bluuebunny/crossref_metadata_2025 huggingface dataset:
In-depth analysis of T cell immunity and antibody responses in heterologous prime-boost-boost vaccine regimens against SARS-CoV-2 and Omicron variant
Authors: Heinen Natalie , Marheinecke Corinna Sophie , Bessen Clara , Blazquez-Navarro Arturo , Roch Toralf , Stervbo Ulrik , Anft Moritz , Plaza-Sirvent Carlos , Busse Sandra , Klöhn Mara , Schrader Jil , Vidal Blanco Elena , Urlaub Doris , Watzl Carsten , Hoffmann Markus , Pöhlmann Stefan , Tenbusch Matthias , Steinmann Eike , Todt Daniel , Hagenbeck Carsten , Zimmer Gert , Schmidt Wolfgang Ekkehard , Quast Daniel Robert , Babel Nina , Schmitz Ingo , Pfänder Stephanie
Published: December 2022

With the emergence of novel Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Variants of Concern (VOCs), vaccination studies that elucidate the efficiency and effectiveness of a vaccination campaign are critical to assess the durability and the protective immunity provided by vaccines. SARS-CoV-2 vaccines have been found to induce robust humoral and cell-mediated immunity in individuals vaccinated with homologous vaccination regimens. Recent studies also suggest improved immune response against SARS-CoV-2 when heterologous vaccination strategies are employed. Yet, few data exist on the extent to which heterologous prime-boost-boost vaccinations with two different vaccine platforms have an impact on the T cell-mediated immune responses with a special emphasis on the currently dominantly circulating Omicron strain. In this study, we collected serum and peripheral blood mononuclear cells (PBMCs) from 57 study participants of median 35-year old’s working in the health care field, who have received different vaccination regimens. Neutralization assays revealed robust but decreased neutralization of Omicron VOC, including BA.1 and BA.4/5, compared to WT SARS-CoV-2 in all vaccine groups and increased WT SARS-CoV-2 binding and neutralizing antibodies titers in homologous mRNA prime-boost-boost study participants. By investigating cytokine production, we found that homologous and heterologous prime-boost-boost-vaccination induces a robust cytokine response of CD4+ and CD8+ T cells. Collectively, our results indicate robust humoral and T cell mediated immunity against Omicron in homologous and heterologous prime-boost-boost vaccinated study participants, which might serve as a guide for policy decisions.
When secretion turns into excretion – the different roles of IgA
Authors: Strugnell Richard A.
Published: December 2022

IgA deficiency is the commonest immunodeficiency affecting up to 1 in 700 individuals. The effects of IgA deficiency are difficult to see in many individuals, are mild in many fewer and severe in fewer still. While monovalent IgA is found in serum, dimeric IgA is secreted through mucosal surfaces where it helps to maintain epithelial homeostasis. Studies with knockout mice have taught us that there are subtle inflammatory consequences of removing secretory IgA (sIgA), and the best explanation for these changes can be related by the loss of the ‘excretory’ immune system. The excretion of antigens is a logical process in regulating the immune system, given the long half-life of complement fixing antibodies. But the function of IgA as an immune or inflammation regulator may go beyond antigen removal.
TRPV4 activation prevents lipopolysaccharide-induced painful bladder hypersensitivity in rats by regulating immune pathways
Authors: Yoshizumi Masaru , Tazawa Naoya , Watanabe Chizuko , Mizoguchi Hirokazu
Published: December 2022

Chronic inflammation in the urinary bladder is a potential risk factor for bladder dysfunction, including interstitial cystitis/bladder pain syndrome (IC/BPS). Although several studies have reported that activation of transient receptor potential vanilloid 4 (TRPV4) contributes to bladder pain and overactive bladder with a cardinal symptom of acute or chronic cystitis, others have reported its involvement in the protective response mediated by lipopolysaccharides (LPS) to secrete anti-inflammatory/pro-resolution cytokines. Therefore, we investigated the potential benefit of an intravesical TRPV4 agonist for painful bladder hypersensitivity in a rat model of LPS-induced cystitis and determined whether its effects modulate the LPS signal for inflammatory reaction, cytokine release, and macrophage phenotype change. Previously, we showed that repeated intravesical instillations of LPS induce long-lasting bladder inflammation, pain, and overactivity in rats. In the present study, concurrent instillation of the selective TRPV4 agonist GSK1016790A (GSK) with LPS into the rat bladder improved LPS-induced bladder inflammation and reduced the number of mast cells. Furthermore, co-instillation of GSK prevented an increase in bladder pain-related behavior and voiding frequency caused by LPS. Cytokine profiling showed that LPS-stimulated inflammatory events, such as the production and secretion of pro-inflammatory cytokines (CXCL1, CXCL5, CXCL9, CXCL10, CCL3, CCL5, CCL20, and CX3CL1), are suppressed by GSK. Furthermore, TRPV4 activation switched LPS-stimulated pro-inflammatory M1-type macrophages to anti-inflammatory M2-type macrophages. These results suggest that TRPV4 activation in the bladder negatively regulates the pro-inflammatory response induced by LPS and prevents bladder hypersensitivity. These TRPV4 functions may be promising therapeutic targets for refractory IC/BPS.
MiR-451a and let-7i-5p loaded extracellular vesicles attenuate heme-induced inflammation in hiPSC-derived endothelial cells
Authors: Thomas Justin J. , Harp Keri Oxendine , Bashi Alaijah , Hood Joshua L. , Botchway Felix , Wilson Michael D. , Thompson Winston E. , Stiles Jonathan K. , Driss Adel
Published: December 2022

