The association between Barrett's esophagus and Helicobacter pylori infection: a meta-analysis

Objective: The effect of Helicobacter pylori on Barrett’s esophagus is poorly understood. We conducted a meta‐analysis to summarize the existing literature examining the effect that H. pylori has on Barrett’s esophagus. Design: We performed a comprehensive search to identify studies pertaining to the association between H. pylori and Barrett’s esophagus. We conducted meta‐regression analyses to identify sources of variation in the effect of H. pylori on Barrett’s esophagus. Results: Our analysis included a total of 49 studies that examined the effect of H. pylori on Barrett’s esophagus and seven studies that examined the effect of cag A positivity on Barrett’s esophagus. Overall, H. pylori, and even more so cag A, tended to be protective for Barrett’s esophagus in most studies; however, there was obvious heterogeneity across studies. The effect of H. pylori on Barrett’s esophagus varied by geographic location and in the presence of selection and information biases. Only four studies were found without obvious selection and information bias, and these showed a protective effect of H. pylori on Barrett’s esophagus (Relative risk = 0.46 [95% CI: 0.35, 0.60]). Conclusions: Estimates for the effect of H. pylori on Barrett’s esophagus were heterogeneous across studies. We identified selection and information bias as potential sources of this heterogeneity. Few studies without obvious selection and information bias have been conducted to examine the effect of H. pylori on Barrett’s esophagus, but in these, H. pylori infection is associated with a reduced risk of Barrett’s esophagus.     

Super‐achromatic optical coherence tomography capsule for ultrahigh‐resolution imaging of esophagus

Endoscopic optical coherence tomography (OCT) is a noninvasive technology allowing for imaging of tissue microanatomies of luminal organs in real time. Conventional endoscopic OCT operates at 1300 nm wavelength region with a suboptimal axial resolution limited to 8‐20 μm. In this paper, we present the first ultrahigh‐resolution tethered OCT capsule operating at 800 nm and offering about 3‐ to 4‐fold improvement of axial resolution (plus enhanced imaging contrast). The capsule uses diffractive optics to manage chromatic aberration over a full ~200 nm spectral bandwidth centering around 830 nm, enabling to achieve super‐achromaticity and an axial resolution of ~2.6 μm in air. The performance of the OCT capsule is demonstrated by volumetric imaging of swine esophagus ex vivo and sheep esophagus in vivo, where fine anatomic structures including the sub‐epithelial layers are clearly identified. The ultrahigh resolution and excellent imaging contrast at 800 nm of the tethered capsule suggest the potential of the technology as an enabling tool for surveillance of early esophageal diseases on awake patients without the need for sedation.      

Theoretical evaluation of magnetoreception of power‐frequency fields

Several effects of power‐frequency (50/60 Hz) magnetic fields (PF‐MF) of weak intensity have been hypothesized in animals and humans. No valid mechanism, however, has been proposed for an interaction between PF‐MF and biological tissues and living beings at intensities relevant to animal and human exposure. Here we proposed to consider PF‐MF as disrupters of the natural magnetic signal. Under exposure to these fields, an oscillating field exists that results from the vectorial summation of both the PF‐MF and the geomagnetic field. At a PF‐MF intensity (rms) of 0.5 µT, the peak‐to‐peak amplitude of the axis and/or intensity variations of this resulting field exceeds the related discrimination threshold of magnetoreception (MR) in migrating animals. From our evaluation of the 50/60 Hz responsiveness of the putative mechanisms of MR, single domain particles (Kirschvink's model) appear unable to transduce that oscillating signal. On the contrary, radical pair reactions are able to, as well as interacting multidomain iron–mineral platelets and clusters of superparamagnetic particles (Fleissner/Solov'yov's model). It is, however, not yet known whether the reception of 50/60 Hz oscillations of the natural magnetic signal might be of consequence or not. Bioelectromagnetics 31:371–379, 2010. © 2010 Wiley‐Liss, Inc.     

