Electromigration in Nano-Interconnects: Determining Reliability Margins in Redundant Mesh Networks Using a Scalable Physical-Statistical Hybrid Paradigm.

This paper presents a hybrid modelling approach that combines physics-based electromigration modelling (PEM) and statistical methods to evaluate the electromigration (EM) limits of nano-interconnects in mesh networks. The approach, which is also compatible with standard Place and Route (P&R) tools and practises, takes into account the positive impact of network redundancy on EM current limits. The numerical simulations conducted in this study show that conventional methods underestimate the EM current limits of a power delivery network (PDN) unit-cell by 80% due to their lack of consideration for redundancy. Additionally, the time-to-failure (TTF) distributions of a PDN unit-cell obtained by the developed modelling framework adhered to a lognormal distribution, where the lognormal sigma, σlogn, exhibits a 55% reduction compared to that of the single constituent interconnects. The study also found the negative voltage (i.e., ground or Vss) grid to be more susceptible to EM than the positive voltage, i.e., Vdd grid. In the examined grid unit-cell design, both the number of interconnect sites prone to voiding and also the magnitude of the peak tensile stress within the nano-interconnects were found to be two times as high in the Vss case compared to Vdd. The lognormal sigma of TFF for the grid unit-cells, σlogn-tile, show a marked reduction compared to the lognormal sigma of the constituent single interconnects, σlogn, with a 50% and 66% decrease compared to single interconnects, for downstream (Vss) and upstream (Vdd), respectively. In addition, σlogn-tile was three times higher for downstream (Vss) compared to upstream (Vdd), whilst, in contrast, this difference was only 2-fold at the single interconnect level. TTF50% was predicted to be 4.13-fold higher at the grid unit-cell level for the upstream compared to downstream operation, which was also more pronounced than in the single interconnect level where the difference was only 2-fold. This research provides valuable insights into the EM ageing of nano-interconnects in mesh networks and could pragmatically enhance the accuracy of EM compliance evaluation methods.

A Deep Learning-Derived Transdiagnostic Signature Indexing Hypoarousal and Impulse Control: Implications for Treatment Prediction in Psychiatric Disorders.

BACKGROUND: Psychiatric disorders are traditionally classified within diagnostic categories, but this approach has limitations. Research Domain Criteria (RDoC) constitute a research classification system for psychiatric disorders based on dimensions within domains that cut across these psychiatric diagnoses. The overall aim of RDoC is to better understand mental illness in terms of dysfunction in fundamental neurobiological and behavioral systems, leading to better diagnosis, prevention and treatment. METHODS: A unique electroencephalographic (EEG) feature, referred to as spindling excessive beta (SEB), has been studied in relation to impulse control and sleep, as part of the arousal/regulatory systems RDoC domain. Here, we study EEG frontal beta activity as a potential transdiagnostic biomarker capable of diagnosing and predicting impulse control and sleep problems. RESULTS: We show in the first dataset (n=3279) that the probability of having SEB, classified by a deep learning algorithm, is associated with poor sleep maintenance and low daytime impulse control. Furthermore, in two additional, independent datasets (iSPOT-A, n=336; iSPOT-D, n=1008), we revealed that conventional frontocentral beta power and/or SEB probability, referred to as Brainmarker-III, is associated with a diagnosis of attention deficit hyperactivity disorder (ADHD), with remission to methylphenidate in children with ADHD in a sex-specific manner, and with remission to antidepressant medication in adults with a major depressive disorder in a drug-specific manner. CONCLUSION: Our results demonstrate the value of the RDoC approach in psychiatry research for the discovery of biomarkers with diagnostic and treatment prediction capacities.

Structural insights into the binding of nanobodies to the Staphylococcal enterotoxin B.