Hemolysis is associated with many pathologies, including trauma, sepsis, hemorrhagic stroke, malaria, and genetic disorders such as sickle cell disease (SCD). When hemolysis occurs, free-heme drives vascular inflammation, resulting in oxidative tissue damage and cardiometabolic complications. A better understanding of heme clearance and detoxification is essential to preventing sustained tissue damage. Human induced pluripotent stem cell (hiPSC)-derived endothelial cells (hiPSC-ECs) provide a novel source of patient-specific cells and tissues for disease modeling, drug discovery, and regenerative therapeutics. Here we report the use of hiPSC-ECs to elucidate the role of miR-451a and let-7i-5p-loaded extracellular vesicles (EVs, such as exosomes) in the inflammatory response to free-heme as a model for heme-induced inflammation. We provide evidence of a significant correlation between miR-451a and let-7i-5p-loaded circulating exosomes in plasmodium-infected patients with reported clinical benchmarks of malaria-severity (e.g., Hemoglobin (Hb) levels, white blood cell counts). Additionally, we determined that exposure of Plasmodium falciparum (Pf) parasites to EVs, loaded with either miRNA, significantly reduces their counts in vitro. Using hiPSCs derived from individuals with wild-type Hb (HbAA) or homozygous sickle cell mutated Hb (HbSS) genotypes, we demonstrate that heme-treated hiPSC-ECs secreted inflammatory products (cytokines, chemokines and growth factors) into supporting media at concentrations that were similar to that reported in HbAA and HbSS serum. This inflammatory response was attenuated by exposure with miR-451a or let-7i-5p-loaded EVs. We also found a decrease in transcription of ICAM1 and P-Selectin, as well as the secretion of key inflammatory cytokines (e.g., CXCL10, TNF-α, and IFN-γ). Based on these findings, we propose a model in which increased levels of exosomal miR-451a and let-7i-5p in Plasmodium-infected individuals will attenuate inflammatory responses to free-heme and parasite-derived products. As a result, infected erythrocytes will less likely adhere to the endothelium, sequester in brain micro vessels, and reduce vaso-occlusive crises that exacerbate cerebral malaria.
The role of interferons in ovarian cancer progression: Hinderer or promoter?
Authors: Liu Taiqing , Li Yinqi , Wang Xiaoyu , Yang Xiaodong , Fu Yunhai , Zheng Yeteng , Gong Hanlin , He Zhiyao
Published: December 2022

Ovarian cancer (OC) is a common gynecologic malignancy with poor prognosis and high mortality. Changes in the OC microenvironment are closely related to the genesis, invasion, metastasis, recurrence, and drug-resistance. The OC microenvironment is regulated by Interferons (IFNs) known as a type of important cytokines. IFNs have a bidirectional regulation for OC cells growth and survival. Meanwhile, IFNs positively regulate the recruitment, differentiation and activation of immune cells. This review summarizes the secretion and the role of IFNs. In particular, we mainly elucidate the actions played by IFNs in various types of therapy. IFNs assist radiotherapy, targeted therapy, immunotherapy and biotherapy for OC, except for some IFN pathways that may cause chemo-resistance. In addition, we present some advances in OC treatment with the help of IFN pathways. IFNs have the ability to powerfully modulate the tumor microenvironment and can potentially provide new combination strategies for OC treatment.
Epigenetics and endoplasmic reticulum in podocytopathy during diabetic nephropathy progression
Authors: Wang Xiaokang , Zhao Jingqian , Li Yuanqing , Rao Jiaoyu , Xu Gengrui
Published: December 2022

Proteinuria or nephrotic syndrome are symptoms of podocytopathies, kidney diseases caused by direct or indirect podocyte damage. Human health worldwide is threatened by diabetic nephropathy (DN), the leading cause of end-stage renal disease (ESRD) in the world. DN development and progression are largely dependent on inflammation. The effects of podocyte damage on metabolic disease and inflammatory disorders have been documented. Epigenetic and endoplasmic reticulum (ER) stress are also evident in DN. Targeting inflammation pathway and ER stress in podocytes may be a prospective therapy to prevent the progression of DN. Here, we review the mechanism of epigenetics and ER stress on podocyte inflammation and apoptosis, and discuss the potential amelioration of podocytopathies by regulating epigenetics and ER stress as well as by targeting inflammatory signaling, which provides a theoretical basis for drug development to ameliorate DN.
ALFA-PRF: a novel approach to detect murine perforin release from CTLs into the immune synapse
Authors: Rudd-Schmidt Jesse A. , Laine Romain F. , Noori Tahereh , Brennan Amelia J. , Voskoboinik Ilia
Published: December 2022

