The evolution of the 9aaTAD domain in Sp2 proteins: inactivation with valines and intron reservoirs.
We described the origin and evolutionary history of 9aaTADs. The 9aaTADs of the ancestral Sp2 gene became inactivated in early chordates. We next discovered that an accumulation of valines in 9aaTADs inactivated their transactivation function and enabled their strict conservation during evolution. Subsequently, in chordates, Sp2 has duplicated and created new paralogs, Sp1, Sp3, and Sp4 (the SP1-4 clade). During chordate evolution, the dormancy of the Sp2 activation domain lasted over 100 million years. The dormant but still intact ancestral Sp2 activation domains allowed diversification of the SP1-4 clade into activators ...
Source: Cellular and Molecular Life Sciences : CMLS - August 2, 2019 Category: Cytology Authors: Piskacek M, Havelka M, Jendruchova K, Knight A, Keegan LP Tags: Cell Mol Life Sci Source Type: research

Two of a kind: transmissible Schwann cell cancers in the endangered Tasmanian devil (Sarcophilus harrisii).
In this study, we compared the transcriptome and proteome of DFT2 tumours to DFT1 and normal Tasmanian devil tissues to determine the tissue-of-origin of the DFT2 cancer. Our findings demonstrate that DFT2 expresses a range of Schwann cell markers and exhibits expression patterns consistent with a similar origin to the DFT1 cancer. Furthermore, DFT2 cells express genes associated with the repair response to peripheral nerve damage. These findings suggest that devils may be predisposed to transmissible cancers of Schwann cell origin. The combined effect of factors such as frequent nerve damage from biting, Schwann cell plas...
Source: Cellular and Molecular Life Sciences : CMLS - August 2, 2019 Category: Cytology Authors: Patchett AL, Coorens THH, Darby J, Wilson R, McKay MJ, Kamath KS, Rubin A, Wakefield M, Mcintosh L, Mangiola S, Pye RJ, Flies AS, Corcoran LM, Lyons AB, Woods GM, Murchison EP, Papenfuss AT, Tovar C Tags: Cell Mol Life Sci Source Type: research

Leishmania heme uptake involves LmFLVCRb, a novel porphyrin transporter essential for the parasite.
ute;n JJG, Pérez-Victoria JM Abstract Leishmaniasis comprises a group of neglected diseases caused by the protozoan parasite Leishmania spp. As is the case for other trypanosomatid parasites, Leishmania is auxotrophic for heme and must scavenge this essential compound from its human host. In mammals, the SLC transporter FLVCR2 mediates heme import across the plasma membrane. Herein we identify and characterize Leishmania major FLVCRb (LmFLVCRb), the first member of the FLVCR family studied in a non-metazoan organism. This protein localizes to the plasma membrane of the parasite and is able to bind heme. LmF...
Source: Cellular and Molecular Life Sciences : CMLS - August 1, 2019 Category: Cytology Authors: Cabello-Donayre M, Orrego LM, Herráez E, Vargas P, Martínez-García M, Campos-Salinas J, Pérez-Victoria I, Vicente B, Marín JJG, Pérez-Victoria JM Tags: Cell Mol Life Sci Source Type: research

Programmable RNA manipulation in living cells.
Abstract RNAs are responsible for mediating genetic information flow within the cell. RNA splicing, modification, trafficking, translation, and stability are all controlled at the transcript level. However, biological tools to study and manipulate them in a programmable fashion are currently limited. In this review, we summarize recent advances regarding available RNA-targeting systems discovered so far, including CRISPR-based technologies-Cas9 and Cas13, and programmable RNA-binding proteins-PUF and PPR. These tools allow transcript-specific manipulation in gene expression. PMID: 31367845 [PubMed - as suppli...
Source: Cellular and Molecular Life Sciences : CMLS - July 31, 2019 Category: Cytology Authors: Pei Y, Lu M Tags: Cell Mol Life Sci Source Type: research

Early trypsin activation develops independently of autophagy in caerulein-induced pancreatitis in mice.
In conclusion, during the initiating phase of caerulein-induced pancreatitis, premature protease activation develops independently of autophagolysosome formation and in vesicles arising from the secretory pathway. However, autophagy is likely to regulate overall intracellular trypsin activity during the later stages of this disease. PMID: 31363815 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - July 30, 2019 Category: Cytology Authors: Malla SR, Krueger B, Wartmann T, Sendler M, Mahajan UM, Weiss FU, Thiel FG, De Boni C, Gorelick FS, Halangk W, Aghdassi AA, Reinheckel T, Gukovskaya AS, Lerch MM, Mayerle J Tags: Cell Mol Life Sci Source Type: research

S100 proteins in obesity: liaisons dangereuses.
Abstract Obesity is an endemic pathophysiological condition and a comorbidity associated with hypercholesterolemia, hypertension, cardiovascular disease, type 2 diabetes mellitus, and cancer. The adipose tissue of obese subjects shows hypertrophic adipocytes, adipocyte hyperplasia, and chronic low-grade inflammation. S100 proteins are Ca2+-binding proteins exclusively expressed in vertebrates in a cell-specific manner. They have been implicated in the regulation of a variety of functions acting as intracellular Ca2+ sensors transducing the Ca2+ signal and extracellular factors affecting cellular activity via ligat...
Source: Cellular and Molecular Life Sciences : CMLS - July 30, 2019 Category: Cytology Authors: Riuzzi F, Chiappalupi S, Arcuri C, Giambanco I, Sorci G, Donato R Tags: Cell Mol Life Sci Source Type: research

