DON WHITLEY SCIENTIFIC – THE LEADING INTERNATIONAL SUPPLIER TO THE MICROBIOLOGY AND TISSUE CULTURE INDUSTRIES


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Hypoxystations

Decorate Your Workstation and Win!

Shrewsbury Cabinet at Christmas 2Have you decorated your lab and your Whitley Workstation? If so you can win a DWS goody bag for your efforts!

To celebrate the Christmas period we are inviting you to send us photographs of your Whitley Workstation dressed in a festive fashion. The best decorations will win a bag of DWS goodies.

We encourage you to be creative with your decorations but please don’t put yourselves or your research at risk (don’t decorate the inside of the workstation!)

Send in your photos via Twitter @dw_scientific or email Alex_Rhodes@dwscientific.co.uk

We will announce the winner on the 22nd of December. You have until the 21st to get your entries in!

Whitley Hypoxystation

Hypoxia and the Hallmarks of Cancer: Metabolic Reprogramming

Hanahan and Weinberg’s seminal papers on the Hallmarks of Cancer describe how cancer cells accommodate the frenzied growth characteristic of tumours. Low oxygen is eminently characteristic of tumours, and in this hypoxic environment, metabolism is reprogrammed to satisfy energetic and synthetic needs of the cells.

 

Our series on Hypoxia and the Hallmarks of Cancer has showcased research on how hypoxia in the tumour microenvironment affects 8 of the Hallmarks, and in the fifth and final chapter, we look more closely at how researchers are using the Hypoxystation to delineate the Hallmark Metabolic Reprogramming.

The Hypoxystation creates authentic cell culture conditions with regard to oxygen, CO2, temperature, and humidity.  Glove-less access to culture and manipulate cells under physiological atmosphere, in a HEPA-clean environment, allows cancer researchers to re-create the hypoxic tumour microenvironment. Hypoxystation user Dr Ali Tavassolli states that “We have only ever used the H35. I like the ease with which we can regulate and change the oxygen concentration”. And our user Dr. Brad Wouters at the Princess Margaret Cancer Centre in Toronto, who recently purchased his fourth Hypoxystation, says, “The continuous hypoxia we achieve in the workstation is a prerequisite for studies with hypoxia-activated drugs used in cancer therapy strategies.”

 

Metabolic Reprogramming

Changes in energy metabolism feature prominently in aggressive malignancy, and tumour hypoxia and the responding signalling pathways, featuring many HIF target genes, clearly interface with reprogrammed tumour metabolism. Reprogramming of conventional metabolic pathways serves to satisfy burgeoning energetic and anabolic needs of the tumour cells; many cancer cells may preferentially utilise glycolysis over oxidative phosphorylation, uncoupling mitochondrial metabolism from oxygen availability. Hypoxia-induced HIF’s attenuate mitochondrial function through diverse mechanisms, including down-regulation of enzymes in the electron transport chain and suppression of biogenesis of mitochondria. Signalling pathways involving HIF’s and many products of oncogenes and tumour suppressor genes interact to balance the energy needs of dividing cells with the requirement for bio-synthetic intermediates. Activation of lipid biosynthesis and other pathways with biosynthetic significance, such as the pentose phosphate pathway, is another metabolic consequence of hypoxia and HIF up-regulation. Reactive oxygen species ROS produced by the mitochondria stabilise HIF-1, influence redox homeostasis, and provide protective antioxidants to the cancer cells.

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m45

Just Enough Oxygen: Cultivating Fastidious Pathogens in Microaerobic Workstations

A sustainable microaerophilic environment for incubation and manipulation of microbiological samples is crucial to culturing Campylobacter jejuni, Helicobacter pylori, and other fastidious pathogens. The ability to provide a customisable low level of oxygen for pathogens that can’t be cultivated successfully in ambient air or under strictly anaerobic conditions is a prerequisite for culturing these microorganisms.

The M series microaerobic workstations by Don Whitley Scientific, provide precise gas control of up to four gasses for a customisable low oxygen environment that doesn’t require expensive custom gas mixes. The entire temperature-controlled interior of the chamber serves as the work and incubation area, ensuring that growing cultures are never exposed to ambient conditions. Though the robust MACS VA workstations are still being used in many laboratories, we have invested considerable resources into developing the next generation microaerobic workstation, the M series, with increased atmospheric precision and a touchscreen interface. A range of sizes with capacities from ~600 to ~1400 plates will accommodate every workflow and space requirement. Options such as data logging, internal HEPA filtration, gas pressure monitoring and automated humidity control provide protection and accountability.

