Longtail News
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Longtail News
@longtail.news
An experiment in posting articles from less common sites and topics, as many posts as Bluesky allows per day. Please mute or block if the volume is annoying.

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Feed: "Bethesda Magazine"
By: Josephine Jack on Friday, December 26, 2025
Best of Bethesda 2026 Readers’ Picks: Food & Drink
Best of Bethesda 2026 Readers’ Picks: Food & Drink. Read about the best bagels, brunches, burgers and more in Montgomery County.
bethesdamagazine.com
December 26, 2025 at 4:47 PM
Feed: "Avibirds.com"
By: Richard (Dick) Daniels on Friday, December 26, 2025
17 Types of Finches in North America (with Pictures and ID Tips)
Discover the finches of North America through clear identification tips, habitat use, and behaviors that help with field recognition.
avibirds.com
December 26, 2025 at 4:47 PM
Feed: "48 hills"
By: John-Paul Shiver on Friday, December 26, 2025
Under the Stars: Noise Pop’s latest scores? Jay Som, Giraffage, CupcakKe, Open Eagle Mike…
Plus: A perfect, purple way to spend NYE, RIP Jellybean Johnson of the Time, Say She She, Altın Gün, more music news.
48hills.org
December 26, 2025 at 4:46 PM
Feed: "48 hills"
By: Charles Lewis III on Friday, December 26, 2025
Drama Masks: Year on Stage 2025, part 1—the not-so-great stuff
A year of devastating cuts, wild uncertainty, and unexpected departures left their marks on the SF scene.
48hills.org
December 26, 2025 at 4:46 PM
Feed: "A Year (Or More) Of Photos"
By: noreply@blogger.com (feminist writer - Robin Shwedo) on Friday, December 26, 2025
Jumping, Horse Show
Jumping, Horse Show NFS
a-year-of-photos.blogspot.com
December 26, 2025 at 4:46 PM
Feed: "JCI Insight -- New Articles"
A rebrand for proteasome inhibition in solid tumors via continuous hepatic artery infusion
insight.jci.org
December 26, 2025 at 4:35 PM
Feed: "JCI Insight -- New Articles"
Mutation in IR or IGF1R produces features of long-lived mice while maintaining metabolic health
Insulin/insulin growth factor signaling is a conserved pathway that regulates lifespan. However, long-lived loss-of-function mutants often produce insulin resistance, slow growth, and impair reproduction. Recently, a gain-of-function mutation in the kinase insert domain (KID) of the Drosophila insulin/IGF receptor was seen to dominantly extend lifespan without impairing insulin sensitivity, growth, or reproduction. This substitution occurs within residues conserved in mammalian insulin receptor (IR) and insulin growth factor-1 receptor (IGF-1R). We produced 2 knock-in mouse strains that carry the homologous KID Arg/Cys substitution in murine IR or IGF-1R, and we replicated these genotypes in human cells. Cells with heterodimer receptors of IR or IGF-1R induce receptor phosphorylation and phospho-Akt when stimulated with insulin or IGF. Heterodimer receptors of IR fully induce pERK, but ERK was less phosphorylated in cells with IGF-1R heterodimers. Adults with a single KID allele (producing heterodimer receptors) have normal growth and glucose regulation. At 4 months, these mice variably display hormonal markers that associate with successful aging counteraction, including elevated adiponectin and FGF21, as well as reduced leptin and IGF-1. Livers of IGF-1R females show decreased transcriptome-based biological age, which may point toward delayed aging and warrants an actual lifespan experiment. These data suggest that KID mutants may slow mammalian aging while they avoid the complications of insulin resistance.
insight.jci.org
December 26, 2025 at 4:35 PM
Feed: "JCI Insight -- New Articles"
By: Ben Yamine Mallouki, Loubna Boukhzar, Ludovic Dumont, Azénor Abgrall, Marjorie Gras, Agathe Prieur, David Alexandre, David Godefroy, Yves Tillet, Nathalie Rives, Luca Grumolato, Fatiha Chigr, Youssef Anouar
Central SELENOT deficiency impairs gonadotrope axis function, sexual behavior, and fertility in male and female mice
Reproductive disorders can result from a defective action of the neuropeptide gonadotropin-releasing hormone (GnRH), the master regulator of reproduction. We have previously shown that selenoprotein T (SELENOT), a newly described thioredoxin-like selenoprotein highly expressed in endocrine and neuroendocrine cells, plays a role in hormone secretion and neuroprotection. However, whether SELENOT is involved in neuroendocrine regulation in vivo is totally unknown. We found that SELENOT deficiency in the brain impaired sexual behavior, leading to a decline in fertility in both male and female mice. Biochemical and histological analyses of the gonadotrope axis of these mice revealed a higher expression of GnRH, which is associated with circulating luteinizing hormone (LH) excess, and elevated steroid hormones in males and a polycystic ovary syndrome–like phenotype in females. In addition, SELENOT deficiency impaired LH pulse secretion in both male and female mice. These changes were reverted after administration of a GnRH antagonist. Together, our data demonstrate for the first time to our knowledge the role of a selenoprotein in the central control of sexual behavior and reproduction, and identify a redox effector of GnRH neuron activity impacting both male and female reproductive function.
