Candida albicans Modulates Murine and Human Beta Defensin-1 during Vaginitis

Vulvovaginal candidiasis (VVC) and recurrent vulvovaginal candidiasis (RVVC) are two forms of a disease caused by Candida spp. β-defensin (BD) is one of the most important families of antimicrobial peptides in the female genital tract and includes molecules that exert essential local functions as antimicrobial and PMN chemoattractant peptides. However, the information on their role during murine and human VVC and RVVC is limited. Thus, we analyzed the behavior and contribution of BD1 to the local response in a VVC mice model and the local cytokine profile and human BD1 and BD3 expression in cervicovaginal lavage from patients with VVC and RVVC. We demonstrated that, in patients with RVVC BD1, mRNA and protein expression were severely diminished and that the aspartate proteinase and lipase secreted by C. albicans are involved in that decrease. This study provides novel information about the pathogenesis of VVC and describes a highly efficient C. albicans escape strategy for perpetuating the infection; these results may contribute to the development of new or combined treatment approaches.

Massively parallel identification of zipcodes in primary cortical neurons

Cells adopt highly polarized shapes and form distinct subcellular compartments largely due to the localization of many mRNAs to specific areas, where they are translated into proteins with local functions. This mRNA localization is mediated by specific cis-regulatory elements in mRNAs, commonly called "zipcodes." Their recognition by RNA-binding proteins (RBPs) leads to the integration of the mRNAs into macromolecular complexes and their localization. While there are hundreds of localized mRNAs, only a few zipcodes have been characterized. Here, we describe a novel neuronal zipcode identification protocol (N-zip) that can identify zipcodes across hundreds of 3'UTRs. This approach combines a method of separating the principal subcellular compartments of neurons – cell bodies and neurites - with a massively parallel reporter assay. Our analysis identifies the let-7 binding site and (AU)n motif as de novo zipcodes in mouse primary cortical neurons and suggests a strategy for detecting many more.

Non-directive play therapy with autistic adolescents: a qualitative study of therapists’ interactional practices

This case study identifies and examines interactional practices of non-directive play therapists during their therapeutic sessions with autistic adolescents. The study involved two therapists and two adolescents (siblings) on the autism spectrum. The video-recorded sessions took place at participants’ home and were conducted in Polish. Employing insights and tools from discourse-analytic approaches, in particular conversation analysis (CA), the findings show how clients and therapists are both involved in co-constructing therapeutic interactions by orienting to each other’s utterances. CA is presented in this article as a useful tool for recognizing and describing the therapists’ interactional contributions and their local functions. The therapeutic practices identified in the analysis (talk-in-practice) – e.g. mirroring, meaning expansion, recast and scaffolding – are further juxtaposed with theories concerning interactional practices in non-directive therapies (talk-in-theory) in order to provide a more detailed picture of these practices as well as complete them. The findings from this study expand the current state of knowledge of non-directive play therapies of autism spectrum disorder (ASD) and carry practical implications for specialists involved in ASD treatment.

Massively parallel identification of zipcodes in primary cortical neurons

Cells adopt highly polarized shapes and form distinct subcellular compartments largely due to the localization of many mRNAs to specific areas, where they are translated into proteins with local functions. This mRNA localization is mediated by specific cis-regulatory elements in mRNAs, commonly called "zipcodes." Their recognition by RNA-binding proteins (RBPs) leads to the integration of the mRNAs into macromolecular complexes and their localization. While there are hundreds of localized mRNAs, only a few zipcodes have been characterized. Here, we describe a novel neuronal zipcode identification protocol (N-zip) that can identify zipcodes across hundreds of 3'UTRs. This approach combines a method of separating the principal subcellular compartments of neurons - cell bodies and neurites - with a massively parallel reporter assay. Our analysis identifies the let-7 binding site and (AU)n motif as de novo zipcodes in mouse primary cortical neurons and suggests a strategy for detecting many more.

On classical and quantum deformations of gauge theories

We elaborate the generalizations of the approach to gauge-invariant deformations of the gauge theories developed in our previous work (Buchbinder and Lavrov in JHEP 06:097, 2021). In the given paper we construct the exact transformations defying the gauge-invariant deformed theory on the base of initial gauge theory with irreducible open gauge algebra. Like in [1], for the theories with open gauge algebras these transformations are the shifts of the initial gauge fields $$A \rightarrow A+h(A)$$ A → A + h ( A ) , with the help of the arbitrary and in general non-local functions h(A). The results are applied to study the quantum aspects of the deformed theories. We derive the exact relation between the quantum effective actions for the above classical theories, where one is obtained from another with the help of the deformation.

