Search

The detection of shouted speech is crucial in audio surveillance and monitoring. Although it is desirable for a security system to be able to identify emergencies, existing corpora provide only a binary label (i.e., shouted or normal) for each speech sample, making it difficult to predict the shout intensity. Furthermore, most corpora comprise only utterances typical of hazardous situations, meaning that classifiers cannot learn to discriminate such utterances from shouts typical of less hazardous situations such as cheers. Thus, this paper presents a novel research source, the RItsumeikan Shout Corpus (RISC), which contains wide variety types of shouted speech samples collected in recording experiments. Each shouted speech sample in RISC has a shout type and is also assigned shout intensity ratings via a crowdsourcing service. We also present a comprehensive performance comparison among deep learning approaches for speech type classification tasks and a shout intensity prediction task. The results show that feature learning based on the spectral and cepstral domains achieves high performance, no matter which network architecture is used. The results also demonstrate that shout type classification and intensity prediction are still challenging tasks, and RISC is expected to contribute to further development in this research area.

Background: Ablation is an effective, parenchymal-sparing treatment for primary liver cancer and liver metastases. The purpose of this study was to report our initial experience with laparoscopic microwave ablation regarding postoperative complications, rate of conversions to open procedure, and technical efficacy. Methods: This was a quality improvement project carried out at a tertiary care center in Denmark. Patients ≥ 18 years old with liver malignancies, not available for percutaneous ablation, and treated with ultrasound-guided laparoscopic ablation were included. Results: From March 2023 to December 2023, 39 patients were referred for laparoscopic ablation after a multidisciplinary team conference. Of these, two procedures were converted to open procedures due to adhesion and tumor progression. Three patients rejected the sharing of medical information, two procedures were canceled and in one case the strategy was changed perioperatively. Therefore, 32 procedures in 31 patients were available for analysis. Complete ablation was evaluated after 1 month and was achieved in 100% of the procedures. None of the patients died, and no complications were reported in 21 cases (65.6%). Most patients with complications had a grade 1 complication based on the Clavien–Dindo classification, which among others included abdominal and shoulder pain, atrial fibrillation, and subcutaneous hematoma. Two patients had a complication grade 2 (wound infection and decompensated cirrhosis) and one had a grade 4b (sepsis due to pneumonia and urinary tract infection). The median Comprehensive Complication Index was 12.2 (interquartile range 8.7–24.2). Furthermore, univariable logistic regression showed that ≥ 2 tumors treated were associated with a higher risk of complications (odds ratio 6.37, 95% confidence interval [1.20;33.85], p-value = 0.0297). Conclusion: Ultrasound-guided laparoscopic microwave ablation of liver malignancies is feasible and safe with little risk for complications, a high technical efficacy, and a low rate of conversions to open procedures.

Background and objective: Minimally invasive liver surgery is evolving worldwide, and robot-assisted liver surgery (RLS) can deliver obvious benefits for patients. However, so far no large case series have documented the learning curve for RLS.Methods: We conducted a retrospective study for robotic liver surgery (RLS) from June 2019 to June 2022 where 100 patients underwent RLS by the same surgical team. Patients’ variables, short-term follow-up, and the learning curve were analyzed. A review of the literature describing the learning curve in RLS was also conducted.Results: Mean patient age was 63.1 years. The median operating time was 246 min and median estimated blood loss was 100 mL. Thirty-two patients underwent subsegmentectomy, 18 monosegmentectomies, 25 bisegmentectomies, and 25 major hepatectomies. One patient (1.0%) required conversion to open surgery. Five patients (5%) experienced postoperative major complications, and no mortalities occurred. Median length of hospital stay was 3 days. R0 resection was achieved in 93.4% of the malignant cases. The learning curve consisted of three stages; there were no significant differences in operative time, transfusion rate, or complication rate among the three groups. Postoperative complications were similar in each group despite an increase in surgical difficulty scores. The learning effect was highlighted by significantly shorter hospital stays in cohorts I, II, and III, respectively. The included systematic review suggested that the learning curve for RLS is similar to, or shorter, than that of laparoscopic liver surgery.Conclusions: In our experience, RLS has achieved good clinical results, albeit in the short term. Standardization of training leads to increasing proficiency in RLS with reduced blood loss and low complication rates even in more advanced liver resections. Our study suggests that a minimum of 30 low-to-moderate difficulty robotic procedures should be performed before proceeding to more difficult resections.

