NAD is a pyridine nucleotide. It provides the oxidation and reduction power for generation of ATP by mitochondria. For many years it was believed that the primary function of NAD/NADH in cells was to harness and transfer energy from glucose, fatty and amino acids through pathways like glycolysis, beta-oxidation and the citric acid cycle.
Today, however, NAD is recognized as an important cell signaling molecule and substrate. The many regulatory pathways now known to use NAD+ in signaling include multiple aspects of cellular homeostasis, energy metabolism, lifespan regulation, apoptosis, DNA repair and telomere maintenance.
If we’ve learned nothing else since February or March of 2020, we’ve learned that emerging infectious diseases are a real threat to human health globally. In a bad news/good news kind of way, Bartonellosis is an emerging infectious disease; however, it’s not spread by airborne droplets or respiration.
But if any of your family pets bring a flea or tick into the house, or if you live in proximity to mice, rats, ground squirrels, rabbits, sheep, horses or cattle–you could be at risk.
Bartonella sp. is a Gram negative, rod-shaped bacteria that has been around since ancient times. It’s the bacteria responsible for cat scratch disease (1) and for Trench fever (2), which affected soldiers during WWs I and II, and affects people living in over-crowded, unsanitary conditions around the world today.
Bartonella sp. are known to be spread by vectors such as fleas, which are part of the transmission cycle for cat scratch disease and the human body louse, the vector for transmission of Trench fever (3).
This animal-to-human transmission of Bartonella sp. classifies it as a zoonosis.
Infection due to Bartonella sp. often appear to be self-limiting, such as swelling in regional lymph nodes due to a cat scratch disease. In such cases, symptoms can subside without intervention. But Bartonella sp. have a nasty habit of hiding in red blood cells and in cells lining blood vessels, where they can remain undetected for a substantial period of time. This hiding place affects a host’s ability to mount an immune response, as well as affecting the ability of antibiotics to attack the bacteria.
Antibody-based immune checkpoint inhibitors remain a major focus of immuno-oncology drug research and development efforts because of their recent success in providing long-term anti-tumor responses. However, the range of response of different tumor types to these drugs is hugely varied. Small molecule kinase inhibitors that block signaling pathways involved in regulation of tumor immunity at multiple points in the “cancer immunity cycle” may provide alternate, effective therapeutics. One kinase that may be a target for such small molecule inhibitors is Hematopoietic Progenitor Kinase 1 or HPK1; the potential of this kinase as a therapeutic target was reviewed by Sawasdikosol and Burakoff (1). HPK1, also known as MAP4K1, is a member of the MAP kinase protein kinase family that negatively regulates signal transduction in T-cells, B-cells and dendritic cells of the immune system.
A year after COVID-19 was declared a pandemic, collaborative efforts among pharma/biotech and academic researchers have led to remarkable progress in vaccine development. These efforts include novel mRNA vaccine technology, as well as more conventional approaches using adenoviral vectors. While vaccine deployment understandably has captured the spotlight in the fight against COVID-19, there remains an urgent need to develop therapeutic agents directed against SARS-CoV-2.
In the March 12 issue of Science, an editorial by Dr. Francis Collins, director of the U.S. National Institutes of Health (NIH), examines lessons learned over the past 12 months (1). Collins points out that many clinical trials of potential therapeutics were not designed to suit a public health emergency. Some were poorly designed or underpowered, yet they received considerable publicity—as was the case with hydroxychloroquine. Collins advises developing antiviral agents targeted at all major known classes of pathogens, to head off the next potential pandemic before it becomes one. A news feature in the same issue discusses the current state of coronavirus drug development (2).
The present crop of drug candidates is remarkably diverse, including repurposed drugs that were originally developed to treat diseases quite different from COVID-19. Typically, however, the mainstream candidates belong to two broad classes: small-molecule antiviral agents and large-molecule monoclonal antibodies (mAbs).
Among the one trillion or so species that share space on our planet, complex relationships have emerged over time. Such relationships, in which two or more species closely interact, are collectively termed symbiosis. Although it’s commonly assumed that symbiotic relationships are mutually beneficial, this example constitutes only one type of symbiosis (known as mutualism). The traditional predator-prey relationship, clearly a one-sided arrangement, is also an example of symbiosis.
The sheer diversity of microbial species has led to the development of many well-characterized relationships with plants and animals. Perhaps the best-known example of mutualism in this context is the process of nitrogen fixation. In this process, various types of bacteria that live in water, soil or root nodules convert atmospheric nitrogen into forms that are readily used by plants. On the other hand, some types of bacteria-plant relationships are parasitic: the bacteria rely on the plant for survival but end up damaging their host. Parasitic relationships can have devastating ecological and economic consequences when they affect food crops.
Food contamination is a serious global health issue. According to the WHO, an estimated 600 million, almost 1 in 10 people globally, suffer from illness after eating contaminated food—and 420,000 die. Developing new technologies for more effective testing of food contaminants can help reduce that number and improve public health.
A recent application of bioluminescent technology could change the way we test for mycotoxins in the future. Dr. Jae-Hyuk Yu, Professor of Bacteriology at the University of Wisconsin-Madison, and his then graduate student, Dr. Tawfiq Alsulami, collaborated with Promega to develop a bioluminescent biosensor that enables simple and rapid detection of mycotoxins in food samples.
Did dinosaurs get cancer? That isn’t an easy question to answer. Finding and diagnosing cancer in dinosaur fossils has proven difficult. Any soft tissue, the typical location of tumors, has degraded over the millennia. Fossilized bones millions of years old are subject to wear and tear, making it hard to distinguish bone damage from possible pathology. By using the knowledge and expertise gained from diagnosing cancer in humans, a team reported in The Lancet Oncology that they found the first known case of osteosarcoma in a lower leg bone from a horned dinosaur found in southern Alberta, Canada.
This case of bone cancer discovered in a specimen of Centrosaurus apertus found in the Canadian Dinosaur Park Formation was confirmed by examining the bone surface along with radiographic and histological analysis. The 77–75.5-million-year-old case was compared to both a normal C. apertus fibula from the Oldman formation also in southern Alberta, Canada, as well as a human fibula with an osteosarcoma.
A new article in Nature Scientific Reports answers open questions about TOPBP1, a protein involved in repairing DNA double-strand breaks (DSBs). The study used cell-free protein expression and a unique DSB system to identify domains that were important for activation of a protein kinase.
The term ICOS —inducible T cell co-stimulators— has been prominent in my work as a science writer at Promega, recently. Here is a brief look at ICOS, how it works, and how it can be used in therapeutics research and development.
T cells do amazing things, like driving or blocking production of B cells and their related antibodies and antibody maturation, and they are the primary drivers of innate immunity. T cells have a variety of surface molecules, the primary and omnipresent T cell receptor (TCR), as well as CD3.
In the past 15 years or so, researchers have identified other, inducible receptors on T cells. These receptors appear when T cells are stimulated, enabling interactions with other cell types. The following information is summarized from a Frontiers in Immunology review by Wikenheiser et al.
COVID-19 vaccine distribution efforts are underway in several countries. Recently, the Serum Institute of India celebrated the nationwide rollout of its Covishield vaccine, kicking off the country’s largest ever vaccination program. Meanwhile, many other vaccines against the coronavirus that causes COVID-19 are in either preclinical studies or clinical trials. At present, 19 vaccine candidates are in Phase 3 clinical trials, while 8 vaccines have been granted emergency use authorization (EUA) in at least one country.
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