Staphylococcal Enterotoxin Type B (SEB), produced by Staphylococcus aureus bacteria, is notorious for inducing severe food poisoning and toxic shock syndrome. While nanobody-based treatments hold promises for combating SEB-induced diseases, the lack of structural information between SEB and nanobodies has hindered the development of nanobody-based therapeutics. Here, we present crystal structures of SEB-Nb3, SEB-Nb6, SEB-Nb8, SEB-Nb11, and SEB-Nb20 at resolutions ranging from 1.59 Å to 2.33 Å. Crystallographic analysis revealed that Nb3, Nb8, Nb11, and Nb20 bind to SEB at the T-cell receptor (TCR) interface, while Nb6 binds at the major histocompatibility complex (MHC) interface, suggesting their potential to inhibit SEB function by disrupting interactions with TCR or MHC molecules. Molecular biological analyses confirmed the thermodynamic and kinetic parameters of Nb3, Nb5, Nb6, Nb8, Nb11, Nb15, Nb18, and Nb20 to SEB. The competitive inhibition was further confirmed by cell-based experiments demonstrating nanobody neutralization. These findings elucidate the structural basis for developing specific nanobodies to neutralize SEB threats, providing crucial insights into the underlying mechanisms and offering significant assistance for further optimization towards future therapeutic strategies.

Investigation of activation-induced markers (AIM) in porcine T cells by flow cytometry.

Activation-induced markers (AIMs) are frequently analyzed to identify re-activated human memory T cells. However, in pigs the analysis of AIMs is still not very common. Based on available antibodies, we designed a multi-color flow cytometry panel comprising pig-specific or cross-reactive antibodies against CD25, CD69, CD40L (CD154), and ICOS (CD278) combined with lineage/surface markers against CD3, CD4, and CD8α. In addition, we included an antibody against tumor necrosis factor alpha (TNF-α), to study the correlation of AIM expression with the production of this abundant T cell cytokine. The panel was tested on peripheral blood mononuclear cells (PBMCs) stimulated with phorbol 12-myristate 13-acetate (PMA)/ionomycin, Staphylococcus enterotoxin B (SEB) or PBMCs from African swine fever virus (ASFV) convalescent pigs, restimulated with homologous virus. PMA/ionomycin resulted in a massive increase of CD25/CD69 co-expressing T cells of which only a subset produced TNF-α, whereas CD40L expression was largely associated with TNF-α production. SEB stimulation triggered substantially less AIM expression than PMA/ionomycin but also here CD25/CD69 expressing T cells were identified which did not produce TNF-α. In addition, CD40L-single positive and CD25+CD69+CD40L+TNF-α- T cells were identified. In ASFV restimulated T cells TNF-α production was associated with a substantial proportion of AIM expressing T cells but also here ASFV-reactive CD25+CD69+TNF-α- T cells were identified. Within CD8α+ CD4 T cells, several CD25/CD40L/CD69/ICOS defined phenotypes expanded significantly after ASFV restimulation. Hence, the combination of AIMs tested will allow the identification of primed T cells beyond the commonly used cytokine panels, improving capabilities to identify the full breadth of antigen-specific T cells in pigs.

Targeting staphylococcal enterotoxin B binding to CD28 as a new strategy for dampening superantigen-mediated intestinal epithelial barrier dysfunctions.

Staphylococcus aureus is a gram-positive bacterium that may cause intestinal inflammation by secreting enterotoxins, which commonly cause food-poisoning and gastrointestinal injuries. Staphylococcal enterotoxin B (SEB) acts as a superantigen (SAg) by binding in a bivalent manner the T-cell receptor (TCR) and the costimulatory receptor CD28, thus stimulating T cells to produce large amounts of inflammatory cytokines, which may affect intestinal epithelial barrier integrity and functions. However, the role of T cell-mediated SEB inflammatory activity remains unknown. Here we show that inflammatory cytokines produced by T cells following SEB stimulation induce dysfunctions in Caco-2 intestinal epithelial cells by promoting actin cytoskeleton remodelling and epithelial cell-cell junction down-regulation. We also found that SEB-activated inflammatory T cells promote the up-regulation of epithelial-mesenchymal transition transcription factors (EMT-TFs) in a nuclear factor-κB (NF-κB)- and STAT3-dependent manner. Finally, by using a structure-based design approach, we identified a SEB mimetic peptide (pSEB116-132) that, by blocking the binding of SEB to CD28, dampens inflammatory-mediated dysregulation of intestinal epithelial barrier.

First Report of Food Poisoning Due to Staphylococcal Enterotoxin Type B in Döner Kebab (Italy).

