bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selected commensals educate the intestinal vascular and immune system for immunocompetence
Authors: Romero Rossana , Zarzycka Agnieszka , Preussner Mathieu , Fischer Florence , Hain Torsten , Herrmann Jan-Paul , Roth Katrin , Keber Corinna U. , Suryamohan Kushal , Raifer Hartmann , Luu Maik , Leister Hanna , Bertrams Wilhelm , Klein Matthias , Shams-Eldin Hosam , Jacob Ralf , Mollenkopf Hans-Joachim , Rajalingam Krishnaraj , Visekruna Alexander , Steinhoff Ulrich 
Published: September 2022

Abstract
Background
The intestinal microbiota fundamentally guides the development of a normal intestinal physiology, the education, and functioning of the mucosal immune system. The Citrobacter rodentium-carrier model in germ-free (GF) mice is suitable to study the influence of selected microbes on an otherwise blunted immune response in the absence of intestinal commensals.

Results
Here, we describe that colonization of adult carrier mice with 14 selected commensal microbes (OMM12 + MC2) was sufficient to reestablish the host immune response to enteric pathogens; this conversion was facilitated by maturation and activation of the intestinal blood vessel system and the step- and timewise stimulation of innate and adaptive immunity. While the immature colon of C. rodentium-infected GF mice did not allow sufficient extravasation of neutrophils into the gut lumen, colonization with OMM12 + MC2 commensals initiated the expansion and activation of the visceral vascular system enabling granulocyte transmigration into the gut lumen for effective pathogen elimination.

Conclusions
Consortium modeling revealed that the addition of two facultative anaerobes to the OMM12 community was essential to further progress the intestinal development. Moreover, this study demonstrates the therapeutic value of a defined consortium to promote intestinal maturation and immunity even in adult organisms.
Empowering local research ethics review of antibacterial mass administration research
Authors: Sewankambo Nelson K. , Kutyabami Paul 
Published: September 2022

Abstract
Background
Recent studies using mass drug administration (MDA) of antibiotics to entire communities have focused global attention on the unique ethical challenges of MDA of antibiotics in research and public health interventions. However, there is no specific guidance for Research Ethics Committees (RECs) or Institutional Review Boards (IRBs) to review such trials. We surveyed the literature to identify the unique ethical challenges and to strengthen the competencies of RECs or IRBs in low- and middle-income countries (LMICs) in their ethical reviews of these trials.

Methods
We employed a desk review. We searched PubMed, Web of Science, and Google Scholar, combining terms for “mass drug administration” with terms for “research ethics committees,” “institutional review boards,” and “ethics.” We reviewed citations of search results to retrieve additional articles. Only articles published and indexed in the above databases up to 6 January 2022 in English were included. Abstracts (without full articles), books and articles that had exclusive veterinary and environmental focus were excluded. We synthesized the literature to identify particularly challenging ethical issues relevant to antibacterial MDA trials in LMICs.

Results
The most challenging ethical issues can be categorised into four broad domains: determining the social value of MDA, assessing risks and benefits, engaging all stakeholders meaningfully, and study design-related ethical challenges. These four domains interact and impact each other. Together, they reveal the need for RECs/IRBs to review MDA studies through a broader lens than that of clinical trials per se. From our findings, we propose a framework to guide the RECs and IRBs in LMICs to perform the initial and continuing review of antibiotic MDA trials. We also recommend strengthening the competencies of LMIC RECs or IRBs through ongoing training and collaboration with RECs or IRBs from high-income countries.

Conclusions
REC/IRB review of research using MDA of antibiotics plays a critical role in assuring the ethical conduct of MDA studies. Local RECs/IRBs should be empowered to review MDA studies comprehensively and competently in order to advance scientific knowledge about MDA and promote improved global health.
Pulsed infrared thermographic study of a Chinese Bronze Lei
Authors: Yang Xue , Chen Beichen , Hu Gangbo , Wang Xiangyu , Fang Wei , Zhang Jianan , Tao Ning , Yuan Guangkuo 
Published: September 2022

