Predicting the unexpected in stomatal gas exchange: not just an open-and-shut case.
tt MR Abstract Plant membrane transport, like transport across all eukaryotic membranes, is highly non-linear and leads to interactions with characteristics so complex that they defy intuitive understanding. The physiological behaviour of stomatal guard cells is a case in point in which, for example, mutations expected to influence stomatal closing have profound effects on stomatal opening and manipulating transport across the vacuolar membrane affects the plasma membrane. Quantitative mathematical modelling is an essential tool in these circumstances, both to integrate the knowledge of each transport process and ...
Source: Biochemical Society Transactions - May 26, 2020 Category: Biochemistry Authors: Klejchová M, Hills A, Blatt MR Tags: Biochem Soc Trans Source Type: research

Investigating the importance of individual mitochondrial genotype in susceptibility to drug-induced toxicity.
Abstract The mitochondrion is an essential organelle responsible for generating cellular energy. Additionally, mitochondria are a source of inter-individual variation as they contain their own genome. Evidence has revealed that mitochondrial DNA (mtDNA) variation can confer differences in mitochondrial function and importantly, these differences may be a factor underlying the idiosyncrasies associated with unpredictable drug-induced toxicities. Thus far, preclinical and clinical data are limited but have revealed evidence in support of an association between mitochondrial haplogroup and susceptibility to specific ...
Source: Biochemical Society Transactions - May 26, 2020 Category: Biochemistry Authors: Penman SL, Carter AS, Chadwick AE Tags: Biochem Soc Trans Source Type: research

Inhibitors in AKTion: ATP-competitive vs allosteric.
Abstract Aberrant activation of the PI3K pathway is one of the commonest oncogenic events in human cancer. AKT is a key mediator of PI3K oncogenic function, and thus has been intensely pursued as a therapeutic target. Multiple AKT inhibitors, broadly classified as either ATP-competitive or allosteric, are currently in various stages of clinical development. Herein, we review the evidence for AKT dependence in human tumours and focus on its therapeutic targeting by the two drug classes. We highlight the future prospects for the development and implementation of more effective context-specific AKT inhibitors aided b...
Source: Biochemical Society Transactions - May 26, 2020 Category: Biochemistry Authors: Lazaro G, Kostaras E, Vivanco I Tags: Biochem Soc Trans Source Type: research

Monolysocardiolipin (MLCL) interactions with mitochondrial membrane proteins.
Abstract Monolysocardiolipin (MLCL) is a three-tailed variant of cardiolipin (CL), the signature lipid of mitochondria. MLCL is not normally found in healthy tissue but accumulates in mitochondria of people with Barth syndrome (BTHS), with an overall increase in the MLCL:CL ratio. The reason for MLCL accumulation remains to be fully understood. The effect of MLCL build-up and decreased CL content in causing the characteristics of BTHS are also unclear. In both cases, an understanding of the nature of MLCL interaction with mitochondrial proteins will be key. Recent work has shown that MLCL associates less tightly t...
Source: Biochemical Society Transactions - May 26, 2020 Category: Biochemistry Authors: Duncan AL Tags: Biochem Soc Trans Source Type: research

Three-dimensional genome rewiring during the development of antibody-secreting cells.
Abstract The development of B lymphocytes into antibody-secreting plasma cells is central to the adaptive immune system in that it confers protective and specific antibody response against invading pathogen. This developmental process involves extensive morphological and functional alterations that begin early after antigenic stimulation. These include chromatin restructuring that is critical in regulating gene expression, DNA rearrangement and other cellular processes. Here we outline the recent understanding of the three-dimensional architecture of the genome, specifically focused on its contribution to the proc...
Source: Biochemical Society Transactions - May 26, 2020 Category: Biochemistry Authors: Chan WF, Johanson TM, Allan RS Tags: Biochem Soc Trans Source Type: research

Hydrogen peroxide reactivity and specificity in thiol-based cell signalling.
This article discusses potential mechanisms, focussing on recent evidence for oxidation being localised within the cell, redox relays involving peroxiredoxins operating in some signalling pathways, and mechanisms for facilitated or directed oxidation of specific targets. These findings help define conditions that enable redox signalling but there is still much to learn regarding mechanisms. PMID: 32412042 [PubMed - as supplied by publisher] (Source: Biochemical Society Transactions)
Source: Biochemical Society Transactions - May 15, 2020 Category: Biochemistry Authors: Winterbourn CC Tags: Biochem Soc Trans Source Type: research

