This year’s Nobel Prize for Physiology or Medicine was awarded for work elucidating circadian rhythm molecular pathways. Greater understanding of circadian rhythm and its implications bring with it exciting discoveries. A role for circadian rhythm in ischemic cardiac protection has been identified in several studies

• The incidence of myocardial infarction (Ml) is known to be higher in the morning1 and there is a higher

rate of greater ischemic injury when the Ml occurs in the early morning2 . Additionally, the light elicited, circadian rhythm protein Per2, has been shown to have a cardioprotective role in ischemic cardiac events3 .

The cardiac metabolic response to ischemia is the source of tremendous damage to heart tissue. A lack of oxygen during cardiac ischemia, disrupts aerobic, oxidative phosphorylation resulting in an ATP deficit that leads to cell death. Products of glycolysis are shifted away  from  oxidative  phosphorylation to the production of lactate – this shift results in damaging acidosis and less efficient ATP production. Studies on cardiac metabolism have found a key role for light induced expression  increase of Per2  in  the transcriptional induction of glycolytic enzymes, enhancing oxygen efficient glycolysis, making the heart better prepared to adapt to ischemia.4• 5 .

In a recent study, Dr. Colleen M. Bartman and her colleagues set out to clarify how PER2 exerts its cardioprotective effects on oxygen efficient pathways, to identify new therapeutic targets. To identify PER2- dependent miRNA elements of cardioprotective pathways, QIAGEN RF Kits were used to  isolate  miRNA from wildtype and PER2^-/- mice and compare expression in miRNA PCR arrays. Of the 352 most abundantly expressed PER2-dependent miRNAs, miR-21 stood out.

To confirm miR-21 as a downstream PER2 target, wildtype and PER^-/- mice were exposed to cardioprotective ischemic preconditioning (IPC – 4 cycles of 5 min. ischemia/5 min reperfusion) and heart miR-21 expression was analyzed via qPCR using QIAGEN miSCRIPT miRNA probes. IPC resulted in a 2.4- fold induction of miR-21 in wildtype mice,  with  no  upregulation  observed  in Per2^-/-mice.  The group  was then able to show an increase in miR-21 and PER2 with exposure to light. Exposing wildtype mice to

l4h/day of intense light increased cardiac miR-21 levels 6-fold and PER2 levels 4-fold.  Next, wildtype controls or miR-21^-/- mice were exposed to 3 hours of intense light prior to myocardial ischemia and reperfusion injury. Light exposure significantly reduced infarct sizes in wildtype controls but failed to induce cardioprotection in miR-21^-/- mice. These finding suggests that miR-21  is a downstream  target of light / PER2 in exerting cardioprotective effects.

In humans, one week of intense light exposure in 8 human subjects increased  their blood plasma  miR-21 levels 3.5-fold and phosphofructokinase (PFK) activity increased 49%. PFK expression was monitored as it is the key regulatory enzyme in the glycolytic pathway. The significant increase in PFK  activity indicates  miR- 21’s cardioprotective effects could come from enhancement of glycolysis.

1. Muller JE, Stone PH, Turi ZG, Rutherford JD, Czeisler CA, Parker C, et al. Circadian variation in the frequency of onset of acute myocardial infarction. N Engl J Med. 1985;313(21):1315–22
2. Reiter R, Swingen C, Moore L, Henry TD, Traverse JH (2012) Circadian dependence of infarct size and left ventricular function after ST elevation myocardial infarction. Circ Res 110: 105–110
3. Suarez‐Barrientos et al (2011) Circadian variations of infarct size in acute myocardial infarction. Heart 97: 970–976
4. Gary D.Lopaschuk, Jagdip S. Jaswal (2012) A Role for Period 2 in Cardioprotection. Cell Met 16: 2-4
5. Tobias Eckel et al (2012) Adora2b-elicited Per2 stabilization promotes a HIF-dependent metabolic switch crucial for myocardial adaptation to ischemia. Nature Medicine 18, 774–782

Diabetes mellitus is one of the most common chronic diseases, globally. The prevalence has risen from 4.7% of adults over 18 years of age in 1980 to 8.5% in 2014¹. Plagued by treatment non-compliance, it is estimated that approximately 50% of Type 2 Diabetics fail to achieve adequate glycemic control². The positive association between diabetes and Alzheimer’s disease is well known – A large population-based study from Rotterdam suggested that diabetes can almost double the risk of developing Alzheimer’s disease and vascular dementia.³ The link, however between the metabolic disorder and the devastating neurological disease has remained the object of speculation.

