The Drosophila STIM1 orthologue, dSTIM, has roles in cell fate specification and tissue patterning.

BACKGROUND: Mammalian STIM1 and STIM2 and the single Drosophila homologue dSTIM have been identified as key regulators of store-operated Ca2+ entry in cells. STIM proteins function both as molecular sensors of Ca2+concentration in the endoplasmic reticulum (ER) and the molecular triggers that activate SOC channels in the plasma membrane. Ca2+ is a crucial intracellular messenger utilised in many cellular processes, and regulators of Ca2+ homeostasis in the ER and cytosol are likely to play important roles in developmental processes. STIM protein expression is altered in several tumour types but the role of these proteins in developmental signalling pathways has not been thoroughly examined. RESULTS: We have investigated the expression and developmental function of dSTIM in Drosophila and shown that dSTIM is widely expressed in embryonic and larval tissues. Using the UAS-Gal4 induction system, we have expressed full-length dSTIM protein and a dsRNAi construct in different tissues. We demonstrate an essential role for dSTIM in larval development and survival, and a tissue-specific role in specification of mechanosensory bristles in the notum and specification of wing vein thickness. CONCLUSION: Our studies show that dSTIM regulates growth and patterning of imaginal discs and indicate potential interactions with the Notch and Wingless signaling pathways. These interactions may be relevant to studies implicating STIM family proteins in tumorigenesis.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Energy conversion theorems for some linear steady-states

One of the main issues that real energy converters present, when they produce effective work, is the inevitable entropy production. Within the context of Non-equilibrium Thermodynamics, entropy production tends to energetically degrade man-made or living systems. On the other hand, it is also not useful to think about designing an energy converter that works in the so-called minimum entropy production regime since the effective power output and efficiency are zero. In this manuscript, we establish some \textit{Energy Conversion Theorems} similar to Prigogine's one with constrained forces, their purpose is to reveal trade-offs between design and the so-called operation modes for $\left(2\times2\right)$--linear isothermal energy converters. The objective functions that give rise to those thermodynamic constraints show stability. A two--meshes electric circuit was built as an example to demonstrate the Theorems' validity. Likewise, we reveal a type of energetic hierarchy for power output, efficiency and dissipation function when the circuit is tuned to any of the operating regimes studied here: maximum power output ($MPO$), maximum efficient power ($MP\eta$), maximum omega function ($M\Omega$), maximum ecological function ($MEF$), maximum efficiency ($M\eta$) and minimum dissipation function ($mdf$).Comment: 33 pages, 15 figures, 2 table

tRNA-derived small RNAs target transposable element transcripts

tRNA-derived RNA fragments (tRFs) are 18-26 nucleotide small RNAs that are not random degradation products, but are rather specifically cleaved from mature tRNA transcripts. Abundant in stressed or viral-infected cells, the function and potential targets of tRFs are not known. We identified that in the unstressed wild-type male gamete containing pollen of flowering plants, and analogous reproductive structure in non-flowering plant species, tRFs accumulate to high levels. In the reference plant Arabidopsis thaliana, tRFs are processed by Dicer-like 1 and incorporated into Argonaute1 (AGO1), akin to a microRNA. We utilized the fact that many plant small RNAs direct cleavage of their target transcripts to demonstrate that the tRF-AGO1 complex acts to specifically target and cleave endogenous transposable element (TE) mRNAs produced from transcriptionally active TEs. The data presented here demonstrate that tRFs are bona-fide regulatory microRNA-like small RNAs involved in the regulation of genome stability through the targeting of TE transcripts

The miRNome function transitions from regulating developmental genes to transposable elements during pollen maturation

Animal and plant microRNAs (miRNAs) are essential for the spatio-temporal regulation of development. Together with this role, plant miRNAs have been proposed to target transposable elements (TEs) and stimulate the production of epigenetically active small interfering RNAs. This activity is evident in the plant male gamete containing structure, the male gametophyte or pollen grain. How the dual role of plant miRNAs, regulating both genes and TEs, is integrated during pollen development and which mRNAs are regulated by miRNAs in this cell type at a genome-wide scale are unknown. Here, we provide a detailed analysis of miRNA dynamics and activity during pollen development in Arabidopsis thaliana using small RNA and degradome parallel analysis of RNA end high-throughput sequencing. Furthermore, we uncover miRNAs loaded into the two main active Argonaute (AGO) proteins in the uninuclear and mature pollen grain, AGO1 and AGO5. Our results indicate that the developmental progression from microspore to mature pollen grain is characterized by a transition from miRNAs targeting developmental genes to miRNAs regulating TE activity.sRNA, PARE, and AGO-IP sequencing uncovered the role of miRNAs during pollen development, showing that miRNAs transition from regulating genes involved in development to transposable elements