Gut microbiota and metabolites in the pathogenesis of endocrine disease.
Abstract Type 1 diabetes (T1D) and Hashimoto's thyroiditis (HT) are the two most common autoimmune endocrine diseases that have rising global incidence. These diseases are caused by the immune-mediated destruction of hormone-producing endocrine cells, pancreatic beta cells and thyroid follicular cells, respectively. Both genetic predisposition and environmental factors govern the onset of T1D and HT. Recent evidence strongly suggests that the intestinal microbiota plays a role in accelerating or preventing disease progression depending on the compositional and functional profile of the gut bacterial communities. A...
Source: Biochemical Society Transactions - May 15, 2020 Category: Biochemistry Authors: Fenneman AC, Rampanelli E, Yin YS, Ames J, Blaser MJ, Fliers E, Nieuwdorp M Tags: Biochem Soc Trans Source Type: research

Mass spectrometry-based methods for structural biology on a proteome-wide scale.
Abstract Mass spectrometry (MS) has long been used to study proteins mainly via sequence identification and quantitation of expression abundance. In recent years, MS has emerged as a tool for structural biology. Intact protein structural analysis has been enabled by the development of methods such as native MS, top-down proteomics, and ion mobility MS. Other MS-based structural methods include affinity purification MS, chemical cross-linking, and protein footprinting. These methods have enabled the study of protein-protein and protein-ligand interactions and regions of conformational change. The coupling of MS wit...
Source: Biochemical Society Transactions - May 15, 2020 Category: Biochemistry Authors: Jones LM Tags: Biochem Soc Trans Source Type: research

Extracellular matrix stiffness and Wnt/ β-catenin signaling in physiology and disease.
Extracellular matrix stiffness and Wnt/β-catenin signaling in physiology and disease. Biochem Soc Trans. 2020 May 15;: Authors: Astudillo P Abstract The Wnt/β-catenin signaling pathway plays fundamental roles during development, stem cell differentiation, and homeostasis, and its abnormal activation can lead to diseases. In recent years, it has become clear that this pathway integrates signals not only from Wnt ligands but also from other proteins and signaling routes. For instance, Wnt/β-catenin signaling involves YAP and TAZ, which are transcription factors with crucial roles in mecha...
Source: Biochemical Society Transactions - May 15, 2020 Category: Biochemistry Authors: Astudillo P Tags: Biochem Soc Trans Source Type: research

Mutations in genes encoding regulators of mRNA decapping and translation initiation: links to intellectual disability.
Abstract Intellectual disability (ID) affects at least 1% of the population, and typically presents in the first few years of life. ID is characterized by impairments in cognition and adaptive behavior and is often accompanied by further delays in language and motor skills, as seen in many neurodevelopmental disorders (NDD). Recent widespread high-throughput approaches that utilize whole-exome sequencing or whole-genome sequencing have allowed for a considerable increase in the identification of these pathogenic variants in monogenic forms of ID. Notwithstanding this progress, the molecular and cellular consequenc...
Source: Biochemical Society Transactions - May 15, 2020 Category: Biochemistry Authors: Weil D, Piton A, Lessel D, Standart N Tags: Biochem Soc Trans Source Type: research

Using automated reasoning to explore the metabolism of unconventional organisms: a first step to explore host-microbial interactions.
We describe its usage to over-approximate metabolic responses of biological systems and solve gap-filling problems. In this review, we compare steady-states and Boolean abstractions of metabolic models and illustrate their complementarity via applications to the metabolic analysis of macro-algae. Ongoing applications of this formalism explore the emerging field of systems ecology, notably elucidating interactions between a consortium of microbes and a host organism. As the first step in this field, we will illustrate how the reduction in microbiotas according to expected metabolic phenotypes can be addressed with gap-filli...
Source: Biochemical Society Transactions - May 7, 2020 Category: Biochemistry Authors: Frioux C, Dittami SM, Siegel A Tags: Biochem Soc Trans Source Type: research

Systems approach to rational combination therapy: PARP inhibitors.
Abstract Poly (ADP-ribose) polymerase inhibitors (PARPi) have demonstrated activity across a broad spectrum of molecular backgrounds and tumor types, with the greatest activity observed in patients with aberrations in the homologous recombination DNA damage repair pathway. Despite remarkable responses in a subset of patients, the response is usually modest and transient due to the almost inevitable emergence of resistance. Tumors develop resistance through rapid adaptation to the effects of PARPi as well as by generation or selection of genomic aberration. Although adaptive responses results in drug resistance, it...
Source: Biochemical Society Transactions - May 7, 2020 Category: Biochemistry Authors: Sun C, Fang Y, Labrie M, Li X, Mills GB Tags: Biochem Soc Trans Source Type: research

