Fabry disease: characterisation of the plasma proteome pre- and post-enzyme replacement therapy.

BACKGROUND: Fabry disease is characterised by the progressive accumulation of globotriaosylceramide (Gb3) and related glycosphingolipids in vascular endothelial cells. Enzyme replacement therapy (ERT) clears this accumulation. We analysed plasma proteome profiles before and after ERT to characterise its molecular pathology. METHODS: Two-dimensional electrophoresis and matrix-assisted laser desorption/ionisation-time of flight tandem mass spectrometry (MALDI-TOF MS) and tandem mass spectrometry (MS/MS) were done using plasma samples before and after ERT in eight patients with classical Fabry disease RESULTS: After short-term ERT (4-12 months), the levels of 15 plasma proteins involved in inflammation, oxidative and ischaemic injury, or complement activation were reduced significantly. Among them, ß-actin (ACTB), inactivated complement C3b (iC3b), and C4B were elevated significantly in pre-ERT Fabry disease plasma compared with control plasma. After longer-term ERT (46-96 months), iC3b levels gradually decreased, whereas the levels of other proteins varied. The gradual reduction of iC3b was comparable to that of Gb3 levels. In addition, iC3b increased significantly in pre-ERT Fabry disease mouse plasma, and C3 deposits were notable in renal tissues of pre-enzyme replacement therapy patients. CONCLUSION: These results indicated that C3-mediated complement activation might be altered in Fabry disease and ERT might promote its stabilisation.

Where to fix in rejuvenation surgeries?: tensile strength of the periosteum.

The aim of this study is to elucidate the tensile strength of the periosteum relating to facial rejuvenation surgeries.Twelve hemifaces of 6 formalin-fixed Korean adult cadavers were used. Two horizontal incision lines were made 3 cm above the supraorbital rim and 1 cm below the infraorbital rim. Another 2 vertical incisions were on the medial orbital rim and 2 cm lateral to the lateral orbital rim. Elevated flaps were turned over, and the undersurfaces of the periosteum were exposed. A silk string was passed below the periosteum with a 3-mm bite and wound. A 3-cm loop was made, and this was pulled away using the tensiometer. The breaking strength was measured.The breaking strengths of the periosteum were different according to the location (P = 0.000, analysis of variation). The strongest point was 2 cm above the supraorbital rim at the medial one third of the orbit (14.05 [2.50] N) followed by 1 cm above the frontozygomatic suture (13.35 [4.70] N). The weakest point was the infraorbital rim at the lateral one third of the orbit (6.93 [3.76] N) followed by the lateral orbital rim at the level of the lateral canthus (7.60 [3.49] N). Breaking strengths of the periosteum of the medial side (11.44 [3.83] N) were significantly greater (P = 0.021, t-test) than the lateral side (9.32 [3.76] N). In the supraorbital area, the breaking strengths of the periosteum of the upper points (12.91 [3.00] N) were significantly greater (P = 0.000, t-test) than the lower points (9.36 [2.76] N).The results of this study can be of use when choosing a fixation point in rejuvenation surgeries.

Skin tension related to tension reduction sutures.

The aim of this study was to compare the skin tension of several fascial/subcutaneous tensile reduction sutures. Six upper limbs and 8 lower limbs of 4 fresh cadavers were used. At the deltoid area (10 cm below the palpable acromion) and lateral thigh (midpoint from the palpable greater trochanter to the lateral border of the patella), and within a 3 × 6-cm fusiform area of skin, subcutaneous tissue defects were created. At the midpoint of the defect, a no. 5 silk suture was passed through the dermis at a 5-mm margin of the defect, and the defect was approximated. The initial tension to approximate the margins was measured using a tensiometer.The tension needed to approximate skin without any tension reduction suture (S) was 6.5 ± 4.6 N (Newton). The tensions needed to approximate superficial fascia (SF) and deep fascia (DF) were 7.8 ± 3.4 N and 10.3 ± 5.1 N, respectively. The tension needed to approximate the skin after approximating the SF was 4.1 ± 3.4 N. The tension needed to approximate the skin after approximating the DF was 4.9 ± 4.0 N. The tension reduction effect of approximating the SF was 38.8 ± 16.4% (2.4 ± 1.5 N, P = 0.000 [ANOVA, Scheffé]). The tension reduction effect of approximating the DF was 25.2% ± 21.9% (1.5 ± 1.4 N, P = 0.001 [ANOVA, Scheffé]). The reason for this is thought to be that the SF is located closely to the skin unlike the DF. The results of this study might be a basis for tension reduction sutures.

