Reporting and reproducibility: Proteomics of fish models in environmental toxicology and ecotoxicology  ScienceDirect.com

To show their support of a future Madame President, Gov. Tim Walz and others in the party are publicly relinquishing male power and privilege.

En los municipios afectados por la DANA hay 33 perros guías que están en constante estudio ante el temor que puedan contraer alguna enfermedad Leer

Hundreds of thousands of veterans have received additional benefits in the past year after President Joe Biden signed legislation expanding coverage for conditions connected to burn pits that were used to destroy trash and potentially toxic materials. The first anniversary of the law is Thursday, and Biden will mark the occasion at a Veterans Affairs hospital in Salt Lake City. Administration officials are trying to encourage as many people as possible to sign up by Wednesday, which would allow their benefits to be retroactive to when the law was signed. The agency is also trying to hire more people to handle the influx of claims, which is expected to cause larger backlogs over the coming months.

The post Veterans see historic expansion of benefits for toxic exposure as new law nears anniversary first appeared on Federal News Network.

Federal Deposit Insurance Corp. Chairman Martin Gruenberg is sitting for a second day of grilling on Capitol Hill, this time at the Senate Banking Committee,

The post FDIC chair is grilled on Capitol Hill after report outlines agency’s toxic workplace culture first appeared on Federal News Network.

Dana Laake and her special guest Wendy Myers will discuss toxic metals that cause fatigue and how to detox them.

The post Toxic Metals that Cause Fatigue – and How to Detox Them first appeared on Federal News Network.

The Senate has given final approval to a bill enhancing health care and disability benefits for millions of veterans exposed to toxic burn pits while serving in Iraq and Afghanistan.

The post Senate approves bill to aid vets exposed to toxic burn pits first appeared on Federal News Network.

Location: Electronic Resource- 

Location: Electronic Resource- 

Location: Engineering Library- TD442.5.M4586 2016

A new study found that as Central Valley residents go about their day, they regularly breathe in pesticides, including one banned in California.

Zymo Research, Unravel Biosciences, and Channel Islands Marine & Wildlife Institute team up to combat increasing cases of domoic acid poisoning in sea lions.

Ridley Scott's The Last Duel opens with two hardened 14th-century French warriors preparing for ritual combat, but don't be fooled: This isn't a historical epic about brave men headed off to war…

El flúor y su toxicidad.

Del Rio was a defensive coordinator and interim head coach for the Broncos from the 2012-14 seasons.

The water was known to have been contaminated for years.

Police are appealing for assistance in locating a female who, in what was apparently an intoxicated state, walked away from a taxi driver in the early hours of Saturday morning. A police spokesperson said, “Police responded to an incident that took place at 1am on Saturday February 14th on Harbour Road in the area of […]

Between 1948 and 1961, barges laden with industrial waste, including high concentrations of once-ubiquitous agricultural insecticide, Dichlorodiphenyltrichloroethane (DDT), were indiscriminately discharged into the Pacific Ocean.…

The post DDT is a Deep-Sea Toxic Time Capsule first appeared on Deep Sea News.

The ROV Global Explorer reaches bottom at around 9:01 am, nearly 3.5 kilometers deep  in the Gulf of Mexico.  The 1.5-ton machine flies nimbly through…

The post Surviving Toxic Havens first appeared on Deep Sea News.

Over 1,500 Android devices have been infected by a new strain of Android banking malware called ToxicPanda that allows threat actors to conduct fraudulent banking transactions. "ToxicPanda's main goal is to initiate money transfers from compromised devices via account takeover (ATO) using a well-known technique called on-device fraud (ODF)," Cleafy researchers Michele Roviello, Alessandro Strino

In the 2024 election, Donald Trump easily carried many predominantly Hispanic rural areas like Hidalgo County, Texas, and some mostly non-white precincts, such as mostly Asian areas of Brooklyn. As journalist Josh Kraushaar noted, “Trump carried PASSAIC County, New Jersey. Majority/Hispanic electorate and home to a sizable Orthodox Jewish constituency. Was a Dem stronghold for […]

The post Prominent law professor blames Harris loss on ‘white supremacy’ and ‘toxic masculinity’ appeared first on Liberty Unyielding.