Intercoupling surface plasmon resonance and diffusion reflection measurements for real‐time cancer detection

Spatial diffusion reflection (DR) measurements of gold nanorods (GNR) were recently suggested as a simple and highly sensitive non‐invasive and non‐ionizing method for real‐time cancer detection. In this paper we demonstrate that wavelength dependent DR measurements enable the spectral red‐shift observation of highly concentrated GNR. By conjugating targeting moieties to the GNR, large density of GNR can specifically home onto cancer cells. The inter‐particle plasmon resonance pattern of the highly concentrated GNR leads to an extension and a red‐shift (Δλ) in the absorption spectrum of the concentrated GNR. Dark‐field microscopy was used in order to measure the expected Δλ in different GNR concentrations in vitro. Double‐wavelength DR measurements of tissue‐like phantoms and tumor bearing mice containing different GNR concentrations are presented. We show that the DR profile of the highly concentrated GNR directly correlate with the spectral extension and red‐shift. This presented work suggests that wavelength dependent DR method can serve as a promising tool for real‐time superficial tumor detection. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Optical‐resolution photoacoustic microscopy with ultrafast dual‐wavelength excitation

Fast functional and molecular photoacoustic microscopy requires pulsed laser excitations at multiple wavelengths with enough pulse energy and short wavelength‐switching time. Recent development of stimulated Raman scattering in optical fiber offers a low‐cost laser source for multiwavelength photoacoustic imaging. In this approach, long fibers temporally separate different wavelengths via optical delay. The time delay between adjacent wavelengths may eventually limits the highest A‐line rate. In addition, a long‐time delay in fiber may limit the highest pulse energy, leading to poor image quality. In order to achieve high pulse energy and ultrafast dual‐wavelength excitation, we present optical‐resolution photoacoustic microscopy with ultrafast dual‐wavelength excitation and a signal separation method. The signal separation method is validated in numerical simulation and phantom experiments. We show that when two photoacoustic signals are partially overlapped with a 50‐ns delay, they can be recovered with 98% accuracy. We apply this ultrafast dual‐wavelength excitation technique to in vivo OR‐PAM. Results demonstrate that A‐lines at two wavelengths can be successfully separated, and sO₂ values can be reliably computed from the separated data. The ultrafast dual‐wavelength excitation enables fast functional photoacoustic microscopy with negligible misalignment among different wavelengths and high pulse energy, which is important for in vivo imaging of microvascular dynamics.     

Electrostatic potentials of the S‐locus F‐box proteins contribute to the pollen S specificity in self‐incompatibility in Petunia hybrida

Self‐incompatibility (SI) is a self/non‐self discrimination system found widely in angiosperms and, in many species, is controlled by a single polymorphic S‐locus. In the Solanaceae, Rosaceae and Plantaginaceae, the S‐locus encodes a single S‐RNase and a cluster of S‐locus F‐box (SLF) proteins to control the pistil and pollen expression of SI, respectively. Previous studies have shown that their cytosolic interactions determine their recognition specificity, but the physical force between their interactions remains unclear. In this study, we show that the electrostatic potentials of SLF contribute to the pollen S specificity through a physical mechanism of ‘like charges repel and unlike charges attract’ between SLFs and S‐RNases in Petunia hybrida. Strikingly, the alteration of a single C‐terminal amino acid of SLF reversed its surface electrostatic potentials and subsequently the pollen S specificity. Collectively, our results reveal that the electrostatic potentials act as a major physical force between cytosolic SLFs and S‐RNases, providing a mechanistic insight into the self/non‐self discrimination between cytosolic proteins in angiosperms.     

