Age of onset of cannabis use and substance use problems: A systematic review of prospective studies.

Background: The association between the age of cannabis use (CU) onset and substance use (SU) problems has been extensively studied, yet findings remain inconsistent.

Aims: This systematic review aimed to examine prospective studies on the association between age of CU onset and later SU problems, controlling for key individual, social, and SU-related risk factors.

Methods: PsycINFO, Web of Science and PubMed were searched for studies published between January 2000 and December 2024.

Clustering-independent estimation of cell abundances in bulk tissues using single-cell RNA-seq data.

Single-cell RNA sequencing has transformed the study of biological tissues by enabling transcriptomic characterizations of their constituent cell states. Computational methods for gene expression deconvolution use this information to infer the cell composition of related tissues profiled at the bulk level. However, current deconvolution methods are restricted to discrete cell types and have limited power to make inferences about continuous cellular processes such as cell differentiation or immune cell activation.

Clustering-independent estimation of cell abundances in bulk tissues using single-cell RNA-seq data.

Single-cell RNA-sequencing has transformed the study of biological tissues by enabling transcriptomic characterizations of their constituent cell states. Computational methods for gene expression deconvolution use this information to infer the cell composition of related tissues profiled at the bulk level. However, current deconvolution methods are restricted to discrete cell types and have limited power to make inferences about continuous cellular processes like cell differentiation or immune cell activation.

Pro-inflammatory cytokines mediate the epithelial-to-mesenchymal-like transition of pediatric posterior fossa ependymoma.

Pediatric ependymoma is a devastating brain cancer marked by its relapsing pattern and lack of effective chemotherapies. This shortage of treatments is due to limited knowledge about ependymoma tumorigenic mechanisms. By means of single-nucleus chromatin accessibility and gene expression profiling of posterior fossa primary tumors and distal metastases, we reveal key transcription factors and enhancers associated with the differentiation of ependymoma tumor cells into tumor-derived cell lineages and their transition into a mesenchymal-like state.

Single-cell transcriptomic analysis of mIHC images via antigen mapping.

Highly multiplexed immunohistochemistry (mIHC) enables the staining and quantification of dozens of antigens in a tissue section with single-cell resolution. However, annotating cell populations that differ little in the profiled antigens or for which the antibody panel does not include specific markers is challenging. To overcome this obstacle, we have developed an approach for enriching mIHC images with single-cell RNA sequencing data, building upon recent experimental procedures for augmenting single-cell transcriptomes with concurrent antigen measurements.

Nutritional factors in sport-related concussion.

Background: Sports concussion is a major problem that affects thousands of people every year. Concussion-related neurometabolic changes are thought to underlie neurophysiological alterations and post-concussion symptoms, such as headaches and sensitivity to light and noise, disabilities of concentration and tiredness. The injury triggers a complex neurometabolic cascade involving multiple mechanisms.

Blood biomarkers of mild traumatic brain injury: State of art.

Background: Mild traumatic brain injury (mTBI) is one of the most common causes of emergency department visits around the world. Up to 90% of injuries are classified as mTBI. Cranial computed tomography (CCT) is a standard diagnosis tool to identify intracranial complications in adults with mTBI.

Why and how are you attached to your social group? Investigating different forms of social identification.

Social identity is a key social psychological variable to understand intergroup behaviours. Over and above the different dimensions of social identity (e.g.

Optimized manual and automated recovery of amplifiable DNA from tissues preserved in buffered formalin and alcohol-based fixative.

Archival tissue preserved in fixative constitutes an invaluable resource for histological examination, molecular diagnostic procedures and for DNA typing analysis in forensic investigations. However, available material is often limited in size and quantity. Moreover, recovery of DNA is often severely compromised by the presence of covalent DNA-protein cross-links generated by formalin, the most prevalent fixative.

NMR assignment of the N-terminal TRAF-like RING zinc finger domain of human FLN29.

Resistance of cancer cells to oncotherapeutics designed to trigger programmed cell death (a.k.a.

Application of human mini-satellite VNTR probes to genotyping in cynomolgus macaques.