Reduced salivary oxytocin after an empathic induction task in Intimate Partner Violence perpetrators: Importance of socio-affective functions and its impact on prosocial behavior

Intimate Partner Violence (IPV) has been linked to difficulties in socio-affective functions. Nevertheless, the underlying psychobiological mechanisms that might be responsible for them remain unclear. Oxytocin (OXT) stands out as an important hormone that may favor the salience of social information, due to its relevance in empathy and prosocial behavior. Thus, the study of salivary OXT (sOXT) may provide further information about potential impairments in social cognition in IPV perpetrators. This study analyzed the effects of an empathic induction task, performed through negative emotion-eliciting videos, on endogenous sOXT levels, mood state, and emotional perception in 30 IPV perpetrators compared to 32 controls. Additionally, we explored their performance on prosocial behavior after the empathic induction task, using Hare''s donation procedure. Lower sOXT levels were found in IPV perpetrators after the task compared to controls, along with a general decreasing tendency in their sOXT levels. Additionally, IPV perpetrators exhibited no change in their mood state and perceived others'' emotions as more positive and less intense. Moreover, the mood state response and alexithymia traits, respectively, positively and negatively predicted the sOXT levels after the empathic induction task in the entire sample. Finally, we did not observe a lower appearance of prosocial behaviors in IPV perpetrators; however, higher sOXT levels after the empathic induction task were found in subjects who donated when considering the whole sample. In sum, IPV perpetrators exhibited differences in their sOXT levels when empa-thizing, compared to controls, with alexithymia and the emotional response potentially explaining the sOXT levels after the task. Furthermore, prosocial behavior was more related to these sOXT levels than to IPV. As our knowledge about the emotional processing of IPV perpetrators increases, we will be better able to develop and include coadjutant treatments in current psychotherapeutic programs, in order to focus on their emotional needs, which, in turn, would reduce the future risk of recidivism

Analysis of the oscillations induced by a supersonic jet applied to produce nanofibers

Financiado para publicación en acceso aberto: Universidade de Vigo/CISUGHigh-performance fibers are key components for enhancing the mechanical properties of composite materials. The development of high strength nanofibers augurs the production of new nano-composites with outstanding features. However, the robust production of continuous glass nanofibers that can be feasible processed for efficiently manufacturing nanocomposites is still challenging. Recently, Cofiblas (Continuous Fiberizing by Laser melting and Supersonic dragging) was demonstrated as a technique capable of producing continuous glass nanofibers with unlimited length. Cofiblas process has some similarities with the widely known melt blowing technique for the production of polymeric fibers. In both techniques, the design of the gas nozzle is key to ensure the feasibility of the process since the turbulences of the gas jet may induce strong whipping of the filament. This paper gives novel experimental evidences on the correlation of the supersonic gas jet instabilities with the oscillation of the filament in the melt-blowing and Cofiblas processes, relating these oscillations with the presence of shock waves and unsteadiness in the flow, and gives valuable insight into the use of supersonic jets in the melt blowing process as an effective approach for the formation of nanofibers. A thin 3D-axisymmetric model in OpenFOAM® was put to test by comparing the performance of different solvers which were validated by flow visualization of the exit jet using digital holography (DH). In order to perform a realistic and thorough validation, we simulated the optical measurements of the flow from the CFD simulations of the mass density by Abel transform and numerical differentiation. The application of digital holography as the flow visualization technique makes possible both a precise validation of the density maps obtained from the Abel transformation of the 2D-alike results, and the analysis of the shockwave pattern in the air jet. Conversely, the numerical reconstruction of time-averaged holograms is employed to detect unsteadiness in the flow and to analyze the fiber oscillation, which is essential to assess the stability of the process. Lastly, the analysis and comparison of the vibration of the filament using the basic design and the optimized nozzle demonstrates a clear influence of the shock waves and flow unsteadiness in the stability of the filament.Agencia Estatal de Investigación | Ref. PGC2018-094900-B-I00Xunta de Galicia | Ref. ED431C 2019/23Ministerio de Universidades | Ref. FPU20/0311

Dietary supplementation with vitamins C and E prevents downregulation of endothelial NOS expression in hypercholesterolemia in vivo and in vitro

