Aberrant proximal tubule DNA methylation underlies phenotypic changes related to kidney dysfunction in patients with diabetes.

Epigenetic mechanisms are considered to contribute to diabetic nephropathy by maintaining memory of poor glycemic control during the early stages of diabetes. However, DNA methylation changes in the human kidney are poorly characterized, because of the lack of cell type-specific analysis. We examined DNA methylation in proximal tubules purified from diabetic nephropathy patients and identified differentially methylated CpG sites, given the critical role of proximal tubules in the kidney injury. Hypermethylation was observed at CpG sites annotated to genes responsible for proximal tubule functions, including gluconeogenesis, nicotinamide adenine dinucleotide synthesis, transporters of glucose, water, phosphate, and drugs, in diabetic kidneys, while genes involved in oxidative stress and the cytoskeleton exhibited demethylation. Methylation levels of CpG sites annotated to ACTN1, BCAR1, MYH9, UBE4B, AFMID, TRAF2, TXNIP, FOXO3, and HNF4A were correlated with the estimated glomerular filtration rate, while methylation of the CpG site in RUNX1 was associated with interstitial fibrosis and tubular atrophy. Hypermethylation of G6PC and HNF4A was accompanied by decreased expression in diabetic kidneys. Proximal tubule-specific hypomethylation of metabolic genes related to HNF4A observed in control kidneys was compromised in diabetic kidneys, suggesting a role for aberrant DNA methylation in the dedifferentiation process. Multiple genes with aberrant DNA methylation in diabetes overlapped genes with altered expressions in maladaptive proximal tubule cells, including transcription factors PPARA and RREB1. In conclusion, DNA methylation derangement in the proximal tubules of patients with diabetes may drive phenotypic changes, characterized by inflammatory and fibrotic features, along with impaired function in metabolism and transport.

Digital whole-slide imaging of changes in amyloid after peripheral blood stem cell transplantation in patients with amyloid light-chain amyloidosis.

Peripheral blood stem cell transplantation (PBSCT) has made amyloid light-chain (AL) amyloidosis treatable. After PBSCT, hematological complete remission (HCR) can be achieved, leading to improved renal prognosis. The purpose of this study was to evaluate whether whole slide imaging of biopsy samples shows a post-treatment reduction in amyloid deposits in patients with AL amyloidosis. Patients were divided into three groups: Group A (n = 8), not eligible for PBSCT and treated with other therapies; Group B (n = 11), treated with PBSCT and achieved HCR; and Group C (n = 5), treated with PBSCT but did not achieve HCR. Clinical findings and amyloid deposition in glomeruli, interstitium, and blood vessels were compared before and after treatment using digital whole-slide imaging. Proteinuria and hypoalbuminemia improved more in Group B than in the other groups, and in Group B, amyloid deposition improved more in the glomeruli than in the interstitium and blood vessels. The long-term renal and survival prognosis was better in Group B than in the other groups. PBSCT can be expected to improve long-term clinical and renal histological prognosis in patients with AL amyloidosis who achieve HCR. Amyloid disappearance from renal tissue may take a long time even after clinical HCR.

A case of hepatoid adenocarcinoma of the lung harboring KRAS G12C responded favorably to sotorasib.

Hepatoid adenocarcinoma of the lung is a rare variant of adenocarcinoma. We describe a case of hepatoid adenocarcinoma of the lung that harbored KRAS G12C and responded favorably to sotorasib. A man in his 70s was found to have an abnormality on his chest X-ray. He underwent right middle lobectomy, and a pathological examination of the surgical specimen showed conventional invasive adenocarcinoma with highly focal hepatoid adenocarcinoma. He received chemoradiotherapy and concurrent radiation, followed by durvalumab for postoperative recurrence. After three doses of durvalumab, he reported feeling short of breath. A computed tomography scan showed emerging broad consolidation in the right lower lobe. Transbronchial lung biopsy specimens from the consolidation showed hepatoid adenocarcinoma harboring KRAS G12C mutation. Therefore, he was started on sotorasib 960 mg daily. Eight days later, a computed tomography scan showed that the area of consolidation had reduced in size. Progressive disease was detected after 42 days of treatment with sotorasib. The patient died 1 month after cessation of sotorasib and 3 months after postoperative recurrence. We have encountered what we believe to be the first case of hepatoid adenocarcinoma of the lung with KRAS G12C mutation that responded favorably to treatment with sotorasib.

