Developmental critical period in gentic redox dysregulation: animal and human studies in schizophrenia

Converging evidence favors an abnormal susceptibility to oxidative stress in schizophrenia. Decreased levels of glutathione (GSH), the major cellular antioxidant and redox regulator, was observed in cerebrospinal-fluid and prefrontal cortex of patients. Importantly, abnormal GSH synthesis of genetic origin was observed: Two case-control studies showed an association with a GAG trinucleotide repeat (TNR) polymorphism in the GSH key synthesizing enzyme glutamate-cysteine-ligase (GCL) catalytic subunit (GCLC) gene. The most common TNR genotype 7/7 was more frequent in controls, whereas the rarest TNR genotype 8/8 was three times more frequent in patients. The disease associated genotypes (35% of patients) correlated with decreased GCLC protein, GCL activity and GSH content. Similar GSH system anomalies were observed in early psychosis patients. Such redox dysregulation combined with environmental stressors at specific developmental stages could underlie structural and functional connectivity anomalies. In pharmacological and knock-out (KO) models, GSH deficit induces anomalies analogous to those reported in patients. (a) morphology: spine density and GABA-parvalbumine immunoreactivity (PV-I) were decreased in anterior cingulate cortex. KO mice showed delayed cortical PV-I at PD10. This effect is exacerbated in mice with increased DA from PD5-10. KO mice exhibit cortical impairment in myelin and perineuronal net known to modulate PV connectivity. (b) physiology: In cultured neurons, NMDA response are depressed by D2 activation. In hippocampus, NMDA-dependent synaptic plasticity is impaired and kainate induced g-oscillations are reduced in parallel to PV-I. (c) cognition: low GSH models show increased sensitivity to stress, hyperactivity, abnormal object recognition, olfactory integration and social behavior. In a clinical study, GSH precursor N-acetyl cysteine (NAC) as add on therapy, improves the negative symptoms and decreases the side effects of antipsychotics. In an auditory oddball paradigm, NAC improves the mismatched negativity, an evoked potential related to pre-attention and to NMDA receptors function. In summary, clinical and experimental evidence converge to demonstrate that a genetically induced dysregulation of GSH synthesis combined with environmental insults in early development represent a major risk factor contributing to the development of schizophrenia Conclusion Based on these data, we proposed a model for PSIP1 promoter activity involving a complex interplay between yet undefined regulatory elements to modulate gene expression.

Determination of the critical period of weed control in corn using a thermal basis

Field studies were conducted over 3 years in southeast Buenos Aires, Argentina, to determine the critical period of weed control in maize (Zea mays L.). The treatments consisted of two different periods of weed interference, a critical weed-free period, and a critical time of weed removal. The Gompertz and logistic equations were fitted to relative yields representing the critical weed-free and the critical time of weed removal, respectively. Accumulated thermal units were used to describe each period of weed-free or weed removal. The critical weed-free period and the critical time of weed removal ranged from 222 to 416 and 128 to 261 accumulated thermal units respectively, to prevent yield losses of 2.5%. Weed biomass proved to be inverse to the crop yield for all the years studied. When weeds competed with the crop from emergence, a large increase in weed biomass was achieved 10 days after crop emergence. However, few weed seedlings emerged and prospered after the 5-6 leaf maize stage (10-20 days after emergence).

Developmental critical period in genetic redox dysregulation: animal and human studies in schizophrenia

