Research Event

Event participants

Louise Mushikiwabo, Secretary General, Organisation Internationale de la Francophonie (OIF)
Chair: Bob Dewar CMG, Associate Fellow, Africa Programme, Chatham House

This article has been withdrawn by the authors as part of this review overlapped with the contents of Pietrangelo A and Ridgway ND. 2018. Cellular and Molecular Life Sciences. 75; 3079-98.

In quantitative proteomics work, the differences in expression of many separate proteins are routinely examined to test for significant differences between treatments. This leads to the multiple hypothesis testing problem: when many separate tests are performed many will be significant by chance and be false positive results. Statistical methods such as the false discovery rate (FDR) method that deal with this problem have been disseminated for more than one decade. However a survey of proteomics journals shows that such tests are not widely implemented in one commonly used technique, quantitative proteomics using two-dimensional electrophoresis (2-DE). We outline a selection of multiple hypothesis testing methods, including some that are well known and some lesser known, and present a simple strategy for their use by the experimental scientist in quantitative proteomics work generally. The strategy focuses on the desirability of simultaneous use of several different methods, the choice and emphasis dependent on research priorities and the results in hand. This approach is demonstrated using case scenarios with experimental and simulated model data.

The histidine kinase Hik33 plays important roles in mediating cyanobacterial response to divergent types of abiotic stresses including cold, salt, high light (HL), and osmotic stresses. However, how these functions are regulated by Hik33 remains to be addressed. Using a hik33-deficient strain (hik33) of Synechocystis sp. PCC 6803 (Synechocystis) and quantitative proteomics, we found that Hik33 depletion induces differential protein expression highly similar to that induced by divergent types of stresses. This typically includes downregulation of proteins in photosynthesis and carbon assimilation that are necessary for cell propagation, and upregulation of heat shock proteins, chaperons, and proteases that are important for cell survival. This observation indicates that depletion of Hik33 alone mimics divergent types of abiotic stresses, and that Hik33 could be important for preventing abnormal stress response in the normal condition. Moreover, we found the majority of proteins of plasmid origin were significantly upregulated in hik33, though their biological significance remains to be addressed. Together, the systematically characterized Hik33-regulated cyanobacterial proteome, which is largely involved in stress responses, builds the molecular basis for Hik33 as a general regulator of stress responses.

NADPH facilitates glucose-stimulated insulin secretion (GSIS) in pancreatic islet (PI) β-cells by an as yet unknown mechanism. We found NADPH oxidase, isoform-4 (NOX4), to be the major producer of cytosolic H₂O₂, essential for GSIS, while the increase in ATP/ADP alone was insufficient. The fast GSIS phase was absent in PIs from NOX4-null, β-cell-specific knockout mice (NOX4βKO) (not NOX2KO), and NOX4-silenced or catalase-overexpressing INS-1E cells. Lentiviral NOX4 overexpression or H₂O₂ rescued GSIS in PIs from NOX4βKO mice. NOX4 silencing suppressed Ca²⁺ oscillations and the patch-clamped ATP-sensitive potassium channel (K_ATP) opened more frequently at high glucose. Mitochondrial H₂O₂, decreasing upon GSIS, provided an alternative redox signaling when 2-oxo-isocaproate or fatty acid oxidation formed superoxide by electron-transport flavoprotein:Q-oxidoreductase. Unlike GSIS, this ceased with mitochondrial antioxidant SkQ1. Both NOX4KO and NOX4βKO strains exhibited impaired glucose tolerance and peripheral insulin resistance. Thus the redox signaling previously suggested to cause β-cell-self-checking – hypothetically induces insulin resistance when absent. In conclusion, ATP plus H₂O₂ elevations constitute an essential switch-on signal of insulin exocytosis for glucose and branched-chain oxoacids as secretagogues (partly for fatty acids). Redox signaling could be impaired by cytosolic antioxidants, hence those targeting mitochondria should be preferred for clinical applications to treat (pre)diabetes at any stage.

