bluuebunny/crossref_metadata_2025 huggingface dataset:
Natural and artificial sources of genetic variation used in crop breeding: A baseline comparator for genome editing
Authors: Martínez-Fortún Jorge , Phillips Dylan W. , Jones Huw D.
Published: August 2022

Traditional breeding has successfully selected beneficial traits for food, feed, and fibre crops over the last several thousand years. The last century has seen significant technological advancements particularly in marker assisted selection and the generation of induced genetic variation, including over the last few decades, through mutation breeding, genetic modification, and genome editing. While regulatory frameworks for traditional varietal development and for genetic modification with transgenes are broadly established, those for genome editing are lacking or are still evolving in many regions. In particular, the lack of “foreign” recombinant DNA in genome edited plants and that the resulting SNPs or INDELs are indistinguishable from those seen in traditional breeding has challenged development of new legislation. Where products of genome editing and other novel breeding technologies possess no transgenes and could have been generated via traditional methods, we argue that it is logical and proportionate to apply equivalent legislative oversight that already exists for traditional breeding and novel foods. This review analyses the types and the scale of spontaneous and induced genetic variation that can be selected during traditional plant breeding activities. It provides a base line from which to judge whether genetic changes brought about by techniques of genome editing or other reverse genetic methods are indeed comparable to those routinely found using traditional methods of plant breeding.
Differential gene expression and identification of growth-related genes in the pituitary gland of South African goats
Authors: Ncube Keabetswe T. , Dzomba Edgar F. , Rosen Ben D. , Schroeder Stephen G. , Van Tassell Curt P. , Muchadeyi Farai. C.
Published: August 2022

Growth and carcass quality are economically important traits in goat production. This study investigated differentially expressed genes from the caprine pituitary gland transcriptome of South African indigenous goat breeds of varying growth performances and carcass quality parameters. Tissues were harvested from the pituitary gland of three South African Boer goats and three village ecotype goats all raised under similar conditions simulating intensive commercial production systems. Three additional tissues were harvested from village ecotype goats that were raised extensively on village farms. Between breed differences were investigated by comparing differential gene expression among three South African Boer and three village goats that were both raised under intensive commercial production system at a research farm. Within-breed differences were investigated by comparing differential gene expression among three village goats raised under extensive conditions (on-farm in Pella, S.A. village farming community) and three village goats raised under intensive commercial production system (at ARC research farm in Pretoria, South Africa. Total RNA was isolated from the pituitary gland of 36-week-old animals (n = 9) and sequenced individually in triplicates. An average of 28,298,512 trimmed, and quality-controlled reads/animal were mapped to the goat genome (Capra_hircus.ARS1.94) using HiSat2 software. Transcript assembly and quantification yielded 104 differentially expressed genes for village goats raised under extensive system and 62 for village goats raised under the intensive production system at the false discovery rate (FRD) of ≤0.05 and a fold change of ≥2. Growth-related genes such as POU3F4 and TSHZ1 were highly expressed within breeds raised under both production systems. Conversely, growth-related genes such as FGFR2 and SMPX genes were highly expressed between breeds raised under similar production systems. Ballgown analysis revealed a high expression of GH1 and IGF1 in the intensively raised compared to extensively raised goats. Both genes were also highly expressed in the village goats when compared to the Boer. The differential gene expression data provided insights into genes and molecular mechanisms associated with growth and growth development in goats.
Associations of cognitive impairment in patients with schizophrenia with genetic features and with schizophrenia-related structural and functional brain changes
Authors: Zhuo Chuanjun , Tian Hongjun , Chen Jiayue , Li Qianchen , Yang Lei , Zhang Qiuyu , Chen Guangdong , Cheng Langlang , Zhou Chunhua , Song Xueqin
Published: August 2022

Cognitive impairment is highly prevalent in patients with major psychiatric disorders (MPDs), including schizophrenia (SCZ), bipolar disorder, major depressive disorder, in whom it can be highly disruptive to community functioning and worsen prognosis. Previously, genetic factors and cognitive impairments in MPD patients have been examined mostly in isolated circuits rather than in the whole brain. In the present study, genetic, neuroimaging, and psychometric approaches were combined to investigate the relationship among genetic factors, alterations throughout the brain, and cognitive impairments in a large cohort of patients diagnosed with SCZ, with a reference healthy control (HC) group. Single nucleotide polymorphisms (SNPs) in SCZ-risk genes were found to be strongly related to cognitive impairments as well as to gray matter volume (GMV) and functional connectivity (FC) alterations in the SCZ group. Annotating 136 high-ranking SNPs revealed 65 affected genes (including PPP1R16B, GBBR2, PDE4B, CANCNA1C, SLC12AB, SATB2, MAG12, and SATB2). Only one, a PDE4B SNP (rs1006737), correlated with GMV (r = 0:19 p = 0.015) and FC (r = 0.21, p = 0.0074) in SCZ patients. GMV and FC alterations correlated with one another broadly across brain regions. Moreover, the present data demonstrate three-way SNP-FC-GMV associations in patients with SCZ, thus providing clues regarding potential genetic bases of cognition impairments in SCZ. SNP-FC-GMV relationships correlated with visual learning and reasoning dimensions of cognition. These data provide evidence that SCZ-related cognitive impairments may reflect genetically underlain whole-brain structural and functional alterations.
Comprehensive analysis for clarifying transcriptomics landscapes of spread through air spaces in lung adenocarcinoma
Authors: Zeng Yuan , Zhou Lingli , Jia Dexin , Pan Bo , Li Xiaomei , Yu Yan
Published: August 2022

