The resin of Boswellia species is a major anti-inflammatory agent that has been used for centuries to treat various conditions including injuries and inflammatory conditions. Incensole acetate (IA), a major constituent of this resin, has been shown to inhibit NF-κB activation and concomitant inflammation. Here we show that IA protects against ischemic neuronal damage and reperfusion injury in mice, attenuating the inflammatory nature of ischemic damage. IA given post-ischemia, reduced infarct volumes and improved neurological activities in the mouse model of ischemic injury in a dose dependent fashion. The protection from damage was accompanied by inhibition of TNF-α, IL-1β and TGF-β expression, as well as NF-κB activation following injury. In addition, IA is shown to have a therapeutic window of treatment up to 6 hours after ischemic injury. Finally, the protective effects of IA were partially mediated by the TRPV3 channels as determined by the TRPV3 deficient mice and channel blocker studies. This study suggests that the anti-inflammatory and neuroprotective activities of IA may serve as a novel therapeutic treatment for ischemic and reperfusion injury, and as a tool in the ongoing research of mechanisms for neurological damage.
Cerebral ischemia; inflammation; NF-κB; neuroprotection; incensole acetate; Boswellia
Patients with gestational diabetes mellitus (GDM) have been reported to exhibit the same genetic susceptibility as that observed in those with type 2 diabetes mellitus (T2DM). Recent polymorphism studies have shown that several genes are related to T2DM and GDM. The aim of this study was to examine whether certain candidate genes, previously shown to be associated with T2DM, also offer a specific genetic predisposition to GDM.
Materials and Methods
The current study was conducted in 136 Korean pregnant women, who gave birth at Gil Hospital, from October 2008 to May 2011. These study subjects included 95 subjects with GDM and 41 non-diabetic controls. We selected the specific genes of PPARγ2, IGF2BP2, and KCNQ1 for study and amplified them using the polymerase chain reaction. This was followed by genotyping for single nucleotide polymorphisms. We then compared the genotype frequencies between patients with GDM and non-diabetic controls using the χ2 test. We obtained and analyzed clinical information using Student's t-test, and statistical analyses were conducted using logistic regression with SPSS Statistics software, version 19.0.
Significant differences were observed in maternal age, body mass index, weight gain and weight at time of delivery between the groups compared. Among pregnant women, polymorphisms in PPARγ2 and IGF2BP2 were shown to be highly correlated with GDM occurrence, whereas no correlation was found for KCNQ1 polymorphisms.
Our results indicated that genetic polymorphisms could also be of value in predicting the occurrence and diagnosis of GDM.
Gestational diabetes mellitus; type 2 diabetes mellitus; gene; single nucleotide polymorphism
Attributional style, especially external personal attribution bias, was found to play a pivotal role in clinical and non-clinical paranoia. The study of the relationship of the tendency to infer/perceive hostility and blame with theory of mind skills has significant theoretical importance as it may provide additional information on how persons process social situations. The aim of this study was whether hostility perception bias and blame bias might be associated with theory of mind skills, neurocognition and emotional factors in healthy persons.
Total 263 participants (133 male and 130 female) were recruited. The attributional style was measured by using the Ambiguous Intentions Hostility Questionnaire (AIHQ). Participants were requested to complete a Brüne's Theory of Mind Picture Stories task, neurocognitive task including Standard Progressive Matrices (SPM) and digit span, and other emotional dysregulation trait scales including Rosenberg's self-esteem, Spielberg's trait anxiety inventory, and Novaco anger scale.
Multiple regression analysis showed that hostility perception bias score in ambiguous situation were found to be associated with theory of mind questionnaire score and emotional dysregulation traits of Novaco anger scale. Also, composite blame bias score in ambiguous situation were found to be associated with emotional dysregulation traits of Novaco anger scale and Spielberg's trait anxiety scale.
The main finding was that the attributional style of hostility perception bias might be primarily contributed by theory of mind skills rather than neurocognitive function such as attention and working memory, and reasoning ability. The interpretations and implications would be discussed in details.
