Zika virus NS1 affects the junctional integrity of human brain microvascular endothelial cells.
Abstract Zika virus (ZIKV) infection leads to microcephaly in newborns. Flaviviruses are known to secrete NS1 protein extracellularly and its concentration in serum directly co-relate to disease severity. The presence of ZIKV-NS1 near the brain microvascular endothelial cells (BMVECs) affects blood-brain-barrier, which is composed of tight junctions (TJs) and adherens junctions (AJs). Viruses utilize different strategies to circumvent this barrier to enter in brain. The present study demonstrated the mechanism of junctional integrity disruption in BMVECs by ZIKV-NS1 protein exposure. The Transendothelial Electrica...
Source: Biochimie - July 5, 2020 Category: Biochemistry Authors: Rastogi M, Singh SK Tags: Biochimie Source Type: research
A panel of circulating long non-coding RNAs as liquid biopsy biomarkers for breast and cervical cancers.
Abstract The early detection and diagnosis of cancer is critical to optimize the treatment and management of cancer patients. Typical methods such as imaging and tissue biopsy are invasive, time-consuming, and often imprecise. Thus, recent technological advances of dependable, facile, and minimally invasive collectible oncogenic biomarkers using human biofluids and secretions have been an active area of research. Recently, circulating long non-coding RNAs (lncRNAs) have been identified as promising biomarkers that fulfill many recommended properties of successful biomarkers for cancer diagnosis and prognosis. LncR...
Source: Biochimie - July 4, 2020 Category: Biochemistry Authors: Barwal TS, Sharma U, Vasquez KM, Prakash H, Jain A Tags: Biochimie Source Type: research
The Small Nuclear Ribonucleoprotein Polypeptide A (SNRPA) binds to the G-quadruplex of the BAG-1 5'UTR.
Abstract The protein "BCL-2-associated athanogene-1" (BAG-1), which exists in multiple isoforms, promotes cancer cell survival and is overexpressed in many different cancers. As a result, BAG-1-targeted therapy appears to be a promising strategy with which to treat cancer. It has previously been shown that the 5'UTR of the BAG-1 mRNA contains a guanine rich region that folds into a G-quadruplex structure which can modulate both its cap-dependent and its cap-independent translation. Accumulating data regarding G-quadruplex binding proteins suggest that these proteins can play a central role in gene expres...
Source: Biochimie - July 3, 2020 Category: Biochemistry Authors: Bolduc F, Turcotte MA, Perreault JP Tags: Biochimie Source Type: research
Characterization and modulation of brain lipids content of rainbow trout fed with 100% plant based diet rich in omega-3 long chain polyunsaturated fatty acids DHA and EPA.
In conclusion, this work revealed for the first time in fish model the presence of some selected enzymatic and non-enzymatic oxidation metabolites in brain and the modulation of brain lipid content by dietary DHA and EPA levels. PMID: 32623048 [PubMed - as supplied by publisher] (Source: Biochimie)
Source: Biochimie - July 2, 2020 Category: Biochemistry Authors: Roy J, Vigor C, Vercauteren J, Reversat G, Zhou B, Surget A, Larroquet L, Lanuque A, Sandres F, Terrier F, Oger C, Galano JM, Corraze G, Durand T Tags: Biochimie Source Type: research
Lipid excess affects chaperone-mediated autophagy in hypothalamus.
In this study, we aimed to investigate the role of hypothalamic chaperone-mediated autophagy in response to high-fat diet and also the direct effect of palmitate on hypothalamic neurons. Mice received chow or high-fat diet for 3 days or 1 week. At the end of the experimental protocol, chaperone-mediated autophagy in hypothalamus was investigated, as well as cytokines expression. In other set of experiments, neuronal cell lines were treated with palmitic acid, a saturated fatty acid. We show that chaperone-mediated autophagy is differently regulated in response to high-fat diet intake for 3 days or 1 week. Also, when hypoth...
Source: Biochimie - July 2, 2020 Category: Biochemistry Authors: Portovedo M, Reginato A, Miyamoto JÉ, Simino LA, Hakim MP, Campana M, Leal RF, Ignácio-Souza LM, Torsoni MA, Magnan C, Le Stunff H, Torsoni AS, Milanski M Tags: Biochimie Source Type: research
Structural insights into the formation of oligomeric state by a type I Hsp40 chaperone.
Abstract Molecular chaperones can prevent and repair protein misfolding and aggregation to maintain protein homeostasis in cells. Hsp40 chaperones interact with unfolded client proteins via the dynamic multivalent interaction (DMI) mechanism with their multiple client-binding sites. Here we report that a type I Hsp40 chaperone from Streptococcus pneumonia (spHsp40) forms a concentration-independent polydispersity oligomer state in solution. The crystal structure of spHsp40 determined at 2.75 Å revealed that each monomer has a type I Hsp40 structural fold containing a zinc finger domain and C-terminal domai...
Source: Biochimie - July 1, 2020 Category: Biochemistry Authors: Zhu M, Ou D, Khan MH, Zhao S, Zhu Z, Niu L Tags: Biochimie Source Type: research
Rational design and structure insights for thermostability improvement of Penicillium verruculosum Cel7A cellobiohydrolase.
