Publications by authors named "John Haley"

S-adenosylmethionine (SAM), produced by SAM synthases, is critical for various cellular regulatory pathways and the synthesis of diverse metabolites. Studies have often equated the effects of knocking down one synthase with broader SAM-dependent outcomes such as histone methylation or phosphatidylcholine (PC) production. Humans and many other organisms express multiple SAM synthases.

View Article and Find Full Text PDF
Article Synopsis
  • The text serves as a notice indicating a correction to a previously published article.
  • It references a specific Digital Object Identifier (DOI), which is a unique alphanumeric string used to identify the article and provide a permanent link to its online location.
  • Readers interested in the original article are directed to the DOI for further context on the corrections made.
View Article and Find Full Text PDF

Activating mutations in the epidermal growth factor receptor (EGFR) promote ligand-independent signaling; however, the mechanisms involved are poorly defined, and it is unknown whether this generates specific vulnerabilities. We previously observed robust expression of protein kinase Cα (PKCα) in lung adenocarcinoma (LUAD) with mutant EGFR (mEGFR), which, unlike the activation of PKCα, is independent of mEGFR activity. Here, we identify a critical role for PKCα in anchorage-independent growth and survival of lung cancer cells with mEGFR.

View Article and Find Full Text PDF

Brown adipose tissue (BAT) engages futile fatty acid synthesis-oxidation cycling, the purpose of which has remained elusive. Here, we show that ATP-citrate lyase (ACLY), which generates acetyl-CoA for fatty acid synthesis, promotes thermogenesis by mitigating metabolic stress. Without ACLY, BAT overloads the tricarboxylic acid cycle, activates the integrated stress response (ISR) and suppresses thermogenesis.

View Article and Find Full Text PDF

Diabetic kidney disease (DKD) is the main cause of chronic kidney disease worldwide. While injury to the podocytes, visceral epithelial cells that comprise the glomerular filtration barrier, drives albuminuria, proximal tubule (PT) dysfunction is the critical mediator of DKD progression. Here, we report that the podocyte-specific induction of human KLF6, a zinc-finger binding transcription factor, attenuates podocyte loss, PT dysfunction, and eventual interstitial fibrosis in a male murine model of DKD.

View Article and Find Full Text PDF

Oxidative phosphorylation is an essential metabolic process for cancer proliferation and therapy resistance. The ClpXP complex maintains mitochondrial proteostasis by degrading misfolded proteins. Madera Therapeutics has developed a class of highly potent and selective small-molecule activators (TR compounds) of the ClpXP component caseinolytic peptidase proteolytic subunit (ClpP).

View Article and Find Full Text PDF

Removing pesticides from biological drinking water filters is challenging due to the difficulty in activating pesticide-degrading bacteria within the filters. Bioaugmented bacteria can alter the filter's microbiome, affecting its performance either positively or negatively, depending on the bacteria used and their interaction with native microbes. We demonstrate that adding specific bacteria strains can effectively remove recalcitrant pesticides, like metaldehyde, yielding compliance to regulatory standards for an extended period.

View Article and Find Full Text PDF
Article Synopsis
  • * A pilot study tested a decision-support training intervention called ImPart, focusing on communication and planning between CKD patients and their caregivers through a series of telephone sessions.
  • * The intervention received positive feedback, highlighting three main areas of impact: improved disease communication, better future planning, and strengthened coaching relationships, indicating its potential effectiveness for broader use.
View Article and Find Full Text PDF

Although acute inflammation serves essential functions in maintaining tissue homeostasis, chronic inflammation is causally linked to many diseases. Macrophages are a major cell type that orchestrates inflammatory processes. During inflammation, macrophages undergo polarization and activation, thereby mobilizing pro-inflammatory and anti-inflammatory transcriptional programs that regulate ensuing macrophage functions.

View Article and Find Full Text PDF

Ocean acidification (OA) is recognized as a major stressor for a broad range of marine organisms, particularly shell-building invertebrates. OA can cause alterations in various physiological processes such as growth and metabolism, although its effect on host-pathogen interactions remains largely unexplored. In this study, we used transcriptomics, proteomics, and physiological assays to evaluate changes in immunity of the eastern oyster Crassostrea virginica exposed to OA conditions (pH = 7.

View Article and Find Full Text PDF

The timing of transcription and replication must be carefully regulated for heavily-transcribed genomes of double-stranded DNA viruses: transcription of immediate early/early genes must decline as replication ramps up from the same genome-ensuring efficient and timely replication of viral genomes followed by their packaging by structural proteins. To understand how the prototypic DNA virus Epstein-Barr virus tackles the logistical challenge of switching from transcription to DNA replication, we examined the proteome at viral replication forks. Specifically, to transition from transcription, the viral DNA polymerase-processivity factor EA-D is SUMOylated by the epigenetic regulator and E3 SUMO-ligase KAP1/TRIM28.

View Article and Find Full Text PDF

Sphingosine kinase 1 (SK1) is a key sphingolipid enzyme that is upregulated in several types of cancer, including lymphoma which is a heterogenous group of malignancies. Treatment for lymphoma has improved significantly by the introduction of new therapies; however, subtypes with tumor protein P53 (p53) mutations or deletion have poor prognosis, making it critical to explore new therapeutic strategies in this context. SK1 has been proposed as a therapeutic target in different types of cancer; however, the effect of targeting SK1 in cancers with p53 deletion has not been evaluated yet.

View Article and Find Full Text PDF

Background: While acute inflammation serves essential functions in maintaining tissue homeostasis, chronic inflammation is causally linked to many diseases. Macrophages are a major cell-type that orchestrates inflammatory processes. During inflammation, macrophages undergo polarization and activation, thereby mobilizing pro-inflammatory and anti-inflammatory transcriptional programs that regulate ensuing macrophage functions.