Contributions of Non-Neuronal Cholinergic Systems to the Regulation of Immune Cell Function, Highlighting the Role of α7 Nicotinic Acetylcholine Receptors.

Loewi's discovery of acetylcholine (ACh) release from the frog vagus nerve and the discovery by Dale and Dudley of ACh in ox spleen led to the demonstration of chemical transmission of nerve impulses. ACh is now well-known to function as a neurotransmitter. However, advances in the techniques for ACh detection have led to its discovery in many lifeforms lacking a nervous system, including eubacteria, archaea, fungi, and plants. Notably, mRNAs encoding choline acetyltransferase and muscarinic and nicotinic ACh receptors (nAChRs) have been found in uninnervated mammalian cells, including immune cells, keratinocytes, vascular endothelial cells, cardiac myocytes, respiratory, and digestive epithelial cells. It thus appears that non-neuronal cholinergic systems are expressed in a variety of mammalian cells, and that ACh should now be recognized not only as a neurotransmitter, but also as a local regulator of non-neuronal cholinergic systems. Here, we discuss the role of non-neuronal cholinergic systems, with a focus on immune cells. A current focus of much research on non-neuronal cholinergic systems in immune cells is α7 nAChRs, as these receptors expressed on macrophages and T cells are involved in regulating inflammatory and immune responses. This makes α7 nAChRs an attractive potential therapeutic target.

Differences in the panoramic appearance of cleft alveolus patients with or without a cleft palate.

Purpose: The purpose of this study was to clarify the panoramic image differences of cleft alveolus patients with or without a cleft palate, with emphases on the visibility of the line formed by the junction between the nasal septum and nasal floor (the upper line) and the appearances of the maxillary lateral incisor. Materials and Methods: Panoramic radiographs of 238 patients with cleft alveolus were analyzed for the visibility of the upper line, including clear, obscure or invisible, and the appearances of the maxillary lateral incisor, regarding congenital absence, incomplete growth, delayed eruption and medial inclination. Differences in the distribution ratio of these visibility and appearances were verified between the patients with and without a cleft palate using the chi-square test. Results: There was a significant difference in the visibility distribution of the upper line between the patients with and without a cleft palate (p<0.05). In most of the patients with a cleft palate, the upper line was not observed. In the unilateral cleft alveolus patients, the medial inclination of the maxillary lateral incisor was more frequently observed in patients with a cleft palate than in patients without a cleft palate. Conclusion: Two differences were identified in panoramic appearances. The first was the disappearance (invisible appearance) of the upper line in patients with a cleft palate, and the second was a change in the medial inclination on the affected side maxillary lateral incisor in unilateral cleft alveolus patients with a cleft palate.

Reinstrumentation for progressive hyper-kyphotic deformity after implant removal despite obtaining physiological alignment by posterior corrective surgery for adolescent idiopathic scoliosis with flat back: a case report.

This case report describes a 13-year-old female patient with adolescent idiopathic scoliosis (AIS) and flat back who experienced progressive kyphotic deformity after implant removal despite obtaining physiological alignment postoperatively. The patient underwent multiple surgeries, and a late-developing infection complicated her treatment course. Despite hard bracing to prevent kyphotic change, the kyphosis progressed to 74° within a year after implant removal, leading to a decrease in patient height and back pain. Revision surgery was eventually necessary. Possible factors for the kyphotic progression include injury to paraspinal back muscles due to multiple surgeries or insufficient bony fusion from late-developing infection. This case highlights the importance of thorough evaluation and follow-up for optimal patient outcomes after implant removal in AIS patients, particularly those with flat back.