Attributional style; Theory of Mind skills; Healthy persons
Self-reactive natural antibodies initiate injury following ischemia and reperfusion of certain tissues, but their role in ischemic stroke is unknown. We investigated neoepitope expression in the post-ischemic brain, and the role of natural antibodies in recognizing these epitopes and mediating complement-dependent injury. A novel IgM mAb recognizing a subset of phospholipids (C2) and a previously characterized anti-annexin IV mAb (B4) were used to reconstitute and characterize injury in antibody deficient Rag1−/− mice after 60 minutes of middle cerebral artery occlusion and reperfusion. Reconstitution with C2 or B4 mAb in otherwise protected Rag1−/− mice restored injury to that seen in wild-type mice, as demonstrated by infarct volume, demyelination and neurological scoring. IgM deposition was demonstrated in both wild-type mice and reconstituted Rag1−/− mice, and IgM co-localized with the complement activation fragment, C3d, following B4 mAb reconstitution. Further, recombinant annexin IV significantly reduced infarct volumes in wild-type mice and in Rag1−/− mice administered normal mouse serum, demonstrating that a single antibody reactivity is sufficient to develop cerebral ischemia reperfusion injury in the context of an entire natural antibody repertoire. Finally, C2 and B4 mAbs bound to hypoxic, but not normoxic, human endothelial cells in vitro. Thus, the binding of pathogenic natural IgM to post-ischemic neoepitopes initiates complement-dependent injury following murine cerebral ischemia and reperfusion and, based also on previous data investigating IgM reactivity in human serum, there appears to be a similar recognition system in both mouse and man.
This study is designed to compare and evaluate the diagnostic image quality of dental panoramic radiography between conventional and digital systems. Fifty-four panoramic images were collected and divided into three groups consisting of conventional, digital with and without post processing image. Each image was printed out and scored subjectively by two experienced dentists who were blinded to the exposure parameters and system protocols. The evaluation covers of anatomical coverage and structures, density and image contrast. The overall image quality score revealed that digital panoramic with post-processing scored the highest of 3.45±0.19, followed by digital panoramic system without post-processing and conventional panoramic system with corresponding scores of 3.33±0.33 and 2.06±0.40. In conclusion, images produced by digital panoramic system are better in diagnostic image quality than that from conventional panoramic system. Digital post-processing visualization can improve diagnostic quality significantly in terms of radiographic density and contrast.
Conventional panoramic system; digital panoramic system; image quality assessment; panoramic dental radiography
To evaluate the effectiveness of new management policies on the incidence of invasive Candida infections
This observational study involved a retrospective analysis of the patients' medical records. In total, 99 very low birth weight infants, who were admitted to the neonatal intensive care unit at Ajou University Hospital from January 2010 to December 2011, were enrolled for the study. Period I, defined as the period before the revision of management policies, comprised 57 infants; whereas, period II, defined as the period after the implementation of new management policies, comprised 42 infants. The new management policies entailed a reduction in antibiotic and histamine type 2 receptor blocker (H2 blocker) use, duration of central venous catheterization, and duration of endotracheal intubation.
There was a significant overall decrease in the use of antibiotics including 3rd generation cephalosporin and H2 blockers (P<0.05), and a significantly lower incidence of invasive Candida infections in period II as compared to period I (0/42 vs. 6/57, respectively; P=0.037). Comparison between infants with invasive Candida infections (n=6) and those without (n=93) showed that gestational age (odds ratio [OR], 0.909; 95% confidence interval [CI], 0.829 to 0.996; P=0.042) and the duration of 3rd generation cephalosporin use (OR, 1.093; 95% CI, 1.009 to 1.183; P=0.029) were statistically significant risk factors.
The new management policies effectively decreased overall use of antibiotics, especially 3rd generation cephalosporin, and H2 blockers, which led to a significantly lower incidence of invasive Candida infections.