In this study, the thermostability of Penicillium verruculosum Cel7A cellobiohydrolase was increased through rational design of substitutions with proline. The stabilizing substitution G415P resulted in 3.4-fold increase in half-life time at 60 °C compared to wild-type enzyme. Molecular dynamics simulations indicated a clear effect of the stabilizing substitution G415P and the destabilizing substitutions D62P, S191P, and S273P on the stability of the enzyme tertiary structure. The stabilizing substitution G415P decreased flexibility of the lateral sides of the enzyme active site tunnel, while the considered destabili...
Source: Biochimie - July 1, 2020 Category: Biochemistry Authors: Dotsenko AS, Dotsenko GS, Rozhkova AM, Zorov IN, Sinitsyn AP Tags: Biochimie Source Type: research
How similar or dissimilar cells are produced by bacterial cell division?
Abstract DNA replication, segregation and cell division are vital processes and require an interplay of multiple proteins. These processes are highly conserved across bacteria yet similar or dissimilar progeny are produced after cell division. This review describes the bacterial cell division in considerable detail. This includes studies on model microorganisms which produce similar progeny such as Escherichia coli and Vibrio cholerae, and dissimilar progeny such as sporulating Bacillus subtilis, Actinobacteria, Caulobacter crescentus etc. The mechanism of symmetric and asymmetric cell division and its regulation ...
Source: Biochimie - June 26, 2020 Category: Biochemistry Authors: Singhi D, Srivastava P Tags: Biochimie Source Type: research
CPF-C1 analog with effective antimicrobial and antibiofilm activities against Staphylococcus aureus including MRSA.
In this study, we designed and synthesized a series of analogs to increase the druggability of the natural antimicrobial peptide CPF-C1. Among the analogs, CPF-2 showed high antimicrobial activity against MRSA and multidrug-resistant S. aureus isolated from clinics. In the serum and physiological salt environment, CPF-2 also exhibited effective antimicrobial activity. Importantly, CPF-2 did not determine resistance and showed no hemolytic activity at the active concentration. Concerning the mechanism of action, CPF-2 produced a rapid bactericidal effect by interrupting the bacterial membranes. Even more surprisingly, CPF-2...
Source: Biochimie - June 23, 2020 Category: Biochemistry Authors: Xie J, Li Y, Guo X, Rao J, Yan T, Mou L, Wu X, Xie X, Yang W, Zhang B Tags: Biochimie Source Type: research
Relationship between enzyme concentration and Michaelis constant in enzyme assays.
Abstract The upper bound of enzyme concentration for accurately estimating the parameters in Michaelis-Menten (MM) equation is not completely determined and still under discussion, even though many researchers have investigated the equation's validity for a long time. In the paper, we broadly investigated the correlation between the system of ordinary differential equations for monosubstrate irreversible enzyme reaction (HMM-system) and its derivative MM equation focusing on the relationship between initial enzyme concentration [E]0 and Michaelis constant Km by numerical simulation. According to the results, the i...
Source: Biochimie - June 23, 2020 Category: Biochemistry Authors: Yun KI, Han TS Tags: Biochimie Source Type: research
Nerve growth factor from Indian Russell's viper venom (RVV-NGFa) shows high affinity binding to TrkA receptor expressed in breast cancer cells: Application of fluorescence labeled RVV-NGFa in the clinical diagnosis of breast cancer.
Abstract Nerve growth factor (NGF) is a minor and neglected component of snake venom. Present study describes the purification and characterization of a NGF isoform (RVV-NGFa) from Indian Russell's viper venom (RVV). RVV-NGFa showed a protonated molecular ion [MH+] at m/z 17388.725 Da. The RVV-NGFa induced neuritogenesis in PC-12 cells but did not show cytotoxicity in mammalian cells, hemolytic activity, platelet modulation, and interference in blood coagulation system which are the characteristic pharmacological properties of RVV. By ELISA and immunofluorescence microplate reader assay, the RVV-NGFa showed ap...
Source: Biochimie - June 22, 2020 Category: Biochemistry Authors: Islam T, Majumdar M, Bidkar A, Ghosh SS, Mukhopadhyay R, Utkin Y, Mukherjee AK Tags: Biochimie Source Type: research
The therapeutic potential of targeting CD73 and CD73-derived adenosine in melanoma.
Abstract The hypoxic environment of melanoma results in CD73 upregulation on the surface of various tumor microenvironment (TME) cells including tumor cells, stromal cells and infiltrated immune cells. Consequently, CD73 through both enzymatic and none enzymatic functions affect melanoma progression. Overaccumulation of CD73-derived adenosine through interaction with its four G coupled receptors (A1AR, A2AAR, A2BAR, and A3AR) mediate tumor growth, immune suppression, angiogenesis, and metastasis. This paper aims to comprehensively review the therapeutic potential of CD73 ectonucleotidase targeting in melanoma. To ...
Source: Biochimie - June 22, 2020 Category: Biochemistry Authors: Soleimani A, Farshchi HK, Mirzavi F, Zamani P, Ghaderi A, Amini Y, Khorrami S, Mashayekhi K, Jaafari MR Tags: Biochimie Source Type: research
Alterations in the ribosomal protein bL12 of E. coli affecting the initiation, elongation and termination of protein synthesis.