Cynomolgus macaques (also known as longtail or crab-eating macaques) Macaca fascicularis, are an important non-human primate model for biomedical research. Using a case study involving a suspected occurrence of twin birth, we demonstrate that the highly polymorphic human variable-number tandem repeat (VNTR) mini-satellite probes D1S7, D2S44, D3S42 and D4S184 can be successfully employed as a rapid screening strategy to complement husbandry records in order to establish genetic relatedness in a captive colony.

Inhibition of mitogen-activated protein kinase phosphatase 3 activity by interdomain binding.

Mitogen-activated protein (MAP) kinase phosphatase 3 (MKP3) is a cytoplasmic dual specificity phosphatase that functions to attenuate signaling via dephosphorylation and subsequent deactivation of its substrate and allosteric regulator, extracellular signal-regulated protein kinase 2 (ERK2). Expression of MKP3 has been shown to be under the control of ERK2, thus providing an elegant feedback mechanism for regulating the rate and duration of proliferative signals. Previously published studies suggest that MKP3 might serve as a tumor suppressor; however, significantly elevated, rather than reduced, levels of this protein have been reported in early lesions.

Cytotoxic doses of ketoconazole affect expression of a subset of hepatic genes.

Ketoconazole is a widely prescribed antifungal drug, which has also been investigated as an anticancer therapy in both clinical and pre-clinical settings. However, severe hepatic injuries were reported to be associated with the use of ketoconazole, even in patients routinely monitored for their liver functions. Several questions concerning ketoconazole-induced hepatic injury remain unanswered, including (1) does ketoconazole alter cytochrome P450 expression at the transcriptional level?, (2) what types of gene products responsible for cytotoxicity are induced by ketoconazole?, and (3) what role do the major metabolites of ketoconazole play in this pathophysiologic process? A mouse model was employed to investigate hepatic gene expression following hepatotoxic doses of ketoconazole.

Accurate determination of zygosity in transgenic rice by real-time PCR does not require standard curves or efficiency correction.

A number of quantitative, real-time PCR methods have been developed for determining transgene copy numbers in plants. Here, we demonstrate that the Roche LightCycler system can be used to determine the zygosity of transgenic lines without the use of standard curves or efficiency correction calculations. We have developed a duplex PCR assay which permits the determination of zygosity, relative to a calibrator sample, in transgenic rice lines containing the gene for a viral glycoprotein.

Differential regulation of the lung endothelin system by urban particulate matter and ozone.

Periodic elevation of ambient particulate matter and ozone levels is linked to acute cardiac morbidity and mortality. Increased plasma levels of the potent vasoconstrictor endothelin (ET)-1, a prognostic indicator of cardiac mortality, have been detected in both animal models and humans after exposure to air pollutants. The lungs are the primary source of circulating ET-1, but the direct effects of individual air pollutants and their interaction in modulating the pulmonary endothelin system are unknown.

Poly(ADP-ribosyl)ated chromatin domains: access granted.

The seemingly static architecture of interphase and mitotic chromatin betrays an otherwise elegantly dynamic entity capable of remodelling itself to facilitate DNA replication, transcription, repair and recombination. Remodelling of local chromatin domains in response to physiological cues proceeds, at least in part, through transient cycles of relaxation and condensation that require use of histone variants and post-translational modifications of histones. Studies have connected poly(ADP-ribosyl)ation of histones with virtually every aspect of DNA metabolism and function over the years, most notably with the response to DNA damage, where convincing evidence supports its essential role granting repair machinery access to damaged DNA.

The mixed lineage kinase DLK is oligomerized by tissue transglutaminase during apoptosis.

Current evidence suggests that the mixed lineage kinase family member dual leucine zipper-bearing kinase (DLK) might play a significant role in the regulation of cell growth and differentiation, particularly during the process of tissue remodeling. To further explore this working model, we have investigated the regulation of host and recombinant DLK in NIH3T3 and COS-1 cells undergoing apoptosis. Using calphostin C, a potent and selective inhibitor of protein kinase C and a recognized apoptosis inducer for various cell types, we demonstrate, by immunoblot analysis, that DLK protein levels are rapidly and dramatically down-regulated during the early phases of apoptosis.

p53 status, cellular recovery and cell cycle arrest as prognosticators of in vitro radiosensitivity in human pancreatic adenocarcinoma cell lines.

