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Stowaways in the cargo: Contaminating nucleic acids in rAAV preparations for gene therapy

A useful review on the nucleic acid contaminants found in AAVs, how to detect such contaminants, their biological implications, and how we can minimize nucleic acid contaminants in the future through new manufacturing innovations! #biotech #genetherapy

Brimble and colleagues review nucleic acid heterogeneity of rAAV for gene therapy. Alongside the intended expression cassette, non-therapeutic DNA is present within rAAV preparations. These contaminants can be transferred and can even expressed after delivery. They discuss sources of DNA contamination in rAAV and highlight existing strategies to improve vector purity.

Bernoulli family

Originally from Antwerp, a branch of the family relocated to Basel in 1620. [ 4 ] While their origin in Antwerp is certain, proposed earlier connections with the Dutch family of Italian ancestry called Bornouilla (Bernoullie), or with the Castilian family de Bernuy (Bernoille, Bernouille), are uncertain. [ 4 ]

The first known member of the family was Leon Bernoulli (d. 1561), a doctor in Antwerp, at that time part of the Spanish Netherlands. His son, Jacob, emigrated to Frankfurt am Main in 1570 to escape from the Spanish persecution of the Protestants. Jacob’s grandson, a spice trader, also named Jacob, moved to Basel, Switzerland in 1620, and was granted citizenship in 1622. [ 4 ] His son, Niklaus Bernoulli [de] (Nicolaus, 1623–1708), Leon’s great-great-grandson, married Margarethe Schönauer.

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Metasurfaces could be the next quantum information processors

In the race toward practical quantum computers and networks, photons—fundamental particles of light—hold intriguing possibilities as fast carriers of information at room temperature.

Photons are typically controlled and coaxed into quantum states via waveguides on extended microchips, or through bulky devices built from lenses, mirrors, and beam splitters. The photons become entangled—enabling them to encode and process quantum information in parallel—through complex networks of these . But such systems are notoriously difficult to scale up due to the large numbers and imperfections of parts required to do any meaningful computation or networking.

Could all those optical components be collapsed into a single, flat, ultra-thin array of subwavelength elements that control light in the exact same way, but with far fewer fabricated parts?

Brain Plasticity Modulator p75 Neurotrophin Receptor in Human Urine after Different Acute Brain Injuries—A Prospective Cohort Study

Acute brain injuries (ABIs) pose a substantial global burden, demanding effective prognostic indicators for outcomes. This study explores the potential of urinary p75 neurotrophin receptor (p75NTR) concentration as a prognostic biomarker, particularly in relation to unfavorable outcomes. The study involved 46 ABI patients, comprising sub-cohorts of aneurysmal subarachnoid hemorrhage, ischemic stroke, and traumatic brain injury. Furthermore, we had four healthy controls. Samples were systematically collected from patients treated at the University Hospital of Turku between 2017 and 2019, at early (1.50 ± 0.70 days) and late (9.17 ± 3.40 days) post-admission time points. Urinary p75NTR levels, measured by ELISA and normalized to creatinine, were compared against patients’ outcomes using the modified Rankin Scale (mRS). Early urine samples showed no significant p75NTR concentration difference between favorable and unfavorable mRS groups. In contrast, late samples exhibited a statistically significant increase in p75NTR concentrations in the unfavorable group (p = 0.033), demonstrating good prognostic accuracy (AUC = 70.9%, 95% CI = 53–89%, p = 0.03). Assessment of p75NTR concentration changes over time revealed no significant variation in the favorable group (p = 0.992) but a significant increase in the unfavorable group (p = 0.009). Moreover, p75NTR concentration was significantly higher in ABI patients (mean ± SD 40.49 ± 28.83–65.85 ± 35.04 ng/mg) compared to healthy controls (mean ± SD 0.54 ± 0.44 ng/mg), irrespective of sampling time or outcome (p < 0.0001). In conclusion, late urinary p75NTR concentrations emerged as a potential prognostic biomarker for ABIs, showing increased levels associated with unfavorable outcomes regardless of the specific type of brain injury. While early samples exhibited no significant differences, the observed late increases emphasize the time-dependent nature of this potential biomarker. Further validation in larger patient cohorts is crucial, highlighting the need for additional research to establish p75NTR as a reliable prognostic biomarker across various ABIs. Additionally, its potential role as a diagnostic biomarker warrants exploration.