When killing through the granule exocytosis pathway, cytotoxic lymphocytes release key effector molecules into the immune synapse, perforin and granzymes, to initiate target cell killing. The pore-forming perforin is essential for the function of cytotoxic lymphocytes, as its pores disrupt the target cell membrane and allow diffusion of pro-apoptotic serine proteases, granzyme, into the target cell, where they initiate various cell death cascades. Unlike human perforin, the detection of its murine counterpart in a live cell system has been problematic due its relatively low expression level and the lack of sensitive antibodies. The lack of a suitable methodology to visualise murine perforin secretion into the synapse hinders the study of the cytotoxic lymphocyte secretory machinery in murine models of human disease. Here, we describe a novel recombinant technology, whereby a short ALFA-tag sequence has been fused with the amino-terminus of a mature murine perforin, and this allowed its detection by the highly specific FluoTag®-X2 anti-ALFA nanobodies using both Total Internal Reflection Fluorescence (TIRF) microscopy of an artificial synapse, and confocal microscopy of the physiological immune synapse with a target cell. This methodology can have broad application in the field of cytotoxic lymphocyte biology and for the many models of human disease.
Resting time after phorbol 12-myristate 13-acetate in THP-1 derived macrophages provides a non-biased model for the study of NLRP3 inflammasome
Authors: Giambelluca Sonia , Ochs Matthias , Lopez-Rodriguez Elena
Published: December 2022

Background

The activation of NLRP3 inflammasome in macrophages has been proven to play a crucial role in the development of cardiovascular diseases. THP-1 monocytes can be differentiated to macrophages by incubation with phorbol-12-myristate 13-acetate (PMA), providing a suitable model forin vitrostudies. However, PMA has been shown to have effects on the levels of IL-1β, the main mediator of NLRP3 inflammasome, while the effects on the other mediators of the inflammasome have not been reported before.

Methods

THP-1 monocytes were incubated without (THP-1), with 5ng/ml PMA for 48h (PMA48h) or with 5ng/ml PMA for 48h plus 24h in fresh medium (PMArest). Morphological changes and the expression of macrophage surface markers (CD14, CD11b, CD36 and CD204) were evaluated by flow cytometry. Changes in intracellular levels of inflammasome components (NLRP3, ASC, pro-caspase-1, pro-IL1β) were analyzed by western blot and release of mature IL-1β in cell supernatant was analyzed by ELISA. ASC speck formation was determined by immunofluorescence.

Results

After 48h incubation with PMA or subsequent rest in fresh medium, cells became adherent, and the differential expression of CD36, CD11b, CD14 and CD204 compared to THP-1 cells confirmed that PMArest resemble macrophages from a molecular point of view. Changes in the levels were detected in PMA48h group for all the NLRP3-related proteins, with increase of NLRP3 and pro-IL-1β and secretion of mature IL-1β. In PMArest, no pro-IL-1β and lower amounts of mature IL-1β were detected. No ASC speck was found in PMA treated groups, but the addition of a second stimulus to PMArest resulted in ASC speck formation, together with IL-1β production, confirming the responsiveness of the model.

Conclusion

Differentiation of THP-1 with 5ng/ml PMA followed by 24h resting period provides a model that morphologically and molecularly resembles macrophages. However, even at low concentrations, PMA induces production of IL-1β. The 24h rest period provides for down-regulation of pro-IL-1β in PMArest group, without affecting its ability to respond to a second stimulus through activation of inflammasome.
Single-cell RNA sequencing to dissect the immunological network of liver fibrosis in Schistosoma japonicum-infected mice
Authors: Zhang Yu , Li Junhui , Li Hao , Jiang Jie , Guo Chen , Zhou Chen , Zhou Zhaoqin , Ming Yingzi
Published: December 2022

Introduction

Liver fibrosis is a poor outcome of patients with schistosomiasis, impacting the quality of life and even survival. Eggs deposited in the liver were the main pathogenic factors of hepatic fibrosis in Schistosomiasis japonica. However, the mechanism of hepatic fibrosis in schistosomiasis remains not well defined and there is no effective measure to prevent and treat schistosome-induced hepatic fibrosis.

Methods

In this study, we applied single-cell sequencing to primarily explore the mechanism of hepatic fibrosis in murine schistosomiasis japonica (n=1) and normal mouse was served as control (n=1).

Results

A total of 10,403 cells were included in our analysis and grouped into 18 major cell clusters. Th2 cells and NKT cells were obviously increased and there was a close communication between NKT cells and FASLG signaling pathway. Flow cytometry analysis indicated that the expression of Fasl in NKT cells, CD8+ T cell and NK cell were higher in SJ groups. Arg1, Retnla and Chil3, marker genes of alternatively activated macrophages (M2), were mainly expressed in mononuclear phagocyte(1) (MP(1)), suggesting that Kupffer cells might undergo M2-like polarization in fibrotic liver of schistosomiasis. CXCL and CCL signaling pathway analysis with CellChat showed that Cxcl16-Cxcr6, Ccl6-Ccr2 and Ccl5-Ccr5 were the most dominant L−R and there were close interactions between T cells and MPs.

Conclusion

Our research profiled a preliminary immunological network of hepatic fibrosis in murine schistosomiasis japonica, which might contribute to a better understanding of the mechanisms of liver fibrosis in schistosomiasis. NKT cells and CXCL and CCL signaling pathway such as Cxcl16-Cxcr6, Ccl6-Ccr2 and Ccl5-Ccr5 might be potential targets to alleviate hepatic fibrosis of schistosomiasis.
The morphologies of twins in tetragonal ferroelectrics
Authors: He Ningbo , Li Cuiping , Lei Chihou , Liu Yunya
Published: December 2022

