Jorgensenthorsen4885
Distributed throughout the body, lymph nodes (LNs) constitute an important crossroad where resident and migratory immune cells interact to initiate antigen-specific immune responses supported by a dynamic 3-dimensional network of stromal cells, that is, endothelial cells and fibroblastic reticular cells (FRCs). LNs are organized into four major subanatomically separated compartments the subcapsular sinus (SSC), the paracortex, the cortex, and the medulla. Each compartment is underpinned by particular FRC subsets that physically support LN architecture and delineate functional immune niches by appropriately providing environmental cues, nutrients, and survival factors to the immune cell subsets they interact with. In this review, we discuss how FRCs drive the structural and functional organization of each compartment to give rise to prosperous interactions and coordinate immune cell activities. We also discuss how reciprocal communication makes FRCs and immune cells perfect compatible partners for the generation of potent cellular and humoral immune responses.Cyclophilin A (CypA), a member of the cyclophilin family, plays a vital role in microorganismal infections, inflammatory diseases, and cancers. Interleukin-6 (IL-6) is a pleiotropic cytokine, exerting variety of effects on inflammation, immune response, hematopoiesis, and tumor proliferation. Binding of IL-6 to soluble IL-6 receptor (sIL-6R) induces pro-inflammatory trans-signaling, which has been described to be stronger than anti-inflammatory classic signaling triggered by the binding of IL-6 to membrane-bound IL-6 receptor. Here we found that upon the treatment of IL-6 and sIL-6R, CypA inhibited the ubiquitination-mediated degradation of IL-6 membrane receptor gp130 and enhanced its dimerization, thereby positively regulated the IL-6 trans-signaling and increased the expression of downstream iNOS, IL-6, and CypA. Furthermore, CypA expression could be negatively regulated by suppressor of cytokine signaling 1 (SOCS1). The SH2 and Box domains of SOCS1 interacted with CypA and promoted its K48-linked ubiquitination-mediated degradation, which inhibited the IL-6 trans-signaling pathway. Collectively, our findings reveal an important role of CypA in the positive and negative feedback regulation of the IL-6 trans-signaling pathway.
Human papillomavirus (HPV)-associated subsequent malignant neoplasms (SMN
) in childhood cancer survivors are poorly understood.
The cumulative risk of SMN
was assessed among 24,363 Childhood Cancer Survivor Study participants. Standardized incidence ratios (SIRs) and absolute excess risk were calculated using age-matched, sex-matched, and calendar year rates from the Surveillance, Epidemiology, and End Results program. Poisson regression models identified SMN
risk factors, evaluating relative SIRs (rSIR) and 95% confidence intervals (95% CIs).
In total, 46 survivors developed an SMN
(median age, 31 years [range, 10-56 years]; median time from primary cancer, 21 years [range, 9-35 years]). SMN
sites included oropharynx (N = 44), anorectum (N = 6), uterine cervix (N = 2), and vulva (N = 2). The 33-year cumulative incidence was 0.3% (95% CI, 0.2%-0.4%), and the SIR was nearly 3-fold that of the general population (SIR, 2.86; 95% CI, 2.05-4.00). Female survivors were not at increased risk of cervetiology of SMN and the promotion of HPV vaccination and surveillance guidelines for SMNHPV in cancer survivors is warranted.Latina women, who are at increased risk of hereditary breast and ovarian cancer (HBOC), have lower use of genetic counseling and testing (GCT) than non-Hispanic White women. In a recent study, culturally targeted video improved psychosocial outcomes related to GCT. Additional analyses examine whether the culturally targeted video improved positive reactions in women who focus on difficulties (concrete mindset) versus women who focus on the final goals (abstract mindset). Participants (N = 32) completed surveys before and immediately after watching the video. The surveys measured attitudes, emotions, and women's mindset. Before watching the video, women with a concrete mindset reported more negative attitudes and negative emotions about GCT than women with an abstract mindset. After watching the video, women with a concrete mindset reported negative attitudes and feelings at levels comparable to those of women with an abstract mindset, reflecting a reduction in their negative attitudes and emotions. The sample size limits the power to find statistically significant differences. Results support the relevance of considering the audience's mindset in the development and testing of public health messages to promote the use of GCT.Snow algae are predicted to expand in polar regions due to climate warming, which can accelerate snowmelt by reducing albedo. Green snow frequently occurs near penguin colonies, and red snow distributes widely along ocean shores. However, the mechanisms underpinning the assemblage of algae and heterotrophs in colored snow remain poorly characterized. We investigated algal, bacterial, and fungal communities and their interactions in red and green snows in the Antarctic Peninsula using a high-throughput sequencing method. We found distinct algal community structure in red and green snows, and the relative abundance of dominant taxa varied, potentially due to nutrient status differences. Contrastingly, red and green snows exhibited similar heterotrophic communities (bacteria and fungi), whereas the relative abundance of fungal pathogens was substantially higher in red snow by 3.8-fold. Red snow exhibited a higher network complexity, indicated by a higher number of nodes and edges. Red snow exhibited a higher proportion of negative correlations among heterotrophs (62.2% vs 3.4%) and stronger network stability, suggesting the red-snow network is more resistant to external disturbance. Our study revealed that the red snow microbiome exhibits a more stable microbial network than the green snow microbiome.Over most of the 20th century, evolutionary biologists predominantly subscribed to a strong form of "micro-mutationism," in which adaptive phenotypic divergence arises from allele frequency changes at many loci, each with a small effect on the phenotype. To be sure, there were well-known examples of large-effect alleles contributing to adaptation, yet such cases were generally regarded as atypical and unrepresentative of evolutionary change in general. In 1998, Allen Orr published a landmark theoretical paper in Evolution, which showed that both small- and large-effect mutations are likely to contribute to "adaptive walks" of a population to an optimum. Coupled with a growing set of empirical examples of large-effect alleles contributing to divergence (e.g., from QTL studies), Orr's paper provided a mathematical formalism that converted many evolutionary biologists from micro-mutationism to a more pluralistic perspective on the genetic basis of evolutionary change. We revisit the theoretical insights emerging from Orr's paper within the historical context leading up to 1998, and track the influence of this paper on the field of evolutionary biology through an examination of its citations over the last two decades and an analysis of the extensive body of theoretical and empirical research that Orr's pioneering paper inspired.
