Clinical course of two siblings with potassium voltage-gated channel modifier subfamily V member 2 (KCNV2)-associated retinopathy.

BACKGROUND: KCNV2-associated retinopathy causes a phenotype reported as "cone dystrophy with nyctalopia and supernormal rod responses (CDSRR; OMIM# 610356)," featuring pathognomonic findings on electroretinography (ERG). Here, we report the clinical courses of two siblings with CDSRR. CASE REPORTS: Patient 1: A 3-year-old boy with intermittent exophoria was referred to our hospital. The patient's decimal best-corrected visual acuity (BCVA) at age 6 was 0.7 and 0.7 in the right and left eyes, respectively. Photophobia and night blindness were also observed. Because the ERG showed a delayed and supernormal b-wave with a "squaring (trough-flattened)" a-wave in the DA-30 ERG, and CDSRR was diagnosed. The patient's vision gradually worsened, and faint bilateral bull's eye maculopathy was observed at the age of 27 years, although the fundi were initially unremarkable. Genetic examination revealed a homozygous missense variant, c.529T > C (p.Cys177Arg), in the KCNV2 gene. Patient 2: The second patient was Patient 1's younger sister, who was brought to our hospital at 3 years of age. The patient presented with exotropia, mild nystagmus, photophobia, night blindness, and color vision abnormalities. The patients' decimal BCVA at age 13 was 0.6 and 0.4 in the right and left eyes, respectively, and BCVA gradually decreased until the age of 24 years. The fundi were unremarkable. The siblings had similar ERG findings and the same homozygous missense variant in the KCNV2 gene. CONCLUSIONS: The siblings had clinical findings typical of CDSRR. High-intense flash ERG is recommended for identifying pathognomonic "squaring" a-waves in patients with CDSRR.

Evaluation of clinical effects of a multidisciplinary-collaborated cancer support team for gastrointestinal cancer chemotherapy: prospective observational study protocol of M-CAST study.

BACKGROUND: Although the multidisciplinary-collaborated team approach in cancer treatment has recently become popular, prospectively evaluated evidence is limited. We started a multidisciplinary-collaborated cancer support team (MCST) to facilitate cooperation across multidisciplinary medical staff in our hospital and established clinical evidence of supportive care. This study aimed to prospectively evaluate the clinical activity and effect of MCST in patients with gastrointestinal cancer receiving chemotherapy. METHODS: This is a single-center, single-arm, observational study. Patients with gastrointestinal cancer scheduled to receive chemotherapy are enrolled and supported by the MCST. The primary endpoints are the number of interventions by medical staff and the number of patients who showed improvement in side effects. The secondary endpoints are the severity of side effects, medical expenses, number of consultations, the acceptance rate of prescription recommendations, adjuvant chemotherapy completion rates, dose intensity, and time required for co-medical intervention. In addition, medical staff and attending physicians evaluate all adverse events. DISCUSSION: This study is expected to contribute to establishing new cancer-supportive care teams for patients with gastrointestinal cancer receiving chemotherapy and those with cancer receiving chemotherapy. TRIAL REGISTRATION: This trial was registered in the Japan Registry of Clinical Trials (jRCT) as jRCT1030220495. The date of first registration, 29/11/2022, https://jrct.niph.go.jp/search.

Hypochlorous acid solution is a potent antiviral agent against SARS-CoV-2.

AIM: A novel coronavirus, termed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) suddenly appeared in Wuhan, China, and has caused pandemic. In this study, we evaluated antiviral activity of purified hypochlorous acid (HClO) against coronaviruses such as SARS-CoV-2 and transmissible gastroenteritis virus (TGEV) responsible for pig diseases. MATERIALS AND RESULTS: In a suspension test, 28.1 ppm HClO solution inactivated SARS-CoV-2 in phosphate-buffered saline with the reduction of 104 of 50% tissue culture infectious dose per ml (TCID50 per ml) within 10 s. When its concentration increased to 59.4 ppm, the virus titre decreased to below the detection limit (reduction of 5 logs TCID50 ) within 10 s even in the presence of 0.1% foetal bovine serum. In a carrier test, incubation with 125 ppm HClO solution for 10 min or 250 ppm for 5 min inactivated SARS-CoV-2 by more than 4 logs TCID50 per ml or below the detection limit. Because the titre of TGEV was 10-fold higher, TGEV was used for SARS-CoV-2 in a suspension test. As expected, 56.3 ppm HClO solution inactivated TGEV by 6 logs TCID50 within 30 s. CONCLUSIONS: In a carrier test, 125 ppm HClO solution for 10 min incubation is adequate to inactivate 4 logs TCID50 per ml of SARS-CoV-2 or more while in a suspension test 56.3 ppm HClO is adequate to inactivate 5 logs TCID50 per ml of SARS-CoV-2 when incubated for only 10 s regardless of presence or absence of organic matter. SIGNIFICANCE AND IMPACT OF THE STUDY: Effectiveness of HClO solution against SARS-CoV-2 was demonstrated by both suspension and carrier tests. HClO solution inactivated SARS-CoV-2 by 5 logs TCID50 within 10 s. HClO solution has several advantages such as none toxicity, none irritation to skin and none flammable. Thus, HClO solution can be used as a disinfectant for SARS-CoV-2.

