Hardly vacuous: The parasitophorous vacuolar membrane of malaria parasites

When a malaria parasite invades a host erythrocyte it pushes itself in and invaginates a portion of the host membrane, thereby sealing itself inside and establishing itself in the resulting vacuole. The parasitophorous vacuolar membrane (PVM) that surrounds the parasite is modified by the parasite, using its secretory organelles. To survive within this enveloping membrane, the organism must take in nutrients, secrete wastes, export proteins into the host cell, and eventually egress. Here, we review current understanding of the unique solutions Plasmodium has evolved to these challenges and discuss the remaining questions

Usage-based and emergentist approaches to language acquisition

It was long considered to be impossible to learn grammar based on linguistic experience alone. In the past decade, however, advances in usage-based linguistic theory, computational linguistics, and developmental psychology changed the view on this matter. So-called usage-based and emergentist approaches to language acquisition state that language can be learned from language use itself, by means of social skills like joint attention, and by means of powerful generalization mechanisms. This paper first summarizes the assumptions regarding the nature of linguistic representations and processing. Usage-based theories are nonmodular and nonreductionist, i.e., they emphasize the form-function relationships, and deal with all of language, not just selected levels of representations. Furthermore, storage and processing is considered to be analytic as well as holistic, such that there is a continuum between children's unanalyzed chunks and abstract units found in adult language. In the second part, the empirical evidence is reviewed. Children's linguistic competence is shown to be limited initially, and it is demonstrated how children can generalize knowledge based on direct and indirect positive evidence. It is argued that with these general learning mechanisms, the usage-based paradigm can be extended to multilingual language situations and to language acquisition under special circumstances

FiSSE: A simple nonparametric test for the effects of a binary character on lineage diversification rates

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137596/1/evo13227.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137596/2/evo13227_am.pd

Differential medial temporal lobe morphometric predictors of item- and relational-encoded memories in healthy individuals and in individuals with mild cognitive impairment and Alzheimer's disease.

INTRODUCTION:Episodic memory processes are supported by different subregions of the medial temporal lobe (MTL). In contrast to a unitary model of memory recognition supported solely by the hippocampus, a current model suggests that item encoding engages perirhinal cortex, whereas relational encoding engages parahippocampal cortex and the hippocampus. However, this model has not been examined in the context of aging, neurodegeneration, and MTL morphometrics. METHODS:Forty-four healthy subjects (HSs) and 18 cognitively impaired subjects (nine mild cognitive impairment [MCI] and nine Alzheimer's disease [AD] patients) were assessed with the relational and item-specific encoding task (RISE) and underwent 3T magnetic resonance imaging. The RISE assessed the differential contribution of relational and item-specific memory. FreeSurfer was used to obtain measures of cortical thickness of MTL regions and hippocampus volume. RESULTS:Memory accuracies for both item and relational memory were significantly better in the HS group than in the MCI/AD group. In MCI/AD group, relational memory was disproportionately impaired. In HSs, hierarchical regressions demonstrated that memory was predicted by perirhinal thickness after item encoding, and by hippocampus volume after relational encoding (both at trend level) and significantly by parahippocampal thickness at associative recognition. The same brain morphometry profiles predicted memory accuracy in MCI/AD, although more robustly perirhinal thickness for item encoding (R2 = 0.31) and hippocampal volume and parahippocampal thickness for relational encoding (R2 = 0.31). DISCUSSION:Our results supported a model of episodic memory in which item-specific encoding was associated with greater perirhinal cortical thickness, while relational encoding was associated with parahippocampal thickness and hippocampus volume. We identified these relationships not only in HSs but also in individuals with MCI and AD. In the subjects with cognitive impairment, reductions in hippocampal volume and impairments in relational memory were especially prominent

Duration judgements in patients with schizophrenia

Background. The ability to encode time cues underlies many cognitive processes. In the light of schizophrenic patients' compromised cognitive abilities in a variety of domains, it is noteworthy that there are numerous reports of these patients displaying impaired timing abilities. However, the timing intervals that patients have been evaluated on in prior studies vary considerably in magnitude (e.g. 1 s, 1 min, 1 h etc.). Method. In order to obviate differences in abilities in chronometric counting and place minimal demands on cognitive processing, we chose tasks that involve making judgements about brief durations of time (<1 s). Results. On a temporal generalization task, patients were less accurate than controls at recognizing a standard duration. The performance of patients was also significantly different from controls on a temporal bisection task, in which participants categorized durations as short or long. Although time estimation may be closely intertwined with working memory, patients' working memory as measured by the digit span task did not correlate significantly with their performance on the duration judgement tasks. Moreover, lowered intelligence scores could not completely account for the findings. Conclusions. We take these results to suggest that patients with schizophrenia are less accurate at estimating brief time periods. These deficits may reflect dysfunction of biopsychological timing processes

Discovery and characterization of potent, efficacious, orally available antimalarial Plasmepsin X inhibitors and preclinical safety assessment of UCB7362

Plasmepsin X (PMX) is an essential aspartyl protease controlling malaria parasite egress and invasion of erythrocytes, development of functional liver merozoites (prophylactic activity), and blocking transmission to mosquitoes, making it a potential multistage drug target. We report the optimization of an aspartyl protease binding scaffold and the discovery of potent, orally active PMX inhibitors with in vivo antimalarial efficacy. Incorporation of safety evaluation early in the characterization of PMX inhibitors precluded compounds with a long human half-life