Twins, as a special structure, have been observed in a small number of experiments on ferroelectrics. A good understanding of the morphologies of twins is very important for twin engineering applications in ferroelectric materials. In this work, the morphologies of twins in tetragonal ferroelectrics are investigated using the compatibility analysis of the transformation strains and spontaneous polarization and the energetic analysis. The tetragonal BaTiO3 single crystal is chosen as an example for the material system. The results show that the lamellar twin structures with 111 as the twin plane have been identified by both compatibility analysis and energetic analysis, which is consistent with the experimental observations. In addition to 111 twin structures, 12¯1 and 21¯5 twin structures can also appear in tetragonal ferroelectrics. Furthermore, stable state uncharged twin boundaries and metastable charged twin boundaries are distinguished by energetic analysis, where the spontaneous polarization is compatible across the uncharged twin boundaries, while it is not compatible across the charged twin boundaries. The results predicted by the compatibility analysis and energetic analysis are consistent, thus providing a pathway for understanding the morphologies of twins.
Development of radiopharmaceuticals for targeted alpha therapy: Where do we stand?
Authors: Pallares Roger M. , Abergel Rebecca J.
Published: December 2022

Targeted alpha therapy is an oncological treatment, where cytotoxic doses of alpha radiation are locally delivered to tumor cells, while the surrounding healthy tissue is minimally affected. This therapeutic strategy relies on radiopharmaceuticals made of medically relevant radionuclides chelated by ligands, and conjugated to targeting vectors, which promote the drug accumulation in tumor sites. This review discusses the state-of-the-art in the development of radiopharmaceuticals for targeted alpha therapy, breaking down their key structural components, such as radioisotope, targeting vector, and delivery formulation, and analyzing their pros and cons. Moreover, we discuss current drawbacks that are holding back targeted alpha therapy in the clinic, and identify ongoing strategies in field to overcome those issues, including radioisotope encapsulation in nanoformulations to prevent the release of the daughters. Lastly, we critically discuss potential opportunities the field holds, which may contribute to targeted alpha therapy becoming a gold standard treatment in oncology in the future.
Extracellular matrix and dermal nerve growth factor dysregulation in prurigo nodularis compared to atopic dermatitis
Authors: Deng Junwen , Parthasarathy Varsha , Marani Melika , Bordeaux Zachary , Lee Kevin , Trinh Chi , Cornman Hannah L. , Kambala Anusha , Pritchard Thomas , Chen Shihua , Sutaria Nishadh , Oladipo Olusola O. , Kwatra Madan M. , Alphonse Martin P. , Kwatra Shawn G.
Published: December 2022

Prurigo nodularis (PN) is a chronic, pruritic, inflammatory skin disease characterized by hyperkeratotic nodules on the trunk and extremities. While there is growing research on the immunological basis of PN, the neuropathic and structural components of PN lesions are unknown. This study examines the inflammatory, neuropathic, and structural pathways in PN compared to atopic dermatitis (AD) using RNA-sequencing of the lesional and non-lesional skin tissue of PN and AD patients, as well as immunohistochemistry analysis of nerve growth factor (NGF), a neurotrophic factor that regulates nerve development. Transcriptomic analysis of skin biopsies revealed that compared to lesional AD skin, lesional PN skin had significantly increased expression of NGF, matrix metalloproteinases, OSM, MCEMP1, IL1α, IL1β, CXCL2, CXCL5, CXCL8, and insulin-like growth factors in PN compared to AD, and decreased expression of CCL13, CCL26, EPHB1, and collagens (COL4/6). Gene set enrichment analysis demonstrated higher enrichment of keratinization, cornified envelope, myelin sheath, TGF-beta signaling, extracellular matrix disassembly, metalloendopeptidase activity, and neurotrophin-TRK receptor signaling pathways in PN. On immunohistochemistry, PN lesions demonstrated higher dermal NGF expression compared to AD. We present novel findings demonstrating increased neurotrophic and extracellular matrix remodeling signatures in PN compared to AD, possibly explaining the morphological differences in their lesions. These signatures may therefore be important components of the PN pathogenesis and may serve as therapeutic targets.
The role of the gut microbiome in the intergenerational transmission of the obesity phenotype: A narrative review
Authors: Tang Mabel , Marroquin Elisa
Published: December 2022

Obesity is considered an epidemic by the World Health Organization. In particular, maternal obesity can affect the development of obesity and other related metabolic disorders in infants. Recently, both animal and human studies have pointed to the importance of the gut microbiome in facilitating the transmission of the obesity phenotype from mother to offspring. The gut microbiome changes significantly during the progression of pregnancy, and the microbiota of the amniotic fluid and placenta have recently been shown to colonize the infant gutin utero. Microbial composition, diversity, and richness are significantly altered by maternal obesity, which in turn affects the infant’s acquisition of the gut microbiome and their risk to develop metabolic disorders. C-section has also been shown to affect the colonization of the infant gut and offspring metabolic and immune health. This narrative review seeks to discuss the role of the gut microbiome in the transmission of the obesity phenotype from mother to child, as well as how birth delivery, breastfeeding, and probiotic interventions may modulate this relationship.
Canakinumab as first-line biological therapy in Still’s disease and differences between the systemic and the chronic-articular courses: Real-life experience from the international AIDA registry
Authors: Vitale Antonio , Caggiano Valeria , Maggio Maria Cristina , Lopalco Giuseppe , Emmi Giacomo , Sota Jurgen , La Torre Francesco , Ruscitti Piero , Bartoloni Elena , Conti Giovanni , Fabiani Claudia , Mattioli Irene , Gaggiano Carla , Cardinale Fabio , Dagna Lorenzo , Campochiaro Corrado , Giacomelli Roberto , Balistreri Alberto , Laskari Katerina , Tufan Abdurrahman , Ragab Gaafar , Almaghlouth Ibrahim A. , Więsik-Szewczyk Ewa , Pereira Rosa Maria , Frediani Bruno , Iannone Florenzo , Sfikakis Petros P. , Cantarini Luca
Published: December 2022

Objective

Interleukin (IL)-1 inhibitors are largely employed in patients with Still’s disease; in cases with refractory arthritis, IL-6 inhibitors have shown to be effective on articular inflammatory involvement. The aim of the present study is to assess any difference in the effectiveness of the IL-1β antagonist canakinumab prescribed as first-line biologic agent between the systemic and the chronic-articular Still’s disease.