Purpose: The role of adjuvant external-beam radiotherapy (EBRT) in the treatment of locally advanced papillary thyroid carcinoma (PTC) remains controversial due to the lack of prospective data and the conflicting retrospective data. This study aimed to determine the benefits of adjuvant EBRT in patients with PTC and other organ invasions using propensity score matching to reduce the heterogeneity of the patient population. Methods: Data from patients with PTC with other organ invasions but no distant metastases who underwent surgery and adjuvant radioactive iodine (RAI) alone (Non-EBRT group) or adjuvant EBRT plus RAI (EBRT group) were retrospectively reviewed. Propensity matching was used to reduce heterogeneity. Survival outcomes and toxicities associated with EBRT were evaluated. Results: Between January 2005 and December 2019, 102 patients in the Non-EBRT group and 26 patients in the EBRT group were evaluated. In the 48 propensity score-matched patients, no significant differences in baseline characteristics between the Non-EBRT and EBRT groups were detected. The locoregional recurrence-free survival (LRRFS) and recurrence-free survival (RFS) rates were significantly higher in the EBRT group compared with the rates in the Non-EBRT group (5y-LRRFS: 100% vs. 74%, p= 0.003, 5y-RFS: 91% vs. 74%, p= 0.035). EBRT was well-tolerated, with no grade ≥ 3 toxicity, and all patients completed the therapy as planned. Conclusion: Adjuvant EBRT plus RAI exhibited acceptable toxicity and improved LRRFS and RFS in patients with PTC with other organ invasions compared with RAI alone.

Quantum emitters coupled to optical resonators are quintessential systems for exploring fundamental phenomena in cavity quantum electrodynamics (cQED)1and are commonly used in quantum devices acting as qubits, memories and transducers2. Many previous experimental cQED studies have focused on regimes in which a small number of identical emitters interact with a weak external drive3–6, such that the system can be described with simple, effective models. However, the dynamics of a disordered, many-body quantum system subject to a strong drive have not been fully explored, despite its importance and potential in quantum applications7–10. Here we study how a large, inhomogeneously broadened ensemble of solid-state emitters coupled with high cooperativity to a nanophotonic resonator behaves under strong excitation. We discover a sharp, collectively induced transparency (CIT) in the cavity reflection spectrum, resulting from quantum interference and collective response induced by the interplay between driven inhomogeneous emitters and cavity photons. Furthermore, coherent excitation within the CIT window leads to highly nonlinear optical emission, spanning from fast superradiance to slow subradiance11. These phenomena in the many-body cQED regime enable new mechanisms for achieving slow light12and frequency referencing, pave a way towards solid-state superradiant lasers13and inform the development of ensemble-based quantum interconnects9,10.

Purpose: Papillary thyroid carcinoma (PTC) with other organ invasions is directly related to patient prognosis and quality of life; however, studies on the clinical outcomes of adjuvant radioactive iodine (RAI) for PTC with other organ invasions are limited. This study aimed to clarify the clinical outcomes and prognostic factors for patients with PTC with other organ invasions after adjuvant RAI. Methods: Patients with PTC with other organ invasions without distant metastases who underwent surgery and adjuvant RAI were retrospectively reviewed. We evaluated the initial responses based on the American Thyroid Association guidelines and survival rates. Prognostic factors for locoregional recurrence-free survival (LRRFS) were analyzed. Results: Between January 2005 and December 2019, 102 patients were included in the study. Their median age was 55 years. The median follow-up duration was 92 months (range; 30–231 months). The excellent response rate after RAI was 42%. The 7-year overall survival, LRRFS, and recurrence-free survival rates were 100%, 75%, and 75%, respectively. Metastatic lymph node size, resection margin status, and post-RAI suppressed thyroglobulin level were the independent prognostic factors for LRRFS. Conclusion: We demonstrated that 75% of patients with PTC with other organ invasions could achieve long-term survival without recurrence after adjuvant RAI. Future development of effective treatment strategies for large metastatic lymph nodes, gross residual tumors, and high serum thyroglobulin levels is warranted.

Despite the routine use of sandwich enzyme-linked immunosorbent assays (ELISAs) for quantifying tau levels in CSF and plasma, tau accumulations in the brains of patients with Alzheimer disease (AD) have rarely been evaluated by this method. Thus, by introducing several tau ELISAs that target different epitopes, we evaluated accumulated tau levels in postmortem brains depending on disease stage, brain areas, and other AD-related changes. Notably, tau levels in insoluble fraction determined by each ELISAs differ depending on the epitopes of antibodies: non-AD control samples yield relatively high signals when an antibody against the N-terminal region of tau is used. On the other hand, ELISAs combining antibodies against the later-middle to C-terminal regions of tau produced substantially increased signals from AD samples, compared to those from non-AD controls. Such ELISAs better distinguish AD and non-AD controls, and the results are more closely associated with Braak neurofibrillary tangles stage, Aβ accumulation, and glial markers. Moreover, these ELISAs can reflect the pattern of tau spread across brain regions. In conclusion, Tau ELISAs that combine antibodies against the later-middle to C-terminal regions of tau can better reflect neuropathological tau accumulation, which would enable to evaluate tau accumulation in the brain at a biochemical level.