Patients with spread through air spaces (STAS) have worse postoperative survival and a higher recurrence rate in lung adenocarcinoma, even in the earliest phases of the disease. At present, the molecular pathogenesis of STAS is not well understood. Therefore, to illustrate the underlying pathogenic mechanism of STAS, we accomplished a comprehensive analysis of a microarray dataset of STAS. Differential expression analysis revealed 841 differentially expressed genes (DEGs) between STAS_positive and STAS_negative groups. Additionally, we acquired two hub genes associated with survival. Gene set variation analysis (GSVA) confirmed that the main differential signaling pathways between the two groups were hypoxia VHL targets, PKC, and pyrimidine metabolism pathways. Analysis of immune activity showed that the increased expression of MHC-class-Ⅰ was observed in the STAS_positive group. These findings provided novel insights for a better knowledge of pathogenic mechanisms and potential therapeutic markers for STAS treatment.
Predicting AURKA as a novel therapeutic target for NPC: A comprehensive analysis based on bioinformatics and validation
Authors: Huang Chaobin , Chen Lin , Zhang Yiping , Wang Liyan , Zheng Wei , Peng Fengying , Xu Yuanji
Published: August 2022

This study comprehensively explored the clinical function of Aurora kinase A (AURKA) gene in nasopharyngeal carcinoma (NPC) and analyzed its potential as a therapeutic target in cancer. Data were downloaded from GEO, STRING, GTEx, and CellMiner databases, and subjected to multiple bioinformatic analyses, including differential expression analysis, WCGNA, gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), gene set enrichment analysis (GSEA), gene set variation analysis (GSVA), miRNA-hub gene regulatory network analysis, immune cell infiltration, and drug sensitivity analysis. In-depth analysis of AURKA gene expression in NPC and its corresponding clinicopathological features was performed to explore its potential as a therapeutic target. Moreover, AURKA gene expression in NPC was validated by qRT-PCR in 21 NPC tissues and 17 normal nasopharyngeal epithelial tissues. AURKA was highly expressed in NPC tissues. Enrichment analysis of AURKA and its co-expressed hub genes indicated their oncogenic role in NPC and their potential involvement in cancer-promoting processes through histone kinase activity and microtubule motility activity, cell cycle, and p53 signaling pathways. AURKA high expression group had greater infiltration of neutrophils, macrophages M2, and dendritic cells resting and less infiltration of T cells CD4+ naïve and T cells γδ. Drug susceptibility analysis found that dacarbazine, R-306465, vorinostat, and other antitumor drugs that act on the cell cycle were closely related to AURKA. qRT-PCR verified the high expression of AURKA in NPC tissues (p < 0.05). We confirmed upregulation of AURKA in NPC tissues. Our results support an oncogenic role of AURKA in the context of NPC, and indicate its potential role as a novel therapeutic target.
Beyond race: Recruitment of diverse participants in clinical genomics research for rare disease
Authors: Young Jennifer L. , Halley Meghan C. , Anguiano Beatriz , Fernandez Liliana , Bernstein Jonathan A. , Wheeler Matthew T. , Tabor Holly K. ,   Undiagnosed Diseases Network Consortium
Published: August 2022

Purpose: Despite recent attention to increasing diversity in clinical genomics research, researchers still struggle to recruit participants from varied sociodemographic backgrounds. We examined the experiences of parents from diverse backgrounds with enrolling their children in clinical genomics research on rare diseases. We explored the barriers and facilitators parents encountered and possible impacts of sociodemographic factors on their access to research.

Methods: We utilized semi-structured interviews with parents of children participating in the Undiagnosed Diseases Network. Interview data were analyzed using comparative content analysis.

Results: We interviewed 13 Hispanic, 11 non-Hispanic White, four Asian, and two biracial parents. Participants discussed different pathways to clinical genomics research for rare disease as well as how sociodemographic factors shaped families’ access. Themes focused on variation in: 1) reliance on providers to access research; 2) cultural norms around health communication; 3) the role of social capital in streamlining access; and 4) the importance of language-concordant research engagement.

Conclusion: Our findings suggest that variables beyond race/ethnicity may influence access in clinical genomics research. Future efforts to diversify research participation should consider utilizing varied recruitment strategies to reach participants with diverse sociodemographic characteristics.
Significance of ZEB2 in the immune microenvironment of colon cancer
Authors: Xie Hao , Wu Zhaoying , Li Zhenhan , Huang Yong , Zou Junwei , Zhou Hailang
Published: August 2022

Background: ZEB2 is a protein-coding gene that is differentially expressed in tumors and can regulate the growth of tumor cells. This study investigated the specific regulatory mechanism of ZEB2 in COAD, a common cancer with high rates of morbidity and mortality.