[Intravascular large B-cell lymphoma diagnosed by total hysterectomy].

Intravascular large B-cell lymphoma (IVLBCL) is a rare form of non-Hodgkin B-cell lymphoma which occurs mainly in capillaries and small blood vessels. Successful diagnosis of IVLBCL is challenging since it lacks tumor formation and presents various clinical manifestations. An 82-year-old Asian female patient presented to our emergency department with a history of general fatigue, weight loss, and fever for two weeks. The patient's random skin biopsy was negative, and her bone marrow biopsy revealed hemophagocytic syndrome with no obvious involvement of lymphoma cells. Gallium scintigraphy showed mild uptake in the uterus, pelvis, and spine. The repetitive bone marrow biopsy result and the endometrial cytology/biopsy were negative; however, the pelvic MRI was compatible with lymphoma, revealing lesions in the corpus uteri, pelvis, and vertebral body. After laparoscopic-assisted vaginal total hysterectomy and bilateral salpingo-oophorectomy, the diagnosis of the Asian variant of IVLBCL was made. Although total hysterectomy remains controversial for elderly patients with declining performance status, we could successfully diagnose the condition and initiate the treatment. The patient's general condition improved soon after starting rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone regimen on day 26, and she was discharged on day 45.

The Evaluation of Helicopter Emergency Medical Services With a Physician for Acute Myocardial Infarction in Japan: A Registry-Based Study of Prognosis and Time Reduction.

OBJECTIVE: The aim of this study was to compare the prognosis and time reduction between helicopter emergency medical services (HEMS) with a physician and ground emergency medical services (GEMS) in acute myocardial infarction (AMI) cases. METHODS: This is a registry-based study of the Japan Helicopter Emergency Medical Service Registry from April 1, 2015, to March 31, 2018. RESULTS: A total of 605 cases of AMI were registered in the HEMS group and 794 cases in the GEMS group. In the cases of non-cardiopulmonary arrest (CPA), the prognosis between HEMS and GEMS did not differ significantly. Regarding the road distance, for ranges of 20 to 40 km and > 40 km, the times from the call to the angiography room were significantly shorter with HEMS than GEMS (median 91 vs. 97 minutes, P = .036 and 101 vs. 132 minutes, P = .002, respectively). In cases of CPA, HEMS had a higher rate of return of spontaneous circulation than GEMS (55.3% vs. 36.8%, P = .038), but HEMS had a lower prognosis than GEMS (22.9% vs. 38.9%, P = .036). CONCLUSION: The present study suggested that HEMS had an advantage in reducing the time to angiography in AMI cases of non-CPA. In cases of CPA, HEMS increased the return of spontaneous circulation without improving the prognosis.

The Prognostic Impact of Pretransplantation Inflammatory and Nutritional Status in Adult Patients after Myeloablative Single Cord Blood Transplantation.

Markers of inflammatory and nutritional status, such as the Controlling Nutritional Status (CONUT) score, Prognostic Nutritional Index, Glasgow Prognostic Score, and C-reactive protein-albumin ratio (CAR) has been demonstrated to be associated with poor prognosis in patients with various cancers. Although the relatively low cell dose of a single cord blood unit restricts the indication for cord blood transplantation (CBT) to pediatric and relatively smaller and lighter adult patients, the impact of malnutrition on outcomes after CBT is unclear. We retrospectively analyzed 165 adult patients who underwent myeloablative single-unit CBT in our institute. In multivariate analysis, a higher CONUT score, which is indicative of poor inflammatory and nutritional status, was significantly associated with poor outcomes, including low neutrophil engraftment and development of extensive chronic graft-versus-host disease. A higher CAR, which is also suggestive of poor inflammatory and nutritional status, was significantly associated with poor neutrophil engraftment and higher overall mortality. Body mass index (BMI) was not associated with transplantation outcomes. These data suggest that poor pretransplantation inflammatory and nutritional status might be a more practical parameter than lower BMI, for predicting transplantation outcomes after single CBT for adults.