Even with the same energy supply, differences in energy sources may affect calf growth and metabolism. In this study, we evaluated the effects of feeding 3 different milk replacers (MRs) with different lactose supplies under isoenergetic conditions on calf digestibility, growth, and metabolism-related markers. Fifteen Holstein bull calves were randomly assigned to one of 3 MR-feeding treatments: low-lactose (L:38%), medium-lactose (M:41%), or high-lactose (H:46%). After birth, calves were provided colostrum and treatment MRs were fed from 1 d of age and gradually increased to a maximum feeding rate at 20 d of age (L:1.16 kg/d, M:1.21 kg/d, H:1.26 kg/d DM) without feeding solid feeds during the experimental period. Blood samples were temporarily collected weekly to assess blood concentrations of metabolites and hormones. From 30 to 36 d of age, the calves were euthanized and liver samples were collected to determine growth-related mRNA expression. L calves showed a greater body length than H calves and the highest GHR mRNA expression. Plasma concentrations of total cholesterol, urea nitrogen, total protein, albumin, insulin, and insulin-growth factor-1 were not different, but plasma concentrations of triglycerides were higher in order H, M, and L. These results showed that the difference in lactose content in the MR affected calf metabolism, and the L-MR was suggested to be more likely to enhance growth into the peripheral tissues.

We investigated the effects of a calf starter supplemented with calcium salts of medium-chain fatty acids (MCFA-Ca) on growth and plasma hormone concentration in calves. Twelve Holstein calves were randomly assigned to two dietary groups (without supplementation [CON] and supplemented with MCFA-Ca [MCFA]) from 4 d of age. Calves were fed 1.0 kg/d of milk replacer until 5 wk of age and were completely weaned at 7 wk of age. Calves in the MCFA group received a calf starter containing 1% MCFA-Ca. dry matter intake (DMI) was measured daily, and body weight was measured weekly. Rumen fluid was collected at 13 wk of age to measure pH and volatile fatty acid concentration. Preprandial blood samples were collected weekly to measure the basal plasma hormone and metabolite concentrations. At 4, 8, and 13 wk of age, peri-prandial blood samples were collected every 30 min, from 60 min before feeding to 120 min after feeding, to observe metabolic responses to feeding. In addition, insulin sensitivity was assessed using euglycemic-hyperinsulinemic clamps at 4, 8, and 13 wk of age in three calves from each treatment. There were no differences in starter and hay DMI between the treatments. However, the average daily gain (ADG) after weaning was higher in the MCFA group than in the CON group. Weekly changes in plasma parameters did not differ between the treatments. Plasma concentrations of preprandial ghrelin and postprandial total ketone bodies at 13 wk of age were higher in the MCFA group than in the CON group. At 8 wk of age, peri-prandial plasma insulin concentrations were lower in the MCFA group than in the CON group. There were no differences between the treatments in terms of insulin sensitivity. The present study suggested that feeding weaning calves MCFA-Ca increases the ADG during the postweaning period, which may be mediated by endocrine signals, such as enhanced ghrelin secretion and decreased insulin secretion, without altering insulin sensitivity.Feeding medium-chain fatty acids with calf starter during the weaning period increases the postweaning growth and feed efficiency of calves. This effect may be mediated by the rapid metabolism of medium-chain fatty acids as energy sources and the regulation of hormone secretion, such as ghrelin and insulin.Calves are prone to growth retardation because of insufficient energy intake during the weaning transition period. Starch is the main energy source used in the formulation of calf starters. However, there is a concern that preweaned calves do not have sufficient functional rumen and small intestine to digest large amounts of starch, causing diarrhea, and decreased feed intake. Medium-chain fatty acids are easily accessible to calves and are expected to have functional properties, such as increasing the plasma concentration of ghrelin, which may enhance growth by stimulating growth hormone. The effect of calf starter supplementation with medium-chain fatty acids on growth performance and metabolism has not been evaluated previously and was evaluated in this study. Medium-chain fatty acids were fed in the form of calcium salts as pelleted solid feed. The results showed that feeding medium-chain fatty acids increased plasma ghrelin concentration, decreased insulin concentration, suggesting that these metabolic changes might be beneficial for calf growth performance.