Invasive candidiasis; Very low birth weight infant; Nosocomial infection; Sepsis
Despite the recent advances in single molecule manipulation techniques, purely mechanical approaches can not detect subtle conformational changes in the biologically important regime of weak forces. We developed a hybrid scheme combining force and fluorescence which allowed us to examine the effect of sub-pN forces on the nanometer scale motion of the Holliday junction (HJ) at 100 Hz bandwidth. The HJ is an exquisitely sensitive force sensor whose force response is amplified with an increase in its arm lengths, demonstrating a lever-arm effect at the nanometer length scale. Mechanical interrogation of the HJ in three different directions helped elucidate the structures of the transient species populated during its conformational changes. This method of mapping two dimensional reaction landscapes at low forces is readily applicable to other nucleic acid systems and their interactions with proteins and enzymes.
Palladium-catalyzed C–H activation/C–C bond–forming reactions have emerged as a promising class of synthetic tools in organic chemistry. Among the many different means of forging C–C bonds using Pd-mediated C–H activation, a new horizon in this field is Pd(II)-catalyzed cross-coupling of C–H bonds with organometallic reagents via a Pd(II)/Pd(0) catalytic cycle. While this type of reaction has proven to be effective for the selective functionalization of aryl C(sp2)–H bonds, the focus of this review is on Pd(II)-catalyzed C(sp3)–H activation/C–C cross-coupling, a topic of particular importance because reactions of this type enable fundamentally new methods for bond construction. Since our laboratory’s initial report on cross-coupling of C–H bonds in 2006, this area has expanded rapidly, and the unique ability of Pd(II) catalysts to cleave and functionalize alkyl C(sp3)–H bonds has been exploited to develop protocols for forming an array of C(sp3)–C(sp2) and C(sp3)–C(sp3) bonds. Furthermore, enantioselective C(sp3)–H activation/C–C cross-coupling has been achieved through the use of chiral amino acid-derived ligands, offering a novel technique for producing enantioenriched molecules. Although this nascent field remains at an early stage of development, further investigations hold the potential to revolutionalize the way in which chiral molecules are synthesized in industrial and academic laboratories.
C–H activation; palladium; C–C coupling; organometallic reagent
This study aimed to evaluate the efficacy, toxicity and tolerability of simultaneous modulated accelerated radiation therapy (SMART)-intensity modulated radiotherapy (IMRT) plus cisplatin and 5-fluorouracil (5-FU) chemotherapy for patients with advanced nasopharyngeal cancer (NPC). Forty-five patients with stage II–IV NPC, determined by the American Joint Committee on Cancer system, were treated with prescribed doses of 72 Gy total to the gross tumor volume, 60 Gy to the clinical target volume and metastatic nodal station, and 54 Gy to the clinically-negative neck region. Before radiotherapy, two cycles of cisplatin (30 mg/m2/day on days 1–3) plus 5-FU (400 mg/m2/day on days 1–5) were delivered every three weeks for two cycles. Patients received two cycles of cisplatin (30 mg/m2 day on days 1–3) every three weeks during radiotherapy. In addition, two cycles of cisplatin and 5-FU were given after radiation. All patients completed the prescribed radiotherapy and all scheduled cycles of chemotherapy. Thirty of the 45 patients (66.6%) had a complete response at the end of treatment. Grade 3 mucositis occurred in 4/45 patients (8.8%) and grade 3 dermatitis occurred in 5/45 (11.1%) during radiotherapy. Grade 3 neutropenia occurred in 6/45 (13.3%) during concurrent chemotherapy. There was no treatment-related mortality. After a median follow-up time of 51 months, only three patients’ treatments had failed. Local and distant failure rates were 1.5 and 3.0%, respectively. SMART-IMRT plus cisplatin and 5-FU chemotherapy showed promising activity with manageable toxicity. It is a feasible regimen and improves locoregional disease control.
nasopharyngeal cancer; induction chemotherapy; concurrent chemoradiotherapy; SMART-IMRT; cisplatin
AIM: To investigate the feasibility of a single-use endoscopy as an alternative procedure to nasogastric lavage in patients with acute gastrointestinal (GI) bleeding.
