In a recent reference, Kinoshita and colleagues characterized the phosphorylation dynamics of MEK1 in human cells by using the phosphate affinity electrophoresis technique, Phos-tag sodium dodecyl sulfate–polyacrylamide gel electrophoresis (Phos-tag SDS-PAGE; 1). They found that multiple variants of MEK1 with diferent phosphorylation states are constitutively present in typical human cells.
To investigate the relationships between kinase activity and drug efficacy researchers from the same laboratory group conducted phosphorylation profling of various MEK1 mutants by using Phos-tag SDS- PAGE (2).
Malaria is a life-threatening blood disease that plagues nearly two-thirds of the world’s population. The disease in manifested by parasites of the Plasmodium genus and transmitted to humans through the bite of female Anopheles mosquitoes, which serve as the primary disease vectors. Roughly 200 million people per year are infected with malaria, and approximately 400,000 deaths are reported annually, with children under the age of five comprising the majority of victims.
Africa disproportionately bears the global brunt of this devastating illness, with approximately 92% of all reported cases, as well as 93% of all reported deaths, originating from the continent. This can be partially attributed to the fact that the conditions for transmission are essentially ideal there: the principal vector species Anopheles gambiae are abundant in this region, and not only do they prefer to source their blood from humans over animals, but the mosquitoes also tend to have a longer lifespan, which allows the most common and deadly malaria parasite, Plasmodium falciparum, to complete its life cycle, which contributes to higher disease transmission efficacy.
Though malaria is a preventable disease, often the areas affected most lack access or resources, or are politically unstable, all factors that can contribute to the absence of consistent, functional malaria control programs. Though malaria is also a curable disease, it has long been debated whether eradication was even within the realm of possibility. There are four species of Plasmodium parasites responsible for the pathogenesis of malaria and each exhibit different forms of drug resistance and each responds differently to different medications. This alone makes the prospect of developing a single overarching vaccine for all strains of malaria an improbable achievement and the idea of eradication practically impossible.
In May 2017, a surprising discovery was made in the woods of Bayfield County, Wisconsin, just about a 5-hour drive north of Promega headquarters. Jonathan Martin, Associate Professor of Forestry at Northland College, was exploring the forest with an ultraviolet (UV) light in search of fluorescent lichen or plant life. What he found instead was a bright pink glow coming from a most unexpected source—a flying squirrel.
Think about the last time you gave a presentation. The feeling of having “butterflies in your stomach”. Or when you meet someone for the first time, that “gut feeling” of whether you two will get along. In our day-to-day lives, we often associate what happens in the gut with what goes on in our brain. In fact, scientific evidence suggests that our gut and our brain frequently communicate—through gut microbes. Apparently, the existence of trillions of bacteria and eukaryotes in our gut is not only crucial for our physical health, they may also be important for our mental health.
In recent years, scientists have been able to refine their molecular tools to resurrect ancient DNA from human graves and determine that yes, Yersinia pestis was the causative agent for the Black Death in the 14th century and the Plague of Justinian in the 6th century. As more and more human graves have been uncovered, their DNA has revealed many secrets that scientists even ten years ago were unable to discover. With the ability to sequence entire genomes of bacteria that died with their hosts hundreds and even thousands of years ago, researchers are exploring the rise and possible spread of Y. pestis. Each new member sequence adds to the Y. pestis family tree, pinpointing the origin of this bacteria as it diverged from its ancestor Y. pseudotuberculosis. Peering into the past, scientists have been able to track down a strain of Y. pestis from individuals in a Swedish passage grave that is basal to known strains and that the authors of a Cell article suggest has interesting implications.
This pathogenic journey into history started by analyzing ancient DNA data sets from the teeth of individuals present in a communal passage grave in Gökhem parish, located in western Sweden, for any disease-causing microbial sequences that might be present. Y. pestis was flagged in one 20-year-old female dated 4,867–5,040 years ago. The bacterial sequences from this individual, named Gok2, were more closely aligned with Y. pestis than the Y. pseudotuberculosis reference genome. Continue reading “Expanding the Plague Family Tree: Yersinia pestis in the Neolithic”
Ebola virus (EBOV) and Marburg virus (MARV) are two closely-related viruses in the family Filoviridae. Filoviruses are often pathogenic, causing hemorrhagic fever disease in human hosts. The Ebola outbreak of 2014 caught the world by surprise by spreading so quickly and severely that public health organizations were unprepared. The devastating outcome was a total of over 11,000 deaths by the time the outbreak ended in 2016. Research that provides further understanding of filoviruses and their potential for transmission is important in preventing future outbreaks from occurring. But what if the outbreak comes from a virus we’ve never seen before?
All in the viral family
A recent study published in the journal Nature Microbiology provides evidence of a newly identified filovirus species. Using serum samples taken from bats, a well-known host for filoviruses, Yang et al. isolated and identified viral RNA for an unclassified viral genome sequence using next generation sequencing analysis. This new virus genome sequence was organized with the same open reading frames as other filoviruses, encoding for nucleoprotein (NP), viral protein 35 (VP35), VP40, glycoprotein (GP), VP30, VP24, and RNA-dependent RNA polymerase (L). This new genome sequence shared up to 54% of the nucleotide sequences for the filovirus species Lloviu virus (LLOV), EBOV and MARV, with MARV being the most similar. Their analysis suggested that this novel virus should be classified within the Filoviridae family tree as a separate genus, Dianlovirus, and was named Měnglà virus (MLAV).