High‐speed X‐ray‐induced luminescence computed tomography

X‐ray‐induced luminescence computed tomography (XLCT) is an emerging molecular imaging. Challenges in improving spatial resolution and reducing the scan time in a whole‐body field of view (FOV) still remain for practical in vivo applications. In this study, we present a novel XLCT technique capable of obtaining three‐dimensional (3D) images from a single snapshot. Specifically, a customed two‐planar‐mirror component is integrated into a cone beam XLCT imaging system to obtain multiple optical views of an object simultaneously. Furthermore, a compressive sensing based algorithm is adopted to improve the efficiency of 3D XLCT image reconstruction. Numerical simulations and experiments were conducted to validate the single snapshot X‐ray‐induced luminescence computed tomography (SS‐XLCT). The results show that the 3D distribution of the nanophosphor targets can be visualized much faster than conventional cone beam XLCT imaging method that was used in our comparisons while maintaining comparable spatial resolution as in conventional XLCT imaging. SS‐XLCT has the potential to harness the power of XLCT for rapid whole‐body in vivo molecular imaging of small animals.     

Dingo Howls: The Content and Efficacy of a Long‐Range Vocal Signal

Signals are shaped through selective pressures impacting their information content (i.e. ‘what’ is conveyed) and their efficacy (i.e. ‘how’ is it conveyed). In the case of long‐range communication, a signal's structure should both convey information and allow for detection and discrimination despite the effects of environmental variability during propagation. Canid howls are an ideal example of a long‐range communication signal, although research has mostly focused on the relationships between howls’ acoustic characteristics and their potential information content in wolves, Canis lupus spp., and coyotes, Canis latrans. In this study, we quantified these relationships in another canid, the dingo, Canis familiaris dingo, to determine how their howls compare to that of other wild canids. We found that dingoes’ howls are individually distinctive and may convey gender cues. Playback experiments indicate that dingoes can perform class‐level recognition of familiar and unfamiliar individuals on the basis of vocalizations alone. These results mirror findings for other wild canids such as wolves and coyotes. Lastly, propagation experiments demonstrate that this signal's structure can permit long‐distance detectability and discriminability. We discuss our results in relation to the putative functions of canid howls and propose avenues for future research.     

Review ‐ Helicobacter pylori and non‐malignant upper gastro‐intestinal diseases

This review takes into account recent publications focusing on the relationship between Helicobacter pylori infection and non‐malignant diseases of the upper gastro‐intestinal tract. The authors have summarized current knowledge on associations between the H pylori infection and non‐malignant upper GI conditions including gastroesophageal reflux disease (GERD), Barrett's esophagus, eosinophilic esophagitis (EOE), peptic ulcer disease (PUD), H pylori gastritis, celiac disease and functional dyspepsia. In the field of GERD, current data focusing on different locations of H pylori infection detect significant differences between antrum‐ and corpus predominant gastritis explainable by different changes in acid secretion in different gastric niches. High volume studies from Sweden and Brazil underline the safety of H pylori eradication concerning the risk of Barret's esophagus or adenocarcinoma. The relationship betweenH pylori infection and EOE remains uncertain, but current data supports the concept of expected positive and protective effects of H pylori exposure reducing the risk of EOE. Analyzing biomarkers might be helpful to identify subjects under risk for the development of precancerous lesions after H pylori infection, where microRNAs, IL‐9 and IL‐4, and also Tc17/9 and Th17/9 and microbiota profiles showed promising results to identify subgroups under risk.     

On‐the‐fly detection of changes on and below the surface in epithelium mucosal tissue architecture from scattered light

In this paper we present a technique to raise a flag on the fly when a transition occurs between different mucosal architectures on or below the surface. The segmentation is based on a novel difference metric for detecting an abrupt change in the parameters extracted from a Stochastic Decomposition Method (SDM) that models the scattered light reflected from the mucosal tissue structure over an area (2‐D scan) illuminated by an optical sensor (fiber) emitting light at either one wavelength or with white light. This work has the potential to enhance the endoscopist's ability to locate and identify abnormal mucosal architectures in particular when the disease is developing below the surface and hence becoming hidden during colonoscopy or endoscopic examination. It also has also potential in helping deciding as to when and where to take biopsies; steps that should lead to improvement in the diagnostic yield. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

