Extended approach or usage of nasoseptal flap is a risk factor for olfactory dysfunction after endoscopic anterior skullbase surgery: results from 928 patients in a single tertiary center.

BACKGROUND: The aim of this study was to compare olfactory function change in patients who underwent endoscopic skull-base surgery. METHODOLOGY: A total of 928 patients were included in this retrospective study. Olfactory function was measured using the non- validated Likert scale (0â€"100), the Cross-Cultural Smell Identification Test (CC-SIT) and the butanol threshold test (BTT). Patients were divided into two groups: an endoscopic trans-sellar approach group (ETA, n = 768) and an extended endoscopic endonasal approach group (EEEA, n = 160). The ETA group was sub-divided into Nasoseptal flap (NSF) and no NSF groups. RESULTS: Non-validated olfactory function significantly worsened in the EEEA and ETA-NSF groups compared with that in the ETA- no NSF group for at least 6 months post-operatively. Validated olfactory impairment (BTT and CC-SIT) was also significantly worse in the EEEA and NSF groups compared with that in the ETA-no NSF group 3 months post-operatively. Additionally, the degrees of non-validated and validated olfactory deterioration were not significantly different between the EEEA and ETA-NSF groups. We also found that CC-SIT score changes were significantly impaired in tuberculum sellae meningioma patients than in craniopharyn- gioma patients. CONCLUSIONS: We conclude that NSF was the key factor that led to olfactory impairment after endoscopic skull-base surgery.

Nigrosome 1 Detection at 3T MRI for the Diagnosis of Early-Stage Idiopathic Parkinson Disease: Assessment of Diagnostic Accuracy and Agreement on Imaging Asymmetry and Clinical Laterality.

BACKGROUND AND PURPOSE: In the early stages of idiopathic Parkinson disease, motor symptoms are usually asymmetric. We aimed to assess the feasibility of nigrosome 1 detection at 3T MR imaging to analyze the agreement of its asymmetry and clinical laterality. MATERIALS AND METHODS: High-resolution 3D multiecho imaging was performed at 3T MR imaging in 13 healthy subjects and 24 patients with idiopathic Parkinson disease confirmed by N-3-fluoropropyl-2-ß-carbomethoxy-3-ß-(4-iodophenyl) nortropane ((18)F-FP-CIT) PET. The nigrosome 1 detection findings by using the MR imaging data were rated as "normal," "possibly abnormal," and "abnormal" by 2 independent reviewers. The degree of (18)F-FP-CIT binding was visually assessed in the caudate nucleus and putamen on PET images. Clinical laterality was evaluated by scores of the Unified Parkinson Disease Rating Scale, Part III. Asymmetry of the affected nigrosome 1 and the degree of (18)F-FP-CIT binding were analyzed for agreement with clinical laterality. RESULTS: The diagnostic sensitivity, specificity, and accuracy of the nigrosome 1 detection at 3T MR imaging was 100%, 84.6%, and 94.6%, respectively. Interrater agreements for the abnormality and asymmetry of nigrosome 1 were excellent (κ = 0.863 and 0.835, respectively). In patients with idiopathic Parkinson disease, the agreement of asymmetry between clinical laterality and nigrosome 1 detection was good (κ = 0.724). The degree of the (18)F-FP-CIT PET binding showed fair agreement (κ = 0.235) with clinical laterality. CONCLUSIONS: The abnormality involving nigrosome 1 can be detected at 3T MR imaging with an accuracy of 94.6%. The clinical laterality is in high concordance with the laterality of the nigrosome 1 detection at 3T (κ = 0.724).

Comfort and learnability assessment of a new soft robotic manipulator for minimally invasive surgery.

