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Category: biotech/medical – Page 14

APOE4 Increases Neurons’ Excitability Before Symptoms Appear

The pro-Alzheimer’s allele APOE4 makes hippocampal neurons in mice smaller and hyperexcitable. This effect, which resembles epilepsy and accelerated aging, can be mitigated by manipulating a neuronal protein [1].

Before symptoms arise

Alzheimer’s disease begins long before symptoms appear, building silently for decades. The single strongest genetic risk factor for the common, late-onset form of Alzheimer’s is the ε4 variant of the apolipoprotein (APOE) gene, APOE4. Carrying a single copy of this variant (being heterozygous) roughly triples your Alzheimer’s risk; having two copies increases it about 12-fold.

Comparative Accuracy of TCD, TTE, TEE, and Cardiac CT in Detecting Right-to-Left Shunt in Embolic Stroke of Undetermined Source

This study provides a comprehensive, head-to-head comparison of transcranial Doppler, transthoracic echocardiography, transesophageal echocardiography, and cardiac CT for right-to-left shunt detection in patients with embolic stroke of undetermined source.

Background and Objectives.

Logan’s List of Entrepreneurship Funding/Mentorship Resources

After compiling these entrepreneurship funding/mentorship resources for my own reference, I realized that others may benefit from them as well. I cover accelerators, general funding, nonprofit funding, training programs, and VC firms. Many possibilities!

After compiling these resources for my personal reference, I realized that others may benefit from them as well. As a person of collaborative spirit, I decided to post them here! Although these are focused on early-stage biotech entrepreneurship, many of the resources should also have broader applicability. I should note that some of the items listed may exist transiently, so parts of this compilation might eventually end up out-of-date. I hope that you find this list helpful for your own adventures!

A centimeter-long bacterium with DNA contained in metabolically active, membrane-bound organelles

Volland et al. discovered a type of bacteria which grows to around a centimeter in length! They explore its remarkable biological adaptations as well. A very interesting read!

Candidatus Thiomargarita magnifica contains compartmentalized genomic material and disrupts conceptions of microbial morphology.

Reprogrammed SimCells for antimicrobial therapy

SimCells are a very exciting way of delivering toxins in a targeted fashion to antibiotic resistant bacteria. It reminds me of my past synthetic biology research in an adjacent area. Love this approach!

In addition to the T6SS system, close contact between attacker and prey cells also allows local delivery of high concentrations of antimicrobial compounds around the targeted cells. To exploit this, we introduced a constitutively expressed salicylate hydroxylase (NahG) into our system (SI Appendix, Fig. S8 A), which catalyzes the conversion of acetylsalicylic acid (aspirin) into catechol (70, 71) (Fig. 4 A). Catechol has a broad-spectrum antimicrobial activity (67 – 69) by generating hydrogen peroxide (H2O2) through auto-oxidation processes (SI Appendix, Fig. S7 A –C), during which catechol polymerizes to form cross-linked polymers without external catalysts (80 – 83) (Fig. 4 A). When 800 μM aspirin 84)] was added to the parental cell and SimCell cultures, the filtered supernatants from overnight NahG+ cultures exhibited a dark-brown color (SI Appendix, Fig. S8 B), which is associated with the oxidation products of catechol. The collected supernatants showed a significant inhibitory effect on bacterial cell growth (SI Appendix, Fig. S8 B and C). These results indicate the generation, permeability, and extracellular antimicrobial activity of SimCell-produced catechol and associated production of H2O2.

Open in Viewer.

How an Alzheimer’s Risk Gene Disrupts Brain Circuits Long Before Memory Loss

Researchers at the Gladstone Institute have uncovered the molecular mechanism by which APOE4 — the most significant genetic risk factor for Alzheimer’s disease, present in roughly a quarter of the population — begins damaging neural circuits well before any cognitive symptoms emerge. Studying young mice carrying the APOE4 variant, the team found that the gene triggers overproduction of the protein Nell2, which causes neurons to shrink and become hyperactive. Crucially, the degree of early neuronal hyperactivity predicted the severity of memory impairment later in life, even in animals that still showed normal learning and memory at the time of measurement. Strikingly, targeting Nell2 therapeutically was able to reverse these changes even in adult animals, demonstrating that the neurodegeneration is not irreversible and that a window for intervention may exist even after the disease process has begun. The team is currently continuing preclinical testing of this therapeutic strategy.

New findings on the APOE4 gene variant point to a potential therapeutic target for Alzheimer’s disease. From left to right, Gladstone scientists Misha Zilberter, Yadong Huang, and Dennis Tabuena examine findings from their research, which is published in the journal Nature Aging.

For the millions of people who carry the gene APOE4, the strongest known genetic risk factor for Alzheimer’s disease, their brain activity may begin changing long before any memory problems appear. Now, researchers at Gladstone Institutes have uncovered a precise chain of molecular events behind those early changes and identified a potential way to reverse them.

Published in the journal Nature Aging, their new study in mouse models reveals how APOE4 triggers increased production of the protein Nell2, which makes neurons shrink and become hyperactive. The more hyperactive the neurons were in early life, the more severe were the memory problems the mice developed later in life.

Frequency of AQP4 and MOG Antibodies in Patients With Optic Neuritis Fulfilling Minimal New Multiple Sclerosis MRI Criteria

How pancreatic cancer survives ferroptosis?