Converging evidence favors an abnormal susceptibility to oxidative stress in schizophrenia. Decreased levels of glutathione (GSH), the major cellular antioxidant and redox regulator, was observed in cerebrospinal-fluid and prefrontal cortex of patients. Importantly, abnormal GSH synthesis of genetic origin was observed: Two case-control studies showed an association with a GAG trinucleotide repeat (TNR) polymorphism in the GSH key synthesizing enzyme glutamate-cysteine-ligase (GCL) catalytic subunit (GCLC) gene. The most common TNR genotype 7/7 was more frequent in controls, whereas the rarest TNR genotype 8/8 was three times more frequent in patients. The disease associated genotypes (35% of patients) correlated with decreased GCLC protein, GCL activity and GSH content. Similar GSH system anomalies were observed in early psychosis patients. Such redox dysregulation combined with environmental stressors at specific developmental stages could underlie structural and functional connectivity anomalies. In pharmacological and knock-out (KO) models, GSH deficit induces anomalies analogous to those reported in patients. (a) morphology: spine density and GABA-parvalbumine immunoreactivity (PV-I) were decreased in anterior cingulate cortex. KO mice showed delayed cortical PV-I at PD10. This effect is exacerbated in mice with increased DA from PD5-10. KO mice exhibit cortical impairment in myelin and perineuronal net known to modulate PV connectivity. (b) physiology: In cultured neurons, NMDA response are depressed by D2 activation. In hippocampus, NMDA-dependent synaptic plasticity is impaired and kainate induced g-oscillations are reduced in parallel to PV-I. (c) cognition: low GSH models show increased sensitivity to stress, hyperactivity, abnormal object recognition, olfactory integration and social behavior. In a clinical study, GSH precursor N-acetyl cysteine (NAC) as add on therapy, improves the negative symptoms and decreases the side effects of antipsychotics. In an auditory oddball paradigm, NAC improves the mismatched negativity, an evoked potential related to pre-attention and to NMDA receptors function. In summary, clinical and experimental evidence converge to demonstrate that a genetically induced dysregulation of GSH synthesis combined with environmental insults in early development represent a major risk factor contributing to the development of schizophrenia

Targeting Oxidative Stress and Aberrant Critical Period Plasticity in the Developmental Trajectory to Schizophrenia.

Schizophrenia is a neurodevelopmental disorder reflecting a convergence of genetic risk and early life stress. The slow progression to first psychotic episode represents both a window of vulnerability as well as opportunity for therapeutic intervention. Here, we consider recent neurobiological insight into the cellular and molecular components of developmental critical periods and their vulnerability to redox dysregulation. In particular, the consistent loss of parvalbumin-positive interneuron (PVI) function and their surrounding perineuronal nets (PNNs) as well as myelination in patient brains is consistent with a delayed or extended period of circuit instability. This linkage to critical period triggers (PVI) and brakes (PNN, myelin) implicates mistimed trajectories of brain development in mental illness. Strategically introduced antioxidant treatment or later reinforcement of molecular brakes may then offer a novel prophylactic psychiatry.

Critical period for weed control in potatoes in the Huambo Province (Angola)

The effects of different weed management periods on potatoes were studied in three areas (Bailundo, Chianga and Calenga) of the central highlands of Angola and in three cropping seasons, from June 2005 to May 2007. Six weed-management treatments were used to identify critical periods of competition and to allow the development of more precise management recommendations. Total potato yield ranged from about 22 t ha-1 in weed-free plots to about 3 t ha-1 with no weed control a yield loss of 86%. Major weed species Galinsoga parviflora, Cyperus esculentus, Bidens biternata, Amaranthus hybridus, Nicandra physaloides, Portulaca oleracea and Datura stramonium differed from area to area. The species G. parviflora dominated the weed flora in all three areas 73, 97 and 72 plants m² 50 days after crop emergence in Bailundo, Chianga and Calenga respectively, in dry season trials; while C. esculentus was also present in Chianga and Calenga, with an average density of ca 30 plants m-2 in dry season trials. Gompertz and logistic equations were fitted to data representing increasing periods of weed-free growth and weed interference, respectively. Critical periods for weed control, with a 95% weed-free total yield, were estimated from 26 to 66 and from 20 to 61 days after emergence for the rainy and dry seasons, respectively. Weed competition before or after these critical periods had negligible effects on crop yield.