Laparoscopic surgeons perform precise and time consuming procedures while holding awkward poses in their upper body and arms. There is an ongoing effort to produce robotic tools for laparoscopic surgery that will simplify these tasks and reduce risk of errors to help both the surgeon and the patient. STIFF-FLOP is an ongoing EU FP7 project focusing on this by creating a stiffness controllable soft robotic manipulator. This paper reports on a study to test the soft manipulator's learnability and the effort associated with its use. The tests involved a limited prototype of the manipulator with a custom built test rig and EMG acquisition system. Task times and video recordings along with EMG waveforms from the forearm muscles of participants (n=25) were measured for objective assessment. A questionnaire was also provided to the participants for subjective assessment. The data shows that in average EMG levels were 25.9% less in RMS when using the STIFF-FLOP arm than when conventional laparoscopic tools were used. In terms of learnability, from the first to the second attempt on the STIFF-FLOP manipulator, elapsed time was reduced by an average of 32.1%. Further details and analysis of the EMG signals as well as time and questionnaire results is presented in the paper.

Higher C-peptide levels are associated with regional cortical thinning in 1093 cognitively normal subjects.

BACKGROUND AND PURPOSE: Recent studies have demonstrated an association between increased insulin secretion and cognitive impairment. However, there is no previous study that directly evaluates the association between increased insulin secretion and cortical thickness to our knowledge. Therefore, our aim was to evaluate the effect of hyperinsulinemia, as measured by C-peptide level, on cortical thickness in a large sample of cognitively normal individuals. METHODS: Cortical thickness was measured in 1093 patients who visited the Samsung Medical Health Promotion Center and underwent brain magnetic resonance imaging (MRI) and a blood test to measure C-peptide concentration. Automated surface-based analyses of the MRI data were used to measure cortical thickness. C-peptide levels were divided into quartiles for comparison. Patients in the first to third quartiles were used as the reference category. RESULTS: Patients in the highest quartile group (Q4) of C-peptide levels showed cortical thinning, predominantly in both medial temporal lobes, the right inferior temporal gyrus, both medial prefrontal lobes and the right superior parietal lobule, compared with the lower quartile groups (Q1-Q3) after controlling for age, gender, body mass index, history of hypertension, hyperlipidemia, previous stroke, cardiovascular disease and fasting glucose level. CONCLUSIONS: A higher C-peptide level is associated with regional cortical thinning, even in cognitively normal individuals.

Cortical thickness and hippocampal shape in pure vascular mild cognitive impairment and dementia of subcortical type.

BACKGROUND AND PURPOSE: The progression pattern of brain structural changes in patients with isolated cerebrovascular disease (CVD) remains unclear. To investigate the role of isolated CVD in cognitive impairment patients, patterns of cortical thinning and hippocampal atrophy in pure subcortical vascular mild cognitive impairment (svMCI) and pure subcortical vascular dementia (SVaD) patients were characterized. METHODS: Forty-five patients with svMCI and 46 patients with SVaD who were negative on Pittsburgh compound B (PiB) positron emission tomography imaging and 75 individuals with normal cognition (NC) were recruited. RESULTS: Compared with NC, patients with PiB(-) svMCI exhibited frontal, language and retrieval type memory dysfunctions, which in patients with PiB(-) SVaD were further impaired and accompanied by visuospatial and recognition memory dysfunctions. Compared with NC, patients with PiB(-) svMCI exhibited cortical thinning in the frontal, perisylvian, basal temporal and posterior cingulate regions. This atrophy was more prominent and extended further toward the lateral parietal and medial temporal regions in patients with PiB(-) SVaD. Compared with NC subjects, patients with PiB(-) svMCI exhibited hippocampal shape deformities in the lateral body, whilst patients with PiB(-) SVaD exhibited additional deformities within the lateral head and inferior body. CONCLUSIONS: Our findings suggest that patients with CVD in the absence of Alzheimer's disease pathology can be demented, showing cognitive impairment in multiple domains, which is consistent with the topography of cortical thinning and hippocampal shape deformity.

Exploration of optimal dosing regimens of vancomycin in patients infected with methicillin-resistant Staphylococcus aureus by modeling and simulation.