Alzheimer’s disease (AD) is characterized by two types of brain lesions – extracellular β-amyloid (Aβ) accumulation in amyloid plaques and intracellular aggregation of hyperphosphorylated tau into neurofibrillary tangles⁴. A study detailed in Nature Scientific Reports, investigated the effect of high glucose on β-site amyloid precursor protein cleaving enzyme 1 (BACE1) expression and amyloidogenesis in vivo. BACE1 is the enzyme responsible for initiating β-amyloid (Aβ) generation from amyloid precursor protein (APP). Amyloid deposition begins 10-20 years before Alzheimer’s dementia onset, suggesting an early role in pathogenesis for Aβ accumulation; making BACE1 a desirable target of study⁵.

In their study, Dr. Ho Jae Han and his team showed an increase in Aβ deposition in diabetic, ZDF rat brains, in response to high glucose. ZDF rats were also shown to have higher levels of BACE1 expressions than those in lean control, ZLC rats. To provide a compelling link between diabetes and AD, the mechanism by which high glucose levels affected APP processing was investigated using mouse hippocampal neuron and SK-N-MC cells.

Using the QIAGEN QuantiNova SYBR Green PCR Kit the group was able to demonstrate via real-time PCR gene expression analysis that high glucose conditions increases expression of BACE1 through upregulation of HIF-1α expression. LXRα/ABCA1 were also upregulated in the presence of high glucose and shown to stimulate BACE1 by recruiting it to lipid rafts, where APP cleavage to Aβ occurs.

Further studies and proof that uncontrolled diabetes can lead to serious neurological impairment could spur early diagnosis programs and go a long way towards improved compliance with diabetes treatments. This would have a profound effect not only on the diabetes morbidity and mortality rate², but also on the prevalence of Alzheimer’s disease – having the potential to reduce Alzheimer’s incidence by up to 40%.

You can read more about this study in Nature Scientific Reports here. Explore our Alzheimer’s pathway to build and present your own findings of molecular interactions or visit our online Research Center and advance your understanding in Alzheimer’s disease and neurodegenerative diseases.

1. Global Report on Diabetes 2016. Geneva: World Health Organization
2. Luis-Emilio García-Pérez et. al. Adherence to Therapies in Patients with Type 2 Diabetes. Diabetes Ther. 2013 Dec; 4(2): 175–194.
3. Ott A. et al.: Diabetes mellitus and the risk of dementia: The Rotterdam study. Neurology 1999 10: 1937–1942.
4. Hardy J, Selkoe DJ: The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science 2002, 297: 353-356.
5. T. Ohara, Y. Doi, T. Ninomiya, et al. Glucose tolerance status and risk of dementia in the community. The Hisayama Study. Neurology 2011, 77:1126Hardy J, Selkoe DJ: The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science 2002, 297: 353-356.

I haven’t heard how lucky I am that I get to work from home lately. I am actually. I’d like to help you feel that way too.

The unexpected, mass migration to home-office work has been stressful and disorienting. Leaving your workplace, meant the loss of a social circle and feeling of connection, and also the loss of impromptu encouragement and feedback. These things help you feel grounded and secure in your work.

Working with (and communicating with) people remotely, over digital media is its own beast. I want to give you, some easy to implement, best practices for working with digital media and being heard remotely.

Be unambiguously positive: Subtlety leads to misunderstandings in digital meetings and communications

The subtlety in your tone, facial expressions, gestures are muted or lost over digital media, even video conferences. The loss of body language cues in digital meetings leads to misunderstandings, at the best of times, and these are not the best of times. You must be almost overly positive, now that we are all working remotely – you don’t want to sound like a jerk and you definitely don’t want to be a main contributor to the commiseration portion of group meetings. Let your optimism and kind words help you get your message through, as intended.

Be clear and concise: Long emails get ignored and wordy monologues become daydreaming time

Succinct messages are always the right way to go. With distractions at home, stress from routines being upended, fear for relatives and on and on – now, more than ever, you must fight for your colleagues’ attention.

Your game plan: Define the goal of your communication; what should people do or learn afterwards? Use short bullet points to plan what you will write in an email or slides or what you need to communicate in a meeting. Remove anything that does not further your goal. Use your bullet points in your emails and slides and as the basis for your speech, call, or presentation.