Abstract In bacteria, ribosomal protein bL12 forms the prominent stalk structure on the ribosome and binds to multiple, distinct translational GTPase factors during the sequential steps of translation. Using a genetic selection in E. coli for altered readthrough of UGA stop codons, we have isolated seven different mutations affecting the C-terminal domain of the protein that forms the interaction surface with translation factors. Analysis of these altered proteins, along with four additional alterations previously shown to affect IF2-ribosome interactions, indicates that multiple steps of translation are affected,...
Source: Biochimie - June 19, 2020 Category: Biochemistry Authors: Younkin AD, Gregory ST, O'Connor M Tags: Biochimie Source Type: research
Functional role of annexins in zebrafish caudal fin regeneration - A gene knockdown approach in regenerating tissue.
This study proves that ANXA2a and 2b plays a significant role in epimorphic regeneration of zebrafish caudal fin tissue. PMID: 32561450 [PubMed - as supplied by publisher] (Source: Biochimie)
Source: Biochimie - June 16, 2020 Category: Biochemistry Authors: Quoseena M, Vuppaladadium S, Hussain S, Banu S, Bharathi S, Idris MM Tags: Biochimie Source Type: research
Synthetic antimicrobial peptides: From choice of the best sequences to action mechanisms.
Abstract The emergence of antibiotic-resistant microbes has stimulated research worldwide seeking new biologically active molecules. In this respect, synthetic antimicrobial peptides (SAMPs) have been suggested to overcome this problem. Although there are some online servers that provide putative SAMPs from protein sequences, the choice of the best peptide sequences for further analysis is still difficult. Therefore, the goal of this paper is not to launch a new tool but to provide a friendly workflow to characterize and predict potential SAMPs by employing existing tools. Using this proposed workflow, two peptide...
Source: Biochimie - June 11, 2020 Category: Biochemistry Authors: Souza PFN, Marques LSM, Oliveira JTA, Lima PG, Dias LP, Neto NAS, Lopes FES, Sousa JS, Silva AFB, Caneiro RF, Lopes JLS, Ramos MV, Freitas CDT Tags: Biochimie Source Type: research
Role of pyroglutamylated RFamide peptide43 in germ cell dynamics in mice testes in relation to energy metabolism.
In conclusion, our findings suggest that QRFP treatment caused proliferation of germ cells independently from the hypothalamic-pituitary axis via regulation of testicular energy metabolism. PMID: 32504656 [PubMed - as supplied by publisher] (Source: Biochimie)
Source: Biochimie - June 3, 2020 Category: Biochemistry Authors: Patel SK, Singh SK Tags: Biochimie Source Type: research
A promising therapeutic combination for metastatic prostate cancer: Chloroquine as autophagy inhibitor and palladium(II) barbiturate complex.
Abstract Autophagy is a catabolic process for cells that can provide energy sources and allows cancer cells to evade cell death. Therefore, studies on the combination of autophagy inhibitors with drugs are increasing as a new treatment modality in cancer. Previously, we reported the anti-tumor activity of a Palladium (Pd)(II) complex against different types of cancer in vitro and in vivo. Chloroquine (CQ), the worldwide used anti-malarial drug, has recently been focused as a chemosensitizer in cancer treatment. The aim of this study was to investigate the efficacy of a combined treatment of these agents that work ...
Source: Biochimie - June 1, 2020 Category: Biochemistry Authors: Erkisa M, Aydinlik S, Cevatemre B, Aztopal N, Akar RO, Celikler S, Yilmaz VT, Ari F, Ulukaya E Tags: Biochimie Source Type: research
The endosomal lipid bis(monoacylglycero) phosphate as a potential key player in the mechanism of action of chloroquine against SARS-COV-2 and other enveloped viruses hijacking the endocytic pathway.
ord M Abstract The anti-malarial drug Chloroquine (CQ) and its derivative hydroxychloroquine have shown antiviral activities in vitro against many viruses, including coronaviruses, dengue virus and the biosafety level 4 Nipah and Hendra paramyxoviruses. The in vivo efficacy of CQ in the treatment of COVID-19 is currently a matter of debate. CQ is a lysosomotrophic compound that accumulates in lysosomes, as well as in food vacuoles of Plasmodium falciparum. In the treatment of malaria, CQ impairs the digestion and growth of the parasite by increasing the pH of the food vacuole. Similarly, it is assumed that the ant...
Source: Biochimie - May 30, 2020 Category: Biochemistry Authors: Carrière F, Longhi S, Record M Tags: Biochimie Source Type: research
SARS-CoV-2 entry in host cells-multiple targets for treatment and prevention.
Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new viral disease that has gained global attention owing to its ability to provoke community and health-care-associated outbreaks of severe infections in human populations. The virus poses serious challenges to clinical management because there are still no approved anti- SARS-CoV-2 drugs available. In this mini-review, we summarize the much updated published reports that demonstrate the mechanism of SARS-CoV-2 entry into host cells, and discuss the availability and development of attractive host-based therapeutic options for SARS-CoV-2 inf...
Source: Biochimie - May 29, 2020 Category: Biochemistry Authors: Mahmoud IS, Jarrar YB, Alshaer W, Ismail S Tags: Biochimie Source Type: research
Contentious role of 'Good Adiponectin' in pulmonary and cardiovascular diseases: Is adiponectin directed therapy a boon or a bane?