Redundancy equips us to survive. We have more than one lung or one kidney for a reason—if one organ in a pair gets damaged, we can still manage if the other is functional. At the cellular level, we have two copies of each chromosome in every non-germline cell. Each copy was inherited originally from a single sperm and ovum, which are “haploid” cells. Consequently, there are two copies of any given gene in non-germline “diploid” cells. In many cases, should one copy of a gene be damaged, the cell can still survive with the other, functional copy of a gene. In plants, this redundancy is common, and many plants exhibit polyploidy. In an extreme example of polyploidy, the large (by bacterial standards) but otherwise unassuming species Epulopiscium contains tens of thousands of copies of its genome.
In almost every environment on earth, such as soil, human
skin and gut, there lives a whole community of microbes—sometimes up to
hundreds of species. It may seem like they all flourish in peace. But just like
you may have friendly or hostile interactions with your neighbors, the
different bacterial species interact in various ways. They may cooperate,
compete or, sometimes, even kill each other. The interaction is complicated,
and scientists have struggled to understand the nature of these microbiome
interactions. How do microbiomes assemble and maintain stability? How do the
interactions among different species affect gene expression?
The extensive and repetitive use of neonicotinoids has led to the development of resistance in several insect species including, the cotton aphid, A. gossypii. A. gossypii is a widely distributed pest that affects watermelons, cucumbers, pumpkin, cotton, and citrus crops, among others, making it one of the most economically important agricultural pests known. Thiamethoxam is a neonicotinoid insecticide that irreversibly binds to the nicotinic acetylcholine receptors (nAChRs) of cells in the nervous system and interferes with the transmission of nerve impulses in insects (1).
To further understand the mechanisms of resistence to thiamethoxam and other neonicotinoids, Wu et al. recently investigated (2) expression changes in the transcripts of P450 in thiamethoxam-susceptible and thiamethoxam-resistant cotton aphid strains. Nine P450 genes were significantly overexpressed in the resistant strain (especially CYP6CY14). The involvement of overexpressed P450s was examined through RNA interference (RNAi) introduced via artificial diet and dsRNA feeding.
Have you ever had a day where you feel exceptionally good? As in take on the world kind of good? You feel so much better than the previous couple of days that you stop to wonder why.
Then it dawns on you.
The sun is out. It’s been cloudy for the past week but now—SUNSHINE.
You go out to lunch or for a walk just to take in those rays. Sure, it feels warmer than your darkened office space, but it’s the light rather than warmth that’s making a difference.
You purposely don’t wear sunglasses and it feels like the light is coming in through your eyes and massaging that part of your brain that is your happy zone. Are you imagining it or is the sun really affecting how you feel?
In a study reported in the September 2018 issue of Cell we learn that this is not a figment of your or my imagination (1). There is, in fact, a type of retinal cell that transports sunlight directly to the part of our brains that affects mood.
Eyes and the Body’s Master Clock
Circadian rhythms are innate time-keeping functions found in all multicellular organisms. This subject of the 2017 Nobel prize in Physiology or Medicine, circadian rhythms are fueled by daily light-dark cycles and are critical to the function of neurologic, immune, musculoskeletal and cardiac tissues (2). Nearly every mammalian cell is affected by circadian rhythms.
The human body has a circadian master clock, the suprachiasmatic nucleus or SCN. The SCN is a highly innervated tissue located in the hypothalamus (see image). It is connected directly to the retina by the optic nerve, and thus is influenced by external light and dark.
The retina of the eye is the light gathering instrument for this organ. Historically, it’s been understood that the retina is composed of two cell types, rods and cones, that function in transmitting light and images to the optic nerve, which sends those signals to the brain.
Studies by Hattar et al. in the early 2000s identified that another cell found in the retina, the melanopsin-containing intrinsically photoactive retinal ganglion cells (ipRGCs) as the transmitter of circadian light signals (3). Through this direct connection to the SCN, the circadian master clock, the ipRGCs can influence a wide range of light-dependent functions independent of image processing (4).
Now Fernandez et al. have identified multiple types of ipRGCs. They showed that ipRGCs that mediate the effects of light on learning work via the SCN, while the pathway for light influencing emotions is different.
They discovered a new target of ipRGC cells, the perihabenular nucleus (PHb). The PHb is a newly recognized thalamic region of the brain. The authors showed that the connection between light and mood is regulated by ipRGCs through the PHb versus the SCN. They show that the PHb is integrated into other mood-regulating centers of the thalamic region.
Daylight, and lack thereof, does affect both our mood and our ability to learn. In this 2018 report, we have learned that the pathways for these effects are distinct, and gain an understanding of a new thalamic region by which the light and mood actions occur. This information could influence development of better drugs and/or therapies for major depressive disorders.
For those of us with seasonal affective disorder, the evidence is undeniable—lack of light can cause issues, from sleep-wake problems, to mood and learning issues.
And while we can’t create sunshine, a special lamp or light box may help to gain some full spectrum light. To learn more about how to choose such a lamp and when to use it, see this Mayo clinic article for details.