Author: Michele Arduengo

by

The Age of the Genome: Commercial DNA Sequencing, Familial Searching and What We Are Learning

Crowd of people at the street, city center

All of these people are 99% the same at the genomic level. The individuals of the human species are far more alike than different.

There are 3 billion (3,000,000,000) bases in my genome—in each of the cells of my body. Likewise, Johanna, the writer who sits next to me at work also has 3 billion bases in her genome. Furthermore, our genomes are 99% the same. Still, that’s a lot of places where my genome can differ from hers, certainly enough to distinguish her DNA from mine if we were both suspected of stealing cookies from the cookie jar. The power of discrimination is what makes genetic identity using DNA markers such a powerful crime solving tool.

The completion of the human genome project in 2003 ushered in a tremendously fast-paced era of genomics research and technology. Just like computers shrank from expensive, building-filling mainframes to powerful hand-held devices we now call mobile phones, genome sequencing has progressed from floor-to-ceiling capillary electrophoresis units filling an entire building to bench top sequencers sitting in a corner of a lab. The $99 genome is a reality, and it’s in the hands of every consumer willing to spit into a tube.

Commercial DNA sequencing services are promising everything from revealing your true ancestry to determining your likelihood to develop dementia or various cancers. Is this progress and promise or is it something more sinister?

As it turns out, that isn’t an easy question to answer. What is probably true is that whole genome sequencing technologies are being put into the hands of the consumer faster than society understands the ethical implications of making all of this genomic information so readily available. Continue reading →

by

Counting Crows: Evidence for Hard-Wired, Inborn Ability to Detect Numerical Sets

“The Great Book of Nature is written in mathematical language” –Galileo Galilei (1)

carrion crow (corvus corone) headshot portrait against a blue background

Carrion Crow (Corvus corone)

If mathematics is the language of the universe, might we find the ability to do math hard-wired in species?

Research in primates has demonstrated that even without training, humans and monkeys possess numerosity, the ability to assess the number of items in a set (2,3).

A paper in Current Biology from Wagener and colleagues provides evidence that crows are born with a subset of neurons that are “hard wired” to perceive the number of items in a set (4). This work provides yet more evidence supporting a hypothesis of an innate “number sense” that is provided by a specific group of “preprogrammed” neurons.

In this study, Wagener’s group measured the responses of single neurons in two “numerically naïve” crows to color dot arrays. They measured neurons in the endbrain region known as the niopallium caudolaterale (NCL), which is thought to be the avian analog of the primate prefrontal cortex. They found that 12% of the neurons in NCL specifically responded to numbers and that specific neurons responded to specific numbers of items with greater or lesser activity.

This is the first such study to investigate the idea of an innate “sense of number” in untrained vertebrates that are not primates, and as such it suggests that a hard-wired, innate “sense of number” is not a special feature of the complex cerebral cortex of the primate brain but is an adaptive property that evolved independently in the differently structured and evolved end brains of birds.

Many questions remain. Are there similarities in the actual neurons involved? What does learning do on a physiological level to these neurons: Increase their number, increase connections to them?  What other vertebrates have similar innate mechanisms for assessing numbers of items? What about other members of the animal kingdom that need to have a sense of number for social or foraging behavior? How is it accomplished?

And finally, one last burning question, if birds are dinosaurs, does that mean that dinosaurs perished because they didn’t do their math homework? Asking for an eleven-year-old I know.

  1. Tyson, Peter. (2001) Describing Nature with math. NOVA  http://www.pbs.org/wgbh/nova/physics/describing-nature-math.html 
  2. Izard, V. et al. (2009) Newborn infants perceive abstract numbers PNAS USA 106, 10382–85.
  3. Viswanahtan, P. and Neider, A. (2013) Neuronal correlates of a visual “sense of number” in primate parietal and prefrontal cortices. PNAS USA 110, 1118–95.
  4. Wagnener, L. et al. (2018) Neurons in the endbrain of numerically naïve crows spontaneously encode visual numerosity Cur. Biol. 28, 1–5.
by

Get Out and Count: The Great Backyard Bird Count of 2018

2018 has been designated “The Year of the Bird”, and beginning today, Friday, February 16, 2018, bird lovers around the world will grab their binoculars, fill their bird feeders, update their eBird app, and look toward the skies. The 21st Annual Great Backyard Bird Count, one of the largest and longest running citizen science projects, begins today, and you can be part of this grand event of data collection.

