Cell wall composition in is media dependent and alters host response, inducing protective immunity.

Introduction: is a basidiomycete fungus that can cause meningoencephalitis, especially in immunocompromised patients. Cryptococcus grows in many different media, although little attention has been paid to the role of growth conditions on the cryptococcal cell wall or on virulence.

Objective: The purpose of this study was to determine how different media influenced the amount of chitin and chitosan in the cell wall, which in turn impacted the cell wall architecture and host response.

Using fimbrin to quantify the endocytic subapical collar during polarized growth in three filamentous fungi.

Filamentous fungi produce specialized cells called hyphae. These cells grow by polarized extension at their apex, which is maintained by the balance of endocytosis and exocytosis at the apex. Although endocytosis has been well characterized in other organisms, the details of endocytosis and its role in maintaining polarity during hyphal growth in filamentous fungi is comparatively sparsely studied.

The conidial coin toss: A polarized conidial adhesive in Colletotrichum graminicola.

Colletotrichum graminicola is an economically significant fungal pathogen of maize. The primary infective conidia of the fungus, falcate conidia, are splash-dispersed during rain events. The adhesion of the falcate conidia triggers germination and is required for the development of infection structures.

The Antidepressant Sertraline Induces the Formation of Supersized Lipid Droplets in the Human Pathogen .

The prevalence and increasing incidence of fungal infections globally is a significant worldwide health problem. Cryptococcosis, primarily caused by the pathogenic yeast , is responsible for approximately 181,000 estimated deaths annually. The scarcity of treatments and the increasing resistance to current therapeutics highlight the need for the development of antifungal agents which have novel mechanisms of action and are suitable for clinical use.

Success and failures of telehealth during COVID-19 should inform digital applications to combat obesity.

Background: In response to the COVID-19 pandemic, telehealth digital applications (apps) permitted the delivery of health care to millions of individuals, including those with poor access to health services.

Aim: To review a body of evidence demonstrating that telehealth and mobile health (mHealth) apps can promote clinically meaningful weight loss, and thus hold potential to increase access to treatment and weight loss care for individuals suffering from obesity.

Results: Data from COVID-19 pandemic revealed that access to telehealth and mHealth remains a challenge for underserved communities that are disproportionately affected by obesity.

Weight Cycling Increases Longevity Compared with Sustained Obesity in Mice.

Objective: Despite the known health benefits of weight loss among persons with obesity, observational studies have reported that cycles of weight loss and regain, or weight cycling, are associated with increased mortality. To study whether weight loss must be sustained to achieve health and longevity benefits, we performed a randomized controlled feeding study of weight cycling in mice.

Methods: In early adult life, obese mice were randomized to ad libitum feeding to sustain obesity, calorie restriction to achieve a "normal" or intermediate body weight, or weight cycling (repeated episodes of calorie restriction and ad libitum refeeding).

Central effects of insulin detemir on feeding, body weight, and metabolism in rats.

Insulin detemir (DET) is a basal insulin analog that, in contrast to other long-acting forms of insulin, has significant weight-gain-sparing effects in diabetic patients. We hypothesized that this effect of DET may be due to its enhanced catabolic action in the central nervous system. We investigated the long-term effects of single third ventricular (3V) microinjections of equimolar doses of DET and regular insulin in normal male rats on feeding, body weight, energy expenditure (EE), and respiratory quotient (RQ).

Anthony Sclafani: Consummate scientist.

In this article we review the scientific contributions of Anthony Sclafani, with specific emphasis on his early work on the neural substrate of the ventromedial hypothalamic (VMH) hyperphagia-obesity syndrome, and on the development of diet-induced obesity (DIO). Over a period of 20 years Sclafani systematically investigated the neuroanatomical basis of the VMH hyperphagia-obesity syndrome, and ultimately identified a longitudinal oxytocin-containing neural tract contributing to its expression. This tract has since been implicated in mediating the effects of at least two gastrointestinal satiety factors.

Sugar-induced cephalic-phase insulin release is mediated by a T1r2+T1r3-independent taste transduction pathway in mice.

