Now online! (Cell 186786–802.e1–e15; February 16, 2023)
Now online! (Cell 186, 786–802.e1–e15; February 16, 2023)
In our original published article, we performed western blots and imaging of induced motor neurons (iMNs) to elucidate the mechanism through which PIKFYVE inhibition causes secretion and clearance of aggregation-prone proteins such as phosphorylated TDP-43 (pTDP-43). Since publication, we have become aware of 3 errors in figure legends or images that we are now correcting.
Structure basis for the activation of KCNQ2 by endogenous and exogenous ligands.
Zhao et al. report cryo-EM structures of human KCNQ2 in complex with QO-58 and QO-83 in multiple conformations, with or without PIP2. Together with electrophysiological and computational analyses, these structures provide insight into the channel’s activation mechanism and support the rational design of targeted anti-epileptic therapies.
In #RadiologicallyIsolatedSyndrome, greater paramagnetic rim lesion burden on MRI was associated with increased risk and earlier development of clinical MultipleSclerosis.
Question Are paramagnetic rim lesions (PRLs) and central vein sign–positive white matter lesions (CVS+L) associated with developing clinical symptoms of multiple sclerosis (MS) in people with radiologically isolated syndrome (RIS)?
Findings In this cohort of 36 people with RIS, a higher PRL count was associated with a shorter time to developing clinical symptoms of MS and was an independent predictor of symptom onset; these findings were validated in an independent cohort of 43 people with RIS.
Meaning Results show that PRLs may have prognostic utility for risk stratification and help guide treatment decisions in people with RIS, the earliest detectable stage of MS.
Complement inhibition showed promising clinical improvement in this single case of dysferlinopathy.
Dysferlinopathy is a rare autosomal recessively inherited myopathy, presenting as several phenotypes, including a proximal weakness dominant limb-girdle muscular dystrophy R2 phenotype and a distal weakness dominant Miyoshi distal myopathy phenotype.1,2 Muscle weakness usually emerges in young adulthood, followed by a progressive motor decline over the first decade, which tends to be more rapid in individuals with earlier onset.3 Dysferlinopathy is caused by pathogenic variants of the DYSF gene that impair function of dysferlin, a protein that cooperates with others to repair membranes and restore skeletal muscle integrity after injury.4
To date, no effective treatment for dysferlinopathy has been clinically validated. Promising approaches, including exon skipping and gene editing targeting the DYSF gene, as well as myoblast transplantation, are still under investigation in preclinical models.5 Although dysferlinopathy often presents with inflammatory features on muscle pathology and is prone to misdiagnosis as myositis, it is characterized by the absence of focal MHC-I expression and complement C5b-9 deposition on nonnecrotic sarcolemma, which help distinguish it from other muscular dystrophies and inflammatory myopathies.6,7 Specially, complement C3 gene knockout in dysferlin-deficient mice has been demonstrated being able to reverse muscle pathology and improve motor function in the previous animal research.
Even with delayed intervention, this neuroprotective agent delivers lasting protection to the hypertensive brain from ischemic injury.
BackgroundIn spite of the advances in understanding the pathophysiology of stroke, successful treatment remains a major challenge. The lack of consideration of preclinical studies with associated comorbidities is a primary factor for the translational failure, as ~94% of patients with stroke have ≥1 preexisting comorbidities. Because hypertension is the most common comorbid condition in patients with stroke and predisposition to hypertension is known to worsen stroke outcome, we evaluated the efficacy of a novel neuroprotective peptide derived from the brain‐enriched and neuron‐specific tyrosine phosphatase striatal enriched phosphatase (STEP) in attenuating ischemic brain damage under hypertensive conditions.
An artificial intelligence algorithm used newborn blood samples to shed light on the biological complexity of what can go wrong after preterm birth, a Stanford Medicine-led study found.
Dr. Natalie Yivgi-Ohana, Ph.D. — CEO, Minovia Therapeutics — Harnessing The Therapeutic Power Of Mitochondria
Is Co-Founder and CEO of Minovia Therapeutics (https://minoviatx.com/), a biotech company dedicated to rapidly advance life-changing therapies that address the unmet need of serious and complex mitochondrial diseases, and are the first clinical-stage company to develop a mitochondrial transplantation approach to treat a broad range of indications generated by a mitochondrial dysfunction which lead to rare-genetic or age-related diseases.
Dr. Yivgi-Ohana has twenty years of experience in mitochondrial research and received her Ph.D. in Biochemistry at The Hebrew University, after which she completed her postdoctoral fellowship at the Weizmann Institute of Science.
Dr. Yivgi-Ohana also has her B.Sc., Medical Sciences Ben-Gurion University of the Negev and her Master’s Degree, Human Reproduction Bar-Ilan University.
Dr. Yivgi-Ohana founded Minovia with a passion to help children and adults with mitochondrial diseases worldwide.
The research extends beyond theoretical analysis by outlining a feasible experimental implementation using integrated photonics. This includes a detailed description of the required optical components and control sequences for realising the ICO gate and performing the quantum sensing measurements. By leveraging the advantages of integrated photonics, the proposed scheme offers a pathway towards compact and scalable quantum sensors with enhanced performance characteristics. The findings pave the way for practical applications in fields such as precision metrology, biomedical imaging, and materials science.
Indefinite Causal Order for Real-Time Error Correction
Realistic noisy devices present significant challenges to quantum technologies. Quantum error correction (QEC) offers a potential solution, but its implementation in quantum sensing is limited by the need for prior noise characterisation, restrictive signal, noise compatibility conditions, and measurement-based syndrome extraction requiring global control. Researchers have now introduced an ICO-based QEC protocol, representing the first application of indefinite causal order (ICO) to QEC. By coherently integrating auxiliary controls and noisy evolution within an indefinite causal order, the resulting noncommutative interference allows an auxiliary system to herald and correct errors in real time.
When we eat, the body turns surplus calories into molecules called “triglycerides”, especially when those calories come from carbs, sugar, fats, and alcohol. Triglycerides are a type of fat or “lipid”, and the body stores them in fat cells to use as fuel between meals.
However, too much of this fat can become harmful. High triglyceride levels can lead to “hypertriglyceridemia” (“excess triglycerides in the blood”), a condition tied to a much higher risk of heart disease, stroke, and pancreatitis. That is why people are widely encouraged to support healthy triglyceride levels through diet and exercise, while more severe cases may require medication.
Earlier work linked the experimental drug ‘IC7Fc’ to improvements in type 2 diabetes, and new research now points to a possible role in cardiovascular health as well. Scientists report that the compound may lower the risk of heart disease by reducing harmful cholesterol in the bloodstream and calming inflammatory activity that damages blood vessels over time.
The findings come from a preclinical study published in Science Advances, led by researchers at Leiden University Medical Centre in the Netherlands in collaboration with Monash University and other international partners.
In experiments involving mice genetically predisposed to heart disease, treatment with IC7Fc led to clear reductions in blood fat (triglycerides) and cholesterol, markers closely linked to the development of cardiovascular complications.