METHODS: Patients who presented with hematemesis, melena or hematochezia were enrolled in this study. EG scan™ and conventional esophagogastroduodenoscopy (EGD) were subsequently performed. Active bleeding was defined as blood in the stomach, and inactive bleeding was defined as coffee ground clots and clear fluid in the stomach. The findings were recorded and compared.
RESULTS: Between January and March, 2011, 13 patients that presented with hematemesis (n = 4), melena (n = 6), or bleeding from a previous nasogastric feeding tube (n = 3), were enrolled in this study. In 12 patients with upper GI bleeding, the EG scan device revealed that 7 patients had active bleeding and 5 patients had inactive bleeding, whereas conventional EGD revealed that 8 patients had active bleeding and 4 patients had inactive bleeding. The sensitivity and specificity of the EG scan device was 87.5% and 100% for active bleeding, with conventional EGD serving as a reference. No complication were reported during the EG scan procedures.
CONCLUSION: The EG scan is a feasible device for screening acute upper GI bleeding. It may replace nasogastric lavage for the evaluation of acute upper GI bleeding.
Gastrointestinal hemorrhage; Bleeding; Endoscopy; Nasogastric tube; Lavage
We have designed a five-year multicentre prospective cohort study in women who are both human papillomavirus (HPV)-positive with either atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL) of cervix. This study aimed to analyze the risk of developing a high-grade squamous intraepithelial lesion (HSIL) from either ASCUS or LSIL in HPV-positive women, so called 'progression' rate, to investigate differences in the progression rates according to HPV type-specific infection, and to evaluate the various factors associated with the persistence or clearance of HPV infection in the Korean population. At present, the study protocol composed of cervical cytology, HPV DNA testing, and questionnaire have been conducted actively since the first participant was enrolled in 2010. This study is the first nationwide Korea HPV cohort study. Our data will provide valuable information about not only the ambiguous cytology results of ASCUS and LSIL but also the effect of the specific HPV type and other various factors on the progression to HSIL. Finally, the results of our study will be helpful and applicable to determine the primary cervical cancer prevention strategies.
Cervical intraepithelial neoplasms; Cohort studies; Human papillomavirus; Uterine cervical neoplasms
Background and Objectives
It has been demonstrated that the anomalous origin of coronary arteries (AOCA) are generally asymptomatic and rare diseases. However, some cases can cause severe life threatening events. To detect these anomalies, coronary angiographies and autopsies were used to detect coronary artery anomalies, but these procedures have limitations because of their invasiveness. The new device, Multidetector Computed Tomography (MDCT), now replaces the method of choice for detecting coronary anomalies. The prevalence of these anomalies in Korea has not been studied yet. This present analysis attempted to determine the prevalence of AOCA in Korean men by MDCT.
Subjects and Methods
1582 Korean male police officers underwent coronary MDCT for their health screening voluntarily. After reconstruction of CT images, we could confirm coronary artery anomalies.
The prevalence of AOCA in Korean men was 1.14% (18 out of 1582 cases). The most common abnormality (11 cases, 0.70%) was the origin of the coronary artery. Anomalies of the coronary artery end point were observed in 5 cases (0.32%). The anomalous location of coronary ostium on the aortic root was observed in 1 case (0.06%). An anomalous collateral vessel was observed in 1 case (0.06%).
The prevalence of coronary artery anomalies in Korean men was 1.14%. Coronary CT is a safe and noninvasive modality for detecting coronary anomalies.
Coronary vessel anomalies; Multidetector computed tomography; Prevalence
AIM: To evaluate the efficacy and safety of tenofovir disoproxil fumarate (TDF) for chronic hepatitis B (CHB) patients after multiple failures.