• Bullet points are easier to read & more likely to keep the reader’s attention (emails, slides)
• Flesh out bullet points with as few words as possible for speeches, calls, presentations

Remember, whether it’s a subject line that gets an email opened or slides that keep people awake, keep it brief and focused on your audience and what they need to get out this communication.

Overcommunicate: Get their attention and make sure they know you’re working

Yes. You are fighting for attention now, AND you will also be fighting the perception (of some) that you are lounging around your house all day. Working from home creates pressure to both make yourself heard and show how productive you are. The solution is the communications staple, repetition. Balancing home and work responsibilities, your work schedule has probably changed. Communicate your schedule often to everyone who needs to know your availability. Have you finished a project or reached a goal? Speak up. Joke about how since you’ve been home, you’ve been telling everyone everything you’ve been doing, a hundred times – then tell them again.

Be “heard” in meetings: Let them know you’re there and contributing

You are probably being invited to even more meetings than usual. A lot of things you used to be able to do quickly at the office, have become meetings. Even when they’re boring, be there. Let them know you were on the call. Contribute something useful. At the very least let your voice be heard with a nice, “Thanks everyone. Bye.”

‘The Visual’ is very important in digital media: at home, that means you

Just look at Twitter. The image is everything. Pay attention to the impression you are making. You may need to counter the bias that you are not really working at home or that your job couldn’t effectively be done from home. Set your alarm, get up and showered. Get dressed for work. You are working, so help them see that by looking the part.

A final tip, for your own peace of mind, assume positive intent from your colleagues – ‘It’ is probably not about you. If you can’t do that, then at least, don’t hit «send» on your angry response.

More to come.

Anissa Heyse, Scientific Writer & Consultant

Savoir Dire Scientific Communications

Gain new skills and connections and feel great doing good

In these uncertain times, charitable organizations will need help – so will our careers

We have started into what is expected to be the largest economic decline since the Great Depression, According to the IMF. With economic shutdowns and millions of job losses around the world, many of us are wondering, how secure our jobs are, and how the companies we work for will weather this crisis.

In uncertain times like this, it’s natural to focus on maintaining your salary and position and easy to lose sight of your longer-term career goals. Maybe the help our communities all need now is our chance to  do something really good for our careers and help our communities during a crisis.

Yes, you do, at any stage of your career, have something valuable to offer a charity

‘What can I offer?’, can be an intimidating question. Like any company, charities need people with all types of skills. More than that, regardless of age or career progression we can all offer: time, ideas, energy and influence.

4 things charity work has to offer

1. Gain work experience: Accelerate your career

How many jobs have you not applied for because you didn’t have the right experience? Many volunteer organizations are small; they need volunteers to step up and fill in whichever vacant roll and perform a wide variety of tasks. Your current professional skills will probably get you in the door. I.e. Do you speak more than one language? You will probably be asked to translate, but perhaps you would like to try your hand at communications. If you show you’re willing, you could learn skills and gain experience, faster than you would in your paid career.

Expand your network: Make connections across industries

You will meet new people with a range of backgrounds and professions, and from every career level. Networking as a volunteer means that everyone you meet  gets to see you working for something you are passionate about – and they share that passion. Recommendations and  references from volunteer work, can be among the best.

Explore a passion without the risk of a career change

Volunteering gives you a low-risk way to explore an interest or a career change. Discover you’re not as passionate about wildlife conservation as you thought you were, or did the  communications projects you tried, just not feel right? Try another department or another charity. There’s a lot of good to be done.

You will feel fantastic

Offering help and working for a cause you care about, is uniquely satisfying and rewarding. Volunteering lets you feel a sense of connection to your community, that not many people ever experience. It’s a certain way to meet like-minded people and make friends.

How to find volunteer opportunities: It’s easier than you think

I live in Switzerland. There are over 13,000 charitable organizations here. America? 1.4 million. It’s not World Wildlife Fund or bust. Wherever you live, you will find a charity that matches your interests. Think about causes you could get passionate about and research charities working in those areas. Once you have narrowed your list, see if you have any connections in the charity or just call them up and ask to talk to the Volunteer Coordinator.

You have a lot to offer and a lot to gain.

Good luck and thank you.

More to come.

Anissa Heyse