Interannual sea‐level variations between the United States (U.S.) Northeast and Southeast Coasts separated by Cape Hatteras are significantly less correlated than those within their respective sectors, but the cause is poorly understood. Here we investigate atmospheric forcing mechanisms that affect the interannual sea‐level co‐variability between these two sectors using an adjoint reconstruction and decomposition approach in the framework of Estimating the Circulation and Climate of the Ocean (ECCO) ocean state estimate. We compare modeled and observed sea‐level changes at representative locations in each sector: Nantucket Island, Massachusetts for the Northeast and Charleston, South Carolina for the Southeast. The adjoint reconstruction and decomposition approach used in this work allows for identification and quantification of the causal mechanisms responsible for observed coastal sea‐level variability. Coherent sea‐level variations in Nantucket and Charleston arise from nearshore wind stress anomalies north of Cape Hatteras and buoyancy forcing, especially from the subpolar North Atlantic, while offshore wind stress anomalies, in contrast, reduce co‐variability. Offshore wind stress contributes much more to interannual sea‐level variation at Charleston than at Nantucket, causing incoherent sea level variations between the two locations. Buoyancy forcing anomalies south of Charleston, including over the Florida shelf, the Gulf of Mexico, and the Caribbean Sea, also reduce co‐variability because they induce sea‐level responses at Charleston but not Nantucket. However, the relative impact of buoyancy forcing on interannual sea‐level co‐variability between the two sectors is much smaller than that of offshore wind stress. The magnitude of year‐to‐year sea‐level variations along the East Coast of the United States (U.S.) can be comparable to that of global mean sea‐level rise over a few decades. These year‐to‐year sea‐level variations contribute to more frequent nuisance floods that affect coastal communities. Year‐to‐year sea‐level variations between the U.S. Northeast and Southeast Coasts separated by Cape Hatteras are significantly less correlated than those within the respective sectors. Understanding causal mechanisms affecting the coherence of year‐to‐year sea‐level variations in the two sectors would help improve sea‐level predictions. Our study attributes year‐to‐year sea‐level variations at Charleston and Nantucket, proxy locations for the U.S. Southeast and Northeast Coasts, to wind and buoyancy forcing (air‐sea heat exchange and precipitation/evaporation at sea surface that both affect seawater buoyancy). We find that nearshore winds north of Cape Hatteras and buoyancy forcing both cause coherent year‐to‐year sea‐level variations between Nantucket and Charleston. Offshore winds affect much more year‐to‐year sea‐level variation at Charleston than that at Nantucket. Offshore winds are the major factor causing less correlated year‐to‐year sea‐level variations between Nantucket and Charleston. Warming/cooling of water south of Charleston affects sea‐level variations at Charleston, but not at Nantucket. However, this effect is smaller than that of the offshore wind. Nearshore winds north of Cape Hatteras and buoyancy forcing cause coherent interannual sea‐level variations between Nantucket and CharlestonOffshore winds contribute much more to interannual sea‐level variation at Charleston than to that at NantucketOffshore winds are the major factor causing incoherent interannual sea‐level variations between Nantucket and Charleston Nearshore winds north of Cape Hatteras and buoyancy forcing cause coherent interannual sea‐level variations between Nantucket and Charleston Offshore winds contribute much more to interannual sea‐level variation at Charleston than to that at Nantucket Offshore winds are the major factor causing incoherent interannual sea‐level variations between Nantucket and Charleston

Jakobshavn Isbrae has been the single largest source of mass loss from the Greenland Ice Sheet over the last 20 years. During that time, it has been retreating, accelerating and thinning. Here we use airborne altimetry and satellite imagery to show that since 2016 Jakobshavn has been re-advancing, slowing and thickening. We link these changes to concurrent cooling of ocean waters in Disko Bay that spill over into Ilulissat Icefjord. Ocean temperatures in the bay’s upper 250 m have cooled to levels not seen since the mid 1980s. Observations and modelling trace the origins of this cooling to anomalous wintertime heat loss in the boundary current that circulates around the southern half of Greenland. Longer time series of ocean temperature, subglacial discharge and glacier variability strongly suggest that ocean-induced melting at the front has continued to influence glacier dynamics after the disintegration of its floating tongue in 2003. We conclude that projections of Jakobshavn’s future contribution to sea-level rise that are based on glacier geometry are insufficient, and that accounting for external forcing is indispensable.

The lectin-like oxidized LDL receptor 1 (LOX-1) is a key player in the development of atherosclerosis. LOX-1 promotes endothelial activation and dysfunction by mediating uptake of oxidized LDL and inducing pro-atherogenic signaling. However, little is known about modulators of LOX-1–mediated responses. Here, we show that the function of LOX-1 is controlled proteolytically. Ectodomain shedding by the metalloprotease ADAM10 and lysosomal degradation generate membrane-bound N-terminal fragments (NTFs), which we identified as novel substrates of the intramembrane proteases signal peptide peptidase–like 2a and b (SPPL2a/b). SPPL2a/b control cellular LOX-1 NTF levels which, following self-association via their transmembrane domain, can activate MAP kinases in a ligand-independent manner. This leads to an up-regulation of several pro-atherogenic and pro-fibrotic targets including ICAM-1 and the connective tissue growth factor CTGF. Consequently, SPPL2a/b-deficient mice, which accumulate LOX-1 NTFs, develop larger and more advanced atherosclerotic plaques than controls. This identifies intramembrane proteolysis by SPPL2a/b as a novel atheroprotective mechanism via negative regulation of LOX-1 signaling.