Post-translational modification and protein sorting to small extracellular vesicles including exosomes by ubiquitin and UBLs.
Abstract Exosomes, a type of small extracellular vesicles (sEVs), are secreted membrane vesicles that are derived from various cell types, including cancer cells, mesenchymal stem cells, and immune cells via multivesicular bodies (MVBs). These sEVs contain RNAs (mRNA, miRNA, lncRNA, and rRNA), lipids, DNA, proteins, and metabolites, all of which mediate cell-to-cell communication. This communication is known to be implicated in a diverse set of diseases such as cancers and their metastases and degenerative diseases. The molecular mechanisms, by which proteins are modified and sorted to sEVs, are not fully understo...
Source: Cellular and Molecular Life Sciences : CMLS - July 30, 2019 Category: Cytology Authors: Ageta H, Tsuchida K Tags: Cell Mol Life Sci Source Type: research

Versatile cell ablation tools and their applications to study loss of cell functions.
n X Abstract Targeted cell ablation is a powerful approach for studying the role of specific cell populations in a variety of organotypic functions, including cell differentiation, and organ generation and regeneration. Emerging tools for permanently or conditionally ablating targeted cell populations and transiently inhibiting neuronal activities exhibit a diversity of application and utility. Each tool has distinct features, and none can be universally applied to study different cell types in various tissue compartments. Although these tools have been developed for over 30 years, they require additional imp...
Source: Cellular and Molecular Life Sciences : CMLS - July 29, 2019 Category: Cytology Authors: Liu F, Dai S, Feng D, Peng X, Qin Z, Kearns AC, Huang W, Chen Y, Ergün S, Wang H, Rappaport J, Bryda EC, Chandrasekhar A, Aktas B, Hu H, Chang SL, Gao B, Qin X Tags: Cell Mol Life Sci Source Type: research

The biological functions and clinical applications of exosomes in lung cancer.
Abstract Lung cancer remains the leading cause of cancer-related death worldwide, and the high incidence rates are worrisome. Exosomes are a class of extracellular vesicles secreted by most cells, including RNAs, proteins and lipids. Exosomes can mediate cell-to-cell communication in both physiologic and pathologic processes. Accumulated evidences show that cancer-derived exosomes aid in the recruitment and reprogramming of constituents correlated with tumor microenvironment. Furthermore, exosome-based clinical trials have been completed in advanced lung cancer patients. In this review, we discuss the roles of exo...
Source: Cellular and Molecular Life Sciences : CMLS - July 27, 2019 Category: Cytology Authors: Chen R, Xu X, Qian Z, Zhang C, Niu Y, Wang Z, Sun J, Zhang X, Yu Y Tags: Cell Mol Life Sci Source Type: research

Robust dengue virus infection in bat cells and limited innate immune responses coupled with positive serology from bats in IndoMalaya and Australasia.
Abstract Natural reservoir hosts can sustain infection of pathogens without succumbing to overt disease. Multiple bat species host a plethora of viruses, pathogenic to other mammals, without clinical symptoms. Here, we detail infection of bat primary cells, immune cells, and cell lines with Dengue virus. While antibodies and viral RNA were previously detected in wild bats, their ability to sustain infection is not conclusive. Old-world fruitbat cells can be infected, producing high titres of virus with limited cellular responses. In addition, there is minimal interferon (IFN) response in cells infected with MOIs l...
Source: Cellular and Molecular Life Sciences : CMLS - July 27, 2019 Category: Cytology Authors: Irving AT, Rozario P, Kong PS, Luko K, Gorman JJ, Hastie ML, Chia WN, Mani S, Lee BP, Smith GJD, Mendenhall IH, Larman HB, Elledge SJ, Wang LF Tags: Cell Mol Life Sci Source Type: research

Adipocyte-progenitor cell communication that influences adipogenesis.
Abstract Adipose tissue is located in discrete depots that are differentially associated with elevated risk of metabolic complications, with fat accretion in visceral depots being most detrimental to metabolic health. Currently, the regulation of specific adipose depot expansion, by adipocyte hypertrophy and hyperplasia and consequently fat distribution, is not well understood. However, a growing body of evidence from in vitro investigations indicates that mature adipocytes secrete factors that modulate the proliferation and differentiation of progenitor, adipose-derived stem cells (ADSCs). It is therefore plausib...
Source: Cellular and Molecular Life Sciences : CMLS - July 27, 2019 Category: Cytology Authors: Haylett WL, Ferris WF Tags: Cell Mol Life Sci Source Type: research

Epigenetic control of embryo-uterine crosstalk at peri-implantation.
Abstract Embryo implantation is one of the pivotal steps during mammalian pregnancy, since the quality of embryo implantation determines the outcome of ongoing pregnancy and fetal development. A large number of factors, including transcription factors, signalling transduction components, and lipids, have been shown to be indispensable for embryo implantation. Increasing evidence also suggests the important roles of epigenetic factors in this critical event. This review focuses on recent findings about the involvement of epigenetic regulators during embryo implantation. PMID: 31352535 [PubMed - as supplied by ...
Source: Cellular and Molecular Life Sciences : CMLS - July 27, 2019 Category: Cytology Authors: Kong S, Zhou C, Bao H, Ni Z, Liu M, He B, Huang L, Sun Y, Wang H, Lu J Tags: Cell Mol Life Sci Source Type: research