Staphylococcal food poisoning results from the consumption of food contaminated by staphylococcal enterotoxins. In July 2022, the Turin local health board was notified of a suspected foodborne outbreak involving six children who had consumed döner kebab purchased from a takeaway restaurant. The symptoms (vomiting and nausea) were observed 2-3 h later. A microbiological analysis of the food samples revealed high levels (1.5 × 107 CFU/g) of coagulase-positive staphylococci (CPS). The immunoassay detected a contamination with staphylococcal enterotoxins type B (SEB). The whole genome sequencing of isolates from the food matrix confirmed the staphylococcal enterotoxin genes encoding for type B, which was in line with the SEB detected in the food. This toxin is rarely reported in staphylococcal food poisoning, however, because there is no specific commercial method of detection. The involvement of enterotoxin type P (SEP) was not confirmed, though the corresponding gene (sep) was detected in the isolates. Nasal swabs from the restaurant food handlers tested positive for CPS, linking them to the likely source of the food contamination.

Structural, Electronic, and Mechanical Properties of Zr2SeB and Zr2SeN from First-Principle Investigations.

MAX phases have exhibited diverse physical properties, inspiring their promising applications in several important research fields. The introduction of a chalcogen atom into a phase of MAX has further facilitated the modulation of their physical properties and the extension of MAX family diversity. The physical characteristics of the novel chalcogen-containing MAX 211 phase Zr2SeB and Zr2SeN have been systematically investigated. The present investigation is conducted from a multi-faceted perspective that encompasses the stability, electronic structure, and mechanical properties of the system, via the employment of the first-principles density functional theory methodology. By replacing C with B/N in the chalcogen-containing MAX phase, it has been shown that their corresponding mechanical properties are appropriately tuned, which may offer a way to design novel MAX phase materials with enriched properties. In order to assess the dynamical and mechanical stability of the systems under investigation, a thorough evaluation has been carried out based on the analysis of phonon dispersions and elastic constants conditions. The predicted results reveal a strong interaction between zirconium and boron or nitrogen within the structures of Zr2SeB and Zr2SeN. The calculated band structures and electronic density of states for Zr2SeB and Zr2SeN demonstrate their metallic nature and anisotropic conductivity. The theoretically estimated Pugh and Poisson ratios imply that these phases are characterized by brittleness.

Social, Emotional, and Behavioral Skills: Age and Gender Differences at 12 to 19 Years Old.

Individuals use social, emotional, and behavioral (SEB) skills to build and maintain social relationships, regulate emotions, and manage goal-directed behaviors. A promising integrative framework of SEB skills was recently proposed, showing that they matter for positive outcomes during adolescence. Nothing is known about how and whether they differ between 12 and 19 years old and whether such differences depend on gender (males or females). Uncovering their age trajectories is fundamental because SEB skills are highly needed during this period of life. Educators, psychologists, and policymakers need to understand when, why, and how interventions concerning SEB skills should be proposed, potentially considering male and female profiles. To cover this gap, we cross-sectionally analyzed data from 4106 participants (2215 females, 12-19 years old). We highlighted age and gender differences in the five domains of SEB skills (self-management, innovation, cooperation, social engagement, and emotional resilience). Our results show that each SEB skill follows a specific age trend: emotional resilience and cooperation skills increase naturally between 12 and 19 years old, while innovation, social engagement, and self-management skills decline, especially between 12 and 16 years old, and grow later. The trajectories of self-management, social engagement, and emotional resilience skills also differ between males and females. Importantly, we detected declines in SEB skills (especially for social engagement and innovation skills) that can inform policies and interventions to sustain SEB skills in youths to favor their well-being and success in this crucial period.

Research on Temperature Dependence of Single-Event Burnout in Power MOSFETs.

Power MOSFETs are found to be very vulnerable to single-event burnout (SEB) in space irradiation environments, and the military components generally require that devices could operate reliably as the temperature varies from 218 K to 423 K (-55 °C to 150 °C); thus, the temperature dependence of single-event burnout (SEB) in power MOSFETs should be investigated. Our simulation results showed that the Si power MOSFETs are more tolerant to SEB at a higher temperature at the lower LET (10 MeV∙cm2/mg) due to the decrease of the impact ionization rate, which is in good agreement with the previous research. However, the state of the parasitic BJT plays a primary role in the SEB failure mechanism when the LET value is greater than 40 MeV∙cm2/mg, which exhibits a completely different temperature dependence from that of 10 MeV∙cm2/mg. Results indicate that with the temperature increasing, the lower difficulty to turn on the parasitic BJT and the increasing current gain all make it easier to build up the regenerative feedback process responsible for SEB failure. As a result, the SEB susceptibility of power MOSFETs increases as ambient temperature increases when the LET value is greater than 40 MeV∙cm2/mg.