METHODS: A total of 29 CHB patients who had a suboptimal response or developed resistance to two or more previous nucleoside/nucleotide analogue (NA) treatments were included. Study subjects were treated with TDF alone (n = 13) or in combination with lamivudine (LAM, n = 12) or entecavir (ETV, n = 4) for ≥ 6 mo. Complete virologic response (CVR) was defined as an achievement of serum hepatitis B virus (HBV) DNA level ≤ 60 IU/mL by real-time polymerase chain reaction method during treatment. Safety assessment was based on serum creatinine and phosphorus level. Eleven patients had histories of LAM and adefovir dipivoxil (ADV) treatment and 18 patients were exposed to LAM, ADV, and ETV. Twenty-seven patients (93.1%) were hepatitis B e antigen (HBeAg) positive and the mean value of the baseline serum HBV DNA level was 5.5 log IU/mL ± 1.7 log IU/mL. The median treatment duration was 16 mo (range 7 to 29 mo).
RESULTS: All the patients had been treated with LAM and developed genotypic and phenotypic resistance to it. Resistance to ADV was present in 7 patients and 10 subjects had a resistance to ETV. One patient had a resistance to both ADV and ETV. The cumulative probabilities of CVR at 12 and 24 mo of TDF containing treatment regimen calculated by the Kaplan Meier method were 86.2% and 96.6%, respectively. Although one patient failed to achieve CVR, serum HBV DNA level decreased by 3.9 log IU/mL from the baseline and the last serum HBV DNA level during treatment was 85 IU/mL, achieving near CVR. No patients in this study showed viral breakthrough or primary non-response during the follow-up period. The cumulative probability of HBeAg clearance in the 27 HBeAg positive patients was 7.4%, 12%, and 27% at 6, 12, and 18 mo of treatment, respectively. Treatment efficacy of TDF containing regimen was not statistically different according to the presence of specific HBV mutations. History of prior exposure to specific antiviral agents did not make a difference to treatment outcome. Treatment efficacy of TDF was not affected by combination therapy with LAM or ETV. No patient developed renal toxicity and no cases of hypophosphatemia associated with TDF therapy were observed. There were no other adverse events related to TDF therapy observed in the study subjects.
CONCLUSION: TDF can be an effective and safe rescue therapy in CHB patients after multiple NA therapy failures.
Tenofovir; Chronic hepatitis B; Treatment failure
Accumulating evidence has revealed that the resting-state functional connectivity (RSFC) is frequency specific and functional system dependent. Determination of dominant frequency of RSFC (RSFCdf) within a functional system, therefore, is of importance for further understanding the brain interaction and accurately assessing the RSFC within the system. Given the unique advantages over other imaging techniques, functional near-infrared spectroscopy (fNIRS) holds distinct merits for RSFCdf determination. However, an obstacle that hinders fNIRS from potential RSFCdf investigation is the interference of various global noises in fNIRS data which could bring spurious connectivity at the frequencies unrelated to spontaneous neural activity. In this study, we first quantitatively evaluated the interferences of multiple systemic physiological noises and the motion artifact by using simulated data. We then proposed a functional system dependent and frequency specific analysis method to solve the problem by introducing anatomical priori information on the functional system of interest. Both the simulated and real resting-state fNIRS experiments showed that the proposed method outperforms the traditional one by effectively eliminating the negative effects of the global noises and significantly improving the accuracy of the RSFCdf estimation. The present study thus provides an effective approach to RSFCdf determination for its further potential applications in basic and clinical neurosciences.
Systematic ligand development has led to the identification of novel mono-N-protected amino acid ligands for Pd(II)-catalyzed enantioselective C–H activation of cyclopropanes. A diverse range of organoboron reagents could be used as coupling partners, and the reaction was found to proceed under mild conditions. These results provide a new retrosynthetic disconnection for the construction of enantioenriched cis-substituted cyclopropanecarboxylic acids.