Methods: Multi-omics panoramic display of expression and function of ZEB2 in colon cancer. R software was used to study the expression of ZEB2 in 33 types of cancer. Furthermore, RT-PCR was used to detect the expression of ZEB2 in colon cancers and para-cancer tissues, as well as in colon cancer cells and normal cells. The ssGSEA was then used to explore the relationship between ZEB2 and immune cells, with UALCAN, EWAS and MEXPRESS applied to explore the methylation of ZEB2. The relationship between immunomodulators and chemokines (or receptors) based on expression data, copy number data, methylation data, and mutation data of ZEB2 was investigated using TISIDB. Finally, a protein interaction network of ZEB2 was constructed, and GO and KEGG analyses were performed on the differentially expressed genes.

Results: ZEB2 is downregulated in most cancers, including COAD. The infiltration of the immune cells NK CD56 and Th17 cells was negatively correlated with ZEB2 expression, while the other 22 cells were positively correlated with ZEB2 expression. The DNA methylation of ZEB2 and the methylation of the ZEB2 protein on the EWAS website increased significantly. Analysis of the methylation levels and ZEB2 expression revealed that only the DNA methylation level and the expression of ZEB2 were significantly negatively correlated. The tumor-infiltrating lymphocytes positively correlated with the expression of ZEB2 but negatively correlated with the methylation of ZEB2. The same trend was observed for immunomodulators, chemokines, and receptors. The network showed that the protein performed certain biological functions, thereby affecting disease symptoms.

Conclusion: These findings provide evidence that ZEB2-based therapy may represent a powerful treatment strategy for COAD.
CD47 as a promising therapeutic target in oncology
Authors: Zhao Hai , Song Shuangshuang , Ma Junwei , Yan Zhiyong , Xie Hongwei , Feng Ying , Che Shusheng
Published: August 2022

CD47 is ubiquitously expressed on the surface of cells and plays a critical role in self-recognition. By interacting with SIRPα, TSP-1 and integrins, CD47 modulates cellular phagocytosis by macrophages, determines life span of individual erythrocytes, regulates activation of immune cells, and manipulates synaptic pruning during neuronal development. As such, CD47 has recently be regarded as one of novel innate checkpoint receptor targets for cancer immunotherapy. In this review, we will discuss increasing awareness about the diverse functions of CD47 and its role in immune system homeostasis. Then, we will discuss its potential therapeutic roles against cancer and outlines, the possible future research directions of CD47- based therapeutics against cancer.
Innate immunity to malaria: The good, the bad and the unknown
Authors: Pohl Kai , Cockburn Ian A.
Published: August 2022

Malaria is the cause of 600.000 deaths annually. However, these deaths represent only a tiny fraction of total malaria cases. Repeated natural infections with the causative agent, Plasmodium sp. parasites, induce protection from severe disease but not sterile immunity. Thus, immunity to Plasmodium is incomplete. Conversely, immunization with attenuated sporozoite stage parasites can induce sterile immunity albeit after multiple vaccinations. These different outcomes are likely to be influenced strongly by the innate immune response to different stages of the parasite lifecycle. Even small numbers of sporozoites can induce a robust proinflammatory type I interferon response, which is believed to be driven by the sensing of parasite RNA. Moreover, induction of innate like gamma-delta cells contributes to the development of adaptive immune responses. Conversely, while blood stage parasites can induce a strong proinflammatory response, regulatory mechanisms are also triggered. In agreement with this, intact parasites are relatively weakly sensed by innate immune cells, but isolated parasite molecules, notably DNA and RNA can induce strong responses. Thus, the innate response to Plasmodium parasite likely represents a trade-off between strong pro-inflammatory responses that may potentiate immunity and regulatory processes that protect the host from cytokine storms that can induce life threatening illness.
Roles of mitochondria in neutrophils
Authors: Cao Ziming , Zhao Meng , Sun Hao , Hu Liang , Chen Yunfeng , Fan Zhichao
Published: August 2022

Neutrophils are the most abundant leukocyte in human blood. They are critical for fighting infections and are involved in inflammatory diseases. Mitochondria are indispensable for eukaryotic cells, as they control the biochemical processes of respiration and energy production. Mitochondria in neutrophils have been underestimated since glycolysis is a major metabolic pathway for fuel production in neutrophils. However, several studies have shown that mitochondria are greatly involved in multiple neutrophil functions as well as neutrophil-related diseases. In this review, we focus on how mitochondrial components, metabolism, and related genes regulate neutrophil functions and relevant diseases.
Neutrophil extracellular traps: New players in cancer research
Authors: Zhao Junjie , Jin Jiaqi
Published: August 2022

NETs are chromatin-derived webs extruded from neutrophils as a result of either infection or sterile stimulation using chemicals, cytokines, or microbes. In addition to the classical role that NETs play in innate immunity against infection and injuries, NETs have been implicated extensively in cancer progression, metastatic dissemination, and therapy resistance. The purpose of this review is to describe recent investigations into NETs and the roles they play in tumor biology and to explore their potential as therapeutic targets in cancer treatment.
New perspectives on the regulation of germinal center reaction via αvβ8- mediated activation of TGFβ
Authors: This Sébastien , Paidassi Helena
Published: August 2022

