A review of HER2 overexpression and somatic mutations in cancers.

The Human Epidermal Growth Factor Receptor (HER) proteins family, which includes HER2, are membrane-bound receptors that activate many intracellular pathways associated with growth and development. When there are mutations in HER2, or when it becomes overexpressed, it can cause oncogenesis and offer differential prognosis and treatment across almost all cancer types. Both mutations in HER2 and its overexpression have distinct mechanisms by which they can cause these effects in cancers. This review outlines how HER2's normal pathway is altered in both overexpression and mutation and compiles all the well-known mechanisms by which HER2 can cause oncogenesis. Finally, this review briefly outlines how HER2 mutants and HER2 overexpression is detected, and how their detection can lead to different prognosis and treatment in cancers.

An accurate wearable hydration sensor: Real-world evaluation of practical use.

A wearable body hydration sensor employing photoplethysmographic and galvanic biosensors was field evaluated using 240 human participants with equal numbers of men and women volunteers. Monitoring of water mass loss due to perspiration was performed by medical balance measurements following one of two different treadmill physical exercise regimens over 90 minutes in 15-minute intervals with intervening 10-minute rest periods. Participants wore two different models of the dehydration body monitor device mated to commercially-available smartwatches (Samsung Gear S2 and Samsung Gear Fit2). Device output was recorded by Bluetooth wireless link to a standard smartphone in 20-second blocks. Comparison of the devices with the standard measurement method (change in body mass measured by medical balance) indicated very close agreement between changes in body water mass and device output (percent normalized mean root square error averaged approximately 2% for all participants). Bland-Altman analyses of method agreement indicated that <5% of participant values fell outside of the 95% confidence interval limits of agreement and all measured value differences were normally distributed around the line of equality. The results of this first-ever field trial of a practical, wearable hydration monitor suggests that this device will be a reliable tool to aid in geriatric hydration monitoring and physical training scenarios.

Gut microbiota determines the social behavior of mice and induces metabolic and inflammatory changes in their adipose tissue.

The link between the gut microbiota and social behavior has been demonstrated, however the translational impact of a certain microbiota composition on stable behavioral patterns is yet to be elucidated. Here we employed an established social behavior mouse model of dominance (Dom) or submissiveness (Sub). A comprehensive 16S rRNA gene sequence analysis of Dom and Sub mice revealed a significantly different gut microbiota composition that clearly distinguishes between the two behavioral modes. Sub mice gut microbiota is significantly less diverse than that of Dom mice, and their taxa composition uniquely comprised the genera Mycoplasma and Anaeroplasma of the Tenericutes phylum, in addition to the Rikenellaceae and Clostridiaceae families. Conversely, the gut microbiota of Dom mice includes the genus Prevotella of the Bacteriodetes phylum, significantly less abundant in Sub mice. In addition, Sub mice show lower body weight from the age of 2 weeks and throughout their life span, accompanied with lower epididymis white adipose tissue (eWAT) mass and smaller adipocytes together with substantially elevated expression of inflammation and metabolic-related eWAT adipokines. Finally, fecal microbiota transplantation into germ-free mice show that Sub-transplanted mice acquired Sub microbiota and adopted their behavioral and physiological features, including depressive-like and anti-social behaviors alongside reduced eWAT mass, smaller adipocytes, and a Sub-like eWAT adipokine profile. Our findings demonstrate the critical role of the gut microbiome in determining dominance vs. submissiveness and suggest an association between gut microbiota, the eWAT metabolic and inflammatory profile, and the social behavior mode.

Link between personality and response to THC exposure.

The effects of cannabis reported by users range from experiences of euphoria and anxiolytic effects to paranoia, anxiety, and increased risk of depression. Attempts to reconcile the apparent contradictions in user response have not been conclusive. Here, we utilized selectively-bred stress-resilient socially dominant (Dom) and stress-sensitive socially submissive (Sub) mice to elucidate this contradiction. Following short-term, repeated treatment with delta-9-tetrahydrocannabinol (THC) at two different doses (1.5 mg/kg and 15 mg/kg), Sub mice presented significant place-aversion in a Conditioned Place Preference paradigm at a high dose, whereas Dom mice displayed no place preference or aversion. Forced Swim test conducted after 6-week of washout period, revealed differential impact of the two THC doses depending upon behavioral pattern. Specifically, the low dose alleviated depressive-like behavior in Sub mice, while the high dose produced the opposite effect in Dom mice. Interestingly, corticosterone concentration in serum was elevated at the high dose regardless of the mice-population tested. We conclude here that differences in dominance behavior and stress vulnerability are involved in the regulation of cannabis response among users and should be considered when prescribing THC-containing medications to patients.