Abstract After two decades of its discovery, numerous facts of adiponectin (APN) biology has been uncovered, yet, APN remains an elusive adipokine. Findings from clinical studies and animal models established APN's ameliorative role in cardiovascular disease (CVD) and pulmonary disease (PD) but the same condition is prognostic for mortality in the same set of patients which cornered APN towards a dubious state. A repertoire of mechanisms associated with the positive association of APN in both lean/cachectic or obese CVD and PD patients from past publications are evaluated. Newer pharmacological agent may be explor...
Source: Biochimie - May 27, 2020 Category: Biochemistry Authors: Pathak MP, Das A, Patowary P, Chattopadhyay P Tags: Biochimie Source Type: research
Crystal structure of histidine ammonia-lyase from Trypanosoma cruzi.
lek J Abstract Chagas disease is one of seventeen neglected tropical diseases according to the World Health Organization (WHO). The histidine-glutamate metabolic pathway is an oxidative route that has shown to be relevant for the bioenergetics in Trypanosoma cruzi, the etiological agent for Chagas disease. Histidine ammonia-lyase participates in the first stage of the histidine catabolism, catalyzing the conversion of l-histidine into urocanate. This work presents the three-dimensional (3D) structure of Trypanosoma cruzi histidine ammonia-lyase enzyme (TcHAL) and some comparisons of it to homologous structures. Th...
Source: Biochimie - May 25, 2020 Category: Biochemistry Authors: Miranda RR, Silva M, Barisón MJ, Silber AM, Iulek J Tags: Biochimie Source Type: research
Zika virus subversion of chaperone GRP78/BiP expression in A549 cells during UPR activation.
ml;cken W Abstract Flaviviruses replicate in membranous factories associated with the endoplasmic reticulum (ER). Significant levels of flavivirus polyprotein integration contribute to ER stress and the host cell may exhibit an Unfolded Protein Response (UPR) to this protein accumulation, stimulating appropriate cellular responses such as adaptation, autophagy or cell death. These different stress responses support other antiviral strategies initiated by infected cells and can help to overcome viral infection. In epithelial A549 cells, a model currently used to study the flavivirus infection cycle and the host c...
Source: Biochimie - May 25, 2020 Category: Biochemistry Authors: Turpin J, Frumence E, Harrabi W, Haddad JG, El Kalamouni C, Desprès P, Krejbich-Trotot P, Viranaïcken W Tags: Biochimie Source Type: research
Phosphorylation of the acyl-CoA binding pocket of the FadR transcription regulator in Sulfolobus acidocaldarius.
Abstract The archaeal model organism Sulfolobus acidocaldarius possesses a TetR-like transcription factor that represses a 30-kb gene cluster encoding fatty acid metabolism enzymes. Interaction of this regulator, FadR, with acyl-CoA molecules causes a DNA dissociation, which may lead to a derepression of the gene cluster. Previously, a phosphoproteome analysis revealed the phosphorylation of three consecutive amino acids in the acyl-CoA ligand binding pocket. Here, we study this phosphorylation event and show that ArnC, a Hanks-type protein kinase, targets a threonine within the phosphoacceptor motif in vitro. Ele...
Source: Biochimie - May 23, 2020 Category: Biochemistry Authors: Maklad HR, Gutierrez GJ, Esser D, Siebers B, Peeters E Tags: Biochimie Source Type: research
Vitexin abrogates invasion and survival of hepatocellular carcinoma cells through targeting STAT3 signaling pathway.
This study was designed to examine the effect of vitexin on STAT3 signaling and important hallmarks of cancer. HCC cells were employed to decipher the impact of vitexin on activation of STAT3 signaling using Western blotting, EMSA, immunocytochemistry, and reporter assay. The combinational apoptotic effects of vitexin with approved anti-cancer drugs was examined by live-dead assay, and its anti-invasive potential was studied using matrigel assay. The results obtained in cell-based assays were verified using in silico analysis. Vitexin effectively inhibited sustained activation of JAK1, JAK2, Src, and STAT3 in HCC cells. Vi...
Source: Biochimie - May 20, 2020 Category: Biochemistry Authors: Lee JH, Mohan CD, Shanmugam MK, Rangappa S, Sethi G, Siveen KS, Chinnathambi A, Alahmadi TA, Alharbi SA, Basappa S, Rangappa KS, Ahn KS Tags: Biochimie Source Type: research
Preventive as well as therapeutic significances of linoleic acid in the containment of Leishmania donovani infection.
Abstract People suffering from malnutrition show compromised levels of ω-6 fatty acid and malnutrition is frequently observed among visceral leishmaniasis (VL) patients as disease inflicts primarily the socioeconomic destitute communities. Dietary linoleic acid (LA, 18:2; ω-6 fatty acid) is the principal source of essential fatty acid and its derivatives i.e. eicosanoids possess immune-modulatory activities. However, its role in VL is not yet established. LA was measured in VL human subjects (serum) as well as in Leishmania donovani infected hamsters (serum and visceral organs). Organ-specific mRNA exp...
Source: Biochimie - May 18, 2020 Category: Biochemistry Authors: Saini S, Kottarath SK, Dinda AK, Dube A, Sahasrabuddhe AA, Thakur CP, Bhat M, Rai AK Tags: Biochimie Source Type: research
The beclin 1 interactome: Modification and roles in the pathology of autophagy-related disorders.