Acupuncture regulates inflammation process and growth factors by increasing blood circulation in affected areas. In this study, we examined whether acupuncture has an effect on wound healing in injured rat. Rats were assigned randomly into two groups: control group and acupuncture group. Acupuncture treatment was carried out at 8 sites around the wounded area. We analyzed the wound area, inflammatory cytokines, proliferation of resident cells, and angiogenesis and induction of extracelluar matrix remodeling. At 7 days after-wounding the wound size in acupuncture-treat group was decreased more significantly compared to control group. In addition, the protein levels of proinflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were significantly decreased compared to the control at 2 and 7 days post-wounding. Also, we analyzed newly generated cells by performing immunostaining for PCNA and using several phenotype markers such as CD-31, α-SMA, and collagen type I. In acupuncture-treated group, PCNA-positive cell was increased and PCNA labeled CD-31-positive vessels, α-SMA- and collagen type I-positive fibroblastic cells, were increased compared to the control group at 7 days post-wounding. These results suggest that acupuncture may improve wound healing through decreasing pro-inflammatory response, increasing cell proliferation and angiogenesis, and inducing extracellular matrix remodeling.
Activated vitamin D analog, paricalcitol, has been shown to attenuate the development of cardiac hypertrophy in Dahl salt sensitive (DSS) rats. To determine whether an anti-hypertrophic effect is class specific, we tested if doxercalciferol (a pro-hormone vitamin D2 analog) could also attenuate the development of cardiac hypertrophy in DSS rats.
Methods and Results
Male DSS rats were fed a high salt (HS) diet for 6 weeks beginning at 6 weeks of age. Doxercalciferol was administered intraperitoneally (i.p.) at 150ng, 3 times a week (Mon, Wed, Fri) for six weeks. Pathological and echocardiographic findings demonstrated that rats on HS diet with doxercalciferol administration had significant decrease in cardiac hypertrophy and improved cardiac function compared to the HS + vehicle. In addition, there was a significant decrease in plasma brain natriuretic peptide (BNP) level and tissue atrial natriuretic factor (ANF) mRNA level with doxercalciferol treatment. Doxercalciferol also significantly reduced the level of protein kinase C-α (PKCα) suggesting that PKC-mediated cardiac hypertrophy may be associated with vitamin D deficiency.
Administration of doxercalciferol attenuated the development of HS diet induced cardiac hypertrophy and cardiac dysfunction in DSS rats.
heart failure; high salt; Dahl rats; cardiac dysfunction
Precocious puberty is defined as breast development before the age of 8 years in girls. The present study aimed to reveal the diagnosis of Korean girls referred for precocious puberty and to compare the constitutional and endocrinological features among diagnosis groups.
The present study used a retrospective chart review of 988 Korean girls who had visited a pediatric endocrinology clinic from 2006 to 2010 for the evaluation of precocious puberty. Study groups comprised fast puberty, true precocious puberty (PP), pseudo PP, premature thelarche, and control. We determined the height standard deviation score (HSDS), weight standard deviation score (WSDS), and body mass index standard deviation score (BMISDS) of each group using the published 2007 Korean growth charts. Hormone tests were performed at our outpatient clinic.
The PP groups comprised fast puberty (67%), premature thelarche (17%), true PP (15%), and pseudo PP (1%). Advanced bone age and levels of estradiol, basal luteinizing hormone (LH), and peak LH after gonadotropin-releasing hormone stimulation testing were significantly high in the fast puberty and true PP groups compared with the control group. HSDS, WSDS, and BMISDS were significantly higher in the true PP group than in the control group (P<0.05).
The frequent causes of PP were found to be fast puberty, true PP, and premature thelarche. Furthermore, BMISDS were significantly elevated in the true PP group. Therefore, we emphasize the need for regular follow-up of girls who are heavier or taller than others in the same age group.