Anatomy of the tenth costal cartilage for a columella strut in an Asian rhinoplasty.

The aim of this study was to elucidate the precise radiological and surface anatomy of the 10th costal cartilage for the usage of a columella strut in an Asian rhinoplasty.Three hundred abdominal computed tomography scans were reviewed and measured (166 males, 134 females), and the location of the 10th costochondral junction (CCJ) was measured in reference to the anterior superior iliac spine (ASIS) and umbilicus. Sixteen 10th costal cartilages were harvested from 10 Korean adult cadavers (7 males, 3 females), and the length, width, and thickness of each cartilage were measured.Distance from the anterior ASIS to the umbilicus was 155.4 ± 15.1 mm (male: 157.9 ± 15.5 mm, female: 152.2 ± 14.1 mm). Distance from the umbilicus to the 10th CCJ was 170.7 ± 23.0 mm (male: 179.2 ± 22.8 mm, female: 160.3 ± 18.7 mm). Distance from the ASIS to the 10th CSJ angle was 181.8 ± 21.8 mm (male: 184.7 ± 21.3 mm, female: 178.2 ± 22.1 mm). The ASIS-umbilicus-10th CSJ angle was 56.3 ± 5.6 degrees (male: 55.1 ± 5.5 degrees, female: 57.8 ± 5.3 degrees). The average length of the cartilage was 64.1 ± 19.7 mm. The average curved length of the cartilage was 69.6 ± 21.0 mm. The average greatest width was 11.0 ± 2.1 mm, and the width at its mid-length was 8.3 ± 1.7 mm. The average thickness of the cartilage was 5.7 ± 0.9 mm. In a 33-year-old woman, the 10th costal cartilage was used for columella strut.It is thought that the 10th costal cartilage can provide a sufficient amount and shape for a columella strut and tip in an onlay graft.

Neurovascular distribution within the abdominal head of the pectoralis major muscle: Application to breast and flap surgery.

The abdominal head of the pectoralis major (AHPM) is important in cosmetic and flap surgeries. Few studies have reported on its neurovascular entry points and distribution patterns. We aimed to determine the entry points and distribution patterns of the neurovascular structures within the AHPM. Thirty-two hemithoraxes were dissected, and the distribution patterns of the neurovascular structures were classified into several categories. The neurovascular entry points were measured at the horizontal line passing through the jugular notch (x-axis) and the midclavicular line (y-axis). The AHPM was innervated by the communication branches of the medial pectoral nerve (MPN) and the lateral pectoral nerve (LPN) in 78.1% of the specimens and of the MPN without the communication branches in 21.9%. All the LPNs had communication branches, which could be classified as independent in 46.9% of the samples, with the MPN in 21.9%, and with the LPN in 9.3%. The blood supply of the AHPM was composed of branches from the lateral thoracic artery (LTA) in 62.5% of the specimens, the thoracoacromial artery (TA) in 15.6%, and the LTA with the TA in 21.9%. The mean distance of the entry point was 6.3 cm ± 1.3 cm lateral to the y-axis, 8.1 cm ± 3.3 cm below the x-axis in the nerves, 6.5 cm ± 1.2 cm lateral to the y-axis, and 8.6 cm ± 3.0 cm below the x-axis in the arteries. This study defined the average neurovascular entry point and distribution pattern in detail using standard lines to enable the AHPM to be better understood.

Effect of sodium butyrate on the assembly, charge variants, and galactosylation of antibody produced in recombinant Chinese hamster ovary cells.