10-Hydroxy-cis-12-octadecenoic acid (10-HOE, 10-OH C181), an emerging functional fatty acid, has anti-fungal and anti-inflammatory effects. 10-HOE is synthesized by bacterial 10-linoleic acid hydratase (10-LHT) with linoleic acid as the substate. However, the characterization of 10-LHT and its targeted synthesis of 10-HOE have been rarely reported. In this study, the recombinant 10-LHT from Lactiplantibacillus plantarum ZS2058 was characterized, and the biocatalysis of 10-HOE using crude enzyme was optimized.
The recombinant 10-LHT catalyzed the conversion of linoleic acid (C182) to 10-HOE as identified using gas chromatography-mass spectrometry (GC-MS). It showed a molecular weight of about 70 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and was a flavin adenine dinucleotide (FAD)-dependent enzyme. The activity of 10-LHT was optimal at pH6.5 and 25 °C, and it was pH-stable but thermo-sensitive. The optimal condition for the 10-HOE biosynthesis using crude enzyme was 5g L
linoleic acid (C182), 148.0U mL
10-LHT, 0.05 mmol L
FAD, 2% methanol and 100 mmol L
sodium chloride at 25 °C and pH6.5. A conversion yield of 47.8 ± 1.5% and the corresponding 10-HOE concentration of 2.4 ± 0.1g L
were achieved at 48 h under the optimal reaction conditions.
This work achieved the highest conversion yield of 10-HOE with the highest substrate concentration, and provides some useful information for the industrial production of 10-HOE. © 2021 Society of Chemical Industry.
This work achieved the highest conversion yield of 10-HOE with the highest substrate concentration, and provides some useful information for the industrial production of 10-HOE. © 2021 Society of Chemical Industry.Although forced displacement may lead to many adverse psychological problems, this experience may also result in positive psychological consequences. Given the increasing disturbance in countries, many people are forcibly displaced, a comprehensive understanding of the posttraumatic growth (PTG) experiences of refugees is warranted. In this study, we examined 12 primary studies exploring PTG among refugees using the qualitative metasynthesis method. Our analysis of the primary studies consisting of 319 adults revealed four themes (a) improved psychologic functioning; (b) enhanced interpersonal relationships; (c) reconstruction of the meaning of life; and (d) positive future direction. Selleck Ulixertinib These findings indicate that no matter how traumatic experiences are painful, people can hold on to life, build a new life, and grow from adversity.The human RecQ helicase BLM is involved in the DNA damage response, DNA metabolism, and genetic stability. Loss of function mutations in BLM cause the genetic instability/cancer predisposition syndrome Bloom syndrome. However, the molecular mechanism underlying the regulation of BLM in cancers remains largely elusive. Here, we demonstrate that the deubiquitinating enzyme USP37 interacts with BLM and that USP37 deubiquitinates and stabilizes BLM, thereby sustaining the DNA damage response (DDR). Mechanistically, DNA double-strand breaks (DSB) promotes ATM phosphorylation of USP37 and enhances the binding between USP37 and BLM. Moreover, knockdown of USP37 increases BLM polyubiquitination, accelerates its proteolysis, and impairs its function in DNA damage response. This leads to enhanced DNA damage and sensitizes breast cancer cells to DNA-damaging agents in both cell culture and in vivo mouse models. Collectively, our results establish a novel molecular mechanism for the USP37-BLM axis in regulating DSB repair with an important role in chemotherapy and radiotherapy response in human cancers.The interaction of transcription factors with their response elements in DNA is emerging as a highly complex process, whose characterization requires measuring the full distribution of binding and dissociation times in a well-controlled assay. Here, we present a single-molecule assay that exploits the thermal fluctuations of a DNA hairpin to detect the association and dissociation of individual, unlabeled transcription factors. We demonstrate this new approach by following the binding of Egr1 to its consensus motif and the three binding sites found in the promoter of the Lhb gene, and find that both association and dissociation are modulated by the 9 bp core motif and the sequences around it. In addition, CpG methylation modulates the dissociation kinetics in a sequence and position-dependent manner, which can both stabilize or destabilize the complex. Together, our findings show how variations in sequence and methylation patterns synergistically extend the spectrum of a protein's binding properties, and demonstrate how the proposed approach can provide new insights on the function of transcription factors.
