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Background: Melanocytic nevi are frequently observed in the pediatric population. While newly acquired nevi can appear during childhood, congenital nevi can continue to grow and clinically change, making patient caregivers concerned. Reflectance confocal microscopy (RCM) in vivo is a noninvasive tool that might enhance the diagnostic accuracy of dermoscopy, reducing the rate of unnecessary surgical procedures. This study aimed to assess the utility of RCM in increasing the diagnostic accuracy of pediatric melanocytic nevi that show pigmentation changes or grow rapidly. Methods: Pediatric patients who presented between January 2022 and February 2023 in a single institution with rapidly growing melanocytic nevi or nevi that presented changes in the pigmentation were included in the study. All nevi were evaluated by means of dermoscopy and RCM. Results: Forty‐two patients with a total of 42 melanocytic nevi were included. Most lesions showed a honeycombed pattern (n = 21, 50%). On RCM, only 3 of 42 nevi presented atypical cells within the epidermis (7.1%). Evaluation of the dermoepidermal junction (DEJ) revealed the predominance of the meshwork pattern (n = 22, 52.4%). Notably, features considered significant for atypical melanocytic nevi included 9 nevi with scant atypical melanocytes (21.4%) and 3 nevi with nonedge papillae (7.1%). None of the studied lesions required biopsy among this cohort. Conclusions: Most rapidly growing and clinically changing nevi rarely exhibit single atypical cells in the DEJ. The RCM served as a valuable adjunct to dermoscopy, allowing reassurance in the evaluation of these lesions. [ABSTRACT FROM AUTHOR]

Summary: Computer supported design of materials with tailored properties is an important part of computational science so that developments of new effective algorithms is a key issue. Molecular magnetism deals with complex objects described by the quantum physics and their simulations come up against the computational constraints. In this work, we consider a numerical version of a recently developed hybrid approach that combines the ab initio DFT method with the exact diagonalization of the microscopic Hubbard model (HM). The latter avoids the prior perturbative framework but increases computing resources needed for solving the eigenvalue problem of the matrix representation of HM. We demonstrate that in the case of the ring‐shape molecular nanomagnets the computational demands can be curbed due to efficient numerical matrix construction algorithms provided. These algorithms pertain both to the calculation of the single nonzero matrix elements and to their localization in the final sparse matrix that is subsequently diagonalized. Their implementation executed on a simple six‐core‐computer system and the Mathematica environment leads to a significant gain in the computing time for the exemplary chromium‐based molecule denoted Cr8$$ {}_8 $$, running the code sequentially. We claim, referring to the numerical diagonalization of the spin Hamiltonian matrices, that the parallelization flaws related to the high‐level programming approach can be all removed, porting the code to the appropriate HPC environment. A prospective implementation of the code, based on some dedicated and optimized mathematical libraries, will ultimately open a window for further applications of the Hubbard model in molecular magnetism. [ABSTRACT FROM AUTHOR]

Objective: The objective was to evaluate available characteristics and financial costs of malpractice cases among advanced practice providers (APPs; nurse practitioners [NPs] and physician assistants [PAs]), trainees (medical students, residents, fellows), and attending physicians. Methods: This study was a retrospective analysis of claims occurring in the emergency department (ED) from January 1, 2010, to December 31, 2019, contained in the Candello database. Cases were classified according to the provider type(s) involved: NP, PA, trainee, or cases that did not identify an extender as being substantially involved in the adverse event that resulted in the case ("no extender"). Results: There were 5854 cases identified with a total gross indemnity paid of $1,007,879,346. Of these cases, 193 (3.3%) involved an NP, 513 (8.8%) involved a PA, 535 (9.1%) involved a trainee, and 4568 (78.0%) were no extender. Cases where a trainee was involved account for the highest average gross indemnity paid whereas no‐extender cases are the lowest. NP and PA cases differed by contributing factors compared to no‐extender cases: clinical judgment (NP 89.1% vs. no extender 76.8%, p < 0.0001; PA 84.6% vs. no extender, p < 0.0001), documentation (NP 23.3% vs. no extender 17.8%, p = 0.0489; PA 25.9% vs. no extender, p < 0.0001), and supervision (NP 22.3% vs. no extender 1.8%, p < 0.0001; PA 25.7% vs. no extender p < 0.0001). Cases involving NPs and PAs had a lower percentage of high‐severity cases such as loss of limb or death (NP 45.6% vs. no extender 50.2%, p = 0.0004; PA 48.3% vs. no extender, p < 0.0001). Conclusions: APPs and trainees comprise approximately 21% of malpractice cases and 33% of total gross indemnity paid in this large national ED data set. Understanding differences in characteristics of malpractice claims that occur in emergency care settings can be used to help to mitigate provider risk. [ABSTRACT FROM AUTHOR]