Sodium butyrate (NaBu) is known to increase the specific productivity of recombinant Chinese hamster ovary (rCHO) cells. To understand the effects of NaBu on the product quality, rCHO cells producing monoclonal antibody (Mab) were cultivated at various concentrations of NaBu (0 to 4 mM). NaBu increased correctly assembled Mab. In the absence of NaBu, the proportions of intact Mab (2H2L) and heavy chain dimer (2H) were 81 and 15 %. At 1 mM NaBu, the proportion of 2H2L increased to 93 %, whereas the proportion of 2H decreased to 2 %. No further increase in the proportion of 2H2L was obtained at a higher NaBu concentration. NaBu also affected the charge heterogeneity of Mab, which may affect the efficacy of Mab. The basic charge variants of Mabs increased with an increase in the NaBu concentration. In addition, NaBu affected the galactosylation of Mab negatively. Overall, the data obtained here show that NaBu used in rCHO cell cultures for improved Mab production affects certain quality aspects of Mab, in this case, the charge heterogeneity and galactosylation.

A real-time PCR-based amelogenin Y allele dropout assessment model in gender typing of degraded DNA samples.

Allelic dropout due to stochastic variation in degraded small quantity DNA appears to be one of the most serious genotyping errors. Most methods require PCR replication to address this problem. The small amounts of valuable samples are often a limitation for such replications. We report a real-time PCR-based amelogonin Y (AMELY) allele dropout estimation model in an AMEL-based gender typing. We examined 915 replicates of AMELY-positive modern male DNA with varying amounts of DNA and humic acid. A male-specific AMEL fragment (AMELy) dropped out in 143 genuine male replicates, leading to gender typing errors. By graphing a scatter plot of the crossing point versus the end cycle fluorescence of the male replicates, a standard graph model for the estimation of the AMELy allele dropout was constructed with the dropout-prone and dropout-free zones. This model was then applied to ancient DNA (aDNA) samples. Nine samples identified as female were found in the dropout-prone zone; with higher DNA concentrations, six were shifted to the dropout-free zone. Among them, two female identifications were converted to male. All the aDNA gender was confirmed by sex-determination region Y marker amplification. Our data suggest that this model could be a basic approach for securing AMELy allele dropout-safe data from the stochastic variation of degraded inhibitory DNA samples.

Item Response Theory True Score Equating for the Bifactor Model Under the Common-Item Nonequivalent Groups Design.

Applying item response theory (IRT) true score equating to multidimensional IRT models is not straightforward due to the one-to-many relationship between a true score and latent variables. Under the common-item nonequivalent groups design, the purpose of the current study was to introduce two IRT true score equating procedures that adopted different dimension reduction strategies for the bifactor model. The first procedure, which was referred to as the integration procedure, linked the latent variable scales for the bifactor model and integrated out the specific factors from the item response function of the bifactor model. Then, IRT true score equating was applied to the marginalized bifactor model. The second procedure, which was referred to as the PIRT-based procedure, projected the specific dimensions onto the general dimension to obtain a locally dependent unidimensional IRT (UIRT) model and linked the scales of the UIRT model, followed by the application of IRT true score equating to the locally dependent UIRT model. Equating results obtained with the two equating procedures along with those obtained with the unidimensional three-parameter logistic (3PL) model were compared using both simulated and real data. In general, the integration and PIRT-based procedures provided equating results that were not practically different. Furthermore, the equating results produced by the two bifactor-based procedures became more accurate than the results returned by the 3PL model as tests became more multidimensional.

Mitochondrial Haplogroup Classification of Ancient DNA Samples Using Haplotracker.

