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Background: A seasonal transmission environment including seasonal variation of snail population density and human-snail contact patterns can affect the dynamics of Schistosoma infection and the success of control interventions. In projecting control outcomes, conventional modeling approaches have often ignored seasonality by using simplified intermediate-host modeling, or by restricting seasonal effects through use of yearly averaging.Methods: We used mathematical analysis and numerical simulation to estimate the impact of seasonality on disease dynamics and control outcomes, and to evaluate whether seasonal averaging or intermediate-host reduction can provide reliable predictions of control outcomes. We also examined whether seasonality could be used as leverage in creation of effective control strategies.Results: We found models that used seasonal averaging could grossly overestimate infection burden and underestimate control outcomes in highly seasonal environments. We showed that proper intraseasonal timing of control measures could make marked improvement on the long-term burden reduction for Schistosoma transmission control, and we identified the optimal timing for each intervention. Seasonal snail control, implemented alone, was less effective than mass drug administration, but could provide additive impact in reaching control and elimination targets.Conclusions: Seasonal variation makes Schistosoma transmission less sustainable and easier to control than predicted by earlier modeling studies. [ABSTRACT FROM AUTHOR]

The sodium-bicarbonate cotransporter NBC1 is targeted exclusively at the basolateral membrane. Mutagenesis of a dihydrophobic FL motif (residues 1013-1014) in the C-terminal domain disrupts the targeting of NBC1. In the present study, we determined the precise constraints of the FL motif required for basolateral targeting of NBC1 by expressing epitope-tagged wild-type and mutant NBC1 in MDCK cells and RNA-injected Xenopus oocytes and examining their subcellular localization. We assayed the functional activity of the mutants by measuring bicarbonate-induced currents in oocytes. Wild-type NBC1 (containing PFLS) was expressed exclusively on the basolateral membrane in MDCK cells. Reversal of the FL motif (PLFS) had no effect on basolateral targeting or activity. Shifting the FL motif one residue upstream (FLPS) resulted in mistargeting of the apical membrane but the FLPS mutant retained its functional activity in oocytes. Shifting the FL motif one residue downstream resulted in a mutant (PSFL) that did not efficiently translocate to the plasma membrane and was instead colocalized with the ER marker, protein disulfide isomerase (PDI). Analysis of circular dichroism (CD) revealed that a short peptide, 20 amino acid residues, of wild-type NBC1 contained a significant alpha-helical structure, whereas peptides in which the FL motif was reversed or C-terminally shifted were disordered. We therefore propose that the specific orientation and the precise location of the FL motif in the primary sequence of NBC1 are strict requirements for the alpha-helical structure of the C-terminal cytoplasmic domain and for targeting of NBC1 to the basolateral membrane. [ABSTRACT FROM AUTHOR]

Introduction: The distinction between the schizophrenia spectrum and other types of disorders may be clinically relevant in terms of its predictive validity as suggested by studies showing schizophrenia spectrum patients have more unfavourable outcomes compared to other psychotic disorders. The present study aimed to investigate whether basic self-disturbances and neurocognitive processes that have been linked to psychosis risk have discriminative power for schizophrenia spectrum disorders in patients presenting with first episode psychosis (FEP) and at ultra-high risk for psychosis (UHR).Methods: 38 FEP patients, 48 UHR patients, and 33 healthy controls were assessed for basic self-disturbances (using the Examination of Anomalous Self-Experience, EASE, interview), source monitoring and aberrant salience (behavioural tasks to measure neurocognitive constructs). Clinical groups were divided into patients with schizophrenia spectrum disorders and those with other non-spectrum disorders and were further compared on measures controlling for symptom severity and age.Results: Basic self-disturbances distinguished schizophrenia spectrum from non-spectrum disorders in the 'FEP only' sample, F = 19.76, p < 0.001, η2partial = 0.37, and also in the combined UHR/FEP sample, F = 23.56, p < 0.001, η2partial = 0.22. Additionally, some processes related to source monitoring deficits were elevated in schizophrenia spectrum disorders. In contrast, the two groups (schizophrenia spectrum vs other diagnoses) performed similarly in aberrant salience tasks. Comparable results were obtained for analyses performed with an FEP/UHR combined sample and the 'FEP only' sample.Discussion: Basic self-disturbances at the phenomenological level and source monitoring deficits on the neurocognitive level may be useful in identifying risk of schizophrenia spectrum disorders at the earliest clinical presentation. [ABSTRACT FROM AUTHOR]