insight.jci.org
December 26, 2025 at 4:35 PM
Feed: "JCI Insight -- New Articles"
By: Ha Thu Nguyen, Luong Dai Ly, Thuy Thi Thanh Ngo, Soo Kyung Lee, Carlos Noriega Polo, Subo Lee, Taesic Lee, Seung-Kuy Cha, Xaviera Riani Yasasilka, Kae Won Cho, Myung-Shik Lee, Andreas Wiederkehr, Claes B. Wollheim, Kyu-Sang Park
Palmitate impairs autophagic degradation via oxidative stress/perilysosomal Ca2+ overload/mTORC1 activation pathway in pancreatic β cells
Saturated fatty acids impose lipotoxic stress on pancreatic β cells, leading to β cell failure and diabetes. In this study, we investigate the critical role of organellar Ca2+ disturbance on defective autophagy and β cell lipotoxicity. Palmitate, a saturated fatty acid, induced perilysosomal Ca2+ elevation, sustained mTOR complex 1 (mTORC1) activation on the lysosomal membrane, suppression of the lysosomal transient receptor potential mucolipin 1 (TRPML1) channel, and accumulation of undigested autophagosomes in β cells. These Ca2+ aberrations with autophagy defects by palmitate were prevented by an mTORC1 inhibitor or a mitochondrial superoxide scavenger. To alleviate perilysosomal Ca2+ overload, strategies such as lowering extracellular Ca2+, employing voltage-gated Ca2+ channel blocker or ATP-sensitive K+ channel opener, effectively abrogated mTORC1 activation and preserved autophagy. Furthermore, redirecting perilysosomal Ca2+ into the endoplasmic reticulum (ER), with an ER Ca2+ ATPase activator, restored TRPML1 activity, promoted autophagic flux, and improved survival of β cells exposed to palmitate-induced lipotoxicity. Our findings suggest oxidative stress/Ca2+ overload/mTORC1 pathway involvement in TRPML1 suppression and defective autophagy during β cell lipotoxicity. Restoring perilysosomal Ca2+ homeostasis emerges as a promising therapeutic strategy for metabolic diseases.
insight.jci.org
December 26, 2025 at 4:35 PM
Feed: "JCI Insight -- New Articles"
By: Shokichi Takahama, Takahiro Tomiyama, Sachiyo Yoshio, Yuta Nagatsuka, Hirotomo Murakami, Takuto Nogimori, Mami Kochi, Shoko Ochiai, Hidenori Kimura, Akihisa Fukushima, Tatsuya Kanto, Takuya Yamamoto
Preclinical assessment of oral TLR7 agonist SA-5 in a nonhuman primate model
TLR7 agonists are promising immunostimulatory agents for the treatment of chronic infections and cancer. However, their systemic toxicity remains a challenge. In this study, SA-5, a potentially novel liver-targeted, orally available TLR7 agonist, was evaluated for pharmacokinetics, safety, and efficacy in young and aged macaques across 1–10 mg/kg repeated doses. Safety was evaluated through hematologic, biochemical, and flow cytometric profiling, while efficacy was assessed via IFN-α production, gene expression of IFN-stimulated genes, and plasmacytoid dendritic cell activation. A principal component analysis–based (PCA-based) composite scoring system was used to integrate multimodal parameters. SA-5 induced dose-dependent type I IFN with limited systemic inflammation, with 3 mg/kg showing optimal balance. SA-5 had comparable immunostimulatory activity to GS-9620 but with reduced adverse biomarker shifts. In aged macaques, efficacy was maintained with modestly increased safety responses. These findings support SA-5 as a safer next-generation TLR7 agonist effective across age groups, highlighting integrated biomarker profiling in preclinical immunomodulatory drug development.
