Carbohydrate-binding modules (CBMs) are found in many carbohydrate-active enzymes. CBMs bind to a range of polysaccharides, their primary function being to increase the catalytic efficiency of the ...carbohydrate-active enzymes against soluble and/or insoluble substrates. CBMs bind to their target ligands with high specificities and affinities. Thus, CBM systems are excellent models to study the mechanism of protein-carbohydrate interaction. To date, CBMs have been classified into 45 different families and many structural and functional studies have been reported. At present, three-dimensional structures of CBMs from 31 different families have been determined. These structures demonstrate that the fold most commonly found in CBMs is the β-sandwich. In the past few years, about 10 new structures from different families have been reported. These enable detailed classification of CBM structures. This article reviews recent structural and functional studies of CBMs and discusses the sub-classification of β-sandwich CBMs.
In this retrospective analysis using the Transplant Registry Unified Management Program, we identified 145 patients with human herpesvirus (HHV)-6 encephalitis among 6593 recipients. The cumulative ...incidences of HHV-6 encephalitis at 100 days after transplantation in all patients, recipients of bone marrow or PBSCs and recipients of cord blood were 2.3%, 1.6% and 5.0%, respectively. Risk factors identified in multivariate analysis were male sex, type of transplanted cells (relative risk in cord blood transplantation, 11.09, P<0.001; relative risk in transplantation from HLA-mismatched unrelated donor, 9.48, P<0.001; vs transplantation from HLA-matched related donor) and GvHD prophylaxis by calcineurin inhibitor alone. At 100 days after transplantation, the overall survival rate was 58.3% and 80.5% among patients with and without HHV-6 encephalitis, respectively (P<0.001). Neuropsychological sequelae remained in 57% of 121 evaluated patients. With both foscarnet and ganciclovir, full-dose therapy (foscarnet ⩾180 mg/kg, ganciclovir ⩾10 mg/kg) was associated with better response rate (foscarnet, 93% vs 74%, P=0.044; ganciclovir, 84% vs 58%, P=0.047). HHV-6 encephalitis is not rare not only in cord blood transplant recipients but also in recipients of HLA-mismatched unrelated donors. In this study, development of HHV-6 encephalitis was associated with a poor survival rate, and neurological sequelae remained in many patients.
Background
Recent studies in the USA have shown a lower postoperative mortality rate in mildly obese patients, described as the ‘obesity paradox’. The results from the relatively obese population in ...Western countries may not be generalizable to Asian countries, prompting the present study to investigate the relationship between body mass index (BMI) and outcomes after gastrointestinal surgery.
Methods
Patients who underwent gastrectomy or colorectal resection for stage I–III cancer between July and December 2010 were identified from a nationwide inpatient database in Japan. Multivariable logistic regression models for in‐hospital mortality and postoperative complications, and a linear regression model for total costs were established, with adjustment for age, sex, co‐morbidities, cancer stage and BMI. Restricted cubic spline functions were used to consider potential non‐linear associations between BMI and the outcomes.
Results
Among 30 765 eligible patients, associations between BMI and the outcomes were U‐shaped, with the lowest mortality, morbidity and total costs in patients with a BMI of around 23·0 kg/m2. A BMI of 18·5 kg/m2 was associated with significantly greater mortality (odds ratio (OR) 2·04, 95 per cent confidence interval 1·64 to 2·55), postoperative complications (OR 1·10, 1·03 to 1·18) and total costs (difference €1389, 1139 to 1640) compared with a BMI of 23·0 kg/m2. Patients with a BMI exceeding 30·0 kg/m2 had significantly higher rates of postoperative complications and total costs than those with a BMI of 23·0 kg/m2, but no significant association was evident between a BMI of more than 23·0 kg/m2 and in‐hospital death.
Conclusion
Unlike previous studies in the USA, in the present national Japanese cohort of patients undergoing surgery for gastrointestinal cancer, those who were either underweight or overweight had more postoperative complications and greater perioperative costs than those of normal weight.
Japanese patients really are different
The COVID-19 pandemic has forced people to change many behaviours, including physical distancing, hygiene measures and lifestyles. This study aimed to evaluate the indirect impact of the COVID-19 ...pandemic on the incidence of non–COVID-19 infections and medical care costs/visits using health insurance claims.