A paradox of eukaryotic cells is that while some species assemble a complex actin cytoskeleton from a single ortholog, other species utilize a greater diversity of actin isoforms. The physiological consequences of using different actin isoforms, and the molecular mechanisms by which highly conserved actin isoforms are segregated into distinct networks, are poorly known. Here, we sought to understand how a simple biological system, composed of a unique actin and a limited set of actin‐binding proteins, reacts to a switch to heterologous actin expression. Using yeast as a model system and biomimetic assays, we show that such perturbation causes drastic reorganization of the actin cytoskeleton. Our results indicate that defective interaction of a heterologous actin for important regulators of actin assembly limits certain actin assembly pathways while reinforcing others. Expression of two heterologous actin variants, each specialized in assembling a different network, rescues cytoskeletal organization and confers resistance to external perturbation. Hence, while species using a unique actin have homeostatic actin networks, actin assembly pathways in species using several actin isoforms may act more independently. SYNOPSIS: Why assembly of a complex actin cytoskeleton involves a single ortholog in some species and multiple isoforms in others is unclear. Here, actin gene swapping is used to understand how the yeast molecular machinery uses different actin variants, revealing a mechanism for functional segregation of similar actin isoforms into distinct networks. Reducing actin expression by half has negligible effects on budding yeast cell behavior.Minor modifications of the actin protein can disrupt interaction with an actin regulator, and funnel actin preferentially into assembly pathways not promoted by this regulator.Combination of two specialized actin variants that promote different actin organizations restores wild‐type actin configuration in yeast.Use of multiple specialized variants hampers efficient redistribution of actin between the different networks of the yeast cell. [ABSTRACT FROM AUTHOR]

Background: Dermatofibroma (DF) is a common benign skin lesion in a majority of cases located on the legs or upper limbs. The etiology of DF is still unclear. Objectives: Reflectance confocal microscopy features of DF were described. Methods: Forty patients with DF diagnosis confirmed by dermoscopy were examined using reflectance confocal microscopy VivaScope 1500 from March 2018 to April 2019. Results: DF was more common in females (80%) than males (20%). Thirty‐six lesions (90%) were located on the limbs while four (10%) were on the trunk. Dermoscopically, 18 lesions (45%) revealed typical features: central white area with a brown network in the periphery. Twenty‐two DFs (55%) were found with a central white patch and globular‐like structures, surrounded by a thin brown network. In reflectance confocal microscopy, all revealed a typical honeycombed pattern, although in some cases (30%), streaming was observed. In two lesions (5%) in epidermis, few dendritic cells were observed, and one DF revealed roundish pagetoid cells (2.5%). The dermoepidermal junction (DEJ) in all lesions was abounded in dilated vessels. The most common observable feature of DF was bright "rings" composed of monomorphic, regular cells surrounding dark dermal papillae. In five lesions (12.5%), rings were "double" because of exceptionally pigmented DF. Conclusion: Reflectance confocal microscopy enables us to describe microscopic features of DF. There are four confocal microscopic features observable in each DF: in the epidermis, normal honeycombed pattern, sometimes with local streaming, in DEJ, edged papillae, bright rings, and dilated vessels. [ABSTRACT FROM AUTHOR]