αKlotho-FGF23 interactions and their role in kidney disease: a molecular insight.
αKlotho-FGF23 interactions and their role in kidney disease: a molecular insight. Cell Mol Life Sci. 2019 Jul 26;: Authors: Smith ER, Holt SG, Hewitson TD Abstract Following the serendipitous discovery of the ageing suppressor, αKlotho (αKl), several decades ago, a growing body of evidence has defined a pivotal role for its various forms in multiple aspects of vertebrate physiology and pathology. The transmembrane form of αKl serves as a co-receptor for the osteocyte-derived mineral regulator, fibroblast growth factor (FGF)23, principally in the renal tubules. However, compelli...
Source: Cellular and Molecular Life Sciences : CMLS - July 26, 2019 Category: Cytology Authors: Smith ER, Holt SG, Hewitson TD Tags: Cell Mol Life Sci Source Type: research

FA-SAT ncRNA interacts with PKM2 protein: depletion  of this complex induces a switch from cell proliferation to apoptosis.
FA-SAT ncRNA interacts with PKM2 protein: depletion of this complex induces a switch from cell proliferation to apoptosis. Cell Mol Life Sci. 2019 Jul 25;: Authors: Ferreira D, Escudeiro A, Adega F, Anjo SI, Manadas B, Chaves R Abstract FA-SAT is a highly conserved satellite DNA sequence transcribed in many Bilateria species. To disclose the cellular and functional profile of FA-SAT non-coding RNAs, a comprehensive experimental approach, including the transcripts location in the cell and in the cell cycle, the identification of its putative protein interactors, and silencing/ectopic expressi...
Source: Cellular and Molecular Life Sciences : CMLS - July 25, 2019 Category: Cytology Authors: Ferreira D, Escudeiro A, Adega F, Anjo SI, Manadas B, Chaves R Tags: Cell Mol Life Sci Source Type: research

Review: immunoassays in DNA damage and instability detection.
Abstract The review includes information on the current state of knowledge of immunometric methods with emphasis on the possibility of deoxyribonucleic acid (DNA) damage detection. Beginning with basic immunoassay enzyme-linked immunosorbent assay (ELISA), this review describes methods such as tyramide signal amplification (TSA), enhanced polymer one-step staining (EPOS), and time resolved amplified cryptate emission (TRACE) as improvements of ELISA's developed over time to obtain more accurate results. In the second part of the review, surface plasmon resonance (SPR) and quantum dots (QDs)&nbs...
Source: Cellular and Molecular Life Sciences : CMLS - July 24, 2019 Category: Cytology Authors: Boguszewska K, Szewczuk M, Urbaniak S, Karwowski BT Tags: Cell Mol Life Sci Source Type: research

CCL21/CCR7 signaling in macrophages promotes joint inflammation and Th17-mediated osteoclast formation in rheumatoid arthritis.
In this study, we aimed to characterize the functional significance of CCL21/CCR7 signaling in different phases of RA pathogenesis. We determined that CCR7 is a hallmark of RA M1 synovial fluid (SF) macrophages, and its expression in RA monocytes and in vitro differentiated macrophages is closely associated with disease activity score (DAS28). In early stages of RA, monocytes infiltrate the synovial tissue. However, blockade of SF CCL21 or CCR7 prevents RA SF-mediated monocyte migration. CCR7 expression in the newly migrated macrophages can be accentuated by LPS and IFNγ and suppressed by IL-4 treatment. We also unco...
Source: Cellular and Molecular Life Sciences : CMLS - July 24, 2019 Category: Cytology Authors: Van Raemdonck K, Umar S, Palasiewicz K, Volkov S, Volin MV, Arami S, Chang HJ, Zanotti B, Sweiss N, Shahrara S Tags: Cell Mol Life Sci Source Type: research

An interplay of structure and intrinsic disorder in the functionality of peptidylarginine deiminases, a family of key autoimmunity-related enzymes.
Abstract Citrullination is a post-translation modification of proteins, where the proteinaceous arginine residues are converted to non-coded citrulline residues. The immune tolerance to such citrullinated protein can be lost, leading to inflammatory and autoimmune diseases. Citrullination is a chemical reaction mediated by peptidylarginine deiminase enzymes (PADs), which are a family of calcium-dependent cysteine hydrolase enzymes that includes five isotypes: PAD1, PAD2, PAD3, PAD4, and PAD6. Each PAD has specific substrates and tissue distribution, where it modifies the arginine to produce a citrullinated protein...
Source: Cellular and Molecular Life Sciences : CMLS - July 24, 2019 Category: Cytology Authors: Alghamdi M, Al Ghamdi KA, Khan RH, Uversky VN, Redwan EM Tags: Cell Mol Life Sci Source Type: research

Dichotomous roles of claudins as tumor promoters or suppressors: lessons from knockout mice.
Abstract Claudins are a family of integral tight junction proteins that regulate paracellular permeability in polarized epithelia. Overexpression or reduction of claudins can both promote and limit cancer progression, revealing complex dichotomous roles for claudins depending on cellular context. In contrast, recent studies demonstrating tumor formation in claudin knockout mouse models indicate a role for several claudin family members in suppressing tumor initiation. For example, intestine-specific claudin-7 knockout mice spontaneously develop atypical hyperplasia and intestinal adenomas, while claudin-18 knockou...
Source: Cellular and Molecular Life Sciences : CMLS - July 23, 2019 Category: Cytology Authors: Kage H, Flodby P, Zhou B, Borok Z Tags: Cell Mol Life Sci Source Type: research

Correction to: Saturation of acyl chains converts cardiolipin from an antagonist to an activator of Toll-like receptor-4.
nt CE Abstract In the published article, the Fig. 2 was published incorrectly. The correct Fig. 2 is given below. PMID: 31338554 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - July 23, 2019 Category: Cytology Authors: Pizzuto M, Lonez C, Baroja-Mazo A, Martínez-Banaclocha H, Tourlomousis P, Gangloff M, Pelegrin P, Ruysschaert JM, Gay NJ, Bryant CE Tags: Cell Mol Life Sci Source Type: research

