Exciting developments in zinc biology
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ISSF Fellowship | Centre for Experimental Medicine | Queen's University Belfast

ISSF Fellowship | Centre for Experimental Medicine | Queen's University Belfast | Exciting developments in zinc biology | Scoop.it
Exciting fellowship opportunity in eye research in Belfast.
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Zinc: an Antidepressant

Zinc: an Antidepressant | Exciting developments in zinc biology | Scoop.it
Zinc is an essential mineral which may be lacking in modern processed and strict vegetarian diets. Learn how it modulates depression and immune response and the best foods to keep your zinc levels up to par.
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Mice harboring the human SLC30A8 R138X loss-of-function mutation have increased insulin secretory capacity

Mice harboring the human SLC30A8 R138X loss-of-function mutation have increased insulin secretory capacity | Exciting developments in zinc biology | Scoop.it
The zinc transporter SLC30A8 is primarily expressed in islets of the endocrine pancreas. Human SLC30A8 loss-of-function mutations protect against type 2 diabetes. However, Slc30a8 knockout mice do not show this protection.
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Role for zinc and zinc transporters in vascular protection and cardiovascular disease | Supervisor Connect

Role for zinc and zinc transporters in vascular protection and cardiovascular disease | Supervisor Connect | Exciting developments in zinc biology | Scoop.it
Description  The micronutrient zinc has many different physiological functions: it assists hundreds of different proteins in assuming the correct functional conformation, it is part of the catalytic domain of more than 300 enzymes (1), a recent comprehensive esteem concluded that zinc is an essential component of about 10% of the human proteome (2). Zinc is involved also in intracellular signalling (3). We have shown that a layer of zinc protects the tracheobronchial epithelium from oxidative damage, apoptosis and inflammation. In a murine model, we have demonstrated that nutritional zinc deficiency increased the hyper-responsiveness of bronchioles to contract, suggesting that Zn may play, directly or indirectly, a role in smooth muscle contraction, also sufficient intracellular zinc is critical for the integrity and function of the vascular endothelium (4; 5). Zinc is transported across biological membranes through the activity of specialised membrane-embedded zinc transporters (3), we and others reported that specific zinc transporter genes are expressed in vascular and airway epithelium and are responsible for zinc uptake and distribution in these specialised cell types (6; 7). We are now investigating the role of zinc and its transporters in cardiovascular disorders (CVD); this research project uses molecular and biochemical approaches as well as nutritional assessment methods to extend the significance of the findings to human pathophysiology. We will investigate the role of zinc transporter genes and their genetic variants in the onset and severity of CVD. By assessing dietary Zn intake, we will be able to establish whether a correlation exists between nutritional Zn status and endothelial Zn homeostasis in CVD patients and the potential rationale for a Zn interventional clinical trial for CVD patients. We are looking to include in this research program a motivated graduate student that is interested in studying the relationships between diet, risk and severity of chronic disorders. This study is supported by a 3-year National Health & Medical Research Council (NHMRC) project grant and is conducted in collaboration with the University of Adelaide in South Australia. References: 1. Livingstone C (2015) Zinc: physiology, deficiency, and parenteral nutrition. Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition 30, 371-382. 2. Leoni G, Rosato A, Perozzi G et al. (2014) Zinc proteome interaction network as a model to identify nutrient-affected pathways in human pathologies. Genes & nutrition 9, 436. 3. Hara T, Takeda TA, Takagishi T et al. (2017) Physiological roles of zinc transporters: molecular and genetic importance in zinc homeostasis. The journal of physiological sciences : JPS 67, 283-301. 4. Truong-Tran AQ, Ruffin RE, Foster PS et al. (2002) Altered zinc homeostasis and caspase-3 activity in murine allergic airway inflammation. American journal of respiratory cell and molecular biology 27, 286-296. 5. Lang C, Murgia C, Leong M et al. (2007) Anti-inflammatory effects of zinc and alterations in zinc transporter mRNA in mouse models of allergic inflammation. American journal of physiology Lung cellular and molecular physiology 292, L577-584. 6. Zalewski P, Murgia C, Roscioli E et al. (2010) Apical Localization of Zinc Transporter Znt4 in Human Airway Epithelial Cells and Its Loss in a Murine Model of Allergic Airway Inflammation. Respirology 15, 41-41. 7. Thambiayya K, Wasserloos K, Kagan VE et al. (2012) A critical role for increased labile zinc in reducing sensitivity of cultured sheep pulmonary artery endothelial cells to LPS-induced apoptosis. American journal of physiology Lung cellular and molecular physiology 302, L1287-1295. Essential criteria:  Minimum entry requirements can be found here: https://www.monash.edu/admissions/entry-requirements/minimum Keywords  Nutrition; Zinc deficiency, Vascular Endothelium, School  School of Clinical Sciences at Monash Health / Hudson Institute of Medical Research Available options  PhD/Doctorate Graduate Diploma Time commitment  Full-time Part-time Top-up scholarship funding available  No Physical location  BASE facility, Notting Hill Co-supervisors  Dr  Tracy McCaffrey Dr  Peter Zalewski (External)
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The zinc transporter SLC39A7 (ZIP7) is essential for regulation of cytosolic zinc levels

