Idelalisib, a phosphoinositide 3-kinase delta (PI3Kδ) inhibitor, effectively treats relapsed chronic lymphocytic leukemia (CLL). While this targeted approach offers a therapeutic edge, particularly in B-cell malignancies, it is associated with complications such as pneumonitis. This report details idelalisib-induced pneumonitis, highlighting the importance of early diagnosis and tailored treatment in achieving a favorable patient outcome.
View Article and Find Full Text PDFSpatial memory encoding depends in part on cholinergic modulation. How acetylcholine supports spatial memory encoding is not well understood. Prior studies indicate that acetylcholine release is correlated with exploration, including epochs of rearing onto hind legs.
View Article and Find Full Text PDFSpatial memory encoding depends in part on cholinergic modulation. How acetylcholine supports spatial memory encoding is not well understood. Prior studies indicate that acetylcholine release is correlated with exploration, including epochs of rearing onto hind legs.
View Article and Find Full Text PDFBackground: Recent advances in circulating cell-free DNA (cfDNA) analysis from biofluids have opened new avenues for liquid biopsy (LB). However, current cfDNA LB assays are limited by the availability of existing information on established genotypes associated with tumor tissues. Certain cancers present with a limited list of established mutated cfDNA biomarkers, and thus, nonmutated cfDNA characteristics along with alternative biofluids are needed to broaden the available cfDNA targets for cancer detection.
View Article and Find Full Text PDFBackground: Recent advances in circulating cell-free DNA (cfDNA) analysis from biofluids have opened new avenues for liquid biopsy (LB). However, current cfDNA LB assays are limited by the availability of existing information on established genotypes associated with tumor tissues. Certain cancers present with a limited list of established mutated cfDNA biomarkers, and thus, nonmutated cfDNA characteristics along with alternative biofluids are needed to broaden the available cfDNA targets for cancer detection.
View Article and Find Full Text PDFDespite the recent precipitous decline in the cost of genome sequencing, library preparation for RNA-seq is still laborious and expensive for applications such as high throughput screening. Limited availability of RNA generated by some experimental workflows poses an additional challenge and increases the cost of RNA library preparation. In a search for low cost, automation-compatible RNA library preparation kits that maintain strand specificity and are amenable to low input RNA quantities, we systematically tested two recent commercial technologies-Swift RNA and Swift Rapid RNA, presently offered by Integrated DNA Technologies (IDT) -alongside the Illumina TruSeq stranded mRNA, the de facto standard workflow for bulk transcriptomics.
View Article and Find Full Text PDFSirtuin 1 (Sirt1) is an NAD-dependent class III deacetylase that functions as a cellular energy sensor. In addition to its well-characterized effects in peripheral tissues, evidence suggests that SIRT1 in neurons plays a role in the central regulation of energy balance and reproduction, but no studies have addressed the contribution of astrocytes. We show here that overexpression of SIRT1 in astrocytes causes markedly increased food intake, body weight gain, and glucose intolerance, but expression of a deacetylase-deficient SIRT1 mutant decreases food intake and body weight and improves glucose tolerance, particularly in female mice.
View Article and Find Full Text PDFSirt1 is an NAD-dependent, class III deacetylase that functions as a cellular energy sensor. In addition to its well-characterized effects in peripheral tissues, emerging evidence suggests that neuronal Sirt1 activity plays a role in the central regulation of energy balance and glucose metabolism. In this study, we generated mice expressing an enzymatically inactive form (-MUT) or wild-type (WT) SIRT1 (-OX) in mature neurons.
View Article and Find Full Text PDFHuman cleft lip with or without cleft palate (CL/P) is a common craniofacial abnormality caused by impaired fusion of the facial prominences. We have previously reported that, in the mouse embryo, epithelial apoptosis mediates fusion at the seam where the prominences coalesce. Here, we show that apoptosis alone is not sufficient to remove the epithelial layers.
View Article and Find Full Text PDFRobustness to perturbation is a fundamental feature of complex organisms. Mutations are the raw material for evolution, yet robustness to their effects is required for species survival. The mechanisms that produce robustness are poorly understood.