GH30 Glucuronoxylan-Specific Xylanase from Streptomyces turgidiscabies C56.

Endoxylanases are important enzymes in bioenergy research because they specifically hydrolyze xylan, the predominant polysaccharide in the hemicellulose fraction of lignocellulosic biomass. For effective biomass utilization, it is important to understand the mechanism of substrate recognition by these enzymes. Recent studies have shown that the substrate specificities of bacterial and fungal endoxylanases classified into glycoside hydrolase family 30 (GH30) were quite different. While the functional differences have been described, the mechanism of substrate recognition is still unknown. Therefore, a gene encoding a putative GH30 endoxylanase was cloned from Streptomyces turgidiscabies C56, and the recombinant enzyme was purified and characterized. GH30 glucuronoxylan-specific xylanase A of Streptomyces turgidiscabies (StXyn30A) showed hydrolytic activity with xylans containing both glucuronic acid and the more common 4-O-methyl-glucuronic acid side-chain substitutions but not on linear xylooligosaccharides, suggesting that this enzyme requires the recognition of glucuronic acid side chains for hydrolysis. The StXyn30A limit product structure was analyzed following a secondary ß-xylosidase treatment by thin-layer chromatography and mass spectrometry analysis. The hydrolysis products from both glucuronoxylan and 4-O-methylglucuronoxylan by StXyn30A have these main-chain substitutions on the second xylopyranosyl residue from the reducing end. Because previous structural studies of bacterial GH30 enzymes and molecular modeling of StXyn30A suggested that a conserved arginine residue (Arg296) interacts with the glucuronic acid side-chain carboxyl group, we focused on this residue, which is conserved at subsite -2 of bacterial but not fungal GH30 endoxylanases. To help gain an understanding of the mechanism of how StXyn30A recognizes glucuronic acid substitutions, Arg296 mutant enzymes were studied. The glucuronoxylan hydrolytic activities of Arg296 mutants were significantly reduced in comparison to those of the wild-type enzyme. Furthermore, limit products other than aldotriouronic acid were observed for these Arg296 mutants upon secondary ß-xylosidase treatment. These results indicate that a disruption of the highly conserved Arg296 interaction leads to a decrease of functional specificity in StXyn30A, as indicated by the detection of alternative hydrolysis products. Our studies allow a better understanding of the mechanism of glucuronoxylan recognition and enzyme specificity by bacterial GH30 endoxylanases and provide further definition of these unique enzymes for their potential application in industry.IMPORTANCE Hemicellulases are important enzymes that hydrolyze hemicellulosic polysaccharides to smaller sugars for eventual microbial assimilation and metabolism. These hemicellulases include endoxylanases that cleave the ß-1,4-xylose main chain of xylan, the predominant form of hemicellulose in lignocellulosic biomass. Endoxylanases play an important role in the utilization of plant biomass because in addition to their general utility in xylan degradation, they can also be used to create defined compositions of xylooligosaccharides. For this, it is important to understand the mechanism of substrate recognition. Recent studies have shown that the substrate specificities of bacterial and fungal endoxylanases that are classified into glycoside hydrolase family 30 (GH30) were distinct, but the difference in the mechanisms of substrate recognition is still unknown. We performed characterization and mutagenesis analyses of a new bacterial GH30 endoxylanase for comparison with previously reported fungal GH30 endoxylanases. Our study results in a better understanding of the mechanism of substrate specificity and recognition for bacterial GH30 endoxylanases. The experimental approach and resulting data support the conclusions and provide further definition of the structure and function of GH30 endoxylanases for their application in bioenergy research.

A cross-sectional study on late taste disorders in survivors of allogeneic hematopoietic cell transplantation.

