Miracle-dz/UniFAR-FTUs huggingface dataset:
MyD88-Dependent and MyD88-Independent Pathways in Synergy, Priming, and Tolerance between TLR Agonists1

TLRs sense components of microorganisms and are critical host mediators of inflammation during infection. Different TLR agonists can profoundly alter inflammatory effects of one another, and studies suggest that the sequence of exposure to TLR agonists may importantly impact on responses during infection. We tested the hypothesis that synergy, priming, and tolerance between TLR agonists follow a pattern that can be predicted based on differential engagement of the MyD88-dependent (D) and the MyD88-independent (I) intracellular signaling pathways. Inflammatory effects of combinations of D and I pathway agonists were quantified in vivo and in vitro. Experiments used several D-specific agonists, an I-specific agonist (poly(I:C)), and LPS, which acts through both the D and I pathways. D-specific agonists included: peptidoglycan-associated lipoprotein, Pam3Cys, flagellin, and CpG DNA, which act through TLR2 (peptidoglycan-associated lipoprotein and Pam3Cys), TLR5, and TLR9, respectively. D and I agonists were markedly synergistic in inducing cytokine production in vivo in mice. All of the D-specific agonists were synergistic with poly(I:C) in vitro in inducing TNF and IL-6 production by mouse bone marrow-derived macrophages. Pretreatment of bone marrow-derived macrophages with poly(I:C) led to a primed response to subsequent D-specific agonists and vice versa, as indicated by increased cytokine production, and increased NF-κB translocation. Pretreatment with a D-specific agonist augmented LPS-induced IFN-β production. All D-specific agonists induced tolerance to one another. Thus, under the conditions studied here, simultaneous and sequential activation of both the D and I pathways causes synergy and priming, respectively, and tolerance is induced by agonists that act through the same pathway.
INTERPERSONAL RELATIONS AND GROUP PROCESSES Individual Differences in the Regulation of Intergroup Bias: The Role of Conflict Monitoring and Neural Signals for Control

Low-prejudice people vary considerably in their ability to regulate intergroup responses. The authors hypothesized that this variability arises from a neural mechanism for monitoring conflict between automatic race-biased tendencies and egalitarian intentions. In Study 1, they found that low-prejudice participants whose nonprejudiced responses are motivated by internal (but not external) factors exhibited better control on a stereotype-inhibition task than did participants motivated by a combination of internal and external factors. This difference was associated with greater conflict-monitoring activity, measured by event-related potentials, when responses required stereotype inhibition. Study 2 demonstrated that group differences were specific to response control in the domain of prejudice. Results indicate that conflict monitoring, a preconscious component of response control, accounts for variability in intergroup bias among low-prejudice participants.
Salivary hormones and IgA in relation to physical performance in football

Abstract Salivary biomarkers have shown to be useful to assess physiological stress in football, but their relationship with physical performance is unknown. The aims of this study were to investigate the effect of a football match on salivary cortisol, testosterone and immunoglobulin A (IgA) concentrations in elite footballers, and to examine the relationship of physical performance during the match to these biomarkers. Nine elite football players were assessed before, during and after a friendly international match. Physical performance during the match was measured by time-motion analysis, whilst salivary cortisol, testosterone and IgA were measured before and 10 min post-match. The results showed that players covered an average of 9463 ± 458 m during the match. Salivary cortisol did not change post-match. Testosterone and IgA concentrations decreased by 30.6% and 74.5%, respectively. The testosterone/cortisol (T/C) ratio decreased by 64.2% after the match. Changes in testosterone concentrations correlated (r = 0.85) with distance covered. Pre- and post-match testosterone levels correlated with post-match IgA concentrations (r = 0.8 and 0.89, respectively). These results suggest that a football match induces catabolic stress as indicated by the decreased T/C ratio. It seems that footballers with smaller decreases in testosterone levels covered more distance and decreased their immune function less.
Constitutive Delivery of Bovine β-Lactoglobulin to the Digestive Tracts of Gnotobiotic Mice by Engineered Lactobacillus casei

