomyces cerevisiae/genetics
10.
Anesth Analg ; 67(9): 828-32, 1988 Sep.
Article in English | MEDLINE | ID: mdl-3414992

ABSTRACT

The incidence of tourniquet pain was evaluated in 40 patients having orthopedic surgery of the lower extremities during spinal anesthesia using 15 mg of a plain solution of either 0.5% tetracaine or 0.5% bupivacaine. The drugs were administered in a randomized fashion, and measurement of the levels of sensory anesthesia to pinprick and motor blockade as well as the occurrence of tourniquet pain were made by an independent blinded observer. The onset and maximum cephalad spread of sensory anesthesia and the onset and degree of motor block were similar in both groups of patients. However, the duration of sensory anesthesia was significantly longer in patients in whom tetracaine was used. The incidence of tourniquet pain was significantly greater in patients given tetracaine (60%) than in patients given bupivacaine (25%). The occurrence of tourniquet pain was not related to the level of sensory anesthesia, because patients in the tetracaine group had a higher level of sensory anesthesia (mean T6) than did patients in the bupivacaine group (mean T10) at the onset of tourniquet pain. It is speculated that during spinal anesthesia both A and C fibers (mediating fast and slow pain, respectively) are initially equally inhibited. However, as the concentration of local anesthetic in the cerebrospinal fluid declines, C fibers may become unblocked earlier with tetracaine than A fibers, resulting in tourniquet pain in the presence of an otherwise satisfactory spinal anesthetic.


Subject(s)
Anesthesia, Spinal , Bupivacaine , Pain/etiology , Tetracaine , Tourniquets/adverse effects , Aged , Bupivacaine/administration & dosage , Female , Humans , Male , Middle Aged , Nerve Fibers/drug effects , Nervous System/drug effects , Pain/metabolism , Tetracaine/administration & dosage
11.
Pediatr Res ; 19(12): 1268-71, 1985 Dec.
Article in English | MEDLINE | ID: mdl-4080444

ABSTRACT

Hyperventilation (respiratory alkalosis) is an important treatment for persistent pulmonary hypertension in neonates. The precise way that hyperventilation attenuates hypoxic pulmonary vasoconstriction is unclear. We studied the effect of alkalosis on hypoxia-induced pulmonary vasoconstriction in 13 acutely instrumented, pentobarbital anesthetized, neonatal lambs. We specifically examined the relative effects of a metabolic alkalosis versus a respiratory alkalosis on hypoxic pulmonary vasoconstriction and compared these results to the control response to hypoxia without alkalosis. Hypoxic pulmonary vasoconstriction was significantly milder whenever the animal was alkalotic, regardless of whether the alkalosis was respiratory of metabolic. Thus, the elevated pHa rather than decreased PaCO2 during hyperventilation appears to be the major factor in moderating the response of the pulmonary vessels to acute hypoxia in this neonatal lamb model.


Subject(s)
Alkalosis, Respiratory/physiopathology , Hypoxia/physiopathology , Pulmonary Circulation , Vasoconstriction , Animals , Animals, Newborn , Blood Pressure , Humans , Hypertension, Pulmonary/congenital , Hypertension, Pulmonary/therapy , Infant, Newborn , Sheep , Vascular Resistance
13.
Clin Obstet Gynecol ; 27(1): 125-33, 1984 Mar.
Article in English | MEDLINE | ID: mdl-6705306

ABSTRACT

The experienced obstetrician knows that depressed neonates do not always herald their coming, and that the potential liability for failure to intervene promptly is great. It is imperative that all personnel involved in the delivery and care of newborns be familiar with these principles of newborn resuscitation.


Subject(s)
Asphyxia Neonatorum/therapy , Resuscitation , Acidosis/etiology , Animals , Animals, Newborn , Apgar Score , Asphyxia Neonatorum/etiology , Asphyxia Neonatorum/metabolism , Central Nervous System/physiopathology , Emergencies , Female , Glycolysis , Heart Rate , Humans , Infant, Newborn , Infant, Premature , Macaca mulatta , Meconium , Pregnancy , Respiration, Artificial , Risk
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