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Biochemical Society Transactions

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https://www.readbyqxmd.com/read/30242121/cell-cycle-dependent-phosphorylation-and-regulation-of-cellular-differentiation
#1
REVIEW
Laura J A Hardwick, Roberta Azzarelli, Anna Philpott
Embryogenesis requires an exquisite regulation of cell proliferation, cell cycle withdrawal and differentiation into a massively diverse range of cells at the correct time and place. Stem cells also remain to varying extents in different adult tissues, acting in tissue homeostasis and repair. Therefore, regulated proliferation and subsequent differentiation of stem and progenitor cells remains pivotal throughout life. Recent advances have characterised the cell cycle dynamics, epigenetics, transcriptome and proteome accompanying the transition from proliferation to differentiation, revealing multiple bidirectional interactions between the cell cycle machinery and factors driving differentiation...
September 20, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30242120/extracellular-vesicles-translational-challenges-and-opportunities
#2
REVIEW
Hannah Clemmens, Daniel W Lambert
Extracellular vesicles (EVs) are a heterogeneous group of small lipid-enclosed structures with myriad roles in physiology and disease. The recent surge of interest in EVs has led to greater understanding of their biology and appreciation of how they might be utilised as diagnostic and therapeutic tools. There remain, however, a number of challenges that must be overcome before EVs may be used routinely in the clinic. In this review we will discuss the translational potential of EVs and the current technologies available to isolate, purify and analyse EVs and their contents...
September 20, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30242119/the-golgi-architecture-and-cell-sensing
#3
REVIEW
Christian Makhoul, Prajakta Gosavi, Paul A Gleeson
An array of signalling molecules are located at the Golgi apparatus, including phosphoinositides, small GTPases, kinases, and phosphatases, which are linked to multiple signalling pathways. Initially considered to be associated predominantly with membrane trafficking, signalling pathways at the Golgi are now recognised to regulate a diverse range of higher-order functions. Many of these signalling pathways are influenced by the architecture of the Golgi. In vertebrate cells, the Golgi consists of individual stacks fused together into a compact ribbon structure and the function of this ribbon structure has been enigmatic...
September 20, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30242118/emerging-role-of-extracellular-vesicles-in-mediating-cancer-cachexia
#4
REVIEW
Sai V Chitti, Pamali Fonseka, Suresh Mathivanan
Cancer cachexia is a multifactorial metabolic syndrome characterized by the rapid loss of skeletal muscle mass with or without the loss of fat mass. Nearly 50-80% of all cancer patients' experience rapid weight loss results in ∼20% of cancer-related deaths. The levels of pro-inflammatory and pro-cachectic factors were significantly up-regulated in cachexia patients when compared with the patients who were without cachexia. It is becoming evident that these factors work synergistically to induce cancer cachexia...
September 20, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30242117/protein-structure-and-computational-drug-discovery
#5
REVIEW
Tracy L Nero, Michael W Parker, Craig J Morton
The first protein structures revealed a complex web of weak interactions stabilising the three-dimensional shape of the molecule. Small molecule ligands were then found to exploit these same weak binding events to modulate protein function or act as substrates in enzymatic reactions. As the understanding of ligand-protein binding grew, it became possible to firstly predict how and where a particular small molecule might interact with a protein, and then to identify putative ligands for a specific protein site...
September 20, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30242116/lipids-and-lipid-domains-of-the-yeast-vacuole
#6
REVIEW
Takuma Tsuji, Toyoshi Fujimoto
The membrane raft has been a focus of intensive research for the past two decades. Liquid-ordered domains form in artificial liposomes containing sterol and saturated lipids, but their presence in living cell membranes has been controversial. The yeast vacuole is exceptional in that micron-sized raft-like domains form in the stationary phase and under several other conditions. The sterol content of the vacuole in the log phase is much lower than that of liposomes showing liquid-ordered domains, suggesting that sterols may need to be supplied to the vacuole for the raft-like domain formation...
September 20, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30242115/the-creatine-kinase-system-as-a-therapeutic-target-for-myocardial-ischaemia-reperfusion-injury
#7
REVIEW
Fang Cao, Sevasti Zervou, Craig A Lygate
Restoring blood flow following an acute myocardial infarction saves lives, but results in tissue damage due to ischaemia-reperfusion injury (I/R). Ameliorating this damage is a major research goal to improve recovery and reduce subsequent morbidity due to heart failure. Both the ischaemic and reperfusion phases represent crises of cellular energy provision in which the mitochondria play a central role. This mini-review will explore the rationale and therapeutic potential of augmenting the creatine kinase (CK) energy shuttle, which constitutes the primary short-term energy buffer and transport system in the cardiomyocyte...
