Interaction imaging with amplitude-dependence force spectroscopy

Knowledge of surface forces is the key to understanding a large number of processes in fields ranging from physics to material science and biology. The most common method to study surfaces is dynamic atomic force microscopy (AFM). Dynamic AFM has been enormously successful in imaging surface topography, even to atomic resolution, but the force between the AFM tip and the surface remains unknown during imaging. Here, we present a new approach that combines high accuracy force measurements and high resolution scanning. The method, called amplitude-dependence force spectroscopy (ADFS) is based on the amplitude-dependence of the cantilever's response near resonance and allows for separate determination of both conservative and dissipative tip-surface interactions. We use ADFS to quantitatively study and map the nano-mechanical interaction between the AFM tip and heterogeneous polymer surfaces. ADFS is compatible with commercial atomic force microscopes and we anticipate its wide-spread use in taking AFM toward quantitative microscopy

Emerging pharmacotherapy of tinnitus

Tinnitus, the perception of sound in the absence of an auditory stimulus, is perceived by about 1 in 10 adults, and for at least 1 in 100, tinnitus severely affects their quality of life. Because tinnitus is frequently associated with irritability, agitation, stress, insomnia, anxiety and depression, the social and economic burdens of tinnitus can be enormous. No curative treatments are available. However, tinnitus symptoms can be alleviated to some extent. The most widespread management therapies consist of auditory stimulation and cognitive behavioral treatment, aiming at improving habituation and coping strategies. Available clinical trials vary in methodological rigor and have been performed for a considerable number of different drugs. None of the investigated drugs have demonstrated providing replicable long-term reduction of tinnitus impact in the majority of patients in excess of placebo effects. Accordingly, there are no FDA or European Medicines Agency approved drugs for the treatment of tinnitus. However, in spite of the lack of evidence, a large variety of different compounds are prescribed off-label. Therefore, more effective pharmacotherapies for this huge and still growing market are desperately needed and even a drug that produces only a small but significant effect would have an enormous therapeutic impact. This review describes current and emerging pharmacotherapies with current difficulties and limitations. In addition, it provides an estimate of the tinnitus market. Finally, it describes recent advances in the tinnitus field which may help overcome obstacles faced in the pharmacological treatment of tinnitus. These include incomplete knowledge of tinnitus pathophysiology, lack of well-established animal models, heterogeneity of different forms of tinnitus, difficulties in tinnitus assessment and outcome measurement and variability in clinical trial methodology. © 2009 Informa UK Ltd.Fil: Langguth, Berthold. Universitat Regensburg; AlemaniaFil: Salvi, Richard. State University of New York; Estados UnidosFil: Elgoyhen, Ana Belen. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentin

Flexible Strategies for Coping with Rainfall Variability: Seasonal Adjustments in Cropped Area in the Ganges Basin

One of the main manifestations of climate change will be increased rainfall variability. How to deal with this in agriculture will be a major societal challenge. In this paper we explore flexibility in land use, through deliberate seasonal adjustments in cropped area, as a specific strategy for coping with rainfall variability. Such adjustments are not incorporated in hydro-meteorological crop models commonly used for food security analyses. Our paper contributes to the literature by making a comprehensive model assessment of inter-annual variability in crop production, including both variations in crop yield and cropped area. The Ganges basin is used as a case study. First, we assessed the contribution of cropped area variability to overall variability in rice and wheat production by applying hierarchical partitioning on time-series of agricultural statistics. We then introduced cropped area as an endogenous decision variable in a hydro-economic optimization model (WaterWise), coupled to a hydrology-vegetation model (LPJmL), and analyzed to what extent its performance in the estimation of inter-annual variability in crop production improved. From the statistics, we found that in the period 1999–2009 seasonal adjustment in cropped area can explain almost 50% of variability in wheat production and 40% of variability in rice production in the Indian part of the Ganges basin. Our improved model was well capable of mimicking existing variability at different spatial aggregation levels, especially for wheat. The value of flexibility, i.e. the foregone costs of choosing not to crop in years when water is scarce, was quantified at 4% of gross margin of wheat in the Indian part of the Ganges basin and as high as 34% of gross margin of wheat in the drought-prone state of Rajasthan. We argue that flexibility in land use is an important coping strategy to rainfall variability in water stressed regions

Short- and long-lasting tinnitus relief induced by transcranial direct current stimulation

A significant proportion of the population suffers from tinnitus, a bothersome auditory phantom perception that can severely alter the quality of life. Numerous experimental studies suggests that a maladaptive plasticity of the auditory and limbic cortical areas may underlie tinnitus. Accordingly, repetitive transcranial magnetic stimulation (rTMS) has been repeatedly used with success to reduce tinnitus intensity. The potential of transcranial direct current stimulation (tDCS), another promising method of noninvasive brain stimulation, to relieve tinnitus has not been explored systematically. In a double-blind, placebo-controlled and balanced order design, 20 patients suffering from chronic untreatable tinnitus were submitted to 20 minutes of 1 mA anodal, cathodal and sham tDCS targeting the left temporoparietal area. The primary outcome measure was a change in tinnitus intensity or discomfort assessed with a Visual Analogic Scale (VAS) change-scale immediately after tDCS and 1 hour later. Compared to sham tDCS, anodal tDCS significantly reduced tinnitus intensity immediately after stimulation; whereas cathodal tDCS failed to do so. The variances of the tinnitus intensity and discomfort VAS change-scales increased dramatically after anodal and cathodal tDCS, whereas they remained virtually unchanged after sham tDCS. Moreover, several patients unexpectedly reported longer-lasting effects (at least several days) such as tinnitus improvement, worsening, or changes in tinnitus features, more frequently after real than sham tDCS. Anodal tDCS is a promising therapeutic tool for modulating tinnitus perception. Moreover, both anodal and cathodal tDCS seem able to alter tinnitus perception and could, thus, be used to trigger plastic changes

Gipc3 mutations associated with audiogenic seizures and sensorineural hearing loss in mouse and human

Sensorineural hearing loss affects the quality of life and communication of millions of people, but the underlying molecular mechanisms remain elusive. Here, we identify mutations in Gipc3 underlying progressive sensorineural hearing loss (age-related hearing loss 5, ahl5) and audiogenic seizures (juvenile audiogenic monogenic seizure 1, jams1) in mice and autosomal recessive deafness DFNB15 and DFNB95 in humans. Gipc3 localizes to inner ear sensory hair cells and spiral ganglion. A missense mutation in the PDZ domain has an attenuating effect on mechanotransduction and the acquisition of mature inner hair cell potassium currents. Magnitude and temporal progression of wave I amplitude of afferent neurons correlate with susceptibility and resistance to audiogenic seizures. The Gipc3343A allele disrupts the structure of the stereocilia bundle and affects long-term function of auditory hair cells and spiral ganglion neurons. Our study suggests a pivotal role of Gipc3 in acoustic signal acquisition and propagation in cochlear hair cells