The long non-coding RNA H19: an active player with multiple facets to sustain the hallmarks of cancer.
Abstract Cancer cells exhibit hallmarks in terms of proliferation, resistance to cell death, angiogenesis, invasion, metastasis, and genomic instability. Despite the progress in cancer research and the comprehension of tumorigenesis mechanisms, cancer remains a major issue in public health. A better understanding of the molecular factors associated with the appearance or progression of cancer may allow the development of therapeutic alternatives. Increasing data highlight the role of long non-coding RNAs in many diseases, including cancer. The long non-coding RNA H19 was the first discovered riboregulator, and it ...
Source: Cellular and Molecular Life Sciences : CMLS - July 23, 2019 Category: Cytology Authors: Lecerf C, Le Bourhis X, Adriaenssens E Tags: Cell Mol Life Sci Source Type: research

The nucleolus: a central response hub for the stressors that drive cancer progression.
Abstract The nucleolus is a sub-nuclear body known primarily for its role in ribosome biogenesis. Increased number and/or size of nucleoli have historically been used by pathologists as a prognostic indicator of cancerous lesions. This increase in nucleolar number and/or size is classically attributed to the increased need for protein synthesis in cancer cells. However, evidences suggest that the nucleolus plays critical roles in many cellular functions in both normal cell biology and disease pathologies, including cancer. As new functions of the nucleolus are elucidated, there is mounting evidence to support the ...
Source: Cellular and Molecular Life Sciences : CMLS - July 23, 2019 Category: Cytology Authors: Weeks SE, Metge BJ, Samant RS Tags: Cell Mol Life Sci Source Type: research

EI24 tethers endoplasmic reticulum and mitochondria to regulate autophagy flux.
Abstract Etoposide-induced protein 2.4 (EI24), located on the endoplasmic reticulum (ER) membrane, has been proposed to be an essential autophagy protein. Specific ablation of EI24 in neuronal and liver tissues causes deficiency of autophagy flux. However, the molecular mechanism of the EI24-mediated autophagy process is still poorly understood. Like neurons and hepatic cells, pancreatic β cells are also secretory cells. Pancreatic β cells contain large amounts of ER and continuously synthesize and secrete insulin to maintain blood glucose homeostasis. Yet, the effect of EI24 on autophagy of pancreatic &...
Source: Cellular and Molecular Life Sciences : CMLS - July 22, 2019 Category: Cytology Authors: Yuan L, Liu Q, Wang Z, Hou J, Xu P Tags: Cell Mol Life Sci Source Type: research

Discovering the chloride pathway in the CFTR channel.
űs T Abstract Cystic fibrosis (CF), a lethal monogenic disease, is caused by pathogenic variants of the CFTR chloride channel. The majority of CF mutations affect protein folding and stability leading overall to diminished apical anion conductance of epithelial cells. The recently published cryo-EM structures of full-length human and zebrafish CFTR provide a good model to gain insight into structure-function relationships of CFTR variants. Although, some of the structures were determined in the phosphorylated and ATP-bound active state, none of the static structures showed an open pathway for chloride permeation....
Source: Cellular and Molecular Life Sciences : CMLS - July 20, 2019 Category: Cytology Authors: Farkas B, Tordai H, Padányi R, Tordai A, Gera J, Paragi G, Hegedűs T Tags: Cell Mol Life Sci Source Type: research

Prenatal programming by testosterone of follicular theca cell functions in ovary.
-Tran R, Fabre S Abstract In mammalian ovaries, the theca layers of growing follicles are critical for maintaining their structural integrity and supporting androgen synthesis. Through combining the postnatal monitoring of ovaries by abdominal magnetic resonance imaging, endocrine profiling, hormonal analysis of the follicular fluid of growing follicles, and transcriptomic analysis of follicular theca cells, we provide evidence that the exposure of ovine fetuses to testosterone excess activates postnatal follicular growth and strongly affects the functions of follicular theca in adulthood. Prenatal exposure to tes...
Source: Cellular and Molecular Life Sciences : CMLS - July 20, 2019 Category: Cytology Authors: Monniaux D, Genêt C, Maillard V, Jarrier P, Adriaensen H, Hennequet-Antier C, Lainé AL, Laclie C, Papillier P, Plisson-Petit F, Estienne A, Cognié J, di Clemente N, Dalbies-Tran R, Fabre S Tags: Cell Mol Life Sci Source Type: research

ZNFX1 anti-sense RNA 1 promotes the tumorigenesis of prostate cancer by regulating c-Myc expression via a regulatory network of competing endogenous RNAs.
Abstract ZNFX1 anti-sense RNA 1 (ZFAS1) has been indicated in the tumorigenesis of various human cancers. However, the role of ZFAS1 in prostate cancer (PCa) progression and the underlying mechanisms remain incompletely understood. In the present study, we discovered that ZFAS1 is upregulated in PCa and that ZFAS1 overexpression predicted poor clinical outcomes. ZFAS1 overexpression notably promoted the proliferation, invasion, and epithelial-mesenchymal transition of PCa cells. Furthermore, we not only discovered that miR-27a/15a/16 are targeted by ZFAS1, which binds to their miRNA-response elements, but also rev...
Source: Cellular and Molecular Life Sciences : CMLS - July 18, 2019 Category: Cytology Authors: Cui X, Piao C, Lv C, Lin X, Zhang Z, Liu X Tags: Cell Mol Life Sci Source Type: research