Transforming growth factor-β (TGFβ) is a long-known modulator of immune responses but has seemingly contradictory effects on B cells. Among cytokines, TGFβ has the particularity of being produced and secreted in a latent form and must be activated before it can bind to its receptor and induce signaling. While the concept of controlled delivery of TGFβ signalingviaαvβ8 integrin-mediated activation has gained some interest in the field of mucosal immunity, the role of this molecular mechanism in regulating T-dependent B cell responses is just emerging. We review here the role of TGFβ and its activation, in particular by αvβ8 integrin, in the regulation of mucosal IgA responses and its demonstrated and putative involvement in regulating germinal center (GC) B cell responses. We examine both the direct effect of TGFβ on GC B cells and its ability to modulate the functions of helper cells, namely follicular T cells (Tfh and Tfr) and follicular dendritic cells. Synthetizing recently published works, we reconcile apparently conflicting data and propose an innovative and unified view on the regulation of the GC reaction by TGFβ, highlighting the role of its activation by αvβ8 integrin.
Purinergic receptors are a key bottleneck in tumor metabolic reprogramming: The prime suspect in cancer therapeutic resistance
Authors: Aria Hamid , Rezaei Marzieh , Nazem Shima , Daraei Abdolreza , Nikfar Ghasem , Mansoori Behnam , Bahmanyar Maryam , Tavassoli Alireza , Vakil Mohammad Kazem , Mansoori Yaser
Published: August 2022

ATP and other nucleoside phosphates have specific receptors named purinergic receptors. Purinergic receptors and ectonucleotidases regulate various signaling pathways that play a role in physiological and pathological processes. Extracellular ATP in the tumor microenvironment (TME) has a higher level than in normal tissues and plays a role in cancer cell growth, survival, angiogenesis, metastasis, and drug resistance. In this review, we investigated the role of purinergic receptors in the development of resistance to therapy through changes in tumor cell metabolism. When a cell transforms to neoplasia, its metabolic processes change. The metabolic reprogramming modified metabolic feature of the TME, that can cause impeding immune surveillance and promote cancer growth. The purinergic receptors contribute to therapy resistance by modifying cancer cells’ glucose, lipid, and amino acid metabolism. Limiting the energy supply of cancer cells is one approach to overcoming resistance. Glycolysis inhibitors which reduce intracellular ATP levels may make cancer cells more susceptible to anti-cancer therapies. The loss of the P2X7R through glucose intolerance and decreased fatty acid metabolism reduces therapeutic resistance. Potential metabolic blockers that can be employed in combination with other therapies will aid in the discovery of new anti-cancer immunotherapy to overcome therapy resistance. Therefore, therapeutic interventions that are considered to inhibit cancer cell metabolism and purinergic receptors simultaneously can potentially reduce resistance to treatment.
Delineating the role of extracellular vesicles in cancer metastasis: A comprehensive review
Authors: Majood Misba , Rawat Sonali , Mohanty Sujata
Published: August 2022

Extracellular vesicles (EVs) are subcellular messengers that aid in the formation and spread of cancer by enabling tumor-stroma communication. EVs develop from the very porous structure of late endosomes and hold information on both the intrinsic “status” of the cell and the extracellular signals absorbed by the cells from their surroundings. These EVs contain physiologically useful components, including as nucleic acids, lipids, and proteins, which have been found to activate important signaling pathways in tumor and tumor microenvironment (TME) cells, aggravating tumor growth. We highlight critical cell biology mechanisms that link EVS formation to cargo sorting in cancer cells in this review.Sorting out the signals that control EVs creation, cargo, and delivery will aid our understanding of carcinogenesis. Furthermore, we reviewed how cancer development and spreading behaviors are affected by coordinated communication between malignant and non-malignant cells. Herein, we studied the reciprocal exchanges via EVs in various cancer types. Further research into the pathophysiological functions of various EVs in tumor growth is likely to lead to the discovery of new biomarkers in liquid biopsy and the development of tumor-specific therapies.
Metabolic profiling reveals new serum signatures to discriminate lupus nephritis from systemic lupus erythematosus
Authors: Zhang Yamei , Gan Lingling , Tang Jie , Liu Dan , Chen Gang , Xu Bei
Published: August 2022

Background

Lupus nephritis (LN) occurs in 50% of patients with systemic lupus erythematosus (SLE), causing considerable morbidity and even mortality. Previous studies had shown the potential of metabolic profiling in the diagnosis of SLE or LN. However, few metabonomics studies have attempted to distinguish SLE from LN based on metabolic changes. The current study was designed to find new candidate serum signatures that could differentiate LN from SLE patients using a non-targeted metabonomics method based on ultra high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS).

Method

Metabolic profiling of sera obtained from 21 healthy controls, 52 SLE patients and 43 LN patients. We used SPSS 25.0 for statistical analysis. Principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) and metabolic pathway analysis were used to analyze the metabolic data.

Results

Upon comparison of SLE and LN groups, 28 differential metabolites were detected, the majority of which were lipids and amino acids. Glycerolphospholipid metabolism, pentose and glucuronate interconversions and porphyrin and chlorophyll metabolism were obviously enriched in LN patients versus those with SLE. Among the 28 characteristic metabolites, five key serum metabolites including SM d34:2, DG (18:3(9Z,12Z,15Z)/20:5(5Z,8Z,11Z,14Z,17Z)/0:0), nervonic acid, Cer-NS d27:4, and PC (18:3(6Z,9Z,12Z)/18:3(6Z,9Z,12Z) performed higher diagnostic performance in discriminating LN from SLE (all AUC > 0.75). Moreover, combined analysis of neuritic acid, C1q, and CysC (AUC = 0.916) produced the best combined diagnosis.