Comparative accuracy of optical sensor-based wearable system for non-invasive measurement of blood glucose concentration.

Non-invasive biosensors for indirect evaluation of routinely-measured blood components by sweat analysis have broad potential clinical applications. This trial tested a wrist-borne non-invasive glucose monitor (NIGM) to measure blood glucose (BG) levels using photoplethysmographic (PPG) optical sensors. Our aim was to determine the accuracy of the device in comparison with a standard, invasive clinical method for blood glucose monitoring. Adult participants (n = 200) of both sexes from 18 to 75 were recruited for the study. Exclusion criteria: hemophilia and other serious coagulation disorders, impaired venous access, other serious medical conditions. A biosensor was placed on the right wrist of each participant for a non-invasive indirect BG measurement. In parallel, blood from the antecubital vein was collected and glucose levels were assessed with YSI 2300 Bioanalyzer. The measurements were performed twice: before and after food intake, with a 1-h interval between measurements. There were no limitations to food type and quantity. In both anteprandial (ρ = 0.8994, p < 0.0001) and postprandial (ρ =0.9382, p < 0.0001) glucose measurements, NIGM correlated with values obtained by the YSI 2300 reference device - there was no significant difference between the two methods. Plotted on a Parkes Error Grid for Type II diabetes, NIGM readings did not deviate from those of the YSI 2300 in any clinically-significant way, with the majority of correlated readings falling within Parkes zone A. Very few readings fell within Parkes zone B. In anteprandial measurements, the mean bias between methods for all patient volunteers was 3.705 ±â€¯7.838. In postprandial measurements gave a mean bias of 1.362 ±â€¯10.15 for all patient glucose data. The mean absolute relative difference of currently available glucometer models ranges from 5.6% to 20.8%. The NIGM falls in the lower end of this error range at 7.40-7.54%, indicating that PPG-chemochrome sensors are capable of producing results comparable with those of direct measure glucometers. Data presented here demonstrates the reliability and accuracy of the NIGM system as an adjunctive, and perhaps substitutive, non-invasive tool for blood glucose monitoring.

Yeast red pigment modifies Amyloid beta growth in Alzheimer disease models in both Saccharomyces cerevisiae and Drosophila melanogaster.

The effect of yeast red pigment on amyloid-ß (Aß) aggregation and fibril growth was studied in yeasts, fruit flies and in vitro. Yeast strains accumulating red pigment (red strains) contained less amyloid and had better survival rates compared to isogenic strains without red pigment accumulation (white strains). Confocal and fluorescent microscopy was used to visualise fluorescent Aß-GFP aggregates. Yeast cells containing less red pigment had more Aß-GFP aggregates despite the lower level of overall GFP fluorescence. Western blot analysis with anti-GFP, anti-Aß and A11 antibodies also revealed that red cells contained a considerably lower amount of Aß GFP aggregates as compared to white cells. Similar results were obtained with exogenous red pigment that was able to penetrate yeast cells. In vitro experiments with thioflavine and TEM showed that red pigment effectively decreased Aß fibril growth. Transgenic flies expressing Aß were cultivated on medium containing red and white isogenic yeast strains. Flies cultivated on red strains had a significant decrease in Aß accumulation levels and brain neurodegeneration. They also demonstrated better memory and learning indexes and higher locomotor ability.

Apolipoprotein E-mimetics inhibit neurodegeneration and restore cognitive functions in a transgenic Drosophila model of Alzheimer's disease.

BACKGROUND: Mutations of the amyloid precursor protein gene (APP) are found in familial forms of Alzheimer's disease (AD) and some lead to the elevated production of amyloid-beta-protein (Abeta). While Abeta has been implicated in the causation of AD, the exact role played by Abeta and its APP precursor are still unclear. PRINCIPAL FINDINGS: In our study, Drosophila melanogaster transgenics were established as a model to analyze AD-like pathology caused by APP overexpression. We demonstrated that age related changes in the levels and pattern of synaptic proteins accompanied progressive neurodegeneration and impairment of cognitive functions in APP transgenic flies, but that these changes may be independent from the generation of Abeta. Using novel peptide mimetics of Apolipoprotein-E, COG112 or COG133 proved to be neuroprotective and significantly improved the learning and memory of APP transgenic flies. CONCLUSIONS: The development of neurodegeneration and cognitive deficits was corrected by injections of COG112 or COG133, novel mimetics of apolipoprotein-E (apoE) with neuroprotective activities.