The E. coli MinCDE system in the regulation of protein patterns and gradients.
Abstract Molecular self-organziation, also regarded as pattern formation, is crucial for the correct distribution of cellular content. The processes leading to spatiotemporal patterns often involve a multitude of molecules interacting in complex networks, so that only very few cellular pattern-forming systems can be regarded as well understood. Due to its compositional simplicity, the Escherichia coli MinCDE system has, thus, become a paradigm for protein pattern formation. This biological reaction diffusion system spatiotemporally positions the division machinery in E. coli and is closely related to ParA-type ATP...
Source: Cellular and Molecular Life Sciences : CMLS - July 17, 2019 Category: Cytology Authors: Ramm B, Heermann T, Schwille P Tags: Cell Mol Life Sci Source Type: research

Stem cells in tissues, organoids, and cancers.
Abstract Stem cells give rise to all cells and build the tissue structures in our body, and heterogeneity and plasticity are the hallmarks of stem cells. Epigenetic modification, which is associated with niche signals, determines stem cell differentiation and somatic cell reprogramming. Stem cells play a critical role in the development of tumors and are capable of generating 3D organoids. Understanding the properties of stem cells will improve our capacity to maintain tissue homeostasis. Dissecting epigenetic regulation could be helpful for achieving efficient cell reprograming and for developing new drugs for ca...
Source: Cellular and Molecular Life Sciences : CMLS - July 17, 2019 Category: Cytology Authors: Wang X Tags: Cell Mol Life Sci Source Type: research

Chondromodulin-1 in health, osteoarthritis, cancer, and heart disease.
Abstract The human chondromodulin-1 (Chm-1, Chm-I, CNMD, or Lect1) gene encodes a 334 amino acid type II transmembrane glycoprotein protein with characteristics of a furin cleavage site and a putative glycosylation site. Chm-1 is expressed most predominantly in healthy and developing avascular cartilage, and healthy cardiac valves. Chm-1 plays a vital role during endochondral ossification by the regulation of angiogenesis. The anti-angiogenic and chondrogenic properties of Chm-1 are attributed to its role in tissue development, homeostasis, repair and regeneration, and disease prevention. Chm-1 promotes chondrocyt...
Source: Cellular and Molecular Life Sciences : CMLS - July 17, 2019 Category: Cytology Authors: Zhu S, Qiu H, Bennett S, Kuek V, Rosen V, Xu H, Xu J Tags: Cell Mol Life Sci Source Type: research

miR-221 and -222 target CACNA1C and KCNJ5 leading to altered cardiac ion channel expression and current density.
r B Abstract MicroRNAs (miRs) contribute to different aspects of cardiovascular pathology, among others cardiac hypertrophy and atrial fibrillation. The aim of our study was to evaluate the impact of miR-221/222 on cardiac electrical remodeling. Cardiac miR expression was analyzed in a mouse model with altered electrocardiography parameters and severe heart hypertrophy. Next generation sequencing revealed 14 differentially expressed miRs in hypertrophic hearts, with miR-221 and -222 being the strongest regulated miR-cluster. This increase was restricted to cardiomyocytes and not observed in cardiac fibroblasts. Ad...
Source: Cellular and Molecular Life Sciences : CMLS - July 16, 2019 Category: Cytology Authors: Binas S, Knyrim M, Hupfeld J, Kloeckner U, Rabe S, Mildenberger S, Quarch K, Strätz N, Misiak D, Gekle M, Grossmann C, Schreier B Tags: Cell Mol Life Sci Source Type: research

Cell-surface molecule-mediated cell-cell interactions in the regulation of ILC2-driven allergic inflammation.
Abstract Group 2 innate lymphoid cells (ILC2s) are a subset of innate immune cells that do not express antigen receptors. ILC2-mediated type 2 responses, which are mainly characterized by the production of interleukin (IL)-5 and IL-13, play key roles in inducing inflammation, protecting against infection, and maintaining tissue homeostasis. Although recent years have largely enhanced our understanding of the transcriptional networks and soluble mediators that regulate ILC2 development or function, emerging evidence suggests that ILC2s express a variety of cell-surface molecules and interact with themselves or othe...
Source: Cellular and Molecular Life Sciences : CMLS - July 16, 2019 Category: Cytology Authors: Lei A, Zhou J Tags: Cell Mol Life Sci Source Type: research

Src and Fyn define a new signaling cascade activated by canonical and non-canonical Wnt ligands and required for gene transcription and cell invasion.
tilde;ach M Abstract Wnt ligands signal through canonical or non-canonical signaling pathways. Although both routes share common elements, such as the Fz2 receptor, they differ in the co-receptor and in many of the final responses; for instance, whereas canonical Wnts increase β-catenin stability, non-canonical ligands downregulate it. However, both types of ligands stimulate tumor cell invasion. We show here that both the canonical Wnt3a and the non-canonical Wnt5a stimulate Fz2 tyrosine phosphorylation, Fyn binding to Fz2, Fyn activation and Fyn-dependent Stat3 phosphorylation. Wnt3a and Wnt5a require Src f...
Source: Cellular and Molecular Life Sciences : CMLS - July 16, 2019 Category: Cytology Authors: Villarroel A, Del Valle-Pérez B, Fuertes G, Curto J, Ontiveros N, Garcia de Herreros A, Duñach M Tags: Cell Mol Life Sci Source Type: research