Abstract
In this paper, pulsed infrared thermography is applied to the study of a mold casting Chinese bronze lei 罍 dated to the late Shang dynasty (c.a.1250–1050 BC), currently housed in the Capital Normal University Museum. Many spacers and a defective area of this ancient bronze are partly covered with repair material. By analyzing thermographic images using a one-layer thermal diffusion model, it is found that the spacers were specifically made for this bronze. The thickness of the repairing material in the defective area is measured using thermal quadrupole modelling in multi-layer materials. This is the first application of this method to the field of cultural heritage conservation. These results provide a deeper understanding of the manufacturing process of ancient Chinese bronzes from the viewpoint of archaeological research. They also help assess the repair status from the conservation viewpoint.
Combining statistics: the role of phonotactics on cross-situational word learning
Authors: Dal Ben Rodrigo , Souza Débora de Hollanda , Hay Jessica F. 
Published: September 2022

AbstractLanguage learners can rely on phonological and semantic information to learn novel words. Using a cross-situational word learning paradigm, we explored the role of phonotactic probabilities on word learning in ambiguous contexts. Brazilian-Portuguese speaking adults (N = 30) were exposed to two sets of word-object pairs. Words from one set of labels had slightly higher phonotactic probabilities than words from the other set. By tracking co-occurrences of words and objects, participants were able to learn word-object mappings similarly across both sets. Our findings contrast with studies showing a facilitative effect of phonotactic probability on word learning in non-ambiguous contexts.
Innate lymphoid cells in antitumor immunity
Authors: Salomé Bérengère , Jandus Camilla 
Published: September 2022

Abstract
Innate lymphoid cells (ILCs) are the most recently characterized subset of innate lymphocytes. Based on their specific transcriptional regulation, cytokine secretion pattern and effector functions ILCs mirror the different CD4 T helper cell subsets, with the unique attributes of acting locally in early phases of immune responses, in an antigen-independent manner. In this review, we discuss how ILCs have been implicated in tumorigenesis. Their presence might favor or inhibit tumor growth, depending on the cytokines released and the specific tumor microenvironment. As our understanding of ILCs’ contribution to antitumor responses advances, clinical options to target ILCs in antitumor therapies are also emerging.
Evaluation of the expression of NADPH oxidase components during maturation of HL-60 cells to neutrophil lineage
Authors: Hua Jian , Hasebe Takeshi , Someya Akimasa , Nakamura Shinji , Sugimoto Koichi , Nagaoka Isao 
Published: September 2022

Abstract
To understand the expression of NADPH oxidase components during neutrophil maturation, we examined the expression of mRNAs and proteins for NADPH oxidase components, and the superoxide-producing activity using HL-60 cells incubated with dimethyl sulfoxide (DMSO). Northern blot and Western blot analyses revealed that gp91phox, p67phox, and p47phox were expressed after myelocyte stages, whereas p22phox, p40phox, and rac-2 were expressed from the promyelocyte stage. Furthermore, immunocytochemical staining of DMSO-induced HL-60 cells indicated that gp91phox, p67phox, and p47phox were detected only after myelocyte stages (myelocytes, metamyelocytes, band cells, and segmented cells), whereas p22phox, p40phox, and rac-2 were detected from the promyelocyte stage. In addition, nitro blue tetrazolium (NBT) assay showed that superoxide could be produced after myelocyte stages but not produced before promyelocyte stages. Moreover, almost the same results as those with DMSO-induced HL-60 cells were obtained using human bone-marrow cells by immunocytochemical staining and NBT assay, except that p22phox was detected by immunocytochemical staining after myelocyte stages in bone-marrow cells. Together, these observations indicate that all the components for NADPH oxidase are expressed, and the superoxide-producing activity is obtained after myelocyte stages during neutrophil maturation.
Lipopolysaccharide-triggered desensitization of TNF-α mRNA expression involves lack of phosphorylation of IκBα in a murine macrophage-like cell line, P388D1
Authors: Fujihara Mitsuhiro , Wakamoto Shinobu , Ito Takatoshi , Muroi Masashi , Suzuki Tsuneo , Ikeda Hisami , Ikebuchi Kenji 
Published: September 2022

AbstractActivation of nuclear factor κB (NF-κB) is thought to be required for cytokine production by lipopolysaccharide (LPS)-responsive cells. Here, we investigated the contribution of NF-κB in preventing LPS-induced transcription of the tumor necrosis factor α (TNF-α) gene in a murine macrophage cell line, P388D1, when tolerance was induced in the cells with a short exposure to a higher dose of LPS. Electrophoretic mobility shift assays with the κB elements of the murine TNF-α promoter and enhancer revealed that nuclear mobilization of heterodimers of p65/p50, c-rel/p50 and p65/c-rel, and homodimers of p65 was markedly reduced in LPS-tolerant cells, whereas that of p50 homodimers was only slightly increased. Western blot analysis showed that the phosphorylation of Ser32 on IκBα and its transient degradation did not occur in LPS-tolerant cells. These results thus suggest that desensitization of TNF-α gene expression in this LPS-tolerant state is closely associated with down-regulation of transactivating NF-κB and may involve a defect in the LPS-induced IκBα kinase pathway.
Kinins and kinin receptors: importance for the activation of leukocytes
Authors: Böckmann Sabine , Paegelow Inge 
Published: September 2022