The Catholic Church is the largest religious denomination in the United States, yet political science lacks a comprehensive account of how the cross‐pressures created by its policy prescriptions structure Catholic political behavior. Because Catholicism's policy positions land on both sides of the contemporary partisan divide—its cultural concerns aligning with the Republican Party and its pro‐social justice stance compatible with Democratic priorities—adherence to Church teaching creates electoral dilemmas for Catholic voters. By juxtaposing existing work on Catholic political behavior with the psychological literature on cognitive dissonance, we form expectations about Catholic adherence to Church policy prescriptions and its implications for electoral choice. We focus empirically on "Seamless Garment Catholics" (SGCs)—those Catholics who share the Church's policy positions—finding that seamless‐garment views are uncommon among Catholic voters, are more common among religiously committed and Latino Catholics, and are discouraged by ties to the two major parties. SGCs are more likely than other Catholics to employ psychological coping mechanisms, such as avoidance and selective perception, to reduce Church‐inspired cognitive dissonance. Our research provides insight into an important electoral bloc that is cross‐pressured uniquely by its faith commitments. [ABSTRACT FROM AUTHOR]

Introduction: Halo nevi named also Sutton's nevi are uncommon melanocytic lesions occurring especially among adolescents. There are two effective diagnostic methods: dermoscopy and in vivo reflectance confocal microscopy (RCM), which can help us to observe many structural elements and characteristic features of Sutton's nevi. Objectives: The aim of this study was to describe reflectance confocal microscopy features of halo nevi. Methods: Eleven patients with fourteen halo nevi were examined by FotoFinder Medicam 800 dermoscope and reflectance confocal microscope Viva Scope 1500 between May of 2018 and September of 2019. Results: Dermoscopic examination revealed 78.6% nevi with a globular pattern, while 21.4% showed a homogenous pattern. In RCM, a typical honeycombed pattern was observed in 57.1% of nevi. 42.9% of nevi showed a disarray of the epidermis and presence of dendritic cells. 35.7% of all lesions presented roundish atypical cells in the epidermis. Roundish pagetoid cells in the dermo‐epidermal junction were detected in 14.2% of nevi. Non‐edged papillae were observed in 50% of lesions. In each nevus, there were dilated vessels. 50% of nevi revealed dense nests in the periphery, although in case of one lesion the dishomogeneous nests were observed. Conclusions: Halo nevi are important "melanoma simulators" in confocal microscopy. [ABSTRACT FROM AUTHOR]

The diagnosis of melanoma is challenging for both dermatologists and oncologists. Incidence of melanoma increases at a rate of 3–7% per year. Usage of modern tools such as dermoscopy and in vivo reflectance confocal microscopy improve early diagnosis and can save a life. There are a few melanoma simulators which can cause confusion and mislead in the differential diagnosis. This study aims to present skin lesions which can be similar to melanoma in confocal microscopy and to emphasize the importance of a detailed differential diagnosis. We describe five melanocytic lesions similar to melanoma and misleading confocal features. Although in vivo reflectance confocal microscopy is very useful in differentiating melanocytic lesions, histopathology evaluation in cases of melanoma mimics is definitive. [ABSTRACT FROM AUTHOR]

The absence of clefting in some tumour areas appears to be the common, but nonsignificant RCM feature for TB recognition. Although RCM appears to be useful in differential diagnosis of BCC and TB, the final diagnosis is made after histopathological evaluation, which is recommended for all lesions of that kind. Trichoblastoma (TB) is a benign adnexal tumour that is difficult to differentiate from basal cell carcinoma (BCC). [Extracted from the article]

Dear Editor, Necrobiosis lipoidica (NL) is an uncommon skin disease of unknown B pathogenesis b with an average age at onset of about 40 years. The histopathological evaluation performed after a biopsy confirmed the diagnosis of necrobiosis lipoidica. About 40% of patients with necrobiosis lipoidica have type 2 diabetes.1 Usually, the diagnosis of necrobiosis lipoidica is based on clinical examination; however, it can sometimes be indistinguishable from granuloma annulare, sarcoidosis or other necrobiotic disorders. [Extracted from the article]