Sensory stimulation from foods elicits cephalic phase responses, which facilitate digestion and nutrient assimilation. One such response, cephalic-phase insulin release (CPIR), enhances glucose tolerance. Little is known about the chemosensory mechanisms that activate CPIR.

Weight-sparing effect of insulin detemir: a consequence of central nervous system-mediated reduced energy intake?

Insulin therapy is often associated with adverse weight gain. This is attributable, at least in part, to changes in energy balance and insulin's anabolic effects. Adverse weight gain increases the risk of poor macrovascular outcomes in people with diabetes and should therefore be mitigated if possible.

A retrospective analysis of RET translocation, gene copy number gain and expression in NSCLC patients treated with vandetanib in four randomized Phase III studies.

Background: To determine the prevalence of RET rearrangement genes, RET copy number gains and expression in tumor samples from four Phase III non-small-cell lung cancer (NSCLC) trials of vandetanib, a selective inhibitor of VEGFR, RET and EGFR signaling, and to determine any association with outcome to vandetanib treatment.

Methods: Archival tumor samples from the ZODIAC ( NCT00312377 , vandetanib ± docetaxel), ZEAL ( NCT00418886 , vandetanib ± pemetrexed), ZEPHYR ( NCT00404924 , vandetanib vs placebo) and ZEST ( NCT00364351 , vandetanib vs erlotinib) studies were evaluated by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) in 944 and 1102 patients.

Results: The prevalence of RET rearrangements by FISH was 0.

Metabolic vs. hedonic obesity: a conceptual distinction and its clinical implications.

Body weight is determined via both metabolic and hedonic mechanisms. Metabolic regulation of body weight centres around the 'body weight set point', which is programmed by energy balance circuitry in the hypothalamus and other specific brain regions. The metabolic body weight set point has a genetic basis, but exposure to an obesogenic environment may elicit allostatic responses and upward drift of the set point, leading to a higher maintained body weight.

Phase I study of vandetanib with radiation therapy with or without cisplatin in locally advanced head and neck squamous cell carcinoma.

Background: Vandetanib, added to cisplatin and radiation therapy (RT) overcomes chemoradiation therapy (CRT) and epidermal growth factor receptor (EGFR) inhibitor resistance in head and neck squamous cell carcinoma (HNSCC) lines and models.

Methods: Patients with previously untreated HNSCC received vandetanib daily for 14 days (starting dose 100 mg) and then vandetanib + RT (2.2 Gy/day, 5 days/week) for 6 weeks (regimen 1) or vandetanib + RT (2 Gy/day, 5 days/week) + cisplatin (30 mg/m(2) weekly) for 7 weeks (regimen 2).

Using Caenorhabditis elegans as a Model for Obesity Pharmacology Development.

The Caenorhabditis elegans model is a rapid and inexpensive method to address pharmacologic questions. We describe the use of C. elegans to explore 2 pharmacologic questions concerning candidate antiobesity drugs and illustrate its potential usefulness in pharmacologic research: (1) to determine a ratio of betahistine-olanzapine that blocks the olanzapine-induced intestinal fat deposition (IFD) as detected by Nile red staining and (2) to identify the mechanism of action of a pharmaceutical candidate AB-101 that reduces IFD.

Spexin is a novel human peptide that reduces adipocyte uptake of long chain fatty acids and causes weight loss in rodents with diet-induced obesity.

Objective: Microarray studies identified Ch12:orf39 (Spexin) as the most down-regulated gene in obese human fat. Therefore, we examined its role in obesity pathogenesis.

Methods: Spexin effects on food intake, meal patterns, body weight, respiratory exchange ratio (RER), and locomotor activity were monitored electronically in C57BL/6J mice or Wistar rats with diet-induced obesity (DIO).

Note: ion source design for ion trap systems.

A small plasma (glow discharge) based ion source and circuit are described in this work. The ion source works by producing a high voltage pulsed discharge between two electrodes in a pressure range of 50-100 mTorr. A third mesh electrode is used for ion extraction.

Characterization system for research on energy storage capacitors.