ABSTRACT The gut microbiota is critical for maturation of the immune system. Recent evidence suggests that early establishment of lactobacilli in the intestinal microbiota, during neonatal colonization or by probiotic supplementation, could prevent the development of allergic disorders. Postnatal maturation of the gut immune system with allergen-producing lactobacilli colonizing the digestive tract could then affect the development of further allergic sensitization. In this paper, we describe construction of a recombinant Lactobacillus casei strain that can constitutively deliver bovine β-lactoglobulin (BLG), a major cow's milk allergen, to the guts of gnotobiotic mice. The blg gene was inserted into the L. casei chromosome downstream of an endogenous promoter. BLG production was improved by fusing the propeptide LEISSTCDA (LEISS) to the BLG mature moiety. This led to a 10-fold increase in LEISS-BLG production compared to the production obtained without the propeptide and also led to enhanced secretion corresponding to 5% of the total production. After inoculation into germfree C3H/HeN mice, the genetic stability of the recombinant strain and in vivo BLG production were confirmed for at least 10 weeks. BLG stimulation of spleen cells from mice monoassociated with the BLG-producing lactobacilli induced secretion of the Th1 cytokine gamma interferon and, to a lesser extent, the Th2 cytokine interleukin-5. No BLG-specific immunoglobulin G1 (IgG1), IgG2a, or IgA was detected in sera or in fecal samples. These results suggest that gut colonization with allergen-producing lactobacilli could provide a useful model for studying the modulation of allergic disorders.
Dataset integration identifies transcriptional regulation of microRNA genes by PPARγ in differentiating mouse 3T3-L1 adipocytes

Peroxisome proliferator-activated receptor γ (PPARγ) is a key transcription factor in mammalian adipogenesis. Genome-wide approaches have identified thousands of PPARγ binding sites in mouse adipocytes and PPARγ upregulates hundreds of protein-coding genes during adipogenesis. However, no microRNA (miRNA) genes have been identified as primary PPARγ-targets. By integration of four separate datasets of genome-wide PPARγ binding sites in 3T3-L1 adipocytes we identified 98 miRNA clusters with PPARγ binding within 50 kb from miRNA transcription start sites. Nineteen mature miRNAs were upregulated ≥2-fold during adipogenesis and for six of these miRNA loci the PPARγ binding sites were confirmed by at least three datasets. The upregulation of five miRNA genes miR-103-1 (host gene Pank3), miR-148b (Copz1), miR-182/96/183, miR-205 and miR-378 (Ppargc1b) followed that of Pparg. The PPARγ-dependence of four of these miRNA loci was demonstrated by PPARγ knock-down and the loci of miR-103-1 (Pank3), miR-205 and miR-378 (Ppargc1b) were also responsive to the PPARγ ligand rosiglitazone. Finally, chromatin immunoprecipitation analysis validated in silico predicted PPARγ binding sites at all three loci and H3K27 acetylation was analyzed to confirm the activity of these enhancers. In conclusion, we identified 22 putative PPARγ target miRNA genes, showed the PPARγ dependence of four of these genes and demonstrated three as direct PPARγ target genes in mouse adipogenesis.
A Bayesian Analysis of Return Dynamics with Stochastic Volatility and Levy Jumps

We develop Bayesian Markov chain Monte Carlo methods for inferences of continuoustime models with stochastic volatility and infinite-activity Levy jumps using discretely sampled data. Simulation studies show that (i) our methods provide accurate joint identification of diffusion, stochastic volatility, and Levy jumps, and (ii) affine jumpdiffusion models fail to adequately approximate the behavior of infinite-activity jumps. In particular, the affine jump-diffusion models fail to capture the infinitely many small Levy jumps which are too big for Brownian motion to model and too small for compound Poisson process to capture. Empirical studies show that infinite-activity Levy jumps are essential for modeling the S&P 500 index returns. Disciplines Statistics and Probability Comments This preprint was published as H. Li, M.T. Wells, and C.L. Yu, "A Bayesian Analysis of Return Dynamics with Levy Jumps", Review of Financial Studies (2008): 2345-2378, doi: 10.1093/rfs/hhl036. This article is available at Iowa State University Digital Repository: http://lib.dr.iastate.edu/stat_las_preprints/113 A Bayesian Analysis of Return Dynamics with Stochastic Volatility and Lévy Jumps Haitao Li,1 Matin T. Wells,2 and Cindy L. Yu3
Central Antinociceptive and Mechanism of Action of Pereskia bleo Kunth Leaves Crude Extract, Fractions, and Isolated Compounds

Pereskia bleo (Kunth) DC. (Cactaceae) is a plant commonly used in popular medicine in Malaysia. In this work, we evaluate the antinociceptive effect of P. bleo leaf extracts and isolated compounds in central antinociceptive model. Ethanol extract (E), hexane (H), ethyl acetate (EA), or butanol (B) fractions (30, 50, or 100 mg/kg, p.o.), sitosterol (from hexane) and vitexin (from ethyl acetate), were administered to mice. Antinociceptive effect was evaluated in the hot plate and capsaicin- or glutamate-induced licking models. Morphine (1 mg/kg, p.o.) was used as reference drug. Naloxone (1 mg/kg, i.p.), atropine (1 mg/kg, i.p.), and L-nitro arginine methyl ester (L-NAME, 3 mg/kg, i.p.) were administered 30 min earlier (100 mg/kg, p.o.) in order to evaluate the mechanism of the antinociceptive action. Higher dose of B developed an effect significantly superior to morphine-treated group. Naloxone prevented the antinociceptive effect of all fractions. L-NAME demonstrated effect against E, EA, and B. In all fractions, sitosterol and vitexin reduced the licking time after capsaicin injection. Glutamate-induced licking response was blocked by H, EA, and B. Our results indicate that Pereskia bleo fractions, sitosterol and vitexin, possessed a central antinociceptive effect. Part of this effect is mediated by opioid receptors and nitrergic pathway.
Analysis of Microsatellite DNA Markers Reveals no Genetic Differentiation between Wild and Hatchery Populations of Pacific Threadfin in Hawaii