All it takes is a mobile device (or computer) to log your results, an account at gbbc.birdcount.org , and 15 minutes of your time during the four-day event.

Can’t tell a red-tailed hawk from a red-winged black bird? That’s okay. The GBBC web site provides a handy online bird guide.  The web site also provides a guide for tricky bird IDs, including: Which Red Finch is it, Identifying Some Common Sparrows, and Identifying Doves.

I recently spent some time talking to Brian Schneider, one of the educators at the Aldo Leopold Nature Center in Monona, WI, to get some tips for first-time birders. Continue reading →

by

Optimizing Your Scientific Conference Experience

When I was in graduate school (a really long time ago), I remember going to my first big conference—American Society for Cell Biology—and being completely overwhelmed. I walked in with my Annual Conference Proceedings (back then it was all paper—no apps—and those books were thick, heavy and took up a ridiculous amount of space in your luggage). I had highlighted at least 100 posters that I was going to visit, along with one talk at every session that remotely applied to my work. And of course, I was not going to miss a single platform presentation. I was grimly determined to learn everything.

After a day-and-a-half, I was too tired to even troll the exhibition floor for freebies.

In my current job, I spend time monitoring hashtags for scientific conferences, and I occasionally notice a plaintive tweet from a conference attendee awash in a sea of posters and platform presentations—wondering where to start or where to stop.

So I asked our scientists at Promega what their tips are for getting the most out of a conference. Here are our Conference ProTips:

Continue reading →

by

Deubiquitinases: A Backdoor into Undruggable Targets?

Molecular model of the yeast proteasome.

Molecular model of the yeast proteasome.

Ubiquitin modification of a protein directs events such as targeting for proteasomal degradation. Targeting a protein for degradation through ubiquitin modification is one way to regulate the amount of time a signaling protein, such as a kinase or other enzyme, is available to participate in cell signaling events. Deubiquitinases (DUBs) are enzymes that cleave the ubiquitin tags from proteins, and they have been implicated in several diseases, including cancer.

With their roles in the stabilization of proteins involved in cell cycle progression and other critical processes, DUBs are promising targets for small molecule inhibitors, particularly since they may provide a “back door” for targeting otherwise intractable, undruggable proteins by modulating their half lives. However, finding small molecule inhibitors of the ubiquitin proteases to date has not been trivial. Here we highlight two papers describing the identification and characterization of small molecule inhibitors against the DUB USP7. Continue reading →

by

Activating the Inflammasome: A New Tool Brings New Understanding

Innate immunity, the first line of immune defense, uses a system of host pattern recognition receptors (PRRs) to recognize signals of “danger” including invariant pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). These signals in turn recruit and assemble protein complexes called inflammasomes, resulting in the activation of caspase-1, the processing and release of the pro-inflammatory cytokines IL-1ß and IL-18, and the induction of programmed, lytic cell death known as pyroptosis.

Innate immunity and the activity of the inflammasome are critical for successful immunity against a myriad of environmental pathogens. However dysregulation of inflammasome activity is associated with many inflammatory diseases including type 2 diabetes, obesity-induced asthma, and insulin resistance. Recently, aberrant NLRP3 inflammasome activity also has been associated with age-related macular degeneration and Alzheimer disease. Understanding the players and regulators involved in inflammasome activity and regulation may provide additional therapeutic targets for these diseases.