Abstract: Light detection and ranging (LiDAR) technology provides ecologists with high‐resolution data on three‐dimensional vegetation structure. Large LiDAR datasets challenge predictive ecologists, who commonly simplify point clouds into structural attributes (namely LiDAR‐based metrics such as canopy height), which are used as predictors in ecological models, potentially with loss of relevant information. We illustrate an efficient alternative approach to reduce the dimensionality of LiDAR data that aims at minimal data filtering with no a priori assumptions on the ecology of the target species. We first fit the ecological model exploiting the full variability in the LiDAR point cloud, then we explain the results using post‐modelling LiDAR‐data classification for ecological interpretation only. This is the classical logic of explorative, hypothesis generating and predictive statistics, rather than testing specific vegetation‐structural hypotheses. First, we reduce the dimensionality of the LiDAR point cloud by principal component analysis (PCA) to fewer predictors. Second, we show that LiDAR‐PCs are capable to outperforming commonly used environmental predictors in ecological modelling, including LiDAR‐based metrics. We exemplify this by modelling red deer (Cervus elaphus) and roe deer (Capreolus capreolus) resource selection in the Bavarian Forest National Park, Germany. After fitting the ecological model, we provide an interpretation of the information included in LiDAR‐PCs, which allows users to draw conclusions whenever using them as predictors. We make use of the PCA rotation matrix and post‐modelling data classification, and document deer selection for understorey vegetation at unprecedented fine scale. Our approach is the first attempt in animal ecology to avoid the use of LiDAR‐based metrics as model predictors, but rather generate principal components able to capture most of the LiDAR point cloud variability. Our study demonstrates that LiDAR‐PCs can boost ecological models. We envision a potential use of LiDAR‐PCs in several applications, particularly species distribution and habitat suitability models. We demonstrate an application of our approach by building suitability maps for both deer species, which can be used by practitioners to visualize model spatial predictions and understand the type of forest structures selected by deer. [ABSTRACT FROM AUTHOR]

Background: U.S. POINTER is testing whether multidomain lifestyle interventions focused on physical exercise, nutrition, cognitive challenge, and risk factor management reduces risk of cognitive decline in a heterogeneous population of at‐risk older adults in America. The study adapts the FINGER (Finnish Intervention Geriatric Study to Prevent Cognitive Impairment and Disability) interventions to fit the United States culture and delivers the intervention within the community at 5 sites across the country. Method: U.S. POINTER is a 2‐year RCT that will enroll 2000 cognitively unimpaired older adults who are at risk for cognitive decline due sedentary lifestyle, poor diet and other factors. Participants are randomized to one of two lifestyle intervention groups that differ in format and intensity. In 2020, the COVID‐19 pandemic presented a number of challenges for the study that affected recruitment, assessment schedules, and intervention delivery. Result: As of March 2020, when COVID‐19 incidence was on an exponential rise in the US, 240 participants had been enrolled in U.S. POINTER. In response to local and national safety mandates, study activities were paused from March 23rd to July 13th. During the pause, sites remained in contact with study candidates and enrolled participants to provide ongoing support to keep them engaged in the trial. Enrollees also received regular telephone calls to encourage continued adherence to their assigned lifestyle intervention. In response to the multiple pandemic‐related challenges, study protocols and procedures were adapted to facilitate and encourage participant adherence to intervention activities. At study re‐start, retention was 98%. Despite climbing COVID‐19 infection rates nationwide, enrollment at all 5 sites has continued at a steady rate (N=540 as of Jan2021), virtual Team Meeting attendance for both lifestyle groups exceeds 80%, and participants continue to successfully work toward their intervention goals. Conclusion: The COVID‐19 pandemic presented unprecedented challenges, but it also provided a unique opportunity to adapt intervention delivery so that a nonpharmacological community‐based trial could continue – even during a debilitating global health crisis. U.S. POINTER's adaptations to pandemic‐related challenges may ultimately increase the resilience of its interventions to even the most challenging of circumstances that older adults will face now and in the future. [ABSTRACT FROM AUTHOR]