Abstract
In this article, we analyzed the role of kinins and kinin receptors with respect to the activation of leukocytes. In these cells, the biological effects of kinin peptides are mediated by kinin receptor subtypes B1, B2, or both, depending on species and cell type. In contrast to the other leukocytes, neutrophils contain the complete system for the synthesis and release of bioactive kinins. Consequently, very high concentrations of these peptides can be reached in the close neighborhood of the kinin receptors, in particular at the site of inflammation. Kinins are responsible for many effects in leukocytes including the release of other inflammatory mediators, such as cytokines, prostaglandins, leukotrienes, and reactive oxygen species. Obviously, the potency of kinins to stimulate leukocytes is dependent on the differentiation and especially on the activation stage of these cells. An upregulation of kinin receptors on neutrophils and macrophages appears to be involved in increasing the sensitivity of these cells to kinins at the site of inflammation.
Modulation of nitric oxide-evoked apoptosis by the p53-downstream target p21WAF1/CIP1
Authors: Yang Fan , von Knethen Andreas , Brüne Bernhard 
Published: September 2022

Abstract
When produced in excess, the inflammatory mediator nitric oxide (NO) attenuates cell-cycle progression at the G1 phase in tight correlation with p21WAF1/CIP1 expression, provokes accumulation of the tumor suppressor p53, and initiates apoptosis/necrosis as judged on cell accumulation in the sub-G1 phase. To verify the role of p21WAF1/CIP1 in modulating cell-cycle arrest vs. apoptosis, we transfected stably antisense p21WAF1/CIP1-encoding plasmids. Following NO exposure, accumulation of p21WAF1/CIP1, but not p53, was largely attenuated in antisense p21WAF1/CIP1 transfectants. Moreover, the G1 cell-cycle arrest was abrogated, and cells were sensitized toward apoptosis compared with parent macrophages. In contrast, antisense elimination of p53 attenuated p53 as well as p21WAF1/CIP1 expression, abolished the G1 cell-cycle arrest, and prevented apoptosis. We conclude that p21WAF1/CIP1 is a downstream target of p53 in macrophages that modulate the sensitivity toward the immune-modulator NO.
The role of architectural transcription factors in cytokine gene transcription
Authors: Shannon M F , Coles L S , Attema J , Diamond P 
Published: September 2022

AbstractThe strict control of cytokine gene transcription is required for the correct regulation of an immune response. Cytokine gene transcription is generally inducible and can also be cell-type specific. Promoter and enhancer regions that control the expression of these genes assemble complex arrays of transcription factors known as enhanceosomes. One important aspect of the organization of these multi-protein complexes is the presence of proteins known as architectural transcription factors. Architectural proteins influence structural aspects of enhanceosomes through protein:DNA as well as protein:protein interactions. The high mobility group I(Y) and the cold shock domain families of architectural proteins have been shown to play roles in cytokine gene transcription and will be discussed here. These families of proteins interact with specific structural features of DNA, modulate transcription factor binding to DNA, and interact directly with other transcription factors. The mechanisms by which they affect inducible cytokine gene transcription will be discussed.
Molecular motors involved in T cell receptor clusterings
Authors: Krawczyk Connie , Penninger Josef M 
Published: September 2022

AbstractEngagement of antigen receptors on T and B cells triggers reorganization of the cytoskeleton and ordered clustering of cell surface receptors. These receptor clusters constitute spatially organized signaling machines and form the immune synapse with antigen-presenting cells. Formation of supramolecular activation clusters appear to be essential to induce functional lymphocyte responses and have been implicated as molecular mechanisms of costimulation. The Vav1-Rho-GTPase-WASP pathway constitutes a molecular motor that relays antigen receptor stimulation to changes in the cytoskeleton and receptor clustering.
Eosinophil recruitment into sites of delayed-type hypersensitivity reactions in mice
Authors: Teixeira Mauro M , Talvani André , Tafuri Wagner L , Lukacs Nicholas W , Hellewell Paul G 
Published: September 2022