Simulation Studies on Single-Event Effects and the Mechanisms of SiC VDMOS from a Structural Perspective.

The single-event effect reliability issue is one of the most critical concerns in the context of space applications for SiC VDMOS. In this paper, the SEE characteristics and mechanisms of the proposed deep trench gate superjunction (DTSJ), conventional trench gate superjunction (CTSJ), conventional trench gate (CT), and conventional planar gate (CT) SiC VDMOS are comprehensively analyzed and simulated. Extensive simulations demonstrate the maximum SET current peaks of DTSJ-, CTSJ-, CT-, and CP SiC VDMOS, which are 188 mA, 218 mA, 242 mA, and 255 mA, with a bias voltage VDS of 300 V and LET = 120 MeV·cm2/mg, respectively. The total charges of DTSJ-, CTSJ-, CT-, and CP SiC VDMOS collected at the drain are 320 pC, 1100 pC, 885 pC, and 567 pC, respectively. A definition and calculation of the charge enhancement factor (CEF) are proposed. The CEF values of DTSJ-, CTSJ-, CT-, and CP SiC VDMOS are 43, 160, 117, and 55, respectively. Compared with CTSJ-, CT-, and CP SiC VDMOS, the total charge and CEF of the DTSJ SiC VDMOS are reduced by 70.9%, 62.4%, 43.6% and 73.1%, 63.2%, and 21.8%, respectively. The maximum SET lattice temperature of the DTSJ SiC VDMOS is less than 2823 K under the wide operating conditions of a drain bias voltage VDS ranging from 100 V to 1100 V and a LET value ranging from 1 MeV·cm2/mg to 120 MeV·cm2/mg, while the maximum SET lattice temperatures of the other three SiC VDMOS significantly exceed 3100 K. The SEGR LET thresholds of DTSJ-, CTSJ-, CT-, and CP SiC VDMOS are approximately 100 MeV·cm2/mg, 15 MeV·cm2/mg, 15 MeV·cm2/mg, and 60 MeV·cm2/mg, respectively, while the value of VDS = 1100 V.

The SEB1741 Aptamer Is an Efficient Tool for Blocking CD4+ T Cell Activation Induced by Staphylococcal Enterotoxin B.

Staphylococcal enterotoxin B (SEB) is a protein produced by Staphylococcus aureus, which is toxic to humans. It is well known for its ability to stimulate the exacerbated activation of proinflammatory CD4+ T cells (Th1 profile), and in vitro studies have been conducted to understand its mechanism of action and its potential use as an immune therapy. However, the efficiency of the SEB1741 aptamer in blocking SEB has not been experimentally demonstrated. METHODS: Enrichment CD4+ T cells were stimulated with SEB, and as a blocker, we used the SEB1741 aptamer, which was previously synthesised by an "in silico" analysis, showing high affinity and specificity to SEB. The efficiency of the SEB1741 aptamer in blocking CD4+ T cell activation was compared with that of an anti-SEB monoclonal antibody. Flow cytometry and Bio-Plex were used to evaluate the T-cell function. RESULTS: In vitro, SEB induced the activation of CD4+ T cells and favoured a Th1 profile; however, the SEB1741 aptamer was highly efficient in decreasing the frequency of CD4+ T cells positive to ki-67 and CD69 cells, this means that proliferation and activation of CD4+ T cells was decreased. Moreover, the production of interleukin 2 (IL-2) and interferon-gamma (IFN-γ) was affected, suggesting that the Th1 profile is not present when the SEB1441 aptamer is used. Thus, the SEB1741 function was similar to that of anti-SEB. CONCLUSIONS: The SEB1741 aptamer is a valuable tool for blocking CD4+ T cell activation and the subsequent release of proinflammatory cytokines by SEB stimulation.

Resveratrol attenuates staphylococcal enterotoxin B-activated immune cell metabolism via upregulation of miR-100 and suppression of mTOR signaling pathway.