Biomolecular complex viewed by dynamic nuclear polarization solid-state NMR spectroscopy.
This article highlights the emerging MAS-DNP approaches and their applications to the analysis of biomolecular composites and intact cells to determine the folding pathway and ligand binding of proteins, the structural polymorphism of low-populated biopolymers, as well as the physical interactions between carbohydrates, proteins, and lignin. These structural features provide an atomic-level understanding of many cellular processes, promoting the development of better biomaterials and inhibitors. It is anticipated that the capabilities of MAS-DNP in biomolecular and biomaterial research will be further enlarged by the rapid...
Source: Biochemical Society Transactions - May 7, 2020 Category: Biochemistry Authors: Chakraborty A, Deligey F, Quach J, Mentink-Vigier F, Wang P, Wang T Tags: Biochem Soc Trans Source Type: research

Elevator-type mechanisms of membrane transport.
Abstract Membrane transporters are integral membrane proteins that mediate the passage of solutes across lipid bilayers. These proteins undergo conformational transitions between outward- and inward-facing states, which lead to alternating access of the substrate-binding site to the aqueous environment on either side of the membrane. Dozens of different transporter families have evolved, providing a wide variety of structural solutions to achieve alternating access. A sub-set of structurally diverse transporters operate by mechanisms that are collectively named 'elevator-type'. These transporters have one common c...
Source: Biochemical Society Transactions - May 5, 2020 Category: Biochemistry Authors: Garaeva AA, Slotboom DJ Tags: Biochem Soc Trans Source Type: research

Caught in the act: structural dynamics of replication origin activation and fork progression.
Abstract This review discusses recent advances in single-particle cryo-EM and single-molecule approaches used to visualise eukaryotic DNA replication reactions reconstituted in vitro. We comment on the new challenges facing structural biologists, as they turn to describing the dynamic cascade of events that lead to replication origin activation and fork progression. PMID: 32369549 [PubMed - as supplied by publisher] (Source: Biochemical Society Transactions)
Source: Biochemical Society Transactions - May 5, 2020 Category: Biochemistry Authors: Lewis JS, Costa A Tags: Biochem Soc Trans Source Type: research

Functional heterogeneity in senescence.
Abstract Senescence is a tumour suppressor mechanism which is cell-intrinsically activated in the context of cellular stress. Senescence can further be propagated to neighbouring cells, a process called secondary senescence induction. Secondary senescence was initially shown as a paracrine response to the secretion of cytokines from primary senescent cells. More recently, juxtacrine Notch signalling has been implicated in mediating secondary senescence induction. Primary and secondary senescent induction results in distinct transcriptional outcomes. In addition, cell type and the stimulus in which senescence is in...
Source: Biochemical Society Transactions - May 5, 2020 Category: Biochemistry Authors: Kirschner K, Rattanavirotkul N, Quince MF, Chandra T Tags: Biochem Soc Trans Source Type: research

Decellularized bone extracellular matrix in skeletal tissue engineering.
Abstract Bone possesses an intrinsic regenerative capacity, which can be compromised by aging, disease, trauma, and iatrogenesis (e.g. tumor resection, pharmacological). At present, autografts and allografts are the principal biological treatments available to replace large bone segments, but both entail several limitations that reduce wider use and consistent success. The use of decellularized extracellular matrices (ECM), often derived from xenogeneic sources, has been shown to favorably influence the immune response to injury and promote site-appropriate tissue regeneration. Decellularized bone ECM (dbECM), uti...
Source: Biochemical Society Transactions - May 5, 2020 Category: Biochemistry Authors: Rothrauff BB, Tuan RS Tags: Biochem Soc Trans Source Type: research

Towards the routine use of in silico screenings for drug discovery using metabolic modelling.
Abstract Currently, the development of new effective drugs for cancer therapy is not only hindered by development costs, drug efficacy, and drug safety but also by the rapid occurrence of drug resistance in cancer. Hence, new tools are needed to study the underlying mechanisms in cancer. Here, we discuss the current use of metabolic modelling approaches to identify cancer-specific metabolism and find possible new drug targets and drugs for repurposing. Furthermore, we list valuable resources that are needed for the reconstruction of cancer-specific models by integrating various available datasets with genome-scale...
Source: Biochemical Society Transactions - May 5, 2020 Category: Biochemistry Authors: Bintener T, Pacheco MP, Sauter T Tags: Biochem Soc Trans Source Type: research

Materno-fetal cholesterol transport during pregnancy.
Abstract Cholesterol is a major nutrient required for fetal growth. It is also a precursor for the synthesis of steroid hormones and essential for the development and maturation of fetal organs. During pregnancy, the placenta controls the transport of cholesterol from the mother to the fetus and vice versa. Cholesterol originating from the maternal circulation has to cross two main membrane barriers to reach the fetal circulation: Firstly, cholesterol is acquired by the apical side of the syncytiotrophoblast (STB) from the maternal circulation as high-density lipoprotein (HDL)-, low-density lipoprotein (LDL)- or v...
Source: Biochemical Society Transactions - May 5, 2020 Category: Biochemistry Authors: Kallol S, Albrecht C Tags: Biochem Soc Trans Source Type: research