Mitochondrial DNA haplogroup classification is used to study maternal lineage of ancient human populations. The haplogrouping of ancient DNA is not easy because the DNA is usually found in small pieces in limited quantities. We have developed Haplotracker, a straightforward and efficient high-resolution haplogroup classification tool optimized specifically for ancient DNA samples. Haplotracker offers a user-friendly input interface for multiple mitochondrial DNA sequence fragments in a sample. It provides accurate haplogroup classification with full-length mitochondrial genome sequences and provides high-resolution haplogroup predictions for some fragmented control region sequences using a novel algorithm built on Phylotree mtDNA Build 17 (Phylotree) and our haplotype database (n = 118,869). Its performance for accuracy was demonstrated to be high through haplogroup classification using 8,216 Phylotree full-length and control region mitochondrial DNA sequences compared with HaploGrep 2, one of the most accurate current haplogroup classifiers. Haplotracker provides a novel haplogroup tracking solution for fragmented sequences to track subhaplogroups or verify the haplogroups efficiently. Using Haplotracker, we classified mitochondrial haplogroups to the final subhaplogroup level in nine ancient DNA samples extracted from human skeletal remains found in 2,000-year-old elite Xiongnu cemetery in Northeast Mongolia. Haplotracker can be freely accessed at https://haplotracker.cau.ac.kr.

Regulation of PDGF signalling and vascular remodelling by peroxiredoxin II.

Platelet-derived growth factor (PDGF) is a potent mitogenic and migratory factor that regulates the tyrosine phosphorylation of a variety of signalling proteins via intracellular production of H2O2 (refs 1, 2-3). Mammalian 2-Cys peroxiredoxin type II (Prx II; gene symbol Prdx2) is a cellular peroxidase that eliminates endogenous H2O2 produced in response to growth factors such as PDGF and epidermal growth factor; however, its involvement in growth factor signalling is largely unknown. Here we show that Prx II is a negative regulator of PDGF signalling. Prx II deficiency results in increased production of H2O2, enhanced activation of PDGF receptor (PDGFR) and phospholipase Cgamma1, and subsequently increased cell proliferation and migration in response to PDGF. These responses are suppressed by expression of wild-type Prx II, but not an inactive mutant. Notably, Prx II is recruited to PDGFR upon PDGF stimulation, and suppresses protein tyrosine phosphatase inactivation. Prx II also leads to the suppression of PDGFR activation in primary culture and a murine restenosis model, including PDGF-dependent neointimal thickening of vascular smooth muscle cells. These results demonstrate a localized role for endogenous H2O2 in PDGF signalling, and indicate a biological function of Prx II in cardiovascular disease.

Interval estimation procedures for true scores of a test composed of polytomous items: An application of the multinomial error model.

When a person takes alternative forms of the same test across replications of the testing procedure, the test taker's observed scores on the alternative forms are rarely identical. In educational and psychological measurement, inconsistencies in a test taker's scores that are irrelevant to the construct being measured are attributed to errors of measurement. Typically, errors of measurement are summarized as the standard deviation of a test taker's observed scores over replication of the same testing procedure. Assuming that errors of measurement follow a multinomial distribution (i.e., multinomial error model), the main goal of this study was to propose two interval estimation procedures, which are referred to as the score-like and Perks procedures, for true scores of a test with polytomous items. The performance of the score-like and Perks procedures was compared with that of two normal approximation procedures under the multinomial error model and a procedure based on item response theory (IRT) through simulation. In general, the score-like and Perks procedures outperformed the other three procedures when data were generated under the multinomial error theory framework and showed reasonable results when data were generated under the IRT framework. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

A western Eurasian male is found in 2000-year-old elite Xiongnu cemetery in Northeast Mongolia.