Taste disorders are one of the most common complications in patients undergoing allogeneic hematopoietic cell transplantation (HCT). They persist in some patients as a late complication 3 months or more after HCT. Therefore, we conducted a cross-sectional study to evaluate the prevalence and predictive factors of late taste disorders, with the help of a self-reporting and closed-ended questionnaire, which was distributed among 91 patients in our institute. The median age at this study was 50 (range, 25-69) years. The median follow-up period was 54 (range, 3-234) months after HCT. Taste disorders were observed in 43 patients (47%). The most frequent form of late taste disorders was reduced appetite in 18 patients (20%). The most frequent form of decline of basic taste was umami, which was observed in 12 patients (13%). Almost all taste disorders were mild in their severity. Multivariate logistic regression analyses showed that the duration of less than 1 year post HCT and the presence of oral chronic graft-versus-host disease are important risk factors for late taste disorders in survivors of HCT. These data suggested that taste disorders usually return to normal levels more than a year after HCT in most recipients.

Incidence and index of severity of hemolytic uremic syndrome in a 26 year period in Fukushima Prefecture, Japan.

BACKGROUND: There have been a number of reports on large outbreaks of hemolytic uremic syndrome (HUS), but there have been no long-term studies of sporadic HUS in Japan. This study therefore investigated the epidemiology and prognosis of HUS in Fukushima Prefecture over a 26 year period. METHODS: The medical records of 26 patients with HUS between 1987 and 2012 were collected. These children were divided into two groups: those with HUS following an episode of gastroenteritis, often with bloody diarrhea (D + HUS; n = 24) and those with HUS not associated with prodromal diarrhea (D-HUS; n = 2). The D + HUS group was further subdivided into group A (11 patients requiring dialysis) and group B (13 patients not requiring dialysis). The epidemiological and clinical data, as well as prognosis, were retrospectively investigated for each group. RESULTS: Approximately 90% of HUS patients belonged to the D + HUS group. In this group, the mean number of patients per year from 1987 to 1999, and from 2000 to 2012 was 0.92 ± 0.95, and 1.08 ± 0.86, respectively. On admission, lactate dehydrogenase (LDH), alanine aminotransferase (ALT), blood urea nitrogen (BUN), serum creatinine and serum fibrinogen degradation product (FDP) levels in group A were all higher than in group B. Serum albumin level and estimated glomerular filtration rate (eGFR) in group A were lower than in group B. At 6 months after the onset of HUS in the D + HUS group, renal function was normal. CONCLUSIONS: The frequency of HUS was constant from 1987 to 2012 in Fukushima. and serum LDH, ALT, BUN, creatinine, and FDP levels as well as eGFR might be risk factors for dialysis in D + HUS children.

Uniqueness of ductal carcinoma in situ of the breast concurrent with papilloma: implications from a detailed topographical and histopathological study of 50 cases treated by mastectomy and wide local excision.

AIMS: To clarify the diagnostic clues of ductal carcinomas in situ (DCIS) associated with papilloma and optimal clinical management of papilloma diagnosed on core needle biopsy (CNB). METHODS AND RESULTS: A total of 50 surgically resected cases were examined histopathologically and topographically. Thirty-nine cases (78%) spread in segmental fashion. Papilloma and DCIS were intermingled closely in 44 cases (88%), occupying the same areas in varying proportions from DCIS-predominant to papilloma-predominant. The two components occupied discrete areas and collided focally in six cases (12%). Most were non-high-grade. Cribriform and solid architectures with fibrovascular stroma were frequent. The cribriform pattern was unique, consisting of fused tubules separated by fibrovascular stroma. Intraductal myoepithelial cells were present to varying degrees in 40 cases (80%). In 38 cases (76%), points were identified where papilloma and DCIS coexisted or collided within a single lumen (CC point). Forty-eight cases (96%) had either intraductal myoepithelial cells or CC points, implying that DCIS and papilloma existed in the same duct system. Radiology showed segmental abnormalities in 83% of the available cases. CONCLUSIONS: Intraductal myoepithelial cells do not always guarantee benignity. Surgical resection is recommended for papilloma in CNB when radiology shows segmental abnormalities.

Relapse of minimal change nephrotic syndrome after intravitreal bevacizumab.