AbstractThe selective accumulation of eosinophils in tissue is a characteristic feature of allergic diseases where there is a predominance of lymphocytes expressing a Th2 phenotype. In an attempt to define factors determining specific eosinophil accumulation in vivo, we have used a radiolabeled technique to assess the occurrence and the mechanisms underlying 111In-eosinophil recruitment into Th1- and Th2-predominant, delayed-type hypersensitivity (DTH) reactions. Eosinophils were purified from the blood of IL-5 transgenic mice, labeled with 111In and injected into nontransgenic CBA/Ca mice. Th1- and Th2-predominant, DTH reactions were induced in mice by immunization with methylated bovine serum albumin (MBSA) in Freund's complete adjuvant or with Schistosoma mansoni eggs, respectively. In these animals, 111In-eosinophils were recruited in skin sites in an antigen-, time-, and concentration-dependent manner. Depletion of CD4+ lymphocytes abrogated 111In-eosinophil recruitment in both reactions. Pretreatment of animals with anti-IFN-γ mAb abrogated111In-eosinophil recruitment in MBSA-immunized and -challenged animals, whereas anti-IL-4 inhibited111In-eosinophil recruitment in both models. Local pretreatment with an anti-eotaxin polyclonal antibody inhibited the MBSA and SEA reactions by 51% and 39%, respectively. These results demonstrate that, although eosinophilia is not a feature of Th1-predominant, DTH reactions, these reactions produce the necessary chemoattractants and express the necessary cell adhesion molecules for eosinophil migration. The control of the circulating levels of eosinophils appears to be a most important strategy in determining tissue eosinophilia.
Genetic background of attenuatedSalmonella typhimuriumhas profound influence on infection and cytokine patterns in human dendritic cells
Authors: Dreher Donatus , Kok Menno , Cochand Laurence , Gitahi Kiama Stephen , Gehr Peter , Pechère Jean-Claude , Nicod Laurent Pierre 
Published: September 2022

AbstractSalmonella typhimurium (ST) can cause infection inman, and attenuated strains are under consideration as live vaccinevectors. However, little is known about the interaction of ST withhuman dendritic cells (DC). Here, we compared the consequences ofexposure of human, monocyte-derived DC with different attenuatedstrains of ST. Infection was observed with all four strains tested(wild type, PhoP−, PhoPc, and AroA), but the PhoPc strainwas by far the most efficient. Intracellular persistence of wild typeand PhoP− was longer than that of PhoPc and AroA, both ofwhich were largely eliminated within 24 h. Most DC survivedinfection by the attenuated strains, although apoptosis was observed ina fraction of the exposed cells. All strains induced DC maturation,independent from the extent of infection. Although all strainsstimulated secretion of TNF-α and IL-12 strongly, PhoPc inducedsignificantly less IL-10 than the other three strains and as much as 10times less IL-10 than heat-killed PhoPc, suggesting that this mutantsuppressed the secretion of IL-10 by the DC. These data indicate thatinfectivity, bacterial elimination, and cytokine secretion in human DCare controlled by the genetic background of ST.
Superantigen antagonist blocks Th1 cytokine gene induction and lethal shock
Authors: Arad Gila , Hillman Dalia , Levy Revital , Kaempfer Raymond 
Published: September 2022

AbstractBacterial superantigens trigger an excessive, Th1-cytokine response leading to toxic shock. We designed a peptide antagonist that inhibits SEB-induced expression of human genes for IL-2, IFN-γ, and TNF-β, cytokines that mediate shock. The peptide antagonist shows homology to a β-strand-hinge-α-helix domain that is conserved structurally in superantigens produced by Staphylococcus aureus andStreptococcus pyogenes yet remote from known binding sites for the major histocompatibility class II molecule and T-cell receptor. For Th1-cell activation, superantigens depend on this domain. The peptide protected mice against lethal challenge with SEB or SEA. Moreover, it rescued mice undergoing toxic shock. Surviving mice rapidly developed broad-spectrum, protective immunity, which rendered them resistant to further lethal challenges with different staphylococcal and streptococcal superantigens. Thus, the lethal effect of superantigens, mediated by Th1 cytokines, can be blocked with a peptide antagonist that inhibits their action at the top of the toxicity cascade, before activation of T cells takes place.
Chemokine receptors in human basophils: inducible expression of functional CXCR4
Authors: Iikura Motoyasu , Miyamasu Misato , Yamaguchi Masao , Kawasaki Hiroshi , Matsushima Kouji , Kitaura Motoji , Morita Yutaka , Yoshie Osamu , Yamamoto Kazuhiko , Hirai Koichi 
Published: September 2022