GTS-21 Enhances Regulatory T Cell Development from T Cell Receptor-Activated Human CD4+ T Cells Exhibiting Varied Levels of CHRNA7 and CHRFAM7A Expression.

Immune cells such as T cells and macrophages express α7 nicotinic acetylcholine receptors (α7 nAChRs), which contribute to the regulation of immune and inflammatory responses. Earlier findings suggest α7 nAChR activation promotes the development of regulatory T cells (Tregs) in mice. Using human CD4+ T cells, we investigated the mRNA expression of the α7 subunit and the human-specific dupα7 nAChR subunit, which functions as a dominant-negative regulator of ion channel function, under resting conditions and T cell receptor (TCR)-activation. We then explored the effects of the selective α7 nAChR agonist GTS-21 on proliferation of TCR-activated T cells and Treg development. Varied levels of mRNA for both the α7 and dupα7 nAChR subunits were detected in resting human CD4+ T cells. mRNA expression of the α7 nAChR subunit was profoundly suppressed on days 4 and 7 of TCR-activation as compared to day 1, whereas mRNA expression of the dupα7 nAChR subunit remained nearly constant. GTS-21 did not alter CD4+ T cell proliferation but significantly promoted Treg development. These results suggest the potential ex vivo utility of GTS-21 for preparing Tregs for adoptive immunotherapy, even with high expression of the dupα7 subunit.

Current findings on the efficacy of incretin-based drugs for diabetic kidney disease: A narrative review.

Diabetic kidney disease (DKD) is the most common cause of chronic kidney disease (CKD), leading end-stage renal disease. Thus, DKD is one of the most important diabetic complications. Incretin-based therapeutic agents, such as glucagon-like peptide-1 (GLP-1) receptor agonizts and dipeptidyl peptidase-4 (DPP-4) inhibitors have been reported to elicit vasotropic actions, suggesting a potential for effecting reduction in DKD. Glucose-dependent insulinotropic polypeptide (GIP) is also classified as an incretin. However, the insulin action after GIP secretion is known to be drastically reduced in patients with type 2 diabetes. Therefore, GIP has been formally considered unsuitable as a treatment for type 2 diabetes in the past. This concept is changing as it has been reported that resistance to GIP can be reversed and its effect restored with improved glycemic control. The development of novel dual- or triple- receptor agonizts that can bind to the receptors, not only for GLP-1 but also to GIP and glucagon receptors, is intended to simultaneously address several metabolic pathways including protein, lipid, and carbohydrate metabolism. These led to the development of GIP receptor agonist-based drugs for type 2 diabetes. The possibility of combined GIP/GLP-1 receptor agonist was also explored. The novel dual GIP and GLP-1 receptor agonist tirzepatide has recently been launched (Mounjaro®, Lilly). We have revealed precise mechanisms of the renoprotective effect of GLP-1 receptor agonizts or DPP-4 inhibitors, while the long-term effect of tirzepatide will need to be determined and its potential effects on kidneys should be properly tested.

[HUMIDIFIER LUNG WITH ORGANIZING PNEUMONIA DETECTED BY BRONCHOSCOPY: A CASE REPORT].

A 58-year-old man presented with dyspnea on exertion and diffuse ground-glass opacities with mosaicism on chest computed tomography in April 201X. A transbronchial lung biopsy revealed organizing pneumonia and lymphocytic infiltration, and steroids were administered. During steroid tapering, the shortness of breath and ground-glass opacities recurred, and a transbronchial lung re-biopsy revealed organizing pneumonia without a granuloma again. Based on the clinical history, imaging features, and amount of humidifier usage, hypersensitivity pneumonitis caused by a humidifier was suspected. The inhalation challenge test was considered positive, and the diagnosis was confirmed. There have been some reports of unidentified granuloma in patients with humidifier lungs. Therefore, this case suggests that humidifier lung should be considered as a possibility even if pathological examination does not reveal granulomas and inflammatory changes such as organizing pneumonia are the only findings.