Reported herein is a case of relapse of nephrotic syndrome (NS) after intravitreal injection of bevacizumab, a monoclonal antibody that binds to vascular endothelial growth factor (VEGF), in a 16-year-old girl. She had a diagnosis of steroid-dependent NS and had been treated with prednisolone, and remained in remission. The patient had had visus brevior 10 years previously, and was diagnosed with severe myopic choroidal neovascularization (mCNV). Intravitreal bevacizumab was given for mCNV. At 9 days after intravitreal injection of bevacizumab, proteinuria was positive. The patient had relapse of NS caused by bevacizumab, and steroid pulse therapy was then given and the proteinuria resolved. It is necessary to take particular care to prevent NS relapses in patients with mCNV treated with intravitreal bevacizumab.

[Perioperative management in children with sleep apnea syndrome (SAS) undergoing adenoidotonsillectomy].

We should take care of the occurrences of apnea and hypopnea after emergence from general anesthesia in the children with sleep apnea syndrome (SAS) due to an increase in sensitivity to opioid agonists given for previous recurrent hypoxia. Preoperative assessment for SAS with apnea hypopnea index (AHI), oxygen desaturation index (ODI), and minimum artery oxygen saturation by pulse oxymetry (lowest SpO2) obtained from polysomnography (PSG) test could help to predict the postoperative respiratory depression. In perioperative management in the children with SAS who are candidates for adenotonsillectomy, the dose of opioid agonists during anesthesia maintenance for purpose of postoperative analgesia and sedation should be reduced; postoperative respiratory and circulatory management with monitoring of respiratory movement of the thoracoabdominal part, and electrographic (ECG) and SpO2 monitoring should be continued intensively under long-term oxygen administration; and airway management, nasal continuous positive airway pressure (nCPAP), and artificial ventilation should be prepared for the occurrence of postoperative respiratory depression.

Development of an educational program for healthcare professionals who provide appearance care for patients with cancer: Feasibility study of an e-learning program.

This study aimed to evaluate the feasibility and utility of an e-learning training program to improve healthcare professionals' knowledge about providing appearance care to patients with cancer. Healthcare professionals who provide appearance support were invited to participate voluntarily and complete a survey before and after the program. Participation request letters were distributed to 133 individuals, including 75 from four facilities invited via professional connections, and agreed to participate in the study and 58 participated in the National Cancer Center's appearance care training and indicated an interest in participating in the study. The 100 participants (75.2%) included 96 females, with an average age of 40.5 years. The participants reported high levels of satisfaction with the program, where more than 90% responded "satisfied" or "somewhat satisfied" and eager to use the content they learned in the program when they returned to their workplaces. However, the participants identified several barriers to applying their newly acquired knowledge including lack of knowledge (about 80%). Participant knowledge scores about appearance support were significantly higher after program participation. The survey results indicated the high feasibility of the e-learning program through improved knowledge about appearance care and high satisfaction with the program. The program needs further improvements for its practical utility.

X-ray free electron laser observation of ultrafast lattice behaviour under femtosecond laser-driven shock compression in iron.

Over the past century, understanding the nature of shock compression of condensed matter has been a major topic. About 20 years ago, a femtosecond laser emerged as a new shock-driver. Unlike conventional shock waves, a femtosecond laser-driven shock wave creates unique microstructures in materials. Therefore, the properties of this shock wave may be different from those of conventional shock waves. However, the lattice behaviour under femtosecond laser-driven shock compression has never been elucidated. Here we report the ultrafast lattice behaviour in iron shocked by direct irradiation of a femtosecond laser pulse, diagnosed using X-ray free electron laser diffraction. We found that the initial compression state caused by the femtosecond laser-driven shock wave is the same as that caused by conventional shock waves. We also found, for the first time experimentally, the temporal deviation of peaks of stress and strain waves predicted theoretically. Furthermore, the existence of a plastic wave peak between the stress and strain wave peaks is a new finding that has not been predicted even theoretically. Our findings will open up new avenues for designing novel materials that combine strength and toughness in a trade-off relationship.

Pre-anesthesia systolic blood pressure increases with age regardless of sex.