The zinc transporter SLC39A7 (ZIP7) is essential for regulation of cytosolic zinc levels | Exciting developments in zinc biology | Scoop.it
Zinc homeostasis is a highly regulated process in mammalian cells that is critical for normal growth and development. Movement of zinc across cell compartments is controlled by two classes of transporters: Slc39a family members transport zinc into the cytosol from either the extracellular space or from intracellular stores such as the endoplasmic reticulum (ER), while the SSLC30A family mediates zinc efflux from the cytosol. Here we report that genetic ablation of SLC39A7 (ZIP7) results in decreased cytosolic zinc levels, increased ER zinc levels, impaired cell proliferation, and induction of ER stress. Confirmatory of impaired zinc transport as the causal mechanism, both the increased ER stress and impaired cell proliferation were rescued by increasing cytosolic zinc. Furthermore, using these robust cellular phenotypes we implemented a small molecule library screen with 2,800 compounds and identified one small molecule capable of rescuing ER stress and cell proliferation in ZIP7 deficient cells in the low micromolar range.
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ZIP4 Promotes Pancreatic Cancer Progression by Repressing ZO-1 and Claudin-1 through a ZEB1-Dependent Transcriptional Mechanism

ZIP4 Promotes Pancreatic Cancer Progression by Repressing ZO-1 and Claudin-1 through a ZEB1-Dependent Transcriptional Mechanism | Exciting developments in zinc biology | Scoop.it
Purpose: ZIP4 is overexpressed in human pancreatic cancer and promotes tumor growth. However, little is known about the role of ZIP4 in advanced stages of this dismal neoplasm. Our goal is to study the underlying mechanism and define a novel signaling pathway controlled by ZIP4-modulating...
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Zinc deficiency and cellular oxidative stress: prognostic implications in cardiovascular diseases

Zinc deficiency and cellular oxidative stress: prognostic implications in cardiovascular diseases | Exciting developments in zinc biology | Scoop.it
Review Article...
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Overload of Zinc in Muscles to Blame for Wasting Syndrome in Cancer