 

Clinical and research institutions worldwide are using our microaerophilic workstations to cultivate fastidious microorganisms with confidence.

Researchers are taking advantage of the stable microaerophilic atmosphere generated in our workstations to investigate the expression of H. pylori toxin in gastric pathology, integration of selected genes onto the C. jejuni chromosome, spectroscopic differentiation of foodborne Campylobacter strains and the epidemiology of antibiotic-resistance in Campylobacter in cattle.

2016    Horemans et al.    In-vivo evaluation of apocynin for prevention of Helicobacter  pylori-induced gastric carcinogenesis

2016    Fontenete et al.    Fluorescence In Vivo Hybridization (FIVH) for Detection of Helicobacter pylori Infection in a C57BL/6 Mouse Model

2016    Sinnett et al.    Helicobacter pylori vacA transcription is genetically determined and stratifies the level of human gastric inflammation and atrophy

2016    Su et al.    Combination of OipA, BabA, and SabA as candidate biomarkers for predicting Helicobacter pylori-related gastric cancer

2016    Muhamadali  et al.    Chicken, beams, and Campylobacter : rapid differentiation of foodborne bacteria via vibrational spectroscopy and MALDI-mass spectrometry

2015    Jervis et al.    Chromosomal integration vectors allowing flexible expression of foreign genes in Campylobacter jejuni


Please feel free to contact us on +44 (0) 1274 595728 or email at sales@dwscientific.co.uk


KONICA MINOLTA DIGITAL CAMERA

Culturing Cells in Ambient Air is Far From Physiological

Based on the premise that the physiological range of oxygen in tissues is between 1- 8%, and pathologies from cancer to diabetes are characterised by much lower oxygen levels, researchers worldwide are cultivating their cell cultures in the Hypoxystation by Don Whitley Scientific. The Hypoxystation provides physiologically relevant conditions for cell culture and manipulation to ensure authentic behaviour of cells. User-defined parameters for temperature, CO2, O2 and humidity, plus the workstation format, where cells reside throughout the entire duration of the assays, minimise the extra-physiologic oxygen shock that is known to negatively impact cell metabolism and growth.

Numerous recent publications by our Hypoxystation users demonstrate that cell culture conditions which mimic physioxia, are essential in avoiding the significantly impaired growth rates, reduced lifespan, and altered molecular behaviour encountered in cells cultivated at ambient conditions. Oxygen levels in tissues are in constant flux; they change in response to functional status and blood delivery in the organs, and this too can be re-created in the Hypoxystation through programmed oxygen profiling.

Recent research using the Hypoxystation to investigate hypoxia inducible factors and the array of signalling pathways that regulate angiogenesis, metabolism, redox homeostasis, inflammation, and cell death, and the many other processes which enable the cellular and organismal response to hypoxia, “highlights the importance of oxygen as a cell culture parameter when making physiological inferences” (Timpano and Uniacke, 2016).

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From: Burr et al. (2016) “Mitochondrial Protein Lipoylation and the 2-Oxoglutarate Dehydrogenase Complex Controls HIF1a Stability in Aerobic Conditions” Cell Metabolism 25, 740–752


To find out more about Hypoxystations or other DWS products, please call +44 (0) 1274 595728 or email sales@dwscientific.co.uk


 

Whitley Hypoxystation

World Heart Day: Hypoxia in Cardiovascular Disease Research

Cardiovascular disease, including heart disease and stroke, is responsible for approximately 1 in 3 deaths in the US, according to the American Heart Association. World Heart Day on 29 September serves as a platform to educate people on how to take control of their heart health.

Don Whitley Scientific and our US/Canadian distributor HypOxygen would like to take this opportunity to highlight cardiovascular research being carried out around the world – and to say “thank you for being committed to our health.”

Adverse cardiac remodeling after infarction exacerbates myocardial ischemia and increases the likelihood of heart failure. Revuelta-Lopez et al. in Spain present new data showing that in the hypoxic areas of the infarct zone, expression of low-density lipoprotein receptor-related protein 1 (LRP1) is linked to activation of Matrix metalloproteinase (MMP) through Pyk2 phosphorylation, and propose that LRP1 modulation may be a very effective pharmacological target in heart disease. Their H35 Hypoxystation with its controlled low oxygen environment creates physiologically more relevant parameters for cell culture, mimicking ischemia/reperfusion events.