Methods

Data were drawn from the retrospective phase of the AutoInflammatory Disease Alliance (AIDA) international registry dedicated to Still’s disease. Patients with Still’s disease classified according to internationally accepted criteria (Yamaguchi criteria and/or Fautrel criteria) and treated with canakinumab as first-line biologic agent were enrolled.

Results

A total of 26 patients (17 females, 9 males; 18 patients developing Still’s disease after the age of 16 years) were enrolled; 16 (61.5%) patients suffered from the systemic pattern of the disease; 10 (38.5%) patients suffered from the chronic-articular type. No differences were observed between the systemic and the chronic-articular Still’s disease in the frequency of complete response, of flares after the start of canakinumab (p = 0.701) and in the persistence in therapy (p = 0.62). No statistical differences were observed between the two groups after 3 months, 12 months and at the last assessment in the decrease of: the systemic activity score (p = 0.06, p = 0.17, p = 0.17, respectively); the disease activity score on 28 joints (p = 0.54, p = 0.77, p = 0.98, respectively); the glucocorticoid dosage (p = 0.15, p = 0.50, and p = 0.50, respectively); the use of concomitant disease modifying anti-rheumatic drugs (p = 0.10, p = 1.00, and p = 1.00, respectively). No statistically significant differences were observed in the decrease of erythrocyte sedimentation rate (p = 0.34), C reactive protein (p = 0.48), and serum ferritin levels (p = 0.34) after the start of canakinumab.

Conclusion

Canakinumab used for Still’s disease has been effective in controlling both clinical and laboratory manifestations disregarding the type of disease course when used as first-line biotechnological agent. These excellent results might have been further enhanced by the early start of IL-1 inhibition.
Massively parallel sequencing of endometrial lavage specimens for the detection of cancer-associated mutations in atypical and non-atypical endometrial hyperplasia
Authors: Weng Cindy Hsuan , Wu Kai-Yun , Wang Chin-Jung , Huang Huei-Jean , Tsai Chia-Lung , Lin Chiao-Yun , Ro Aileen , Lai Chyong-Huey , Chao An-Shine , Wu Ren-Chin , Chao Angel
Published: December 2022

Background

Endometrial hyperplasia (EH), particularly with atypia, is considered an antecedent of endometrial adenocarcinoma. In this study, we aimed to apply massively parallel sequencing of endometrial lavage specimens for the detection of cancer-associated mutations in atypical (AEH) and non-atypical endometrial hyperplasia (NEH). The identified alterations were compared with those detected in tissue samples.

Materials and methods

Endometrial lavage specimens and parallel biopsy samples (n = 11 for AEH and n = 9 for NEH) were obtained from 18 women (9 with AEH and 9 with NEH) who received an office hysteroscopy for suspected endometrial lesions. All samples were tested for somatic mutations in hotspot regions of 72 cancer-associated genes by massively parallel sequencing.

Results

On analyzing sequencing data, the presence of at least one cancer-associated gene mutation was identified in 72.7 and 44.4% of endometrial lavage specimens obtained from women with AEH and NEH, respectively (p = 0.362, 95% confidence interval = 0.72-3.70). The concordance rates between mutations identified in endometrial lavage specimens and endometrial biopsies were 54.5 and 0% from women with AEH and NEH, respectively (p = 0.014). A patient with NEH harbored mutations in endometrial lavage with the same mutations found in the tissue specimen at low allele frequency below detection cutoff, raising the suspicion of missed focal atypia.

Conclusion

Endometrial hyperplasia is characterized by a high burden of cancer-associated mutations, particularly in the presence of atypia. Our study, albeit performed with a relatively small number of samples, indicates that their detection by massively parallel sequencing of endometrial lavage is feasible. Our findings may allow tailoring of endometrial biopsies to the individual risk of AEH; additionally, they can pave the way toward less invasive surveillance protocols in patients with known EH.
Bortezomib is an effective enhancer for chemical probe-dependent superoxide detection
Authors: Matsumoto Misaki , Sawada Hikari , Iwata Kazumi , Ibi Masakazu , Asaoka Nozomi , Katsuyama Masato , Shintani-Ishida Kaori , Ikegaya Hiroshi , Takegami Shigehiko , Umemura Atsushi , Yabe-Nishimura Chihiro
Published: December 2022