Purpose: To investigate the factors contributing to the in vitro radiosensitivity of four human pancreatic adenocarcinoma cell lines differing in p53 status, and the basis for the lack of post-irradiation G1 arrest in the two cell lines that have retained a wild-type p53 allele.

Materials And Methods: Cells were X-irradiated and the parameters related to radiosensitivity, as well as the modulation of gene products linked to regulation of cell cycle transit (p53, p21/WAF1/CIP1, pRb) or DNA replication and repair (DNA topoisomerase I and II), were determined.

Results: Both cell lines expressing either mutant (mt) R248W or R273H p53 proteins were more radioresistant.

Inhibitory and stimulatory effects of somatostatin on two human pancreatic cancer cell lines: a primary role for tyrosine phosphatase SHP-1.

Somatostatin (SS-14) and its structural analogue SMS 201-995 (SMS) are recognized as physiological inhibitors of multiple organs and tissue functions through specific membrane receptors (sst1-sst5). The effects of SS-14 and SMS in the growth control of the pancreatic cancer cell lines MIA PaCa-2 and PANC-1 were investigated to identify and clarify the intracellular events involved. In PANC-1 cells, SS-14 and SMS caused inhibition of their basal growth, and that stimulated by epidermal growth factor, with a maximal effect at 0.

DNA topoisomerase I content of a pair of human melanoma cell lines with very different radiosensitivities correlates with their in vitro sensitivities to camptothecin.

In this study, we set out to determine if the differential sensitivities to CPT between a radioresistant (Sk-Mel-3) and a radiosensitive (HT-144) human melanoma cell line, and also between cultures with a different growth phase in each cell line, were related to endogenous differences in cellular transport of CPT or to DNA topo I catalytic activities and content. Cultures of HT-144 and Sk-Mel-3 cells in both the exponential, or plateau (i.e.

Interlaboratory comparison of autoradiographic DNA profiling measurements: precision and concordance.

Knowledge of the expected uncertainty in restriction fragment length polymorphism (RFLP) measurements is required for confident exchange of such data among different laboratories. The total measurement uncertainty among all Technical Working Group for DNA Analysis Methods laboratories has previously been characterized and found to be acceptably small. Casework cell line control measurements provided by six Royal Canadian Mounted Police (RCMP) and 30 U.

Pharmacological and biochemical evidence for the regulation of osteocalcin secretion by potassium channels in human osteoblast-like MG-63 cells.

Previous reports have suggested the involvement of voltage-activated calcium (Ca2+) channels in bone metabolism and in particular on the secretion of osteocalcin by osteoblast-like cells. We now report that potassium (K+) channels can also modulate the secretion of osteocalcin by MG-63 cells, a human osteosarcoma cell line. When 1,25-dihydroxyvitamin D3(1,25(OH)2D3)-treated MG-63 cells were depolarized by step increases of the extracellular K+ concentration ([K+]out) from 5-30 mM, osteocalcin (OC) secretion increased from a control value of 218 +/- 13 to 369 +/- 18 ng/mg of protein/48 h (p < 0.

Ensuring recovery of intact RNA from rat pancreas.

The isolation of intact RNA from rat pancreas is compromised by autolysis and by the presence of endogenous ribonucleases. In order to ameliorate recovery we systematically investigated available RNA extraction methods and paid particular attention to the influence of frozen storage and ribonuclease inhibition strategies on overall yield and quality of RNA. Modifications to the basic procedure of Chomczynski and Sacchi (1987) are described which allow, reproducibly, to obtain rat pancreatic RNA suitable for Northern blot hybridization, RT-PCR, and differential display analysis.

Selective effect of thiazides on the human osteoblast-like cell line MG-63.

Thiazide diuretics have been shown to decrease bone-loss rate and to improve bone mineral density in patients using this medication. However, the exact role of thiazides on bone cells is still debated. In the present work, we studied whether thiazides could affect the normal features of osteoblasts using the human model cell line MG-63.