Currently inflammasome activation is monitored using antibody-based techniques such as Western blotting or ELISA’s to detect processed caspase-1 or processed IL-1ß. These techniques are tedious and are only indirect measures of caspase activity. Further, gaining information about kinetics—relating inflammasome assembly, caspase-1 activation and pyroptosis in time—is very difficult using these methods. O’Brien et al. describe a one-step, high-throughput method that enables the direct measurement of caspase-1 activity. The assay can be multiplexed with a fluorescent viability assay, providing information about the timing of cell death and caspase-1 activity from the same sample. Continue reading →

by

Genes to Cells to Genomes: Where Will Your Research Questions Take You?

Award presentation

Dr. Walter Blum wins trip to Promega headquarters as part of Promega Switzerland’s 25th Anniversary celebration.

Walter Blum knew how normal cells worked. He had studied and read about the pathways that regulated cell cycles, growth and development; he saw the cell as an amazingly well programmed, intricate machine. What he wanted to understand was: “Why does a cell become crazy? How does it escape immune system surveillance?”

Last week I had the opportunity to sit down with Dr. Blum, a customer of our Promega Switzerland branch. Dr. Blum won a trip to visit our campus in Madison for a week as part of an anniversary celebration for our Switzerland branch. While here, he got an inside peek at research and manufacturing operations, chatted with our scientists, met with our marketing teams and saw the sights in Madison. We talked about his work and what he learned and is taking back with him from his trip to Madison. Continue reading →

by

An Unexpected History Lesson

Hillside Trail, Muir Woods National Monument

Hiking the Hillside Trail in Muir Woods National Monument

This land is your land, this land is my land
From California to the New York Island
From the Redwood Forest, to the Gulf stream waters
This land was made for you and me

–Woodie Guthrie

When my daughter was in preschool, she learned the lyrics to Woodie Guthrie’s folk song This Land Is Your Land. After one summer vacation, while she played in the Gulf stream waters off the coast of Florida, she asked, “Can we go see the Redwood Forest now?”

I had never seen the Redwood Forest, and my daughter’s request piqued my curiosity. I thought about my own childhood, when I had accompanied my older sister on a botany class project to collect plants and how curious I was about the plants and where they grew and what their names meant. Suddenly I wanted to see the Redwoods, and the Giant Sequoias.

It took a few years, but we managed to design a vacation trip that satisfied my daughter’s request to see the Redwood Forest and my growing curiosity, and I am so glad we did.  Continue reading →

by

Just in Time for Wisconsin’s Invasive Species Month: Goats

Invasive kudzu vine

Invasive kudzu vine covering a forest

“In Georgia, the legend says
That you must close your windows
At night to keep it out of the house
The glass is tinged with green, even so
As tendrils crawl over the fields…”
—James Dickey (1)

I grew up in Georgia, where on a hot, humid summer day you could almost hear the hiss of growing vegetation, especially the Kudzu as it climbed over fence posts and encroached upon the roadside, the king of invasive species. In Florida you worry about the alligators along the roadside if you have a flat tire; in Georgia, beware the Kudzu.

Invasive species, animal and plant, are an issue in all ecosytems. Imported from distant (and not-so-distant) areas both by accident and misguided intent, invasive species are species that have escaped the checks and balances of natural competitors and predators that existed in their native habitats. This lack of predation and competition enables them to outcompete and overrun other species.

Kudzu may be one of the most recognized invasive species in the United States, but it’s probably not the worst. The zebra mussel is an aquatic animal that has invaded our waterways in Wisconsin. Oak savannahs and prairie ecosystems in the Midwest United States are threatened by many invasive plant species like garlic mustard and blister parsnip. The Wisconsin DNR lists nearly 150 restricted and/or prohibited invasive plant species in Wisconsin, including Kudzu (2). Continue reading →

by

March for Science—Every Day

Kindergarten teacher and children looking at bird's nest in librEarth Day, April 22, saw one of many of the marches on Washington, D.C. that 2017 has produced: The March for Science.

A march is a shout, a “Hey, over here, you need to hear this” one-time event. It is not a conversation. It really isn’t even action. It’s a start that requires follow up.

But how do you follow up a massive, organized march that happened across the globe? Consider following it up with little things, at every opportunity:

First, say “yes” to opportunities to be an ambassador for science. Continue reading →