Abstract Beclin 1 a yeast Atg6/VPS30 orthologue has a significant role in autophagy process (Macroautophagy) and protein sorting. The function of beclin 1 depends on the interaction with several autophagy-related genes (Atgs) and other proteins during the autophagy process. The role mediated by beclin 1 is controlled by various conditions and factors. Beclin 1 is regulated at the gene and protein levels by different factors. These regulations could subsequently alter the beclin 1 induced autophagy process. Therefore, it is important to study the components of beclin 1 interactome and factors affecting its expressi...
Source: Biochimie - May 16, 2020 Category: Biochemistry Authors: Kaur S, Changotra H Tags: Biochimie Source Type: research
GRP78 and next generation cancer hallmarks: An underexplored molecular target in cancer chemoprevention research.
The objective of this review is to provide a concise and integrated information on GRP78 and its association with tumor glycolysis and immune evasion which will revive and draw attention of the researchers to consider GRP78 as a potential drug target for cancer intervention and it also highlights few potential natural products investigated so far as GRP78 inhibitors. PMID: 32422159 [PubMed - as supplied by publisher] (Source: Biochimie)
Source: Biochimie - May 15, 2020 Category: Biochemistry Authors: Madhavan S, Nagarajan S Tags: Biochimie Source Type: research
Crystal structures and RNA-binding properties of Lsm proteins from archaea Sulfolobus acidocaldarius and Methanococcus vannielii: Similarity and difference of the U-binding mode.
Abstract Sm and Sm-like (Lsm) proteins are considered as an evolutionary conserved family involved in RNA metabolism in organisms from bacteria and archaea to human. Currently, the function of Sm-like archaeal proteins (SmAP) is not well understood. Here, we report the crystal structures of SmAP proteins from Sulfolobus acidocaldarius and Methanococcus vannielii and a comparative analysis of their RNA-binding sites. Our data show that these SmAPs have only a uridine-specific RNA-binding site, unlike their bacterial homolog Hfq, which has three different RNA-binding sites. Moreover, variations in the amino acid com...
Source: Biochimie - May 15, 2020 Category: Biochemistry Authors: Lekontseva N, Mikhailina A, Fando M, Kravchenko O, Balobanov V, Tishchenko S, Nikulin A Tags: Biochimie Source Type: research
Acute exposure to bis(2-ethylhexyl)phthalate disrupts calcium homeostasis, energy metabolism and induces oxidative stress in the testis of Danio rerio.
va FR Abstract Bis(2-ethylhexyl)phthalate (BEHP) negatively affects testicular functions in different animal species, disturbing reproductive physiology and male fertility. The present study investigated the in vitro acute effect of BEHP on the mechanism of action of ionic calcium (Ca2+) homeostasis and energy metabolism. In addition, the effect of BEHP on oxidative stress was studied in vitro and in vivo in the testis of Danio rerio (D. rerio). Testes were treated in vitro for 30 min with 1 μM BEHP for 45Ca2+ influx measurements. Testes were also incubated with 1 μM BEHP for 1 h (in vitro) or 12 h...
Source: Biochimie - May 14, 2020 Category: Biochemistry Authors: Batista-Silva H, Dambrós BF, Rodrigues K, Cesconetto PA, Zamoner A, Sousa de Moura KR, Gomes Castro AJ, Van Der Kraak G, Mena Barreto Silva FR Tags: Biochimie Source Type: research
A glance into the evolution of template-free protein structure prediction methodologies.
Abstract Prediction of protein structures using computational approaches has been explored for over two decades, paving a way for more focused research and development of algorithms in comparative modelling, ab intio modelling and structure refinement protocols. A tremendous success has been witnessed in template-based modelling protocols, whereas strategies that involve template-free modelling still lag behind, specifically for larger proteins (>150 a.a.). Various improvements have been observed in ab initio protein structure prediction methodologies overtime, with recent ones attributed to the usage of deep l...
Source: Biochimie - May 14, 2020 Category: Biochemistry Authors: Dhingra S, Sowdhamini R, Cadet F, Offmann B Tags: Biochimie Source Type: research
Tough synthetic spider-silk fibers obtained by titanium dioxide incorporation and formaldehyde cross-linking in a simple wet-spinning process.
Abstract Due to its unique mechanical properties, spider silk shows great promise as a strong super-thin fiber in many fields. Although progress has been made in the field of synthesizing spider-silk fiber from recombinant spidroin (spider silk protein) in the last few decades, methods to obtain synthetic spider-silk fibers as tough as natural silk from small-sized recombinant protein with a simple spinning process have eluded scientists. In this paper, a recombinant spidroin (MW: 93.4 kDa) was used to spin tough synthetic spider-silk fibers with a simple wet-spinning process. Titanium oxide incorporation and fo...
Source: Biochimie - May 14, 2020 Category: Biochemistry Authors: Zhu H, Sun Y, Yi T, Wang S, Mi J, Meng Q Tags: Biochimie Source Type: research
Protein promiscuity in drug discovery, drug-repurposing and antibiotic resistance.
Abstract Proteins are supposed to bind to their substrates/ligands in a specific manner via their pre-formed binding sites, according to classical biochemistry. In recent years, several types of deviations from this norm have been observed and called promiscuous behavior. Enzymatic promiscuities allow several biochemical functions to be carried out by the same enzyme. The promiscuous activity can also be the origin of "new proteins" via gene duplication. In more recent years, proteins from prokaryotes, eukaryotes and viruses have been found to have intrinsic disorder and lack a preformed binding site. In...
