Acoustic reflectometry for an in vitro model of a human upper airway using sinusoidal wave packets and the Ware–Aki algorithm

Acoustic reflectometry is often used for estimating the cross-sectional area of a cylindrical cavity when used in combination with an acoustic pulse. The objective of this research is to sweep a spectral bandwidth from 50 Hz to 10 kHz at steps of 50 Hz, with Gaussian sinusoidal wave packets, and to apply the Ware–Aki algorithm. In practice, not only it is difficult to generate a broad spectral bandwidth, but also robust methods are required to compensate for attenuation in the propagating wave and to eliminate a DC offset component generated in its impulse response. This paper looks at using numerical techniques to compute the impulse response and estimate the cross-sectional area as a function of an increment in the frequency response. Preliminary results show that both simulated and reconstructed cross-sectional areas for an in vitro model of a human upper airway may be estimated with an appropriate resolution, suggesting that this method is suitable for such applications.     

Sharks modulate their escape behavior in response to predator size,speed and approach orientation

Escape responses are often critical for surviving predator–prey interactions. Nevertheless, little is known about how predator size, speed and approach orientation impact escape performance, especially in larger prey that are primarily viewed as predators. We used realistic shark models to examine how altering predatory behavior and morphology (size, speed and approach orientation) influences escape behavior and performance in Squalus acanthias, a shark that is preyed upon by apex marine predators. Predator models induced C-start escape responses, and increasing the size and speed of the models triggered a more intense response (increased escape turning rate and acceleration). In addition, increased predator size resulted in greater responsiveness from the sharks. Among the responses, predator approach orientation had the most significant impact on escapes, such that the head-on approach, as compared to the tail-on approach, induced greater reaction distances and increased escape turning rate, speed and acceleration. Thus, the anterior binocular vision in sharks renders them less effective at detecting predators approaching from behind. However, it appears that sharks compensate by performing high-intensity escapes, likely induced by the lateral line system, or by a sudden visual flash of the predator entering their field of view. Our study reveals key aspects of escape behavior in sharks, highlighting the modulation of performance in response to predator approach.     

Determination of the serum metallothionein (MT)1/2 concentration in patients with Wilson's disease and Menkes disease

We have developed an easy and specific enzyme-linked immunoassay (ELISA) for the simultaneous determination of serum metallothinein-1 (MT-1) and 2 (MT-2) in both humans and experimental animals. A competitive ELISA was established using a specific polyclonal antibody against rat MT-2. The antibody used for this ELISA had exhibited the same cross-reactivity with MT in humans and experimental animals. The NH₂ terminal peptide of MT containing acetylated methionine was shown to be the epitope of this antibody. The reactivity of this ELISA system with the liver, kidney and brain in MT1/2 knock-out mice was significantly low, but was normal in an MT-3 knock-out mouse. The lowest detection limit of this ELISA was 0.6 ng/ml and the spiked MT-1was fully recovered from the plasma.We investigated the normal range of MT1/2 (25–75%tile) in 200 healthy human serum and found it to be 27–48 ng/ml, and this was compared with the serum levels in various liver diseases. The serum MT1/2 levels in chronic hepatitis C (HCV) patients were significantly lower than healthy controls and also other liver diseases. In the chronic hepatitis cases, the MT1/I2 levels increased gradually, followed by the progression of the disease to liver cirrhosis and hepatocellular carcinoma. In particular, we found significantly elevated MT1/2 plasma levels in Wilson's disease patients, levels which were very similar to those in the Long–Evans Cinnamon (LEC) rat (model animal of Wilson's disease). Furthermore, a significantly elevated MT1/2 level was found in patients with Menkes disease, an inborn error of copper metabolism such as Wilson's disease.     

Can nitroxides evoke the Keap1–Nrf2–ARE pathway in skin?