On the role of interference in laser‐based mid‐infrared widefield microspectroscopy

A laser's high degree of coherence leads to interferences, which—in the absence of precautions—can cause severe image distortions such as fringes and speckles and which thereby strongly hamper a meaningful interpretation of hyperspectral images in laser‐based widefield microspectroscopy. While images and spectra of homogenous samples may already suffer from interferences, any structured object such as a tissue thin section will add to these distortions due to wavelength‐ and, in particular, sample‐dependent phase shifts (structure sizes, absorption coefficients, refractive indices). This effect is devastating for the universal applicability of laser‐based microspectroscopy especially in the mid‐infrared (MIR), where cell sizes are of the same dimension as the wavelength of the illumination source. Here, we show that the impact of interferences is strongly mitigated by reducing the time‐averaged spatiotemporal coherence properties of the illumination using a moving plus a stationary scatterer. In this case, the illumination path provides a pseudothermal radiation source and spatially resolved spectra can be obtained at the quality of the reference method, that is, Fourier‐transform infrared microspectroscopy, without compromising spectral or spatial resolution.      

Self‐referenced axial chromatic dispersion measurement in multiphoton microscopy through 2‐color third‐harmonic generation imaging

With tunable excitation light, multiphoton microscopy is widely used for imaging biological structures at subcellular resolution. Axial chromatic dispersion, present in virtually every transmissive optical system including the multiphoton microscope, leads to focal (and the resultant image) plane separation. Here, we experimentally demonstrate a technique to measure the axial chromatic dispersion in a multiphoton microscope, using simultaneous 2‐color third‐harmonic generation imaging excited by a 2‐color soliton source with tunable wavelength separation. Our technique is self‐referenced, eliminating potential measurement error when 1‐color tunable excitation light is used which necessitates reciprocating motion of the mechanical translation stage. Using this technique, we demonstrate measured axial chromatic dispersion with 2 different objective lenses in a multiphoton microscope. Further measurement in a biological sample also indicates that this axial chromatic dispersion, in combination with 2‐color imaging, may open up opportunity for simultaneous imaging of 2 different axial planes.      

A cytotoxicity,optical spectroscopy and computational binding analysis of 4‐[3‐acetyl‐5‐(acetylamino)‐2‐methyl‐2,3‐dihydro‐1,3,4‐thiadiazole‐2‐yl]phenyl benzoate in calf thymus DNA

In this study the interaction mechanism between newly synthesized 4‐(3‐acetyl‐5‐(acetylamino)‐2‐methyl‐2, 3‐dihydro‐1,3,4‐thiadiazole‐2‐yl) phenyl benzoate (thiadiazole derivative) anticancer active drug with calf thymus DNA was investigated by using various optical spectroscopy techniques along with computational technique. The absorption spectrum shows a clear shift in the lower wavelength region, which may be due to strong hypochromic effect in the ctDNA and the drug. The results of steady state fluorescence spectroscopy show that there is static quenching occurring while increasing the thiadiazole drug concentration in the ethidium bromide‐ctDNA system. Also the binding constant (K), thermo dynamical parameters of enthalpy change (ΔH°), entropy change (ΔS°) Gibbs free energy change (ΔG°) were calculated at different temperature (293 K, 298 K) and the results are in good agreement with theoretically calculated MMGBSA binding analysis. Time resolved emission spectroscopy analysis clearly explains the thiadiazole derivative competitive intercalation in the ethidium bromide‐ctDNA system. Further, molecular docking studies was carried out to understand the hydrogen bonding and hydrophobic interaction between ctDNA and thiadiazole derivative molecule. In addition the docking and molecular dynamics charge distribution analysis was done to understand the internal stability of thiadiazole derivative drug binding sites of ctDNA. The global reactivity of thiadiazole derivative such as electronegativity, electrophilicity and chemical hardness has been calculated.     