It's been just over a year since director Macon Blair premiered his new reboot of The Toxic Avenger at Fantastic Fest in Austin, Texas. The new film stars Peter Dinklage as the eponymous hideously deformed creature of superhuman size and strength, along with Elijah Wood, Kevin Bacon, and more—but has unfortunately struggled to find support for a wider distribution, according to The Hollywood Reporter. — Read the rest

The post The new TOXIC AVENGER comic book is great appeared first on Boing Boing.

Nica M. Borradaile
Dec 1, 2006; 47:2726-2737
Research Articles

Genetic mutations related to ALS, a progressive neurological disease, have been discovered in the gene encoding σ-1 receptor (σ1R). We previously reported that σ1RE102Q elicits toxicity in cells. The σ1R forms oligomeric states that are regulated by ligands. Nevertheless, little is known about the effect of ALS-related mutations on oligomer formation. Here, we transfected NSC-34 cells, a motor neuronal cell line, and HEK293T cells with σ1R-mCherry (mCh), σ1RE102Q-mCh, or nontagged forms to investigate detergent solubility and subcellular distribution using immunocytochemistry and fluorescence recovery after photobleaching. The oligomeric state was determined using crosslinking procedure. σ1Rs were soluble to detergents, whereas the mutants accumulated in the insoluble fraction. Within the soluble fraction, peak distribution of mutants appeared in higher sucrose density fractions. Mutants formed intracellular aggregates that were co-stained with p62, ubiquitin, and phosphorylated pancreatic eukaryotic translation initiation factor-2-α kinase in NSC-34 cells but not in HEK293T cells. The aggregates had significantly lower recovery in fluorescence recovery after photobleaching. Acute treatment with σ1R agonist SA4503 failed to improve recovery, whereas prolonged treatment for 48 h significantly decreased σ1RE102Q-mCh insolubility and inhibited apoptosis. Whereas σ1R-mCh formed monomers and dimers, σ1RE102Q-mCh also formed trimers and tetramers. SA4503 reduced accumulation of the four types in the insoluble fraction and increased monomers in the soluble fraction. The σ1RE102Q insolubility was diminished by σ1R-mCh co-expression. These results suggest that the agonist and WT σ1R modify the detergent insolubility, toxicity, and oligomeric state of σ1RE102Q, which may lead to promising new treatments for σ1R-related ALS.

Neurodegeneration in Parkinson's disease (PD) can be recapitulated in animals by administration of α-synuclein preformed fibrils (PFFs) into the brain. However, the mechanism by which these PFFs induce toxicity is unknown. Iron is implicated in PD pathophysiology, so we investigated whether α-synuclein PFFs induce ferroptosis, an iron-dependent cell death pathway. A range of ferroptosis inhibitors were added to a striatal neuron-derived cell line (STHdhQ7/7 cells), a dopaminergic neuron–derived cell line (SN4741 cells), and WT primary cortical neurons, all of which had been intoxicated with α-synuclein PFFs. Viability was not recovered by these inhibitors except for liproxstatin-1, a best-in-class ferroptosis inhibitor, when used at high doses. High-dose liproxstatin-1 visibly enlarged the area of a cell that contained acidic vesicles and elevated the expression of several proteins associated with the autophagy-lysosomal pathway similarly to the known lysosomal inhibitors, chloroquine and bafilomycin A1. Consistent with high-dose liproxstatin-1 protecting via a lysosomal mechanism, we further de-monstrated that loss of viability induced by α-synuclein PFFs was attenuated by chloroquine and bafilomycin A1 as well as the lysosomal cysteine protease inhibitors, leupeptin, E-64D, and Ca-074-Me, but not other autophagy or lysosomal enzyme inhibitors. We confirmed using immunofluorescence microscopy that heparin prevented uptake of α-synuclein PFFs into cells but that chloroquine did not stop α-synuclein uptake into lysosomes despite impairing lysosomal function and inhibiting α-synuclein toxicity. Together, these data suggested that α-synuclein PFFs are toxic in functional lysosomes in vitro. Therapeutic strategies that prevent α-synuclein fibril uptake into lysosomes may be of benefit in PD.

