Sex andEimeria: a molecular perspective

SUMMARYEimeriais a common genus of apicomplexan parasites that infect diverse vertebrates, most notably poultry, causing serious disease and economic loss. Like all apicomplexans, eimerians have a complex life cycle characterized by asexual divisions that amplify the parasite population in preparation for sexual reproduction. This can be divided into three events: gametocytogenesis, producing gametocytes from merozoites; gametogenesis, producing microgametes and macrogametes from gametocytes; and fertilization of macrogametes by microgametes, producing diploid zygotes with ensuing meiosis completing the sexual phase. Sexual development inEimeriadepends on the differential expression of stage-specific genes, rather than presence or absence of sex chromosomes. Thus, it involves the generation of specific structures and, implicitly, storage of proteins and regulation of protein expression in macrogametes, in preparation for fertilization. InEimeria, the formation of a unique, resilient structure, the oocyst wall, is essential for completion of the sexual phase and parasite transmission. In this review, we piece together the molecular events that underpin sexual reproduction inEimeriaand use additional details from analogous events inPlasmodiumto fill current knowledge gaps. The mechanisms governing sexual stage formation and subsequent fertilization may represent targets for counteracting parasite transmission.

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A Comprehensive Review on Solitary Fibrous Tumor: New Insights for New Horizons

Cancers ◽

10.3390/cancers13122913 ◽

2021 ◽

Vol 13 (12) ◽

pp. 2913

Author(s):

Javier Martin-Broto ◽

Jose L. Mondaza-Hernandez ◽

David S. Moura ◽

Nadia Hindi

Keyword(s):

Solitary Fibrous Tumor ◽

Fusion Gene ◽

Current Knowledge ◽

Fusion Transcript ◽

Chemotherapeutic Agents ◽

Comprehensive Review ◽

Molecular Events ◽

In Series ◽

Prospective Phase ◽

Fibrous Tumor

Solitary fibrous tumor (SFT) is a rare mesenchymal, ubiquitous tumor, with an incidence of 1 new case/million people/year. In the 2020 WHO classification, risk stratification models were recommended as a better tool to determine prognosis in SFT, to the detriment of “typical” or “malignant” classic terms. The risk for metastasis is up to 35–45%, or even greater, in series with a longer follow-up. Over the last few decades, advances in immunohistochemistry and molecular diagnostics identified STAT6 nuclear protein expression and the NAB2–STAT6 fusion gene as more precise tools for SFT diagnosis. Recent evidence taken from retrospective series and from two prospective phase II clinical trials showed that antiangiogenics are active and their sequential use from first line should be considered, except for dedifferentiated SFT for which chemotherapy is the best option. Since the fusion transcript driver’s first description in 2013, new insights have been brought on key molecular events in SFT. This comprehensive review mainly focuses on the superior efficacy of antiangiogenics over chemotherapeutic agents in SFT, provides the current knowledge of key molecules that could co-drive the SFT behavior, and suggests new target candidates that deserve to be explored in preclinical and clinical research in SFT.

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The β-oxidation pathway is downregulated during diapause termination in Calanus copepods

Scientific Reports ◽

10.1038/s41598-019-53032-5 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 1

Author(s):

Elise Skottene ◽

Ann M. Tarrant ◽

Anders J. Olsen ◽

Dag Altin ◽

Mari-Ann Østensen ◽

...

Keyword(s):

Current Knowledge ◽

Juvenile Fish ◽

Sampling Site ◽

Geographical Location ◽

Keystone Species ◽

Calanoid Copepods ◽

Diapause Termination ◽

Molecular Events ◽

High Lipid ◽

Field Samples

Abstract Calanus copepods are keystone species in marine ecosystems, mainly due to their high lipid content, which is a nutritious food source for e.g. juvenile fish. Accumulated lipids are catabolized to meet energy requirements during dormancy (diapause), which occurs during the last copepodite stage (C5). The current knowledge of lipid degradation pathways during diapause termination is limited. We characterized changes in lipid fullness and generated transcriptional profiles in C5s during termination of diapause and progression towards adulthood. Lipid fullness of C5s declined linearly during developmental progression, but more β-oxidation genes were upregulated in early C5s compared to late C5s and adults. We identified four possible master regulators of energy metabolism, which all were generally upregulated in early C5s, compared to late C5s and adults. We discovered that one of two enzymes in the carnitine shuttle is absent from the calanoid copepod lineage. Based on the geographical location of the sampling site, the field-samples were initially presumed to consist of C. finmarchicus. However, the identification of C. glacialis in some samples underlines the need for performing molecular analyses to reliably identify Calanus species. Our findings contributes to a better understanding of molecular events occurring during diapause and diapause termination in calanoid copepods.

