Author: Kari Kenefick

Kinase Inhibitors as Therapeutics: A Review

Posted on by Kari Kenefick

This blog was originally published in April of 2018. This update includes the paper, “Quantitative, Wide-Spectrum Kinase Profiling in Live Cells for Assessing the Effect of Cellular ATP on Target Engagement” from Cell Chemical Biology, demonstrating the power of NanoBRET™ target engagement kinase assays in the study of kinase inhibitors.

The review “Kinase Inhibitors: the road ahead” was recently published in Nature Reviews Drug Discovery. In it, authors Fleur Ferguson and Nathanael Gray provide an up-to-date look at the “biological processes and disease areas that kinase-targeting small molecules are being developed against”. They note the related challenges and the strategies and technologies being used to efficiently generate highly-optimized kinase inhibitors.

This review describes the state of the art for kinase inhibitor therapeutics. To understand why kinase inhibitors are so important in the development of cancer (and other) therapeutics research, let’s start with the role of kinases in cellular physiology.

The road ahead for kinase inhibitor studies.

Why Kinases? Continue reading “Kinase Inhibitors as Therapeutics: A Review”

A Surprising New Role for Body Fat?

Posted on by Kari Kenefick
This cloaked fat cell just might be a superhero.

Forty-some years ago fat was just fat. And it was regarded with disdain, to say the least.

An entire industry existed to help get rid of fat, using what was then the latest mass media technology, television. If you wanted to get rid of fat you could exercise with Jack LaLanne as he worked out on television. We exercised in elementary school PE class to a vinyl recording of “Chicken Fat”. You could strap into a device that employed shaking to get rid of the fat from your “hips”, or eat a piece of chocolate fudge with a hot beverage before meals to curb your appetite.

Fat was not our friend. We knew long before the current diabetes epidemic that being overweight was not good for our health.

Fast forward to the 21st century, where we’ve learned that some forms of fat are actually good for you–important in metabolism, growth and immunity. The variety of types of mammalian fat include brown adipose tissue, beige adipose tissue and white adipose tissue, and it’s possible to convert one to the other under certain conditions. For details on these types of adipose tissue, read this article —after you finish this blog.

Continue reading “A Surprising New Role for Body Fat?”

It’s a Girl! Welcoming Black-Footed Ferret Kit Elizabeth Ann!!

Posted on by Kari Kenefick

Updated February 2021.

In February 2018 we wrote about a resurrection effort to bring the then endangered black-footed ferret back from the brink of extinction in western U.S. This effort was undertaken by the U.S. Fish and Wildlife Service, with assistance from Revive & Restore and partners ViaGen Pets & Equine, San Diego Zoo Global and the Association of Zoos and Aquariums.

On February 18, the U.S. Fish and Wildlife Service announced announced the successful cloning of a black-footed ferret, introducing the world to a 38-day-old black-footed ferret kit “Elizabeth Ann” cloned from cells of a female ferret that died in 1988.

Photos of Elizabeth Ann, the first cloned black footed ferret. Image credit: US Fish and Wildlife Service

Cells from ferret, “Willa” were preserved by freezing, and when somatic cell nuclear transfer (SCNT) became a possibility, Willa’s cells were used to create Elizabeth Ann, the kit born just over one month ago.

Before Elizabeth Ann’s birth there were upwards of 1,000 black-footed ferrets alive in the western U.S., but they were all descendants of just 7 ferrets, and thus genetically very similar.

Analysis of Elizabeth Ann’s genome has revealed more than three times the genetic variants found in the existing wild U.S. ferrets. This means that if she is able to reproduce, her contribution to the genetic diversity of wild ferrets would be huge.

Interested in learning more about ferrets and the challenges they’ve faced in surviving and thriving in the wild? Below is our original 2018 blog with those details. Don’t miss the video clip of a young black-footed ferret doing the “weasel war dance” (below).

Continue reading “It’s a Girl! Welcoming Black-Footed Ferret Kit Elizabeth Ann!!”

Glycosyltransferases: What’s New in GT Assays?

Posted on by Kari Kenefick

In his 2014 blog, “Why We Care About Glycosyltransferases” Michael Curtin, Promega Global Product Manager for Cell Signaling, wrote:

“Glycobiology is the study of carbohydrates and their role in biology. Glycans, defined as ‘compounds consisting of a large number of monosaccharides linked glycosidically’ are present in all living cells; They coat cell membranes and are integral components of cell walls. They play diverse roles, including critical functions in cell signaling, molecular recognition, immunity and inflammation. They are the cell-surface molecules that define the ABO blood groups and must be taken into consideration to ensure successful blood transfusions.

The process by which a sugar moiety is attached to a biological compound is referred to as glycosylation. Protein glycosylation is a form of post-translational modification, which is important for many biological processes and often serves as an analog switch that modulates protein activity. The class of enzymes responsible for transferring the sugar moiety onto proteins is called a glycosyltransferase (GT).”

Continue reading “Glycosyltransferases: What’s New in GT Assays?”

Ancient Images of Dogs Include Restraints?

Posted on by Kari Kenefick
This dog is wearing a leash.

You, like me, may occasionally find youself in need of a canine control device. While I’m not a fan of the dog tie out, I do walk dogs on leash—as is required by our county and city government here in Madison, WI.

If you have read Temple Grandin’s books about dogs, you might feel a tug at your heartstrings while enduring a tug on the leash. Aren’t dogs meant to run freely? Don’t we love to watch them run? Are leashes humane?

When walking dogs I feel the need to protect them, but also a desire to let them live like dogs, sniffing, marking and other behaviors that are all limited when the dog is leashed.

When a report in Science last week showed evidence that our ancient ancestors were using leashes 8,000-9,000 years ago I was: 1) surprised; and 2) felt vindicated from self-imposed dog owner guilt.