Acute Respiratory Distress Syndrome (ARDS) is triggered by a variety of insults, such as bacterial and viral infections, including SARS-CoV-2, leading to high mortality. In the murine model of ARDS induced by Staphylococcal enterotoxin-B (SEB), our previous studies showed that while SEB triggered 100% mortality, treatment with Resveratrol (RES) completely prevented such mortality by attenuating inflammation in the lungs. In the current study, we investigated the metabolic profile of SEB-activated immune cells in the lungs following treatment with RES. RES-treated mice had higher expression of miR-100 in the lung mononuclear cells (MNCs), which targeted mTOR, leading to its decreased expression. Also, Single-cell RNA-seq (scRNA seq) unveiled the decreased expression of mTOR in a variety of immune cells in the lungs. There was also an increase in glycolytic and mitochondrial respiration in the cells from SEB + VEH group in comparison with SEB + RES group. Together these data suggested that RES alters the metabolic reprogramming of SEB-activated immune cells, through suppression of mTOR activation and its down- and upstream effects on energy metabolism. Also, miR-100 could serve as novel potential therapeutic molecule in the amelioration of ARDS.

Staphylococcal enterotoxin B as DNA vaccine against breast cancer in a murine model.

Recently, many efforts have been made to treat cancer using recombinant bacterial toxins and this strategy has been used in clinical trials of various cancers. Therapeutic DNA cancer vaccines are now considered as a promising strategy to activate the immune system against cancer. Cancer vaccines could induce specific and long-lasting immune responses against tumors. This study aimed to evaluate the antitumor potency of the SEB DNA vaccine as a new antitumor candidate against breast tumors in vivo. To determine the effect of the SEB construct on inhibiting tumor cell growth in vivo, the synthetic SEB gene, subsequent codon optimization, and embedding the cleavage sites were sub-cloned to an expression vector. Then, SEB construct, SEB, and PBS were injected into the mice. After being vaccinated, 4T1 cancer cells were injected subcutaneously into the right flank of mice. Then, the cytokine levels of IL-4 and IFN-γ were estimated by the ELISA method to evaluate the antitumor activity. The spleen lymphocyte proliferation, tumor size, and survival time were assessed. The concentration of IFN-γ in the SEB-Vac group showed a significant increase compared to other groups. The production of IL-4 in the group that received the DNA vaccine did not change significantly compared to the control group. The lymphocyte proliferation increased significantly in the mice group that received SEB construct than PBS control group (p < 0.001). While there was a meaningful decrease in tumor size (p < 0.001), a significant increase in tumor tissue necrosis (p < 0.01) and also in survival time of the animal model receiving the recombinant construct was observed. The designed SEB gene construct can be a new model vaccine for breast cancer because it effectively induces necrosis and produces specific immune responses. This structure does not hurt normal cells and is a safer treatment than chemotherapy and radiation therapy. Its slow and long-term release gently stimulates the immune system and cellular memory. It could be applied as a new model for inducing apoptosis and antitumor immunity to treat cancer.

PD-1/PD-L1 Control of Antigen-Specifically Activated CD4 T-Cells of Neonates.

Newborns are highly susceptible to infections; however, the underlying mechanisms that regulate the anti-microbial T-helper cells shortly after birth remain incompletely understood. To address neonatal antigen-specific human T-cell responses against bacteria, Staphylococcus aureus (S. aureus) was used as a model pathogen and comparatively analyzed in terms of the polyclonal staphylococcal enterotoxin B (SEB) superantigen responses. Here, we report that neonatal CD4 T-cells perform activation-induced events upon S. aureus/APC-encounter including the expression of CD40L and PD-1, as well as the production of Th1 cytokines, concomitant to T-cell proliferation. The application of a multiple regression analysis revealed that the proliferation of neonatal T-helper cells was determined by sex, IL-2 receptor expression and the impact of the PD-1/PD-L1 blockade. Indeed, the treatment of S. aureus-activated neonatal T-helper cells with PD-1 and PD-L1 blocking antibodies revealed the specific regulation of the immediate neonatal T-cell responses with respect to the proliferation and frequencies of IFNγ producers, which resembled in part the response of adults' memory T-cells. Intriguingly, the generation of multifunctional T-helper cells was regulated by the PD-1/PD-L1 axis exclusively in the neonatal CD4 T-cell lineage. Together, albeit missing memory T-cells in neonates, their unexperienced CD4 T-cells are well adapted to mount immediate and strong anti-bacterial responses that are tightly controlled by the PD-1/PD-L1 axis, thereby resembling the regulation of recalled memory T-cells of adults.