Impaired endothelium-dependent vasodilation has been associated with decreased NO bioavailability in hypercholesterolemia. This study aimed to determine whether antioxidant vitamins C and E could improve hypercholesterolemia-derived endothelial dysfunction in the porcine model, and whether observed in vivo results could be reproduced in vitro by incubation of coronary endothelial cells (EC) in the presence of native low-density lipoproteins (LDL). Adult mini-pigs were fed standard (C), cholesterol rich (HC) or cholesterol rich diet supplemented with vitamins C and E (HCV). Endothelium-dependent blood flow increase in response to acetylcholine was determined. Endothelial nitric oxide synthase (eNOS) expression was measured in arterial samples and in EC incubated with LDL isolated from porcine plasma. Vasomotor response to acetylcholine in HC was significantly lower (P<0.05) than control and HCV. There was a significant (P<0.05) decrease in eNOS immunoreactivity in HC, compared with HCV and control. Native LDL from HC, but not from HCV, induced a significant decrease in eNOS expression. Vitamins C and E treatment improved the endothelium-dependent vasomotor capacity and prevented decreased expression of eNOS in hypercholesterolemic pigs. A similar effect could be demonstrated in vitro, by incubation of EC with native LDL, suggesting that the effect of physiologically-modified LDL on eNOS could have a role in recovering vascular function

Study of the genetic diversity of the aflatoxin biosynthesis cluster in \u3ci\u3eAspergillus\u3c/i\u3e section \u3ci\u3eFlavi\u3c/i\u3e using insertion/deletion markers in peanut seeds from Georgia, USA

Aflatoxins are among themost powerful carcinogens in nature. The major aflatoxin-producing fungi are Aspergillus flavus and A. parasiticus. Numerous crops, including peanut, are susceptible to aflatoxin contamination by these fungi. There has been an increased use of RNA interference (RNAi) technology to control phytopathogenic fungi in recent years. In order to develop molecular tools targeting specific genes of these fungi for the control of aflatoxins, it is necessary to obtain their genome sequences. Although high-throughput sequencing is readily available, it is still impractical to sequence the genome of every isolate. Thus, in this work, the authors proposed a workflow that allowed prescreening of 238 Aspergillus section Flavi isolates from peanut seeds from Georgia, USA. The aflatoxin biosynthesis cluster (ABC) of the isolates was fingerprinted at 25 InDel (insertion/deletion) loci using capillary electrophoresis. All isolates were tested for aflatoxins using ultra-high-performance liquid chromatography. The neighbor- joining, three-dimension (3D) principal coordinate, and Structure analyses revealed that the Aspergillus isolates sampled consisted of three main groups determined by their capability to produce aflatoxins. Group I comprised 10 non-aflatoxigenic A. flavus; Group II included A. parasiticus; and Group III includedmostly aflatoxigenic A. flavus and the three non-aflatoxigenic A. caelatus.Whole genomes of 10 representative isolates from different groups were sequenced. Although InDels in Aspergillus have been used by other research groups, this is the first time that the cluster analysis resulting from fingerprinting was followed by whole-genome sequencing of representative isolates. In our study, cluster analysis of ABC sequences validated the results obtained with fingerprinting. This shows that InDels used here can predict similarities at the genome level. Our results also revealed a relationship between groups and their capability to produce aflatoxins. The database generated of Aspergillus spp. can be used to select target genes and assess the effectiveness of RNAi technology to reduce aflatoxin contamination in peanut. Supplementary file folder attached below

Cefiderocol Heteroresistance Associated With Mutations in TonB-Dependent Receptor Genes in Pseudomonas aeruginosa of Clinical Origin

The siderophore-cephalosporin cefiderocol (FDC) presents a promising treatment option for carbapenem-resistant (CR) P. aeruginosa (PA). FDC circumvents traditional porin and efflux-mediated resistance by utilizing TonB-dependent receptors (TBDRs) to access the periplasmic space. Emerging FDC resistance has been associated with loss of function mutations within TBDR genes or the regulatory genes controlling TBDR expression. Further, difficulties with antimicrobial susceptibility testing (AST) and unexpected negative clinical treatment outcomes have prompted concerns for heteroresistance, where a single lineage isolate contains resistant subpopulations not detectable by standard AST. This study aimed to evaluate the prevalence of TBDR mutations among clinical isolates of P. aeruginosa and the phenotypic effect on FDC susceptibility and heteroresistance. We evaluated the sequence of pirR, pirS, pirA, piuA, or piuD from 498 unique isolates collected before the introduction of FDC from four clinical sites in Portland, OR (1), Houston, TX (2), and Santiago, Chile (1). At some clinical sites, TBDR mutations were seen in up to 25% of isolates, and insertion, deletion, or frameshift mutations were predicted to impair protein function were seen in 3% of all isolates (n = 15). Using population analysis profile testing, we found that P. aeruginosa with major TBDR mutations were enriched for a heteroresistant phenotype and undergo a shift in the susceptibility distribution of the population as compared to susceptible strains with wild-type TBDR genes. Our results indicate that mutations in TBDR genes predate the clinical introduction of FDC, and these mutations may predispose to the emergence of FDC resistance