Why all counter-evidence to the critical period hypothesis in second language acquisition is not equal or problematic

That adult and child language acquisitions differ in route and outcome is observable. Notwithstanding, there is controversy as to what this observation means for the Critical Period Hypothesis’ (CPH) application to adult second language acquisition (SLA). As most versions of the CPH applied to SLA claim that differences result from maturational effects on in-born linguistic mechanisms, the CPH has many implications that are amendable to empirical investigation. To date, there is no shortage of literature claiming that the CPH applies or does not apply to normal adult SLA. Herein, I provide an epistemological discussion on the conceptual usefulness of the CPH in SLA (cf. Singleton 2005) coupled with a review of Long's (2005) evaluation of much available relevant research. Crucially, I review studies that Long did not consider and conclude differently that there is no critical/sensitive period for L2 syntactic and semantic acquisition.

The critical period of American history, 1783-1789.

Bibliography: p. [351]-356.

The critical period of American history, 1783-1789 /

Includes index.

Adult cortical plasticity depends on an early postnatal critical period

Development of the cerebral cortex is influenced by sensory experience during distinct phases of postnatal development known as critical periods. Disruption of experience during a critical period produces neurons that lack specificity for particular stimulus features, such as location in the somatosensory system. Synaptic plasticity is the agent by which sensory experience affects cortical development. Here, we describe, in mice, a developmental critical period that affects plasticity itself. Transient neonatal disruption of signaling via the C-terminal domain of "disrupted in schizophrenia 1" (DISC1)-a molecule implicated in psychiatric disorders-resulted in a lack of long-term potentiation (LTP) (persistent strengthening of synapses) and experience-dependent potentiation in adulthood. Long-term depression (LTD) (selective weakening of specific sets of synapses) and reversal of LTD were present, although impaired, in adolescence and absent in adulthood. These changes may form the basis for the cognitive deficits associated with mutations in DISC1 and the delayed onset of a range of psychiatric symptoms in late adolescence.

Rainfall erosivity and rainfall return period in the experimental watershed of Aracruz, in the coastal plain of Espirito Santo, Brazil

Knowledge on the factors influencing water erosion is fundamental for the choice of the best land use practices. Rainfall, expressed by rainfall erosivity, is one of the most important factors of water erosion. The objective of this study was to determine rainfall erosivity and the return period of rainfall in the Coastal Plains region, near Aracruz, a town in the state of Espírito Santo, Brazil, based on available data. Rainfall erosivity was calculated based on historic rainfall data, collected from January 1998 to July 2004 at 5 min intervals, by automatic weather stations of the Aracruz Cellulose S.A company. A linear regression with individual rainfall and erosivity data was fit to obtain an equation that allowed data extrapolation to calculate individual erosivity for a 30-year period. Based on this data the annual average rainfall erosivity in Aracruz was 8,536 MJ mm ha-1 h-1 yr-1. Of the total annual rainfall erosivity 85 % was observed in the most critical period October to March. Annual erosive rains accounted for 38 % of the events causing erosion, although the runoff volume represented 88 % of the total. The annual average rainfall erosivity return period was estimated to be 3.4 years.

Prolonged Period of Cortical Plasticity upon Redox Dysregulation in Fast-Spiking Interneurons.

BACKGROUND: Oxidative stress and the specific impairment of perisomatic gamma-aminobutyric acid circuits are hallmarks of the schizophrenic brain and its animal models. Proper maturation of these fast-spiking inhibitory interneurons normally defines critical periods of experience-dependent cortical plasticity. METHODS: Here, we linked these processes by genetically inducing a redox dysregulation restricted to such parvalbumin-positive cells and examined the impact on critical period plasticity using the visual system as a model (3-6 mice/group). RESULTS: Oxidative stress was accompanied by a significant loss of perineuronal nets, which normally enwrap mature fast-spiking cells to limit adult plasticity. Accordingly, the neocortex remained plastic even beyond the peak of its natural critical period. These effects were not seen when redox dysregulation was targeted in excitatory principal cells. CONCLUSIONS: A cell-specific regulation of redox state thus balances plasticity and stability of cortical networks. Mistimed developmental trajectories of brain plasticity may underlie, in part, the pathophysiology of mental illness. Such prolonged developmental plasticity may, in turn, offer a therapeutic opportunity for cognitive interventions targeting brain plasticity in schizophrenia.