Learn how your darkest emotions can actually be your strongest motivators.

Neuronal cytotoxic edema is implicated in neuronal injury and death, yet mitigating brain edema with osmotic and surgical interventions yields poor clinical outcomes. Importantly, neuronal swelling and its downstream consequences during early brain development remain poorly investigated, and new treatment approaches are needed. We explored Ca²⁺-dependent downstream effects after neuronal cytotoxic edema caused by diverse injuries in mice of both sexes using multiphoton Ca²⁺ imaging in vivo [Postnatal Day (P)12–17] and in acute brain slices (P8–12). After different excitotoxic insults, cytosolic GCaMP6s translocated into the nucleus after a few minutes in a subpopulation of neurons, persisting for hours. We used an automated morphology-detection algorithm to detect neuronal soma and quantified the nuclear translocation of GCaMP6s as the nuclear to cytosolic intensity (N/C ratio). Elevated neuronal N/C ratios occurred concurrently with persistent elevation in Ca²⁺ loads and could also occur independently from neuronal swelling. Electron microscopy revealed that the nuclear translocation was associated with the increased nuclear pore size. The nuclear accumulation of GCaMP6s in neurons led to neocortical circuit dysfunction, mitochondrial pathology, and increased cell death. Inhibiting calpains, a family of Ca²⁺-activated proteases, prevented elevated N/C ratios and neuronal swelling. In summary, in the developing brain, we identified a calpain-dependent alteration of nuclear transport in a subpopulation of neurons after disease-relevant insults leading to long-term circuit dysfunction and cell death. The nuclear translocation of GCaMP6 and other cytosolic proteins after acute excitotoxicity can be an early biomarker of brain injury in the developing brain.

Hyperbilirubinemia (HB) is a key risk factor for hearing loss in neonates, particularly premature infants. Here, we report that bilirubin (BIL)-dependent cell death in the auditory brainstem of neonatal mice of both sexes is significantly attenuated by ZD7288, a blocker for hyperpolarization-activated cyclic nucleotide-gated (HCN) channel-mediated current (I_h), or by genetic deletion of HCN1. GABAergic inhibitory interneurons predominantly express HCN1, on which BIL selectively acts to increase their intrinsic excitability and mortality by enhancing HCN1 activity and Ca²⁺-dependent membrane targeting. Chronic BIL elevation in neonatal mice in vivo increases the fraction of spontaneously active interneurons and their firing frequency, I_h, and death, compromising audition at the young adult stage in HCN1^+/+, but not in HCN1^–/– genotype. We conclude that HB preferentially targets HCN1 to injure inhibitory interneurons, fueling a feedforward loop in which lessening inhibition cascades hyperexcitability, Ca²⁺ overload, neuronal death, and auditory impairments. These findings rationalize HCN1 as a potential target for managing HB encephalopathy.

Newfoundland filmmaker Justin Simms is releasing his latest film called Sons. It was prompted by the birth of his son and left him wondering how traditional masculine behaviour is learned.

A team of researchers from Penn State College of Medicine found that misfolded versions of a protein exhibit tissue-specific toxicity linked to cell degeneration that may be linked to the development of amyotrophic lateral sclerosis (ALS). The study is a step forward in understanding the physiological processes that may contribute to ALS development and progression and identifies a potential therapeutic target, the researchers said.

Invasive cane toads have decimated native freshwater crocodile populations in northern Australia, as the predators don't know they should avoid the toxic amphibians

You might have heard about plans to establish a self‑sustaining city on Mars. Here’s what life would really be like on the Red Planet

You might have heard about plans to establish a self‑sustaining city on Mars. Here’s what life would really be like on the Red Planet

Title: Biden to Sign Bill That Helps Veterans Exposed to Toxic Burn Pits
Category: Health News
Created: 8/10/2022 12:00:00 AM
Last Editorial Review: 8/11/2022 12:00:00 AM

