CCL20/CCR6 blockade enhances immunity to RSV by impairing recruitment of DC

Chemokines are important mediators of the immune response to pathogens, but can also promote chronic inflammatory states. Chemokine receptor 6 (CCR6) is found on immature DC and effector/memory T cells, and binds a single ligand, CCL20, with high affinity. Here, we investigated the role of CCL20 and CCR6 in a pulmonary viral infection caused by RSV, a ubiquitous virus that can cause severe pulmonary complications. Neutralization of CCL20 during RSV infection significantly reduced lung pathology and favored a Th1 effector response. CCR6-deficient animals recapitulated this phenotype, and additionally showed enhanced viral clearance when compared with WT mice. No differences were observed in migration of T cells to the lungs of CCR6 −/− animals; however, a significant reduction was observed in numbers of conventional DC (cDC), but not plasmacytoid DC, in CCR6 −/− mice. A pathogenic phenotype could be reconstituted in CCR6 −/− mice by supplying cDC into the airway, indicating that mere number of cDC dictates the adverse response. Our data suggest that blockade of the CCL20/CCR6 pathway provides an environment whereby the attenuated recruitment of cDC alters the balance of innate immune cells and mediates the efficient antiviral response to RSV.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71373/1/1042_ftp.pd

Lifespan-Extending Effects of Royal Jelly and Its Related Substances on the Nematode Caenorhabditis elegans

One of the most important challenges in the study of aging is to discover compounds with longevity-promoting activities and to unravel their underlying mechanisms. Royal jelly (RJ) has been reported to possess diverse beneficial properties. Furthermore, protease-treated RJ (pRJ) has additional pharmacological activities. Exactly how RJ and pRJ exert these effects and which of their components are responsible for these effects are largely unknown. The evolutionarily conserved mechanisms that control longevity have been indicated. The purpose of the present study was to determine whether RJ and its related substances exert a lifespan-extending function in the nematode Caenorhabditis elegans and to gain insights into the active agents in RJ and their mechanism of action.We found that both RJ and pRJ extended the lifespan of C. elegans. The lifespan-extending activity of pRJ was enhanced by Octadecyl-silica column chromatography (pRJ-Fraction 5). pRJ-Fr.5 increased the animals' lifespan in part by acting through the FOXO transcription factor DAF-16, the activation of which is known to promote longevity in C. elegans by reducing insulin/IGF-1 signaling (IIS). pRJ-Fr.5 reduced the expression of ins-9, one of the insulin-like peptide genes. Moreover, pRJ-Fr.5 and reduced IIS shared some common features in terms of their effects on gene expression, such as the up-regulation of dod-3 and the down-regulation of dod-19, dao-4 and fkb-4. 10-Hydroxy-2-decenoic acid (10-HDA), which was present at high concentrations in pRJ-Fr.5, increased lifespan independently of DAF-16 activity.These results demonstrate that RJ and its related substances extend lifespan in C. elegans, suggesting that RJ may contain longevity-promoting factors. Further analysis and characterization of the lifespan-extending agents in RJ and pRJ may broaden our understanding of the gene network involved in longevity regulation in diverse species and may lead to the development of nutraceutical interventions in the aging process

COVID-19 vaccine effectiveness against severe COVID-19 requiring oxygen therapy, invasive mechanical ventilation, and death in Japan: A multicenter case-control study (MOTIVATE study).