Purpose Gene-modified mice may be used to elucidate molecular mechanisms underlying abnormal myocardial blow flow (MBF). We sought to develop a quantitative myocardial perfusion imaging technique for mice and to test the hypothesis that myocardial perfusion reserve (MPR) is reduced in a mouse model of diet-induced obesity (DIO). Methods A dual-contrast saturation-recovery sequence with ky-t undersampling and a motion-compensated compressed sensing reconstruction algorithm was developed for first-pass MRI on a small-bore 7 Tesla system. Control mice were imaged at rest and with the vasodilators ATL313 and Regadenoson (n = 6 each). In addition, we imaged mice fed a high-fat diet (HFD) for 24 weeks. Results In control mice, MBF was 5.7 ± 0.8 mL/g/min at rest and it increased to 11.8 ± 0.6 mL/g/min with ATL313 and to 10.4 ± 0.3 mL/g/min with Regadenoson. In HFD mice, we detected normal resting MBF (5.6 ± 0.4 versus 5.0 ± 0.3 on control diet), low MBF at stress (7.7 ± 0.4 versus 10.4 ± 0.3 on control diet, P < 0.05), and reduced MPR (1.4 ± 0.2 versus 2.0 ± 0.3 on control diet, P < 0.05). Conclusion Accelerated dual-contrast first-pass MRI with motion-compensated compressed sensing provides spatiotemporal resolution suitable for measuring MBF in free-breathing mice, and detected reduced MPR in DIO mice. These techniques may be used to study molecular mechanisms that underlie abnormal myocardial perfusion. Magn Reson Med 73:1237-1245, 2015. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background and Purpose Impaired function of spinal strychnine-sensitive glycine receptors gives rise to chronic pain states and movement disorders. Therefore, increased activity of glycine receptors should help to treat such disorders. Although compounds targeting glycine receptors with a high selectivity are lacking, halogenated analogues of propofol have recently been considered as potential candidates. Therefore we asked whether 4-bromopropofol attenuated the excitability of spinal neurons by promoting glycine receptor-dependent inhibition. Experimental Approach The actions of sub-anaesthetic concentrations of propofol and 4-bromopropofol were investigated in spinal tissue cultures prepared from mice. Drug-induced alterations in action potential firing were monitored by extracellular multi-unit recordings. The effects on GABAA and glycine receptor-mediated inhibition were quantified by whole-cell voltage-clamp recordings. Key Results Low concentrations of 4-bromopropofol (50 nM) reduced action potential activity of ventral horn neurons by about 30%, compared with sham-treated slices. This effect was completely abolished by strychnine (1 μM). In voltage-clamped neurons, 4-bromopropofol activated glycine receptors, generating a tonic current of 65 ± 10 pA, while GABAA- and glycine receptor-mediated synaptic transmission remained unaffected. Conclusions and Implications The highest glycine levels in the CNS are found in the ventral horn of the spinal cord, a region mediating pain-induced motor reflexes and participating in the control of muscle tone. 4-Bromopropofol may serve as a starting point for the development of non-sedative, non-addictive, muscle relaxants and analgesics to be used to treat low back pain. [ABSTRACT FROM AUTHOR]

In this study, changes in gene effects for milk production traits were analysed over time. Such changes can be expected by investigating daily milk production yields, which increase during the early phase of lactation and then decrease. Moreover, additive polygenic effects on milk production traits estimated in other studies differed throughout the 305 days of lactation, clearly indicating changes in the genetic determination of milk production throughout this period. Our study focused on particular candidate genes known to affect milk production traits and on the estimation of potential changes in the magnitude of their effects over time. With two independent data sets from Holstein-Friesian and Jersey breeds, we show that the effects of the DGAT1:p.Lys232Ala polymorphism on fat and protein content in milk change during lactation. The other candidate genes considered in this study ( leptin receptor, leptin and butyrophilin, subfamily 1, member A1) exhibited effects that vary across time, but these could be observed in only one of the breeds. Longitudinal modelling of SNP effects enables more precise description of the genetic background underlying the variation of complex traits. A gene that changes the magnitude or even the sign of its effect cannot be detected by a time-averaged model. This was particularly evident when analysing the effect of butyrophilin, missed by many previous studies, which considered butyrophilin's effect as constant over time. [ABSTRACT FROM AUTHOR]

