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Category: biotech/medical – Page 35

Mapping mutations at scale in a single gene reveals new neurodevelopmental condition

The ability of different genetic variants—changes to one or more building blocks of DNA—to cause disease, and to what extent, has historically been opaque. Geneticist and Crick group leader Greg Findlay has pioneered a new method in the hope of changing this. Called “saturation genome editing,” the new technique involves mapping every single variant in a given gene to work out what it does and pinpoint which changes are responsible for specific disorders.

While Greg was refining these experiments, Nicky Whiffin, associate professor at the University of Oxford, had identified that mutations in a tiny gene were behind a rare inherited neurodevelopmental disorder, known as ReNU syndrome, which impacts brain function, development and motor skills. Children develop this syndrome if a single copy of the RNU4-2 gene is mutated in a specific way.

Nicky initially found that several distinct mutations in a critical region of the gene caused the condition, and she was keen to understand if some of these genetic variants led to more severe disease.

Mapping pesticide mixtures to cancer risk at the country scale with spatial exposomics

Using an integrative spatial Bayesian framework that merges high-resolution environmental pesticide risk modelling with comprehensive cancer registry data, this analysis reveals spatial patterns of pesticide exposure and liver tissue-derived molecular signatures across Peru, establishing links between pesticide usage and cancer insurgence at the national scale.

ADAMTS-7 Vaccine Confers Renal and Vascular Protection in Chronic Kidney Disease

Yang & colleagues demonstrate a peptide vaccine targeting the metalloproteinase ADAMTS7 mitigates the damage to the kidneys & blood vessels related to chronic kidney disease. Learn more at.

ELetters should relate to an article recently published in the journal and are not a forum for providing unpublished data. Comments are reviewed for appropriate use of tone and language. Comments are not peer-reviewed. Acceptable comments are posted to the journal website only. Comments are not published in an issue and are not indexed in PubMed. Comments should be no longer than 500 words and will only be posted online. References are limited to 10. Authors of the article cited in the comment will be invited to reply, as appropriate.

Abstract: Do cells of different lineages age differently?

https://doi.org/10.1172/JCI195772 Sundeep Khosla & team compare the senescence phenotype of mesenchymal versus immune cells from murine bone and bone marrow, revealing important differences between them.

The figure shows mesenchymal cells exhibit higher absolute levels of senescence signatures than immune cells.

Address correspondence to: Madison L. Doolittle, Center for Regenerative Medicine and Skeletal Development, UConn Health, 263 Farmington Avenue, Farmington, Connecticut 6,030, USA. Phone: 860.679.1757; Email: [email protected]. Or to: Sundeep Khosla, Guggenheim 7, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, Minnesota 55,905, USA. Phone: 507.255.6663; Email: [email protected].

Histone modification clocks for robust cross-species biological age prediction and elucidating senescence regulation

Building upon these insights, we constructed 36 histone modification-based epigenetic clocks, which exhibited robust predictive accuracy (mean Pearson’s r = 0.91) across multiple tissues and marks. Among these, the blood-derived H3K27ac clock emerged as a particularly powerful model, outperforming several established DNA methylation clocks under matched conditions. This performance is remarkable considering that DNA methylation clocks have undergone extensive optimization over the past decade (9, 16, 18), while our histone-based approach represents a first-generation effort.

A distinctive advantage of our histone-based clocks is their resilience to technical and biological noise. When exposed to artificial Gaussian noise, the histone-based clock maintained stable predictive performance, in contrast to the sharp degradation observed in many methylation-based models. This robustness is likely attributable to the broader, structural nature of histone mark signals, which may be less sensitive to local fluctuations than single CpG methylation values. This characteristic makes histone clocks potentially more suitable for noisy, heterogeneous, or clinically derived datasets where sample quality may vary.

The practical utility of our histone-based clocks was further demonstrated by their ability to detect biological age acceleration in leukemia samples and capture age reversal following therapeutic interventions. These applications highlight the potential of histone-based clocks as biomarkers for disease states and treatment responses, offering a complementary approach to existing clinical tools.

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.

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