The emerging complexity of PDGFRs: activation, internalization and signal attenuation.
Abstract The platelet-derived growth factor receptor (PDGFR) family of receptor tyrosine kinases allows cells to communicate with the environment to regulate diverse cellular activities. Here, we highlight recent data investigating the structural makeup of individual PDGFRs upon activation, revealing the importance of the whole receptor in the propagation of extracellular ligand binding and dimerization. Furthermore, we review ongoing research demonstrating the significance of receptor internalization and signal attenuation in the regulation of PDGFR activity. Interactions with internalization machinery, signaling...
Source: Biochemical Society Transactions - May 5, 2020 Category: Biochemistry Authors: Rogers MA, Fantauzzo KA Tags: Biochem Soc Trans Source Type: research

Gene transcription and chromatin regulation in hypoxia.
Abstract Oxygen sensing is an essential feature of metazoan biology and reductions in oxygen availability (hypoxia) have both physiological and pathophysiological implications. Co-ordinated mechanisms have evolved for sensing and responding to hypoxia, which involve diverse biological outputs, with the main aim of restoring oxygen homeostasis. This includes a dynamic gene transcriptional response, the central drivers of which are the hypoxia-inducible factor (HIF) family of transcription factors. HIFs are regulated in an oxygen-dependent manner and while their role in hypoxia is well established, it is apparent th...
Source: Biochemical Society Transactions - May 5, 2020 Category: Biochemistry Authors: Batie M, Rocha S Tags: Biochem Soc Trans Source Type: research

Post-translational modifications and stress adaptation: the paradigm of FKBP51.
Abstract Adaptation to stress is a fundamental requirement to cope with changing environmental conditions that pose a threat to the homeostasis of cells and organisms. Post-translational modifications (PTMs) of proteins represent a possibility to quickly produce proteins with new features demanding relatively little cellular resources. FK506 binding protein (FKBP) 51 is a pivotal stress protein that is involved in the regulation of several executers of PTMs. This mini-review discusses the role of FKBP51 in the function of proteins responsible for setting the phosphorylation, ubiquitination and lipidation of other ...
Source: Biochemical Society Transactions - April 22, 2020 Category: Biochemistry Authors: Rein T Tags: Biochem Soc Trans Source Type: research

The nucleolus-like and precursor bodies of mammalian oocytes and embryos and their possible role in post-fertilization centromere remodelling.
Abstract In nearly all somatic cells, the ribosome biosynthesis is a key activity. The same is true also for mammalian oocytes and early embryos. This activity is intimately linked to the most prominent nuclear organelles - the nucleoli. Interestingly, during a short period around fertilization, the nucleoli in oocytes and embryos transform into ribosome-biosynthesis-inactive structures termed nucleolus-like or nucleolus precursor bodies (NPBs). For decades, researchers considered these structures to be passive repositories of nucleolar proteins used by the developing embryo to rebuild fully functional, ribosome-s...
Source: Biochemical Society Transactions - April 22, 2020 Category: Biochemistry Authors: Fulka H, Rychtarova J, Loi P Tags: Biochem Soc Trans Source Type: research

Targeting NAD-dependent dehydrogenases in drug discovery against infectious diseases and cancer.
Abstract Dehydrogenases are oxidoreductase enzymes that play a variety of fundamental functions in the living organisms and have primary roles in pathogen survival and infection processes as well as in cancer development. We review here a sub-set of NAD-dependent dehydrogenases involved in human diseases and the recent advancements in drug development targeting pathogen-associated NAD-dependent dehydrogenases. We focus also on the molecular aspects of the inhibition process listing the structures of the most relevant molecules targeting this enzyme family. Our aim is to review the most impacting findings regarding...
Source: Biochemical Society Transactions - April 20, 2020 Category: Biochemistry Authors: Ferraris DM, Gelardi ELM, Garavaglia S, Miggiano R, Rizzi M Tags: Biochem Soc Trans Source Type: research

Cell signaling and cytomegalovirus reactivation: what do Src family kinases have to do with it?
Abstract Primary infection with human cytomegalovirus (HCMV) is usually asymptomatic and leads to the establishment of lifelong latent infection. A major site of latency are the CD34+ hematopoietic progenitor cells. Importantly, normal cellular differentiation of CD34+ cells to a macrophage or dendritic cell phenotype is concomitant with viral reactivation. Molecular studies of HCMV latency have shown that the latent viral genome is associated with histone proteins and that specific post-translational modifications of these histones correlates with the transcriptional activity of the genome arguing that expression...
Source: Biochemical Society Transactions - April 20, 2020 Category: Biochemistry Authors: Reeves MB Tags: Biochem Soc Trans Source Type: research