Background: U.S. POINTER aims to test whether a multidomain lifestyle intervention focused on physical and cognitive activity, nutrition, and risk factor management reduces risk of cognitive decline in a heterogeneous population of older adults in the U.S. The study adapts the FINGER (Finnish Intervention Geriatric Study to Prevent Cognitive Impairment and Disability) interventions to fit American culture and works with community partners at 5 sites across the country to develop sustainable community‐based intervention programs. Methods: U.S. POINTER is a 2‐year RCT that is enrolling 2000 cognitively normal older adults (60‐79 years) who are at risk for decline due sedentary lifestyle, poor diet and other factors such as family history of memory impairment and suboptimum cardiovascular health. Recruitment utilizes electronic health records, as well as grassroots approaches to engage traditionally underrepresented groups. Participants are randomized to one of two lifestyle intervention groups – Self‐Guided or Structured Lifestyle Intervention – that differ in format, intensity and accountability. U.S. POINTER includes partnerships with local chapters of the Alzheimer's Association and lifestyle specialists to assist with intervention delivery. The primary outcome is 2‐year change in cognitive function measured with a composite score that permits harmonization with FINGER. Results: Recruitment began in 2019 at the vanguard site in North Carolina. Study progress at all 5 participating sites will be presented. Progress toward harmonization with FINGER and other international study teams in the WW‐FINGERS network will also be discussed. Conclusion: As a member of the WW‐FINGERS network of trials, U.S. POINTER provides an unprecedented opportunity to leverage lessons learned in FINGER and expand this work to test the generalizability of the findings to a heterogeneous American cohort with different cultural needs and practices. The results, in combination with those from other WW‐FINGERS studies, have the potential to identify a strategy to slow cognitive decline on a global scale. [ABSTRACT FROM AUTHOR]

Purpose: To develop and validate modified Look-Locker (MOLLI) protocols to generate myocardial T1 maps within clinically acceptable breath-hold durations and to compare partition coefficients (λ) of gadolinium (Gd)-DTPA determined from either bolus injection (BI) or continuous infusion (CI) techniques.Materials and Methods: T1 mapping was performed in phantoms and in 10 volunteers on a 1.5T scanner using the standard (3-3-5) MOLLI technique and two MOLLI schemes with shorter breath-hold durations. Imaging was performed precontrast and every 5 minutes following a bolus of 0.1 mmol/kg Gd-DTPA and a 15-minute delayed continuous infusion of 0.001 mmol/kg Gd-DTPA until equilibrium T1 in the myocardium was achieved to enable direct comparison of T1 relaxation times between techniques and λ's between the BI and CI methods.Results: There was good agreement of T1 values between the 3-3-5 standard MOLLI protocol and the modified 3-5 MOLLI protocol in both phantom studies over a range of heart rates and in human subjects. Both MOLLI protocols produced similar measurements of λ using both the BI and CI methods.Conclusion: A reduced breath-hold MOLLI T1 mapping protocol combined with the BI method can accurately characterize T1 and λ in clinically applicable breath-hold durations without requiring a long equilibrium phase infusion. [ABSTRACT FROM AUTHOR]

Purpose To develop and validate modified Look-Locker (MOLLI) protocols to generate myocardial T1 maps within clinically acceptable breath-hold durations and to compare partition coefficients (λ) of gadolinium (Gd)-DTPA determined from either bolus injection (BI) or continuous infusion (CI) techniques. Materials and Methods T1 mapping was performed in phantoms and in 10 volunteers on a 1.5T scanner using the standard (3-3-5) MOLLI technique and two MOLLI schemes with shorter breath-hold durations. Imaging was performed precontrast and every 5 minutes following a bolus of 0.1 mmol/kg Gd-DTPA and a 15-minute delayed continuous infusion of 0.001 mmol/kg Gd-DTPA until equilibrium T1 in the myocardium was achieved to enable direct comparison of T1 relaxation times between techniques and λ's between the BI and CI methods. Results There was good agreement of T1 values between the 3-3-5 standard MOLLI protocol and the modified 3-5 MOLLI protocol in both phantom studies over a range of heart rates and in human subjects. Both MOLLI protocols produced similar measurements of λ using both the BI and CI methods. Conclusion A reduced breath-hold MOLLI T1 mapping protocol combined with the BI method can accurately characterize T1 and λ in clinically applicable breath-hold durations without requiring a long equilibrium phase infusion. J. Magn. Reson. Imaging 2013;38:217-224. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Pancreatic β-cell imaging would be useful in monitoring the progression of and therapies for diabetes. The purpose of this study was to develop and evaluate quantitative β-cell MRI using manganese (Mn2+) labeling of β cells, T1 mapping, and a two-site water exchange model. Normal, pharmacologically-treated, and severely diabetic mice underwent injection of MnCl2. Pancreatic water proton T1 relaxation was measured using Look-Locker MRI, and two-site water exchange analysis was used to estimate model parameters including the intracellular water proton relaxation rate constant (R1ic) and the intracellular fraction as indicators of β-cell function and mass, respectively. Logarithmic plots of T1 relaxation revealed two distinct proton pools relaxing with different T1s, and the two-site water exchange model fit the measured T1 relaxation data better than a monoexponential model. The intracellular R1ic time course revealed the kinetics of β-cell Mn2+ labeling. Pharmacological treatments with nifedipine, tolbutamide, and diazoxide altered R1ic, indicating that beta cell function was a determinant of Mn2+ uptake. Intracellular fraction was significantly higher in mice with normal β cell mass than in diabetic mice (14.9% vs. 14.4%, P < 0.05). Two-site water exchange analysis of T1 relaxation of the Mn2+-enhanced pancreas is a promising method for quantifying β cell volume fraction and function. Magn Reson Med, 2011. © 2011 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