Source: Biochimie - May 13, 2020 Category: Biochemistry Authors: Gupta MN, Alam A, Hasnain SE Tags: Biochimie Source Type: research
Human health benefits of very-long-chain polyunsaturated fatty acids from microalgae.
Abstract Microalgae are single-cell, photosynthetic organisms whose biodiversity places them at the forefront of biological producers of high-value molecules including lipids and pigments. Some of these organisms particular are capable of synthesizing n-3 very long chain polyunsaturated fatty acids (VLC-PUFAs), known to have beneficial effects on human health. Indeed, VLC-PUFAs are the precursors of many signaling molecules in humans involved in the complexities of inflammatory processes. This mini-review provides an inventory of knowledge on the synthesis of VLC-PUFAs in microalgae and on the diversity of signali...
Source: Biochimie - May 7, 2020 Category: Biochemistry Authors: Lupette J, Benning C Tags: Biochimie Source Type: research
Folinic acid improves the score of Autism in the EFFET placebo-controlled randomized trial.
cute;ant JL Abstract Autism spectrum disorders (ASD) are influenced by interacting maternal and environmental risk factors. High-dose folinic acid has shown improvement in verbal communication in ASD children. The EFFET randomized placebo-controlled trial (NCT02551380) aimed to evaluate the efficacy of folinic acid (FOLINORAL®) at a lower dose of 5 mg twice daily. Nineteen children were included in the EFFET trial. The primary efficacy outcome was improvement of Autism Diagnostic Observation Schedule (ADOS) score. The secondary outcomes were the improvement in ADOS sub scores communication, social interactio...
Source: Biochimie - May 6, 2020 Category: Biochemistry Authors: Renard E, Leheup B, Guéant-Rodriguez RM, Oussalah A, Quadros EV, Guéant JL Tags: Biochimie Source Type: research
Alternagin-C (ALT-C), a disintegrin-like protein, attenuates alpha2beta1 integrin and VEGF receptor 2 signaling resulting in angiogenesis inhibition.
In conclusion, we suggest that ALT-C, after binding to α2β1 integrin, inhibits VEGF/VEGFR2 signaling, which results in impaired angiogenesis. These results demonstrate that ALT-C may be a potential candidate for the development of antiangiogenic therapies for tumor and metastasis treatment and help to understand the complexity and fundamental role of integrin inhibition in the tumor microenvironment. PMID: 32360415 [PubMed - as supplied by publisher] (Source: Biochimie)
Source: Biochimie - April 29, 2020 Category: Biochemistry Authors: Dos Santos PK, Altei WF, Danilucci TM, Lino RLB, Pachane BC, Nunes ACC, Selistre-de-Araujo HS Tags: Biochimie Source Type: research
Physico-chemical properties of two point mutants of small heat shock protein HspB6 (Hsp20) with abrogated cardioprotection.
Abstract Physico-chemical properties of HspB6 S10F and P20L mutants with abrogated cardioprotective activity and associated with different forms of cardiomyopathy were analyzed. Under normal conditions both the wild-type HspB6 and its mutants formed small size oligomers (dimers) with apparent molecular weight of 50-60 kDa. Under crowding conditions (0.5 M trimethylamine N-oxide, TMAO) the wild-type HspB6 remained predominantly dimeric or formed small molecular weight complexes, whereas both mutants tended to form high molecular weight complexes. Catalytic subunit of cAMP-dependent protein kinase phosphorylated...
Source: Biochimie - April 27, 2020 Category: Biochemistry Authors: Shatov VM, Gusev NB Tags: Biochimie Source Type: research
StpA represses CRISPR-Cas immunity in H-NS deficient Escherichia coli.
Abstract Functional CRISPR-Cas systems provide many bacteria and most archaea with adaptive immunity against invading DNA elements. CRISPR arrays store DNA fragments of previous infections while products of cas genes provide immunity by integrating new DNA fragments and using this information to recognize and destroy invading DNA. Escherichia coli contains the CRISPR-Cas type I-E system in which foreign DNA targets are recognized by Cascade, a crRNA-guided complex comprising five proteins (CasA, CasB, CasC, CasD, CasE), and degraded by Cas3. In E. coli the CRISPR-Cas type I-E system is repressed by the histone-lik...
Source: Biochimie - April 27, 2020 Category: Biochemistry Authors: Mitić D, Radovčić M, Markulin D, Ivančić-Baće I Tags: Biochimie Source Type: research
Conformational selection in the flaviviral NS2B-NS3 protease.
Abstract The first x-ray structures of flaviviral proteases defined two conformational states, open and closed, depending on the relative position of NS2B with respect to NS3, a feature that affects the shape of the binding site. The degree of flexibility in the active site was limited to changes in the fold of NS2B rather than NS3 and an induced-fit mechanism was regarded as the main factor for ligand binding. A minor degree of conformational plasticity in NS3 is observed in the two protein chains in the asymmetric unit for the structure of Zika protease with a dipeptide boronate, synthesized in our group. We hyp...