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Cancer-associated fibroblasts (CAFs) in thyroid papillary carcinoma: molecular networks and interactions

Journal of Clinical Pathology ◽

10.1136/jclinpath-2020-207357 ◽

2021 ◽

pp. jclinpath-2020-207357

Author(s):

Jeehoon Ham ◽

Bin Wang ◽

Joseph William Po ◽

Amandeep Singh ◽

Navin Niles ◽

...

Keyword(s):

Cell Growth ◽

Cancer Cells ◽

Cancer Cell ◽

Stromal Cells ◽

Cancer Metastasis ◽

Current Knowledge ◽

Molecular Networks ◽

Cancer Cell Growth ◽

Molecular Events

In 1989, Stephen Paget proposed the ‘seed and soil’ theory of cancer metastasis. This theory has led to previous researchers focusing on the role of a tumour as a cancer seed and antiangiogenesis agents as cancer soil fumigant; for the latter to be effective, it is important for them to be able to distinguish cancer cells from stromal cells. However, antiangiogenesis agents have not produced dramatic survival benefits in vivo. This may be related to their inability to destroy the supporting stroma that promote cancer cell growth. Therefore, in order to effectively arrest cancer cell growth for therapeutic purposes, a paradigm shift is required in our fundamental approach to decipher the molecular events and networks in the stromal environment that cancer cells can thrive and proliferate. The pathogenesis of cancer is a multidimensional process of pathological molecular and cellular pathways, influencing different stromal properties and achieving a mutually negotiated crosstalk between cancer cells and stromal cells. This review summarises the clinical presentation of current knowledge of classical papillary thyroid carcinoma (PTC), emerging molecular diagnostics and future directions of classical PTC research.

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Targeting Genome Integrity in Mycobacterium Tuberculosis: From Nucleotide Synthesis to DNA Replication and Repair

Molecules ◽

10.3390/molecules25051205 ◽

2020 ◽

Vol 25 (5) ◽

pp. 1205 ◽

Cited By ~ 1

Author(s):

Riccardo Miggiano ◽

Castrese Morrone ◽

Franca Rossi ◽

Menico Rizzi

Keyword(s):

Mycobacterium Tuberculosis ◽

Drug Discovery ◽

Genome Stability ◽

Current Knowledge ◽

Genome Integrity ◽

Dna Integrity ◽

Dna Metabolism ◽

Nucleotide Synthesis ◽

Antitubercular Drugs ◽

Molecular Events

Mycobacterium tuberculosis (MTB) is the causative agent of tuberculosis (TB), an ancient disease which still today causes 1.4 million deaths worldwide per year. Long-term, multi-agent anti-tubercular regimens can lead to the anticipated non-compliance of the patient and increased drug toxicity, which in turn can contribute to the emergence of drug-resistant MTB strains that are not susceptible to first- and second-line available drugs. Hence, there is an urgent need for innovative antitubercular drugs and vaccines. A number of biochemical processes are required to maintain the correct homeostasis of DNA metabolism in all organisms. Here we focused on reviewing our current knowledge and understanding of biochemical and structural aspects of relevance for drug discovery, for some such processes in MTB, and particularly DNA synthesis, synthesis of its nucleotide precursors, and processes that guarantee DNA integrity and genome stability. Overall, the area of drug discovery in DNA metabolism appears very much alive, rich of investigations and promising with respect to new antitubercular drug candidates. However, the complexity of molecular events that occur in DNA metabolic processes requires an accurate characterization of mechanistic details in order to avoid major flaws, and therefore the failure, of drug discovery approaches targeting genome integrity.

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Human Tibroviruses: Commensals or Lethal Pathogens?

Viruses ◽

10.3390/v12030252 ◽

2020 ◽

Vol 12 (3) ◽

pp. 252 ◽

Cited By ~ 1

Author(s):

Jens H. Kuhn ◽

Hào Pān ◽

Charles Y. Chiu ◽

Matthew Stremlau

Keyword(s):

Rabies Virus ◽

Current Knowledge ◽

Diverse Group ◽

Biting Midges ◽

Pathogenic Potential ◽

Western Africa ◽

Healthy Cattle ◽

Vesicular Stomatitis ◽

Serious Disease ◽

Negative Sense

Rhabdoviruses are a large and ecologically diverse family of negative-sense RNA viruses (Mononegavirales: Rhabdoviridae). These viruses are capable of infecting an unexpectedly wide variety of plants, vertebrates, and invertebrates distributed over all human-inhabited continents. However, only a few rhabdoviruses are known to infect humans: a ledantevirus (Le Dantec virus), several lyssaviruses (in particular, rabies virus), and several vesiculoviruses (e.g., Chandipura virus, vesicular stomatitis Indiana virus). Recently, several novel rhabdoviruses have been discovered in the blood of both healthy and severely ill individuals living in Central and Western Africa. These viruses—Bas-Congo virus, Ekpoma virus 1, and Ekpoma virus 2—are members of the little-understood rhabdoviral genus Tibrovirus. Other than the basic genomic architecture, tibroviruses bear little resemblance to well-studied rhabdoviruses such as rabies virus and vesicular stomatitis Indiana virus. These three human tibroviruses are quite divergent from each other, and each of them clusters closely with tibroviruses currently known only from biting midges or healthy cattle. Seroprevalence studies suggest that human tibrovirus infections may be common but are almost entirely unrecognized. The pathogenic potential of this diverse group of viruses remains unknown. Although certain tibroviruses may be benign and well-adapted to humans, others could be newly emerging and produce serious disease. Here, we review the current knowledge of tibroviruses and argue that assessing their impact on human health should be an urgent priority.