Conclusion

This study identified five serum metabolites that are potential indicators for the differential diagnosis of SLE and LN. Glycerolphospholipid metabolism may play an important role in the development of SLE to LN. The metabolites we screened can provide more references for the diagnosis of LN and more support for the pathophysiological study of SLE progressed to LN.
Case report: Drug rash with eosinophilia and systemic symptoms syndrome in a patient with anti–interferon-γ autoantibody–associated immunodeficiency
Authors: Nie Yuxue , Wang Han , Dong Xiying , Pan Siqi , Zhang Ting , Ran Jun , Zhang Ying , Fan Junping , Zhang Linqi , Wang Jinglan
Published: August 2022

A 56-year-old Chinese woman with previous disseminated mycobacterium avium complex infection and recurrent cervical abscesses from Burkholderia cepacia complex visited our hospital. She was diagnosed with adult-onset immunodeficiency (AOID) and tested positive for interferon-γ–neutralizing autoantibody. Ceftazidime was administered as the initial antimicrobial treatment, which was later combined with sulfamethoxazole-trimethoprim (SMZ-TMP). She developed drug rash with eosinophilia and systemic symptoms (DRESS) syndrome after SMZ-TMP administration and improved after withdrawal of the culprit antibiotic and systemic glucocorticoids treatment. Her cervical infection was eventually cured after combined therapy of long-term antibiotics and anti–IFN-γ autoantibodies (AIGA) titer-lowering treatments including glucocorticoids, rituximab, and plasmapheresis. This is the first case of DRESS syndrome in the setting of AIGA-induced AOID and is worthy of notice.
Pooled human bone marrow-derived mesenchymal stromal cells with defined trophic factors cargo promote dermal wound healing in diabetic rats by improved vascularization and dynamic recruitment of M2-like macrophages
Authors: Willer Hélène , Spohn Gabriele , Morgenroth Kimberly , Thielemann Corinna , Elvers-Hornung Susanne , Bugert Peter , Delorme Bruno , Giesen Melanie , Schmitz-Rixen Thomas , Seifried Erhard , Pfarrer Christiane , Schäfer Richard , Bieback Karen
Published: August 2022

Human Mesenchymal Stromal Cells (hMSCs) are a promising source for cell-based therapies. Yet, transition to phase III and IV clinical trials is remarkably slow. To mitigate donor variabilities and to obtain robust and valid clinical data, we aimed first to develop a manufacturing concept balancing large-scale production of pooled hMSCs in a minimal expansion period, and second to test them for key manufacture and efficacy indicators in the clinically highly relevant indication wound healing. Our novel clinical-scale manufacturing concept is comprised of six single donor hMSCs master cell banks that are pooled to a working cell bank from which an extrapolated number of 70,000 clinical doses of 1x106 hMSCs/cm2 wound size can be manufactured within only three passages. The pooled hMSC batches showed high stability of key manufacture indicators such as morphology, immune phenotype, proliferation, scratch wound healing, chemotactic migration and angiogenic support. Repeated topical hMSCs administration significantly accelerated the wound healing in a diabetic rat model by delivering a defined growth factor cargo (specifically BDNF, EGF, G-CSF, HGF, IL-1α, IL-6, LIF, osteopontin, VEGF-A, FGF-2, TGF-β, PGE-2 and IDO after priming) at the specific stages of wound repair, namely inflammation, proliferation and remodeling. Specifically, the hMSCs mediated epidermal and dermal maturation and collagen formation, improved vascularization, and promoted cell infiltration. Kinetic analyses revealed transient presence of hMSCs until day (d)4, and the dynamic recruitment of macrophages infiltrating from the wound edges (d3) and basis (d9), eventually progressing to the apical wound on d11. In the wounds, the hMSCs mediated M2-like macrophage polarization starting at d4, peaking at d9 and then decreasing to d11. Our study establishes a standardized, scalable and pooled hMSC therapeutic, delivering a defined cargo of trophic factors, which is efficacious in diabetic wound healing by improving vascularization and dynamic recruitment of M2-like macrophages. This decision-making study now enables the validation of pooled hMSCs as treatment for impaired wound healing in large randomized clinical trials.
Seasonal approach to forecast the suitability of spawning habitats of a temperate small pelagic fish under a high-emission climate change scenario
Authors: Lima André R. A. , Garrido Susana , Riveiro Isabel , Rodrigues Diana , Angélico Maria M. P. , Gonçalves Emanuel J. , Peck Myron A. , Silva Gonçalo
Published: August 2022