Overload of Zinc in Muscles to Blame for Wasting Syndrome in Cancer | Exciting developments in zinc biology | Scoop.it
In the study, Acharyya’s team looked in the muscles of mice with cachexia to see if they could find differences compared with normal muscles. The analysis revealed greater activity of a protein called ZIP14, which is typically expressed in liver cells to facilitate metal transport but was found to be abnormally expressed in muscles of the cancer models. They also found high levels of ZIP14 in samples of muscle tissue from cancer patients with cachexia, suggesting a link between ZIP14 and cachexia in people. Excess zinc uptake in muscle leads to muscle wasting in cancer, the researchers found, by breaking down mature muscle cells and preventing stem cells from making new muscle fibers. The reason why ZIP14 pumps more zinc into muscles in cachexia was traced back to the systemic effects of cancer. The researchers found that two factors—TNF-alpha and TGF-beta, which are associated with advanced cancer—increase ZIP14 expression in muscle. “We often think cancer injures the body by spreading and invading vital organs,” Acharyya says. “But cancer can also injure in another way, by releasing substances that affect other areas of the body that are cancer-free. This is an area that is often overlooked in cancer biology research, but addressing it during cancer treatment could have an important impact on patient survival and quality of life.” The discovery of zinc and ZIP14’s connection with cachexia may lead to ways to reduce cachexia’s impact on patients. In the study, reducing ZIP14 in muscle cells markedly reduced cachexia, suggesting that drugs that inhibit ZIP14 could improve cancer survival and quality of life. “Zinc is essential for maintaining many functions in our body and is often taken as a supplement,” says Acharyya. “But excess zinc supplementation may not always be a good thing, because we saw that giving excess zinc supplements to mice with tumors accelerated their muscle wasting and weight loss. With more translational studies, clinicians and patients may need to reconsider the practice of using zinc supplements, especially if they have tumors commonly associated with cachexia.” Acharyya is working with Anup Biswas, PhD, one of the lead authors of this study, to design strategies to inactivate ZIP14. These efforts could lead to the development of therapies to combat cancer cachexia. The paper is titled “Metastatic cancers promote cachexia through ZIP14 upregulation in skeletal muscle.” The other contributors are Gang Wang (CUIMC), Wanchao Ma (CUIMC), Manoj Kandpal (Northwestern University Feinberg School of Medicine, Chicago, IL), Courtney Coker (CUIMC), Paul M. Grandgenett (University of Nebraska Medical Center, Omaha, NE), Michael A. Hollingsworth (University of Nebraska Medical Center), Rinku Jain (Icahn School of Medicine at Mount Sinai, New York, NY), Kurenai Tanji (CUIMC), Sara Lόpez-Pintado (CUIMC), Alain Borczuk (Weill Cornell Medicine, New York, NY), Doreen Hebert (CUIMC), Supak Jenkitkasemwong (University of Florida, Gainesville, FL), Shintaro Hojyo (Deutsches Rheuma-Forschungszentrum Berlin, Osteoimmunology, Charitéplatz, Berlin, Germany), Ramana Davuluri (Northwestern University Feinberg School of Medicine), Mitchell D. Knutson (University of Florida), and Toshiyuki Fukada (Tokushima Bunri University, Yamashiro, Tokushima, Japan). The study was supported in part by the National Cancer Institute (R00CA172697-02), CUIMC startup funds, and a pilot grant to S.A. from the Herbert Irving Comprehensive Cancer Center through the National Cancer Institute (P30CA013696). Source: Columbia University Irving Medical Center
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Multiple Mechanisms of Zinc-Mediated Inhibition for the Apoptotic Caspases-3, -6, -7, and -8 - ACS Chemical Biology (ACS Publications)

Multiple Mechanisms of Zinc-Mediated Inhibition for the Apoptotic Caspases-3, -6, -7, and -8 - ACS Chemical Biology (ACS Publications) | Exciting developments in zinc biology | Scoop.it
Multiple Mechanisms of Zinc-Mediated Inhibition for the Apoptotic Caspases-3, -6, -7, and -8
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Significant Association of Urinary Toxic Metals and Autism-Related Symptoms—A Nonlinear Statistical Analysis with Cross Validation