AbstractWe examined the expression profile of chemokine receptors in humanbasophils and their regulation by cytokines. Basophils expressedtranscripts of CC chemokine receptors (CCR)1, CCR2, CCR3, and CCR5 andCXC chemokine receptors (CXCR)1, CXCR2, and CXCR4. In contrast to theother receptors, surface-CXCR4 expression was not detected in fresh-and whole-blood basophils, but it became apparent gradually duringincubation. Among 16 chemokines tested, eotaxin induced the most potentbasophil migration. SDF-1 also induced a strong, migratory responsecomparable with that induced by eotaxin in 24-h, cultured basophils,but it failed to induce degranulation. IL-3 abrogated CXCR4 expressioncompletely, and it only down-regulated CCR2 and CCR3 expressionslightly. IL-5, GM-CSF, and IL-4 also down-regulated CXCR4 expression.Thus, expression of CXCR4 was the most strongly affected by cytokines,and this may represent an alternative mechanism for control ofcell-specific, biological responses to SDF-1.
A cytokine-to-chemokine axis between T lymphocytes and keratinocytes can favor Th1 cell accumulation in chronic inflammatory skin diseases
Authors: Albanesi Cristina , Scarponi Claudia , Sebastiani Silvia , Cavani Andrea , Federici Monica , Sozzani Silvano , Girolomoni Giampiero 
Published: September 2022

AbstractThe recruitment of T cells into the skin is regulated by chemokines released by resident cells. In this study, we found that normal human keratinocytes activated with Th1-derived supernatant (sup) expressed early (6–12 h) IP-10/CXCL10, MCP-1/CCL2, IL-8/CXCL8, and I-309/CCL1 mRNAs and with slower kinetics (24–96 h), RANTES/CCL5 and MDC/CCL22 mRNAs. Upon stimulation with the Th1 sup, keratinocytes secreted high levels of RANTES, IP-10, MCP-1, and IL-8 and moderate levels of I-309 and MDC. Although much less efficiently, Th2 sup could also induce keratinocyte expression of IL-8, IP-10, RANTES, and MCP-1 but not of I-309 and MDC. TARC/CCL17 was not significantly induced by any stimuli. Sup from keratinocytes activated with Th1-derived cytokines elicited a strong migratory response of Th1 cells and a limited migration of Th2 cells, whereas sup from Th2-activated keratinocytes promoted a moderate migration of Th1 and Th2 lymphocytes. Thus, keratinocytes appear considerably more sensitive to Th1- than to Th2-derived lymphokines in terms of chemokine release and can support the preferential accumulation of Th1 lymphocytes in the skin.
Uptake of apoptotic leukocytes by synovial lining macrophages inhibits immune complex–mediated arthritis
Authors: van Lent P L E M , Licht R , Dijkman H , Holthuysen A E M , Berden J H M , van den Berg W B 
Published: September 2022

AbstractPreviously we have shown that synovial lining macrophages (SLMs) determine the onset of experimental immune complex–mediated arthritis (ICA). During joint inflammation, many leukocytes undergo apoptosis, and removal of leukocytes by SLMs may regulate resolution of inflammation. In this study we investigated binding and uptake of apoptotic leukocytes by SLMs and its impact on the onset of murine experimental arthritis. We used an in vitro model to evaluate phagocytosis of apoptotic cells on chemotaxis. Phagocytosis of apoptotic thymocytes resulted in a significant decrease (58%) of chemotactic activity for polymorphonuclear neutrophils (PMNs). If apoptotic cells were injected directly into a normal murine knee joint, SLMs resulted in a prominent uptake of cells. After ICA induction, electron micrographs showed that apoptotic leukocytes were evidently present in SLMs on days 1 and 2. Injection of apoptotic leukocytes into the knee joint 1 h before induction of ICA significantly inhibited PMN infiltration into the knee joint at 24 h (61% decrease). This study indicates that uptake of apoptotic leukocytes by SLM reduces chemotactic activity and inhibits the onset of experimental arthritis. These findings indicate an important mechanism in the resolution of joint inflammation.