This study investigates the variability of the Southern Hemisphere super gyre (SHSG), using remotely sensed altimeter measurements, in situ Argo observations, and results from an ocean state estimate of the Consortium for Estimating the Circulation and Climate of the Ocean. Analyses of altimeter data show large trends of sea surface height, and their positive‐negative contrast suggests a strengthening of subtropical gyres in all the three Southern Hemisphere oceans since 1993. Analyses of Argo data and the Estimating the Circulation and Climate of the Ocean estimate indicate that these dynamic signals of southern subtropical gyres extend to at least 2,000 m. The three southern subtropical gyres are interconnected through the Tasman and Agulhas leakages and vary consistently during the period 1993–2016. The Tasman and Agulhas leakages also show an increasing trend of inter‐ocean water exchange with a typical increase of ~2 Sv (1 Sv = 106m3/s) per decade, indicative of a two‐decade‐long spin‐up of the SHSG. The strengthening and poleward shift of westerly winds are associated with an increasing southern annular mode, which affect the midlatitude and high‐latitude Southern Hemisphere oceans and contribute to the spin‐up of the SHSG. The Southern Hemisphere super gyre (SHSG) is an interconnected circulation system of the southern subtropical gyres. It sweeps out of the Tasman Sea, transports water westward, and feeds the upper limb of the Atlantic thermohaline circulation through the Tasman and Agulhas leakages. The SHSG absorbs substantial quantities of atmospheric gases, such as oxygen and CO2, thus directly contributing to climate change. In this study, we analyze remotely sensed altimeter measurements, in situ observations, and outputs of an ocean general circulation model. The results reveal a two‐decade‐long spin‐up of the SHSG. The inter‐ocean exchange through the Tasman and Agulhas leakages shows an increasing trend during the period 1993–2016. This long‐term trend may be attributed to changes in westerly winds associated with an increasing southern annular mode. The Southern Hemisphere super gyre has been strengthening for more than two decadesThe inter‐ocean water exchanges through Tasman and Agulhas leakages have also been strengthening during the past two decadesThe strengthening and poleward shift of westerly winds associated with SAM contribute to the spin‐up of Southern Hemisphere super gyre

Differentiation of ABO mosaics from chimeras is performed using flow cytometry (FCM) analysis. Although mosaics and chimeras have been distinguished by presence or absence of clear resolution using FCM analysis, the lack of quantitative metrics and definitive criteria for this differentiation has made some cases difficult to differentiate. In this study, therefore, we attempted to establish a definitive and quantitative criterion for this differentiation. When FCM histogram gates for group “A” or “B” antigen-negative and -positive red blood cells (RBCs) were set such that group O RBCs were classified as 99 percent negative and group A or B RBCs as 99 percent positive, the percentages of RBCs in the middle region of six chimeras and 23 mosaics (12 A mosaics and 11 B mosaics) were 0.1–0.6 percent and 7.0–19.0 percent, respectively. This result suggested that ABO mosaics and chimeras can be unambiguously differentiated when the cutoff point of the intermediate region is set to 1 percent. Immunohematology2015;31:24–28.

Speech enhancement has been widely investigated for several decades, but by modifying only the amplitude spectrum of a speech signal, ignoring the phase spectrum, which has been regarded as an unimportant feature. However, it was recently reported that the phase spectrum plays an important role in speech quality and intelligibility. In this paper, we propose a phase reconstruction method based on harmonic enhancement using the fundamental frequency and phase distortion feature. This feature is known to show fluctuations in the phase spectrum with respect to time and frequency. We estimate the speech phase spectrum by considering the relationship between harmonic phase spectra. Experimental evaluations indicate that the proposed phase reconstruction method improves speech quality in various noisy environments.

During the 1960s, the University of California, Los Angeles (UCLA) hosted research surveys focused on two of Southern California’s largest communities of color: the Japanese American Research Project (JARP, 1962–1970) and the Mexican American Study Project (MASP, 1964–1968). While conceived in separate sectors of the university’s research apparatus, JARP and MASP together exemplify UCLA’s gradual institutionalization of racial diversity over the course of the decade. In the years before UCLA could claim a critical mass of nonwhite scholars and students, these projects inaugurated campus-community relations with local civil rights organizations as both collaborators and critics. Together, JARP and MASP demonstrate that the multiracial integration of California’s higher education system was a prolonged process, first requiring the state’s predominantly white public universities to develop institutional vocabularies of racial difference where none existed prior.

