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Brain-based index may reveal Alzheimer’s risk patterns in adults as young as 30

Over the past few decades, neuroscientists and medical researchers worldwide have been trying to leverage available health records, brain scans and other medical data to uncover biological markers associated with the onset of specific diseases or neuropsychiatric disorders. The identification of these biomarkers could help to devise new tools to predict the risk that individual patients will develop a specific condition, allowing doctors to intervene early, preventing or delaying its emergence or slowing down its progression.

Researchers at the University of Texas Health Science Center, UTHealth Houston School of Behavioral Health Sciences, Keck School of Medicine of USC, and University of Maryland School of Medicine recently devised a new brain-based index that could be used to track early risk factors that, in specific people, may lead to the development of Alzheimer’s disease (AD). AD is a progressive neurodegenerative condition that prompts the deterioration and death of brain cells, leading to progressive memory loss and a decline in mental functions. AD has very limited treatment options after the diagnosis but the brain changes that culminate in AD take decades, thus suggesting that public effort should be focused on prevention.

The researchers devised an index that could be used to quantify patterns in a person’s brain that measure the similarity to those observed in individuals diagnosed with AD and followed as a part of the research studies such as Alzheimer’s Disease Neuroimaging Initiative (ADNI). This index, introduced in a paper published in Molecular Psychiatry, was derived by performing a mega-analysis of publicly available brain imaging data collected from people with and without AD.

‘Solar-blind’ 2D heterostructure delivers 422-fold responsivity gain for UV sensing

Photodetectors remain a critical component in the development of advanced electronics and photonics, particularly in the role of signal readout through the conversion of photons into electrons. These digital imaging components are ubiquitous in sensors, cameras, adaptive displays, telecommunications, LiDAR systems, health monitoring wearables, and oximeters.

In the quest toward the next generation of optoelectronic devices, the spotlight lands upon ultrathin 2D materials with improved performance for integrated circuits and wearable electronics. In a recent study published in ACS Applied Electronic Materials, a team of researchers led by Haizhao Zhi and Eng Tuan Poh introduced a series of wide bandgap 2D materials—transition metal thio(seleno)phosphates into the light.

The team focused on manganese thiophosphate (MnPS3), a wide-bandgap semiconductor that is naturally “solar-blind,” meaning it is highly sensitive to UV light while remaining transparent to much of the visible spectrum. While MnPS3 is an excellent candidate for UV sensing, its performance as a standalone material is often limited by low carrier mobility—it acts almost like a “near-perfect insulator.”

Physical exercise protects against Toxoplasma gondii infection-induced muscle atrophy and microvascular rarefaction

FNDC5/irisin detection was performed by a sandwich ELISA reaction using DuoSet® ELISA Development Systems kit (R&D Systems), according to manufacturer’s instructions. Blood samples were collected at 10 or 40 dpi, allowed to sit for at least 1 h, and then centrifuged for 10 min at 224 g in a refrigerated centrifuge (4 °C) to isolate the serum. Samples were stored at −80 °C until irisin detection.

Serum samples were assayed for TNF-α, INF-γ, IL-2, IL-4, IL-6, IL-10, and IL-17a using a Cytometric Bead Array (CBA) Th1/ Th2/ Th17 kit (BD Biosciences), according to the manufacturer’s instructions. Data were acquired using a Cytoflex S (Beckman Coulter) flow cytometer. After data acquisition, dedicated software (FCAP Array, BD Biosciences) was used to analyze the results by gating bead populations, calculating MFI values, generating standard curves, and determining analyte concentrations. These analyses were performed at the Flow Cytometry Facility of the Instituto Oswaldo Cruz (Fiocruz).

T. gondii infection was quantified using RT-qPCR with bag1 and enolase2 primers to detect bradyzoite and tachyzoite forms, respectively, according to49. Ct values were compared to a standard curve amplification, derived from known T. gondii RNA concentrations. The standard curve was constructed with six 10-fold dilutions, starting with 6.0 × 106 parasites for either bradyzoites or tachyzoites. Primer sequences are available in Table 2.