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Regulation of ST6GAL1 sialyltransferase expression in cancer cells

Glycobiology ◽

10.1093/glycob/cwaa110 ◽

2020 ◽

Author(s):

Kaitlyn A Dorsett ◽

Michael P Marciel ◽

Jihye Hwang ◽

Katherine E Ankenbauer ◽

Nikita Bhalerao ◽

...

Keyword(s):

Cancer Cells ◽

Translational Regulation ◽

Molecular Mechanisms ◽

Current Knowledge ◽

Sialic Acids ◽

Invasion Resistance ◽

Cell Behaviors ◽

Molecular Events ◽

Wide Range

Abstract The ST6GAL1 sialyltransferase, which adds α2–6 linked sialic acids to N-glycosylated proteins, is overexpressed in a wide range of human malignancies. Recent studies have established the importance of ST6GAL1 in promoting tumor cell behaviors such as invasion, resistance to cell stress, and chemoresistance. Furthermore, ST6GAL1 activity has been implicated in imparting cancer stem cell characteristics. However, despite the burgeoning interest in the role of ST6GAL1 in the phenotypic features of tumor cells, insufficient attention has been paid to the molecular mechanisms responsible for ST6GAL1 upregulation during neoplastic transformation. Evidence suggests that these mechanisms are multifactorial, encompassing genetic, epigenetic, transcriptional, and post-translational regulation. The purpose of this review is to summarize current knowledge regarding the molecular events that drive enriched ST6GAL1 expression in cancer cells.

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Proteomic and Transcriptomic Analyses Indicate Metabolic Changes and Reduced Defense Responses in Mycorrhizal Roots of Oeceoclades maculata (Orchidaceae) Collected in Nature

Journal of Fungi ◽

10.3390/jof6030148 ◽

2020 ◽

Vol 6 (3) ◽

pp. 148

Author(s):

Rafael B. S. Valadares ◽

Silvia Perotto ◽

Adriano R. Lucheta ◽

Eder C. Santos ◽

Renato M. Oliveira ◽

...

Keyword(s):

Plant Defense ◽

De Novo ◽

Current Knowledge ◽

Defense Responses ◽

Mycorrhizal Symbiosis ◽

Label Free ◽

Molecular Events ◽

Mycorrhizal Roots ◽

Steady State Levels ◽

Isobaric Tagging

Orchids form endomycorrhizal associations with fungi mainly belonging to basidiomycetes. The molecular events taking place in orchid mycorrhiza are poorly understood, although the cellular changes necessary to accommodate the fungus and to control nutrient exchanges imply a modulation of gene expression. Here, we used proteomics and transcriptomics to identify changes in the steady-state levels of proteins and transcripts in the roots of the green terrestrial orchid Oeceoclades maculata. When mycorrhizal and non-mycorrhizal roots from the same individuals were compared, 94 proteins showed differential accumulation using the label-free protein quantitation approach, 86 using isobaric tagging and 60 using 2D-differential electrophoresis. After de novo assembly of transcriptomic data, 11,179 plant transcripts were found to be differentially expressed, and 2175 were successfully annotated. The annotated plant transcripts allowed the identification of up- and down-regulated metabolic pathways. Overall, proteomics and transcriptomics revealed, in mycorrhizal roots, increased levels of transcription factors and nutrient transporters, as well as ethylene-related proteins. The expression pattern of proteins and transcripts involved in plant defense responses suggested that plant defense was reduced in O. maculata mycorrhizal roots sampled in nature. These results expand our current knowledge towards a better understanding of the orchid mycorrhizal symbiosis in adult plants under natural conditions.

