A preliminary investigation into the effects of antipsychotics on sub-chronic phencyclidine-induced deficits in attentional set-shifting in female rats

YesRationale The NMDA receptor antagonist, phencyclidine (PCP), has been shown to induce symptoms characteristic of schizophrenia. A loss in executive function and the ability to shift attention between stimulus dimensions is impaired in schizophrenia; this can be assessed in rodents by the perceptual attentional set-shifting task. Objective The aim of this study was to investigate whether the deficits induced by sub-chronic PCP in attentional set-shifting could be reversed by sub-chronic administration of clozapine, risperidone or haloperidol. Methods Adult female hooded-Lister rats received sub-chronic PCP (2 mg/kg) or vehicle (1 ml/kg) i.p. twice daily for 7 days, followed by a 7-day washout period. PCP-treated rats then received clozapine, risperidone, haloperidol or vehicle once daily for 7 days and were then tested in the perceptual set-shifting task. Results PCP significantly (p < 0.01) increased the number of trials to reach criterion in the EDS phase when compared to vehicle and this deficit was significantly (p < 0.01) attenuated by sub-chronic clozapine (2.5 mg/kg) and risperidone (0.2 mg/kg), but not by sub-chronic haloperidol treatment (0.05 mg/kg). Conclusions These data show that sub-chronic PCP produced a robust deficit within the EDS phase in the attentional set-shifting task, in female rats. Atypical antipsychotics, clozapine and risperidone, but not the classical agent, haloperidol, significantly improved the PCP-induced cognitive deficit

Pollen-inferred regional vegetation patterns and demographic change in Southern Anatolia through the Holocene

Southern Anatolia is a highly significant area within the Mediterranean, particularly in terms of understanding how agriculture moved into Europe from neighbouring regions. This study uses pollen, palaeoclimate and archaeological evidence to investigate the relationships between demography and vegetation change, and to explore how the development of agriculture varied spatially. Data from 21 fossil pollen records have been transformed into forested, parkland and open vegetation types using cluster analysis. Patterns of change have been explored using non-metric multidimensional scaling (nMDS) and through analysis of indicator groups, such as an Anthropogenic Pollen Index, and Simpson’s Diversity. Settlement data, which indicate population densities, and summed radiocarbon dates for archaeological sites have been used as a proxy for demographic change. The pollen and archaeological records confirm that farming can be detected earlier in Anatolia in comparison with many other parts of the Mediterranean. Dynamics of change in grazing indicators and the OJCV (Olea, Juglans, Castanea and Vitis) index for cultivated trees appear to match cycles of population expansion and decline. Vegetation and land use change is also influenced by other factors, such as climate change. Investigating the early impacts of anthropogenic activities (e.g. woodcutting, animal herding, the use of fire and agriculture) is key to understanding how societies have modified the environment since the mid–late Holocene, despite the capacity of ecological systems to absorb recurrent disturbances. The results of this study suggest that shifting human population dynamics played an important role in shaping land cover in central and southern Anatolia

Supernovae without host galaxies? The low surface brightness host of SN 2009Z

A remarkable fraction of supernovae (SNe) have no obvious host galaxy. Two possible explanations are that (i) the host galaxy is simply not detected within the sensitivity of the available data or that (ii) the progenitor is a hypervelocity star that has escaped its parent galaxy. We use the Type IIb SN 2009Z as a prototype of case (i), an example of how a very faint (here Low Surface Brightness; LSB) galaxy can be discovered via the observation of a seemingly host-less SN. By identifying and studying LSB galaxies that host SNe related to the death of massive stars, we can place constraints on the stellar population and environment of LSB galaxies, which at present are poorly understood. From an HI spectrum, a redshift of z = 0.02513+-0.00001 and an HI mass of (2.96+-0.12) 10^9 M_sun are computed. This redshift is consistent with that obtained from optical emission lines of SN 2009Z. Furthermore, a gas mass fraction of f_g = 0.87+-0.04 is obtained, one of the highest fractions ever measured. The host galaxy shows signs of recently enhanced star formation activity with a far-UV derived extinction-corrected Star Formation Rate (SFR) of 0.44+-0.34 M_sun/yr. Based on the B-band luminosity we estimate an extinction-corrected metallicity following the calibration by Pilyugin (2001) of 12 + log(O/H) = 8.24+-0.70. The presence of a Type IIb SN in an LSB galaxy suggests, contrary to popular belief, that massive stars can be formed in this type of galaxies. Furthermore, our results imply that LSB galaxies undergo phases of small, local burst activity intermittent with longer phases of inactivity.Comment: 9 pages, 6 figures, accepted for publication in A&A, abstract abridged due to arXiv requirement

Cerebrospinal fluid proteomics define the natural history of autosomal dominant Alzheimer's disease

