This study investigated the role of a low-frequency Nav1.8 variant, c.618A G (p. I206M), in the pathogenesis of persistent ocular pain after corneal refractive surgery.
Background and Objectives.
Category: biotech/medical – Page 217
Spatial profiling of patient-matched HER2 positive gastric cancer reveals resistance mechanisms to targeted therapy
Sheng et al. present “” via https://bit.ly/4spB5XM (Original research, GI cancer section).
Why do targeted therapies stop working? Using spatial transcriptomics, this study reveals how tumour heterogeneity, immune escape and metabolic shifts drive resistance in HER2-positive gastric cancer. A must-read for anyone interested in precision oncology and treatment optimisation.
Background Human epidermal growth factor receptor 2 (HER2; ERBB2) is overexpressed or amplified in 15–20% of gastric cancers (HER2+ GC). Within individual HER2+ GCs, HER2/ ERBB2 expression is often variable. Although HER2 therapeutic targeting improves outcomes for HER2+ GC patients, acquired resistance is frequent.
Objective To spatially interrogate HER2+ GC interpatient and intrapatient heterogeneity and resistance mechanisms associated with HER2-targeting agents (trastuzumab, trastuzumab deruxtecan (T-DXd)).
Design Spatial transcriptomic analysis (GeoMx Digital Spatial Profiler) was applied to 1,500 regions of interest in 30 GCs—these contained 15 HER2+ GCs treated with trastuzumab and T-DXd subsequently. Analysis of patient-matched samples with acquired trastuzumab or T-DXd resistance revealed escape mechanisms.
Liquids can fracture like solids—researchers discover the breaking point
In a development that could shift our basic understanding of fluid mechanics, researchers from Drexel University have reported that, given the right circumstances, it is possible to induce a simple liquid to fracture like a solid object. Recently published in the journal Physical Review Letters, the research shows how viscous liquids can suddenly break if stretched with enough force.
The fracturing behavior suggests that viscosity—a liquid’s resistance to flowing—may play a more prominent role in its mechanical properties than previously understood. It also raises new possibilities for how liquids might be manipulated in everything from hydraulics to 3D printers to blood vessels.
“Our findings show that if pulled apart with enough force per area, a simple liquid—a liquid that flows—will reach what we call a point of ‘critical stress,” when it will actually fracture like a solid. And this is likely true for all simple liquids, including common examples, such as water and oil,” said Thamires Lima, Ph.D., an assistant research professor in Drexel’s College of Engineering, who helped to lead the research. “This fundamentally changes our understanding of fluid dynamics.”
Light switch for life: Controlling molecular droplets with UV
Biomolecular condensates are tiny, droplet-like structures made up of molecules that help organize key processes in living organisms. Because they are so small and constantly changing, it has been difficult for scientists to measure their physical properties or control how they behave. Leiden researchers at the Mashaghi Lab have now discovered a surprising new way to shape and control tiny droplets of molecules found in living organisms. The breakthrough could lead to smarter biomaterials, improve drug delivery and even new insights into the emergence of life on Earth. The work is published in Nature Communications.
“Our lab works at the interface of biophysics, molecular engineering and medicine,” says Alireza Mashaghi. “We explore how molecular interactions drive the emergent properties of biological materials.”
Inside the condensates, Mashaghi and his team triggered a reaction normally associated with DNA damage from UV light (like that seen in skin cancer). Known as thymine dimer formation, this process causes two neighboring thymine bases to bond together. By harnessing this reaction as a molecular “switch” within the condensates, the researchers were able to alter the internal connectivity of the molecules, allowing them to control how the condensates behave.
Quantum researchers engineer extremely precise phonon lasers
When lasers were invented in the 1960s, they opened new avenues for scientific discovery and everyday applications, from scanners at the grocery store to corrective eye surgery. Conventional lasers control photons—individual particles of light—but over the past 20 years, scientists have invented lasers that control other fundamental particles, including phonons—individual particles of vibration or sound. Controlling phonons could open even more possibilities with lasers, such as taking advantage of unique quantum properties like entanglement.
A new squeezed phonon laser developed by researchers at the University of Rochester and Rochester Institute of Technology provides precise control over phonons at the nanoscale level. This could give new insights into the nature of gravity, particle acceleration, and quantum physics.
In a paper in Nature Communications, the researchers describe how they coax these individual particles of mechanical motion to behave like a laser.
High-Level Alzheimer Disease Neuropathological Change Following Iatrogenic Exposure
Patients treated with cadaveric pituitary-derived human growth hormone contaminated with amyloid-β developed early-onset AlzheimerDisease with prominent language deficits and histopathological features consistent with AD.
Question What are the clinical and postmortem findings in iatrogenic Alzheimer disease (iAD) consequent to treatment with cadaveric pituitary–derived human growth hormone (c-hGH)?
Findings This case series describes a c-hGH recipient with early-onset dementia and prominent language involvement, in whom postmortem examination showed unequivocal neuropathological features of AD, including severe tauopathy. Three additional c-hGH recipients have similar cognitive syndromes characterized by prominent language involvement.
Meaning These results demonstrate that patients with iAD can have histopathological findings classically found in sporadic AD and that prominent language involvement might be an important phenotypic feature in this AD subtype.