Knockout of beta-2 microglobulin enhances cardiac repair by modulating exosome imprinting and inhibiting stem cell-induced immune rejection.
CONCLUSION: Our findings demonstrate that modulation of exosome's imprinting via B2M knockout is an efficient strategy to prevent the immune rejection of alloUMSCs. This study paved the way to the development of new strategies for tissue repair and regeneration without the need for HLA matching. PMID: 31312880 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - July 16, 2019 Category: Cytology Authors: Shao L, Zhang Y, Pan X, Liu B, Liang C, Zhang Y, Wang Y, Yan B, Xie W, Sun Y, Shen Z, Yu XY, Li Y Tags: Cell Mol Life Sci Source Type: research

Long non-coding RNA PVT1 interacts with MYC and its downstream molecules to synergistically promote tumorigenesis.
Abstract Numerous studies have shown that non-coding RNAs play crucial roles in the development and progression of various tumor cells. Plasmacytoma variant translocation 1 (PVT1) mainly encodes a long non-coding RNA (lncRNA) and is located on chromosome 8q24.21, which constitutes a fragile site for genetic aberrations. PVT1 is well-known for its interaction with its neighbor MYC, which is a qualified oncogene that plays a vital role in tumorigenesis. In the past several decades, increasing attention has been paid to the interaction mechanism between PVT1 and MYC, which will benefit the clinical treatment and prog...
Source: Cellular and Molecular Life Sciences : CMLS - July 15, 2019 Category: Cytology Authors: Jin K, Wang S, Zhang Y, Xia M, Mo Y, Li X, Li G, Zeng Z, Xiong W, He Y Tags: Cell Mol Life Sci Source Type: research

The Tousled-like kinases regulate genome and epigenome stability: implications in development and disease.
Abstract The Tousled-like kinases (TLKs) are an evolutionarily conserved family of serine-threonine kinases that have been implicated in DNA replication, DNA repair, transcription, chromatin structure, viral latency, cell cycle checkpoint control and chromosomal stability in various organisms. The functions of the TLKs appear to depend largely on their ability to regulate the H3/H4 histone chaperone ASF1, although numerous TLK substrates have been proposed. Over the last few years, a clearer picture of TLK function has emerged through the identification of new partners, the definition of specific roles in developm...
Source: Cellular and Molecular Life Sciences : CMLS - July 13, 2019 Category: Cytology Authors: Segura-Bayona S, Stracker TH Tags: Cell Mol Life Sci Source Type: research

Impact of 17 β-HSD12, the 3-ketoacyl-CoA reductase of long-chain fatty acid synthesis, on breast cancer cell proliferation and migration.
Impact of 17β-HSD12, the 3-ketoacyl-CoA reductase of long-chain fatty acid synthesis, on breast cancer cell proliferation and migration. Cell Mol Life Sci. 2019 Jul 13;: Authors: Tsachaki M, Strauss P, Dunkel A, Navrátilová H, Mladenovic N, Odermatt A Abstract Metabolic reprogramming of tumor cells involves upregulation of fatty acid (FA) synthesis to support high bioenergetic demands and membrane synthesis. This has been shown for cytosolic synthesis of FAs with up to 16 carbon atoms. Synthesis of long-chain fatty acids (LCFAs), including ω-6 and ω-3 polyunsaturated FAs...
Source: Cellular and Molecular Life Sciences : CMLS - July 13, 2019 Category: Cytology Authors: Tsachaki M, Strauss P, Dunkel A, Navrátilová H, Mladenovic N, Odermatt A Tags: Cell Mol Life Sci Source Type: research

Building bridges between chromosomes: novel insights into the abscission checkpoint.
Abstract In the presence of chromatin bridges, mammalian cells delay completion of cytokinesis (abscission) to prevent chromatin breakage or tetraploidization by regression of the cleavage furrow. This abscission delay is called "the abscission checkpoint" and is dependent on Aurora B kinase. Furthermore, cells stabilize the narrow cytoplasmic canal between the two daughter cells until the DNA bridges are resolved. Impaired abscission checkpoint signaling or unstable intercellular canals can lead to accumulation of DNA damage, aneuploidy, or generation of polyploid cells which are associated with tumouri...
Source: Cellular and Molecular Life Sciences : CMLS - July 13, 2019 Category: Cytology Authors: Petsalaki E, Zachos G Tags: Cell Mol Life Sci Source Type: research

Molecular characterization of an aquaporin-2 mutation causing a severe form of nephrogenic diabetes insipidus.
This study aimed to determine the cell biological consequences of this mutation on AQP2 function. Studies were performed in HEK293 and MDCK type I cells, transfected with wildtype (WT) AQP2 or an AQP2-L137P mutant. AQP2-L137P was predominantly detected as a high-mannose form of AQP2, whereas AQP2-WT was observed in both non-glycosylated and complex glycosylated forms. In contrast to AQP2-WT, the AQP2-L137P mutant did not accumulate on the apical plasma membrane following stimulation with forskolin. Ubiquitylation of AQP2-L137P was different from AQP2-WT, with predominance of non-distinct protein bands at various molecular ...
Source: Cellular and Molecular Life Sciences : CMLS - July 13, 2019 Category: Cytology Authors: Saglar Ozer E, Moeller HB, Karaduman T, Fenton RA, Mergen H Tags: Cell Mol Life Sci Source Type: research