WHAT IS KNOWN AND OBJECTIVE: Vancomycin is the drug of choice for methicillin-resistant Staphylococcus aureus (MRSA) infection and shows time-dependent bacterial killing. The current study evaluated the pharmacokinetics (PK) and pharmacodynamics (PD) of vancomycin and explored its optimal dosing regimens by modeling and simulation. METHODS: Pharmacokinetics study was performed for 20 patients who were treated with vancomycin intravenously, 1000 mg, every 12 h, and blood for PK was randomly drawn within prespecified time windows. PD study was in vitro time-kill experiment for vancomycin against 20 MRSA strains independent of the PK study, where bacterial titre was measured at 0, 2, 4, 8, 24 h after the beginning of vancomycin exposure at 0, 1, 2, 4, 8, 16, 32× minimum inhibitory concentrations. PK and PD models were built from each data set, and simulation for MRSA titre changes over time in human body was performed for various vancomycin dosing regimens using NONMEM(®) . RESULTS: Vancomycin followed a two-compartment PK model, and creatinine clearance was the significant covariate affecting the clearance of vancomycin. PD model described the in vitro time-kill data well. The PK/PD model predicted clear dose-response relationships of vancomycin. The therapeutic dosing regimens of vancomycin, suggested by the simulation studies, showed good agreement with the current clinical practice guidance, which indicates that this PK/PD modeling and simulation approach could prove useful for identifying optimal dosing regimens of other antibiotics and expediting novel antibiotic development. Using PD model from in vitro time-kill study and human PK model from phase 1 study, we could predict whether the drug is going to be efficacious or obtain insight into the optimal dosing regimens for a novel antibiotic agent in the early phases of drug development process.

Endoscopic add-on stiffness probe for real-time soft surface characterisation in MIS.

This paper explores a novel stiffness sensor which is mounted on the tip of a laparoscopic camera. The proposed device is able to compute stiffness when interacting with soft surfaces. The sensor can be used in Minimally Invasive Surgery, for instance, to localise tumor tissue which commonly has a higher stiffness when compared to healthy tissue. The purely mechanical sensor structure utilizes the functionality of an endoscopic camera to the maximum by visually analyzing the behavior of trackers within the field of view. Two pairs of spheres (used as easily identifiable features in the camera images) are connected to two springs with known but different spring constants. Four individual indenters attached to the spheres are used to palpate the surface. During palpation, the spheres move linearly towards the objective lens (i.e. the distance between lens and spheres is changing) resulting in variations of their diameters in the camera images. Relating the measured diameters to the different spring constants, a developed mathematical model is able to determine the surface stiffness in real-time. Tests were performed using a surgical endoscope to palpate silicon phantoms presenting different stiffness. Results show that the accuracy of the sensing system developed increases with the softness of the examined tissue.

Comparison of cortical thickness in patients with early-stage versus late-stage amnestic mild cognitive impairment.

BACKGROUND AND PURPOSE: Disappointing outcomes from clinical trials involving amyloid-modifying therapies for Alzheimer's disease (AD) have prompted more focus on the concept of early-stage (E) amnestic mild cognitive impairment (E-aMCI). However, limited evidence suggests that E-aMCI may represent aMCI at a very early stage of AD. Furthermore, the nature of the progression of E-aMCI to late-stage aMCI (L-aMCI) remains unclear. Therefore, the aim of the present study was to characterize patterns of cortical thinning in both E-aMCI and L-aMCI patients. METHODS: Cortical thicknesses were measured in 190 patients with aMCI and 147 subjects with normal cognition. In accordance with memory test scores involving delayed recall items, aMCI patients were divided into two subgroups, containing 73 E-aMCI subjects with milder memory impairment [scores between -1.5 standard deviation (SD) and -1.0 SD compared with age- and education-matched norms] and 117 L-aMCI subjects with more severe memory impairment (scores lower than -1.5 SD). RESULTS: Compared with controls, the E-aMCI group exhibited cortical thinning in the left medial temporal and insular regions, whereas the L-aMCI group showed cortical thinning in widespread regions, including the bilateral dorsolateral prefrontal, anterior and medial temporal, and temporo-parietal association cortices, and the precuneus. When the two aMCI groups were directly compared, the L-aMCI group showed greater cortical thinning in the right superior prefrontal, medial temporal, posterior cingulate and lateral parietal cortices. CONCLUSION: Our findings suggest that E-aMCI might represent an early symptomatic stage of AD. Furthermore, L-aMCI might resemble AD more closely than E-aMCI, in terms of the topography of cortical thinning.