Femtomolar detection of staphylococcal enterotoxin 'B' using a fluorescent quantum dot based hybrid Apta-immunosensor.

Food poisoning is a gastrointestinal illness caused by food-borne enterotoxin produced by the bacterium Staphylococcus aureus. The effective dose of Staphylococcal enterotoxin 'B' (SEB) is estimated to be 0.4 ng/kg of body weight, whereas the 50 % lethal dose is found to be 20 ng/kg of body weight for humans exposed by the inhalation route. The present report highlights the development of a fluorescence resonance energy transfer (FRET) based assay for the detection of Staphylococcal enterotoxin. Highly fluorescent, aqueous quantum dots were synthesized and conjugated with Staphylococcal enterotoxin 'B' specific bioreceptors. SEB specific aptamer and SEB antibody were labeled with fluorescent quantum dots for recognizing and binding two separate epitopes in the SEB. A combination of two probes against different epitopic regions in a homogeneous sandwich assay format enhanced the sensitivity and specificity of SEB detection. In the presence of the enterotoxin, both the aptamer and antibody came in close proximity with each other and FRET was observed. A linear decrease in the fluorescence at 562 nm and a corresponding increase in the signal at 644 nm was observed with increasing concentrations of SEB, when excited at the absorption maximum of quantum dots. The limit of detection for the developed assay obtained was less than 1 ng/ml. The method was employed in apple juice and quantitated using Enzyme-linked Immunosorbent Assay (ELISA). The designed assay was rapid and robust and can be extrapolated as a platform for the detection of various disease-causing agents of biomedical significance.

SARS-CoV-2 Spike Does Not Possess Intrinsic Superantigen-like Inflammatory Activity.

Multisystem inflammatory syndrome in children (MIS-C) is a rare hyperinflammatory disease occurring several weeks after SARS-CoV-2 infection. The clinical similarities between MIS-C and the toxic shock syndrome, together with the preferential expansion of T cells with a T-cell receptor variable ß chain (TCRVß) skewing, suggested a superantigen theory of MIS-C. For instance, recent in silico modelling evidenced the presence of a highly conserved motif within SARS-CoV-2 spike protein similar in structure to the superantigenic fragment of staphylococcal enterotoxin B (SEB). However, experimental data on the superantigenic activity of the SARS-CoV-2 spike have not yet been provided. Here, we assessed the superantigenic activity of the SARS-CoV-2 spike by analysing inflammatory cytokine production in both Jurkat cells and the peripheral blood CD4+ T cells stimulated with the SARS-CoV-2 spike or SEB as a control. We found that, unlike SEB, the SARS-CoV-2 spike does not exhibit an intrinsic superantigen-like activity.

Resolution of Eczema with Multivalent Peptides.

The integrity of the skin is an important aspect of QOL. Whether caused by genetic deficiencies or environmental insults, disruption of the surface barrier allows irritants and allergens to penetrate the skin, which initiates inflammatory responses by immune cells that often lead to life-long allergies. In this study, eczema was induced on depilated mouse skin with topical lipopolysaccharide or a mixture of Staphylococcal enterotoxin B and an extract of house dust mites, which resulted in thickening of the epidermis, epidermal disruption, and abundant neutrophils in the dermis. Within 14 days of topical treatment with 1 µM svL4, a tetravalent peptide, neutrophils were absent, and the epidermis had returned to a normal morphology. The sequence of svL4 contains glutamine residues that serve as a cross-linking substrate for transglutaminase 2, which gains access to the skin surface where the epidermis becomes disrupted. In contrast, topical application of 1 µM svH1C, a peptide mimetic of sialic acid that lacks glutamine residues, or 1 µM dexamethasone was ineffective in restoring normal epidermal morphology. The data suggest that svL4 would be a powerful treatment for resolving severe eczema.

Comparison of Transcriptional Signatures of Three Staphylococcal Superantigenic Toxins in Human Melanocytes.

