Multiple models and experiments underscore large uncertainty in soil carbon dynamics

Soils contain more carbon than plants or the atmosphere, and sensitivities of soil organic carbon (SOC) stocks to changing climate and plant productivity are a major uncertainty in global carbon cycle projections. Despite a consensus that microbial degradation and mineral stabilization processes control SOC cycling, no systematic synthesis of long-term warming and litter addition experiments has been used to test process-based microbe-mineral SOC models. We explored SOC responses to warming and increased carbon inputs using a synthesis of 147 field manipulation experiments and five SOC models with different representations of microbial and mineral processes. Model projections diverged but encompassed a similar range of variability as the experimental results. Experimental measurements were insufficient to eliminate or validate individual model outcomes. While all models projected that CO₂ efflux would increase and SOC stocks would decline under warming, nearly one-third of experiments observed decreases in CO₂ flux and nearly half of experiments observed increases in SOC stocks under warming. Long-term measurements of C inputs to soil and their changes under warming are needed to reconcile modeled and observed patterns. Measurements separating the responses of mineral-protected and unprotected SOC fractions in manipulation experiments are needed to address key uncertainties in microbial degradation and mineral stabilization mechanisms. Integrating models with experimental design will allow targeting of these uncertainties and help to reconcile divergence among models to produce more confident projections of SOC responses to global changes.     

Hesr1 and Hesr2 may act as early effectors of Notch signaling in the developing cochlea

In cochlear development, the Notch signaling pathway is required for both the early prosensory phase and a later lateral inhibition phase. While it is known that Hes genes are important downstream mediators of Notch function in lateral inhibition, it is not known what genes function as mediators of the early prosensory function of Notch. We report that two members of the Hes-related gene family, Hesr1 and Hesr2, are expressed in the developing cochlea at a time and place that makes them excellent candidates as downstream mediators of Notch during prosensory specification. We also show that treatment of cochlear explant cultures at the time of prosensory specification with a small-molecule inhibitor of the Notch pathway mimics the results of conditional Jag1 deletion. This treatment also reduces Hesr1 and Hesr2 expression by as much as 80%. These results support the hypothesis that Hesr1 and Hesr2 are the downstream mediators of the prosensory function of Notch in early cochlear development.     

Time and frequency domain responses of the mechanomyogram and electromyogram during isometric ramp contractions: a comparison of the short-time Fourier and continuous wavelet transforms.

The purposes of this study were to examine the mechanomyographic (MMG) and electromyographic (EMG) time and frequency domain responses of the vastus lateralis (VL) and rectus femoris (RF) muscles during isometric ramp contractions and compare the time-frequency of the MMG and EMG signals generated by the short-time Fourier transform (STFT) and continuous wavelet transform (CWT). Nineteen healthy subjects (mean+/-SD age=24+/-4 years) performed two isometric maximal voluntary contractions (MVCs) before and after completing 2-3, 6-s isometric ramp contractions from 5% to 100% MVC with the right leg extensors. MMG and surface EMG signals were recorded from the VL and RF muscles. Time domains were represented as root mean squared amplitude values, and time-frequency representations were generated using the STFT and CWT. Polynomial regression analyses indicated cubic increases in MMG amplitude, MMG frequency, and EMG frequency, whereas EMG amplitude increased quadratically. From 5% to 24-28% MVC, MMG amplitude remained stable while MMG frequency increased. From 24-28% to 76-78% MVC, MMG amplitude increased rapidly while MMG frequency plateaued. From 76-78% to 100% MVC, MMG amplitude plateaued (VL) or decreased (RF) while MMG frequency increased. EMG amplitude increased while EMG frequency changed only marginally across the force spectrum with no clear deflection points. Overall, these findings suggested that MMG may offer more unique information regarding the interactions between motor unit recruitment and firing rate that control muscle force production during ramp contractions than traditional surface EMG. In addition, although the STFT frequency patterns were more pronounced than the CWT, both algorithms produced similar time-frequency representations for tracking changes in MMG or EMG frequency.     

Detecting and treating cancer with nanotechnology

Nanotechnology offers many opportunities for enhanced diagnostic and therapeutic medicine against cancer and other diseases. In this review, the special properties that result from the nanoscale size of quantum dots, metal colloids, superparamagnetic iron oxide, and carbon-based nanostructures are reviewed and interpreted against a background of the structural and electronic detail that gives rise to their nanotechnologic behavior. The detection and treatment of cancer is emphasized, with special attention paid to the biologic targeting of the disease. The future of nanotechnology in cancer research and clinical practice is projected to focus on 'theranostic' nanoparticles that are both diagnostic and therapeutic by design.     

Evaluation of amino acid-based linkers in potent macrocyclic inhibitors of farnesyl-protein transferase.

A series of amino acid-based linkers was used to investigate the effects of various substituents upon the potency, pharmacokinetic properties, and conformation of macrocyclic farnesyl-protein transferase inhibitors (FTIs). As a result of the studies described herein, highly potent FTIs with improved pharmacokinetic profiles have been identified.     

Development of potent, allosteric dual Akt1 and Akt2 inhibitors with improved physical properties and cell activity

This letter describes the development of potent, allosteric dual Akt1 and Akt2 inhibitors with improved aqueous solubility (approximately 18 mg/mL) that translates into enhanced cell activity and caspase-3 induction.     

Common relationships among proximate composition components in fishes

Relationships between the various body proximate components and dry matter content were examined for five species of fishes, representing anadromous, marine and freshwater species: chum salmon Oncorhynchus keta, Chinook salmon Oncorhynchus tshawytscha, brook trout Salvelinus fontinalis, bluefish Pomatomus saltatrix and striped bass Morone saxatilis. The dry matter content or per cent dry mass of these fishes can be used to reliably predict the per cent composition of the other components. Therefore, with validation it is possible to estimate fat, protein and ash content of fishes from per cent dry mass information, reducing the need for costly and time‐consuming laboratory proximate analysis. This approach coupled with new methods of non‐lethal estimation of per cent dry mass, such as from bioelectrical impedance analysis, can provide non‐destructive measurements of proximate composition of fishes.     

Discovery of triarylethanolamine inhibitors of the Kv1.5 potassium channel

A series of triarylethanolamine inhibitors of the Kv1.5 potassium channel have been prepared and evaluated for their effects in vitro and in vivo. The structure–activity relationship (SAR) studies described herein led to the development of potent, selective and orally active inhibitors of Kv1.5.     

Discovery of 2,3,5-trisubstituted pyridine derivatives as potent Akt1 and Akt2 dual inhibitors

This letter describes the discovery of a novel series of dual Akt1/Akt2 kinase inhibitors, based on a 2,3,5-trisubstituted pyridine scaffold. Compounds from this series, which contain a 5-tetrazolyl moiety, exhibit more potent inhibition of Akt2 than Akt1.