We analyzed mitochondrial DNA (mtDNA), Y-chromosome single nucleotide polymorphisms (Y-SNP), and autosomal short tandem repeats (STR) of three skeletons found in a 2,000-year-old Xiongnu elite cemetery in Duurlig Nars of Northeast Mongolia. This study is one of the first reports of the detailed genetic analysis of ancient human remains using the three types of genetic markers. The DNA analyses revealed that one subject was an ancient male skeleton with maternal U2e1 and paternal R1a1 haplogroups. This is the first genetic evidence that a male of distinctive Indo-European lineages (R1a1) was present in the Xiongnu of Mongolia. This might indicate an Indo-European migration into Northeast Asia 2,000 years ago. Other specimens are a female with mtDNA haplogroup D4 and a male with Y-SNP haplogroup C3 and mtDNA haplogroup D4. Those haplogroups are common in Northeast Asia. There was no close kinship among them. The genetic evidence of U2e1 and R1a1 may help to clarify the migration patterns of Indo-Europeans and ancient East-West contacts of the Xiongnu Empire. Artifacts in the tombs suggested that the Xiongnu had a system of the social stratification. The West Eurasian male might show the racial tolerance of the Xiongnu Empire and some insight into the Xiongnu society.

Approximating Bifactor IRT True-Score Equating With a Projective Item Response Model.

Item response theory (IRT) true-score equating for the bifactor model is often conducted by first numerically integrating out specific factors from the item response function and then applying the unidimensional IRT true-score equating method to the marginalized bifactor model. However, an alternative procedure for obtaining the marginalized bifactor model is through projecting the nuisance dimensions of the bifactor model onto the dominant dimension. Projection, which can be viewed as an approximation to numerical integration, has an advantage over numerical integration in providing item parameters for the marginalized bifactor model; therefore, projection could be used with existing equating software packages that require item parameters. In this paper, IRT true-score equating results obtained with projection are compared to those obtained with numerical integration. Simulation results show that the two procedures provide very similar equating results.

Skin Pigmentation Differences between Mongolian, Korean, and Uzbekistan Ancient Human DNA Samples.

BACKGROUND: This study reports the use of real-time PCR to identify the SNP rs1545397 in the intron region on the OCA2 gene from ancient and degraded DNA isolated from ancient human bones from Mongolia, Korea, and Uzbekistan. This SNP is a marker for skin pigmentation. LightCycler-based probes (HybProbes) were designed. A LightCycler (version 2.0) system was used for the real-time PCR. RESULTS: The results of the real-time PCRs of three different genotypes of SNP rs1545397 were compared with those of the direct sequencing. Melting curve analysis was used for genotype determination. Three genotypes were distinguished: the homozygous T (T/T) SNP type formed a distinct melting peak at 53.3 ± 0.14°C, the homozygous A (A/A) SNP type formed a distinct melting peak at 57.8 ± 0.12°C, and the heterozygous A/T SNP type formed two distinct melting peaks at 53.3 ± 0.17°C and 57.8 ± 0.15°C. Mongolian aDNA samples tested in this study carried all three types of the SNP (A/T, A/A, and T/T) with no distinctly predominant type observed. In contrast, Korean aDNA samples carried the Asian genotype (T/T), while the Uzbekistan aDNA samples carried the European genotype (A/A) more often than the Asian genotype (T/T). CONCLUSIONS: Human Mongolian aDNA samples had A/T, A/A, and T/T SNP rs1545397 with no distinct predominant genotype. When combined with the archeological and aDNA studies of other coupling morphologies with aDNA, our results infer that Mongolia's prehistoric population had considerable heterogeneity of skin color and morphological traits and that in the Neolithic period, a Eurasian or mixed population inhabited the western part of Mongolia.

Both Intracranial and Intravenous Administration of Functionalized Carbon Nanotubes Protect Dopaminergic Neuronal Death from 6-Hydroxydopamine.