Biomechanical evaluation of the phases during simulated endotracheal intubation (ETI): pilot study on the effect of different laryngoscopes.

Endotracheal Intubation (ETI) is a common airway procedure used to connect the larynx and the lungs through a windpipe in patients under emergency situations. The process is carried out by a laryngoscope inserted into the mouth, used to help doctors in visualizing the glottis and inserting the tube. Currently, very few studies on objective evaluation of the biomechanics of the doctors during the procedure have been done. Additionally, these studies have been concentrated only on the overall performance analysis, without any segmentation, with a consequent loss of important information. In this paper, the authors present a preliminary study on a methodology to objectively evaluate and segment the biomechanical performance of doctors during the ETI, using surface electromyography and inertial measurement units. In particular, the validation has been performed by comparing three kinds of laryngoscopes involving an expert doctor. Finally, results are presented and commented.

Inhibition of oxidative stress by coenzyme Q10 increases mitochondrial mass and improves bioenergetic function in optic nerve head astrocytes.

Oxidative stress contributes to dysfunction of glial cells in the optic nerve head (ONH). However, the biological basis of the precise functional role of mitochondria in this dysfunction is not fully understood. Coenzyme Q10 (CoQ10), an essential cofactor of the electron transport chain and a potent antioxidant, acts by scavenging reactive oxygen species (ROS) for protecting neuronal cells against oxidative stress in many neurodegenerative diseases. Here, we tested whether hydrogen peroxide (100 µM H2O2)-induced oxidative stress alters the mitochondrial network, oxidative phosphorylation (OXPHOS) complex (Cx) expression and bioenergetics, as well as whether CoQ10 can ameliorate oxidative stress-mediated alterations in mitochondria of the ONH astrocytes in vitro. Oxidative stress triggered the activation of ONH astrocytes and the upregulation of superoxide dismutase 2 (SOD2) and heme oxygenase-1 (HO-1) protein expression in the ONH astrocytes. In contrast, CoQ10 not only prevented activation of ONH astrocytes but also significantly decreased SOD2 and HO-1 protein expression in the ONH astrocytes against oxidative stress. Further, CoQ10 prevented a significant loss of mitochondrial mass by increasing mitochondrial number and volume density and by preserving mitochondrial cristae structure, as well as promoted mitofilin and peroxisome-proliferator-activated receptor-γ coactivator-1 protein expression in the ONH astrocyte, suggesting an induction of mitochondrial biogenesis. Finally, oxidative stress triggered the upregulation of OXPHOS Cx protein expression, as well as reduction of cellular adeonsine triphosphate (ATP) production and increase of ROS generation in the ONH astocytes. However, CoQ10 preserved OXPHOS protein expression and cellular ATP production, as well as decreased ROS generation in the ONH astrocytes. On the basis of these observations, we suggest that oxidative stress-mediated mitochondrial dysfunction or alteration may be an important pathophysiological mechanism in the dysfunction of ONH astrocytes. CoQ10 may provide new therapeutic potentials and strategies for protecting ONH astrocytes against oxidative stress-mediated mitochondrial dysfunction or alteration in glaucoma and other optic neuropathies.