September 20, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30242114/roles-for-er-endosome-membrane-contact-sites-in-ligand-stimulated-intraluminal-vesicle-formation
#8
REVIEW
Louise H Wong, Emily R Eden, Clare E Futter
Multivesicular endosomes/bodies (MVBs) sort membrane proteins between recycling and degradative pathways. Segregation of membrane proteins onto intraluminal vesicles (ILVs) of MVBs removes them from the recycling pathway and facilitates their degradation following fusion of MVBs with lysosomes. Sorting of many cargos onto ILVs depends on the ESCRT (Endosomal Sorting Complex Required for Transport) machinery, although ESCRT-independent mechanisms also exist. In mammalian cells, efficient sorting of ligand-stimulated epidermal growth factor receptors onto ILVs also depends on the tyrosine phosphatase, PTP1B, an ER-localised enzyme that interacts with endosomal targets at membrane contacts between MVBs and the ER...
September 20, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30190332/the-discovery-of-hydrogen-bonds-in-dna-and-a-re-evaluation-of-the-1948-creeth-two-chain-model-for-its-structure
#9
REVIEW
Stephen E Harding, Guy Channell, Mary K Phillips-Jones
We recall the experimental approaches involved in the discovery of hydrogen bonds in deoxyribonucleic acid (DNA) made 70 years ago by a team of scientists at University College Nottingham led by J.M. Gulland, and in relation to previous studies. This discovery proved an important step in the elucidation of the correct structure for DNA made by J.D. Watson and F.H.C. Crick, as acknowledged in ' The Double Helix '. At that time of the discovery, however, it was impossible to delineate between inter- and intra-chain hydrogen bonds...
September 6, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30190331/recent-advances-in-threshold-dependent-gene-drives-for-mosquitoes
#10
REVIEW
Philip T Leftwich, Matthew P Edgington, Tim Harvey-Samuel, Leonela Z Carabajal Paladino, Victoria C Norman, Luke Alphey
Mosquito-borne diseases, such as malaria, dengue and chikungunya, cause morbidity and mortality around the world. Recent advances in gene drives have produced control methods that could theoretically modify all populations of a disease vector, from a single release, making whole species less able to transmit pathogens. This ability has caused both excitement, at the prospect of global eradication of mosquito-borne diseases, and concern around safeguards. Drive mechanisms that require individuals to be released at high frequency before genes will spread can therefore be desirable as they are potentially localised and reversible...
September 6, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30190330/dissecting-the-role-of-his-domain-protein-tyrosine-phosphatase-ptpn23-and-escrts-in-sorting-activated-epidermal-growth-factor-receptor-to-the-multivesicular-body
#11
REVIEW
Lydia Tabernero, Philip Woodman
Sorting of activated epidermal growth factor receptor (EGFR) into intraluminal vesicles (ILVs) within the multivesicular body (MVB) is an essential step during the down-regulation of the receptor. The machinery that drives EGFR sorting attaches to the cytoplasmic face of the endosome and generates vesicles that bud into the endosome lumen, but somehow escapes encapsulation itself. This machinery is termed the ESCRT (endosomal sorting complexes required for transport) pathway, a series of multi-protein complexes and accessory factors first identified in yeast...
September 6, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30190329/lipids-modulate-the-insertion-and-folding-of-the-nascent-chains-of-alpha-helical-membrane-proteins
#12
REVIEW
Nicola J Harris, Kalypso Charalambous, Heather E Findlay, Paula J Booth
Membrane proteins must be inserted into a membrane and folded into their correct structure to function correctly. This insertion occurs during translation and synthesis by the ribosome for most α-helical membrane proteins. Precisely how this co-translational insertion and folding occurs, and the role played by the surrounding lipids, is still not understood. Most of the work on the influence of the lipid environment on folding and insertion has focussed on denatured, fully translated proteins, and thus does not replicate folding during unidirectional elongation of nascent chains that occurs in the cell...
September 6, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30190328/do-nitric-oxide-carbon-monoxide-and-hydrogen-sulfide-really-qualify-as-gasotransmitters-in-bacteria
#13
REVIEW
Lauren K Wareham, Hannah M Southam, Robert K Poole
A gasotransmitter is defined as a small, generally reactive, gaseous molecule that, in solution, is generated endogenously in an organism and exerts important signalling roles. It is noteworthy that these molecules are also toxic and antimicrobial. We ask: is this definition of a gasotransmitter appropriate in the cases of nitric oxide, carbon monoxide and hydrogen sulfide (H2 S) in microbes? Recent advances show that, not only do bacteria synthesise each of these gases, but the molecules also have important signalling or messenger roles in addition to their toxic effects...