Isoform‐specific effects of apolipoprotein E on cognitive performance in targeted‐replacement mice overexpressing human APP

The ε4 allele of apolipoprotein E (apoE4) is the predominant genetic risk factor for late‐onset Alzheimer's disease (AD) and is also implicated in cognitive deficits associated with normal aging. The biological mechanisms by which APOE genotype affects cognitive processes or AD pathogenesis remain unclear, but interactions of apoE with amyloid β peptide (Aβ) are thought to play an important role in mediating apoE's isoform‐specific effects on brain function. Here, we investigated the potential isoform‐dependent effects of apoE on behavioral and cognitive performance in human apoE3 and apoE4 targeted‐replacement (TR) mice that also overexpress the human amyloid precursor protein (APP). Beginning at 6–7 months of age, female APP‐Yac/apoE3‐TR (‘poE3’) and APP‐Yac/apoE4‐TR (‘poE4’) mice were tested on a battery of tests to evaluate basic sensorimotor functioning, spatial working memory, spatial recognition, episodic‐like memory and attentional processing. Compared with apoE3 mice, a generalized reduction in locomotor activity was observed in apoE4 mice. Moderate, but significant, cognitive impairments were also detected in apoE4 mice in the novel object‐location preference task, the contextual fear conditioning test, and a two‐choice visual discrimination/detection test, however spontaneous alternation performance in the Y‐maze was spared. These results offer additional support for the negative impact of apoE4 on both memory and attention and further suggest that APP‐Yac/apoE‐TR mice provide a novel and useful model for investigating the role of apoE in mediating susceptibility to cognitive decline.     

Activity‐regulated cytoskeleton‐associated protein (Arc/Arg3.1) regulates anxiety‐ and novelty‐related behaviors

The activity‐regulated cytoskeleton‐associated protein (Arc, also known as Arg3.1) regulates glutamatergic synapse plasticity and has been linked to neuropsychiatric illness; however, its role in behaviors associated with mood and anxiety disorders remains unclear. We find that stress upregulates Arc expression in the adult mouse nucleus accumbens (NAc)—a brain region implicated in mood and anxiety behaviors. Global Arc knockout mice have altered AMPAR‐subunit surface levels in the adult NAc, and the Arc‐deficient mice show reductions in anxiety‐like behavior, deficits in social novelty preference, and antidepressive‐like behavior. Viral‐mediated expression of Arc in the adult NAc of male, global Arc KO mice restores normal levels of anxiety‐like behavior in the elevated plus maze (EPM). Consistent with this finding, viral‐mediated reduction of Arc in the adult NAc reduces anxiety‐like behavior in male, but not female, mice in the EPM. NAc‐specific reduction of Arc also produced significant deficits in both object and social novelty preference tasks. Together our findings indicate that Arc is essential for regulating normal mood‐ and anxiety‐related behaviors and novelty discrimination, and that Arc's function within the adult NAc contributes to these behavioral effects.     

Real‐time functional optical‐resolution photoacoustic microscopy using high‐speed alternating illumination at 532 and 1064 nm

Optical‐resolution photoacoustic microscopy (OR‐PAM), which has been widely used and studied as a noninvasive and in vivo imaging technique, can yield high‐resolution and absorption contrast images. Recently, metallic nanoparticles and dyes, such as gold nanoparticles, methylene blue, and indocyanine green, have been used as contrast agents of OR‐PAM. This study demonstrates real‐time functional OR‐PAM images with high‐speed alternating illumination at 2 wavelengths. To generate 2 wavelengths, second harmonic generation at 532 nm with an LBO crystal and a pump wavelength of 1064 nm is applied at a pulse repetition rate of 300 kHz. For alternating illumination, an electro‐optical modulator is used as an optical switch. Therefore, the A‐line rate for the functional image is 150 kHz, which is half of the laser repetition rate. To enable fast signal processing and real‐time displays, parallel signal processing using a graphics processing unit (GPU) is performed. OR‐PAM images of the distribution of blood vessels and gold nanorods in a BALB/c‐nude mouse's ear can be simultaneously obtained with 500 × 500 pixels and real‐time display at 0.49 fps.      