Targeted therapy and drug resistance in triple-negative breast cancer: the EGFR axis.
Abstract Targeting of estrogen receptor is commonly used as a first-line treatment for hormone-positive breast cancer patients, and is considered as a keystone of systemic cancer therapy. Likewise, HER2-targeted therapy significantly improved the survival of HER2-positive breast cancer patients, indicating that targeted therapy is a powerful therapeutic strategy for breast cancer. However, for triple-negative breast cancer (TNBC), an aggressive breast cancer subtype, there are no clinically approved targeted therapies, and thus, an urgent need to identify potent, highly effective therapeutic targets. In this mini-...
Source: Biochemical Society Transactions - April 20, 2020 Category: Biochemistry Authors: Lev S Tags: Biochem Soc Trans Source Type: research

Cross-talk between redox signalling and protein aggregation.
Abstract It is well established that both an increase in reactive oxygen species (ROS: i.e. O2•-, H2O2 and OH•), as well as protein aggregation, accompany ageing and proteinopathies such as Parkinson's and Alzheimer's disease. However, it is far from clear whether there is a causal relation between the two. This review describes how protein aggregation can be affected both by redox signalling (downstream of H2O2), as well as by ROS-induced damage, and aims to give an overview of the current knowledge of how redox signalling affects protein aggregation and vice versa. Redox signalling has been shown to pl...
Source: Biochemical Society Transactions - April 20, 2020 Category: Biochemistry Authors: van Dam L, Dansen TB Tags: Biochem Soc Trans Source Type: research

The role of SUMOylation during development.
Abstract During the development of multicellular organisms, transcriptional regulation plays an important role in the control of cell growth, differentiation and morphogenesis. SUMOylation is a reversible post-translational process involved in transcriptional regulation through the modification of transcription factors and through chromatin remodelling (either modifying chromatin remodelers or acting as a 'molecular glue' by promoting recruitment of chromatin regulators). SUMO modification results in changes in the activity, stability, interactions or localization of its substrates, which affects cellular processe...
Source: Biochemical Society Transactions - April 20, 2020 Category: Biochemistry Authors: Talamillo A, Barroso-Gomila O, Giordano I, Ajuria L, Grillo M, Mayor U, Barrio R Tags: Biochem Soc Trans Source Type: research

The road to the structure of the mitochondrial respiratory chain supercomplex.
Abstract The four complexes of the mitochondrial respiratory chain are critical for ATP production in most eukaryotic cells. Structural characterisation of these complexes has been critical for understanding the mechanisms underpinning their function. The three proton-pumping complexes, Complexes I, III and IV associate to form stable supercomplexes or respirasomes, the most abundant form containing 80 subunits in mammals. Multiple functions have been proposed for the supercomplexes, including enhancing the diffusion of electron carriers, providing stability for the complexes and protection against reactive oxygen...
Source: Biochemical Society Transactions - April 20, 2020 Category: Biochemistry Authors: Caruana NJ, Stroud DA Tags: Biochem Soc Trans Source Type: research

Methods for protein delivery into cells: from current approaches to future perspectives.
Abstract The manipulation of cultured mammalian cells by the delivery of exogenous macromolecules is one of the cornerstones of experimental cell biology. Although the transfection of cells with DNA expressions constructs that encode proteins is routine and simple to perform, the direct delivery of proteins into cells has many advantages. For example, proteins can be chemically modified, assembled into defined complexes and subject to biophysical analyses prior to their delivery into cells. Here, we review new approaches to the injection and electroporation of proteins into cultured cells. In particular, we focus ...
Source: Biochemical Society Transactions - April 8, 2020 Category: Biochemistry Authors: Chau C, Actis P, Hewitt E Tags: Biochem Soc Trans Source Type: research

MicroRNAs and long non-coding RNAs as novel regulators of ribosome biogenesis.
Abstract Ribosome biogenesis is the fine-tuned, essential process that generates mature ribosomal subunits and ultimately enables all protein synthesis within a cell. Novel regulators of ribosome biogenesis continue to be discovered in higher eukaryotes. While many known regulatory factors are proteins or small nucleolar ribonucleoproteins, microRNAs (miRNAs), and long non-coding RNAs (lncRNAs) are emerging as a novel modulatory layer controlling ribosome production. Here, we summarize work uncovering non-coding RNAs (ncRNAs) as novel regulators of ribosome biogenesis and highlight their links to diseases of defec...
Source: Biochemical Society Transactions - April 8, 2020 Category: Biochemistry Authors: McCool MA, Bryant CJ, Baserga SJ Tags: Biochem Soc Trans Source Type: research