Alzheimer's disease (AD) pathology develops many years before the onset of cognitive symptoms. Two pathological processes-aggregation of the amyloid-& beta;(A & beta;) peptide into plaques and the microtubule protein tau into neurofibrillary tangles (NFTs)-are hallmarks of the disease. However, other pathological brain processes are thought to be key disease mediators of A & beta;plaque and NFT pathology. How these additional pathologies evolve over the course of the disease is currently unknown. Here we show that proteomic measurements in autosomal dominant AD cerebrospinal fluid (CSF) linked to brain protein coexpression can be used to characterize the evolution of AD pathology over a timescale spanning six decades. SMOC1 and SPON1 proteins associated with A & beta;plaques were elevated in AD CSF nearly 30 years before the onset of symptoms, followed by changes in synaptic proteins, metabolic proteins, axonal proteins, inflammatory proteins and finally decreases in neurosecretory proteins. The proteome discriminated mutation carriers from noncarriers before symptom onset as well or better than A & beta;and tau measures. Our results highlight the multifaceted landscape of AD pathophysiology and its temporal evolution. Such knowledge will be critical for developing precision therapeutic interventions and biomarkers for AD beyond those associated with A & beta;and tau. Proteomic analysis of cerebrospinal fluid from individuals with autosomal dominant Alzheimer's disease reveals how this complex and chronic disease evolves over many decades

Cerebrospinal fluid proteomics define the natural history of autosomal dominant Alzheimer’s disease

Alzheimer’s disease (AD) pathology develops many years before the onset of cognitive symptoms. Two pathological processes—aggregation of the amyloid- (A ) peptide into plaques and the microtubule protein tau into neurofibrillary tangles (NFTs)—are hallmarks of the disease. However, other pathological brain processes are thought to be key disease mediators of A plaque and NFT pathology. How these additional pathologies evolve over the course of the disease is currently unknown. Here we show that proteomic measurements in autosomal dominant AD cerebrospinal fluid (CSF) linked to brain protein coexpression can be used to characterize the evolution of AD pathology over a timescale spanning six decades. SMOC1 and SPON1 proteins associated with A plaques were elevated in AD CSF nearly 30 years before the onset of symptoms, followed by changes in synaptic proteins, metabolic proteins, axonal proteins, inflammatory proteins and finally decreases in neurosecretory proteins. The proteome discriminated mutation carriers from noncarriers before symptom onset as well or better than A and tau measures. Our results highlight the multifaceted landscape of AD pathophysiology and its temporal evolution. Such knowledge will be critical for developing precision therapeutic interventions and biomarkers for AD beyond those associated with A and tau

Estimativa do índice de área Foliar (IAF) e biomassa em pastagem no estado de Rondônia, Brasil

Medidas mensais da altura da pastagem, biomassa total, variações de biomassa viva e morta, a área específica foliar (SLA) e o Índice de Área de Folha (IAF) de fevereiro de 1999 a janeiro de 2005 na Fazenda Nossa Senhora (FNS) e em Rolim de Moura (RDM) entre Fevereiro a Março de 1999, Rondônia, Brasil. A pastagem predominante é Urochloa brizantha (Hochst. ex A. Rich) R. D. Webster (99% na FNS e 76% em RDM), com pequenas manchas de Urochloa humidicula (Rendle). A altura média anual da grama foi de ~0,16 m. Com o pastejo, o mínimo mensal foi de 0,09 m (estação seca) e máximo de 0,3 m sem pastejo (estação úmida). O IAF, biomassa total, material morto, vivo e SLA tiveram valores médios de 2,5 m2 m-2 , 2202 kg ha-1, 2916 kg ha-1 e 19 m2 kg-1 respectivamente. A média mensal da biomassa foi 4224 kg ha-1 em 2002 e 6667 kg ha-1 em 2003. Grande variação sazonal do material vivo e morto, sendo mais alto o vivo durante a estação úmida (3229 contra 2529 kg ha-1), sendo o morto maior durante a seca (2542 contra 1894 kg ha-1). O nível de água no solo variou de -3,1 a -6,5 m durante as estações. Em médias anuais os IAF foram de 1,4 em 2000 a 2,8 em 2003 e o SLA entre 16,3 m2 kg-1 em 1999 e 20,4 m2 kg-1 em 2001. As observações do Albedo variaram de 0,18 para 0,16 em relação aos altos valores de IAF

A randomised controlled feasibility trial for an educational school-based mental health intervention: study protocol

Background: With the burden of mental illness estimated to be costing the English economy alone around £22.5 billion a year [1], coupled with growing evidence that many mental disorders have their origins in adolescence, there is increasing pressure for schools to address the emotional well-being of their students, alongside the stigma and discrimination of mental illness. A number of prior educational interventions have been developed and evaluated for this purpose, but inconsistency of findings, reporting standards, and methodologies have led the majority of reviewers to conclude that the evidence for the efficacy of these programmes remains inconclusive. Methods/Design: A cluster randomised controlled trial design has been employed to enable a feasibility study of 'SchoolSpace', an intervention in 7 UK secondary schools addressing stigma of mental illness, mental health literacy, and promotion of mental health. A central aspect of the intervention involves students in the experimental condition interacting with a young person with lived experience of mental illness, a stigma reducing technique designed to facilitate students' engagement in the project. The primary outcome is the level of stigma related to mental illness. Secondary outcomes include mental health literacy, resilience to mental illness, and emotional well-being. Outcomes will be measured pre and post intervention, as well as at 6 month follow-up. Discussion: The proposed intervention presents the potential for increased engagement due to its combination of education and contact with a young person with lived experience of mental illness. Contact as a technique to reduce discrimination has been evaluated previously in research with adults, but has been employed in only a minority of research trials investigating the impact on youth. Prior to this study, the effect of contact on mental health literacy, resilience, and emotional well-being has not been evaluated to the authors' knowledge. If efficacious the intervention could provide a reliable and cost-effective method to reduce stigma in young people, whilst increasing mental health literacy, and emotional well-being. Trial registration: ISRCTN: ISRCTN0740602