10-year Longitudinal MRI Study of Intervertebral Disk Degeneration in Patients With Lumbar Spinal Canal Stenosis After Posterior Lumbar Decompression Surgery.

STUDY DESIGN: A prospective longitudinal magnetic resonance imaging (MRI) study. OBJECTIVE: The objective of this study was to describe the progression of intervertebral disk (IVD) degeneration in patients who underwent posterior decompression surgery for lumbar spinal canal stenosis (LSS). SUMMARY OF BACKGROUND DATA: IVD degeneration contributes to the pathogenesis of LSS; however, the long-term consequences of degenerative changes after decompression surgery remain unknown. MATERIALS AND METHODS: Of 258 consecutive patients who underwent posterior lumbar decompression surgery for LSS, 62 who underwent MRI at their 10-year follow-up were included; 17 age-matched asymptomatic volunteers were analyzed as controls. Three MRI findings representing IVD degeneration were graded on their severity: decrease in signal intensity, posterior disk protrusion (PDP), and disk space narrowing (DSN). Clinical outcome was assessed using the low back pain (LBP) score from the Japanese Orthopaedic Association scoring system. We examined the association between the progression of degenerative changes on MRI and LBP/associated factors using logistic regression adjusting for age at baseline and sex. RESULTS: The severity of IVD degeneration tended to be higher in patients with LSS than asymptomatic volunteers at both baseline and follow-up. IVD degeneration progressed in all patients during the 10-year follow-up period. Progression of decrease in signal intensity and PDP was observed at L1/2 in 73% and at L2/3 in 34%, respectively (the highest frequencies in the lumbar spine). Progression of DSN was highest at L4/5 in 42%. The rates of PDP and DSN progression during the 10-year follow-up period tended to be greater in patients with LSS than in asymptomatic volunteers. No significant difference in the proportion of LBP deterioration was evident for individuals with and without MRI findings of progression. CONCLUSIONS: Our study reveals a natural history of the long-term postoperative course of IVD degeneration after posterior decompression surgery for LSS. Compared with healthy controls, patients with LSS seemed to be predisposed to IVD degeneration. Lumbar decompression surgery may promote the progression of DSN; however, progression of IVD degeneration after lumbar decompression surgery was not associated with worsening LBP scores.

Severe Erythroderma Due to Adult-onset Still's Disease-like Disease Related to Graft-versus-host Disease after Allogeneic Hematopoietic Stem Cell Transplantation.

A 35-year-old woman was treated with chemotherapy for leukemia. One year later, allogeneic hematopoietic stem cell transplantation (HSCT) was performed with umbilical cord blood. After nine months, she developed a spiking fever, sore throat, arthralgia, pleural effusion, hyperferritinemia, and persistent generalized pruritic erythema. A skin biopsy showed dyskeratotic cells in the epidermis, neutrophil infiltration in the epidermis and upper dermis, and neutrophils in the parakeratotic layer. Treatment with tocilizumab was effective. Adult-onset Still's disease (AOSD)-like disease related to graft versus-host disease (GVHD) after HSCT was suspected. Abnormal immune states related to GVHD may cause AOSD-like disease with more severe skin lesions than usual.

Bi-glandular and persistent enterovirus infection and distinct changes of the pancreas in slowly progressive type 1 diabetes mellitus.