PURPOSE: Pre-anesthesia hypertension (PAH) is the temporary elevation of blood pressure (BP), compared with normal ambulatory recorded BP or self-measured BP at home, in patients waiting for operation in the operating room (OR) before anesthesia induction. In general, the incidence of sustained hypertension (SH) increases progressively with age and the increase is greater in males than in females. In this study, we investigated the influence of age and sex on PAH. METHODS: Sampling data on consecutive patients who were more than 20 years old and who had undergone surgery under general, intrathecal, or epidural anesthesia were retrospectively collected from hospital records and anesthesia records. Patients with SH, which was defined as a past history of hypertension and taking oral antihypertensive medications, were excluded from the analyses, and the data of 231 patients, 102 males and 129 females, were used for the analyses. RESULTS: The proportions of male and female patients with a systolic BP (sBP) of more than 140 mmHg in the OR before anesthesia induction were 55.9 and 42.6%, respectively. The proportions of male and female patients with a diastolic BP (dBP) of more than 90 mmHg were 34.3 and 23.3%, respectively. There was no difference in the proportions of male and female patients with PAH. The differences in sBP between measurements in the hospital room (HR) before the operation and those in the OR (ΔsBP) in males and females were 22.9 ± 25.6 and 19.0 ± 24.0 mmHg, respectively. The differences in dBP between measurements in the HR and those in the OR (ΔdBP) in males and females were 12.7 ± 16.5 and 8.4 ± 17.9 mmHg, respectively. There were no differences in ΔsBP and ΔdBP between males and females. The sBP in the OR and the ΔsBP increased significantly with age in both males and females. CONCLUSION: Age is an important clinical factor related to PAH. Pre-anesthesia sBP and the change in pre-anesthesia sBP increase progressively with age regardless of sex. These findings suggest that the higher BP seen in the elderly in the OR before anesthesia induction, as reported previously, might be explained in part by a greater impact of PAH in older people.

Responding to COVID-19: Establishing a nursing system that is appropriate for the new post-epidemic era.

Hospitals that admit patients with COVID-19 face the challenge of not only dealing with these patients but also balancing normal medical care and hospital management to cope with the challenges posed by the new post-epidemic era. Over the past two years of responding to COVID-19 as a front-line clinical nurse, my colleagues and I have fully appreciated the need to establish a nursing system that is appropriate for the new post-epidemic era. The following four aspects should be emphasized: i) the continuation of thorough infection control measures; ii) exploring new approaches to training for new recruits; iii) ensuring nursing workforce and improving the nursing capacity to cope with patients critically ill with COVID-19; and iv) teamwork and team care to provide nurses with timely psychological assistance.

Recurrent proliferative vitreoretinopathy in a patient with morning glory syndrome and intellectual disability.

PURPOSE: To report a case of morning glory syndrome (MGS) with retinal detachment, in whom unusually severe proliferative vitreoretinopathy (PVR) developed after surgery. OBSERVATIONS: A 6-year-old boy with intellectual disability underwent vitrectomy for retinal detachment associated with MGS in the left eye. Vitrectomy was performed five times. C3F8 gas tamponade was used for the first and second surgeries. However, the retina developed PVR with a nearly 360-degree giant retinal tear after the second surgery. The third surgery required 360-degree retinotomy, followed by short-term perfluoro-n-octane (PFO) tamponade, which was removed ten days later. During the fourth surgery, the retina was found to be flipped over in a funnel-shape on the retinal pigment epithelium under the PFO. Silicone oil (SO) tamponade was used. During the fifth surgery, the retina was flipped over under the SO again. We found that the patient shook his head rapidly and vigorously while crying. CONCLUSIONS AND IMPORTANCE: We speculate that excessive head shaking associated with the patient's intellectual disability induced an unusual shape of the retina under PFO or SO. Although difficult to achieve, postoperative resting seems important in preventing such complications in intellectually disabled patients with retinal detachment.

Substrate Specificities of GH8, GH39, and GH52 ß-xylosidases from Bacillus halodurans C-125 Toward Substituted Xylooligosaccharides.