Efficient base editing by RNA-guided cytidine base editors (CBEs) in pigs.
In this study, we showed that the BE4-Gam system induced the targeted C-to-T base conversion in porcine blastocysts at an efficiency of 66.7-71.4% via the injection of a single sgRNA targeting a xeno-antigen-related gene and BE4-Gam mRNA. Furthermore, the efficiency of simultaneous three gene base conversion via the injection of three targeting sgRNAs and BE4-Gam mRNA into porcine parthenogenetic embryos was 18.1%. We also obtained beta-1,4-N-acetyl-galactosaminyl transferase 2, alpha-1,3-galactosyltransferase, and cytidine monophosphate-N-acetylneuraminic acid hydroxylase deficient pig by somatic cell nuclear transfe...
Source: Cellular and Molecular Life Sciences : CMLS - July 13, 2019 Category: Cytology Authors: Yuan H, Yu T, Wang L, Yang L, Zhang Y, Liu H, Li M, Tang X, Liu Z, Li Z, Lu C, Chen X, Pang D, Ouyang H Tags: Cell Mol Life Sci Source Type: research

Biological functions and clinical applications of exosomal non-coding RNAs in hepatocellular carcinoma.
Abstract Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, with a high mortality rate. Its dismal prognosis is attributed to late diagnosis, high risk of recurrence and drug resistance. To improve the survival of patients with HCC, new approaches are required for early diagnosis, real-time monitoring and effective treatment. Exosomes are small membranous vesicles released by most cells that contain biological molecules and play a great role in intercellular communication under physiological or pathological conditions. In cancer, exosomes from tumor cells or non-tumor cells can be tak...
Source: Cellular and Molecular Life Sciences : CMLS - July 12, 2019 Category: Cytology Authors: Li C, Xu X Tags: Cell Mol Life Sci Source Type: research

Molecular control of the female germline stem cell niche size in Drosophila.
Abstract Adult stem cells have a unique capacity to renew themselves and generate differentiated cells that are needed in the body. These cells are recruited and maintained by the surrounding microenvironment, known as the stem cell niche, during organ development. Thus, the stem cell niche is required for proper tissue homeostasis, and its dysregulation is associated with tumorigenesis and tissue degeneration. The identification of niche components and the mechanisms that regulate niche establishment and maintenance, however, are just beginning to be uncovered. Germline stem cells (GSCs) of the Drosophila ovary p...
Source: Cellular and Molecular Life Sciences : CMLS - July 12, 2019 Category: Cytology Authors: Hsu HJ, Bahader M, Lai CM Tags: Cell Mol Life Sci Source Type: research

Degranulation of human cytotoxic lymphocytes is a major source of proteolytically active soluble CD26/DPP4.
Abstract Dipeptidyl peptidase 4 (DPP4, CD26) is a serine protease detected on several immune cells and on epithelial cells of various organs. Besides the membrane-bound enzyme, a catalytically active soluble form (sCD26/DPP4) is detected in several body fluids. Both variants cleave off dipeptides from the N-termini of various chemokines, neuropeptides, and hormones. CD26/DPP4 plays a fundamental role in the regulation of blood glucose levels by inactivating insulinotropic incretins and CD26/DPP4 inhibitors are thus routinely used in diabetes mellitus type 2 therapy to improve glucose tolerance. Such inhibitors mig...
Source: Cellular and Molecular Life Sciences : CMLS - July 12, 2019 Category: Cytology Authors: Lettau M, Dietz M, Vollmers S, Armbrust F, Peters C, Dang TM, Chitadze G, Kabelitz D, Janssen O Tags: Cell Mol Life Sci Source Type: research

Acute hydroxyurea-induced replication blockade results in replisome components disengagement from nascent DNA without causing fork collapse.
In this study, we aimed to understand the mechanisms involved in fork stability maintenance in non-transformed human cells by performing an isolation of proteins on nascent DNA-mass spectrometry analysis in hTERT-RPE cells under different replication stress conditions. Our results show that acute hydroxyurea-induced replication blockade causes the accumulation of large amounts of single-stranded DNA at the fork. Remarkably, this results in the disengagement of replisome components from nascent DNA without compromising fork restart. Notably, Cdc45-MCM-GINS helicase maintains its integrity and replisome components remain ass...
Source: Cellular and Molecular Life Sciences : CMLS - July 11, 2019 Category: Cytology Authors: Ercilla A, Feu S, Aranda S, Llopis A, Brynjólfsdóttir SH, Sørensen CS, Toledo LI, Agell N Tags: Cell Mol Life Sci Source Type: research

Correction to: Dsg2 via  Src-mediated transactivation shapes EGFR signaling towards cell adhesion.
Correction to: Dsg2 via Src-mediated transactivation shapes EGFR signaling towards cell adhesion. Cell Mol Life Sci. 2019 Jul 10;: Authors: Ungewiß H, Rötzer V, Meir M, Fey C, Diefenbacher M, Schlegel N, Waschke J Abstract In the published article, the legend for figure 3 was incorrect. The correct legend is given below. PMID: 31292664 [PubMed - as supplied by publisher] (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - July 10, 2019 Category: Cytology Authors: Ungewiß H, Rötzer V, Meir M, Fey C, Diefenbacher M, Schlegel N, Waschke J Tags: Cell Mol Life Sci Source Type: research

Purinergic P2Y2 receptors modulate endothelial sprouting.
Holnthoner W Abstract Purinergic P2 receptors are critical regulators of several functions within the vascular system, including platelet aggregation, vascular inflammation, and vascular tone. However, a role for ATP release and P2Y receptor signalling in angiogenesis remains poorly defined. Here, we demonstrate that blood vessel growth is controlled by P2Y2 receptors. Endothelial sprouting and vascular tube formation were significantly dependent on P2Y2 expression and inhibition of P2Y2 using a selective antagonist blocked microvascular network generation. Mechanistically, overexpression of P2Y2 in endothelial c...
Source: Cellular and Molecular Life Sciences : CMLS - July 5, 2019 Category: Cytology Authors: Mühleder S, Fuchs C, Basílio J, Szwarc D, Pill K, Labuda K, Slezak P, Siehs C, Pröll J, Priglinger E, Hoffmann C, Junger WG, Redl H, Holnthoner W Tags: Cell Mol Life Sci Source Type: research