September 6, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30154099/flavin-transferase-the-maturation-factor-of-flavin-containing-oxidoreductases
#14
REVIEW
Alexander V Bogachev, Alexander A Baykov, Yulia V Bertsova
Flavins, cofactors of many enzymes, are often covalently linked to these enzymes; for instance, flavin adenine mononucleotide (FMN) can form a covalent bond through either its phosphate or isoalloxazine group. The prevailing view had long been that all types of covalent attachment of flavins occur as autocatalytic reactions; however, in 2013, the first flavin transferase was identified, which catalyzes phosphoester bond formation between FMN and Na+ -translocating NADH:quinone oxidoreductase in certain bacteria...
August 28, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30154098/the-structural-basis-of-cystic-fibrosis
#15
REVIEW
Xin Meng, Jack Clews, Eleanor R Martin, Anca D Ciuta, Robert C Ford
CFTR (ABCC7) is a phospho-regulated chloride channel that is found in the apical membranes of epithelial cells, is gated by ATP and the activity of the protein is crucial in the homeostasis of the extracellular liquid layer in many organs [ Annu. Rev. Biochem. (2008) 77 , 701-726; Science (1989) 245 , 1066-1073]. Mutations in CFTR cause the inherited disease cystic fibrosis (CF), the most common inherited condition in humans of European descent [ Science (1989) 245 , 1066-1073; Pflugers Arch. (2007) 453 , 555-567]...
August 28, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30154097/the-molecular-clock-and-evolutionary-timescales
#16
REVIEW
Arong Luo, Simon Y W Ho
The molecular clock provides a valuable means of estimating evolutionary timescales from genetic and biochemical data. Proposed in the early 1960s, it was first applied to amino acid sequences and immunological measures of genetic distances between species. The molecular clock has undergone considerable development over the years, and it retains profound relevance in the genomic era. In this mini-review, we describe the history of the molecular clock, its impact on evolutionary theory, the challenges brought by evidence of evolutionary rate variation among species, and the statistical models that have been developed to account for these heterogeneous rates of genetic change...
August 28, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30154096/the-role-of-mtor-mediated-signals-during-haemopoiesis-and-lineage-commitment
#17
REVIEW
Natasha Malik, Owen J Sansom, Alison M Michie
The serine/threonine protein kinase mechanistic target of rapamycin (mTOR) has been implicated in the regulation of an array of cellular functions including protein and lipid synthesis, proliferation, cell size and survival. Here, we describe the role of mTOR during haemopoiesis within the context of mTORC1 and mTORC2, the distinct complexes in which it functions. The use of conditional transgenic mouse models specifically targeting individual mTOR signalling components, together with selective inhibitors, have generated a significant body of research emphasising the critical roles played by mTOR, and individual mTOR complexes, in haemopoietic lineage commitment and development...
August 28, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30154095/fantastic-voyage-the-journey-of-intestinal-microbiota-derived-microvesicles-through-the-body
#18
REVIEW
Régis Stentz, Ana L Carvalho, Emily J Jones, Simon R Carding
As part of their life cycle, Gram-negative bacteria produce and release microvesicles (outer membrane vesicles, OMVs) consisting of spherical protrusions of the outer membrane that encapsulate periplasmic contents. OMVs produced by commensal bacteria in the gastrointestinal (GI) tract of animals are dispersed within the gut lumen with their cargo and enzymes being distributed across and throughout the GI tract. Their ultimate destination and fate is unclear although they can interact with and cross the intestinal epithelium using different entry pathways and access underlying immune cells in the lamina propria...
August 28, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30154094/inside-job-how-the-escrts-release-hiv-1-from-infected-cells
#19
REVIEW
James H Hurley, A King Cada
Human immunodeficiency virus type 1 (HIV-1) hijacks the host endosomal sorting complex required for transport (ESCRT) proteins in order to release infectious viral particles from the cell. ESCRT recruitment is virtually essential for the production of infectious virus, despite that the main structural protein of HIV-1, Gag, is capable of self-assembling and eventually budding from membranes on its own. Recent data have reinforced the paradigm of ESCRT-dependent particle release while clarifying why this rapid release is so critical...
August 28, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/30154093/mammalian-dna-methyltransferases-new-discoveries-and-open-questions
#20
REVIEW
Humaira Gowher, Albert Jeltsch
As part of the epigenetic network, DNA methylation is a major regulator of chromatin structure and function. In mammals, it mainly occurs at palindromic CpG sites, but asymmetric methylation at non-CpG sites is also observed. Three enzymes are involved in the generation and maintenance of DNA methylation patterns. DNMT1 has high preference for hemimethylated CpG sites, and DNMT3A and DNMT3B equally methylate unmethylated and hemimethylated DNA, and also introduce non-CpG methylation. Here, we review recent observations and novel insights into the structure and function of mammalian DNMTs (DNA methyltransferases), including new structures of DNMT1 and DNMT3A, data on their mechanism, regulation by post-translational modifications and on the function of DNMTs in cells...
August 28, 2018: Biochemical Society Transactions
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