This systematic review summarizes pharmacogenetic studies on antidepressant response and side effects. Out of the 17 genes we reviewed, 8 genes were entered into the meta-analysis (SLC6A4, HTR1A, ...HTR2A, TPH1, gene encoding the beta-3 subunit, brain-derived neurotrophic factor (BDNF), HTR3A and HTR3B). TPH1 218C/C genotype (7 studies, 754 subjects) was significantly associated with a better response (odds ratio, OR=1.62; P=0.005) with no heterogeneity between ethnicities. A better response was also observed in subjects with the Met variant within the BDNF 66Val/Met polymorphism (4 studies, 490 subjects; OR=1.63, P=0.02). Variable number of tandem repeats polymorphism within intron 2 (STin2) 12/12 genotype showed a trend toward a better response in Asians (STin2: 5 studies, 686 subjects; OR=3.89, P=0.03). As for side effects, pooled ORs of serotonin transporter gene promoter polymorphism (5-HTTLPR) l (9 studies, 2642 subjects) and HTR2A -1438G/G (7 studies, 801 subjects) were associated with a significant risk modulation (OR=0.64, P=0.0005) and (OR=1.91, P=0.0006), respectively. Interestingly, this significance became more robust when analyzed with side effect induced by selective serotonin reuptake inhibitors only (5-HTTLPR: P=0.0001, HTR2A: P<0.0001). No significant result could be observed for the other variants. These results were not corrected for multiple testing in each variant, phenotype and subcategory. This would have required a Bonferroni significance level of P<0.0023. Although some heterogeneity was present across studies, our finding suggests that 5-HTTLPR, STin2, HTR1A, HTR2A, TPH1 and BDNF may modulate antidepressant response.
Foxp3+ T cells play a critical role for the maintenance of immune tolerance. Here we show that in mice, Foxp3+ T cells contributed to diversification of gut microbiota, particularly of species ...belonging to Firmicutes. The control of indigenous bacteria by Foxp3+ T cells involved regulatory functions both outside and inside germinal centers (GCs), consisting of suppression of inflammation and regulation of immunoglobulin A (IgA) selection in Peyer’s patches, respectively. Diversified and selected IgAs contributed to maintenance of diversified and balanced microbiota, which in turn facilitated the expansion of Foxp3+ T cells, induction of GCs, and IgA responses in the gut through a symbiotic regulatory loop. Thus, the adaptive immune system, through cellular and molecular components that are required for immune tolerance and through the diversification as well as selection of antibody repertoire, mediates host-microbial symbiosis by controlling the richness and balance of bacterial communities required for homeostasis.
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•Tfr cells are required for IgA selection•Tfr cells through IgA regulate the diversity and composition of microbiota•Rich and balanced bacterial communities induce Foxp3+ T cells and IgAs•Poor and unbalanced microbiota induce inflammatory T cells and IgGs
It is unclear how T and B cells mediate host-microbial interactions in the gut. Here Kawamoto et al. show that by regulating IgA selection, Foxp3+ T cells contribute to maintenance of diversified and balanced microbiota, which is required for immune homeostasis.
A
bstract
We consider a hybrid Monte Carlo algorithm which is applicable to lattice theories defined on Lefschetz thimbles. In the algorithm, any point (field configuration) on a thimble is ...parametrized uniquely by the flow-direction and the flow-time defined at a certain asymptotic region close to the critical point, and it is generated by solving the gradient flow equation downward. The associated complete set of tangent vectors is also generated in the same manner. Molecular dynamics is then formulated as a constrained dynamical system, where the equations of motion with Lagrange multipliers are solved by the second-order constraint-preserving symmetric integrator. The algorithm is tested in the λ
ϕ
4
model at finite density, by choosing the thimbles associated with the classical vacua for subcritical and supercritical values of chemical potential. For the lattice size
L
= 4, we find that the residual sign factors average to not less than 0.99 and are safely included by reweighting and that the results of the number density are consistent with those obtained by the complex Langevin simulations.