AbstractMagnetotactic bacteria synthesize uniform-sized and regularly shaped magnetic nanoparticles in their organelles termed magnetosomes. Homeostasis of the magnetosome lumen must be maintained for its role accomplishment. Here, we developed a method to estimate the pH of a single living cell of the magnetotactic bacterium Magnetospirillum magneticumAMB-1 using a pH-sensitive fluorescent protein E2GFP. Using the pH measurement, we estimated that the cytoplasmic pH was approximately 7.6 and periplasmic pH was approximately 7.2. Moreover, we estimated pH in the magnetosome lumen and cytoplasmic surface using fusion proteins of E2GFP and magnetosome-associated proteins. The pH in the magnetosome lumen increased during the exponential growth phase when magnetotactic bacteria actively synthesize magnetite crystals, whereas pH at the magnetosome surface was not affected by the growth stage. This live-cell pH measurement method will help for understanding magnetosome pH homeostasis to reveal molecular mechanisms of magnetite biomineralization in the bacterial organelle.

The aim of this study was to investigate how intraduodenal infusions of fatty acids (FA) affect appetite-related gut peptides such as glucagon-like peptide-1 (GLP-1) and ghrelin in sheep. We hypothesized that these peptides can be highly reactive to unsaturated long-chain FA, because they are well known to decrease dry matter intake (DMI). Four ewes were fitted with a duodenal cannula and a jugular vein catheter for a 6-h duodenal infusion of the 9 FA (C8:0, C10:0, C12:0, C14:0, C16:0, C18:0, C18:1, C18:2, and C18:3) and water (control). The concentration of each FA was 1.6 g per metabolic body weight (BW), approximately corresponding to the amount of supplemented fat in a standard dairy cow diet. Each infusion was separated by at least 2 d. During the infusion period, blood samples were collected periodically to determine changes in plasma GLP-1, ghrelin, and metabolite concentrations. Duodenal infusions of C18:1, C18:2, and C18:3 led to higher plasma GLP-1 (P< 0.05) and lower glucose (P< 0.05) than control. Plasma ghrelin concentrations were greater in C18:1 and C18:3 infusions than control (P< 0.05). Plasma ketone bodies were higher in C8:0 and C10:0 infusions (P< 0.05), but plasma triglyceride concentrations were lower in C8:0, C10:0, C12:0, and C16:0 infusions (P< 0.05) than control. Fatty acid infusions except for C18:3 led to higher plasma NEFA concentrations than control (P< 0.05). These results confirmed that the hypophagic effect of dietary unsaturated long-chain FA is mediated by GLP-1 (an anorexigenic effect) secretion. However, we also observed higher plasma ghrelin (an orexigenic effect) partially by unsaturated long-chain FA. Thus, the gut peptide secretions when ruminant animals ingest FA supplements would complexly affect satiety and further studies are needed to determine their each impact on DMI.

AbstractThe hypOgene from Sinorhizobium meliloti, located within the trans-4-hydroxy-L-proline metabolic gene cluster, was first successfully expressed in the host Pseudomonas putida. Purified HypO protein functioned as a FAD-containing cis-4-hydroxy-D-proline dehydrogenase with a homomeric structure. In contrast to other known enzymes, significant activity for D-proline was found, confirming a previously proposed potential involvement in D-proline metabolism.

Leaf beetles (Coleoptera: Chrysomelidae) constitute one of the most species-rich insect families, and live exclusively on leaves or other plant parts. Early histological works described the presence of symbiotic bacteria in gut-associated symbiotic organs of some chrysomelid species, but their microbiological nature has been poorly characterized except for those associated with reed beetles of the subfamily Donaciinae. Here we investigated symbiotic bacteria of the leaf beetle Bromius obscurus(L.) belonging to the subfamily Eumolpinae. Specific bacterial 16S ribosomal RNA and gyrBgene sequences were consistently obtained from the symbiotic organs, which radially surround the foregut-midgut junction, of all adult males and females examined. In adult females, the same sequences were also obtained from a pair of genital accessory organs, which are presumably for vertical symbiont transmission. Whole mount in situ hybridization specifically detected the symbiont in the gut symbiotic organs endocellularly and also in the female genital accessory organs extracellularly. In the gut symbiotic organs, the endocellular symbiont cells were small and rosette-like or aggregated and granule-like, whereas in the female genital organs the extracellular symbiont cells were of a condensed form. Molecular phylogenetic analysis showed that the symbiont of B. obscurusconstitutes a distinct lineage in theGammaproteobacteria. Molecular evolutionary analysis has identified significantly accelerated molecular evolution and a highly adenine–thymine-biased nucleotide composition of the symbiont genes, presumably reflecting reductive evolution of the symbiont genome. These results suggest an intimate and stable host-symbiont association in B. obscurus, in which the symbiont may play some important, though hitherto unknown, biological roles in its herbivorous insect host.