Aversive stimulation during the stress-hyporesponsive period does not affect the number of corticotroph cells in neonatal male rats

Immunohistochemistry was used to evaluate the effects of neonatal handling and aversive stimulation during the first 10 days of life on the number of corticotrophs in the anterior lobe of the pituitary of 11-day-old male Wistar rats. Since adult rats handled during infancy respond with reduced corticosterone secretion in response to stressors and with less behavior inhibition in novel environments, we assumed that neonatal stimulation could affect pituitary morphology during this critical period of cell differentiation. Three groups of animals were studied: intact (no manipulation, N = 5), handled (N = 5) and stimulated (submitted to 3 different aversive stimuli, N = 5). The percentage of ACTH-immunoreactive cells in the anterior lobe of the pituitary (number of ACTH-stained cells divided by total number of cells) was determined by examining three slices per pituitary in which a minimum of 200 cells were counted by two independent researchers. Although animals during the neonatal period are less reactive to stress-like stimulation in terms of ACTH and corticosterone secretion, results showed that the relative number of ACTH-stained cells of neonatal handled (0.25 ± 0.01) and aversive stimulated (0.29 ± 0.03) rats was not significantly different from intact (0.30 ± 0.03) animals. Neonatal stimulation may have a differential effect on the various subpopulations of corticotroph cells in the anterior pituitary

Critical periods of weed control in naturally green colored cotton BRS Verde

Cotton with naturally colored fiber is increasing as a commercial crop due specially to its textile processing with reduced environmental impact, as dying is not necessary. The critical period of weed control and the weed community were studied in a field with the naturally green colored fiber cv. BRS Verde cultivated in Missao Velha, Brazil. Without weed control during all the cycle, a reduction of 82.9% in yield was observed. The critical period of weed control was between 31 and 74 days after emergence for a reduction of 5% in yield. The weed community was composed of 21 species, with higher relative importance and dominance of monocotyledonous species. The beginning of the critical period was found to be more influential on yield than the ending. Thus, defining the right moment to start weed control can be more important to yield than determining the moment to cease it. (C) 2011 Elsevier B.V. All rights reserved.

Expression profiling of purified mouse gonadal somatic cells during the critical time window of sex determination reveals novel candidate genes for human sexual dysgenesis syndromes

Despite the identification of SRY as the testis-determining gene in mammals, the genetic interactions controlling the earliest steps of male sex determination remain poorly understood. In particular, the molecular lesions underlying a high proportion of human XY gonadal dysgenesis, XX maleness and XX true hermaphroditism remain undiscovered. A number of screens have identified candidate genes whose expression is modulated during testis or ovary differentiation in mice, but these screens have used whole gonads, consisting of multiple cell types, or stages of gonadal development well beyond the time of sex determination. We describe here a novel reporter mouse line that expresses enhanced green fluorescent protein under the control of an Sf1 promoter fragment, marking Sertoli and granulosa cell precursors during the critical period of sex determination. These cells were purified from gonads of male and female transgenic embryos at 10.5 dpc (shortly after Sry transcription is activated) and 11.5 dpc (when Sox9 transcription begins), and their transcriptomes analysed using Affymetrix genome arrays. We identified 266 genes, including Dhh, Fgf9 and Ptgds, that were upregulated and 50 genes that were downregulated in 11.5 dpc male somatic gonad cells only, and 242 genes, including Fst, that were upregulated in 11.5 dpc female somatic gonad cells only. The majority of these genes are novel genes that lack identifiable homology, and several human orthologues were found to map to chromosomal loci implicated in disorders of sexual development. These genes represent an important resource with which to piece together the earliest steps of sex determination and gonad development, and provide new candidates for mutation searching in human sexual dysgenesis syndromes.