PURPOSE: Although single-walled nanotubes (SWNTs) with functional groups have been suggested as a potential nanomedicine to treat neuronal disorders, effective routes to administer SWNTs have not been compared thus far. The blood-brain barrier is a considerable challenge for the development of brain-targeting drugs, and therefore functionalized SWNT routes of administration have been needed for testing Parkinson's disease (PD) treatment. Here, effective administration routes of functionalized SWNTs were evaluated in PD mouse model. METHODS: Three different administration routes were tested in PD mouse model. Functionalized SWNTs were injected directly into the lateral ventricle three days before (Method 1) or after (Method 2) 6-hydroxydopamine (6-OHDA) injection to compare the protective effects of SWNTs against dopaminergic neuronal death or functionalized SWNTs were injected intravenously at three and four days after 6-OHDA injection (Method 3). Asymmetric behaviors and histological assessment from all animals were performed at two weeks after 6-OHDA injection. RESULTS: Ventricular injections of SWNTs both before or after 6-OHDA exposure protected dopaminergic neurons both in the substantia nigra and striatum and alleviated rotational asymmetry behavior in PD mice. Moreover, intravenous administration of SWNTs three and four days after 6-OHDA injection also prevented neuronal death and PD mice behavioral impairment without apparent cytotoxicity after six months post-treatment. CONCLUSION: Our study demonstrates that functionalized SWNTs could effectively protect dopaminergic neurons through all administration routes examined herein. Therefore, SWNTs are promising nanomedicine agents by themselves or as therapeutic carriers to treat neuronal disorders such as PD.

A Comparison of the Separate and Concurrent Calibration Methods for the Full-Information Bifactor model.

When calibrating items using multidimensional item response theory (MIRT) models, item response theory (IRT) calibration programs typically set the probability density of latent variables to a multivariate standard normal distribution to handle three types of indeterminacies: (a) the location of the origin, (b) the unit of measurement along each coordinate axis, and (c) the orientation of the coordinate axes. However, by doing so, item parameter estimates obtained from two independent calibration runs on nonequivalent groups are on two different coordinate systems. To handle this issue and place all the item parameter estimates on a common coordinate system, a process called linking is necessary. Although various linking methods have been introduced and studied for the full MIRT model, little research has been conducted on linking methods for the bifactor model. Thus, the purpose of this study was to provide detailed descriptions of two separate calibration methods and the concurrent calibration method for the bifactor model and to compare the three linking methods through simulation. In general, the concurrent calibration method provided more accurate linking results than the two separate calibration methods, demonstrating better recovery of the item parameters, item characteristic surfaces, and expected score distribution.

Immunohistochemical study on the distribution of glycogen synthase kinase 3alpha in the central nervous system of SOD1(G93A) transgenic mice.

OBJECTIVE: To identify glycogen synthase kinase (GSK) 3alpha expression in a mouse model of familial amyotrophic lateral sclerosis (ALS), we investigated the changes of GSK3alpha in the central nervous system of SOD1(G93A) transgenic mice by immunohistochemistry. METHODS: We used 12 SOD1(G93A) transgenic and ten wild-type (wt) SOD1 transgenic mice bred by 'The Jackson Laboratory' under the strain designations B6SJL-TgN (SOD1(G93A)) 1 Gur/J and B6SJL-TgN (SOD1) 2 Gur/J, respectively. Immunohistochemistry was performed in accordance with the free-floating method described earlier. RESULTS: In symptomatic transgenic mice, GSK3alpha-immunoreactive astrocytes were detected in the spinal cord, brainstem and cerebellum of symptomatic SOD1(G93A) transgenic mice. In contrast to symptomatic mice, no GSK3alpha-immunoreactive astrocytes were observed in any brain region of wtSOD1 and pre-symptomatic mice, and the number and intensity of stained cells were not different at the age of 8 and 13 weeks. DISCUSSION: These results provide the first evidence that GSK3alpha-immunoreactive astrocytes were found in the CNS of SOD1(G93A) transgenic mice after clinical symptoms, suggesting a possible role in the pathologic process of ALS. However, the mechanisms underlying the increased immunoreactivity for GSK3alpha and the functional implications require elucidation.

Technical note: improved ancient DNA purification for PCR using ion-exchange columns.

A novel method of ancient DNA (aDNA) purification was developed using ion-exchange columns to improve PCR-amplifiable DNA extraction from ancient bone samples. Thirteen PCR-resistant ancient bone samples aged 500-3,300 years were tested to extract aDNA using a recently reported, silica-based aDNA extraction method and an ion-exchange column method for the further purification. The PCR success rates of the aDNA extracts were evaluated for the amplification ability of the fragments of mitochondrial DNA, a high-copy DNA, and amelogenin, a low-copy DNA. The results demonstrate that the further purification of silica-based aDNA extracts using ion-exchange columns considerably improved PCR amplification. We suggest that the ion-exchange column-based method will be useful for the improvement of PCR-amplifiable aDNA extraction, particularly from the poorly preserved, PCR-resistant, ancient samples.