γ-secretase inhibitors (GSI) are drugs developed to decrease amyloid-β peptide (Aβ) production by inhibiting intramembranous cleavage of β-amyloid protein precursor (βAPP). However, a large phase 3 trial of semagacestat, a potential non-transition state analog (non-TSA) GSI, in patients with Alzheimer’s disease (AD) was terminated due to unexpected aggravation of cognitive deficits and side effects. Here, we show that some semagacestat effects are clearly different from a phenotype caused by a loss of function of presenilins, core proteins in the γ-secretase complex. Semagacestat increases intracellular byproduct peptides, produced along with Aβ through serial γ-cleavage of βAPP, as well as intracellular long Aβ species, in cell-based and in vivo studies of AD model mice. Other potential non-TSA GSIs, but not L685,458, a TSA GSI, have similar effects. Furthermore, semagacestat inhibits release of de novo intramembranous γ-byproducts to the soluble space. Thus, semagacestat is a pseudo-GSI, and therefore, the semagacestat clinical trial did not truly test the Aβ hypothesis.

The subpolar North Atlantic (SPNA) is subject to strong decadal variability, with implications for surface climate and its predictability. In 2004–2005, SPNA decadal upper ocean and sea‐surface temperature trends reversed from warming during 1994–2004 to cooling over 2005–2015. This recent decadal trend reversal in SPNA ocean heat content (OHC) is studied using a physically consistent, observationally constrained global ocean state estimate covering 1992–2015. The estimate's physical consistency facilitates quantitative causal attribution of ocean variations. Closed heat budget diagnostics reveal that the SPNA OHC trend reversal is the result of heat advection by midlatitude ocean circulation. Kinematic decompositions reveal that changes in the deep and intermediate vertical overturning circulation cannot account for the trend reversal, but rather ocean heat transports by horizontal gyre circulations render the primary contributions. The shift in horizontal gyre advection reflects anomalous circulation acting on the mean temperature gradients. Maximum covariance analysis (MCA) reveals strong covariation between the anomalous horizontal gyre circulation and variations in the local wind stress curl, suggestive of a Sverdrup response. Results have implications for decadal predictability. Recent decadal changes in subpolar North Atlantic heat content are due to advective heat flux convergences by midlatitude ocean transportsHorizontal gyre circulations contribute more to advective convergences than vertical overturning circulations at 46°NAnomalous gyre circulation strongly covaries with local wind stress curl, suggesting a role for Sverdrup dynamics

Nuclear pore complexes (NPCs) are the sole turnstile implanted in the nuclear envelope (NE), acting as a central nanoregulator of transport between the cytosol and the nucleus. NPCs consist of ∼30 proteins, termed nucleoporins. About one-third of nucleoporins harbor natively unstructured, intrinsically disordered phenylalanine-glycine strings (FG-Nups), which engage in transport selectivity. Because the barriers insert deeply in the NPC, they are nearly inaccessible. Several in vitrobarrier models have been proposed; however, the dynamic FG-Nups protein molecules themselves are imperceptible in vivo. We show here that high-speed atomic force microscopy (HS-AFM) can be used to directly visualize nanotopographical changes of the nuclear pore inner channel in colorectal cancer (CRC) cells. Furthermore, using MLN8237/alisertib, an apoptotic and autophagic inducer currently being tested in relapsed cancer clinical trials, we unveiled the functional loss of nucleoporins, particularly the deformation of the FG-Nups barrier, in dying cancer cells. We propose that the loss of this nanoscopic resilience is an irreversible dying code in cells. These findings not only illuminate the potential application of HS-AFM as an intracellular nanoendoscopy but also might aid in the design of future nuclear targeted nanodrug delivery tailored to the individual patient.

Objective. Borna disease virus 1 (BoDV-1) was proven to cause fatal encephalitis in humans in 2018. However, the effects of persistent infections remain unclear. Here, we present the case of a 50-year-old woman with a 30-year history of severe schizophrenia, who was exposed to fleas from stray cats prior to disease onset, suggesting the possibility of zoonosis including BoDV-1 infection. The patient had experienced significant social impairment, thought deterioration, delusions, and hallucinations for more than 20 years. Method. A radioligand assay was used to test the patient for IgG and IgM antibodies against BoDV-1 nucleoprotein (N) and phosphoprotein (P). Based on the protocol for hepatitis C, we treated the patient with 400 mg/day ribavirin, which was later increased to 600 mg/day. Results. The serological examination revealed anti-BoDV-1 N IgG. Although only subtle changes were observed over the 24 weeks of treatment, the family noticed that the patient’s Cotard delusions had disappeared 7 months after completing the treatment, accompanied by some improvements in the relationship with the family. Conclusion. Though definite proof was not obtained, this presumed suppression of BoDV-1 by ribavirin leading to improvements in Cotard syndrome-like symptoms suggests that intractable schizophrenia might be one of the BoDV-1 infection phenotypes. Further studies are needed to clarify the effect of persistent BoDV-1 infections in humans.