Staphylococcus aureus, a gram-positive bacterium, causes toxic shock through the production of superantigenic toxins (sAgs) known as Staphylococcal enterotoxins (SE), serotypes A-J (SEA, SEB, etc.), and toxic shock syndrome toxin-1 (TSST-1). The chronology of host transcriptomic events that characterizes the response to the pathogenesis of superantigenic toxicity remains uncertain. The focus of this study was to elucidate time-resolved host responses to three toxins of the superantigenic family, namely SEA, SEB, and TSST-1. Due to the evolving critical role of melanocytes in the host's immune response against environmental harmful elements, we investigated herein the transcriptomic responses of melanocytes after treatment with 200 ng/mL of SEA, SEB, or TSST-1 for 0.5, 2, 6, 12, 24, or 48 h. Functional analysis indicated that each of these three toxins induced a specific transcriptional pattern. In particular, the time-resolved transcriptional modulations due to SEB exposure were very distinct from those induced by SEA and TSST-1. The three superantigens share some similarities in the mechanisms underlying apoptosis, innate immunity, and other biological processes. Superantigen-specific signatures were determined for the functional dynamics related to necrosis, cytokine production, and acute-phase response. These differentially regulated networks can be targeted for therapeutic intervention and marked as the distinguishing factors for the three sAgs.

Neurobiological Basis of Aversion-Resistant Ethanol Seeking in C. elegans.

Persistent alcohol seeking despite the risk of aversive consequences is a crucial characteristic of alcohol use disorders (AUDs). Therefore, an improved understanding of the molecular basis of alcohol seeking despite aversive stimuli or punishment in animal models is an important strategy to understand the mechanism that underpins the pathology of AUDs. Aversion-resistant seeking (ARS) is characterized by disruption in control of alcohol use featured by an imbalance between the urge for alcohol and the mediation of aversive stimuli. We exploited C. elegans, a genetically tractable invertebrate, as a model to elucidate genetic components related to this behavior. We assessed the seb-3 neuropeptide system and its transcriptional regulation to progress aversion-resistant ethanol seeking at the system level. Our functional genomic approach preferentially selected molecular components thought to be involved in cholesterol metabolism, and an orthogonal test defined functional roles in ARS through behavioral elucidation. Our findings suggest that fmo-2 (flavin-containing monooxygenase-2) plays a role in the progression of aversion-resistant ethanol seeking in C. elegans.

A remote sensing-based three-source energy balance model to improve global estimations of evapotranspiration in semi-arid tree-grass ecosystems.

It is well documented that energy balance and other remote sensing-based evapotranspiration (ET) models face greater uncertainty over water-limited tree-grass ecosystems (TGEs), representing nearly 1/6th of the global land surface. Their dual vegetation strata, the grass-dominated understory and tree-dominated overstory, make for distinct structural, physiological and phenological characteristics, which challenge models compared to more homogeneous and energy-limited ecosystems. Along with this, the contribution of grasses and trees to total transpiration (T), along with their different climatic drivers, is still largely unknown nor quantified in TGEs. This study proposes a thermal-based three-source energy balance (3SEB) model, accommodating an additional vegetation source within the well-known two-source energy balance (TSEB) model. The model was implemented at both tower and continental scales using eddy-covariance (EC) TGE sites, with variable tree canopy cover and rainfall (P) regimes and Meteosat Second Generation (MSG) images. 3SEB robustly simulated latent heat (LE) and related energy fluxes in all sites (Tower: LE RMSD ~60 W/m2 ; MSG: LE RMSD ~90 W/m2 ), improving over both TSEB and seasonally changing TSEB (TSEB-2S) models. In addition, 3SEB inherently partitions water fluxes between the tree, grass and soil sources. The modelled T correlated well with EC T estimates (r > .76), derived from a machine learning ET partitioning method. The T/ET was found positively related to both P and leaf area index, especially compared to the decomposed grass understory T/ET. However, trees and grasses had contrasting relations with respect to monthly P. These results demonstrate the importance in decomposing total ET into the different vegetation sources, as they have distinct climatic drivers, and hence, different relations to seasonal water availability. These promising results improved ET and energy flux estimations over complex TGEs, which may contribute to enhance global drought monitoring and understanding, and their responses to climate change feedbacks.