Various chemical probes for the detection of reactive oxygen species have been developed to examine oxidative stress associated with different pathologies. L-012, a luminol-based chemiluminescent probe, is widely used to detect extracellular superoxide because of its high sensitivity. We herein demonstrated that the co-application of the peptide boronic acid proteasome inhibitor, bortezomib, with L-012 significantly increased its luminescence without affecting the background. More than a 5-fold increase was detected in the total luminescence of L-012 in both NADPH oxidase-expressing cells and the xanthine oxidase-dependent cell-free superoxide generation system, but not in their background. Therefore, bortezomib increased the signal-to-background ratio and improved the detection of low levels of superoxide. The application of MLN2238, another peptide boronic acid proteasome inhibitor, also enhanced the luminescence of L-012. In contrast, carfilzomib, an epoxyketone proteasome inhibitor, did not increase luminescence, suggesting that the effects of bortezomib depend on the chemical structure of the peptide boronic acid, but not on its pharmacological effects. Bortezomib-induced enhancements appeared to be specific to the detection of superoxide because the detection of H2O2 by Amplex Red/HRP was not affected by the application of bortezomib. In the quantitative detection of the superoxide-specific oxidative product 2-hydroxyethidium (2-OH-E+), the application of bortezomib resulted in a 2-fold increase in the level of 2-OH-E+. Therefore, bortezomib sensitizes the detection of superoxide in both cell-based and cell-free systems, highlighting a novel feature of compounds containing the peptide boronic acid as powerful enhancers for the detection of superoxide.
A CFD study on the interplay of torsion and vortex guidance by the mitral valve on the left ventricular wash-out making use of overset meshes (Chimera technique)
Authors: Canè Federico , Delcour Lucas , Luigi Redaelli Alberto Cesare , Segers Patrick , Degroote Joris
Published: December 2022

Cardiovascular disease often occurs with silent and gradual alterations of cardiac blood flow that can lead to the onset of chronic pathological conditions. Image-based patient-specific Computational Fluid Dynamics (CFD) models allow for an extensive quantification of the flow field beyond the direct capabilities of medical imaging techniques that could support the clinicians in the early diagnosis, follow-up, and treatment planning of patients. Nonetheless, the large and impulsive kinematics of the left ventricle (LV) and the mitral valve (MV) pose relevant modeling challenges. Arbitrary Lagrangian-Eulerian (ALE) based computational fluid dynamics (CFD) methods struggle with the complex 3D mesh handling of rapidly moving valve leaflets within the left ventricle (LV). We, therefore, developed a Chimera-based (overset meshing) method to build a patient-specific 3D CFD model of the beating LV which includes a patient-inspired kinematic model of the mitral valve (LVMV). Simulations were performed with and without torsion. In addition, to evaluate how the intracardiac LV flow is impacted by the MV leaflet kinematics, a third version of the model without the MV was generated (LV with torsion). For all model versions, six cardiac cycles were simulated. All simulations demonstrated cycle-to-cycle variations that persisted after six cycles but were albeit marginal in terms of the magnitude of standard deviation of velocity and vorticity which may be related to the dissipative nature of the numerical scheme used. The MV was found to have a crucial role in the development of the intraventricular flow by enhancing the direct flow, the apical washout, and the propagation of the inlet jet towards the apical region. Consequently, the MV is an essential feature in the patient-specific CFD modeling of the LV. The impact of torsion was marginal on velocity, vorticity, wall shear stress, and energy loss, whereas it resulted to be significant in the evaluation of particle residence times. Therefore, including torsion could be considered in patient-specific CFD models of the LV, particularly when aiming to study stasis and residence time. We conclude that, despite some technical limitations encountered, the Chimera technique is a promising alternative for ALE methods for 3D CFD models of the heart that include the motion of valve leaflets.
Biogeochemical impacts of fish farming on coastal sediments: Insights into the functional role of cable bacteria
Authors: Vasquez-Cardenas Diana , Hidalgo-Martinez Silvia , Hulst Lucas , Thorleifsdottir Thorgerdur , Helgason Gudmundur Vidir , Eiriksson Thorleifur , Geelhoed Jeanine S. , Agustsson Thorleifur , Moodley Leon , Meysman Filip J. R.
Published: December 2022

Fish farming in sea cages is a growing component of the global food industry. A prominent ecosystem impact of this industry is the increase in the downward flux of organic matter, which stimulates anaerobic mineralization and sulfide production in underlying sediments. When free sulfide is released to the overlying water, this can have a toxic effect on local marine ecosystems. The microbially-mediated process of sulfide oxidation has the potential to be an important natural mitigation and prevention strategy that has not been studied in fish farm sediments. We examined the microbial community composition (DNA-based 16S rRNA gene) underneath two active fish farms on the Southwestern coast of Iceland and performed laboratory incubations of resident sediment. Field observations confirmed the strong geochemical impact of fish farming on the sediment (up to 150 m away from cages). Sulfide accumulation was evidenced under the cages congruent with a higher supply of degradable organic matter from the cages. Phylogenetically diverse microbes capable of sulfide detoxification were present in the field sediment as well as in lab incubations, including cable bacteria (Candidatus Electrothrix), which display a unique metabolism based on long-distance electron transport. Microsensor profiling revealed that the activity of cable bacteria did not exert a dominant impact on the geochemistry of fish farm sediment at the time of sampling. However, laboratory incubations that mimic the recovery process during fallowing, revealed successful enrichment of cable bacteria within weeks, with concomitant high sulfur-oxidizing activity. Overall our results give insight into the role of microbially-mediated sulfide detoxification in aquaculture impacted sediments.
Microbial DNA extraction of high-host content and low biomass samples: Optimized protocol for nasopharynx metagenomic studies
Authors: Rajar Polona , Dhariwal Achal , Salvadori Gabriela , Junges Roger , Åmdal Heidi Aarø , Berild Dag , Fugelseth Drude , Saugstad Ola Didrik , Lausten-Thomsen Ulrik , Greisen Gorm , Haaland Kirsti , Petersen Fernanda Cristina
Published: December 2022

Introduction

Low microbial biomass and high human DNA content in nasopharyngeal aspirate samples hinder comprehensive characterization of microbiota and resistome. We obtained samples from premature infants, a group with increased risk of developing respiratory disorders and infections, and consequently frequent exposure to antibiotics. Our aim was to devise an optimal protocol for handling nasopharyngeal aspirate samples from premature infants, focusing on host DNA depletion and microbiome and resistome characterization.