This was an observational study using patient-based administrative claims covering approximately 800,000 insured persons and their dependents in the Mie Prefecture in Japan.
This study identified non–COVID-19 infectious disease incidences, number of outpatient visits and healthcare costs between 2017 and 2021. Each year was divided into quarters. The adjusted incidence rate ratios (IRRs) during the pandemic (January 2020 to September 2021) and during the prepandemic period (January 2017 to December 2019) were determined using Poisson regression.
The adjusted influenza IRRs from April 2020 were close to zero. The incidence of upper respiratory tract infections and bacterial pneumonia was significantly reduced (IRRs range: 0.39–0.73 and 0.43–0.84, respectively). Gastrointestinal and urinary tract infection incidences decreased by approximately 30% and 10%, respectively. In contrast, sexually transmitted infections (STIs), including syphilis, gonococcal infection and Chlamydia trachomatis infection, did not decrease during the pandemic but increased significantly between April and June 2021 (adjusted IRR, 1.37; 95% confidence interval, 1.18–1.60). The adjusted IRRs for outpatient visits and healthcare costs were 0.86–0.93 and 0.91–0.97, respectively.
In contrast to other infections, STIs did not decrease during the COVID-19 pandemic. The IRR of STIs during the pandemic period is an area of public health concern. Appropriate screening and medical consultations are strongly recommended.
In many phenomena of biological systems, not a majority, but a minority of cells act on the entire multicellular system causing drastic changes in the system properties. To understand the mechanisms ...underlying such phenomena, it is essential to observe the spatiotemporal dynamics of a huge population of cells at sub-cellular resolution, which is difficult with conventional tools such as microscopy and flow cytometry. Here, we describe an imaging system named AMATERAS that enables optical imaging with an over-one-centimeter field-of-view and a-few-micrometer spatial resolution. This trans-scale-scope has a simple configuration, composed of a low-power lens for machine vision and a hundred-megapixel image sensor. We demonstrated its high cell-throughput, capable of simultaneously observing more than one million cells. We applied it to dynamic imaging of calcium ions in HeLa cells and cyclic-adenosine-monophosphate in Dictyostelium discoideum, and successfully detected less than 0.01% of rare cells and observed multicellular events induced by these cells.
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•2-(all-trans-β-ionylideneetinylidene)-indan-1,3-dione (C15Ind) has three conjugated double bonds and two carbonyl groups.•We performed femtosecond pump-probe spectroscopy on C15Ind ...to clarify excited state dynamics.•C15Ind exhibits a strong intramolecular charge transfer character in excited states both in a polar and nonpolar solvent.
Carotenoids are naturally occurring pigments and essential for light-harvesting and photoprotection in photosynthesis of plants, algae, and bacteria. Carbonyl-containing carotenoids exhibit unique excited state properties due to the occurrence of intramolecular charge transfer (ICT) in the excited state. In the present study, we performed femtosecond pump-probe spectroscopy on the short-chain polyene compound 2-(all-trans-β-ionylideneetinylidene)-indan-1,3-dione with three conjugated double bonds and two carbonyl groups, denoted as C15Ind in acetone and in n-hexane. The spectroscopic properties of C15Ind both in polar and nonpolar solvents suggests an ICT character based on the observations of the stimulated emission due to the coupled 1Ag-/ICT state. In acetone, an additional excited state was found to be located below the 1Ag-/ICT state. The ultrafast triplet generation via the 1nπ* state was also observed both in acetone and in n-hexane, while the amplitude of the triplet transient absorption of C15Ind was rather small compared with those in retinal and Retinyl-1 reported previously. Thus, an ICT character of carbonyl-containing carotenoids may prevent a triplet generation upon excitation into the optically allowed 1Bu+ (S2) state.
This paper presents a new method of improving the disturbance-rejection performance of a servo system based on the estimation of an equivalent input disturbance (EID). First, the concept of EID is ...defined. Next, the configuration of an improved servo system employing the new disturbance-estimation method is described. Then, a method of designing a control law employing a disturbance estimate is explained. Finally, the speed control of a rotational control system is used to demonstrate the validity of the method, and some design guidelines are presented.