[Recovery from parkinsonism with N-acetylcysteine-differentiated neurons].

The upregulation of dopaminergic neuronal differentiation is necessary for stem cell therapy in Parkinson's disease (PD). In this study, neuronal differentiation efficiency increased by more than 2 times in P19 embryonic stem cells (ESCs) induced by N-acetylcysteine (NAC) and retinoic acid (RA) as compared to RA alone, with suppressed glial differentiation. The majority of NAC-treated stem cells grafted into brains of PD mice differentiated into dopaminergic neurons and persisted well for 6 weeks. Parkinsonism was also greatly improved after grafting NAC-treated cells in comparison to cells treated with only RA. Our results strongly suggest that NAC treatment may be an effective strategy for generating stem cells fated to become dopaminergic neurons for PD clinical therapy.

N-acetylcysteine enhances neuronal differentiation of P19 embryonic stem cells via Akt and N-cadherin activation.

We examined whether N-acetylcysteine (NAC) enhanced embryonic body (EB) formation and neuronal differentiation in terms of EB formation, neuronal marker (microtubule-associated protein 2; MAP-2) expression, and neuron maturation using P19 embryonic stem cells. The size and numbers of EBs were greatly increased, together with the up-regulated N-cadherin expression. Also, MAP-2 expression and neurite outgrowth were much increased with activation of serine/threonine protein kinase (Akt) and blocked by addition of an Akt inhibitor (LY294002). Our results suggested that NAC increased EB formation by up-regulating the N-cadherin expression. Furthermore, NAC-enhanced neuronal differentiation was mediated by activation of Akt.

Anatomic similarity of the hepatic artery and portal vein according to the donor-recipient relationship.

INTRODUCTION: Anatomic variants of the hepatic vasculature are common, so precise preoperative donor evaluation, including variations in the vasculature, is essential. We analyzed the anatomic similarity according to the donor-recipient relationship. METHODS: Among the cases who underwent living donor liver transplantations from September 2008 to January 2011 we selected 104 cases with clearly defined hepatic artery and portal vein on preoperative computed tomography. They were classified according to Hiatt et al for the hepatic artery and Cheng for the portal vein. We categorized the 104 cases into three groups: parents-child (n=40), sibling (n=24) and no-relation (n=40), for analysis of the concordance of the hepatic artery and portal vein. RESULT: Anatomic variations were observed in 25% of donors and 23.1% of recipients in the hepatic artery and 6.7% of donors and 10.6% of recipients in the portal vein. There was no significant difference in the distribution of the type of hepatic vasculature. Identical anatomic variations between donors and recipients were observed in 62.5% of the parent-child; 66.7% of the sibling and 52.5% of no-related group (P=.493) in the hepatic artery and 92.5%, 100%, and 77.5% (P=.014) in the portal vein respectively. CONCLUSION: There was no similarity in the anatomic variations of the hepatic artery according to the donor-recipient relationship, but a similarity in portal venous anatomy according to the donor-recipient relationship.

Enhanced 355-nm generation using a simple method to compensate for walk-off loss.

We theoretically and experimentally investigated a novel walk-off-compensation method for efficient ultraviolet beam generation. Through theoretical investigation, we described in detail how the power of a generated UV beam can be enhanced by the method; thus, we obtained a brief expression for the output power which has a prediction error of about 30%. In addition, we found that the beam quality can also be enhanced using this method. Through experiments using an alpha barium borate crystal as a walk-off compensator, we found that the power of the generated ultraviolet beam increased 1.9 times.

A new vicious cycle involving glutamate excitotoxicity, oxidative stress and mitochondrial dynamics.