Mutation map reveals how amylin mutations influence type 2 diabetes
Researchers at the Institute for Bioengineering of Catalonia (IBEC) have produced a mutational map showing how mutations in amylin—a hormone that plays a key role in glucose regulation—affect its tendency to form toxic amyloid aggregates in the pancreas. This process is linked to the development of type 2 diabetes. While it was already known that certain mutations could alter this aggregation capacity, understanding of this process was fragmented and based on isolated studies. The research is published in the journal Nature Communications.
“For the first time, we can systematically map how thousands of mutations modulate amylin aggregation, bringing human genetics closer to molecular mechanisms,” says Benedetta Bolognesi, the principal investigator of the Protein Phase Transitions in Health and Disease group at IBEC, who is also the lead author of the study.
“We have created a map that allows us to anticipate the potential impact of these mutations in the population,” adds Marta Badia, a researcher in the same group and first author of the study. “We are not assessing toxicity, but rather the protein’s intrinsic propensity to form fibers. This is a first step, but an extremely necessary one.”
A long-term and scalable system to record from neural organoids
Driving liver inflammation in MASH via multiple pathways.
Metabolic dysfunction-associated steatohepatitis (MASH) if not treated early, may lead to liver cirrhosis and hepatocellular carcinoma (liver cancer).
Hepatic lipotoxicity, intestinal dysbiosis, and pro-inflammatory diets have been attributed to the development of MASH. Moreover, obesity-induced adipose tissue inflammation also contributes to MASH.
The researchers in this review unravel complex, multiple parallel inflammatory mechanisms in MASH and describe how MASH drugs exert their effects. # sciencenewshighlights ScienceMission https://sciencemission.com/liver-inflammation-in-MASH
Intra-and extrahepatic inflammation in MASH is driven by various hits such as lipotoxicity, the gut microbiome, and proinflammatory diets. Inflammation contributes to hepatic and systemic complications, including cardiovascular diseases. Beneficial drugs in MASH might target metabolic and inflammatory pathways.
Abstract: The PIM kinase family is involved in tumorigenesis, yet its role in primary T cells remains largely uncharacterized
https://doi.org/10.1172/JCI192928 Here, Xue-Zhong Yu & team identify Pim2 as a key negative regulator of CD8 T-cell antitumor immunity and validate it as a potential therapeutic target for enhancing cancer immunotherapy.
Electron microscopy images show visible autophagosomes in activated WT T cells, but not in Pim2-KO cells, supporting a model in which the PIM2 promotes T cell autophagy.
Address correspondence to: Xue-Zhong Yu or Yongxia Wu, Department of Microbiology and Immunology, Medical College of Wisconsin, 8,701 Watertown Plank Road, Milwaukee, Wisconsin, 53,226, USA. Phone: 414.955.8187; Email: [email protected] (XZY). Phone: 414.955.8148; Email: [email protected] (YW).
Signal, Speculation, and Standards of Proof in Iatrogenic AD
💬 Editorial: Current evidence supports iatrogenic transmission of cerebral amyloid angiopathy but not AlzheimerDisease; a definitive causal link between contaminated growth hormone exposure and AD remains speculative.
Neurodegenerative diseases caused by protein misfolding (eg, Alzheimer disease [AD], frontotemporal lobar degeneration, Parkinson disease) share many similarities with prion diseases. All demonstrate template-directed protein misfolding and propagation in vivo. However, with 1 exception, they have not exhibited interindividual or zoonotic transmission as observed in iatrogenic Creutzfeldt-Jakob disease and variant Creutzfeldt-Jakob disease, respectively. An important unresolved question is whether other proteinopathies are transmissible between individuals, and if so, their potential impact on public health. To address these concerns, several prion centers have re-assessed cases of iatrogenic Creutzfeldt-Jakob disease due to cadaver-derived human growth hormone (c-hGH) and dura mater grafts. Although amyloid β (Aβ) plaques and cerebral amyloid angiopathy were commonly seen, tau pathology necessary for a diagnosis of AD was not.1,2 Thus, while there is adequate evidence that cerebral amyloid angiopathy may be acquired through iatrogenic mechanisms, iatrogenic transmission of AD pathology remained speculative.3
In 2024, Banerjee et al published an article entitled, “Iatrogenic Alzheimer’s Disease in Recipients of Cadaveric Pituitary-Derived Growth Hormone.”4 This assertion of iatrogenic AD (iAD) was largely predicated on the detection of Aβ seeds contaminating the c-hGH used in 8 recipients who later presented with concerns of cognitive impairment. The recipients had a variety of premorbid neurologic conditions that led to the need for hGH, many of which are themselves associated with later-life neuropathology, perhaps most notably radiotherapy and epilepsy. This report was met with some skepticism, given how the cases were diagnosed and the lack of biological evidence to confirm AD pathology in most participants.5,6
In this issue of JAMA Neurol ogy, the same group presents a report of an autopsy-confirmed case of AD in a c-hGH recipient and describes the clinical phenotype of 3 other c-hGH recipients.7 In their autopsy case, they describe cerebral amyloid angiopathy and high-level AD neuropathologic change (A3B3C3), providing the strongest confirmation of an AD diagnosis in their cohort. Additionally, this individual had limited premorbid medical conditions (complex partial seizures) and required hGH due to idiopathic growth hormone deficiency. They describe the clinical presentation as a mixed primary progressive aphasia phenotype and remark that 3 other c-hGH recipients presented similar primary progressive aphasia phenotypes. One of these was diagnosed with atypical AD due to unspecified single-photon emission computed tomography imaging findings and the other through a reduced Aβ42/40-cerebrospinal fluid ratio.