INTRODUCTION: Since the SARS-CoV-2 Omicron variant became dominant, assessing COVID-19 vaccine effectiveness (VE) against severe disease using hospitalization as an outcome became more challenging due to incidental infections via admission screening and variable admission criteria, resulting in a wide range of estimates. To address this, the World Health Organization (WHO) guidance recommends the use of outcomes that are more specific to severe pneumonia such as oxygen use and mechanical ventilation. METHODS: A case-control study was conducted in 24 hospitals in Japan for the Delta-dominant period (August-November 2021; "Delta") and early Omicron (BA.1/BA.2)-dominant period (January-June 2022; "Omicron"). Detailed chart review/interviews were conducted in January-May 2023. VE was measured using various outcomes including disease requiring oxygen therapy, disease requiring invasive mechanical ventilation (IMV), death, outcome restricting to "true" severe COVID-19 (where oxygen requirement is due to COVID-19 rather than another condition(s)), and progression from oxygen use to IMV or death among COVID-19 patients. RESULTS: The analysis included 2125 individuals with respiratory failure (1608 cases [75.7%]; 99.2% of vaccinees received mRNA vaccines). During Delta, 2 doses provided high protection for up to 6 months (oxygen requirement: 95.2% [95% CI:88.7-98.0%] [restricted to "true" severe COVID-19: 95.5% {89.3-98.1%}]; IMV: 99.6% [97.3-99.9%]; fatal: 98.6% [92.3-99.7%]). During Omicron, 3 doses provided high protection for up to 6 months (oxygen requirement: 85.5% [68.8-93.3%] ["true" severe COVID-19: 88.1% {73.6-94.7%}]; IMV: 97.9% [85.9-99.7%]; fatal: 99.6% [95.2-99.97]). There was a trend towards higher VE for more severe and specific outcomes. CONCLUSION: Multiple outcomes pointed towards high protection of 2 doses during Delta and 3 doses during Omicron. These results demonstrate the importance of using severe and specific outcomes to accurately measure VE against severe COVID-19, as recommended in WHO guidance in settings of intense transmission as seen during Omicron

Fundamental resource specialization of herbivorous butterflies decreases towards lower latitudes

Aim It is generally assumed that the degree of resource specialization in herbivorous insects increases towards lower latitudes. However, latitudinal patterns in herbivore diet breadth at large spatial scales remain poorly understood. In this work, we investigated the drivers of latitudinal variation in lepidopteran ‘fundamental’ resource specialization, which we defined as the host breadth when not limited by interspecific interactions at the same trophic level. Location The Japanese archipelago (22°N–45°N), including hemiboreal, temperate and subtropical zones. Taxon Herbivorous butterflies. Methods Species-specific fundamental host breadth was calculated based on pooled host-use records. We investigated the latitudinal pattern and significant drivers of the degree of specialization in regional species pools at a 10-km grid level. As potential drivers, we focused on geography, current climate and diversity and body size of butterflies. Through Bayesian structural equation modelling, we investigated the complicated relationships between these variables and community-level resource specialization represented by three different indices of host breadth. Results We found that the fundamental resource specialization of butterfly communities increases towards higher latitudes. This pattern is contrary to the presumed general trend found in studies based on realized resource specialization within local communities. We found that the observed pattern is driven mainly by factors related to climate, butterfly diversity and body size in each community. Above all, annual mean temperature most strongly drove community-level fundamental host breadth of herbivorous butterflies. Main conclusions Our findings suggest that the fundamental resource specialization may show different latitudinal patterns from the conventional prediction based on knowledge of realized resource specialization. Our results emphasize the importance of the current climate as a major factor regulating butterfly morphology and fundamental host breadth, regardless of whether the impact is direct or indirect

Fundamental resource specialization of herbivorous butterflies decreases towards lower latitudes

Aim It is generally assumed that the degree of resource specialization in herbivorous insects increases towards lower latitudes. However, latitudinal patterns in herbivore diet breadth at large spatial scales remain poorly understood. In this work, we investigated the drivers of latitudinal variation in lepidopteran ‘fundamental’ resource specialization, which we defined as the host breadth when not limited by interspecific interactions at the same trophic level. Location The Japanese archipelago (22°N–45°N), including hemiboreal, temperate and subtropical zones. Taxon Herbivorous butterflies. Methods Species-specific fundamental host breadth was calculated based on pooled host-use records. We investigated the latitudinal pattern and significant drivers of the degree of specialization in regional species pools at a 10-km grid level. As potential drivers, we focused on geography, current climate and diversity and body size of butterflies. Through Bayesian structural equation modelling, we investigated the complicated relationships between these variables and community-level resource specialization represented by three different indices of host breadth. Results We found that the fundamental resource specialization of butterfly communities increases towards higher latitudes. This pattern is contrary to the presumed general trend found in studies based on realized resource specialization within local communities. We found that the observed pattern is driven mainly by factors related to climate, butterfly diversity and body size in each community. Above all, annual mean temperature most strongly drove community-level fundamental host breadth of herbivorous butterflies. Main conclusions Our findings suggest that the fundamental resource specialization may show different latitudinal patterns from the conventional prediction based on knowledge of realized resource specialization. Our results emphasize the importance of the current climate as a major factor regulating butterfly morphology and fundamental host breadth, regardless of whether the impact is direct or indirect.publishedVersio