Spawning habitats of cold-water, European small pelagic fishes have shifted poleward in the last three decades coincident with gradual ocean warming. We predicted present-day, season-specific habitat suitability for spawning by European sardine Sardina pichardus in the Atlantic Ocean and Mediterranean and Black Seas, and projected climate-driven changes in suitable areas from 2050-2099 under the IPCC – RCP 8.5 scenario. Sea surface temperature and distance to the coast had the greater influences in spawning habitats, reflecting the temperature- and coastal-dependent spawning of sardines. Chlorophyll-a was the third most important explanatory variable for spawning in winter to summer. Winds were predominantly important during autumn, whilst sea surface salinity was an important driver during spring and summer. Present-day, “hotspots” for spawning were identified in regions of highly productive, salty waters, where SST was between 6 and 18°C from autumn to spring or 16 and 25°C during summer and favourable winds occurred that would retain eggs and larvae closer to the coast (< 250 km). For future scenarios, forecasts indicate that environmental optima for spawning is projected to be in regions where SST varies between 11°C and 18°C from autumn to spring; and between 18°C and 24°C during summer. However, a negative relationship between phytoplankton productivity and habitat suitability induced by warming is likely to occur in the future. Projections suggest that suitable spawning habitats in all seasons will shift to higher latitudes, with a prominent range expansion along the coast of Norway during winter and autumn (> 83%). The total spawning area, however, was projected to contract in the future during spring (-10.5%) and autumn (-4.1%) due to losses of currently suitable areas along the Atlantic African Coast and Mediterranean Sea. Such regions currently support the greatest sardine stocks but climate-driven warming and decreased plankton productivity are projected to make these areas unsuitable for spawning and likely also for sardine fisheries in future.
Strategies for the induction of anti-inflammatory mesenchymal stem cells and their application in the treatment of immune-related nephropathy
Authors: Zhou Cheng , Bai Xue-Yuan
Published: August 2022

Mesenchymal stem cells (MSCs) have potent immunomodulatory functions. Animal studies and clinical trials have demonstrated that MSCs can inhibit immune/inflammatory response in tissues and have good therapeutic effects on a variety of immune-related diseases. However, MSCs currently used for treatment are a mixed, undefined, and heterogeneous cell population, resulting in inconsistent clinical treatment effects. MSCs have dual pro-inflammatory/anti-inflammatory regulatory functions in different environments. In different microenvironments, the immunomodulatory function of MSCs has plasticity; therefore, MSCs can transform into pro-inflammatory MSC1 or anti-inflammatory MSC2 phenotypes. There is an urgent need to elucidate the molecular mechanism that induces the phenotypic transition of MSCs to pro-inflammatory or anti-inflammatory MSCs and to develop technical strategies that can induce the transformation of MSCs to the anti-inflammatory MSC2 phenotype to provide a theoretical basis for the future clinical use of MSCs in the treatment of immune-related nephropathy. In this paper, we summarize the relevant strategies and mechanisms for inducing the transformation of MSCs into the anti-inflammatory MSC2 phenotype and enhancing the immunosuppressive function of MSCs.
Prioritizing syphilis control: Now is the time for action
Authors: Tucker Joseph D. , Marley Gifty , Marks Michael , Mabey David
Published: August 2022

Syphilis control programs and research received fewer resources and attention compared to HIV and other sexually transmitted infections (STIs) in the pre-pandemic era. The neglect of syphilis within comprehensive STI control efforts may be related to diagnostic (poor diagnostics), historical (legacies of racism in research), public health (limited partner services), and social problems (limited public engagement). At the same time, there are increasingly compelling reasons to prioritize syphilis control programs and research by harnessing lessons learned and advances during COVID-19. The closure of many STI facilities has accelerated new syphilis diagnostic pathways (e.g., syphilis self-testing), providing new ways for people to be screened outside of clinics. COVID-19 has underlined health inequities that fuel syphilis transmission, providing an opportunity to reckon with the historical legacy of racism that is linked to syphilis research. COVID-19 partner tracing efforts have also contributed to additional resources for partner services which may enhance syphilis control efforts. Finally, COVID-19 has demonstrated the importance of public engagement, making the case for greater public involvement in syphilis control and prevention programs. Urgent action is needed to prioritize syphilis control in a wide range of settings.
Prevalence and associated risk factors of chronic kidney disease: A case study within SIME clinics in Quito, Ecuador 2019–2021
Authors: Eguiguren-Jiménez Lucía , Miles Joshua , Ocampo Jaime , Andrade Jeanette Mary
Published: August 2022

Background

Ecuador has been experiencing an epidemiological transition due to its demographic and lifestyle changes, where non-communicable diseases are the leading cause of death, including chronic kidney disease (CKD). Quito, Ecuador's capital city, is one of the cities burdened by CKD, yet it is unknown the factors that contribute to the rising incidence of this disease. The purpose of this study was to estimate the prevalence of CKD among non-institutionalized adults in Quito between 2019 and 2021, and to examine its associations with various risk factors.

Methods

For the analysis of prevalence, the Kidney Disease: Improving Global Outcomes guidelines were used, where an estimated glomerular filtration rate (eGFR) of < 60 ml/min/1.73 m2 was counted as a presumed case of CKD. The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was used to calculate eGFR. Multiple linear regression models were used to determined associations between blood pressure, blood glucose, sex, and zone with eGFR. A t-test of independence was used to determine difference in means between sex and zone and eGFR.

Results

A prevalence of 7.2% was found, in which almost 45% of the participants were classified within stages 2–4 of this disease. The risk factors that were significantly associated with eGFR were systolic blood pressure (β = −0.43, p < 0.001), sex, and zone (p < 0.001).