Genomic imprinting and its effects on postnatal growth and adult metabolism.
Abstract Imprinted genes display parent-of-origin-specific expression with this epigenetic system of regulation found exclusively in therian mammals. Historically, defined imprinted gene functions were almost solely focused on pregnancy and the influence on the growth parameters of the developing embryo and placenta. More recently, a number of postnatal functions have been identified which converge on resource allocation, both for animals in the nest and in adults. While many of the prenatal functions of imprinted genes that have so far been described adhere to the "parental conflict" hypothesis, no clea...
Source: Cellular and Molecular Life Sciences : CMLS - July 3, 2019 Category: Cytology Authors: Millership SJ, Van de Pette M, Withers DJ Tags: Cell Mol Life Sci Source Type: research

Guidance of circular RNAs to proteins' behavior as binding partners.
Abstract Circular RNAs (circRNAs) are single-stranded and covalently closed back-splicing products of pre-mRNAs. They can be derived from exons, introns, or exons with intron retained between exons of transcripts, as well as antisense transcripts. CircRNAs have been reported to function as microRNA sponges, regulate gene transcription mediated by RNA polymerase II, and modulate the splicing or stability of mRNA. However, emerging studies demonstrate that they affect the behavior of proteins via direct interactions with them. Here, we summarize that by binding directly with proteins; circRNAs can facilitate their n...
Source: Cellular and Molecular Life Sciences : CMLS - July 3, 2019 Category: Cytology Authors: Luo J, Liu H, Luan S, Li Z Tags: Cell Mol Life Sci Source Type: research

Metabolic reprogramming of normal oral fibroblasts correlated with increased glycolytic metabolism of oral squamous cell carcinoma and precedes their activation into carcinoma associated fibroblasts.
Abstract Cancers show a metabolic shift towards aerobic glycolysis. By "corrupting" their microenvironment, carcinoma cells are able to obtain energy substrates to "fuel" their mitochondrial metabolism and cell growth in an autophagy-associated, paracrine manner. However, the metabolic changes and role of normal fibroblasts in this process remain unclear. We devised a novel, indirect co-culture system to elucidate the mechanisms of metabolic coupling between stromal cells and oral squamous cell carcinoma (OSCC) cells. Here, we showed that normal oral fibroblasts (NOFs) and OSCC become metabolic...
Source: Cellular and Molecular Life Sciences : CMLS - July 3, 2019 Category: Cytology Authors: Zhang Z, Gao Z, Rajthala S, Sapkota D, Dongre H, Parajuli H, Suliman S, Das R, Li L, Bindoff LA, Costea DE, Liang X Tags: Cell Mol Life Sci Source Type: research

Cellular expression and function of naturally occurring variants of the human ABCG2 multidrug transporter.
ute;, Homolya L, Orbán TI, Sarkadi B Abstract The human ABCG2 multidrug transporter plays a crucial role in the absorption and excretion of xeno- and endobiotics; thus the relatively frequent polymorphic and mutant ABCG2 variants in the population may significantly alter disease conditions and pharmacological effects. Low-level or non-functional ABCG2 expression may increase individual drug toxicity, reduce cancer drug resistance, and result in hyperuricemia and gout. In the present work we have studied the cellular expression, trafficking, and function of nine naturally occurring polymorphic and mutant var...
Source: Cellular and Molecular Life Sciences : CMLS - June 28, 2019 Category: Cytology Authors: Zámbó B, Mózner O, Bartos Z, Török G, Várady G, Telbisz Á, Homolya L, Orbán TI, Sarkadi B Tags: Cell Mol Life Sci Source Type: research

Mechanisms regulating mammalian spermatogenesis and fertility recovery following germ  cell depletion.
Mechanisms regulating mammalian spermatogenesis and fertility recovery following germ cell depletion. Cell Mol Life Sci. 2019 Jun 28;: Authors: La HM, Hobbs RM Abstract Mammalian spermatogenesis is a highly complex multi-step process sustained by a population of mitotic germ cells with self-renewal potential known as spermatogonial stem cells (SSCs). The maintenance and regulation of SSC function are strictly dependent on a supportive niche that is composed of multiple cell types. A detailed appreciation of the molecular mechanisms underpinning SSC activity and fate is of fundamental importance f...
Source: Cellular and Molecular Life Sciences : CMLS - June 28, 2019 Category: Cytology Authors: La HM, Hobbs RM Tags: Cell Mol Life Sci Source Type: research

Mechanisms of PINK1, ubiquitin and Parkin interactions in mitochondrial quality control and beyond.
Abstract Parkinson's disease (PD) is a degenerative movement disorder resulting from the loss of specific neuron types in the midbrain. Early environmental and pathophysiological studies implicated mitochondrial damage and protein aggregation as the main causes of PD. These findings are now vindicated by the characterization of more than 20 genes implicated in rare familial forms of the disease. In particular, two proteins encoded by the Parkin and PINK1 genes, whose mutations cause early-onset autosomal recessive PD, function together in a mitochondrial quality control pathway. In this review, we will describe re...
Source: Cellular and Molecular Life Sciences : CMLS - June 28, 2019 Category: Cytology Authors: Bayne AN, Trempe JF Tags: Cell Mol Life Sci Source Type: research