Effects of a Free Electronic Book on Systemic Anatomy with Schematics on Student Learning / Efectos de un Libro Electrónico Gratuito sobre Anatomía Sistémica con Esquemas sobre el Aprendizaje de los Estudiantes

SUMMARY: For students in schools of nursing, health sciences, and premed, a systemic anatomy textbook with minimized contents, schematics, and mnemonics may be helpful for learning an otherwise often unappealing subject. In this study, we assess the educational effect of such a textbook. Schematic drawings, anatomy comics, and easily readable text were generated for the chapters of the book (e.g., skeletal system, articular system). The book was presented without charge via a webpage (anatomy.co.kr). Nursing students who were exposed to the book and those who were not exposed were compared; a survey was administered to those who were exposed. The students who read the presented textbook were more knowledgeable than those who used other textbooks. Hours spent reading the presented textbook and scores of fill-in-the-blank questions were positively correlated. In general, the students replied that the presented textbook was helpful for learning systemic anatomy. The systemic anatomy textbook accompanies preexisting textbooks in regional anatomy, neuroanatomy, and the histology, all of which are written by the same authors. We suggest anatomy instructors generate their own books with unique style to enrich the student learning process.

Para los estudiantes de las escuelas de enfermería, ciencias de la salud y premedicina, un libro de texto de anatomía sistémica con contenidos, esquemas y mnemónicos minimizados puede ser útil para aprender un tema que de otro modo sería poco atractivo. En este estudio, evaluamos el efecto educativo de dicho libro de texto. Se generaron dibujos esquemáticos, cómics de anatomía y texto de fácil lectura para los capítulos del libro (por ejemplo, sistema esquelético, sistema articular). El libro se presentó sin costo a través de una página web (anatomy.co.kr). Se compararon los estudiantes de enfermería que estuvieron expuestos al libro y los que no estuvieron expuestos. Se administró una encuesta a quienes estuvieron expuestos. Los estudiantes que leyeron el libro de texto presentado tenían más conocimientos que aquellos que usaron otros libros de texto. Las horas dedicadas a leer el libro de texto presentado y las decenas de preguntas para completar espacios en blanco se correlacionaron positivamente. En general, los estudiantes respondieron que el libro de texto presentado fue útil para aprender anatomía sistémica. El libro de texto de anatomía sistémica acompaña a los libros de texto preexistentes de anatomía regional, neuroanatomía e histología, todos escritos por los mismos autores. Sugerimos que los instructores de anatomía generen sus propios libros con un estilo único para enriquecer el proceso de aprendizaje de los estudiantes.

ERK1/2 activation attenuates TRAIL-induced apoptosis through the regulation of mitochondria-dependent pathway.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) functions as an extracellular signal, which triggers apoptosis in tumor cells. In order to characterize the molecular events involved in TRAIL cytotoxic signaling, we attempted to determine the role of extracellular signal-regulated kinase 1/2 (ERK1/2), as well as its downstream targets in TRAIL-treated HeLa cells. Here we demonstrate that TRAIL exposure resulted in the activation of ERK1/2, and the elevation of anti-apoptotic Bcl-2 protein levels. ERK1/2 inhibition with PD98059 promoted cell death via the down-regulation of Bcl-2 protein levels, together with increasing mitochondrial damage, including the collapse of mitochondrial membrane potential, the release of cytochrome c from mitochondria to cytoplasm and caspase activity. These results suggest that the ERK1/2 activation is a kind of survival mechanism to struggle against TRAIL-induced stress condition in early stage, via activating cellular defense mechanisms like as the up-regulation of the Bcl-2/Bax ratio, as well as several mitochondrial events.