In Silico Analysis of the Chikungunya Virus and SARS-CoV-2 Macrodomain

The chikungunya virus (ChikV) was first isolated during an arthritic disease outbreak in Tanzania in 1952 [1, 2]. ChikV is a mosquito-borne virus that belongs to the Alphavirus genus of the Togaviridae family. ChikV infections have emerged as a global health risk with approximately 16.9 million cases per year [3]. Major symptoms of ChikV infection include severe fever, rashes, and joint pain. Chronic arthritis-like symptoms may persist and can be debilitating [4, 5]. ChikV, a positive-sense RNA virus, encodes 5 structural proteins and 4 nonstructural proteins (NSP1 to NSP4) [6]. Nonstructural protein 3 (NSP3) consists of a conserved macrodomain (Mac1) at the N-terminus, a poorly conserved hypervariable domain, and a central zinc-binding domain known as the alphavirus unique domain [7]. The macrodomain fold is highly conserved across evolution, having been identified in bacteria, algae, and eukaryotes [8, 9]. It has been suggested that ChikV Mac1 suppresses the host immune response through its adenosine diphosphate ribosyl (ADP-ribosyl) hydrolase activity [10], which removes ADP-ribose posttranslational modifications from target host proteins by hydrolyzing mono-ADP-ribosylated aspartate and glutamate residues. Mac1 has therefore emerged as a promising antiviral drug target [10], supported by evidence suggesting that it is a key determinant of ChikV virulence in mice. Despite their therapeutic potential, efforts to identify ChikV inhibitors have had limited success. A fragment screen of ~14,000 compounds identified only weak inhibitors (e.g., 2-pyrimidone-4-carboxylic acid scaffold, with one of the compounds showing IC50 of 23 μM) [11]. Another computational docking and simulation study screened 820 compounds and predicted that natural compounds from plants, including apigetrin, baicalin, baloxavir, luteoloside, rutaecarpine, and amentoflavone [12], are Mac1 inhibitors. The predicted binding affinity of baicalin was −10.8 kcal/mol against ChikV Mac1. Another study identified N-[2-(5-methoxy-1 H-indol-3-yl) ethyl]-2-oxo-1,2-dihydroquinoline-4-carboxamide through virtual screening of 245,532 natural compounds, followed by in vitro validation using a microscale thermophoresis binding assay (binding constant [Kd] of 1.066 × 10−6 ± 0.95 μM) and in vivo inhibition of ChikV replication [13].

Similar to ChikV, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) NSP3 contains 3 tandem macrodomains, with Mac1 serving as the catalytically active macrodomain that binds and hydrolyzes mono-ADP-ribose on posttranslationally modified target host proteins [14,15]. SARS-CoV-2 Mac1 is essential for viral pathogenesis and represents a promising drug target [16,17]. In contrast to ChikV Mac1, it has proven amenable to inhibitor development. An early crystallographic screen of approximately 2,600 compounds revealed 234 fragment structures bound to SARS-CoV-2 Mac1 [18]. Using these hits, several optimized inhibitors were designed, followed by another round of crystallographic screening [19]. Among the resulting top inhibitors was AVI-4206, a potent inhibitor with an IC50 of 20 nM that is effective in an animal model of SARS-CoV-2 infection [20]. Other studies have identified additional promising scaffolds, including 2-amide-3-methylester thiophene scaffold derivatives that bind SARS-CoV-2 Mac1 (IC50 = 1.5 μM) and inhibit viral replication [21], synthetic analogs of ADP-ribose that bind SARS-CoV-2 Mac1 with nanomolar affinity [22], and pyrrolo-pyrimidine-based compounds that inhibit viral replication in SARS-CoV-2 [23].

The structural similarity between ChikV Mac1 and SARS-CoV-2 Mac1 [24] has not translated into similar druggability. One strategy to improve ligand-binding affinity is to exploit the presence of water molecules in the binding site by designing inhibitors that effectively use them to form bridging interactions that strengthen binding to the protein [25]. This strategy is particularly relevant for Mac1 ADP-ribose-binding sites, which are large, solvent exposed, and known to maintain an extensive network of ordered water molecules upon ADP binding. In SARS-CoV-2 Mac1, ADP-ribose forms several water-mediated interactions, resulting in the water network in the ADP-ribose-binding site reorganizing upon ligand binding [18,26].

Two-pronged phage treatment counters resistance in Mycobacterium abscessus lung infections

Scientists from A*STAR Infectious Diseases Labs (A*STAR IDL), Nanyang Technological University, Singapore’s Lee Kong Chian School of Medicine (LKCMedicine), the National University of Singapore (NUS), and international collaborators have uncovered how Mycobacterium abscessus—a bacterium that causes serious lung infections—can evade bacteriophage (phage) therapy, and demonstrated a combination strategy to overcome this resistance, offering a pathway toward more effective and durable treatments. The study was published in the Proceedings of the National Academy of Sciences.

Antimicrobial resistance (AMR) is an escalating health challenge that is expected to place growing strain on health care systems worldwide. As AMR continues to erode the effectiveness of existing antibiotics—with one in six bacterial infections worldwide now resistant to antibiotics—scientists are accelerating efforts to develop new countermeasures such as phage therapy, which uses viruses to target bacteria. These efforts are important for strengthening global health and infectious disease preparedness.

A common nutrient could supercharge cancer treatment

A simple nutrient from everyday vegetables could help supercharge the body’s fight against cancer. A common eye-health nutrient, zeaxanthin, may also help the body fight cancer more effectively. Scientists discovered it strengthens Tcells and enhances the impact of immunotherapy treatments. Found in everyday vegetables and supplements, it’s safe, accessible, and shows strong potential as a cancer therapy booster. Human trials are the next step.