View Article and Find Full Text PDFJ Pharmacol Exp Ther
October 2017
The increasing availability of prescription opioid analgesics for the treatment of pain has been paralleled by an epidemic of opioid misuse, diversion, and overdose. The development of abuse-deterrent formulations (ADFs) of conventional opioids such as oxycodone and morphine represents an advance in the field and has had a positive but insufficient impact, as most opioids are still prescribed in highly abusable, non-ADF forms, and abusers can tamper with ADF medications to liberate the abusable opioid within. The abuse liability of mu-opioid agonists appears to be dependent on their rapid rate of entry into the central nervous system (CNS), whereas analgesic activity appears to be a function of CNS exposure alone, suggesting that a new opioid agonist with an inherently low rate of influx across the blood-brain barrier could mediate analgesia with low abuse liability, regardless of formulation or route of administration.
View Article and Find Full Text PDFThis paper presents a case demonstrating repair of traumatic macular hole and submacular hemorrhage with intravitreal gas tamponade and t-PA in an office setting.
View Article and Find Full Text PDFMouse models provide valuable opportunities for probing the underlying pathology of human birth defects. By using an N-ethyl-N-nitrosourea-based screen for recessive mutations affecting craniofacial anatomy, we isolated a mouse strain, Dogface-like (DL), with abnormal skull and snout morphology. Examination of the skull indicated that these mice developed craniosynostosis of the lambdoid suture.
View Article and Find Full Text PDFEpidermal development and differentiation are tightly controlled processes that culminate in the formation of the epidermal barrier. A critical regulator of different stages of epidermal development and differentiation is the transcription factor p63. More specifically, we previously demonstrated elsewhere that p63 is required for both the commitment to stratification and the commitment to terminal differentiation.
View Article and Find Full Text PDFAdult rats and mice born to dams exposed to alcohol (fetal alcohol-exposed [FAE]) exhibit enhanced activity of their hypothalamic-pituitary-adrenal (HPA) axis when exposed to stressors. However, the mechanisms responsible for this phenomenon remain incompletely understood. Here two possibilities are reviewed: one that pertains to nitric oxide (NO), an unstable gas that stimulates the HPA axis; and one that focuses on catecholamines, which also stimulate this axis.
View Article and Find Full Text PDFTetracycline (tet) resistance in Campylobacter isolated from organically raised broilers was investigated in this study. Two hundred forty-five samples from an organic broiler farm were collected weekly from the first week to the end of the production cycle, and they were cultured for thermophilic Campylobacter. Tetracycline resistance of these Campylobacter isolates was identified by the agar dilution method, whereas DNA fingerprinting profiles of tet-susceptible and tet-resistant strains were determined by pulsed-field gel electrophoresis (PFGE).
View Article and Find Full Text PDFRohon-Beard mechanosensory neurons (RBs), neural crest cells, and neurogenic placodes arise at the border of the neural- and non-neural ectoderm during anamniote vertebrate development. Neural crest cells require BMP expressing non-neural ectoderm for their induction. To determine if epidermal ectoderm-derived BMP signaling is also involved in the induction of RB sensory neurons, the medial region of the neural plate from donor Xenopus laevis embryos was transplanted into the non-neural ventral ectoderm of host embryos at the same developmental stage.
View Article and Find Full Text PDFBackground: Prenatal ethanol exposure results in a spectrum of cognitive and behavioral deficits and affects an estimated thirteen percent of children born in the United States. The basis of prenatal ethanol-induced impairment of brain function has been widely studied in animal models, where significant changes in the physiological and structural plasticity of hippocampal function have been documented. Here, we explored the possibility that exposure to moderate levels of alcohol in utero might also result in long-lasting impairment of adult hippocampal neurogenesis, a novel form of plasticity that occurs throughout adulthood.
View Article and Find Full Text PDFSpecification of both neural crest cells and Rohon-Beard (RB) sensory neurons involves a complex series of interactions between the neural and non-neural ectoderm. The molecular mechanisms directing this process are not well understood. The zebrafish narrowminded (nrd) mutation is unique, since it is one of two mutations in which defects are observed in both cell populations: it leads to a complete absence of RB neurons and a reduction in neural crest cells and their derivatives.
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