Abstract
Tendon self-renewal is a rare occurrence because of the poor vascularization of this tissue; therefore, reconstructive surgery using autologous tendon is often performed in severe injury ...cases. However, the post-surgery re-injury rate is relatively high, and the collection of autologous tendons leads to muscle weakness, resulting in prolonged rehabilitation. Here, we introduce an induced pluripotent stem cell (iPSC)-based technology to develop a therapeutic option for tendon injury. First, we derived tenocytes from human iPSCs by recapitulating the normal progression of step-wise narrowing fate decisions in vertebrate embryos. We used single-cell RNA sequencing to analyze the developmental trajectory of iPSC-derived tenocytes. We demonstrated that iPSC-tenocyte grafting contributed to motor function recovery after Achilles tendon injury in rats via engraftment and paracrine effects. The biomechanical strength of regenerated tendons was comparable to that of healthy tendons. We suggest that iPSC-tenocytes will provide a therapeutic option for tendon injury.
Immunoglobulin A (IgA) is essential to maintain the symbiotic balance between gut bacterial communities and the host immune system. Here we provide evidence that the inhibitory co-receptor programmed ...cell death-1 (PD-1) regulates the gut microbiota through appropriate selection of IgA plasma cell repertoires. PD-1 deficiency generates an excess number of T follicular helper (T FH ) cells with altered phenotypes, which results in dysregulated selection of IgA precursor cells in the germinal center of Peyer's patches. Consequently, the IgAs produced in PD-1-deficient mice have reduced bacteria-binding capacity, which causes alterations of microbial communities in the gut. Thus, PD-1 plays a critical role in regulation of antibody diversification required for the maintenance of intact mucosal barrier.
Matrix metalloproteinase (MMP) inhibition has been shown to reduce dentin caries progression, but its role in dental erosion has not yet been assessed. This study tested the hypothesis that gels ...containing MMP inhibitors (epigallocatechin gallate-EGCG and chlorhexidine) can prevent dental erosion. Volunteers (n = 10) wore palatal devices containing bovine dentin blocks (n = 10/group) treated for 1 min with EGCG at 10 (EGCG10) or 400 µM (EGCG400), chlorhexidine at 0.012%, F at 1.23% (NaF), and no vehicle (placebo). Erosion was performed with Coca-Cola® (5 min) 4X/day during 5 days. The wear, assessed by profilometry (mean ± SD, µm), was significantly reduced by the gels containing MMP inhibitors (0.05 ± 0.02a, 0.04 ± 0.02a, and 0.05 ± 0.02a for EGCG10, EGCG400, and chlorhexidine, respectively) when compared with NaF (0.79 ± 0.35b) and placebo gels (1.77 ± 0.35b) (Friedman and Dunn’s tests, p < 0.01). The use of gels delivering MMP inhibitors was shown to prevent erosion and opens a new perspective for protection against dental erosion.
Sequential anaerobic and aerobic processes have been recommended to treat textile wastewater reliably. In this work, the focus was on finding an energetically more competitive system to remove ...tetra-azo dye Direct Black 22 (DB22). We operated two upflow anaerobic sludge blanket (UASB) reactors (R1 and R2) in three phases (PI, PII, and PIII). R1 was operated as a conventional UASB, while R2 was microaerated in the upper part (0.18 ± 0.05 mg O2. L−1), aiming to remove DB22 simultaneously with the aromatic amine byproducts. PI consisted of feeding reactors with synthetic textile wastewater (STW), PII had higher salinity in the STW, and PIII was the same as PII, plus sulfate. The results showed that color and COD removal efficiencies were similar for both reactors (67–72% for R1 and 59–78% for R2) without a substantial influence of oxygen in R2. However, microaeration played a crucial role in R2 by removing the anaerobically formed aromatic amines; during PIII, the effluent was 16 times less toxic than that of R1. The microbial community that developed in the sludge bed of both reactors was quite similar, with the core microbiome represented by Trichococcus, Syntrophus and Methanosaeta genera. The increase in salinity in PII and PIII promoted a shift in the microbial community, excluding salty-sensitive genera from the core microbiome. The putative genera Brevundimonas and Ornatilinea were associated to aromatic amine microaerobic removal. Therefore, there is a potential application of a compact microaerated anaerobic system for textile wastewater treatment.
•Microaeration in UASB reactor promoted complete removal of azo dye Direct Black 22.•Similar COD and sulfate removal for anaerobic and microaerated UASB reactors.•Effluent toxicity was removed after microaeration.•Putative aromatic amines degraders microbes developed in the microaerobic zone.
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