Abstract Pituitary adenylate-cyclase activating polypeptide (PACAP) has been implicated in the (patho)physiology of stress-adaptation. PACAP deficient (PACAP−/− ) mice show altered anxiety levels and ...depression-like behavior, but little is known about the underlying mechanisms in stress-related brain areas. Therefore, we aimed at investigating PACAP−/− mice in light–dark box, marble burying, open field, and forced swim paradigms. We also analyzed whether the forced swim test-induced c-Fos expression would be affected by PACAP deficiency in the following stress-related brain areas: magno- and parvocellular paraventricular nucleus of the hypothalamus (PVN); basolateral (BLA), medial (MeA), and central (CeA) amygdaloid nuclei; ventral (BSTv), dorsolateral (BSTdl), dorsomedial (BSTdm), and oval (BSTov) nuclei of the bed nucleus of stria terminalis; dorsal (dLS) and ventral parts (vLS) of lateral septal nucleus, central projecting Edinger–Westphal nucleus (EWcp), dorsal (dPAG) and lateral (lPAG) periaqueductal gray matter, dorsal raphe nucleus (DR). Our results revealed that PACAP−/− mice showed greatly reduced anxiety and increased locomotor activity compared with wildtypes. In forced swim test PACAP−/− mice showed increased depression-like behavior. Forced swim exposure increased c-Fos expression in all examined brain areas in wildtypes, whereas this was markedly blunted in the DR, EWcp, BSTov, BSTdl, BSTv, PVN, vLS, dPAG, and in the lPAG of PACAP−/− mice vs. wildtypes, strongly suggesting their involvement in the behavioral phenotype of PACAP−/− mice. PACAP deficiency did not influence the c-Fos response in the CeA, MeA, BSTdm, and dLS. Therefore, we propose that PACAP exerts a brain area-specific effect on stress-induced neuronal activation and it might contribute to stress-related mood disorders.
Much is known about vertebrate DNA methylation and oxidation; however, much less is known about how modified cytosine residues within particular sequences are recognized. Among the known methylated ...DNA-binding domains, the Cys2-His2 zinc finger (ZnF) protein superfamily is the largest with hundreds of members, each containing tandem ZnFs ranging from 3 to >30 fingers. We have begun to biochemically and structurally characterize these ZnFs not only on their sequence specificity but also on their sensitivity to various DNA modifications. Rather than following published methods of refolding insoluble ZnF arrays, we have expressed and purified soluble forms of ZnFs, ranging in size from a tandem array of two to six ZnFs, from seven different proteins. We also describe a fluorescence polarization assay to measure ZnFs affinity with oligonucleotides containing various modifications and our approaches for cocrystallization of ZnFs with oligonucleotides.
There has been no phase III study of comparing the efficacy of first- and second-generation 5-HT3 receptor antagonists in the triplet regimen with dexamethasone and aprepitant for preventing ...chemotherapy-induced nausea and vomiting after highly emetogenic chemotherapy (HEC).
Patients with a malignant solid tumor who would receive HEC containing 50 mg/m2 or more cisplatin were randomly assigned to either palonosetron (0.75 mg) arm (Arm P) or granisetron (1 mg) arm (Arm G), on day 1, both arms with dexamethasone (12 mg on day 1 and 8 mg on days 2–4) and aprepitant (125 mg on day 1 and 80 mg on days 2–3). The primary end point was complete response (CR; no vomiting/retching and no rescue medication) at the 0–120 h period and secondary end points included complete control (CC; no vomiting/retching, no rescue medication, and no more than mild nausea) and total control (TC; no vomiting/retching, no rescue medication, and no nausea).
Between July 2011 and June 2012, 842 patients were enrolled. Of 827 evaluable, 272 of 414 patients (65.7%) in Arm P had a CR at the 0–120 h period when compared with 244 of 413 (59.1%) in Arm G (P = 0.0539). Both arms had the same CR rate of 91.8% at the acute (0–24 h) period, while at the delayed (24–120 h) period, Arm P had a significantly higher CR rate than Arm G (67.2% versus 59.1%; P = 0.0142). In secondary end points, Arm P had significantly higher rates than Arm G at the 0–120 h period (CC rate: 63.8% versus 55.9%, P = 0.0234; TC rate: 47.6% versus 40.7%, P = 0.0369) and delayed periods (CC rate: 65.2% versus 55.9%, P = 0.0053; TC rate: 48.6% versus 41.4%, P = 0.0369).
The present study did not show the superiority of palonosetron when compared with granisetron in the triplet regimen regarding the primary end point.
UMIN000004863.
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