Small nucleolar RNAs: continuing identification of novel members and increasing diversity of their molecular mechanisms of action.
tt MS Abstract Identified five decades ago amongst the most abundant cellular RNAs, small nucleolar RNAs (snoRNAs) were initially described as serving as guides for the methylation and pseudouridylation of ribosomal RNA through direct base pairing. In recent years, however, increasingly powerful high-throughput genomic approaches and strategies have led to the discovery of many new members of the family and surprising diversity in snoRNA functionality and mechanisms of action. SnoRNAs are now known to target RNAs of many biotypes for a wider range of modifications, interact with diverse binding partners, compete w...
Source: Biochemical Society Transactions - April 8, 2020 Category: Biochemistry Authors: Bergeron D, Fafard-Couture É, Scott MS Tags: Biochem Soc Trans Source Type: research

Cytotoxicity of snake venom enzymatic toxins: phospholipase A2 and l-amino acid oxidase.
Abstract The phospholipase A2 (PLA2) and l-amino acid oxidase (LAAO) are two major enzymes found in the venoms from most snake species. These enzymes have been structurally and functionally characterised for their pharmacological activities. Both PLA2 and LAAO from different venoms demonstrate considerable cytotoxic effects on cancer cells via induction of apoptosis, cell cycle arrest and suppression of proliferation. These enzymes produce more pronounced cytotoxic effects in cancer cells than normal cells, thus they can be potential sources as chemotherapeutic agents. It is proposed that PLA2 and LAAO contribute ...
Source: Biochemical Society Transactions - April 8, 2020 Category: Biochemistry Authors: Hiu JJ, Yap MKK Tags: Biochem Soc Trans Source Type: research

Mathematical modelling in cell migration: tackling biochemistry in changing geometries.
Abstract Directed cell migration poses a rich set of theoretical challenges. Broadly, these are concerned with (1) how cells sense external signal gradients and adapt; (2) how actin polymerisation is localised to drive the leading cell edge and Myosin-II molecular motors retract the cell rear; and (3) how the combined action of cellular forces and cell adhesion results in cell shape changes and net migration. Reaction-diffusion models for biological pattern formation going back to Turing have long been used to explain generic principles of gradient sensing and cell polarisation in simple, static geometries like a ...
Source: Biochemical Society Transactions - April 2, 2020 Category: Biochemistry Authors: Stinner B, Bretschneider T Tags: Biochem Soc Trans Source Type: research

S-acylation in plants: an expanding field.
Abstract S-acylation is a common yet poorly understood fatty acid-based post-translational modification of proteins in all eukaryotes, including plants. While exact roles for S-acylation in protein function are largely unknown the reversibility of S-acylation indicates that it is likely able to play a regulatory role. As more studies reveal the roles of S-acylation within the cell it is becoming apparent that how S-acylation affects proteins is conceptually different from other reversible modifications such as phosphorylation or ubiquitination; a new mind-set is therefore required to fully integrate these data int...
Source: Biochemical Society Transactions - April 2, 2020 Category: Biochemistry Authors: Hemsley PA Tags: Biochem Soc Trans Source Type: research

How does methotrexate work?
Abstract Developed over 70 years ago as an anti-folate chemotherapy agent, methotrexate (MTX) is a WHO 'essential medicine' that is now widely employed as a first-line treatment in auto-immune, inflammatory diseases such as rheumatoid arthritis (RA), psoriasis and Crone's disease. When used for these diseases patients typically take a once weekly low-dose of MTX - a therapy which provides effective inflammatory control to tens of millions of people worldwide. While undoubtedly effective, our understanding of the anti-inflammatory mechanism-of-action of low-dose MTX is incomplete. In particular, the long-held dogma...
Source: Biochemical Society Transactions - April 2, 2020 Category: Biochemistry Authors: Alqarni AM, Zeidler MP Tags: Biochem Soc Trans Source Type: research

How do cells sense DNA lesions?
Abstract DNA is exposed to both endogenous and exogenous DNA damaging agents that chemically modify it. To counteract the deleterious effects exerted by DNA lesions, eukaryotic cells have evolved a network of cellular pathways, termed DNA damage response (DDR). The DDR comprises both mechanisms devoted to repair DNA lesions and signal transduction pathways that sense DNA damage and transduce this information to specific cellular targets. These targets, in turn, impact a wide range of cellular processes including DNA replication, DNA repair and cell cycle transitions. The importance of the DDR is highlighted by the...
Source: Biochemical Society Transactions - March 27, 2020 Category: Biochemistry Authors: Colombo CV, Gnugnoli M, Gobbini E, Longhese MP Tags: Biochem Soc Trans Source Type: research