Substrate specificities of glycoside hydrolase families 8 (Rex), 39 (BhXyl39), and 52 (BhXyl52) ß-xylosidases from Bacillus halodurans C-125 were investigated. BhXyl39 hydrolyzed xylotriose most efficiently among the linear xylooligosaccharides. The activity decreased in the order of xylohexaose > xylopentaose > xylotetraose and it had little effect on xylobiose. In contrast, BhXyl52 hydrolyzed xylobiose and xylotriose most efficiently, and its activity decreased when the main chain became longer as follows: xylotetraose > xylopentaose > xylohexaose. Rex produced O-ß-D-xylopyranosyl-(1 → 4)-[O-α-L-arabinofuranosyl-(1 → 3)]-O-ß-D-xylopyranosyl-(1 → 4)-ß-D-xylopyranose (Ara2Xyl3) and O-ß-D-xylopyranosyl-(1 → 4)-[O-4-O-methyl-α-D-glucuronopyranosyl-(l → 2)]-ß-D-xylopyranosyl-(1 → 4)-ß-D-xylopyranose (MeGlcA2Xyl3), which lost a xylose residue from the reducing end of O-ß-D-xylopyranosyl-(1 → 4)-[O-α-L-arabinofuranosyl-(1 → 3)]-O-ß-D-xylopyranosyl-(1 → 4)-ß-D-xylopyranosyl-(1 → 4)-ß-D-xylopyranose (Ara3Xyl4) and O-ß-D-xylopyranosyl-(1 → 4)-[O-4-O-methyl-α-D-glucuronopyranosyl-(1 → 2)]-ß-D-xylopyranosyl-(1 → 4)-ß-D-xylopyranosyl-(1 → 4)-ß-D-xylopyranose (MeGlcA3Xyl4). It was considered that there is no space to accommodate side chains at subsite -1. BhXyl39 rapidly hydrolyzes the non-reducing-end xylose linkages of MeGlcA3Xyl4, while the arabinose branch does not significantly affect the enzyme activity because it degrades Ara3Xyl4 as rapidly as unmodified xylotetraose. The model structure suggested that BhXyl39 enhanced the activity for MeGlcA3Xyl4 by forming a hydrogen bond between glucuronic acid and Lys265. BhXyl52 did not hydrolyze Ara3Xyl4 and MeGlcA3Xyl4 because it has a narrow substrate binding pocket and 2- and 3-hydroxyl groups of xylose at subsite +1 hydrogen bond to the enzyme.

Ultrafast olivine-ringwoodite transformation during shock compression.

Meteorites from interplanetary space often include high-pressure polymorphs of their constituent minerals, which provide records of past hypervelocity collisions. These collisions were expected to occur between kilometre-sized asteroids, generating transient high-pressure states lasting for several seconds to facilitate mineral transformations across the relevant phase boundaries. However, their mechanisms in such a short timescale were never experimentally evaluated and remained speculative. Here, we show a nanosecond transformation mechanism yielding ringwoodite, which is the most typical high-pressure mineral in meteorites. An olivine crystal was shock-compressed by a focused high-power laser pulse, and the transformation was time-resolved by femtosecond diffractometry using an X-ray free electron laser. Our results show the formation of ringwoodite through a faster, diffusionless process, suggesting that ringwoodite can form from collisions between much smaller bodies, such as metre to submetre-sized asteroids, at common relative velocities. Even nominally unshocked meteorites could therefore contain signatures of high-pressure states from past collisions.

Involvement of human multidrug and toxin extrusion 1 in the drug interaction between cimetidine and metformin in renal epithelial cells.

In human proximal tubules, organic cations are taken up from blood into cells by human organic cation transporter 2 [hOCT2/solute carrier (SLC) 22A2] and then eliminated into the lumen by apical H(+)/organic cation antiporters, human multidrug and toxin extrusion 1 (hMATE1/SLC47A1) and hMATE2-K (SLC47A2). To evaluate drug interactions of cationic drugs in the secretion process, epithelial cells engineered to express both hOCT2 and hMATE transporters are required to simultaneously evaluate drug interactions with renal basolateral and apical organic cation transporters. In the present study, therefore, we assessed the drug interaction between cimetidine and metformin with double-transfected Madin-Darby canine kidney cells stably expressing both hOCT2 and hMATE1 as an in vitro model of the proximal tubular epithelial cells. The basolateral-to-apical transport and intracellular accumulation of [(14)C]metformin by a double transfectant were markedly inhibited by 1 mM cimetidine at the basolateral side. On the other hand, 1 microM cimetidine at the basolateral side moderately decreased the basolateral-to-apical transport of [(14)C]metformin and significantly increased the intracellular accumulation of [(14)C]metformin from the basolateral side, suggesting that cimetidine at a low concentration inhibits apical hMATE1, rather than basolateral hOCT2. Actually, in concentration-dependent inhibition studies by a single transporter expression system, such as human embryonic kidney 293 stably expressing hMATE1, hMATE2-K, or hOCT2, cimetidine showed higher affinity for hMATEs than for hOCT2. These results suggest that apical hMATE1 is involved in drug interactions between cimetidine and cationic compounds in the proximal tubular epithelial cells.