In slowly progressive type 1 diabetes mellitus (SPIDDM), the pancreas shows sustained islet inflammation, pancreatitis, pancreatic acinar cell metaplasia/dysplasia (ADM), and intraepithelial neoplasia (PanIN), a precancerous lesion. The mechanisms underlying these changes remain unclear. The presence of enterovirus (EV) encoded-capsid protein 1 (VP1) and -2A protease (2Apro) and the innate immune responses of the pancreas were studied using immunohistochemistry and in situ hybridization in 12 SPIDDM and 19 non-diabetic control pancreases. VP1, 2Apro, and EV-RNA were detected in islets and the exocrine pancreas in all SPIDDM pancreases. Innate immune receptor, melanoma differentiation-associated gene 5 (MDA5), and interferon (IFN)-beta1 were intensified in the islets of SPIDDM patients with short disease duration. However, expressions of MDA5 and IFN-beta1were suppressed in those with longer disease duration. CD3+ T cell infiltration was observed in the VP1- and insulin-positive islets (insulitis) and exocrine acinar cells. CD11c+ dendritic cells (DCs) in islets were scarce in long-term SPIDDM. This study showed the consistent presence of EV, suggesting an association with inflammatory changes in the endocrine and exocrine pancreas in SPIDDM. Suppressed expressions of MDA5 and IFN-beta1, as well as decreased numbers of DCs in the host cells, may contribute to persistent EV infection and induction of ADM/PanIN lesions, which may potentially provide a scaffold for pancreatic neoplasms.

Discrepancy between Clinician-rated and Self-reported Depression Severity is Associated with Adverse Childhood Experience, Autistic-like Traits, and Coping Styles in Mood Disorders.

Objective: This study aimed to determine if the discrepancy between depression severity rated by clinicians and that reported by patients depends on key behavioral/psychological features in patients with mood disorders. Methods: Participants included 100 patients with mood disorders. First, we examined correlations and regressions between scores on the Hamilton Depression Rating Scale (HAMD) and Beck Depression Inventory (BDI). Second, we divided the participants into those who provided 1) greater ratings for the BDI compared with the HAMD (BDI relative- overrating, BO) group, 2) comparable ratings for the BDI and HAMD (BDI relatively concordant, BC) group, or 3) less ratings for the BDI (BDI relative-underrating, BU) group. Adverse childhood experiences, autistic-like traits, and coping styles were evaluated with a six-item short version of the Childhood Trauma Questionnaire (CTQ-6), the Social Responsiveness Scale for Adults (SRS-A), and the Ways of Coping Checklist (WCCL), respectively. Results: A significant correlation was found between HAMD and BDI scores. Total and emotional abuse subscale scores from the CTQ-6, and the self-blame subscale scores from the WCCL were significantly higher for the BO group compared with the BU group. The BO group also elicited significantly higher SRS-A total scores than did the other groups. Conclusion: These findings suggest that patients with adverse emotional experiences, autistic-like traits, and self-blame coping styles perceive greater distress than that evaluated objectively by clinicians. The results indicate the need for inclusion of subjective assessments to effectively evaluate depressive symptoms in patients deemed to have these psycho- behavioral concerns.

Two Complete Genomes of Male-Killing Wolbachia Infecting Ostrinia Moth Species Illuminate Their Evolutionary Dynamics and Association with Hosts.

Wolbachia is an extremely widespread intracellular symbiont which causes reproductive manipulation on various arthropod hosts. Male progenies are killed in Wolbachia-infected lineages of the Japanese Ostrinia moth population. While the mechanism of male killing and the evolutionary interaction between host and symbiont are significant concerns for this system, the absence of Wolbachia genomic information has limited approaches to these issues. We determined the complete genome sequences of wFur and wSca, the male-killing Wolbachia of Ostrinia furnacalis and Ostrinia scapulalis. The two genomes shared an extremely high degree of homology, with over 95% of the predicted protein sequences being identical. A comparison of these two genomes revealed nearly minimal genome evolution, with a strong emphasis on the frequent genome rearrangements and the rapid evolution of ankyrin repeat-containing proteins. Additionally, we determined the mitochondrial genomes of both species' infected lineages and performed phylogenetic analyses to deduce the evolutionary dynamics of Wolbachia infection in the Ostrinia clade. According to the inferred phylogenetic relationship, two possible scenarios were proposed: (1) Wolbachia infection was established in the Ostrinia clade prior to the speciation of related species such as O. furnacalis and O. scapulalis, or (2) Wolbachia infection in these species was introgressively transferred from a currently unidentified relative. Simultaneously, the relatively high homology of mitochondrial genomes suggested recent Wolbachia introgression between infected Ostrinia species. The findings of this study collectively shed light on the host-symbiont interaction from an evolutionary standpoint.

