The choroid plexus-cerebrospinal fluid interface in Alzheimer's disease : more than just a barrier

The choroid plexus is a complex structure which hangs inside the ventricles of the brain and consists mainly of choroid plexus epithelial (CPE) cells surrounding fenestrated capillaries. These CPE cells not only form an anatomical barrier, called the blood-cerebrospinal fluid barrier (BCSFB), but also present an active interface between blood and cerebrospinal fluid (CSF). CPE cells perform indispensable functions for the development, maintenance and functioning of the brain. Indeed, the primary role of the choroid plexus in the brain is to maintain homeostasis by secreting CSF which contains different molecules, such as nutrients, neurotrophins, and growth factors, as well as by clearing toxic and undesirable molecules from CSF. The choroid plexus also acts as a selective entry gate for leukocytes into the brain. Recent findings have revealed distinct changes in CPE cells that are associated with aging and Alzheimer's disease. In this review, we review some recent findings that highlight the importance of the CPE-CSF system in Alzheimer's disease and we summarize the recent advances in the regeneration of brain tissue through use of CPE cells as a new therapeutic strategy

Unconditional-FCIs of Dravidian

We explore a particle combination in Dravidian that occurs across unconditionals and free choice items. We first propose a semantics for the unconditional and then posit an unconditional structure for the polarity items of Dravidian that are formed with this particle combination. This not only unifies the paradigm for the unconditionals and free choice items that is called for by the occurrence of the same morphemes in both cases, but also explains the distribution and licensing of these polarity items

A New Kind of Perspective Sensitivity Cross-linguistically: Primary Predication with -gaa

We argue for a new type of judge-dependence encoding based on Telugu adjectival data (with cross-linguistic parallels in Spanish ser/estar, Finnish Essive case, and, Russian Instrumental case). Uniquely, this kind of predicate gives rise to a transient reading in certain contexts without an overt PP. With other experiencer and tense combinations, it gives rise to subjective, dispositional and evaluative interpretations, similar to PPTs. The general theoretical import comes down to the difference between an experiencer argument in an event mediated predication vs. a non-event-mediated predication. We analyse the transient reading as event mediatedpredication, brought about by the eventive predicator -gaa, with a first-person based generic quantification over the experiencer variable (introduced by -gaa) and judge index. When the experiencer is overt or pro, the interpretation is subjective, and when there is generic quantification over the event variable (interaction of tense) the meaning is evaluative or dispositional. In non- event-mediated predication, without -gaa, the transient reading is absent, and subjectivity is based on the kind of gradable adjective–dimensional, and evaluative adjectives; PPTs

The Quotative Complementizer Says “I’m too Baroque for that”

We build a composite picture of the quotative complementizer (QC) in Dravidian by examining its role in various left-peripheral phenomena – agreement shift, embedded questions; and its particular manifestation in various constructions like noun complement clauses, manner adverbials, rationale clauses, with naming verbs, small clauses, and non-finite embedding, among others. The QC we conclude is instantiated at the very edge of the clause it subordinates, outside the usual left periphery, comes with its own entourage of projections, and is the light verb say which does not extend its projection. It adjoins to the matrix spine at various heights (at the vP level it gets a theta-role, and thus argument properties) when it does extend its projection, and like a verb selects clauses of various sizes (CP, TP, small clause). We take the Telugu QC ani as illustrative, being more transparent in form to function mapping, but draw from the the QC properties of Malayalam, Kannada, Bangla, and Meiteilon too

Identification of a novel mechanism of blood-brain communication during peripheral inflammation via choroid plexus-derived extracellular vesicles

Here, we identified release of extracellular vesicles (EVs) by the choroid plexus epithelium (CPE) as a new mechanism of blood-brain communication. Systemic inflammation induced an increase in EVs and associated pro-inflammatory miRNAs, including miR-146a and miR-155, in the CSF. Interestingly, this was associated with an increase in amount of multivesicular bodies (MVBs) and exosomes per MVB in the CPE cells. Additionally, we could mimic this using LPS-stimulated primary CPE cells and choroid plexus explants. These choroid plexus-derived EVs can enter the brain parenchyma and are taken up by astrocytes and microglia, inducing miRNA target repression and inflammatory gene up-regulation. Interestingly, this could be blocked in vivo by intracerebroventricular (icv) injection of an inhibitor of exosome production. Our data show that CPE cells sense and transmit information about the peripheral inflammatory status to the central nervous system (CNS) via the release of EVs into the CSF, which transfer this pro-inflammatory message to recipient brain cells. Additionally, we revealed that blockage of EV secretion decreases brain inflammation, which opens up new avenues to treat systemic inflammatory diseases such as sepsis

The Dravidian Correlative and the Disjunction Marker

The Dravidian correlative is formed with a wh-item containing clause that has the disjunction marker -oo at the clause edge. The disjunction marker -oo in Dravidian languages besides coordinating elements, also participates in forming indefinites, and questions. Given that the canonical semantics of correlatives (Dayal 1991, 1996) analyses them as definite descriptions, which bind the pronoun variable via predicate abstraction, the issue is what -oo is doing here, and how the semantic composition works. This sketch towards a compositional derivation of the Dravidian correlative based on a question denotation proves that it is not only feasible but also quite advantageous -- we keep a unified semantics of -oo, the disjunction marker that also participates in forming indefinites, and questions, and derive a number of properties of the Dravidian correlative from the semantics of questions and answers. In the literature, the typology of correlatives has been proposed to have two syntactic parameters -- one, the kind of relative clause it originates from -- EHRC, IHRC, FR; and two, the kind of left dislocation involved -- HTLD, CLD, CLLD. We propose to add to this typology a third and semantic parameter, its denotation -- property or propositional (we locate this semantic parameter itself in the denotation of the wh-items of the language, their lexical semantic entry -- as sets of alternatives or as property free variables). We show that the Dravidian correlative is built out of a proposition-based denotation, Externally Headed Relative Clause, and Hanging Topic Left Dislocation

The role of the particle -oo in wh-exclamatives in Telugu and Kannada

A non-degree approach like d’Avis (2002) doesn’t work for degree readings of wh-exclamatives since it is based on a Groenendijk and Stokhof (1984) denotation of questions. The Widening account of Zannutini and Portner (2003) doesn’t work for individual/event read- ings of wh-exclamatives because of a Karttunen (1977) denotation of questions. Degree deno- tation approaches to wh-exclamatives can’t explain the variability either. We propose a solution such that the widening account works if we start with Hamblin alternatives. Evidence for the widening mechanism comes from wh-exclamatives in Telugu/Kannada –the particle -oo which imposes a join requirement on the semantic content of its immediate context (Szabolcsi 2015). We propose that the semantic/pragmatic mechanism of wh-exclamatives involves the following three steps –Generating alternatives: wh-focus or other focus mechanisms; Scale to order the alternatives: lexical degree scale/degree morpheme or a likelihood scale; Widening & Dynamic update: Widening of domain from ES to D2 and Add {p} to FCspkr 

Current research into brain barriers and the delivery of therapeutics for neurological diseases: a report on CNS barrier congress London, UK, 2017.

This is a report on the CNS barrier congress held in London, UK, March 22-23rd 2017 and sponsored by Kisaco Research Ltd. The two 1-day sessions were chaired by John Greenwood and Margareta Hammarlund-Udenaes, respectively, and each session ended with a discussion led by the chair. Speakers consisted of invited academic researchers studying the brain barriers in relation to neurological diseases and industry researchers studying new methods to deliver therapeutics to treat neurological diseases. We include here brief reports from the speakers