Precocious puberty; Puberty; Premature thelarche; Body mass index; Sexual maturation
A highly efficient ligand-accelerated Pd(II)-catalyzed C(sp2)–H/arylboron cross-coupling reaction of phenylacetic acid substrates is reported. Using Ac-Ile-OH as the ligand and Ag2CO3 as the oxidant, a fast, high yielding, operationally simple, and functional group–tolerant protocol has been developed for the cross-coupling of phenylacetic acid substrates with aryltrifluoroborates. This ligand scaffold has also been shown to improve substantially catalysis using 1 atm O2 as the sole reoxidant, which sheds light on the path forward in developing optimized ligands for aerobic C–H/arylboron cross-coupling.
Until recently, sequencing has primarily been carried out in large genome centers which have invested heavily in developing the computational infrastructure that enables genomic sequence analysis. The recent advancements in next generation sequencing (NGS) have led to a wide dissemination of sequencing technologies and data, to highly diverse research groups. It is expected that clinical sequencing will become part of diagnostic routines shortly. However, limited accessibility to computational infrastructure and high quality bioinformatic tools, and the demand for personnel skilled in data analysis and interpretation remains a serious bottleneck. To this end, the cloud computing and Software-as-a-Service (SaaS) technologies can help address these issues.
We successfully enabled the Atlas2 Cloud pipeline for personal genome analysis on two different cloud service platforms: a community cloud via the Genboree Workbench, and a commercial cloud via the Amazon Web Services using Software-as-a-Service model. We report a case study of personal genome analysis using our Atlas2 Genboree pipeline. We also outline a detailed cost structure for running Atlas2 Amazon on whole exome capture data, providing cost projections in terms of storage, compute and I/O when running Atlas2 Amazon on a large data set.
We find that providing a web interface and an optimized pipeline clearly facilitates usage of cloud computing for personal genome analysis, but for it to be routinely used for large scale projects there needs to be a paradigm shift in the way we develop tools, in standard operating procedures, and in funding mechanisms.
Force-based atomic force microscopy (AFM) was used to detect HCV (hepatitis C virus) RNA directly and to quantitatively analyse it without the need for reverse transcription or amplification. Capture and detection DNA probes were designed. The former was spotted onto a substrate with a conventional microarrayer, and the latter was immobilized on an AFM probe. To control the spacing between the immobilized DNAs on the surface, dendron self-assembly was employed. Force–distance curves showed that the mean force of the specific unbinding events was 32 ± 5 pN, and the hydrodynamic distance of the captured RNA was 30–60 nm. Adhesion force maps were generated with criteria including the mean force value, probability of obtaining the specific curves and hydrodynamic distance. The maps for the samples whose concentrations ranged from 0.76 fM to 6.0 fM showed that cluster number has a linear relationship with RNA concentration, while the difference between the observed number and the calculated one increased at low concentrations. Because the detection limit is expected to be enhanced by a factor of 10 000 when a spot of 1 micron diameter is employed, it is believed that HCV RNA of a few copy numbers can be detected by the use of AFM.
It has been proposed that the pro-inflammatory catalytic activity of cyclooxygenase-2 (COX-2) plays a key role in the aging process. However, it remains unclear whether the COX-2 activity is a causal factor for aging and whether COX-2 inhibitors could prevent aging. We here examined the effect of COX-2 inhibitors on aging in the intrinsic skin aging model of hairless mice. We observed that among two selective COX-2 inhibitors and one non-selective COX inhibitor studied, only NS-398 inhibited skin aging, while celecoxib and aspirin accelerated skin aging. In addition, NS-398 reduced the expression of p53 and p16, whereas celecoxib and aspirin enhanced their expression. We also found that the aging-modulating effect of the inhibitors is closely associated with the expression of type I procollagen and caveolin-1. These results suggest that pro-inflammatory catalytic activity of COX-2 is not a causal factor for aging at least in skin and that COX-2 inhibitors might modulate skin aging by regulating the expression of type I procollagen and caveolin-1.
caveolin-1; cyclooxygenase inhibitors; procollagen; skin aging
Proximal spinal muscular atrophy (SMA) is a common neuromuscular disorder resulting in death during childhood. Around 81 ~ 95% of SMA cases are a result of homozygous deletions of survival motor neuron gene 1 (SMN1) gene or gene conversions from SMN1 to SMN2. Less than 5% of cases showed rare subtle mutations in SMN1. Our aim was to identify subtle mutations in Chinese SMA patients carrying a single SMN1 copy.