Significant Association of Urinary Toxic Metals and Autism-Related Symptoms—A Nonlinear Statistical Analysis with Cross Validation | Exciting developments in zinc biology | Scoop.it
Introduction A number of previous studies examined a possible association of toxic metals and autism, and over half of those studies suggest that toxic metal levels are different in individuals with Autism Spectrum Disorders (ASD). Additionally, several studies found that those levels correlate with the severity of ASD. Methods In order to further investigate these points, this paper performs the most detailed statistical analysis to date of a data set in this field. First morning urine samples were collected from 67 children and adults with ASD and 50 neurotypical controls of similar age and gender. The samples were analyzed to determine the levels of 10 urinary toxic metals (UTM). Autism-related symptoms were assessed with eleven behavioral measures. Statistical analysis was used to distinguish participants on the ASD spectrum and neurotypical participants based upon the UTM data alone. The analysis also included examining the association of autism severity with toxic metal excretion data using linear and nonlinear analysis. “Leave-one-out” cross-validation was used to ensure statistical independence of results. Results and Discussion Average excretion levels of several toxic metals (lead, tin, thallium, antimony) were significantly higher in the ASD group. However, ASD classification using univariate statistics proved difficult due to large variability, but nonlinear multivariate statistical analysis significantly improved ASD classification with Type I/II errors of 15% and 18%, respectively. These results clearly indicate that the urinary toxic metal excretion profiles of participants in the ASD group were significantly different from those of the neurotypical participants. Similarly, nonlinear methods determined a significantly stronger association between the behavioral measures and toxic metal excretion. The association was strongest for the Aberrant Behavior Checklist (including subscales on Irritability, Stereotypy, Hyperactivity, and Inappropriate Speech), but significant associations were found for UTM with all eleven autism-related assessments with cross-validation R2 values ranging from 0.12–0.48.
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IJMS | Free Full-Text | Proteomic High Affinity Zn2+ Trafficking: Where Does Metallothionein Fit in?

IJMS | Free Full-Text | Proteomic High Affinity Zn2+ Trafficking: Where Does Metallothionein Fit in? | Exciting developments in zinc biology | Scoop.it
The cellular constitution of Zn-proteins and Zn-dependent signaling depend on the capacity of Zn2+ to find specific binding sites in the face of a plethora of other high affinity ligands. The most prominent of these is metallothionein (MT). It serves as a storage site for Zn2+ under various conditions, and has chemical properties that support a dynamic role for MT in zinc trafficking. Consistent with these characteristics, changing the availability of zinc for cells and tissues causes rapid alteration of zinc bound to MT. Nevertheless, zinc trafficking occurs in metallothionein-null animals and cells, hypothetically making use of proteomic binding sites to mediate the intracellular movements of zinc. Like metallothionein, the proteome contains a large concentration of proteins that strongly coordinate zinc. In this environment, free Zn2+ may be of little significance. Instead, this review sets forth the basis for the hypothesis that components of the proteome and MT jointly provide the platform for zinc trafficking.
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The effects of vitamin and mineral supplementation on symptoms of schizophrenia: a systematic review and meta-analysis | Psychological Medicine

The effects of vitamin and mineral supplementation on symptoms of schizophrenia: a systematic review and meta-analysis - Volume 47 Issue 9 - J. Firth, B. Stubbs, J. Sarris, S. Rosenbaum, S. Teasdale, M. Berk, A. R. Yung
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The six different roles of zinc in pigs

The six different roles of zinc in pigs | Exciting developments in zinc biology | Scoop.it
The trace element zinc is being used in various ways in pig feed – both as an essential nutrition component but also, at pharmacological levels, to suppress scouring. This article aims to identify six different modes of actions of zinc for pigs.
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Zinc deficiency impairs the renewal of hippocampal neural stem cells in adult rats: involvement of FoxO3a activation and downstream p27kip1 expression - Han - 2015 - Journal of Neurochemistry - Wil...

 Zinc plays an important role in the development and maintenance of central neural system. Zinc deficiency has been known to alter normal brain function, whose molecular mechanism remains largely elusive. In the present study, we established a zinc deficiency‐exposed rat model, and, using western blot and

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email : Webview : IZA Update: August 2018

email : Webview : IZA Update: August 2018 | Exciting developments in zinc biology | Scoop.it
The International Zinc Association's recent newsletter.