In this work a characterization system for high energy-density capacitors is described and demonstrated. Capacitors are being designed using thin-film technology in an attempt to achieve higher energy-density levels by operating the devices at a high voltage. These devices are fabricated from layers of 100 nm aluminum and a layer of polyvinylidene fluoride-hexafluoropropylene on a polyethylene naphthalate plastic substrate.

Dietary components in the development of leptin resistance.

Classically, leptin resistance has been associated with increased body fat and circulating leptin levels, and the condition is believed to contribute to the onset and/or maintenance of obesity. Although a great deal is known about the central nervous system mechanisms mediating leptin resistance, considerably less is known about the role of diet in establishing and maintaining this altered hormonal state. An exciting new finding has recently been published demonstrating the existence of leptin resistance in normal-weight rats with lean leptin levels by feeding them a high-concentration-fructose diet.

Lack of a functional VHL gene product sensitizes renal cell carcinoma cells to the apoptotic effects of the protein synthesis inhibitor verrucarin A.

Verrucarin A (VA) is a small molecule derived from the fungal plant pathogen Myrothecium verrucaria and was identified as a selective inhibitor of clear cell renal cell carcinoma (CCRCC) cell proliferation in a high-throughput screen of a library of naturally occurring small molecules. CCRCC arises as a result of loss-of-function mutations in the von Hippel-Lindau (VHL) gene. Here we show that VA inhibits protein translation initiation culminating in apoptosis through the extrinsic signaling pathway.

Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial.

Purpose: There is no effective therapy for patients with advanced medullary thyroid carcinoma (MTC). Vandetanib, a once-daily oral inhibitor of RET kinase, vascular endothelial growth factor receptor, and epidermal growth factor receptor signaling, has previously shown antitumor activity in a phase II study of patients with advanced hereditary MTC.

Patients And Methods: Patients with advanced MTC were randomly assigned in a 2:1 ratio to receive vandetanib 300 mg/d or placebo.

Vandetanib (100 mg) in patients with locally advanced or metastatic hereditary medullary thyroid cancer.

Purpose: Vandetanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor-2 and epidermal growth factor receptor tyrosine kinases that also inhibits rearranged during transfection kinase activity. Vandetanib (300 mg/d) has previously demonstrated antitumor activity in patients with advanced hereditary medullary thyroid cancer (MTC). This study investigated the efficacy and safety of 100 mg/d vandetanib in patients with advanced hereditary MTC.

Vandetanib for the treatment of patients with locally advanced or metastatic hereditary medullary thyroid cancer.

PURPOSE There is no effective therapy for patients with distant metastasis of medullary thyroid carcinoma (MTC). Activating mutations in the RET proto-oncogene cause hereditary MTC, which provides a strong therapeutic rationale for targeting RET kinase activity. This open-label, phase II study assessed the efficacy of vandetanib, a selective oral inhibitor of RET, vascular endothelial growth factor receptor, and epidermal growth factor receptor signaling, in patients with advanced hereditary MTC.

In vivo MRI evaluation of anabolic steroid precursor growth effects in a guinea pig model.

Anabolic steroids are widely used to increase skeletal muscle (SM) mass and improve physical performance. Some dietary supplements also include potent steroid precursors or active steroid analogs such as nandrolone. Our previous study reported the anabolic steroid effects on SM in a castrated guinea pig model with SM measured using a highly quantitative magnetic resonance imaging (MRI) protocol.

Randomized phase II study of vandetanib alone or with paclitaxel and carboplatin as first-line treatment for advanced non-small-cell lung cancer.

Purpose: Vandetanib is a once-daily, oral inhibitor of vascular endothelial growth factor receptor and epidermal growth factor receptor signaling. The antitumor activity of vandetanib monotherapy or vandetanib with paclitaxel and carboplatin (VPC) was compared with paclitaxel and carboplatin (PC) in previously untreated patients with non-small-cell lung cancer (NSCLC).

Patients And Methods: All NSCLC histologies and previously treated CNS metastases were permitted in this partially blinded, placebo-controlled, randomized phase II study.