Species Interactions during Diversification and Community Assembly in an Island Radiation of Shrews

Closely related, ecologically similar species often have adjacent distributions, suggesting competitive exclusion may contribute to the structure of some natural communities. In systems such as island archipelagos, where speciation is often tightly associated with dispersal over oceanic barriers, competitive exclusion may prevent population establishment following inter-island dispersal and subsequent cladogenesis.) species in the Philippines are the result of competitive exclusion preventing secondary invasion of occupied islands. We first compare ecological niche models between two widespread, allopatric species and find statistical support for their ecological similarity, implying that competition for habitat between these species is possible. We then examine dispersion patterns among sympatric species and find some signal for overdispersion of body size, but not for phylogenetic branch length. Finally, we simulate the process of inter-island colonization under a stochastic model of dispersal lacking ecological forces. Results are dependent on the geographic scope and colonization probability employed. However, some combinations suggest that the number of inter-island dispersal events necessary to populate the archipelago may be much higher than the minimum number of colonization events necessary to explain current estimates of species richness and phylogenetic relationships. If our model is appropriate, these results imply that alternative factors, such as competitive exclusion, may have influenced the process of inter-island colonization and subsequent cladogenesis.We interpret the combined results as providing tenuous evidence that similarity in body size may prevent co-occurrence in Philippine shrews and that competitive exclusion among ecologically similar species, rather than an inability to disperse among islands, may have limited diversification in this group, and, possibly other clades endemic to island archipelagos

Parasite Burden and CD36-Mediated Sequestration Are Determinants of Acute Lung Injury in an Experimental Malaria Model

Although acute lung injury (ALI) is a common complication of severe malaria, little is known about the underlying molecular basis of lung dysfunction. Animal models have provided powerful insights into the pathogenesis of severe malaria syndromes such as cerebral malaria (CM); however, no model of malaria-induced lung injury has been definitively established. This study used bronchoalveolar lavage (BAL), histopathology and gene expression analysis to examine the development of ALI in mice infected with Plasmodium berghei ANKA (PbA). BAL fluid of PbA-infected C57BL/6 mice revealed a significant increase in IgM and total protein prior to the development of CM, indicating disruption of the alveolar–capillary membrane barrier—the physiological hallmark of ALI. In contrast to sepsis-induced ALI, BAL fluid cell counts remained constant with no infiltration of neutrophils. Histopathology showed septal inflammation without cellular transmigration into the alveolar spaces. Microarray analysis of lung tissue from PbA-infected mice identified a significant up-regulation of expressed genes associated with the gene ontology categories of defense and immune response. Severity of malaria-induced ALI varied in a panel of inbred mouse strains, and development of ALI correlated with peripheral parasite burden but not CM susceptibility. Cd36−/− mice, which have decreased parasite lung sequestration, were relatively protected from ALI. In summary, parasite burden and CD36-mediated sequestration in the lung are primary determinants of ALI in experimental murine malaria. Furthermore, differential susceptibility of mouse strains to malaria-induced ALI and CM suggests that distinct genetic determinants may regulate susceptibility to these two important causes of malaria-associated morbidity and mortality

Animal models of cognitive dysfunction and negative symptoms of schizophrenia: focus on NMDA receptor antagonism

YesCognitive deficits in schizophrenia remain an unmet clinical need. Improved understanding of the neuro- and psychopathology of these deficits depends on the availability of carefully validated animal models which will assist the development of novel therapies. There is much evidence that at least some of the pathology and symptomatology (particularly cognitive and negative symptoms) of schizophrenia results from a dysfunction of the glutamatergic system which may be modelled in animals through the use of NMDA receptor antagonists. The current review examines the validity of this model in rodents. We review the ability of acute and sub-chronic treatment with three non-competitive NMDA antagonists; phencyclidine (PCP), ketamine and MK801 (dizocilpine) to produce cognitive deficits of relevance to schizophrenia in rodents and their subsequent reversal by first- and second-generation antipsychotic drugs. Effects of NMDA receptor antagonists on the performance of rodents in behavioural tests assessing the various domains of cognition and negative symptoms are examined: novel object recognition for visual memory, reversal learning and attentional set shifting for problem solving and reasoning, 5-Choice Serial Reaction Time for attention and speed of processing; in addition to effects on social behaviour and neuropathology. The evidence strongly supports the use of NMDA receptor antagonists to model cognitive deficit and negative symptoms of schizophrenia as well as certain pathological disturbances seen in the illness. This will facilitate the evaluation of much-needed novel pharmacological agents for improved therapy of cognitive deficits and negative symptoms in schizophrenia