Look at the section on wine :-)
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Cells | Special Issue : Emerging Trends in Metal Biochemistry

Cells | Special Issue : Emerging Trends in Metal Biochemistry | Exciting developments in zinc biology | Scoop.it
Cells, an international, peer-reviewed Open Access journal.
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Researchers discover mechanism controlling zinc

The University of Wisconsin School of Medicine and Public Health in Madison addresses the evolving health care needs of Wisconsin and beyond while building on our innovative tradition of more than 100 years of educating health professionals and expanding boundaries of science through research.
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Three-minute thesis: Zinc and human health | Cosmos

Three-minute thesis: Zinc and human health | Cosmos | Exciting developments in zinc biology | Scoop.it
How important is the role of zinc in diabetes treatment?
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ISZB 2019 – The 6th Meeting for International Society for Zinc Biology

ISZB 2019 – The 6th Meeting for International Society for Zinc Biology | Exciting developments in zinc biology | Scoop.it
Copyright © ISZB 2019 All Rights Reserved.
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Zinc: A Potential Antiviral Against Hepatitis E Virus Infection?

Zinc: A Potential Antiviral Against Hepatitis E Virus Infection? | Exciting developments in zinc biology | Scoop.it
Hepatitis E virus (HEV) is a major cause of viral hepatitis worldwide. Owing to its feco oral transmission route, sporadic as well as epidemic outbreaks recurre...
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ScienceDirect

ScienceDirect | Exciting developments in zinc biology | Scoop.it
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Zinc-Net produced a fantastic compilation of work from the network activities. Please go to the Journal of Trace Elements in Medicine and Biology site and find all these great papers!
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The Role of Chelation in the Treatment of Other Metal Poisonings

The Role of Chelation in the Treatment of Other Metal Poisonings | Exciting developments in zinc biology | Scoop.it
These proceedings will review the role of chelation in five metals—aluminum, cadmium, chromium, cobalt, and uranium—in order to illustrate various chelation concepts. The process of “chelation” can often be oversimplified
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Agronomic biofortification of cereals with zinc: a review - Cakmak - 2018 - European Journal of Soil Science - Wiley Online Library

Summary Zinc (Zn) still represents an important health problem in developing countries, caused mainly by inadequate dietary intake. A large consumption of cereal‐based foods with small concentrations and low bioavailability of Zn is the major reason behind this problem.
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Frontiers | Cyclic AMP Pathway Activation and Extracellular Zinc Induce Rapid Intracellular Zinc Mobilization in Candida albicans | Microbiology

Frontiers | Cyclic AMP Pathway Activation and Extracellular Zinc Induce Rapid Intracellular Zinc Mobilization in Candida albicans | Microbiology | Exciting developments in zinc biology | Scoop.it
Zinc is an essential micronutrient, required for a range of zinc dependent enzymes and transcription factors. In mammalian cells, zinc serves as a second messenger molecule. However, a role for zinc in signaling has not yet been established in the fungal kingdom. Here, we used the intracellular zinc reporter, zinbo 5, which allowed visualization of zinc in the endoplasmic reticulum and other components of the internal membrane system in Candida albicans. We provide evidence for a link between cyclic AMP/PKA- and zinc- signaling in this major human fungal pathogen. Glucose stimulation, which triggers a cyclic AMP spike in this fungus resulted in rapid intracellular zinc mobilization and this “zinc flux” could be stimulated with phosphodiesterase inhibitors and blocked via inhibition of adenylate cyclase or PKA. A similar mobilization of intracellular zinc was generated by stimulation of cells with extracellular zinc and this effect could be reversed with the chelator EDTA. However zinc-induced zinc flux was found to be cyclic AMP independent. In summary, we show that activation of the cyclic AMP/PKA pathway triggers intracellular zinc mobilization in a fungus. To our knowledge, this is the first described link between cyclic AMP signaling and zinc homeostasis in a human fungal pathogen.
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Zinc ion rapidly induces toxic, off-pathway amyloid-β oligomers distinct from amyloid-β derived diffusible ligands in Alzheimer’s disease

Zinc ion rapidly induces toxic, off-pathway amyloid-β oligomers distinct from amyloid-β derived diffusible ligands in Alzheimer’s disease | Exciting developments in zinc biology | Scoop.it
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