Polyhydroxy Acids as Fabaceous Plant Components Induce Oviposition of the Common Grass Yellow Butterfly, Eurema Mandarina.

The common grass yellow butterfly, Eurema mandarina is a Fabaceae-feeding species, the females of which readily oviposit on Albizia julibrissin and Lespedeza cuneata in mainland Japan. We previously demonstrated that the methanolic leaf extracts of these plants, and their highly polar aqueous fractions strongly elicit female oviposition. Furthermore, the three subfractions obtained by ion-exchange chromatographic separation of the aqueous fraction have been found to be less effective alone, but synergistically stimulate female oviposition when combined. This indicates that female butterflies respond to multiple compounds with different acidity. We have previously identified d-pinitol from the neutral/amphoteric subfractions and glycine betaine from the basic subfractions as oviposition stimulants of E. mandarina. The present study aimed to identify active compounds in the remaining acidic subfractions of A. julibrissin and L. cuneata leaf extracts. GC-MS analyses of trimethylsilyl-derivatized samples revealed the presence of six compounds in the acidic subfractions. In bioassays using these authentic chemicals, erythronic acid (EA) and threonic acid (TA) were moderately active in eliciting oviposition responses in E. mandarina, with their d-isomers showing slightly higher activity than their l-isomers. Female responsiveness differed between d-EA and l-TA, the major isomers of these compounds in plants, with the response to d-EA reaching a plateau at concentrations above 0.005% and that to l-TA peaking at a concentration of 0.01%. The natural concentrations of d-EA and l-TA in fresh A. julibrissin and L. cuneata leaves were sufficient to stimulate oviposition. Furthermore, mixing 0.001% d-EA or 0.001% l-TA, to which females are mostly unresponsive, with 0.1% d-pinitol resulted in a synergistic enhancement of the oviposition response. These findings demonstrate that E. mandarina females utilize both polyhydroxy acids, EA and TA, as chemical cues for oviposition.

Risk factors for early reoperation in patients after posterior lumbar interbody fusion surgery. A propensity-matched cohort analysis.

BACKGROUND: Reoperation is usually associated with poor results and increased morbidity and hospital costs. However, the rates, causes, and risk factors for reoperation in patients undergoing lumbar spinal fusion surgery remain controversial. This study aimed to identify the risk factors for early reoperation after posterior lumbar interbody fusion surgery and to compare the clinical outcomes between patients who underwent reoperation and those who did not. METHODS: We investigated a multicenter medical record database of 1263 patients who underwent posterior lumbar interbody fusion surgery between 2012 and 2015. A total of 72 (5.7%) reoperations within two years after surgery were identified and were propensity-matched for age, sex, number of fusion segments, and surgeon's experience. RESULTS: We analyzed a total of 114 patients (57 who underwent reoperation (R group) and 57 who did not (C group)). The mean age was 62.6 ± 13.4 years, with 78 men and 36 women. The mean number of fused segments was 1.2 ± 0.5. Surgical site infection was the most common cause of reoperation. There were significant differences in the incidence of diabetes mellitus (p = 0.024), preoperative ambulation status (p = 0.046), and ASA grade (p < 0.001) between the C and R groups. The recovery rate of the Japanese Orthopaedic Association score was significantly lower in the R group compared to the C group (R: 50.5 ± 28.8%, C: 63.9 ± 33.7%, p = 0.024). There were significant differences in the bone fusion rate (R: 63.2%, C: 96.5%, p < 0.001) and incidence of screw loosening (R: 31.6%; C: 10.5%; p = 0.006). CONCLUSION: Diabetes mellitus, preoperative ambulation status, and ASA grade were significant risk factors for early reoperation following posterior lumbar interbody fusion surgery. The patients who underwent early reoperation had worse clinical outcomes than those who did not.