We examined 14 patients from 13 unrelated families. Multiplex ligation-dependent probe amplification analysis was carried out to determine the copy numbers of SMN1 and SMN2. Reverse transcription polymerase chain reaction (RT-PCR) and clone sequencing were used to detect subtle mutations in SMN1. SMN transcript levels were determined using quantitative RT-PCR.
Six subtle mutations (p.Ser8LysfsX23, p.Glu134Lys, p.Leu228X, p.Ser230Leu, p.Tyr277Cys, and p.Arg288Met) were identified in 12 patients. The p.Tyr277Cys mutation has not been reported previously. The p.Ser8LysfsX23, p.Leu228X, and p.Tyr277Cys mutations have only been reported in Chinese SMA patients and the first two mutations seem to be the common ones. Levels of full length SMN1 (fl-SMN1) transcripts were very low in patients carrying p.Ser8LysfsX23, p.Leu228X or p.Arg288Met compared with healthy carriers. In patients carrying p.Glu134Lys or p.Ser230Leu, levels of fl-SMN1 transcripts were reduced but not significant. The SMN1 transcript almost skipped exon 7 entirely in patients with the p.Arg288Met mutation.
Our study reveals a distinct spectrum of subtle mutations in SMN1 of Chinese SMA patients from that of other ethnicities. The p.Arg288Met missense mutation possibly influences the correct splicing of exon 7 in SMN1. Mutation analysis of the SMN1 gene in Chinese patients may contribute to the identification of potential ethnic differences and enrich the SMN1 subtle mutation database.
Spinal muscular atrophy; Survival motor neuron gene-1; Subtle mutation; Transcript
Pd-catalyzed para-selective C–H arylation of mono-substituted arenes including toluene is developed for the first time using F+ as a bystanding oxidant. This finding provides a new retrosynthetic disconnection for biaryl synthesis.
Rectus abdominis muscle and abdominal subcutaneous fat tissue are useful for reconstruction of the chest wall, and abdominal, vaginal, and perianal defects. Thus, preoperative evaluation of rectus abdominis muscle and abdominal subcutaneous fat tissue is important. This is a retrospective study that measured the thickness of rectus abdominis muscle and abdominal subcutaneous fat tissue using computed tomography (CT) and analyzed the correlation with the patients' age, gestational history, history of laparotomy, and body mass index (BMI).
A total of 545 adult women were studied. Rectus abdominis muscle and abdominal subcutaneous fat thicknesses were measured with abdominopelvic CT. The results were analyzed to determine if the thickness of the rectus abdominis muscle or subcutaneous fat tissue was significantly correlated with age, number of pregnancies, history of laparotomy, and BMI.
Rectus abdominis muscle thicknesses were 9.58 mm (right) and 9.73 mm (left) at the xiphoid level and 10.26 mm (right) and 10.26 mm (left) at the umbilicus level. Subcutaneous fat thicknesses were 24.31 mm (right) and 23.39 mm (left). Rectus abdominismuscle thickness decreased with age and pregnancy. History of laparotomy had a significant negative correlation with rectus abdominis muscle thickness at the xiphoid level. Abdominal subcutaneous fat thickness had no correlation with age, number of pregnancies, or history of laparotomy.
Age, gestational history, and history of laparotomy influenced rectus abdominis muscle thickness but did not influence abdominal subcutaneous fat thickness. These results are clinically valuable for planning a rectus abdominis muscle flap and safe elevation of muscle flap.
Rectus abdominis; Age; Pregnancy; Laparotomy; Body mass index