Pancreatic ductal adenocarcinoma (PDAC) tumors harboring KRAS mutations exhibit relative resistance to iron-dependent form of cell death, ferroptosis, compared with other tumor types but the mechanisms remain unclear.

The researchers reveal that hypoxia and pancreatic tumor interstitial fluid cooperate to suppress ferroptosis in pancreatic cancer through HIF-2 activity.

HIF-2 enables tumor survival by regulating glutathione metabolism through upregulating the expression of both components of the system Xc− cystine transporter and transsulfuration pathway enzymes CBS and CTH to increase intracellular cysteine levels.

HIF-2 also induces the Parkin mitophagy factor and suppresses mitochondrial function and reactive oxygen species (ROS) generation and thus survives metabolically hostile environments, defining a tissue-specific role in pancreatic ductal adenocarcinoma. sciencenewshighlights ScienceMission https://sciencemission.com/HIF-2-and-PDAC

Hubbi et al. reveal that hypoxia and pancreatic tumor interstitial fluid cooperate to suppress ferroptosis in pancreatic cancer through HIF-2 activity. By transcriptionally regulating glutathione metabolism and mitochondrial function, HIF-2 enables tumor survival in metabolically hostile environments, defining a tissue-specific role in pancreatic ductal adenocarcinoma.

Continue reading “Frequency of AQP4 and MOG Antibodies in Patients With Optic Neuritis Fulfilling Minimal New Multiple Sclerosis MRI Criteria” | >

A nanoparticle therapy to treat lung cancer and associated muscle wasting at the same time

Researchers at Oregon State University have developed a technique for simultaneously treating lung cancer and a serious muscle-wasting condition that often accompanies it. The study, published in the Journal of Controlled Release, involves lipid nanoparticles delivering therapeutic genetic material to lung tumors.

In a mouse model, scientists led by Oleh Taraula and Yoon Tae Goo of the OSU College of Pharmacy showed that a type of nanocarrier loaded with follistatin messenger RNA is able to accumulate in tumors. Once there, the mRNA triggers cells to produce the follistatin protein, which plays a key role both in inhibiting tumors and promoting muscle tissue growth.

The lipid nanoparticles, or LNPs, can be administered intravenously and reach the lungs courtesy of another protein, vitronectin, that’s found in blood serum. Lipids are fatty acids and similar organic compounds, including many natural oils and waxes. Nanoparticles are tiny pieces of material ranging in size from one-to 100-billionths of a meter.

Scientists reveal a new way cancer cells survive DNA damage

A cancer drug target already being investigated in clinical trials turns out to be doing something even more consequential than researchers realized. Scientists at Scripps Research have discovered that the enzyme Pol theta (Polθ) drives a DNA repair mechanism directly at broken replication forks—one of the most frequent forms of DNA damage in cancer cells. The findings, published in Molecular Cell on March 16, 2026, help explain how tumors survive relentless replication stress and clarify why Pol theta inhibitors may be an effective strategy to selectively target cancer.

“We’ve uncovered a whole new dimension of how cancer cells cope with DNA damage at replication forks,” says Xiaohua Wu, professor at Scripps Research and senior author of the study.

Every time a cell divides, it must make an exact copy of its entire genome, a process carried out by molecular machinery that unzips the DNA double helix and reads each strand to build a new one. The point where this unzipping and copying actively happens is called a replication fork. But when this replication machinery encounters damage, forks can stall or collapse, leaving behind dangerous one-ended DNA breaks that are particularly difficult to repair and, if left unresolved, can kill the cell. This is particularly true in cancer cells, where replication stress is constant.

Gene signature predicting lung cancer recurrence

Using gene activity measurements, the researcher found more than 400 genes that differ between tumors with and without vascular invasion and confirmed these patterns in an independent cohort. They then developed and validated a machine-learning predictor that predicts whether vascular invasion is present. They found this test worked well at predicting tumor recurrence in other datasets and, crucially, gave accurate results about vascular invasion when measured in tiny biopsy samples taken before surgery.

The researchers believe this predictor will play an important role in picking a treatment matched to how aggressive the tumor is.

According to the researchers, there is growing evidence that vascular invasion is associated with poor prognosis in other kinds of cancer, such as breast, liver and gastric cancer. The researchers need to determine if the same genes that are active in vascular-invasive lung adenocarcinoma are altered in other cancers. ScienceMission sciencenewshighlights.

Lung cancer is the leading cause of death from cancer. It kills more people in the U.S. than breast, prostate and colon cancer combined. When lung adenocarcinoma, the most common primary lung cancer in the U.S., grows into nearby blood vessels (a process called vascular invasion), the tumor is more likely to recur even if surgically removed. Pathologists can identify areas of vascular invasion post-operatively, but surgeons could perform more extensive surgery to lower the risk of recurrence if they could predict which tumors were more likely to have vascular invasion.

Researchers believe they have, for the first time, identified genes whose activity changes in lung tumors with vascular invasion. Additionally, they also discovered that they could detect these changes in small pieces of the tumor collected during a presurgical biopsy procedure.

“We think this is a potential game changer for patients with early-stage lung cancer,” says the corresponding author. “Our findings suggest a simple biopsy-based test could help doctors better identify patients at higher risk of recurrence and guide treatment decisions.”

Continue reading “Gene signature predicting lung cancer recurrence” | >

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