Temporary Monosegmental Fixation Using Multiaxial Percutaneous Pedicle Screws for Surgical Management of Bony Flexion-Distraction Injuries of the Thoracolumbar Spine: A Technical Note.

Introduction: The efficacy of minimally invasive surgeries for thoracolumbar flexion-distraction injuries (FDIs) has been reported, but those surgeries were monosegmental fusion surgeries of two adjacent vertebrae with bone grafts or temporary fixations using percutaneous pedicle screws (PPSs) that were at least bisegmental. Our idea was to fuse the fracture itself, not to fuse the fractured vertebra with an adjacent vertebra or to stabilize the fractured vertebra by bridging rostrally/caudally adjacent intact vertebrae, specifically when the displacement is minimal. This study aimed to present the surgical techniques of reduction and temporary monosegmental fixation of neurologically intact thoracolumbar bony FDIs using multiaxial PPSs, which can minimize the surgical invasiveness and preserve all motion segments, as well as report three cases treated with this procedure. Technical Note: When the fracture extended from the vertebral body to the spinous process at the same level, screws were placed into the fractured vertebra rostrally to the fracture along the rostral endplate, and the caudally adjacent vertebra was instrumented beyond the fracture line. When the fracture extended from the vertebral body to the spinous process of the rostrally adjacent vertebra, screws were placed into the fractured vertebra caudally to the fracture line, and the rostrally adjacent vertebra was instrumented. The kyphotic deformity was reduced through ligamentotaxis by using MPPSs in the rostral vertebra as rigid joysticks to apply direct buttress leverage to the rostral endplate. Intraoperative blood loss was minimal. The correction of kyphotic deformity and its durability were acceptable, and the segmental range of motion of the two affected vertebrae from flexion to extension was maintained after implant removal. Conclusions: This surgery can act as the least-invasive option for the management of thoracolumbar bony FDIs to allow early ambulation without external bracing and to preserve all the motion segments.

A Wolbachia factor for male killing in lepidopteran insects.

Bacterial symbionts, such as Wolbachia species, can manipulate the sexual development and reproduction of their insect hosts. For example, Wolbachia infection induces male-specific death in the Asian corn borer Ostrinia furnacalis by targeting the host factor Masculinizer (Masc), an essential protein for masculinization and dosage compensation in lepidopteran insects. Here we identify a Wolbachia protein, designated Oscar, which interacts with Masc via its ankyrin repeats. Embryonic expression of Oscar inhibits Masc-induced masculinization and leads to male killing in two lepidopteran insects, O. furnacalis and the silkworm Bombyx mori. Our study identifies a mechanism by which Wolbachia induce male killing of host progeny.

A new device for endoscopic band ligation for colorectal diverticular bleeding.

Background and study aims Endoscopic band ligation (EBL) has been reported to be effective for colorectal diverticular bleeding. However, current EBL devices have some limitations, and we have developed a novel EBL device. Methods This novel EBL device has a tapered hood attached to the tip of the endoscope and an outer cylinder that loads two EBL bands. Twelve EBL procedures were performed in a live porcine model alternately using a conventional EBL device (Group C) and the novel EBL device (Group N). Results EBL was successful in all cases in both groups. There were no cases of perforation in the 10 days after EBL. After ligation, the mean major axis of the ridge was significantly larger in Group N than Group C (9.7 ±â€Š1.4 mm vs 7.2 ±â€Š1.4 mm, P  = 0.011). Pathological examination revealed disruption of the muscularis propria at four of the six ligation sites in Group C and at five of the six ligation sites in Group N. Conclusions Using this novel EBL device, it was possible to perform multiple ligation procedures in succession with a good field of view. No perforation was observed, but disruption of the muscularis propria was observed at approximately three-quarters of the ligation sites pathologically.