Glutamate excitotoxicity leads to fragmented mitochondria in neurodegenerative diseases, mediated by nitric oxide and S-nitrosylation of dynamin-related protein 1, a mitochondrial outer membrane fission protein. Optic atrophy gene 1 (OPA1) is an inner membrane protein important for mitochondrial fusion. Autosomal dominant optic atrophy (ADOA), caused by mutations in OPA1, is a neurodegenerative disease affecting mainly retinal ganglion cells (RGCs). Here, we showed that OPA1 deficiency in an ADOA model influences N-methyl-D-aspartate (NMDA) receptor expression, which is involved in glutamate excitotoxicity and oxidative stress. Opa1(enu/+) mice show a slow progressive loss of RGCs, activation of astroglia and microglia, and pronounced mitochondrial fission in optic nerve heads as found by electron tomography. Expression of NMDA receptors (NR1, 2A, and 2B) in the retina of Opa1(enu/+) mice was significantly increased as determined by western blot and immunohistochemistry. Superoxide dismutase 2 (SOD2) expression was significantly decreased, the apoptotic pathway was activated as Bax was increased, and phosphorylated Bad and BcL-xL were decreased. Our results conclusively demonstrate that not only glutamate excitotoxicity and/or oxidative stress alters mitochondrial fission/fusion, but that an imbalance in mitochondrial fission/fusion in turn leads to NMDA receptor upregulation and oxidative stress. Therefore, we propose a new vicious cycle involved in neurodegeneration that includes glutamate excitotoxicity, oxidative stress, and mitochondrial dynamics.

Correlation between the immature characteristics of umbilical cord blood-derived mesenchymal stem cells and engraftment of hematopoietic stem cells in NOD/SCID mice.

Umbilical cord blood (UCB)-derived mesenchymal stem cells (MSC) facilitate the engraftment of human (h) hematopoietic stem cells when transplanted simultaneously in animal and human studies. However, the type of MSCs that preferentially enhance the engraftment of HSCs is unknown. Recent studies have shown that MSCs derived from a single source are heterogeneous in terms of cell size, morphology, proliferation rate, and differentiation potential. This study was designed to investigate the properties of UCB-MSCs, which influence the engraftment of hHSCs in a NOD/SCID mouse model. We categorized MSCs as being the most effective (UCB-352 MSCs) or the least effective (UCB-156 MSCs) at promoting the homing and engraftment of HSCs, and compared the characteristics of these 2 MSC populations. We observed that the 2 populations showed differences in characteristics typical of immature MSCs, and related to proliferation potential. We showed that UCB-352 MSCs, which proliferate quickly, preferentially enhanced the engraftment of HSCs in NOD/SCID mice. In addition, we observed differences in the pattern of both PODXL and Oct4 expression, and in the levels of cytokines such as SDF-1 and SCF using flow cytometry and membrane arrays. The more effective UCB-352 MSCs expressed higher levels of PODXL and Oct4, which were associated with immaturity, than did the UCB-156 MSCs. Furthermore, UCB-352 cells secreted greater levels of SDF-1 and SCF, both of which are required for hematopoiesis. We propose that the proliferation potential of UCB-MSCs, coupled with their immature characteristics, may serve as a novel standard to promote the homing and engraftment of HSCs.

Mode tailoring in a ridge-type periodically poled lithium niobate waveguide.

We present a simple and powerful method for mode generation and transformation in a ridge-type periodically poled lithium niobate (PPLN) waveguide by the use of second-order nonlinear effect and local-temperature-control technique. We show that a Hermite-Gaussian (HG) mode wave (among HG(00) to HG(22)) can be selectively generated via the quasi-phase-matching (QPM) nonlinear process in a PPLN waveguide by tuning the wavelength of fundamental wave or the temperature of the waveguide. As well, it is demonstrated that HG mode can be transformed into Laguerre-Gaussian (LG) one via combination of HG modes which are simultaneously generated in a single PPLN waveguide with local-temperature-control technique.

Expression of Ca2+ -activated K+ channels in human dermal fibroblasts and their roles in apoptosis.