Methods

Three depletion and three DNA extraction protocols were compared, using RT-PCR and whole metagenome sequencing to determine the efficiency of human DNA removal, taxonomic profiling and assignment of antibiotic resistance genes. Protocols were tested using mock communities, as well as pooled and individual patient samples.

Results

The only extraction protocol to retrieve the expected DNA yield from mock community samples was based on a lytic method to improve Gram positive recovery (MasterPure™). Host DNA content in non-depleted aliquots from pooled patient samples was 99%. Only samples depleted with MolYsis™ showed satisfactory, but varied reduction in host DNA content, in both pooled and individual patient samples, allowing for microbiome and resistome characterisation (host DNA content from 15% to 98%). Other depletion protocols either retrieved too low total DNA yields, preventing further analysis, or failed to reduce host DNA content. By using Mol_MasterPure protocol on aliquots from pooled patient samples, we increased the number of bacterial reads by 7.6 to 1,725.8-fold compared to non-depleted reference samples. PCR results were indicative of achieved microbial enrichment. Individual patient samples processed with Mol_MasterPure protocol varied greatly in total DNA yield, host DNA content (from 40% to 98%), species and antibiotic resistance gene richness.

Discussion

Despite high human DNA and low microbial biomass content in nasopharynx aspirates of preterm infants, we were able to reduce host DNA content to levels compatible with downstream shotgun metagenomic analysis, including bacterial species identification and coverage of antibiotic resistance genes. Whole metagenomic sequencing of microbes colonizing the nasopharynx may contribute to explaining the possible role of airway microbiota in respiratory conditions and reveal carriage of antibiotic resistance genes.
Harnessing the genomic diversity of Pseudomonas strains against lettuce bacterial pathogens
Authors: Zboralski Antoine , Biessy Adrien , Ciotola Marie , Cadieux Mélanie , Albert Daphné , Blom Jochen , Filion Martin
Published: December 2022

Lettuce is a major vegetable crop worldwide that is affected by numerous bacterial pathogens, including Xanthomonas hortorum pv. vitians, Pseudomonas cichorii, and Pectobacterium carotovorum. Control methods are scarce and not always effective. To develop new and sustainable approaches to contain these pathogens, we screened more than 1,200 plant-associated Pseudomonas strains retrieved from agricultural soils for their in vitro antagonistic capabilities against the three bacterial pathogens under study. Thirty-five Pseudomonas strains significantly inhibited some or all three pathogens. Their genomes were fully sequenced and annotated. These strains belong to the P. fluorescens and P. putida phylogenomic groups and are distributed in at least 27 species, including 15 validly described species. They harbor numerous genes and clusters of genes known to be involved in plant-bacteria interactions, microbial competition, and biocontrol. Strains in the P. putida group displayed on average better inhibition abilities than strains in the P. fluorescens group. They carry genes and biosynthetic clusters mostly absent in the latter strains that are involved in the production of secondary metabolites such as 7-hydroxytropolone, putisolvins, pyochelin, and xantholysin-like and pseudomonine-like compounds. The presence of genes involved in the biosynthesis of type VI secretion systems, tailocins, and hydrogen cyanide also positively correlated with the strains’ overall inhibition abilities observed against the three pathogens. These results show promise for the development of biocontrol products against lettuce bacterial pathogens, provide insights on some of the potential biocontrol mechanisms involved, and contribute to public Pseudomonas genome databases, including quality genome sequences on some poorly represented species.
Populus root exudates are associated with rhizosphere microbial communities and symbiotic patterns
Authors: Li Mengjie , Song Zhen , Li Zhanbiao , Qiao Rongye , Zhang Pingdong , Ding Changjun , Xie Jianbo , Chen Yinglong , Guo Hui
Published: December 2022

Introduction

Microbial communities in the plant rhizosphere are critical for nutrient cycling and ecosystem stability. However, how root exudates and soil physicochemical characteristics affect microbial community composition in Populus rhizosphere is not well understood.

Methods

This study measured soil physiochemistry properties and root exudates in a representative forest consists of four Populus species. The composition of rhizosphere bacterial and fungal communities was determined by metabolomics and high-throughput sequencing.

Results

Luvangetin, salicylic acid, gentisic acid, oleuropein, strigol, chrysin, and linoleic acid were the differential root exudates extracted in the rhizosphere of four Populus species, which explained 48.40, 82.80, 48.73, and 59.64% of the variance for the dominant and key bacterial or fungal communities, respectively. Data showed that differential root exudates were the main drivers of the changes in the rhizosphere microbial communities. Nitrosospira, Microvirga, Trichoderma, Cortinarius, and Beauveria were the keystone taxa in the rhizosphere microbial communities, and are thus important for maintaining a stable Populus microbial rhizosphere. The differential root exudates had strong impact on key bacteria than dominant bacteria, key fungi, and dominant fungi. Moreover, strigol had positively effects with bacteria, whereas phenolic compounds and chrysin were negatively correlated with rhizosphere microorganisms. The assembly process of the community structure (keystone taxa and bacterial dominant taxa) was mostly determined by stochastic processes.