Hypothesizing that Tumor necrosis factor-Related Apoptosis-Inducing Ligand plays a role in ischemic injury during acute myocardial infarction, Jiang et al. have found evidence for a novel immune regulatory mechanism involving TRAIL, ER stress and NF-κB signaling pathways. Culturing their cells in the Hypoxystation H35 at 0.3% oxygen allowed the lab to simulate the ischemia/reperfusion processes that cause cardiomyocyte loss and increase mortality in Coronary Heart Disease.

Hypoxia in the embryonic environment supports maintenance of a primitive glycosaminoglycan-rich heart valve matrix, the specific composition of which determines proper function, and as hypoxia decreases after birth, the extracellular matrix matures. Amofa et al. at Cincinnati’s Children’s Medical Center, using the H35 Hypoxystation, provide new data that exposure of adult heart tissue to hypoxia induces hyaluronan remodeling, GAG accumulation, and degeneration of the extracellular matrix in the heart valve, effects that are implicated in Myxomatous mitral valve disease.

Dr. Michael Cross, Molecular and Clinical Pharmacology Department, University of Liverpool, says of his work with cardiac spheroids : “The H35 allows us to generate oxygen levels that reflect the in vivo physiology these cells would be exposed to. We chose the Hypoxystation with its oxygen profiling feature, which allows us to recreate cycles of ischemia, where oxygen levels typically sink to 1-3%”.

Revuelta-Lopez et al 2017

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Image from: Revuelta-Lopez et al. “Relationship among LRP1 expression, Pyk2 phosphorylation and MMP-9 activation in left ventricular remodelling after myocardial infarction” J Cell Mol Med. 2017 Sep;21(9):1915-1928

 

Amofa et al 2017

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Hypoxia increases GAGs, Sox9 nuclear localization and Hyal2 expression in cAVOCs.

Image from: Amofa et al. (2017) “Hypoxia promotes primitive glycosaminoglycan-rich extracellular matrix composition in developing heart valves” Am J Physiol Heart Circ Physiol. 2017 Aug 25:ajpheart.00209.2017

 

 

 

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Hypoxia and the Hallmarks of Cancer: Angiogenesis and Metastasis

The following was provided by HypOxygen, our distributor of Hypoxic Workstations in the US

Hanahan and Weinberg’s “Hallmarks of Cancer” are at the root of the multi-step progression of cancer, and they are all influenced by hypoxia in the tumor microenvironment. In this mini-review series, HypOxygen has been taking a closer look at the way Hypoxystation users worldwide are delineating the effects of hypoxia on the Hallmarks of Cancer: so far, we’ve showcased Avoiding Immune Destruction and Tumor Promoting Inflammation and Genome Instability and Mutation and Enabling Replicative Immortality.

In the Hypoxystation, researchers working with cells in culture can mimic the physiological conditions that produce those characteristic Hallmarks. The Hypoxystation enables glove-less access to cultivate and manipulate cells under physiological conditions, in a HEPA-clean environment. Oxygen levels in the Hypoxystation can be reliably and accurately adjusted to below 1%, reflecting the high metabolism, low perfusion tumor microenvironment.

 

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1. Inducing Angiogenesis

Angiogenesis and tumor-associated neo-vascularization are central to the progression of cancer, and hypoxia in the fast-growing, poorly perfused tumor setting is one of the main factors driving the formation of new vessels. Hypoxia in the tumor activates the hypoxia stress response, which is mediated at the cellular level by HIF, VEGF and many other cytokines, growth factors and guidance molecules. As a consequence, endothelial cells and pericytes proliferate and form new blood vessels, which are, however, disorderly and leaky, in turn exacerbating hypoxia in the tumor. Cancer treatment strategies striving to normalize tumor vessels for the purpose of improved drug delivery and alleviation of hypoxia in the tumor are showing great promise.

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2. Activating Invasion and Metastasis

As with the other Hallmarks of Cancer, metastasis and cancer progression are correlated with low oxygen levels in the tumor. HIF’s activate the expression of more than 1000 genes, numerous of which play a role in inducing genes involved in the EMT, through direct interactions with HRE’s at promotor sites and other mechanisms such as epigenetic alterations, like methylation/demethylation. Hypoxia promotes migration and invasion by facilitating the endothelial-mesenchymal transition, altering cell-cell contacts, and reducing adhesion to the extra-cellular matrix. Cancer cells and neighboring cells such as fibroblasts are all influenced by hypoxia, and all contribute to the restructuring of the tumor microenvironment. The effects of the Hallmarks of Cancer continually perturb and promote each other, as when hypoxia-driven metabolic reprogramming causes acidification of the extracellular microenvironment through increased production and secretion of lactate, in turn augmenting ECM remodeling and immune evasion. Similarly, formation of novel blood vessels enables extravasation and migration of cancer cells to form new tumors.