Pacific threadfin, Polydactylus sexfilis, is popular fish in recreational fishing, as well as aquaculture in Hawaii. Its natural population has been continuously declining in the past several decades. Microsatellite DNA markers are useful DNA-based tool for monitoring Pacific threadfin populations. In this study, fifteen Microsatellite (MS) DNA markers were identified from a partial genomic Pacific threadfin DNA library enriched in CA repeats, and six highly-polymorphic microsatellite loci were employed to analyze genetic similarity and differences between the wild population and hatchery population in Oahu Island. A total of 37 alleles were detected at the six MS loci in the two populations. Statistical analysis of fixation index (FST) and analysis of molecular variance (AMOVA) showed no genetic differentiation between the wild and hatchery populations (FST=0.001, CI95%= -0.01-0.021). Both high genetic diversity (Ho=0.664-0.674 and He=0.710-0.715) and Hardy-Weinberg equilibrium were observed in the wild and hatchery populations. Results of genetic bottleneck analysis indicated that the hatchery was founded with sufficient numbers of brooders as inbreeding coefficient is very low (FIS=0.052-0.072) in both wild and hatchery populations. Further studies are needed for comprehensive determinations of genetic varieties of primary founder broodstocks and successive offspring of the hatchery and wild populations with increased number of Pacific threadfin sample collections.
The influence of shame on posttrauma disorders: have we failed to see the obvious?

Background While fear is known to be the dominant affect associated with posttraumatic stress disorder (PTSD), the presence and possible influence of other emotions is less well explored. Recent changes to diagnostic criteria have added anger, guilt and shame alongside fear as significant emotional states associated with the disorder. This article suggests that shame is a frequent, often poorly recognised sequel to trauma, occurring as a result of the meaning the individual places on the traumatic experience and on subsequent interpersonal and environmental events. Methods The article reviews the literature on the socio-interpersonal aspects of the posttraumatic experience with particular emphasis on the emotion of shame as both primary and secondary emotion, in its intrapersonal and interpersonal contexts, and in adaptive and maladaptive forms. Results The review suggests that posttrauma shame, and maladaptive shame regulation strategies, often manifesting as anger, substance abuse, social withdrawal or depression, may play an important role in the maintenance or exacerbation of the symptoms of PTSD and the development of co-morbidities. Conclusion The recognition of shame and maladaptive shame regulation strategies in PTSD treatment and management is critical. However, because shame is frequently considered a painful and discomforting emotion, it may fail to be addressed in the therapeutic setting by both client and therapist. Examination of potential shame-related changes in self-concept, close interpersonal relationships and social inclusion are recommended for individuals who have experienced a range of traumas to identify and address any underlying unacknowledged shame.
Steps to Health in Cognitive Aging: Effects of Physical Activity on Spatial Attention and Executive Control in the Elderly

The purpose of this study was to investigate whether physical activity (PA) habits may positively impact performance of the orienting and executive control networks in community-dwelling aging individuals and diabetics, who are at risk of cognitive dysfunction. To this aim, we tested cross-sectionally whether age, ranging from late middle-age to old adulthood, and PA level independently or interactively predict different facets of the attentional performance. Hundred and thirty female and male individuals and 22 adults with type 2 diabetes aged 55–84 years were recruited and their daily PA (steps) was objectively measured by means of armband monitors. Participants performed a multifunctional attentional go/no-go reaction time (RT) task in which spatial attention was cued by means of informative direct cues of different sizes followed by compound stimuli with local and global target features. The performance efficiency of the orienting networks was estimated by computing RT differences between validly and invalidly cued trials, that of the executive control networks by computing local switch costs that are RT differences between switch and non-switch trials in mixed blocks of global and local target trials. In regression analyses performed on the data of non-diabetic elderlies, overall RTs and orienting effects resulted jointly predicted by age and steps. Age predicted overall RTs in low-active individuals, but orienting effects and response errors in high-active individuals. Switch costs were predicted by age only, with larger costs at older age. In the analysis conducted with the 22 diabetics and 22 matched non-diabetic elderlies, diabetic status and daily steps predicted longer and shorter RTs, respectively. Results suggest that high PA levels exert beneficial, but differentiated effects on processing speed and attentional networks performance in aging individuals that partially counteract the detrimental effects of advancing age and diabetic status. In conclusion, adequate levels of overall PA may positively impinge on brain efficiency and attentional control and should be therefore promoted by actions that support lifelong PA participation and impact the built environment to render it more conducive to PA.
Low prevalence of transmitted K65R and other tenofovir resistance mutations across different HIV-1 subtypes: implications for pre-exposure prophylaxis