Mitochondrial hyperfusion: a friend or a foe.
Abstract The cellular mitochondrial population undergoes repeated cycles of fission and fusion to maintain its integrity, as well as overall cellular homeostasis. While equilibrium usually exists between the fission-fusion dynamics, their rates are influenced by organellar and cellular metabolic and pathogenic conditions. Under conditions of cellular stress, there is a disruption of this fission and fusion balance and mitochondria undergo either increased fusion, forming a hyperfused meshwork or excessive fission to counteract stress and remove damaged mitochondria via mitophagy. While some previous reports sugges...
Source: Biochemical Society Transactions - March 27, 2020 Category: Biochemistry Authors: Das R, Chakrabarti O Tags: Biochem Soc Trans Source Type: research

Signal-regulated oxidation of proteins via MICAL.
This article provides an overview of the functions of MICAL proteins in the redox regulation of cellular functions. PMID: 32219383 [PubMed - as supplied by publisher] (Source: Biochemical Society Transactions)
Source: Biochemical Society Transactions - March 27, 2020 Category: Biochemistry Authors: Ortegón Salas C, Schneider K, Lillig CH, Gellert M Tags: Biochem Soc Trans Source Type: research

Recent advances in understanding prodrug transport through the SLC15 family of proton-coupled transporters.
Abstract Solute carrier (SLC) transporters play important roles in regulating the movement of small molecules and ions across cellular membranes. In mammals, they play an important role in regulating the uptake of nutrients and vitamins from the diet, and in controlling the distribution of their metabolic intermediates within the cell. Several SLC families also play an important role in drug transport and strategies are being developed to hijack SLC transporters to control and regulate drug transport within the body. Through the addition of amino acid and peptide moieties several novel antiviral and anticancer age...
Source: Biochemical Society Transactions - March 27, 2020 Category: Biochemistry Authors: Minhas GS, Newstead S Tags: Biochem Soc Trans Source Type: research

Current research into snake antivenoms, their mechanisms of action and applications.
Abstract Snakebite is a major public health issue in the rural tropics. Antivenom is the only specific treatment currently available. We review the history, mechanism of action and current developments in snake antivenoms. In the late nineteenth century, snake antivenoms were first developed by raising hyperimmune serum in animals, such as horses, against snake venoms. Hyperimmune serum was then purified to produce whole immunoglobulin G (IgG) antivenoms. IgG was then fractionated to produce F(ab) and F(ab')2 antivenoms to reduce adverse reactions and increase efficacy. Current commercial antivenoms are polyclonal...
Source: Biochemical Society Transactions - March 20, 2020 Category: Biochemistry Authors: Silva A, Isbister GK Tags: Biochem Soc Trans Source Type: research

Visualizing protein structures - tools and trends.
Abstract Molecular visualization is fundamental in the current scientific literature, textbooks and dissemination materials. It provides an essential support for presenting results, reasoning on and formulating hypotheses related to molecular structure. Tools for visual exploration of structural data have become easily accessible on a broad variety of platforms thanks to advanced software tools that render a great service to the scientific community. These tools are often developed across disciplines bridging computer science, biology and chemistry. This mini-review was written as a short and compact overview for ...
Source: Biochemical Society Transactions - March 20, 2020 Category: Biochemistry Authors: Martinez X, Chavent M, Baaden M Tags: Biochem Soc Trans Source Type: research

Redox signalling and ageing: insights from Drosophila.
e; HM Abstract Ageing and age-related diseases are major challenges for the social, economic and healthcare systems of our society. Amongst many theories, reactive oxygen species (ROS) have been implicated as a driver of the ageing process. As by-products of aerobic metabolism, ROS are able to randomly oxidise macromolecules, causing intracellular damage that accumulates over time and ultimately leads to dysfunction and cell death. However, the genetic overexpression of enzymes involved in the detoxification of ROS or treatment with antioxidants did not generally extend lifespan, prompting a re-evaluation of the c...
Source: Biochemical Society Transactions - March 20, 2020 Category: Biochemistry Authors: Lennicke C, Cochemé HM Tags: Biochem Soc Trans Source Type: research

Bacterial phenotypic heterogeneity in DNA repair and mutagenesis.
Abstract Genetically identical cells frequently exhibit striking heterogeneity in various phenotypic traits such as their morphology, growth rate, or gene expression. Such non-genetic diversity can help clonal bacterial populations overcome transient environmental challenges without compromising genome stability, while genetic change is required for long-term heritable adaptation. At the heart of the balance between genome stability and plasticity are the DNA repair pathways that shield DNA from lesions and reverse errors arising from the imperfect DNA replication machinery. In principle, phenotypic heterogeneity ...
Source: Biochemical Society Transactions - March 20, 2020 Category: Biochemistry Authors: Vincent MS, Uphoff S Tags: Biochem Soc Trans Source Type: research