insight.jci.org
December 26, 2025 at 4:35 PM
Feed: "JCI Insight -- New Articles"
By: Antonia Beitzen-Heineke, Matthew A. Muller, Yuhe Xia, Elliot Luttrell-Williams, Florencia Schlamp, Deepak Voora, Kelly V. Ruggles, Michael S. Garshick, Tessa J. Barrett, Jeffrey S. Berger
A platelet transcriptomic signature of thromboinflammation predicts cardiovascular risk
BACKGROUND Platelets are increasingly recognized as active participants in immune signaling and systemic inflammation. Upon activation, platelets form monocyte platelet aggregates (MPA) representing the crossroads of thrombosis and inflammation. We hypothesized that platelet transcriptomics could capture this thromboinflammatory axis and identify individuals at elevated cardiovascular risk.METHODS: MPA levels, defined as CD14+CD61+ cells, were measured using flow cytometry at 2 time points, 4 weeks apart, in healthy individuals Platelets were isolated and sequenced. Individuals were categorized as MPAhi or MPAlo based on consistently high or low MPA levels across time points.RESULTS Among 149 participants (median age 52 years, 57% female, 50% non-White), MPAhi individuals exhibited increased expression of platelet activation markers P-selectin (P < 0.001), PAC-1 (P = 0.021), and CD40L (P < 0.001) and enriched immune signaling pathways. Informed by MPA levels and derived from the platelet transcriptome, we developed a 42-gene thromboinflammation platelet signature (TIPS), which correlated with MPA levels in multiple cohorts and was reproducible over time. TIPS was elevated in patients with COVID-19 (P = 0.0002) and myocardial infarction (Padj = 0.008), and as in predicted future cardiovascular events in patients who underwent lower extremity revascularization after a median follow-up of 18 months (adjusted for age, sex, race, and ethnicity [adjHR] 1.55, P = 0.006). Notably, TIPS was modifiable by ticagrelor (P = 0.002) but not aspirin.CONCLUSION These findings establish MPA as a biomarker of thromboinflammation and introduce TIPS, a platelet RNA signature, that captures thromboinflammation and provides a promising tool for cardiovascular risk stratification and a potential therapeutic target.TRIAL REGISTRATION NCT04369664FUNDING NIH R35HL144993, NIH R01HL139909, and AHA 16SFRN2873002 to JSB, DFG Walter-Benjamin-Programme 537070747 to AB.
insight.jci.org
December 26, 2025 at 4:34 PM
Feed: "JCI Insight -- New Articles"
Bronchial epithelial transcriptome reveals dysregulated interferon and inflammatory responses to rhinovirus in exacerbation-prone pediatric asthma
Host factors influencing susceptibility to rhinovirus-induced asthma exacerbations remain poorly characterized. Using organotypic bronchial epithelial cultures from well-characterized children with asthma and healthy children, this study investigated viral load kinetics and resultant host responses by bulk and single-cell transcriptomics and targeted protein analyses. Bronchial epithelium from exacerbation-prone children exhibited greater rhinovirus replication and a cascade of exaggerated downstream interferon (IFN), inflammatory, epithelial stress, and remodeling responses. These transcriptional patterns were confirmed and further refined using single-cell transcriptomics, revealing cell type–specific contributions — particularly from non-ciliated cell populations including secretory immune response, tuft, and basal cells. We observed that these post-infection differences were associated with lower pre-infection IFN-stimulated gene (ISG) expression and protein levels of the ISG CXCL10. Prophylactic IFN-β treatment reduced viral replication and normalized downstream responses, supporting low baseline (pre-infection) IFN tone as a modifiable causal determinant of host susceptibility to adverse rhinovirus-induced responses in exacerbation-prone children with asthma.
insight.jci.org
December 26, 2025 at 4:34 PM
Feed: "JCI Insight -- New Articles"
Chromosomal instability in circulating tumor cells and cabazitaxel resistance in metastatic castration-resistant prostate cancer
BACKGROUND Predictive biomarkers to guide chemotherapy decisions for metastatic castration–resistant prostate cancer (mCRPC) are lacking. Preclinical studies indicate that circulating tumor cell (CTC) studies of chromosomal instability (CTC-CIN) can predict taxane resistance.METHODS The CARD trial randomized individuals with mCRPC progressing within a year of treatment with an androgen receptor pathway inhibitor (ARPI; enzalutamide or abiraterone acetate plus prednisolone/prednisone) to cabazitaxel or the alternative ARPI. As a preplanned biomarker analysis, CTCs were isolated from blood samples obtained at baseline, cycle 2, and the end of treatment. Associations between baseline CTC and CTC-CIN counts with imaging-based progression-free survival (ibPFS), overall survival (OS), time to prostate-specific antigen (PSA) progression, RECIST 1.1 objective response rate (ORR), and PSA50 response rate were assessed. RESULTS High baseline CTC-CIN counts significantly associated with worse OS after adjustment for confounding variables (median OS, 15.3 vs. 8.9 months; univariate HR, 2.16; 95% CI, 1.52–3.06; P < 0.001; multivariate HR, 1.56; 95% CI, 1.01–2.43; P = 0.047). Detectable CTC-CIN counts at baseline may predict a lack of ibPFS and OS benefit when comparing cabazitaxel with ARPI. CONCLUSION This preplanned analysis of biomarker data from the CARD trial confirms that CTC-CIN counts are a clinically useful prognostic and predictive biomarker of taxane resistance in mCRPC. Detectable CTC-CIN at baseline defines a patient subpopulation with unmet clinical needs in which alternative therapeutics should be tested.TRIAL REGISTRATION ClinicalTrials.gov number NCT02485691.FUNDING Funded by Sanofi and Epic Sciences.
insight.jci.org
December 26, 2025 at 4:34 PM