Title: Is Graves’ Disease the Same as Thyrotoxicosis?
Category: Diseases and Conditions
Created: 7/8/2022 12:00:00 AM
Last Editorial Review: 7/8/2022 12:00:00 AM

Title: Thyroid Storm vs Thyrotoxicosis: Differences
Category: Diseases and Conditions
Created: 7/8/2022 12:00:00 AM
Last Editorial Review: 7/8/2022 12:00:00 AM

Title: Before Volcano Buried Pompeii, Toxic Water May Have Plagued Residents
Category: Health News
Created: 8/29/2017 12:00:00 AM
Last Editorial Review: 8/30/2017 12:00:00 AM

Title: Even at Low Levels, Toxic Metals Put Heart at Serious Risk: Study
Category: Health News
Created: 8/30/2018 12:00:00 AM
Last Editorial Review: 8/30/2018 12:00:00 AM

Title: Picture of Phototoxic Dermatitides
Category: Images
Created: 2/23/2010 2:33:00 PM
Last Editorial Review: 6/28/2022 12:00:00 AM

Bacterial regulatory RNAs (sRNAs) are important players to control gene expression. In Staphylococcus aureus, SprC is an antivirulent trans-acting sRNA known to base-pair with the major autolysin atl mRNA, preventing its translation. Using MS2-affinity purification coupled with RNA sequencing, we looked for its sRNA-RNA interactome and identified 14 novel mRNA targets. In vitro biochemical investigations revealed that SprC binds two of them, czrB and deoD, and uses a single accessible region to regulate its targets, including Atl translation. Unlike Atl regulation, the characterization of the SprC-czrB interaction pinpointed a destabilization of the czrAB cotranscript, leading to a decrease of the mRNA level that impaired CzrB zinc efflux pump expression. On a physiological standpoint, we showed that SprC expression is detrimental to combat against zinc toxicity. In addition, phagocyctosis assays revealed a significant, but moderate, increase of czrB mRNA levels in a sprC-deleted mutant, indicating a functional link between SprC and czrB upon internalization in macrophages, and suggesting a role in resistance to both oxidative and zinc bursts. Altogether, our data uncover a novel pathway in which SprC is implicated, highlighting the multiple strategies used by S. aureus to balance virulence using an RNA regulator.

ATP-binding cassette transporter subfamily G member 2 (ABCG2) is a membrane-bound transporter responsible for the efflux of various xenobiotics and endobiotics, including protoporphyrin IX (PPIX), an intermediate in the heme biosynthesis pathway. Certain genetic mutations and chemicals impair the conversion of PPIX to heme and/or increase PPIX production, leading to PPIX accumulation and toxicity. In mice, deficiency of ABCG2 protects against PPIX-mediated phototoxicity and hepatotoxicity by modulating PPIX distribution. In addition, in vitro studies revealed that ABCG2 inhibition increases the efficacy of PPIX-based photodynamic therapy by retaining PPIX inside target cells. In this review, we discuss the roles of ABCG2 in modulating the tissue distribution of PPIX, PPIX-mediated toxicity, and PPIX-based photodynamic therapy.

The precision medicine initiative has driven a substantial change in the way scientists and health care practitioners think about diagnosing and treating disease. While it has long been recognized that drug response is determined by the intersection of genetic, environmental, and disease factors, improvements in technology have afforded precision medicine guided dosing of drugs to improve efficacy and reduce toxicity. Pharmacometabolomics aims to evaluate small molecule metabolites in plasma and/or urine to help evaluate mechanisms that predict and/or reflect drug efficacy and toxicity. In this mini review, we provide an overview of pharmacometabolomic approaches and methodologies. Relevant examples where metabolomic techniques have been used to better understand drug efficacy and toxicity in major depressive disorder and cancer chemotherapy are discussed. In addition, the utility of metabolomics in drug development and understanding drug metabolism, transport, and pharmacokinetics is reviewed. Pharmacometabolomic approaches can help describe factors mediating drug disposition, efficacy, and toxicity. While important advancements in this area have been made, there remain several challenges that must be overcome before this approach can be fully implemented into clinical drug therapy.

