T Cells Newly Discovered Role in Alzheimer’s and Related Diseases Could Offer Another Therapeutic Approach

Alzheimer’s disease is a devastating, progressive degenerative brain condition that starts with mild   dementia symptoms like memory issues and gradually worsens to the point where you can no longer communicate or care for yourself. For anyone with personal experience with it, Alzheimer’s looms like a specter over the natural process of aging.

In the beginning phase of Alzheimer’s, abnormal plaques of the protein, amyloid-β, develop. These protein clumps can accumulate for decades with no detectable impact on cognitive ability or brain health. Eventually, a second protein, tau, begins to gather and form intercellular, fibrous, tangles. It is with the formation of these tau tangles that symptoms first appear. The combined presence of these extracellular plaques and intercellular tangles are the hallmarks of Alzheimer’s disease.

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Conversations: Nerve-Tumor Crosstalk in the Tumor Microenvironment

Cancer cells are characterized by features such as metabolic reprogramming and uncontrolled proliferation all of which are supported by underlying genomic instability, inflammation and the tumor microenvironment.

Cancer cells can be distinguished from normal cells by a variety of features including their ability to inappropriately activate signals for cell proliferation, evade growth suppression from contact inhibition or tumor suppressor activity, evade cell death signals, replicate DNA continually, induce angiogenesis, invade new tissues, reprogram their metabolism to provide energy for rapid proliferation, and evade immune detection (1) . Several biological processes are responsible for these features including genomic instability, inflammation, and the creation of a tumor microenvironment.

The tumor microenvironment is the network of non-malignant cells, connective tissue and blood vessels that surround and infiltrate the tumor. These surrounding “normal” cells interact with each other and the cancer cells and are important players in tumorigenesis. One cell type that is often found in the tumor microenvironment are nerve cells. In fact, cancer cells often express proteins that encourage nerve growth into the tumor microenvironment such as growth factors and axon-guidance molecules (2). Crosstalk between nerve cells and tumor cells can facilitate development of several cancer types (2) including pancreatic, head and neck, oral, prostate, and colorectal cancers.

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Monoclonal Antibody (mAb) Therapy to Delay the Onset of Type 1 Diabetes

On November 18, 2022, the US Food and Drug Administration (FDA) announced the approval of the first drug to delay the onset of stage 3 type 1 diabetes (T1D). The monoclonal antibody (mAb) drug, teplizumab, was approved for use in adults and pediatric patients 8 years and older.

3D illustration of a monoclonal antibody

The road to approval has been a bumpy one for the manufacturer, Provention Bio. In 2020, the FDA rejected the application for teplizumab due to several concerns, including the small size of the clinical trial. With the current approval, based on new clinical trial results, Provention Bio confirmed a co-promotion agreement with Sanofi US. The agreement included a $35 million Sanofi equity investment in the company.

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New Vaccine for Honeybees Could Take the Sting Out of Devastating American Foulbrood Disease

Our world is a complex, interdependent system, and invertebrate pollinators such as honeybees play a pivotal role in its survival. Threats to populations numbers of pollinators like honeybees can be equated to threats to the overall health and survival of the ecosystem in which they live. Of the over 20,000 known bee species, one—the western honeybee (Apis mellifera)—acts as the single most frequent pollinator for crops worldwide (1). Found on every continent except Antarctica, the western honeybee owes its status as a top pollinator to its widespread geographic distribution, generalist foraging behavior and competence as pollinators (1).

Deadly American Foulbrood Disease

Honeybees are the most economically valuable pollinators and are threatened by several pathogens (2). Perhaps the biggest threat to honeybee colony health and survival is the bacterial disease, American Foulbrood (AFB; (3). Caused by the spore-forming, Gram+ bacteria, Paenibacillus larvae, the highly contagious AFB disease affects the young brood of colonies.  When newly hatched larvae are fed spore-contaminated food, the spores germinate and replicate causing septicemia and death. P. larvae spores are incredibly resilient and can remain viable for decades (3). Each infected larva can produce over 1 billion new spores.  Thus, a colony can produce large numbers of spores with just a few cases of symptomatic brood (4).

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suPAR: A New Approach to Treating Cardiovascular Disease

Cardiovascular disease (CVD), continues to be the leading cause of death in the United States and worldwide. Many patients with CVD have signs of chronic kidney disease (CKD), and those with CKD are often times disproportionately affected by CVD.

This interconnectedness was further explored in a recent study published in the Journal of Clinical Investigation that identified a new immune target, suPAR, as a protein that causes kidney disease and atherosclerosis, the most common form of CVD. Unlike traditional approaches to treating CVD such as controlling blood pressure and lowering cholesterol, this breakthrough research offers a new approach to treatment from an entirely different perspective.

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Left-Handed DNA: Is That Right?

There’s a certain group of people (including this blog post author) who derive no small amount of amusement from seeing stock photos of DNA and pointing out flaws in the structure. It’s even more amusing when these photos are used in marketing by life science companies. The most common flaw: the DNA molecule is a left-handed double helix.

What does that even mean? DNA, like many organic chemicals in biology, is a chiral molecule. That is, it can exist in two structural forms that are mirror images of each other but are not superimposable (enantiomers). Just like your left and right hands are mirror images of each other, the two DNA structures are left-handed and right-handed double helices. The DNA double helix is chiral, because its building blocks (nucleotides) are chiral.