Conclusions

Overall a high prevalence of CKD was found among adults who visited SIME clinics in Quito. Associations between main risk factors and eGFR were found, yet further research is needed to explore CKD in Ecuador and its main cities.
Non-pharmacological interventions of travel restrictions and cancelation of public events had a major reductive mortality affect during pre-vaccination coronavirus disease 2019 period
Authors: Wen Haoyu , Shi Fang , Liu Yan , Xie Cong , Qin Guiyu , Wang Fang , Liu Xiaoxue , Bai Jianjun , Hong Qiumian , Ma Runxue , Yu Chuanhua
Published: August 2022

Background

The coronavirus disease 2019 (COVID-19) is a severe acute respiratory disease that poses a continuous threat to global public health. Many non-pharmacological interventions (NPIs) have been implemented to control the COVID-19 pandemic since the beginning. The aim of this study was to assess the impact of various NPIs on COVID-19 mortality during pre-vaccination and vaccination periods.

Methods

The COVID-19 data used in this study comes from Our World in Data, we used the Oxford Strict Index (OSI) and its five combination interventions as independent variables. The COVID-19 mortality date (MRT) was defined as a date when daily rate of 0.02 COVID-19 deaths per 100,000 population in a country was reached, and the COVID-19 vaccination date (VRT) was defined as people vaccinated reaching 70%. Linear regression and random forest models were used to estimate the impact of various NPI implementation interventions during pre-vaccination and vaccination periods. The performance of models was assessed among others with Shapley Additive Explanations (SHAP) explaining the prediction capability of the model.

Results

During the pre-vaccination period, the various NPIs had strong protective effect. When the COVID-19 MRT was reached, for every unit increase in OSI, the cumulative mortality as of June 30, 2020 decreased by 0.71 deaths per 100,000 people. Restrictions in travel (SHAP 1.68) and cancelation of public events and gatherings (1.37) had major reducing effect on COVID-19 mortality, while staying at home (0.26) and school and workplace closure (0.26) had less effect. Post vaccination period, the effects of NPI reduced significantly: cancelation of public events and gatherings (0.25), staying at home (0.22), restrictions in travel (0.14), and school and workplace closure (0.06).

Conclusion

Continued efforts are still needed to promote vaccination to build sufficient immunity to COVID-19 in the population. Until herd immunity is achieved, NPI is still important for COVID-19 prevention and control. At the beginning of the COVID-19 pandemic, the stringency of NPI implementation had a significant negative association with COVID-19 mortality; however, this association was no longer significant after the vaccination rate reached 70%. As vaccination progresses, “cancelation of public events and gatherings” become more important for COVID-19 mortality.
Serous retinal detachment secondary to an unsuccessful transarterial embolization in a post-traumatic carotid-cavernous sinus fistula patient: A case report
Authors: Lee Chia-Yi , Lee Wan-Ju Annabelle
Published: August 2022

A carotid-cavernous sinus fistula (CCF) is an abnormal communication between the cavernous sinus and the carotid arterial system. Direct CCFs arise from a direct connection between the cavernous sinus and the cavernous portion of the internal carotid artery. Nowadays, endovascular neurosurgery has become the first-line treatment modality for direct CCFs owing to the high complete obliteration rate. However, reversal of the clinical symptoms may not always be congruous after the endovascular intervention. Herein, we present a 50-year-old patient who manifested diplopia, ophthalmoplegia, and orbital congestion after a traffic accident. He had suffered head injury with right side frontal intracranial hemorrhage 1 month before the ophthalmic presentation. He came to our department primarily because of declining vision and for the above symptoms, and was diagnosed with direct type CCF, for which he received transarterial coil embolization. Unexpectedly, he later presented with serous retinal detachment accompanied by ocular ischemic syndrome secondary to recurrent CCF 1 month after the intervention, so repeat coil embolization was performed.
Can nitrogen supersede host identity in shaping the community composition of foliar endophytic fungi in an alpine meadow ecosystem?
Authors: Meng Yiming , Zhang Qi , Shi Guoxi , Liu Yongjun , Du Guozhen , Feng Huyuan
Published: August 2022

The availability of limiting nutrients plays a crucial role in shaping communities of endophytes. Moreover, whether fungal endophytes are host-specific remains controversial. We hypothesized that in a harsh and nitrogen (N)-deficient area, diversity and community composition of foliar endophytic fungi (FEFs) varied substantially among plots with experimentally elevated levels of macronutrients, and thus, N availability, instead of host species identity, would have a greater influence in structuring fungal communities at different scales. We also expected an important subset of taxa shared among numerous host species and N gradients to form a community-wide core microbiome. We measured the leaf functional traits and community structures of FEFs of three commonly seen species in an alpine meadow nested with a long-term N fertilization experiment. We found that host plant identity was a powerful factor driving the endophytic fungal community in leaves, even in habitats where productivity was strongly limited by nitrogen (p< 0.001). We also found that within the same host, nitrogen was an important driving force for the composition of the endophytic fungi community (p< 0.05). In addition, the leaf carbon content was the most important functional trait that limited the diversity of endophytic fungi (p< 0.001). Finally, we documented a distinct core microbiome shared among our three focal species and N gradients.
Experimental evolution of Vibrio cholerae identifies hypervesiculation as a way to increase motility in the presence of polymyxin B
Authors: Giacomucci Sean , Mathieu-Denoncourt Annabelle , Vincent Antony T. , Jannadi Hanen , Duperthuy Marylise
Published: August 2022