A reliable description and quantification of the complex physiology and reactions of living cells requires a multimodal analysis with various measurement techniques. We have investigated the integration of different techniques into a biophotonic workstation that can provide biological researchers with these capabilities. The combination of a micromanipulation tool with three different imaging principles is accomplished in a single inverted microscope which makes the results from all the techniques directly comparable. Chinese Hamster Ovary (CHO) cells were manipulated by optical tweezers while the feedback was directly analyzed by fluorescence lifetime imaging, digital holographic microscopy and dynamic phase-contrast microscopy. (© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [ABSTRACT FROM AUTHOR]

Cell transfection using femtosecond lasers is gaining importance for its proven ability to achieve selective transfection in a sterile and relatively non-invasive manner. However, the net efficiency of this technique is limited due to a number of factors that ultimately makes it difficult to be used as a viable and widely used technique. We report here a method to achieve significant enhancement in the efficiency of femtosecond optical transfection. The transfection procedure is modified by incorporating a suitable synthetic peptide containing nuclear localization and DNA binding sequences, assisting DNA import into the nucleus. We achieved a 3-fold enhancement in the transfection efficiency for adherent Chinese Hamster Ovary (CHO-K1) cells with this modified protocol. Further, in the presence of this biochemical reagent, we were able to reduce the required plasmid concentration by ∼70% without compromising the transfection efficiency. Also, we report for the first time the successful photo-transfection of recently trypsinised cells with significantly high transfection efficiency when transfected with modified plasmid. This paves the way for the development of high throughput microfluidic optical transfection devices. (© 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [ABSTRACT FROM AUTHOR]

We demonstrate the advantages of a dynamic diffractive optical element, namely a spatial light modulator (SLM) for the controlled and enhanced optoinjection and phototransfection of mammalian cells with a femtosecond light source. The SLM provides full control over the lateral and axial positioning of the beam with sub-micron precision. Fast beam translation enables time-sequenced irradiation, which is shown to enhance the optoinjection efficiency and alleviate the problem of exact beam positioning on the cell membrane. We show that irradiation in three axial positions doubles the number of viably optoinjected cells when compared with a single dose. The presented system also enables untargeted raster scan irradiation which provides a higher throughput transfection of adherent cells at the rate of 1 cell per second. Additionally, fluorescent imaging is used to demonstrate cell selective two-step gene therapy. (© 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [ABSTRACT FROM AUTHOR]