Source: Biochimie - April 23, 2020 Category: Biochemistry Authors: Behnam MAM, Klein CDP Tags: Biochimie Source Type: research
Murine cellular model of mucopolysaccharidosis, type IIIB (MPS IIIB) - A preliminary study with particular emphasis on the non-oxidative l-cysteine metabolism.
bel M Abstract The lack of the N-alpha-glucosaminidase (Naglu) is responsible for the incidence of a rare disease - mucopolysaccharidosis, type IIIB (MPS IIIB). To date, studies have been conducted based on cells derived from patients suffering from MPS or using in vivo MPS mouse models. These limitations have allowed for defining our research goal - to create and characterize the first in vitro murine cellular MPS IIIB model. In the current work we present a new, stable cell line with confirmed accumulation of glycosaminoglycans. The line stability was achieved by immortalization using a lentivirus carrying the T...
Source: Biochimie - April 23, 2020 Category: Biochemistry Authors: Kaczor-Kamińska M, Stalińska K, Kamiński K, Pisarek A, Maziarz U, Feldman A, Wróbel M Tags: Biochimie Source Type: research
SPCA1 governs the stability of TMEM165 in Hailey-Hailey disease.
Abstract TMEM165 is a Golgi protein whose deficiency causes a Congenital Disorder of Glycosylation (CDG). We have demonstrated that Mn2+ supplementation could suppress the glycosylation defects observed in TMEM165-deficient cells and that TMEM165 was a Mn2+-sensitive protein. In the Golgi, the other transmembrane protein capable to regulate Mn2+/Ca2+ homeostasis is SPCA1, encoded by the ATP2C1 gene. A loss of one copy of the ATP2C1 gene leads to Hailey-Hailey Disease (HHD), an acantholytic skin disorder in Humans. Our latest results suggest an unexpected functional link between SPCA1 and TMEM165. In order to clari...
Source: Biochimie - April 23, 2020 Category: Biochemistry Authors: Roy AS, Miskinyte S, Garat A, Hovnanian A, Krzewinski-Recchi MA, Foulquier F Tags: Biochimie Source Type: research
Knockdown of the α5 laminin chain affects differentiation of colorectal cancer cells and their sensitivity to chemotherapy.
Knockdown of the α5 laminin chain affects differentiation of colorectal cancer cells and their sensitivity to chemotherapy. Biochimie. 2020 Apr 22;: Authors: Maltseva D, Raygorodskaya M, Knyazev E, Zgoda V, Tikhonova O, Zaidi S, Nikulin S, Baranova A, Turchinovich A, Rodin S, Tonevitsky A Abstract The interaction of tumor cells with the extracellular matrix (ECM) may affect the rate of cancer progression and metastasis. One of the major components of ECM are laminins, the heterotrimeric glycoproteins consisting of α-, β-, and γ-chains (αβγ). Laminins interact wi...
Source: Biochimie - April 22, 2020 Category: Biochemistry Authors: Maltseva D, Raygorodskaya M, Knyazev E, Zgoda V, Tikhonova O, Zaidi S, Nikulin S, Baranova A, Turchinovich A, Rodin S, Tonevitsky A Tags: Biochimie Source Type: research
B vitamins and one carbon metabolism micronutrients in health and disease.
nt JL PMID: 32334044 [PubMed - as supplied by publisher] (Source: Biochimie)
Source: Biochimie - April 22, 2020 Category: Biochemistry Authors: Murphy MM, Guéant JL Tags: Biochimie Source Type: research
Riboflavin supplementation alters global and gene-specific DNA methylation in adults with the MTHFR 677 TT genotype.
This study examined DNA methylation, globally and at key MTHFR regulatory sites, in adults stratified by MTHFR genotype and the effect of riboflavin supplementation on DNA methylation in individuals with the 677 TT genotype. Samples were accessed from participants, screened for the MTHFR C677T polymorphism, who participated in observational (n = 80) and targeted riboflavin (1.6 mg/day) RCTs (n = 80). DNA methylation at LINE-1 and key regulatory regions of the MTHFR locus were analysed by pyrosequencing in peripheral blood leukocytes. LINE-1 (+1.6%; p = 0.011) and MTHFR south shelf (+4.7%, p
Source: Biochimie - April 22, 2020 Category: Biochemistry Authors: Amenyah SD, McMahon A, Ward M, Deane J, McNulty H, Hughes CF, Strain JJ, Horigan G, Purvis J, Walsh CP, Lees-Murdock DJ Tags: Biochimie Source Type: research
Tetracycline derivatives resist the assembly behavior of human islet amyloid polypeptide.
Abstract The misfolding of amyloid proteins is closely correlated with the pathogenesis of protein conformation-related diseases, such as Alzheimer's disease (AD), prion disease, and type 2 diabetes mellitus (T2DM). The deposition of human islet amyloid polypeptide (hIAPP) and amyloid-β (Aβ) protein is entangled in AD and diabetes mellitus. The development of potential inhibitors is a feasible therapeutic strategy to treat these diseases by resisting peptide aggregation. Doxycycline is a typical clinical antibiotic that has been utilized in neurodegenerative studies. However, the roles of tetracyclines i...
Source: Biochimie - April 21, 2020 Category: Biochemistry Authors: Xu J, Zhao C, Huang X, Du W Tags: Biochimie Source Type: research
Impact of the MTHFR C677T polymorphism on one-carbon metabolites: Evidence from a randomised trial of riboflavin supplementation.