View Article and Find Full Text PDF

Nonshivering thermogenesis by brown adipose tissue (BAT) is an adaptive mechanism for maintaining body temperature in cold environments. BAT is critical in rodents and human infants and has substantial influence on adult human metabolism. Stimulating BAT therapeutically is also being investigated as a strategy against metabolic diseases because of its ability to function as a catabolic sink.

View Article and Find Full Text PDF
Article Synopsis
  • The study aims to assess the time Pathologists' Assistants (PAs) take to gross second and third trimester singleton placentas, highlighting the importance of this data for workload management in pathology labs.
  • Seven certified PAs grossed at least 10 placenta specimens each using a standard protocol, with the results showing average grossing times ranging from 11.0 to 17.8 minutes, ultimately leading to an overall average of 14.5 minutes.
  • The analysis revealed that more blocks prepared by PAs correlated with longer grossing times, suggesting a potential prediction model where consistently preparing four blocks might lower the average grossing time to approximately 13.3 minutes.
View Article and Find Full Text PDF

Ceramides impact a diverse array of biological functions and have been implicated in disease pathogenesis. The enzyme neutral ceramidase (nCDase) is a zinc-containing hydrolase and mediates the metabolism of ceramide to sphingosine (Sph), both in cells and in the intestinal lumen. nCDase inhibitors based on substrate mimetics, for example C6-urea ceramide, have limited potency, aqueous solubility, and micelle-free fraction.

View Article and Find Full Text PDF

Receptor tyrosine kinases (RTKs) can show extensive crosstalk, directly and indirectly. Elucidating RTK crosstalk remains an important goal in the clinical combination of anti-cancer therapies. Here, we present mass spectrometry and pharmacological approaches showing the hepatocyte growth factor receptor (MET)-promoting tyrosine phosphorylation of the epidermal growth factor receptor (EGFR) and other membrane receptors in MET-amplified H1993 NSCLC cells.

View Article and Find Full Text PDF

Adaptive thermogenesis by brown adipose tissue (BAT) dissipates calories as heat, making it an attractive anti-obesity target. Yet how BAT contributes to circulating metabolite exchange remains unclear. Here, we quantified metabolite exchange in BAT and skeletal muscle by arteriovenous metabolomics during cold exposure in fed male mice.

View Article and Find Full Text PDF

Bruton's tyrosine kinase (BTK) is a target for treating B-cell malignancies and autoimmune diseases, and several BTK inhibitors are already approved for use in humans. Heterobivalent BTK protein degraders are also in development, based on the premise that proteolysis targeting chimeras (PROTACs) may provide additional therapeutic benefits. However, most BTK PROTACs are based on the BTK inhibitor ibrutinib raising concerns about their selectivity profiles, given the known off-target effects of ibrutinib.

View Article and Find Full Text PDF

Phosphate dosing is the principle strategy used in the United Kingdom to reduce the concentration of lead in tap waters supplied by lead water pipes. The mechanisms of phosphate-mediated lead control are not fully understood, but solid solutions of lead calcium apatite are thought to play an important role. This study investigated the microstructure of a lead pipe, supplied with high-alkalinity tap water, in which the lead calcium apatite crystals were spherulitic having rounded and dumb-bell-shaped morphologies.

View Article and Find Full Text PDF

Lung cancer is the leading cause of cancer-related deaths in the United States with non-small cell lung cancer (NSCLC) accounting for most cases. Despite advances in cancer therapeutics, the 5-year survival rate has remained poor due to several contributing factors, including its resistance to therapeutics. Therefore, there is a pressing need to develop therapeutics that can overcome resistance.

View Article and Find Full Text PDF
Article Synopsis
  • Ocean acidification (OA) is expected to significantly reduce seawater pH and carbonate saturation by the end of the century, threatening marine organisms like the northern quahog clam.
  • This study investigated how clams adapt to OA by examining their hemolymph and extrapallial fluid (EPF) under acidified conditions compared to normal ones for one year.
  • Results showed clams can increase the pH and calcium levels in their bodily fluids and upregulate genes related to biomineralization and acid-base balance, indicating their capability to cope with OA effects.
View Article and Find Full Text PDF

Drawing on data provided by 803 Methodist circuit ministers serving in Great Britain, the present study was designed to test the association between conservative Christian belief and work-related psychological wellbeing as operationalised by the balanced affect model proposed by the Francis Burnout Inventory. After taking into account the effects of personal factors, psychological factors, contextual factors, and experience factors, holding conservative Christian belief was associated with a higher level of positive affect (satisfaction in ministry) but independent of negative affect (emotional exhaustion in ministry).

View Article and Find Full Text PDF

Mechanistic target of rapamycin (mTOR) complex 2 (mTORC2) regulates metabolism, cell proliferation, and cell survival. mTORC2 activity is stimulated by growth factors, and it phosphorylates the hydrophobic motif site of the AGC kinases AKT, SGK, and PKC. However, the proteins that interact with mTORC2 to control its activity and localization remain poorly defined.

View Article and Find Full Text PDF

A PHP Error was encountered

Severity: Warning

Message: fopen(/var/lib/php/sessions/ci_sessioncokens6sohimd67oosdjdctb7ihhhrkm): Failed to open stream: No space left on device

Filename: drivers/Session_files_driver.php

Line Number: 177

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: session_start(): Failed to read session data: user (path: /var/lib/php/sessions)

Filename: Session/Session.php

Line Number: 137

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once