Researchers at the University of Chicago have uncovered a surprising new role for zeaxanthin, a plant-based compound best known for supporting eye health. According to findings published in Cell Reports Medicine, this common carotenoid may also help the immune system fight cancer by enhancing the activity of key immune cells. The discovery points to zeaxanthin as a simple, widely available supplement that could improve how well cancer immunotherapies work.

“We were surprised to find that zeaxanthin, already known for its role in eye health, has a completely new function in boosting anti-tumor immunity,” said Jing Chen, PhD, Janet Davison Rowley Distinguished Service Professor of Medicine and senior author of the study. “Our study show that a simple dietary nutrient could complement and strengthen advanced cancer treatments like immunotherapy.”

Brain motion is driven by mechanical coupling with the abdomen

UNIVERSITY PARK, Pa. — The brain is more mechanically connected to the body than previously appreciated, scientists reported today (April 27) in Nature Neuroscience. Through a study using mice and simulations, the team found a potential biological mechanism underlying why exercise is thought to benefit brain health: abdominal contractions compress blood vessels connected to the spinal cord and the brain, enabling the organ to gently move within the skull. This swaying facilitates the surrounding cerebrospinal fluid to flow over the brain, potentially washing away neural waste that could cause problems for brain function.

According to Patrick Drew, professor of engineering science and mechanics, of neurosurgery, of biology and of biomedical engineering at Penn State, the work builds on previous studies detailing how sleep and neuron loss can influence how and when cerebrospinal fluid flushes through the brain.

“Our research explains how just moving around might serve as an important physiological mechanism promoting brain health,” said Drew, corresponding author on the paper. “In this study, we found that when the abdominal muscles contract, they push blood from the abdomen into the spinal cord, just like in a hydraulic system, applying pressure to the brain and making it move. Simulations show that this gentle brain movement will drive fluid flow in and around the brain. It is thought the movement of fluid in the brain is important for removing waste and preventing neurodegenerative disorders. Our research shows that a little bit of motion is good, and it could be another reason why exercise is good for our brain health.”

Drew, who also holds the title of associate director of the Huck Institutes of the Life Sciences, explained how in a hydraulic system, a pump creates pressure that drives fluid flow. In this case, the pump is the abdominal contraction — which can be as light as the tensing prior to sitting up or taking a step. The contraction puts pressure on the vertebral venous plexus, a network of veins that connect the abdominal cavity to the spinal cavity, causing the brain to move.

Abstract: Nature Neuroscience Brain motion is driven by mechanical coupling with the abdomen.

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The antimetastatic effects of calorie restriction are negated by voluntary exercise in an aggressive breast cancer mouse model

The role of lifestyle interventions in treatment success has become essential for nearly every disease. Healthy dietary habits, regular exercise, and stress management are key pillars that can improve quality of life during treatment, as well as delay disease onset and progression. In this study, we focus on the combination of mild calorie restriction (CR) and voluntary exercise as coadjuvants to chemotherapy in the treatment of triple-negative breast cancer using the 4T1 mouse model. In this model, voluntary exercise did not add benefits beyond chemotherapy plus CR in terms of primary tumor size, body composition, or physical performance, while dampening the antimetastatic effect of CR in the lungs of sedentary mice. These findings highlight the challenges of translating results from one preclinical model to another, and ultimately to humans.

Metabolic inflammation at the adipose-brain axis

Adipose-brain axis in metabolic inflammation.

White adipose tissue (WAT) in addition to storing excess energy also releases cytokines, lipid mediators, adipokines, and extracellular vesicles that influence brain physiology.

The inflammatory mediators disrupt key brain interfaces, including the blood-brain barrier (BBB), perivascular and glymphatic clearance pathways, promoting endothelial dysfunction, altered astrocyte-pericyte support, impaired amyloid-b clearance, and region-specific glial activation.

In the brain, obesity-associated neuroinflammation leads to various neuronal dysfunction including cognition.

The authors discuss the role of adipokines in adipose-brain communication during obesity including how they contribute to neuroinflammation and synaptic dysfunction.

The authors also discuss therapeutic strategies targeting the adipose-brain axis, including exercise and dietary interventions and pharmacological approaches such as orlistat and incretin-based therapies. sciencenewshighlights ScienceMission https://sciencemission.com/adipose-brain-axis

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Scientists Develop New Antibody For Virus That Infects 95% of People

The Epstein-Barr virus (EBV) is one of the world’s most common viruses, thought to be lurking in 95 percent of adults. For most, it causes no obvious symptoms.

But EBV is more than a short-term infection.

Once it enters the body, EBV can stay for life, and it has been linked to several cancers, multiple sclerosis, and other severe health complications. Now, new research has given us a promising way to fight it.

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