BACKGROUNDS/AIMS: Cell proliferation and apoptosis are responsible for maintaining normal tissue homeostasis, and K(+) currents play important roles in regulating the physiological balance between them. This function of Ca(2+)-activated K(+) (K(Ca)) channels has been demonstrated in many types of tissues, but not in dermal fibroblasts. We investigated the expression of K(Ca) channels and their effects on proliferation and apoptosis in human dermal fibroblasts. METHODS: We used discoidin domain receptor 2 immunostaining to identify human dermal fibroblasts, and reverse transcription polymerase chain reaction, Western blot analysis and electrophysiological patch clamp recordings to evaluate the expression and characteristics of 3 members of the K(Ca) channel family, large-conductance K(Ca) (BK), intermediate-conductance K(Ca) (IK) and small-conductance K(Ca) channels. We also used the 3-(4,5-dimethyl-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry, Hoechst 33258 staining and Depsipher staining to investigate the effects of K(Ca) channels on cell proliferation and the mechanisms involved. RESULTS AND CONCLUSIONS: All 3 members of the K(Ca) channel family were found in fibroblasts. 1,3-Dihydro-1-[2-hydroxy-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-2H-benzimidazol-2-one (NS1619, a BK channel activator) or 1-ethyl-2-benzimidazolinone (EBIO, an IK channel activator) decreased the proliferation of fibroblasts and induced apoptotic changes by mitochondrial membrane potential disruption. However, a pan-caspase inhibitor (Z-VAD-fmk) failed to prevent the apoptotic changes. Our findings indicate that 3 types of functional K(Ca) channels are expressed in human dermal fibroblasts and are involved in apoptosis of the cells through the mitochondrial apoptotic pathway, but seemingly in a caspase-independent manner.

Ion spectrometer composed of time-of-flight and Thomson parabola spectrometers for simultaneous characterization of laser-driven ions.

An ion spectrometer, composed of a time-of-flight spectrometer (TOFS) and a Thomson parabola spectrometer (TPS), has been developed to measure energy spectra and to analyze species of laser-driven ions. Two spectrometers can be operated simultaneously, thereby facilitate to compare the independently measured data and to combine advantages of each spectrometer. Real-time and shot-to-shot characterizations have been possible with the TOFS, and species of ions can be analyzed with the TPS. The two spectrometers show very good agreement of maximum proton energy even for a single laser shot. The composite ion spectrometer can provide two complementary spectra measured by TOFS with a large solid angle and TPS with a small one for the same ion source, which are useful to estimate precise total ion number and to investigate fine structure of energy spectrum at high energy depending on the detection position and solid angle. Advantage and comparison to other online measurement system, such as the TPS equipped with microchannel plate, are discussed in terms of overlay of ion species, high-repetition rate operation, detection solid angle, and detector characteristics of imaging plate.

Transcriptional regulation of GSDML gene by antisense-oriented HERV-H LTR element.

During the course of hominoid evolution, a new transcript variant of the GSDML (gasdermin-like protein) gene was formed by the integration of the antisense-oriented HERV-H (human endogenous retrovirus) LTR (long terminal repeat) element. To investigate regions that are critical for transcriptional regulation of the GSDML gene, we generated seven deletion mutants from a full-length clone (clone 1/630) that includes the HERV-H LTR sequence and compared their expression levels relative to the full-length parental clone using a transient transfection assay. In the transient transfection assay, deletion of the 5' flanking region (cellular origin) of the HERV-H LTR sequence led to a 4.5-fold increase in expression compared to the full-length clone, while deletion of the U5 region showed a significant decrease in transcriptional activity. Deletion of the 3' flanking region of the LTR sequence (clone 42/451) showed similar transcriptional activity to a clone missing the 5' flanking region of cellular origin (clone 42/630). Taken together, these data indicate that the HERV-H LTR sequence (viral origin) positively regulates transcriptional activity of the GSDML gene and that the 5' flanking region sequence (cellular origin) exerts negative transcriptional regulation.