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The Hallmarks of Cancer: Genome Instability and Immortality

 

Dr Burga Kalz Fuller continues to look at the way the iconic “Hallmarks of Cancer“, as first described by Douglas Hanahan and Robert Weinberg, are influenced by hypoxia in the tumour microenvironment.

Oxygen around and within the tumour cells is central to metabolism, immunology, epigenetics and therapy resistance of all the cancers; in the lab, oxygen levels during tumour cell culture exert effects on metabolism, maintenance, cell yield, and cell survival. That’s why the authentic physiological cell culture conditions in the Hypoxystation help advance research into tumour progression and other events which determine malignancy and outcome of cancer diseases. The Hypoxystation enables glove-less access to cultivate and manipulate cells under physiological conditions, in a HEPA-clean environment.

In this mini-review series, we take a closer look at the way Hypoxystation users worldwide are delineating Hypoxia and the Hallmarks of Cancer. Previously, we had showcased research by Hypoxystation users involved with Avoiding Immune Destruction and Tumour Promoting Inflammation. Next, we want to show the many ways in which Hypoxystation users are researching the Hallmarks Genome Instability and Mutation and Enabling Replicative Immortality. One of those researchers, Dr. David Ho of the University of Miami, presented his results at the Cell Symposium on Cancer, Inflammation and Immunity in San Diego in June.


Let us show you how Don Whitley Scientific can Define Your Environment.

David Ho

Dr. David Ho from the University of Miami with his poster presentation at the Cell Symposium on Cancer, Inflammation and Immunity

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1. Genome Instability and Mutation

Tumour hypoxia drives genomic instability both by increasing the volume of mutations (DNA strand breaks, base damage, and gene amplification) and by diminishing DNA repair efficiency. The low levels of oxygen typical of the tumor microenvironment decrease transcription of genes related to homologous repair and non-homologous end-joining, leading to the genetic instability observed in hypoxic tumour cells. Hypoxia induces production of reactive oxygen species ROS, which interact with nucleic acids, proteins and lipids, causing cellular damage and mutagenesis. Hypoxic activation of HIF-1 also upregulates expression of certain miRNA’s which suppress DNA repair pathways.

 

LITERATURE:

  • Jiang et al. (2016) “Hypoxia Potentiates the Radiation-Sensitizing Effect of Olaparib in Human Non-Small Cell Lung Cancer Xenografts by Contextual Synthetic Lethality” Int J Radiation Oncol Biol Phys, Vol. 95, No. 2, pp. 772 e781, 2016
    www.redjournal.org/article/S0360-3016(16)00056-0/abstract Hypoxystation user
  • Doherty et al. (2016) “Photodynamic killing of cancer cells by a Platinum(II) complex with cyclometallating ligand” Nature Scientific Reports 6:22668 (2016)
    www.ncbi.nlm.nih.gov/pmc/articles/PMC4778139/ Hypoxystation user
  • Hunter et al. (2016) “Hypoxia-activated prodrugs: paths forward in the era of personalised medicine” Br J Cancer. 2016 May 10; 114(10): 1071–1077
    www.ncbi.nlm.nih.gov/pmc/articles/PMC4865974/Hypoxystation user
  • Leszczynska et al. (2016) “Mechanisms and consequences of ATMIN repression in hypoxic conditions: roles for p53 and HIF-1” Scientific Reports 6:21698 (2016
    www.ncbi.nlm.nih.gov/pmc/articles/PMC4753685/ Hypoxystation user
  • Timpano and Uniacke (2016) “Human Cells Cultured Under Physiological Oxygen Utilize Two Cap-binding Proteins to Recruit Distinct mRNAs for Translation” Journal of Biological Chemistry 291(20):jbc.M116.717363
    www.jbc.org/content/291/20/10772.abstract Hypoxystation user
  • Haider et al. (2016) “Genomic alterations underlie a pan-cancer metabolic shift associated with tumour hypoxia“ Genome Biology (2016) 17:140
    www.ncbi.nlm.nih.gov/pubmed/27358048