Tenofovir‐containing regimens have demonstrated potential efficacy as pre‐exposure prophylaxis (PrEP) in preventing HIV‐1 infection. Transmitted drug resistance mutations associated with tenofovir, specifically the reverse transcriptase (RT) mutation K65R, may impact the effectiveness of PrEP. The worldwide prevalence of transmitted tenofovir resistance in different HIV‐1 subtypes is unknown.
The Evaluation of Glutathione Reductase and Malondialdehyde Levels in Patients With Lumbar Disc Degeneration Disease

Background/Aim: Increased oxidative stress plays a crucial role in pathogenesis of various diseases. The present study aims to investigate glutathione reductase (GR) and malondialdehyde (MDA) enzymes as markers of oxidative stress mechanisms in lumbar disc degeneration disease (LDDD). Patients and Methods: The study group consisted of 39 patients diagnosed with LDD and 37 healthy individuals in the control group. The enzyme-linked immunosorbent assay (ELISA) method was used to determine serum GR and MDA levels in the two study groups. Results: Serum GR levels were significantly lower (p=0.008), while MDA levels were significantly higher in the patient group compared to the controls (p=0.025). Conclusion: Oxidative stress mechanisms play a crucial role in disc degeneration and GR deficiency could be an eligible risk factor for LDDD.
The vav exchange factor is an essential regulator in actin-dependent receptor translocation to the lymphocyte-antigen-presenting cell interface.

During the interaction of a T cell with an antigen-presenting cell (APC), several receptor ligand pairs, including the T cell receptor (TCR)/major histocompatibility complex (MHC), accumulate at the T cell/APC interface in defined geometrical patterns. This accumulation depends on a movement of the T cell cortical actin cytoskeleton toward the interface. Here we study the involvement of the guanine nucleotide exchange factor vav in this process. We crossed 129 vav(-/-) mice with B10/BR 5C.C7 TCR transgenic mice and used peptide-loaded APCs to stimulate T cells from the offspring. We found that the accumulation of TCR/MHC at the T cell/APC interface and the T cell actin cytoskeleton rearrangement were clearly defective in these vav(+/-) mice. A comparable defect in superantigen-mediated T cell activation of T cells from non-TCR transgenic 129 mice was also observed, although in this case it was more apparent in vav(-/-) mice. These data indicate that vav is an essential regulator of cytoskeletal rearrangements during T cell activation.
On the Complexity of Information Spreading in Dynamic Networks

We study how to spread k tokens of information to every node on an n-node dynamic network, the edges of which are changing at each round. This basic gossip problem can be completed in O(n + k) rounds in any static network, and determining its complexity in dynamic networks is central to understanding the algorithmic limits and capabilities of various dynamic network models. Our focus is on token-forwarding algorithms, which do not manipulate tokens in any way other than storing, copying and forwarding them. We first consider the strongly adaptive adversary model where in each round, each node first chooses a token to broadcast to all its neighbors (without knowing who they are), and then an adversary chooses an arbitrary connected communication network for that round with the knowledge of the tokens chosen by each node. We show that Ω(nk/log n + n) rounds are needed for any randomized (centralized or distributed) token-forwarding algorithm to disseminate the k tokens, thus resolving an open problem raised in [KLO10]. The bound applies to a wide class of initial token distributions, including those in which each token is held by exactly one node and well-mixed ones in which each node has each token independently with a constant probability. Our result for the strongly adaptive adversary model motivates us to study the weakly adaptive adversary model where in each round, the adversary is required to lay down the network first, and then each node sends a possibly distinct token to each of its neighbors. We propose a simple randomized distributed algorithm where in each round, along every edge (u, v), a token sampled uniformly at random from the symmetric difference of the sets of tokens held by node u and node v is exchanged. We prove that starting from any well-mixed distribution of tokens where each node has each token independently with a constant probability, this algorithm solves the k-gossip problem in O((n + k) log n log k) rounds with high probability over the initial token distribution and the randomness of the protocol. We then show how the above uniform sampling problem can be solved using O(log n) bits of communication, making the overall algorithm communication-efficient. We next present a centralized algorithm that solves the gossip problem for every initial distribution in O((n + k) log2 n) rounds in the offline setting where the entire sequence of communication networks is known to the algorithm in advance. Finally, we present an O(n min{k, √k log n})-round centralized offline algorithm in which each node can only broadcast a single token to all of its neighbors in each round.