Lifeboat Foundation

Most people have at some point echoed Macbeth’s complaint about the loss of “sleep that knits up the ravelled sleeve of care”. Sleep disorders, such as obstructive sleep apnoea (when breathing temporarily stops, causing both sleep disruption and lack of oxygen in blood) and sleep deprivation, have been associated with an increased risk of atherosclerosis and its harmful cardiovascular effects^,. Atherosclerosis is characterized by the formation of ‘plaques’ in arteries, as white blood cells enter the artery wall, take up cholesterol and other substances from the blood and trigger an inflammatory response. However, the mechanisms linking sleep disruption and atherosclerosis have been largely unknown. Writing in Nature, McAlpine et al. show that persistent sleep disruption causes the brain to signal the bone marrow to increase the production of white blood cells.

McAlpine et al. studied mice that were prone to developing atherosclerosis. The authors induced sleep fragmentation by moving a bar intermittently across the bottom of the animals’ cages during their sleep period (Fig. 1), and compared these animals with animals that slept normally. They found that mice with sleep fragmentation had more-severe atherosclerosis, which was paralleled by increases in the production of white blood cells in the bone marrow and in the numbers of monocytes and neutrophils — two types of white blood cell — in the blood. These effects were absent if the bar was moved when the mice were fully awake. Stress activates the sympathetic nervous system (which is associated with the ‘fight-or-flight’ response), and such activation increases the production of white blood cells and atherosclerosis in other experimental settings. However, the authors did not find evidence for a role of sympathetic activation in their setting.

Imagine taking medicine oblivious to the fact that a food allergy can effect you taking simply medicine.

Certain substances derived from foodstuffs are used as excipients in drugs and vaccines for their pharmaceutical properties. Some of these food-derived excipients contain food proteins either intentionally or unintentionally as contaminants. As such, patients who have IgE antibodies directed against these food proteins are theoretically at risk for allergic reactions when exposed to the food proteins in the medications. However, such reactions are quite rare, usually because the amount of food protein is not present in a large enough quantity to elicit a reaction or because the particular protein is not a common allergen. When the food protein appears as an unintentional contaminant, the amount of protein, if any, that is present might be variable and might elicit reactions only from some lots of medication that happen to contain more of the food protein or illicit reactions only in patients who are exquisitely sensitive or happen to have IgE antibodies directed against a particular epitope in the contaminating protein. In most circumstances these medications should not be routinely withheld from patients who have particular food allergies because the overwhelming majority will tolerate the medications uneventfully. However, if a particular patient has had an apparent allergic reaction to the medication, allergy to the food component should be investigated as a possible cause. Even in this circumstance (ie, an allergic reaction to a medication in a patient allergic to a particular food and the presence of the food protein in the medication), the food protein would still have to be demonstrated to be causal by using appropriate testing because other allergens present in the medication could have been the cause or the medication might be capable of non–IgE-mediated mast cell degranulation.

The sweet smell of success: dogs are a diabetic’s best friend.

Scientists think they’ve identified a previously unknown form of neural communication that self-propagates across brain tissue, and can leap wirelessly from neurons in one section of brain tissue to another – even if they’ve been surgically severed.

The discovery offers some radical new insights about the way neurons might be talking to one another, via a mysterious process unrelated to conventionally understood mechanisms, such as synaptic transmission, axonal transport, and gap junction connections.

“We don’t know yet the ‘So what?’ part of this discovery entirely,” says neural and biomedical engineer Dominique Durand from Case Western Reserve University.

Continue reading “Neuroscientists Say They’ve Found an Entirely New Form of Neural Communication” »

The immune system is incredibly important, thanks to its role in fighting off dangerous invaders in our bodies. But sometimes it gets it wrong, targeting harmless proteins from things like nuts or dairy products and triggering allergic reactions that ironically can themselves be fatal. Now, researchers from Michigan State University have identified a mechanism that helps keep the immune system in check, potentially paving the way for drugs that could prevent allergic reactions before they start.

A toxic antibody is the latest weapon to show promise as a broad spectrum treatment for multiple forms of advanced cancer.

Dubbed a ‘Trojan horse’ approach to chemotherapy, the new drug has proven itself worthy of moving up the chain of clinical trials to being tested on a greater variety of patients. It’s not a fabled cure-all, but this approach might be as close as we’re going to get.

Researchers from The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust tested the new treatment in a clinical trial involving 147 patients to evaluate its potential benefits and risks of side effects.

Continue reading “This New ‘Trojan Horse’ Drug Successfully Treated 6 Types of Cancer Tumor” »

SpaceX is building a steel launch system called Starship for the moon and Mars, but some aerospace experts say Elon Musk’s new design won’t be easy.

The genetic and cellular alterations that define cancer provide the immune system with the means to generate T cell responses that recognize and eradicate cancer cells. However, elimination of cancer by T cells is only one step in the Cancer-Immunity Cycle, which manages the delicate balance between the recognition of nonself and the prevention of autoimmunity. Identification of cancer cell T cell inhibitory signals, including PD-L1, has prompted the development of a new class of cancer immunotherapy that specifically hinders immune effector inhibition, reinvigorating and potentially expanding preexisting anticancer immune responses. The presence of suppressive factors in the tumor microenvironment may explain the limited activity observed with previous immune-based therapies and why these therapies may be more effective in combination with agents that target other steps of the cycle. Emerging clinical data suggest that cancer immunotherapy is likely to become a key part of the clinical management of cancer.

Genetic, epidemiologic, and biochemical evidence suggests that predisposition to Alzheimer’s disease (AD) may arise from altered cholesterol metabolism, although the molecular pathways that may link cholesterol to AD phenotypes are only partially understood. Here, we perform a phenotypic screen for pTau accumulation in AD-patient iPSC-derived neurons and identify cholesteryl esters (CE), the storage product of excess cholesterol, as upstream regulators of Tau early during AD development. Using isogenic induced pluripotent stem cell (iPSC) lines carrying mutations in the cholesterol-binding domain of APP or APP null alleles, we found that while CE also regulate Aβ secretion, the effects of CE on Tau and Aβ are mediated independent pathways. Efficacy and toxicity screening in iPSC- derived astrocytes and neurons showed that allosteric activation of CYP46A1 lowers CE specifically in neurons and is well tolerated by astrocytes. These data reveal that CE independently regulate Tau and Aβ and identify a druggable CYP46A1-CE-Tau axis in AD.

Van der Kant et al. performed a repurposing drug screen in iPSC-derived AD neurons and identified compounds that reduce aberrant accumulation of phosphorylated Tau (pTau). Reduction of cholesteryl ester levels or allosteric activation of CYP46A1 by lead compounds enhanced pTau degradation independently of APP and Aβ.