Nitroxides are stable cyclic radicals of diverse size, charge, and lipophilicity. They are cell-permeative, which effectively protects cells, tissues, isolated organs, and laboratory animals from radical-induced damage. The mechanisms of activity through which nitroxides operate are diverse, including superoxide dismutase-mimetic activity, oxidation of semiquinone radicals, oxidation of reduced metal ions, procatalase-mimetic activity, interruption of radical chain reactions, and indirect modulation of NO levels. Nitroxides possess both a nucleophilic (reducing properties) and an electrophilic (oxidizing properties) nature and, therefore, they may affect different cellular pathways. In the current study, a novel mechanism of action by which nitroxides provide skin protection based on their electrophilic nature is suggested. This study shows that nitroxides may act as electrophiles, directly or indirectly, capable of activating the Keap1–Nrf2–ARE pathway in human keratinocytes (HaCaT) and in human skin (human organ culture model). The high potency of oxoammonium cations versus hydroxylamines in activating the system is demonstrated. The mechanism of action by which nitroxides activate the Keap1–Nrf2–ARE pathway is discussed. Understanding the mechanism of activity may expand the usage of nitroxides as a skin protection strategy against oxidative stress-related conditions.     

Nasopharyngeal carcinoma in dermatomyositis patients: A 10-year retrospective review in Hospital Selayang,Malaysia

AimThe objective of our review is to investigate the association between dermatomyositis patients and nasopharyngeal carcinoma (NPC) together with the clinical presentation of the patients and their management in otorhinolaryngology.BackgroundNPC is a malignant disease with good prognosis on early diagnosis. However, the relationship between the dermatomyositis and NPC and its management is not well defined.Materials and methodsA 10-year retrospective review of case records of 21 dermatomyositis patients seen in Otorhinolaryngology Department of Hospital Selayang from January 2000 to November 2010.ResultsThese patients ranged from 19 to 74 years old and a total of 8 (38%) out of 21 adults with dermatomyositis were detected to have malignancy. Five out of 8 patients had NPC (62.5%). The mean age of patients with NPC and dermatomyositis was 48 years. NPC is diagnosed in 4 out of 5 patients (80%) in the first year of diagnosis of dermatomyositis. The clinical findings of the examination of nasopharynx ranged from hyperemia to exophytic nasopharyngeal mass. Histologically, it is only related to NPC of WHO types II and III.ConclusionsThere is a strong relationship between dermatomyositis and malignancy, especially NPC. Clinicians should have a high index of suspicion for malignancy in all dermatomyositis patients. Rigid nasoendoscopies and biopsies, serum Epstein–Barr viral capsid IgA antibody and imaging studies are helpful in detecting NPC in dermatomyositis patients.     

ATP binding and hydrolysis by Saccharomyces cerevisiae Msh2–Msh3 are differentially modulated by mismatch and double-strand break repair DNA substrates

In Saccharomyces cerevisiae, Msh2–Msh3-mediated mismatch repair (MMR) recognizes and targets insertion/deletion loops for repair. Msh2–Msh3 is also required for 3′ non-homologous tail removal (3′NHTR) in double-strand break repair. In both pathways, Msh2–Msh3 binds double-strand/single-strand junctions and initiates repair in an ATP-dependent manner. However, we recently demonstrated that the two pathways have distinct requirements with respect to Msh2–Msh3 activities. We identified a set of aromatic residues in the nucleotide binding pocket (FLY motif) of Msh3 that, when mutated, disrupted MMR, but left 3′NHTR largely intact. One of these mutations, msh3Y942A, was predicted to disrupt the nucleotide sandwich and allow altered positioning of ATP within the pocket. To develop a mechanistic understanding of the differential requirements for ATP binding and/or hydrolysis in the two pathways, we characterized Msh2–Msh3 and Msh2–msh3Y942A ATP binding and hydrolysis activities in the presence of MMR and 3′NHTR DNA substrates. We observed distinct, substrate-dependent ATP hydrolysis and nucleotide turnover by Msh2–Msh3, indicating that the MMR and 3′NHTR DNA substrates differentially modify the ATP binding/hydrolysis activities of Msh2–Msh3. Msh2–msh3Y942A retained the ability to bind DNA and ATP but exhibited altered ATP hydrolysis and nucleotide turnover. We propose that both ATP and structure-specific repair substrates cooperate to direct Msh2–Msh3-mediated repair and suggest an explanation for the msh3Y942A separation-of-function phenotype.