⁹-Tetrahydrocannabinol (THC) is a psychoactive phytocannabinoid found in the Cannabis sativa plant. THC is primarily metabolized into 11-hydroxy-⁹-tetrahydrocannabinol (11-OH-THC) and 11-nor-9-carboxy-⁹-tetrahydrocannabinol (COOH-THC), which may themselves be psychoactive. There is very little research-based evidence concerning the pharmacokinetics and pharmacodynamics of 11-OH-THC as an individual compound. Male C57BL/6 mice were treated with THC or 11-OH-THC via intraperitoneal injection, tail vein intravenous injection, or oral gavage, and whole-blood compound levels were measured to determine pharmacokinetic parameters [C_max, time to C_max (T_max), elimination half-life, area under the curve, apparent volume of distribution, systemic clearance, terminal rate constant, and absolute bioavailability] while also monitoring changes in catalepsy, body temperature, and nociception. 11-OH-THC achieved a T_max at 30 minutes for all routes of administration. The maximum concentration at 30 minutes was not different between intravenous and intraperitoneal routes, but the oral gavage C_max was significantly lower. THC had a 10-minute time to the maximum concentration, which was the first blood collection time point, for intravenous and intraperitoneal and 60 minutes for oral gavage, with a lower C_max for intraperitoneal and oral gavage compared with intravenous. When accounting for circulating compound levels and ED₅₀ responses, these data suggest that 11-OH-THC was 153% as active as THC in the tail-flick test of nociception and 78% as active as THC for catalepsy. Therefore, 11-OH-THC displayed equal or greater activity than the parent compound THC, even when accounting for pharmacokinetic differences. Thus, the THC metabolite 11-OH-THC likely plays a critical role in the bioactivity of cannabis; understanding its activity when administered directly will aid in the interpretation of future animal and human studies.

The phase 3 VISION trial demonstrated that [¹⁷⁷Lu]Lu-PSMA-617 prolonged progression-free survival and overall survival (OS) in prostate-specific membrane antigen [PSMA]–positive metastatic castration-resistant prostate cancer (mCRPC) patients who progressed on taxane-based chemotherapy and androgen receptor–signaling inhibitors (ARSIs). The U.S. expanded-access program (EAP; NCT04825652) was opened to provide access to [¹⁷⁷Lu]Lu-PSMA-617 for eligible patients until regulatory approval was obtained. This study aimed to evaluate the efficacy and safety profile of [¹⁷⁷Lu]Lu-PSMA-617 within the EAP and compare the results with those from the VISION trial. Methods: Patients enrolled in the EAP at 4 institutions in the United States with available toxicity and outcome data were included. Outcome measures included OS, a prostate-specific antigen (PSA) response rate (RR) of at least 50%, and incidences of toxicity according to Common Terminology Criteria for Adverse Events version 5.0. Differences in baseline characteristics, outcome data, and toxicity between the EAP and VISION were evaluated using t testing of proportions and survival analyses. Results: In total, 117 patients with mCRPC who received [¹⁷⁷Lu]Lu-PSMA-617 within the EAP between May 2021 and March 2022 were eligible and included in this analysis. Patients enrolled in the EAP were more heavily pretreated with ARSI (≥2 ARSI regimens: 70% vs. 46%; P < 0.001) and had worse performance status at baseline (Eastern Cooperative Oncology Group score ≥ 2: 19% vs. 7%; P < 0.001) than VISION patients. EAP and VISION patients had similar levels of grade 3 or higher anemia (18% vs. 13%; P = 0.15), thrombocytopenia (13% vs. 8%; P = 0.13), and neutropenia (3% vs. 3%; P = 0.85) and similar PSA RRs (42% vs. 46%; P = 0.50) and OS (median: 15.1 vs. 15.3 mo; P > 0.05). Conclusion: Patients with PSMA-positive mCRPC who received [¹⁷⁷Lu]Lu-PSMA-617 within the EAP were later in their disease trajectory than VISION patients. Patients enrolled in the EAP achieved similar PSA RRs and OS and had a safety profile similar to that of the VISION trial patients.

You might have heard about plans to establish a self‑sustaining city on Mars. Here’s what life would really be like on the Red Planet