Unbounded phonological processes as Tier-based Strictly Local functions

Whether we analyze phonological processes using a system of rules or constraints, the resulting map from underlying representations to surface pronunciations can be characterized as a function. Viewing processes as mathematical objects in this way allows us to study properties of phonology that hold no matter how it is implemented. Work in this vein has found that a majority of phonological processes only consider information within a finite window, placing them in the highly restrictive class of Strictly Local (SL) functions (Chandlee 2014; Chandlee et al. 2014;2015). Long-distance phonological processes, however, lie outside the capabilities of the SL functions since they consider information that can be arbitrarily distant. The more powerful class of subsequential functions has been offered as a potential upper bound on the complexity of long-distance phonology (Heinz and Lai 2013; Luo 2017; Payne 2017), but we will argue that an even tighter bound is possible. Specifically, by incorporating an autosegmental tier (e.g., Goldsmith 1976) into the structure of an SL function, the non-local information crucial for applying long-distance processes can be rendered local. In addition to assessing the typological coverage of these Tier-based Strictly Local (TSL) functions (Burness and McMullin 2019; Hao and Andersson 2019; Hao and Bowers 2019), we show that they fail to generate a number of pathological patterns that can be characterized as subsequential functions. We therefore conclude that the TSL functions are a better hypothesized upper bound on phonological complexity.

A Dual-Route Perspective of SARS-CoV-2 Infection: Lung- vs. Gut-specific Effects of ACE-2 Deficiency

SARS-CoV-2, primarily considered a respiratory virus, is increasingly recognized as having gastrointestinal aspects based on its presence in the gastrointestinal (GI) tract and feces. SARS-CoV-2 uses as a receptor angiotensin-converting enzyme 2 (ACE-2), a critical member of the renin-angiotensin-aldosterone system (RAAS) involved in the regulation of blood pressure and fluid system. In addition to the systemic endocrine functions, RAAS components are also involved in intracrine and organ-specific local functions. The angiotensin-converting enzyme 2 (ACE-2) is a key component of RAAS and a receptor for SARS-CoV-2. It is expressed in many tissues with gastrointestinal (GI) tract ACE-2 levels far exceeding those in the respiratory tract. SARS-CoV-2 binding to its receptor results in a deficiency of ACE-2 activity in endocrine, intracrine, and local lung and GI tract ACE-2. The local ACE-2 has different organ-specific functions, including hypertension-independent activities; dysregulations of these functions may contribute to multiorgan COVID-19 pathology, its severity, long-term effects, and mortality. We review supporting evidence from this standpoint. Notably, COVID-19 comorbidities involving hypertension, obesity, heart disease, kidney disease, and diabetes are associated with gastrointestinal problems and display ACE-2 deficits. While RAAS inhibitors target both endocrine and intracrine ACE-2 activity, the deficit of the local ACE-2 activity in the lungs and more so in the gut have not been targeted. Consequently, the therapeutic approach to COVID-19 should be carefully reconsidered. Ongoing clinical trials testing oral probiotic bound ACE-2 delivery are promising.

Local Accumulation of Axonal Mitochondria in the Optic Nerve Glial Lamina Precedes Myelination

Mitochondria are essential for neurons and must be optimally distributed along their axon to fulfill local functions. A high density of mitochondria has been observed in retinal ganglion cell (RGC) axons of an unmyelinated region of the optic nerve, called the glial lamina (GL) in mouse (lamina cribrosa in human). In glaucoma, the world's leading cause of irreversible blindness, the GL is the epicenter of RGC degeneration and is connected to mitochondrial dysfunction. It is generally accepted that the local accumulation of mitochondria in the GL is established due to the higher energy requirement of unmyelinated axons. Here we revisit the connection between mitochondrial positioning and myelin in RGC axons. We show that the high density of mitochondria in the GL is restricted to larger axons and is established before myelination. Thus, contrary to a longstanding belief in the field, the myelination pattern is not responsible for the establishment of the local accumulation of mitochondria in GL axons. Our findings open new research avenues likely critical to understanding the pathophysiology of glaucoma.

Multimodal strategies for balancing formality and informality

This paper investigates multimodal strategies for balancing formality and informality online. The analysis of 300 comment-reply interactions on a recipe sharing site in Japan demonstrates that writers tend to avoid being overly formal or informal in their messages. For example, most comments and replies are written in polite forms but many incorporate some plain forms and colloquial expressions. Linguistic features, however, are not the only way through which the writers manage an appropriate level of formality and informality. The study examines the role of kaomoji or Japanese-style emoticons for socio-relational work online. Some kaomoji function locally as cues for interpreting the sentences featuring kaomoji. All kaomoji, including those with local functions, work to enhance the social presence of the writers on the screen via pictographic gaze and gestures, which increases the perception of intimate rapport. The findings underscore the importance of a multimodal perspective in examining how people handle social relationships online.