Vibrio cholerae includes strains responsible for the cholera disease and is a natural inhabitant of aquatic environments. V. cholerae possesses a unique polar flagellum essential for motility, adhesion, and biofilm formation. In a previous study, we showed that motility and biofilm formation are altered in the presence of subinhibitory concentrations of polymyxin B in V. cholerae O1 and O139. In this study, we performed an experimental evolution to identify the genes restoring the motility in the presence of a subinhibitory concentration of polymyxin B. Mutations in five genes have been identified in three variants derived from two different parental strains A1552 and MO10: ihfA that encodes a subunit of the integration host factor (IHF), vacJ (mlaA) and mlaF, two genes belonging to the maintenance of the lipid asymmetry (Mla) pathway, dacB that encodes a penicillin-binding protein (PBP4) and involved in cell wall synthesis, and ccmH that encodes a c-type cytochrome maturation protein. We further demonstrated that the variants derived from MO10 containing mutations in vacJ, mlaF, and dacB secrete more and larger membrane vesicles that titer the polymyxin B, which increases the bacterial survival and is expected to limit its impact on the bacterial envelope and participate in the flagellum’s retention and motility.
Antifungal mechanism of (E)-2-hexenal against Botrytis cinerea growth revealed by transcriptome analysis
Authors: Song Ge , Du Shenglong , Sun Helong , Liang Quanwu , Wang Haihua , Yan Mingli , Zhang Jihong
Published: August 2022

Gray mold caused by Botrytis cinerea, a necrotrophic plant pathogen, is one of the most damaging diseases of tomato, resulting in both pre- and post-harvest losses. (E)-2-Hexenal dose-dependently inhibited the mycelial growth of B. cinerea, and caused distortion of mycelia and loss of the cytoplasm content, thus altering the morphology of B. cinerea hyphae. To understand molecular processes in response to (E)-2-hexenal, transcriptome sequencing was carried out using RNA-Seq technology. RNA-Seq results revealed that a total of 3,893 genes were differentially expressed in B. cinerea samples treated with (E)-2-hexenal fumigation. Among these genes, 1,949 were upregulated and 1,944 were downregulated. Moreover, further analysis results showed 2,113 unigenes were mapped onto 259 pathways in Kyoto Encyclopedia of Genes and Genomes (KEGG). Moreover, (E)-2-hexenal stress affected the expression of genes involved in the pathways of cell wall, cell membrane, and energy metabolism. KEGG pathway analysis showed that the terpenoid backbone biosynthesis and steroid biosynthesis were the most enriched in ergosterol biosynthetic process transcriptome data. Particularly, (E)-2-hexenal fumigation had influenced ergosterol biosynthetic gene expression levels (e.g., ERG1, ERG3, ERG4, ERG7, ERG12, ERG13, ERG24, ERG25, ERG26, and ERG27), which were in good agreement with the experimental measurement results, and the ergosterol content decreased. Collectively, the results of this study increase our current understanding of (E)-2-hexenal inhibition mechanisms in B. cinerea and provide relevant information on postharvest shelf life extension and preservation of fruits and vegetables.
Extremely small and incredibly close: Gut microbes as modulators of inflammation and targets for therapeutic intervention
Authors: Piazzesi Antonia , Putignani Lorenza
Published: August 2022

Chronic inflammation is a hallmark for a variety of disorders and is at least partially responsible for disease progression and poor patient health. In recent years, the microbiota inhabiting the human gut has been associated with not only intestinal inflammatory diseases but also those that affect the brain, liver, lungs, and joints. Despite a strong correlation between specific microbial signatures and inflammation, whether or not these microbes are disease markers or disease drivers is still a matter of debate. In this review, we discuss what is known about the molecular mechanisms by which the gut microbiota can modulate inflammation, both in the intestine and beyond. We identify the current gaps in our knowledge of biological mechanisms, discuss how these gaps have likely contributed to the uncertain outcome of fecal microbiota transplantation and probiotic clinical trials, and suggest how both mechanistic insight and -omics-based approaches can better inform study design and therapeutic intervention.
Microbial lectome versus host glycolipidome: How pathogens exploit glycosphingolipids to invade, dupe or kill
Authors: Bereznicka Anna , Mikolajczyk Krzysztof , Czerwinski Marcin , Kaczmarek Radoslaw
Published: August 2022

Glycosphingolipids (GSLs) are ubiquitous components of the cell membranes, found across several kingdoms of life, from bacteria to mammals, including humans. GSLs are a subclass of major glycolipids occurring in animal lipid membranes in clusters named “lipid rafts.” The most crucial functions of GSLs include signal transduction and regulation as well as participation in cell proliferation. Despite the mainstream view that pathogens rely on protein–protein interactions to survive and thrive in their hosts, many also target the host lipids. In particular, multiple pathogens produce adhesion molecules or toxins that bind GSLs. Attachment of pathogens to cell surface receptors is the initial step in infections. Many mammalian pathogens have evolved to recognize GSL-derived receptors. Animal glycosphingolipidomes consist of multiple types of GSLs differing in terminal glycan and ceramide structures in a cell or tissue-specific manner. Interspecies differences in GSLs dictate host specificity as well as cell and tissue tropisms. Evolutionary pressure exerted by pathogens on their hosts drives changes in cell surface glycoconjugates, including GSLs, and has produced a vast number of molecules and interaction mechanisms. Despite that abundance, the role of GSLs as pathogen receptors has been largely overlooked or only cursorily discussed. In this review, we take a closer look at GSLs and their role in the recognition, cellular entry, and toxicity of multiple bacterial, viral and fungal pathogens.