The developing nervous system is remarkably sensitive to environmental signals, including disruptive toxins, such as polybrominated diphenyl ethers (PBDEs). PBDEs are an environmentally pervasive class of brominated flame retardants whose neurodevelopmental toxicity mechanisms remain largely unclear. Using dissociated cortical neurons from embryonic Rattus norvegicus, we found here that chronic exposure to 6-OH–BDE-47, one of the most prevalent hydroxylated PBDE metabolites, suppresses both spontaneous and evoked neuronal electrical activity. On the basis of our previous work on mitogen-activated protein kinase (MAPK)/extracellular signal-related kinase (ERK) (MEK) biology and our observation that 6-OH–BDE-47 is structurally similar to kinase inhibitors, we hypothesized that certain hydroxylated PBDEs mediate neurotoxicity, at least in part, by impairing the MEK–ERK axis of MAPK signal transduction. We tested this hypothesis on three experimental platforms: 1) in silico, where modeling ligand–protein docking suggested that 6-OH–BDE-47 is a promiscuous ATP-competitive kinase inhibitor; 2) in vitro in dissociated neurons, where 6-OH–BDE-47 and another specific hydroxylated BDE metabolite similarly impaired phosphorylation of MEK/ERK1/2 and activity-induced transcription of a neuronal immediate early gene; and 3) in vivo in Drosophila melanogaster, where developmental exposures to 6-OH–BDE-47 and a MAPK inhibitor resulted in offspring displaying similarly increased frequency of mushroom-body β–lobe midline crossing, a metric of axonal guidance. Taken together, our results support that certain ortho-hydroxylated PBDE metabolites are promiscuous kinase inhibitors and can cause disruptions of critical neurodevelopmental processes, including neuronal electrical activity, pre-synaptic functions, MEK–ERK signaling, and axonal guidance.

Mikael Knip
Dec 1, 2005; 54:S125-S136
Section IV: Polygenic Disease and Environment

Pablo Sandoval said he recruited his friends Gerardo Parra and Yangervis Solarte to the Giants in the offseason.

Invitation Only Research Event

1 June 2012 , Volume 68, Number 4

Eyes in the skies keeping watch on a planet under stress. Click on the PDF link to view the graphic

Oversimplification and lack of evidence stigmatise people with mental illness and impede prevention efforts, says Simon Wessley, professor of psychiatry at King's College London, in an editorial published on thebmj.com. Read the full editorial: http://www.bmj.com/content/354/bmj.i4869

Around 1 in 10 children and young people worldwide have mental health difficulties that substantially affect their lives. Child mental health services often concentrate on risk reduction, at the expense of the wider aspects of a child's wellbeing. As part of the high integrity healthcare series, this podcast focuses on novel ways of providing...

The rapid changes in the global environment have led many scientists to conclude that we are living in a new geological epoch—the Anthropocene—in which human activities have become the dominant driving force transforming the Earth’s natural systems. A recent joint publication by the World Health Organization and Convention on Biological Diversity...

The Senate on Friday paid tribute to distinguished consultant psychiatrist, Frederick Hickling, for his tremendous contribution to persons with intellectual disabilities. Hickling died on Thursday. Senator Dr Saphire Longmore remembered Professor...

2 July 2014 , Volume 90, Number 4

In an effort to help develop their players on and off the field, the D-backs have added a mental skills department to their baseball operations staff.

This policy brief explores the relationship between environmental change and migration to Europe in light of recent scholarship challenging the notion that environmental change triggers mass migration. It presents an overview of European policy response in this area and summarizes the spectrum of proposed solutions.

Environmental change is likely to affect global migration flows in a number of ways. Both long-term trends such as increased flooding and the increasing scarcity of resources as well as shorter term trends like severe weather are likely to contribute to displacement and increased migration for individuals already in vulnerable situations. While often viewed as a negative outcome of climate change, planned migration can also serve as a strategy for mitigating its impact.  