A dual discrimination mode for improved specificity towards let‐7a detection via a single‐base mutated padlock probe‐based exponential rolling circle amplification

MicroRNA (miRNA) family members are usually highly homologous sequences, and it is a challenging task to selectively detect one miRNA member from other family members in medical diagnosis. Here, we describe the design of a dual discrimination mode for improved specificity towards let‐7a detection over the other members of the let‐7 family, in which an intentional base mutation was introduced into the padlock probe of an exponential rolling circle amplification. The inherent discrimination power of the padlock probe and the introduced base mutation constituted a dual discrimination mode, which provided enhanced specificity for let‐7a, even over single‐base mismatched family sequences. Furthermore, the assay enabled the quantitative detection of let‐7a in a dynamic range from 200 amol to 100 fmol. This technique has also been successfully applied to real small RNA samples extracted from human lung cancers. For the first time, through intentionally mutating one base on the padlock probe of the exponential rolling circle amplification (RCA), we improved the discrimination capability for let‐7 family members, while maintaining adequate sensitivity. Overall, this dual discrimination mode and the high amplification strategy have the potential to be extended to other short, but highly homologous, miRNA sequences.     

Climate‐driven body‐size trends in the ostracod fauna of the deep Indian Ocean

Abstract: Body size is a common focus of macroevolutionary, macroecological and palaeontological investigations. Here, we document body‐size evolution in 19 species‐level ostracod lineages from the deep Indian Ocean (Deep Sea Drilling Program Site 253) over the past 40 myr. Body‐size trajectories vary across taxa and time intervals, but most lineages (16/19) show net gains in body size. Because many modern ostracod taxa are larger in colder parts of their geographical range, we compared the timing and magnitude of these size changes to established Cenozoic deep‐water cooling patterns confirmed through δ¹⁸O measurements of benthic foraminifera in the samples studied. These data show a significant negative correlation between size changes and temperature changes (ostracods get larger as temperatures get colder), and that systematic size increases only occur during intervals of sustained cooling. In addition, statistical support for an explicit temperature‐tracking model exceeds that of purely directional evolution. We argue that this Cope’s Rule pattern is driven by secular changes in the environment, rather than any universal or intrinsic advantages to larger body sizes, and we note some difficulties in the attempts to link Cope’s Rule to observations made within a single generation.     

Synthesis of alginate‐silica hybrid hydrogel for biocatalytic conversion by β‐glucosidase in microreactor

The organic–inorganic hybrid materials have been used in different fields to immobilize biomolecules since they offer many advantages. The aim of this study was to optimize and characterize the alginate‐silica hybrid hydrogel as a stable and injectable form for microfluidic systems using internal gelation method and increase the stability and activity of immobilized enzyme for biocatalytic conversions as well. Characterization was carried out by scanning electron microscopy, energy dispersive spectroscopy/mapping, Brunauer–Emmett–Teller, Barrett–Joyner–Halenda, and Fourier‐transform infrared spectroscopy analyses, and the shrinkages of monoliths were evaluated. Subsequent to optimizing the enzyme concentration (40 μg), hydrolytic conversion of 4‐nitrophenyl β‐d ‐glucopyranoside (pNPG) was performed to understand the behavior of the bioconversion in the microfluidic system. The yield was 94% which reached the equilibrium at 24 h indicating that the alginate‐silica gel derived microsystem overcome some drawbacks of monolithic systems. Additionally, bioconversion of Ruscus aculeatus saponins was carried out at the same setup in order to obtain aglycon part, which has pharmaceutical significance. Although pure aglycon could not be achieved, an intermediate compound was obtained based on the HPLC analysis. The developed formulation can be utilized for various life science applications.