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2. Enabling Replicative Immortality

Cancer is characterized by a nearly unlimited capacity of the tumour cells to proliferate. Hypoxia in the rapidly growing tumour supports immortalisation of a subset of cancer cells, the “cancer stem cells”. Factors such as hypoxia in the tumour microenvironment derail signals indicating senescence and initiating apoptosis, enabling an immortal lifespan. Telomerase, Notch, c-Myc, and OCT4 mediate the acquisition of a stem cell-like phenotype through down-regulation of differentiation genes and activation of stem genes, generating CSC’s with aggressive properties. These cancer stem cells residing in an hypoxic tumour niche are uniquely resistant to many therapies, where low oxygen promotes stemness, maintenance, and self-renewal of the CSC’s. Metastasis and invasion by these CSC’s induce the formation of secondary tumours, which in most cases dramatically worsen the prognosis for cancer patients.

LITERATURE:

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A Manic Month Continues for DWS

June continues to be busy for Don Whitley Scientific, with 6 exhibitions and events attended already. And we have two more to go!

In the month of June, we have attended several meetings and exhibitions that featured topics ranging from pathology, cancer research, LIMS systems and more. We helped to administer the 2017 Practical and Clinical Microbiology of Anaerobes Course, hosted by the UK Anaerobe Reference Unit, Cardiff. It was once again a fantastic success.

Next week (26th-28th June) DWS will be attending the Association for Radiation Research Annual Meeting, which this year focuses on the topic “Improving Radiotherapy Response through Radiation Research” featuring speakers from cancer research institutes from around the world. Don Whitley Scientific will have an exhibition stand at this meeting displaying the Whitley H45 Workstation. There will also be an interactive touchscreen presentation, which allows users to explore the full range of Whitley Workstations.

On 4th July we will also have an exhibition stand at the Society for Applied Microbiology Annual Applied Microbiology Conference at the BALTIC Centre in Gateshead. This meeting will focus on new insights into food safety. Here we will exhibit the ProtoCOL and WASP Touch, two products that provide real benefits in food microbiology applications.

 

Scientist Working in Whitley Workstation

Hypoxia in the Tumour Microenvironment

Hypoxia in the tumour microenvironment affects all the characteristic Hallmarks of Cancer, significantly impacting progression of the cancer and the patients’ prognosis. Inflammation and immunity are both acutely influenced by the low oxygen typical of the tumour microenvironment: hypoxia creates an immune-suppressive network supporting tumour growth and metastasis, and it induces sustained inflammation in a “wound that never heals”.

Cancer research depends on recreating a physiologically accurate environment for cell cultures in the lab, and hypoxia in a closed workstation format such as a Whitley Hypoxystation is the best way to do that. Incubate, image, manipulate and assay – all inside the continuous, reliably stable hypoxic environment. HEPA filtered air scrubbed to ISO 14644 class 3 standards, sterile humidity, and containment options make the Hypoxystation the safest, cleanest workstation available for hypoxic cell culture down to 0.1% O2.

Our Hypoxystation users are investigating all aspects of the Hallmarks of Cancer and how they are shaped by hypoxia. We review their recent research on Avoiding Immune Destruction and Tumour Promoting Inflammation here.

 

hypoxia

CHROMAZONA Automatic Colony Counter

BSMT Annual Scientific Conference

Don Whitley Scientific will be exhibiting at the British Society for Microbial Testing annual conference, held on 12th May at Public Health England in Colindale. 

The BSMT conference is aimed at senior biomedical and clinical scientists, other scientists and medical microbiologists. The meeting will feature talks on a wide range of relevant microbiology topics. The programme features UK and international speakers, who will deliver a range of talks on the day. Don Whitley Scientific will be there to exhibit at the event. Sales representatives will be on hand to discuss how our product range can benefit a range of microbiology applications.

The featured product on the Don Whitley Scientific exhibition stand will be the ChromaZona, an automated microbial identification and antibiotic susceptibility testing (AST) system, which provides faster results for busy laboratories. ChromaZona features automatic comparison with EUCAST MIC breakpoint values and provides fully traceable information for UKAS accreditation.

Also on the Don Whitley Scientific stand is the Whitley Interactive Product Presentation. This interactive display will give delegates the option to explore the full range of Whitley Workstations and access in-depth information on each product. Make sure to visit the Don Whitley Scientific exhibition stand if you are attending this event.