Two DNA helices that are mirror images

It can be challenging, at first glance, to tell whether an image of DNA is left-handed or right-handed. Various helpful hints are available; however, the one that I’ve found easiest to remember is described in a blog post by Professor Emeritus Larry Moran at the University of Toronto:

Imagine that the double helix is a spiral staircase, and you’re walking down the staircase. If you’re turning to the right as you descend, the DNA structure is right-handed; if turning to the left, it’s left-handed. In the image shown earlier, the DNA molecule on the right is a right-handed double helix, while its mirror image is left-handed.

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Growing Our Understanding of Rose Rosette Virus Through Reverse Genetics

Viral particle representing lethal Rose Rosette Emaravirus with red rose.

Roses, the universal symbol of love and affection, are one of the most popular ornamental flowering shrubs used by landscapers and home gardeners and account for almost half of the billion-dollar ornamental plant market. The growing prevalence of rose rosette disease poses a significant threat to these industries.  This lethal disease is caused by the Rose rosette emaravirus (RRV) and transmitted by the tiny eriophyid mite, Phyllocoptes fructiphilus. Infection by RRV results in prolific growth of clustered and bunched plant shoots (witches’ broom), malformed flowers and leaves, malformed shoots and enlarged stems and abundant leaf growth and thorniness. This excessive growth depletes the plant’s energy, eventually causing death.

Emerging and Devastating Plant Viruses of the Genus Emaravirus

RRV is a single-stranded, segmented, negative-sense RNA virus belonging to the genus Emaravirus, a relatively new genus that was established in 2012. These emerging viruses can be devastating to trees, herbaceous woody plants and vines. At Texas A&M University, Dr. Jeanmarie Verchot’s lab is working to better characterize and understand these new viruses. In addition to threatening roses, these viruses cause damage to important agriculture crops such as wheat and pigeon peas. They also endanger sensitive ecosystems when they infect plants specialized to a particular habitat, as is the case with Palo verde broom virus infection of palo verde trees of the Sonoran Desert (1).

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The Crows Have Ideas

How smart are crows? A crow stares at a mobile phone

It has become increasingly evident to scientists that the intellectual prowess of your average crow has been roundly underestimated. With remarkable skills including superior social acumen, analogical thinking and the ability to craft and use tools, crows seem to prove themselves more and more clever with every investigation into the inner workings of their small, but mighty, brains.

Recently, new research revealed that crows may be capable of recursive thinking. Recursion can be described as the process of defining something in terms of itself. Humans use recursion in mathematics and language, and it’s a hallmark feature of advanced linguistic ability, as originally posited by Noam Chomsky in his hierarchy of grammars. Recursion in language is used to grow the complexity of sentence structure to contain, in theory, an infinite number of embedded elements or ideas. Put simply, linguistic recursion refers to the nesting of one grammatical structure, this sentence for example, within another of the same kind. Formerly thought to be a skill exclusive to primates, research like that recently published in Science Advances has challenged this assumption.

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Cellular Senescence and Cancer Therapy: Overcoming Immortality?

At the time of writing this post, no scientist had yet discovered the secret to immortality. In our world, we’ve come to accept that living things are born, grow old and die—the circle of life.

And yet, for many years, life scientists believed that the circle of life did not apply to our constituent cells when cultured in a laboratory. That is, cultured normal human cells were immortal, and they would continue to grow and proliferate forever, as long as they were provided with the necessary nutrients.

The animal cell cycle. Image by Kelvinsong; made available under the Creative Commons CC0 1.0 Universal Public Domain Dedication

Pioneering work published in 1961 by Leonard Hayflick and Paul Moorhead challenged that theory (reviewed in 1). Their research showed that normal cells in culture have a finite capacity to replicate. After they reach a certain number of replicative cycles, cells stop dividing. Hayflick and Moorhead made the important distinction between normal human cells and cultured cancer cells, which are truly immortal. In later years, the limit to the number of replicative cycles normal human cells can undergo became known as the Hayflick limit. Although some scientists still express skepticism about these findings, the Hayflick limit is widely recognized as a fundamental principle of cell biology.

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Neanderthal DNA and Modern Humans: Svante Pääbo Receives the 2022 Nobel Prize in Physiology or Medicine

What makes humans “human”?

Neanderthal DNA sequencing from ancient bone samples

On October 3, 2022, the Nobel Assembly at Karolinska Institutet announced the 2022 Nobel Prize in Physiology or Medicine had been awarded to Svante Pääbo, director of the Department of Genetics at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany. The Assembly cited his “discoveries concerning the genomes of extinct hominins and human evolution”. They mentioned the highlight of his research: the seemingly impossible task, at the time, of sequencing the Neanderthal genome. The discoveries that followed from this sequencing project continue to redefine our understanding of modern human origins.

The award showcases the technological advancements made in the analysis of ancient DNA. However, Pääbo’s research had an inauspicious beginning. In 1985, he published the results of his early work, cloning and sequencing DNA fragments from a 2,400-year-old Egyptian mummy (1). Unfortunately, later analysis revealed that the samples could have been contaminated by the researchers’ own DNA (2).

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