Discussion at launch of this MPI-IOM Issue in Brief, Human Rights, Climate Change, Environmental Degradation and Migration: A New Paradigm, which focuses on the vulnerability of environmental migrants and how the international legal framework can better ensure their protection, particularly in the Asia-Pacific region.

This issue brief addresses the rights of migrants whose movement is induced by environmental degradation or climate change, particularly in the highly vulnerable Asia-Pacific region. The brief evaluates the current international legal framework, identifies gaps in the framework and its implementation, and reviews options available to the international community.

This MPI event, in partnership with the International Organization for Migration (IOM), discusses the critical issue of climate-related displacement in the Asia-Pacific region, focusing on the vulnerability of environmental migrants and how the international legal framework can better ensure their protection.

The National Academies of Sciences, Engineering, and Medicine announced March 5 that it does not find that the National Toxicology Program adequately supported its conclusion that fluoride is “presumed” to be a cognitive neurodevelopmental hazard to humans.

Cancer patients on Medicaid or who don't have insurance benefit less from experimental treatments, even if they get into clinical trials, a study published Thursday by JAMA Network Open has found.

What happens when the police are called to handle a mental health emergency? And is the current coronavirus pandemic affecting their response? In today’s podcast, Gabe interviews Sergeant Matt Harris,...

During a time when the world is focused on the current COVID-19 pandemic, a physical health crisis, and all those treating the physical symptoms of this pandemic, we must not...

Originally published in June 1899

-- Read more on ScientificAmerican.com

Somali and Bhutanese refugees are two of the largest groups recently resettled in the United States and Canada. This report examines factors that might promote or undermine the mental health and overall well-being of children of these refugees, with regard to factors such as past exposure to trauma, parental mental health, educational attainment, social support, and discrimination.

One of the primary reasons people seek therapy is to get help with mental health issues. Some of the more common mental disorders affecting individuals today include depression, anxiety, post traumatic stress (PTSD), phobias, addiction, and attention deficit hyperactivity (ADHD). Depending on the type and intensity of your issue, your therapist may adjust his treatment […]

These days, there is huge hype around cannabidiol (also known as CBD), and for good reason.  There are numerous health benefits that are linked to this non-psychoactive all-natural substance. Many people report that CBD has helped them to manage mental and emotional distress. But are those reports true? Can CBD help your mental health? In […]

Some people have the misguided belief that synchronized swimming is just an easy sport performed in beautiful swim team suits. That it’s merely dancing in the water that you can tune in to watch during the Olympic Games. But that is far from true; there is much more to the sport.  Synchro is a dominant […]

Health care workers are under more stress than ever before. How can they protect their mental health while handling new and complex pressures? TED Fellow Laurel Braitman shows how writing and sharing personal stories helps physicians, nurses, medical students and other health professionals connect more meaningfully with themselves and others -- and make their emotional well-being a priority.

Award-winning short documentary about the benefits of digital health tools for mental health.

A lovely short video about a mother who goes through the forensic mental health care system and recovers and regains custody of her son.

By Emily Reynolds. Study finds viewers had slightly more negative perceptions of people with mental illness after seeing the movie.

Keeping up with students’ growing mental-health needs was a concern for districts long before the pandemic began. It’s even harder now, educators and psychologists say.

Keeping up with students’ growing mental-health needs was a concern for districts long before the pandemic began. It’s even harder now, educators and psychologists say.

Students returning to schools in Virginia and New York this fall will be required to participate in mental-health education as part of their health and physical education courses.

Keeping up with students’ growing mental-health needs was a concern for districts long before the pandemic began. It’s even harder now, educators and psychologists say.

Keeping up with students’ growing mental-health needs was a concern for districts long before the pandemic began. It’s even harder now, educators and psychologists say.

Keeping up with students’ growing mental-health needs was a concern for districts long before the pandemic began. It’s even harder now, educators and psychologists say.

"This is a complex and stressful time in our society and the mental health and wellness of our Big Ten family is a critical component of our focus."

Meat industry and trade -- Environmental aspects.