General anaesthetics cause sedation, amnesia and hypnosis. Although these clinically desired actions are indicative of an impairment of neocortical information processing, it is widely held that they are to a large part mediated by subcortical neural networks. Anaesthetic action on brain stem, basal forebrain and thalamus, all of which are known to modulate cortical excitability, would thus ultimately converge on neocortex, perturbing and reducing action potential activity therein. However, as neocortex harbours molecular targets of anaesthetics in high densities, notably GABAA receptors, neocortex itself should be very sensitive to anaesthetics. Here, we performed experiments to reveal the extent to which neocortex proper is a relevant target of the low concentrations of volatile anaesthetics causing sedation and hypnosis. We compared the effects of isoflurane, enflurane and halothane on spontaneous action potential activity of rat neocortical neuronsin vivoand in isolated cortical networksin vitro, i.e. in the presence and absence of subcortical arousal systems. We observed that the anaesthetics decreased spontaneous firing of neurons via intracortical mechanisms; concentrations inducing hypnosis in humans reduced discharge rates bothin vivoandin vitroto the same extent, approximately 50%. This decrease in neuronal activity was paralleled by a significant enhancement of neocortical GABAA receptor-mediated inhibition. These findings challenge the notion of predominantly subcortical effects of volatile anaesthetics and suggest that intracortical targets, among them neocortical GABAA receptors, mediate the sedative and hypnotic properties of volatile anaesthetics. [ABSTRACT FROM AUTHOR]

The lateral leaflets of Desmodium motorium (Houtt.) Merr, exhibit ultradian up- and down movements, which are paralleled by oscillations of the membrane potential of motor cells in the pulvinus. By different treatments we have tested the hypothesis that both oscillation-types are causally related. The reactions of the leaflet movement and the membrane potential were evaluated by the following approaches. (1) Application of vanadate, an inhibitor of the proton pump in the plasmalemma, and N2 suppressed leaflet movements and finally arrested the leaflet in the lower position. Before the oscillations damped out, a strong lengthening in period was found. This indicates that the pump is part of the ultradian clock. A period lengthening and a final suppression of the rhythm by vanadate was also seen in the extracellular electric potential of the pulvinus. Intracellular recordings in situ showed that vanadate application depolarized the motor cells. (2) Light of high fluence rates diminished the amplitude of the oscillations of the membrane potential of single motor cells and shortened the period. The same effects were observed when monitoring the lateral leaflet movement. The leaflet always moved towards the direction of the light, whether it was applied from the abaxial or from the adaxial part of the pulvinus. (3) When light was applied to the pulvinus of lateral leaflets, which had spontaneously stopped moving in an upper position, oscillations were induced transiently. This effect was also found for the membrane potential of motor cells in the pulvinus. - Our results thus provide further evidence that the membrane potential controls the volume state of the motor cells in the pulvinus of lateral leaflets of Desmodium motorium. [ABSTRACT FROM AUTHOR]

We aimed to examine the association between canine I AMY2B i copy number and obesity, as measured by the five-point body condition score (BCS) and body weight. We found no association of obesity with the I AMY2B i copy number (logistic regression BCS 3 vs. 4+5; I P i < 0.189) and no statistically significant differences in the number of copies across BCS groups (ANOVA, I P i < 0.215; Fig. a). [Extracted from the article]

We studied seeds of 25 species of Noccaea and 3 species of Thlaspi s.s. from Europe, southwestern Asia and northern Africa using scanning electron microscopy (SEM). Macro‐ and micromorphological characters, including seed shape, the size and shape of epidermal cells, anticlinal boundaries, outer periclinal cell walls and the outlines of outer cell walls were recorded. Two types of anticlinal cell wall boundaries were recognised and 5 different shapes of outer periclinal walls are described. The secondary sculpture of the cell walls varies from smooth to striate, micro‐papillate to finely foled and rugulate. The epicuticular wax comes in platelets in all the species. SEM examinations at higher magnifications revealed 5 types of seed surface sculpture: colliculate, reticulate, mixed (colliculate‐reticulate), verrucate and foveolate in Noccaea, in addition to ribbed and reticulate patterns in Thlaspi s.s. SEM studies of the taxa showed that the seed patterns are species‐specific and support a clear distinction between Noccaea and Thlaspi. However, some species of Noccaea cannot be separated based on seed size and shape, but may only be identified to their groups. Micromorphological features of the seed surface are thus of great value, both for the differentiation between the genera Noccaea and Thlaspi and for the species‐level taxonomy. A key to the identification of the investigated taxa based on the micromorphological characters is provided. [ABSTRACT FROM AUTHOR]