Continue reading “Ancient Images of Dogs Include Restraints?”

H7N9 Influenza Virus: A Perfect Pathogen?

Posted on by Kari Kenefick
Artist’s rendition of a virus particle.

It’s late October and here in Wisconsin, like many of you, we are experiencing a change of seasons, with the associated drop in temperatures, changes in leaf color and later this week, Halloween.

Another thing that comes with fall is the start of cold and flu season. By “flu”, I mean influenza, caused by avian influenza viruses of the H-N type. Recent research results by teams at UWI-Madison and in Japan, makes the coming influenza season potentially more scary than usual.

In a recent Cell Host & Microbe paper, M. Imai et al. study a seemingly more virulent version of H7N9 avian influenza virus that is startling in its ability to spread from infected to healthy animal models. Based on a current epidemic of H7N9, human-to-human transmission with this strain is increasing.

Continue reading “H7N9 Influenza Virus: A Perfect Pathogen?”

Your New Best Research Partner: The Structural Genomics Consortium

Posted on by Kari Kenefick

Research surrounding drug discovery has historically been highly competitive and expensive. Unfortunately, many late-stage drug failures have occurred over recent years, often due to lack of efficacy. These failures have left the industry searching for new means by which to improve early drug discovery efforts aimed at understanding the drug target and its role in disease. One idea that is gaining traction is partnerships to openly share information at the early, precompetitive stages of drug discovery.

I used to think of open access only in terms of publishing data and information—online sites where you could freely access data without a subscription or membership, and without payment.

Structural Genomics Consortium logo.

Meet the Structural Genomics Consortium (SGC), the international partnership that’s taking open access to a new level in order to advance scientific research for scientists working in a variety of disciplines—structural genomics and beyond. The SGC might just become your new, best laboratory research partner. Continue reading “Your New Best Research Partner: The Structural Genomics Consortium”

Cytotoxicity Testing of 9,667 Tox21 Compounds using Two Real-Time Assays by Promega

Posted on by Kari Kenefick

A recent paper in PLOS One demonstrated real-time cytotoxicity profiling of approximately 10,000 chemical compounds in the Tox21 compound library, using two Promega assays, RealTime-Glo™ MT Cell Viability Assay and CellTox™ Green Cytotoxicity Assay. This is exciting to me, a science writer working at Promega; exciting because it’s tricky figuring out how to write about the utility of our products without sounding like an evangelist.

I don’t know about you, but I tend to shut out evangelists and their messages.

Instead of me telling you about real-time viability and cytotoxicity assays from Promega, here is an example of their use in Tox21 chemical compound library research.

What is the Tox21 compound library?
As described in the article by Hsieh, J-H. et al. (2017) in PLOS One:
“The Toxicology in the 21st Century (Tox21) program is a federal collaboration among the National Institutes of Health, including the National Toxicology Program (NTP) at the National Institute of Environmental Health Sciences and the National Center for Advancing Translational Sciences, the Environmental Protection Agency, and the Food and Drug Administration. Tox21 researchers utilize a screening method called high throughput screening (HTS) that uses automated methods to quickly and efficiently test chemicals for activity across a battery of assays that target cellular processes. These assays are useful for rapidly evaluating large numbers of chemicals to provide insight on potential human health effects.”

Continue reading “Cytotoxicity Testing of 9,667 Tox21 Compounds using Two Real-Time Assays by Promega”

Findings May Reveal Earliest Evidence of Selective Dog Breeding

Posted on by Kari Kenefick
Image showing DeLong chain of islands.
Zhokhov Island is part of the DeLong chain of islands off the north coast of Siberia. Image courtesy of Wikimedia Commons.

A report in the June 2, 2017 edition of Science magazine digs into findings from an ancient archaeological site on the very remote and very, very cold Zhokhov Island, to show that the locals, hardy human hunters, not only lived and worked with dogs, but also quite probably selectively bred the dogs for certain traits.

Archaeologist Vladmir Pitulko with the Russian Academy of Sciences has been excavating on Zhokhov Island since 1989, where he has found dog bones as well as remnants of wooden sleds. With archaezoologist Aleksey Kasparov, also of the RAS, they’ve compared two of the most complete dog skulls found to those of contemporary Siberian Huskies and wolves.

Pitulko and Kasparov wanted to first determine if the skulls were those of dogs or wolves. They first employed two key skull ratios: snout height to skull length and cranium height to skull length. Using these ratios, they were able to reliably distinguish between skulls of a modern wolf and husky.

Continue reading “Findings May Reveal Earliest Evidence of Selective Dog Breeding”

In Healthy Eating Less is More: The Science Behind Intermittent Fasting

Posted on by Kari Kenefick

Mix a love of eating with a desire to live a long, healthy life what do you get? Probably the average 21st-century person looking for a way to continue enjoying food despite insufficient exercise and/or an age-related decline in caloric needs.

Enter intermittent fasting, a topic that has found its way into most news sources, from National Institutes of Health (NIH) and Proceedings of the National Academy of Sciences publications to WebMD and even the popular press. For instance, National Public Radio’s “The Salt” writers have tried and written about their experiences with dietary restriction.

While fasting has enjoyed fad-like popularity over the past several years, it is not new. Fasting, whether purposely not eating or eating a restricted diet, has been practiced for 1,000s of years. What is new is research studies from which we are learning the physiologic effects of fasting and other forms of decreased nutrient intake.

You may have heard the claims that fasting makes people smarter, more focused, and thinner. Researchers today are using cell and animal models, and even human subjects, to measure biochemical responses at the cellular level to restricted nutrient intake and meal timing, in part to prove/disprove such claims (1,2).

Continue reading “In Healthy Eating Less is More: The Science Behind Intermittent Fasting”