Gene expression shapes the patterns of parallel evolution of herbicide resistance in the agricultural weed Monochoria vaginalis.

The evolution of herbicide resistance in weeds is an example of parallel evolution, through which genes encoding herbicide target proteins are repeatedly represented as evolutionary targets. The number of herbicide target-site genes differs among species, and little is known regarding the effects of duplicate gene copies on the evolution of herbicide resistance. We investigated the evolution of herbicide resistance in Monochoria vaginalis, which carries five copies of sulfonylurea target-site acetolactate synthase (ALS) genes. Suspected resistant populations collected across Japan were investigated for herbicide sensitivity and ALS gene sequences, followed by functional characterization and ALS gene expression analysis. We identified over 60 resistant populations, all of which carried resistance-conferring amino acid substitutions exclusively in MvALS1 or MvALS3. All MvALS4 alleles carried a loss-of-function mutation. Although the enzymatic properties of ALS encoded by these genes were not markedly different, the expression of MvALS1 and MvALS3 was prominently higher among all ALS genes. The higher expression of MvALS1 and MvALS3 is the driving force of the biased representation of genes during the evolution of herbicide resistance in M. vaginalis. Our findings highlight that gene expression is a key factor in creating evolutionary hotspots.

Insufficient self-care is an independent risk factor for adverse clinical outcomes in Japanese patients with heart failure.

Self-care is a cornerstone for the successful management of heart failure (HF). The purpose of this study was to examine the impacts of HF self-care on prognosis in Japanese patients with HF. A total of 283 HF outpatients (age 64 ± 14, 70% male, 52% HFrEF) were enrolled. We asked patients to answer about their adhevence to 5 self-care behaviors (medication, eating a low-sodium diet, regular exercise, daily weight check, and treatment seeking behavior). On the basis of the results, we classified patients into a good self-care group and a poor self-care group. The primary outcome was HF hospitalization and/or cardiac death. In total, 65% of patients were classified into the poor self-care group. During a median follow-up of 2 years, cardiac events occurred more frequently in the poor self-care group (22% versus 9.6%, P = 0.013). Poor self-care was an independent risk factor for cardiac events in Cox regression analysis adjusted for clinical parameters (hazard ratio = 2.86, P = 0.005). Poor self-care was also associated with an increased number of HF hospitalizations as well as an extended length of hospital stay for HF. Poor knowledge about HF was an independent determinant for poor self-care in multivariate logistic regression analysis (odds ratio = 0.92, P = 0.019). Insufficient self-care is an independent risk factor for cardiac events in Japanese patients with HF.

Feasibility and acceptability of advance care planning facilitated by nonphysician clinicians in Japanese primary care: Implementation pilot study.

Background: Implementation of advance care planning (ACP) is urgently needed in Japan, which is one of the most aging countries. This study tested the feasibility and acceptability of ACP facilitated by nonphysician clinicians, and identified barriers and enablers to implementing ACP into Japanese primary care. Methods: We trained 10 nonphysician clinicians (seven registered nurses, two medical social workers, and one care manager) in four primary care clinics as ACP facilitators. From April to June 2019, the trained facilitators had 19 ACP conversations with their patients. We conducted semistructured interviews and surveys regarding satisfaction and appropriateness of the ACP with patients, family members, ACP facilitators, and primary care physicians (PCPs) regarding their perceptions about ACP facilitated by nonphysician clinicians. Survey data were analyzed using descriptive statistics, and interviews were analyzed using a qualitative content analysis approach. Results: Majority of patients (75%) and family members (71%) were satisfied with ACP facilitated by nonphysician clinicians. In 71%, ACP facilitators and PCPs thought their ACP facilitation was appropriate and acceptable. Patients stated that they felt comfortable having ACP conversations with nonphysician clinicians. Identified barriers and enablers for ACP included: time restraints, size and organization of the clinics, settings for ACP conversations (ACP at the patient's home), team collaboration, and use of existing system to trigger ACP. Conclusions: Advance care planning facilitated by nonphysician clinicians was feasible and acceptable in Japanese primary care. Further studies are needed to explore strategies to overcome the barriers and enhance the enablers identified in this study.

A complement C3 fragment equivalent to mammalian C3d from the common carp (Cyprinus carpio): generation in serum after activation of the alternative pathway and detection of its receptor on the lymphocyte surface.

A terminal degradation product (C3d) of mammalian complement component C3 plays an important role in modulation of the adaptive immune response through the interaction with complement receptor type 2 (CR2) on B cells. The present study is aimed at determining whether this is a functional bridge between the innate and adaptive immune systems in bony fish. The fragmentation of the complement component C3 in carp (Cyprinus carpio) serum, activated with zymosan, was analysed to ascertain if carp C3 also generates a mammalian C3d-like fragment under physiological conditions. A 35 kDa peptide reactive to the anti-carp C3 alpha-chain was detected on the zymosan particles and in the activated serum. Its N-terminal amino acid sequence identified it as carp C3d derived from the C3-H1 isoform. Another C3 isoform, C3-S, of carp was found to yield a C3d fragment at lower efficiency than C3-H1. Recombinant C3d fragments derived from C3-H1 and C3-S were produced in Escherichia coli as fusion proteins with glutathione-S-transferase (GST), and used for ligands to examine the presence of a possible CR2-like C3d receptor on carp lymphocytes. An enzyme-linked immunoadsorbent assay system, using the recombinant C3d proteins and anti-GST on a microplate to which was attached carp peripheral lymphocytes, detected a significant binding of carp C3d to the lymphocyte. The degree of binding of C3-H1-derived C3d was higher than that of C3-S-derived C3d. In addition, the binding of both ligands was inhibited by anti-C3 alpha-chain, but not by EDTA or EGTA, indicating that the putative C3d receptor does not require divalent cation. These properties agree well with those reported for mammalian CR2.