Membrane-anchored serine proteases as regulators of epithelial function.
Abstract Cleavage of proteins in the extracellular milieu, including hormones, growth factors and their receptors, ion channels, and various cell adhesion and extracellular matrix molecules, plays a key role in the regulation of cell behavior. Among more than 500 proteolytic enzymes encoded by mammalian genomes, membrane-anchored serine proteases (MASPs), which are expressed on the surface of epithelial cells of all major organs, are excellently suited to mediate signal transduction across the epithelia and are increasingly being recognized as important regulators of epithelial development, function, and disease [...
Source: Biochemical Society Transactions - March 20, 2020 Category: Biochemistry Authors: Szabo R, Bugge TH Tags: Biochem Soc Trans Source Type: research

Small molecules that target the ubiquitin system.
Abstract Eukaryotic life depends upon the interplay between vast networks of signaling pathways composed of upwards of 109-1010 proteins per cell. The integrity and normal operation of the cell requires that these proteins act in a precise spatial and temporal manner. The ubiquitin system is absolutely central to this process and perturbation of its function contributes directly to the onset and progression of a wide variety of diseases, including cancer, metabolic syndromes, neurodegenerative diseases, autoimmunity, inflammatory disorders, infectious diseases, and muscle dystrophies. Whilst the individual compone...
Source: Biochemical Society Transactions - March 20, 2020 Category: Biochemistry Authors: Wu HQ, Baker D, Ovaa H Tags: Biochem Soc Trans Source Type: research

Diversity of molecular mechanisms used by anti-CRISPR proteins: the tip of an iceberg?
Abstract Bacteriophages (phages) and their preys are engaged in an evolutionary arms race driving the co-adaptation of their attack and defense mechanisms. In this context, phages have evolved diverse anti-CRISPR proteins to evade the bacterial CRISPR-Cas immune system, and propagate. Anti-CRISPR proteins do not share much resemblance with each other and with proteins of known function, which raises intriguing questions particularly relating to their modes of action. In recent years, there have been many structure-function studies shedding light on different CRISPR-Cas inhibition strategies. As the anti-CRISPR fie...
Source: Biochemical Society Transactions - March 20, 2020 Category: Biochemistry Authors: Hardouin P, Goulet A Tags: Biochem Soc Trans Source Type: research

Targeting BMP signaling in the bone marrow microenvironment of myeloid leukemia.
Abstract The bone morphogenetic protein (BMP) pathway regulates the fate and proliferation of normal hematopoietic stem cells (HSC) as well as interactions with their niche. While BMP2 and BMP4 promote HSC differentiation, only BMP4 maintains HSC pool and favors interactions with their niche. In myeloid leukemia, we have identified intrinsic and extrinsic dysregulations of the BMP pathway in Chronic Myeloid Leukemia (CML) and Acute Myeloid leukemia (AML) responsible for leukemic stem cells (LSC) survival. In AML, BMP pathway alterations sustain and promote resistant immature-like leukemic cells by activating a new...
Source: Biochemical Society Transactions - March 13, 2020 Category: Biochemistry Authors: Lefort S, Maguer-Satta V Tags: Biochem Soc Trans Source Type: research

Burkholderia pseudomallei pathogenesis and survival in different niches.
Abstract Burkholderia pseudomallei (Bp) is the causative agent of melioidosis, a disease of the tropics with high clinical mortality rates. To date, no vaccines are approved for melioidosis and current treatment relies on antibiotics. Conversely, common misdiagnosis and high pathogenicity of Bp hamper efforts to fight melioidosis. This bacterium can be isolated from a wide range of niches such as waterlogged fields, stagnant water bodies, salt water bodies and from human and animal clinical specimens. Although extensive studies have been undertaken to elucidate pathogenesis mechanisms of Bp, little is known about ...
Source: Biochemical Society Transactions - March 13, 2020 Category: Biochemistry Authors: Yip CH, Ghazali AK, Nathan S Tags: Biochem Soc Trans Source Type: research

A peek in the micro-sized world: a review of design principles, engineering tools, and applications of engineered microbial community.
Abstract Microbial communities drive diverse processes that impact nearly everything on this planet, from global biogeochemical cycles to human health. Harnessing the power of these microorganisms could provide solutions to many of the challenges that face society. However, naturally occurring microbial communities are not optimized for anthropogenic use. An emerging area of research is focusing on engineering synthetic microbial communities to carry out predefined functions. Microbial community engineers are applying design principles like top-down and bottom-up approaches to create synthetic microbial communitie...
Source: Biochemical Society Transactions - March 11, 2020 Category: Biochemistry Authors: Gao B, Sabnis R, Costantini T, Jinkerson R, Sun Q Tags: Biochem Soc Trans Source Type: research