Discussion

This study showed the association of rhizosphere microorganisms (dominant and keystone taxa) with differential root exudates in the rhizosphere of Populus plants, and revealed the assembly process of the dominant and keystone taxa. It provides a theoretical basis for the identification and utilization of beneficial microorganisms in Populus rhizosphere.
Microbial diversity gradients in the geothermal mud volcano underlying the hypersaline Urania Basin
Authors: Lazar Cassandre Sara , Schmidt Frauke , Elvert Marcus , Heuer Verena B. , Hinrichs Kai-Uwe , Teske Andreas P.
Published: December 2022

Mud volcanoes transport deep fluidized sediment and their microbial communities and thus provide a window into the deep biosphere. However, mud volcanoes are commonly sampled at the surface and not probed at greater depths, with the consequence that their internal geochemistry and microbiology remain hidden from view. Urania Basin, a hypersaline seafloor basin in the Mediterranean, harbors a mud volcano that erupts fluidized mud into the brine. The vertical mud pipe was amenable to shipboard Niskin bottle and multicorer sampling and provided an opportunity to investigate the downward sequence of bacterial and archaeal communities of the Urania Basin brine, fluid mud layers and consolidated subsurface sediments using 16S rRNA gene sequencing. These microbial communities show characteristic, habitat-related trends as they change throughout the sample series, from extremely halophilic bacteria (KB1) and archaea (Halodesulfoarchaeumspp.) in the brine, toward moderately halophilic and thermophilic endospore-forming bacteria and uncultured archaeal lineages in the mud fluid, and finally ending in aromatics-oxidizing bacteria, uncultured spore formers, and heterotrophic subsurface archaea (Thermoplasmatales, Bathyarchaeota, and Lokiarcheota) in the deep subsurface sediment at the bottom of the mud volcano. Since these bacterial and archaeal lineages are mostly anaerobic heterotrophic fermenters, the microbial ecosystem in the brine and fluidized mud functions as a layered fermenter for the degradation of sedimentary biomass and hydrocarbons. By spreading spore-forming, thermophilic Firmicutes during eruptions, the Urania Basin mud volcano likely functions as a source of endospores that occur widely in cold seafloor sediments.
High fiber diet attenuate the inflammation and adverse remodeling of myocardial infarction via modulation of gut microbiota and metabolites
Authors: Zhao Jinxuan , Cheng Wei , Lu He , Shan Anqi , Zhang Qi , Sun Xuan , Kang Lina , Xie Jun , Xu Biao
Published: December 2022

Introduction

High intake of dietary fiber is associated with lower incidence of cardiovascular diseases. Dietary fiber, functions as a prebiotic, has a significant impact on intestinal bacteria composition and diversity. The intestinal flora and metabolites generated by fermentation of dietary fiber not only affect the health of intestine but also play a role in many extra-intestinal diseases, such as obesity, diabetes and atherosclerosis. However, the role and the mechanism by which a high fiber diet contributes to the development of myocardial infarction is still unclear.

Methods and results

Here we used an in vivo mouse model to investigate whether dietary fiber intake could protect against myocardial infarction. Our study demonstrated high fiber diet significantly improved cardiac function, reduced infarct size and prevented adverse remodeling following myocardial infarction. The protective effects of high fiber diet had a strong relation with its attenuation of inflammation. Moreover, we observed that high fiber diet could modulate the composition of intestinal flora and differentially impacted metabolites production, including the biosynthesis of bile acids and linoleic acid metabolism.

Conclusion

Overall, the findings of this study provided mechanistic insights into the curative effect of dietary fiber on myocardial infarction with a specific emphasis on the potential role of microbiota-metabolism-immunity interactions.
Deep learning strategies for addressing issues with small datasets in 2D materials research: Microbial Corrosion
Authors: Allen Cody , Aryal Shiva , Do Tuyen , Gautum Rishav , Hasan Md Mahmudul , Jasthi Bharat K. , Gnimpieba Etienne , Gadhamshetty Venkataramana
Published: December 2022

Protective coatings based on two dimensional materials such as graphene have gained traction for diverse applications. Their impermeability, inertness, excellent bonding with metals, and amenability to functionalization renders them as promising coatings for both abiotic and microbiologically influenced corrosion (MIC). Owing to the success of graphene coatings, the whole family of 2D materials, including hexagonal boron nitride and molybdenum disulphide are being screened to obtain other promising coatings. AI-based data-driven models can accelerate virtual screening of 2D coatings with desirable physical and chemical properties. However, lack of large experimental datasets renders training of classifiers difficult and often results in over-fitting. Generate large datasets for MIC resistance of 2D coatings is both complex and laborious. Deep learning data augmentation methods can alleviate this issue by generating synthetic electrochemical data that resembles the training data classes. Here, we investigated two different deep generative models, namely variation autoencoder (VAE) and generative adversarial network (GAN) for generating synthetic data for expanding small experimental datasets. Our model experimental system included few layered graphene over copper surfaces. The synthetic data generated using GAN displayed a greater neural network system performance (83-85% accuracy) than VAE generated synthetic data (78-80% accuracy). However, VAE data performed better (90% accuracy) than GAN data (84%-85% accuracy) when using XGBoost. Finally, we show that synthetic data based on VAE and GAN models can drive machine learning models for developing MIC resistant 2D coatings.