This study investigated one carbon metabolites and their responsiveness to riboflavin in adults with the TT genotype. Plasma samples from adults (n 115) screened for the MTHFR genotype, who previously participated in RCTs to lower BP, were analysed for methionine, S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), betaine, choline and cystathionine by liquid chromatography tandem mass spectrometry (LC-MS/MS). The one-carbon metabolite response to riboflavin (1.6 mg/d; n 24) or placebo (n 23) for 16 weeks in adults with the TT genotype was also investigated. Plasma SAM (74.7 ± 21.0 vs 85.2 ± 2...
Source: Biochimie - April 21, 2020 Category: Biochemistry Authors: Rooney M, Bottiglieri T, Wasek-Patterson B, McMahon A, Hughes CF, McCann A, Horigan G, Strain JJ, McNulty H, Ward M Tags: Biochimie Source Type: research
Fusion-PCR generates attL recombination site adaptors and allows Rapid One-Step Gateway (ROG) cloning.
Abstract Gateway recombination-based cloning, which eliminates the use of restriction endonucleases and ligase, has been widely used for the construction of high-throughput (HTP) vectors. However, this approach is very expensive and its two-stage reaction process is laborious and time consuming. Therefore, we developed a Gateway cloning method that uses fusion-PCR to generate attL recombination site adaptors, and the PCR products, which can be directly cloned into destination vectors, giving rise to Rapid One-Step Gateway (ROG) Cloning. 100% of cloning efficiencies were obtained by this ROG method. This method has...
Source: Biochimie - April 20, 2020 Category: Biochemistry Authors: Liao L, Yang L, Xu Y, Li X, Tan G, Fu B, Duan K, Li Z, Yu D, Li C Tags: Biochimie Source Type: research
Differential levels of alpha-1-inhibitor III, Immunoglobulin heavy chain variable region, and Hypertrophied skeletal muscle protein GTF3 in rat mammary tumorigenesis.
Abstract Early detection of breast cancer can be best facilitated by the development of precancerous markers. Serum proteins being the sensitive signatures, can be the ideal choice. We previously demonstrated the reduced levels of two serum proteins at a very early stage of tumorigenesis in a breast cancer model, developed in Wistar rats by 7,12-dimethylbenz[a]anthracene (DMBA) administration. Here we report the dysregulation of three more proteins in the serum collected at another early stage (15 weeks) of tumorigenesis in the same model. The proteins were identified (as Alpha-1-inhibitor III (Mug1), Immunoglobul...
Source: Biochimie - April 20, 2020 Category: Biochemistry Authors: Ganaie IA, Malik MZ, Naqvi SH, Jain SK, Wajid S Tags: Biochimie Source Type: research
Inhibition of nuclease activity by a splice-switching oligonucleotide targeting deoxyribonuclease 1 mRNA prevents apoptosis progression and prolong viability of normal human CD4+ T-lymphocytes.
Abstract The nuclease activity of deoxyribonuclease 1 (DNase I) is regulated by alternative splicing (AS) of its mRNA. The aim of this study was to define the ability of a splice-switching oligonucleotide (SSO) that base-paired with DNase I pre-mRNA to induce AS and inhibit nuclease activity in human T, B and NK lymphocytes. The SSO for DNase I could significantly downregulate the expression of full-length active DNase I and upregulate a truncated splice variant with a deleted exon 4. Such an induction of AS resulted in inhibition of nuclease activity and slowed apoptosis progression in anti-CD95/FAS stimulated ly...
Source: Biochimie - April 18, 2020 Category: Biochemistry Authors: Zhdanov DD, Plyasova AA, Pokrovsky VS, Pokrovskaya MV, Alexandrova SS, Gladilina YA, Sokolov NN Tags: Biochimie Source Type: research
Aberrant interactions between amyloid-beta and alpha5 laminins as possible driver of neuronal disfunction in Alzheimer's disease.
Abstract It has been widely accepted that laminins are involved in pathogenesis of Alzheimer's disease (AD). Amyloid plaques in AD patients are associated with immunostaining using antibodies raised against laminin-111, and laminin-111 has been shown to prevent aggregation of amyloid peptides. Although numerous articles describe small peptides from laminin-111 that are capable to disaggregate amyloid buildups and reduce neurotoxicity in in vitro and in vivo models, there is no approved laminin-111-based therapeutic approaches for treatment of AD. Also, it has been shown that immunoreactivity to laminin-111 appears...
Source: Biochimie - April 17, 2020 Category: Biochemistry Authors: Rodin S, Kozin SA, Kechko OI, Mitkevich VA, Makarov AA Tags: Biochimie Source Type: research
ARE-binding protein ZFP36L1 interacts with CNOT1 to directly repress translation via a deadenylation-independent mechanism.
Abstract Eukaryotic gene expression can be spatiotemporally tuned at the post-transcriptional level by cis-regulatory elements in mRNA sequences. An important example is the AU-rich element (ARE), which induces mRNA destabilization in a variety of biological contexts in mammals and can also mediate translational control. Regulation is mediated by trans-acting factors that recognize the ARE, such as Tristetraprolin (TTP) and BRF1/ZFP36L1. Although both proteins can destabilize their target mRNAs through the recruitment of the CCR4-NOT deadenylation complex, TTP also directly regulates translation. Whether ZFP36L1 c...
Source: Biochimie - April 17, 2020 Category: Biochemistry Authors: Otsuka H, Fukao A, Tomohiro T, Adachi S, Suzuki T, Takahashi A, Funakami Y, Natsume T, Yamamoto T, Duncan KE, Fujiwara T Tags: Biochimie Source Type: research