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Epidermolysis Bullosa-Associated Squamous Cell Carcinoma: From Pathogenesis to Therapeutic Perspectives

International Journal of Molecular Sciences ◽

10.3390/ijms20225707 ◽

2019 ◽

Vol 20 (22) ◽

pp. 5707 ◽

Cited By ~ 9

Author(s):

Angelo Giuseppe Condorelli ◽

Elena Dellambra ◽

Elena Logli ◽

Giovanna Zambruno ◽

Daniele Castiglia

Keyword(s):

Squamous Cell ◽

Epidermolysis Bullosa ◽

Genetic Determinants ◽

Therapeutic Approaches ◽

Molecular Events ◽

Genes Encoding ◽

Skin Fragility ◽

Serious Disease ◽

Almost All

Epidermolysis bullosa (EB) is a heterogeneous group of inherited skin disorders determined by mutations in genes encoding for structural components of the cutaneous basement membrane zone. Disease hallmarks are skin fragility and unremitting blistering. The most disabling EB (sub)types show defective wound healing, fibrosis and inflammation at lesional skin. These features expose patients to serious disease complications, including the development of cutaneous squamous cell carcinomas (SCCs). Almost all subjects affected with the severe recessive dystrophic EB (RDEB) subtype suffer from early and extremely aggressive SCCs (RDEB-SCC), which represent the first cause of death in these patients. The genetic determinants of RDEB-SCC do not exhaustively explain its unique behavior as compared to low-risk, ultraviolet-induced SCCs in the general population. On the other hand, a growing body of evidence points to the key role of tumor microenvironment in initiation, progression and spreading of RDEB-SCC, as well as of other, less-investigated, EB-related SCCs (EB-SCCs). Here, we discuss the recent advances in understanding the complex series of molecular events (i.e., fibrotic, inflammatory, and immune processes) contributing to SCC development in EB patients, cross-compare tumor features in the different EB subtypes and report the most promising therapeutic approaches to counteract or delay EB-SCCs.

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Phosphoinositide 3′-Kinase γ Facilitates Polyomavirus Infection

Viruses ◽

10.3390/v12101190 ◽

2020 ◽

Vol 12 (10) ◽

pp. 1190

Author(s):

Paul Clark ◽

Gretchen V. Gee ◽

Brandon S. Albright ◽

Benedetta Assetta ◽

Ying Han ◽

...

Keyword(s):

Cellular Proteins ◽

Regulatory Subunit ◽

Wild Type ◽

Jc Polyomavirus ◽

Knock Out ◽

Molecular Events ◽

Tumor Viruses ◽

Phosphoinositide 3 Kinase ◽

Serious Disease ◽

Human Polyomaviruses

Polyomaviruses are small, non-enveloped DNA tumor viruses that cause serious disease in immunosuppressed people, including progressive multifocal leukoencephalopathy (PML) in patients infected with JC polyomavirus, but the molecular events mediating polyomavirus entry are poorly understood. Through genetic knockdown approaches, we identified phosphoinositide 3′-kinase γ (PI3Kγ) and its regulatory subunit PIK3R5 as cellular proteins that facilitate infection of human SVG-A glial cells by JCPyV. PI3Kα appears less important for polyomavirus infection than PI3Kγ. CRISPR/Cas9-mediated knockout of PIK3R5 or PI3Kγ inhibited infection by authentic JCPyV and by JC pseudovirus. PI3Kγ knockout also inhibited infection by BK and Merkel Cell pseudoviruses, other pathogenic human polyomaviruses, and SV40, an important model polyomavirus. Reintroduction of the wild-type PI3Kγ gene into the PI3Kγ knock-out SVG-A cells rescued the JCPyV infection defect. Disruption of the PI3Kγ pathway did not block binding of JCPyV to cells or virus internalization, implying that PI3Kγ facilitates some intracellular step(s) of infection. These results imply that agents that inhibit PI3Kγ signaling may have a role in managing polyomavirus infections.

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The clinical spectrum of primary Sjögren’s syndrome: beyond exocrine glands

Reumatismo ◽

10.4081/reumatismo.2017.1032 ◽

2017 ◽

Vol 69 (3) ◽

pp. 93 ◽

Cited By ~ 3

Author(s):

M.C. Leone ◽

A. Alunno ◽

G. Cafaro ◽

V. Valentini ◽

E. Marcucci ◽

...

Keyword(s):

Sjögren’S Syndrome ◽

Sjögren's Syndrome ◽

Current Knowledge ◽

Sjogren’S Syndrome ◽

Sjogren's Syndrome ◽

Primary Sjögren’S Syndrome ◽

Primary Sjogren’S Syndrome ◽

Primary Sjögren's Syndrome ◽

Serious Disease ◽

Sjögren‘S Syndrome

Although primary Sjögren’s syndrome (pSS) is a mild indolent chronic disease mainly characterized by mucosal dryness in the majority of cases, a consistent subgroup of patients display extra-glandular manifestations. Virtually any organs and systems can be affected, leading to a more serious disease prognosis. Therefore, the prompt identification of patients at higher risk of extra-glandular manifestations is necessary to start a thorough follow up and an aggressive treatment. The aim of this review article is to provide an overview of epidemiological, clinical and serological features of extra-glandular manifestations in pSS as well as current knowledge about putative biomarkers useful in clinical practice.

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