Replication data for: How the nature of web services drives vocabulary creation in social tagging

Tagging data of the social network service named RoomClip. This data corresponds to the article "How the nature of web services drives vocabulary creation in social tagging

Comparative Study of Muscle Hardness during Water-Walking and Land-Walking Using Ultrasound Real-Time Tissue Elastography in Healthy Young People

Compared with land-walking, water-walking is considered to be beneficial as a whole-body exercise because of the characteristics of water (buoyancy, viscosity, hydrostatic pressure, and water temperature). However, there are few reports on the effects of exercise in water on muscles, and there is no standard qualitative assessment method for muscle flexibility. Therefore, we used ultrasound real-time tissue elastography (RTE) to compare muscle hardness after water-walking and land-walking. Participants were 15 healthy young adult males (24.8 ± 2.3 years). The method consisted of land-walking and water-walking for 20 min on separate days. The strain ratio of the rectus femoris (RF) and medial head of gastrocnemius (MHGM) muscles were measured before and immediately after walking using RTE to evaluate muscle hardness. In water-walking, the strain ratio significantly decreased immediately after water-walking, with p p < 0.05 for MHGM, indicating a significant decrease in muscle hardness after water-walking. On the other hand, land-walking did not produce significant differences in RF and MHGM. Muscle hardness after aerobic exercise, as assessed by RTE, was not changed by land walking but was significantly decreased by water walking. The decrease in muscle hardness induced by water-walking was thought to be caused by the edema reduction effect produced by buoyancy and hydrostatic pressure

Laparoscopic distal gastrectomy for gastric cancer patient with intestinal malrotation: report of a case

Abstract Background Intestinal malrotation, which arises from incomplete rotation of the embryonic midgut, is one of the congenital anomalies usually diagnosed in infancy. On the other hand, intestinal malrotation detected in asymptomatic adults is very rare. It is frequently diagnosed incidentally during abdominal surgery. We report a case of asymptomatic intestinal malrotation diagnosed during laparoscopic distal gastrectomy for gastric cancer. Case presentation A 59-year-old female was diagnosed with early-stage gastric cancer during health screening and admitted to our hospital for radical surgical treatment. Physical examinations and blood tests revealed nothing of note. The type 0-IIc gastric cancer was located in the posterior wall of the mid-body of the stomach. The histological type was poorly differentiated adenocarcinoma. Esophagogastroduodenoscopy and computed tomography (CT) suggested that the depth of tumor invasion was the submucosal layer without regional lymph node swelling. The clinical stage according to the TNM 7th edition was cT1b N0 M0, cStage I. Laparoscopic distal gastrectomy with D1+ lymph node dissection and Billroth-I method reconstruction was planned. During the infrapyloric lymph node dissection, a part of the pancreatic head showed unusual adherence to the first part of the duodenal wall. For safe and accurate lymphadenectomy while avoiding pancreatic injury, we deliberately focused on tracing the dissectible layer between the pancreatic parenchyma and fatty tissues including lymph nodes. Also, we changed the reconstruction procedure from Billroth-I to Roux-en-Y. After distal gastrostomy, we could not find the ligament of Treitz or jejunum on the left side below the transverse colon. Based on a review of the CT image, this patient was diagnosed with intestinal malrotation. Although the detection of malrotation during the operation was incidental, we could complete radical surgery and Roux-en-Y reconstruction safely. The type of malrotation was non-rotation (90°). She was discharged from our hospital without any complications. Conclusion We encountered a case of adult asymptomatic intestinal malrotation with gastric cancer. Even when encountering such a case during laparoscopic gastrectomy, reviewing CT images carefully to reconsider the anatomical anomalies, and tracing the dissectible layer accurately with adequate countertraction can facilitate safe and successful surgery