Background. Exercise can reduce the pain threshold momentarily and induce analgesia, which is called exercise-induced hypoalgesia (EIH). Exercise therapy for inducing EIH may be an effective treatment option for pain. We aimed at investigating whether continuous passive motion (CPM) on both healthy and affected sides could induce EIH and reduce pain in the operated knee in patients after unilateral total knee arthroplasty (TKA). Patients and Methods. In this prospective randomized controlled trial, participants were randomly assigned to two groups: a bilateral group that received bilateral exercise on the operated and healthy sides and a unilateral group that received exercise therapy only on the affected side. We enrolled 40 patients aged ≥60 years who were scheduled to undergo unilateral TKA. Visual analogue scale (VAS) scores and range of motion (ROM) on the operated side were measured immediately before and after CPM on postoperative days 2, 4, 7, and 14. The primary outcome was the difference in the VAS scores before and after CPM on postoperative day 14. The secondary outcome was the difference in the ROM before and after CPM on postoperative day 14. Results. Comparison of VAS scores before and after CPM showed no significant intergroup differences on all measurement dates. However, there was a significant difference in values on day 14 (P<0.05). Both groups showed an increase in ROM after CPM, with significant increments observed on days 2 and 4 in the bilateral group and on day 14 in the unilateral group. There was no significant difference in values on postoperative day 14. Conclusion. Post-TKA pain was reduced by performing the same exercise on the healthy knee during CPM therapy. This could be due to EIH, and the results indicated that EIH can also influence postoperative pain immediately after surgery.

Among three MAPK disruptants of Neurospora crassa, Δmak-1was sensitive and Δmak-2was hypersensitive to micafungin, a beta-1,3-glucan synthase inhibitor, than the wild-type or Δos-2strains. We identified six micafungin-inducible genes that are involved in cell wall integrity (CWI) and found that MAK-1 regulated the transcription of non-anchored cell wall protein gene, ncw-1,and the beta-1,3-endoglucanase gene, bgt-2, whereas MAK-2 controlled the expression of the glycosylhydrolase-like protein gene, gh76-5, and the C4-dicarboxylate transporter gene, tdt-1. Western blotting analysis revealed that, in the wild-type strain, MAK-1 was constitutively phosphorylated from conidial germination to hyphal development. In contrast, the phosphorylation of MAK-2 was growth phase-dependent, and micafungin induced the phosphorylation of unphosphorylated MAK-2. It should be noted that the phosphorylation of MAK-1 was virtually abolished in the Δmak-2strain, but was significantly induced by micafungin, suggesting functional cross talk between MAK-1 and MAK-2 signalling pathway in CWI.

Magnetosomes are membrane-enveloped bacterial organelles containing nano-sized magnetic particles, and function as a cellular magnetic sensor, which assist the cells to navigate and swim along the geomagnetic field. Localized with each magnetosome is a suite of proteins involved in the synthesis, maintenance and functionalization of the organelle, however the detailed molecular organization of the proteins in magnetosomes is unresolved. MamA is one of the most abundant magnetosome-associated proteins and is anchored to the magnetosome vesicles through protein-protein interactions, but the identity of the protein that interacts with MamA is undetermined. In this study, we found that MamA binds to a magnetosome membrane protein Mms6. Two different molecular masses of Mms6, 14.5-kDa and 6.0-kDa, were associated with the magnetosomes. Using affinity chromatography, we identified that the 14.5-kDa Mms6 interacts with MamA, and the interaction was further confirmed by pull-down, immunoprecipitation and size-exclusion chromatography assays. Prior to this, Mms6 was assumed to be strictly involved with biomineralizing magnetite; however, these results suggest that Mms6 has an additional responsibility, binding to MamA.

Background: Patients with complex regional pain syndrome (CRPS) require long-term treatment. Virtual reality based mirror visual feedback (VR-MVF) can contribute to this treatment. A personal VR-MVF system has been proposed for treating patients at home. Assessment and understanding of a patient's condition is required for medical instruction in order to continue home-based treatment. However, diagnostic questionnaires alone are inadequate for complete assessment of a patient's condition. The purpose of this study was to find movement indices for the improvement of CRPS by comparing hand movements of patients with CRPS to those of normal people. Method: We compared reaching movements of the wrist and elbow during the VR-MVF treatment task. A personal VRMVF system was used for collecting data. Reaching movements were defined as movements from 2 seconds before the grasp of the virtual object to the time at which the object was grasped. Result: The results showed that healthy participants performed reaching movements with their hand. On the other hand, the patients with CRPS tended to perform reaching movements by moving their elbow instead of their hand. In addition, the results showed that the increase in trajectory length of the patients' hand relative to their elbow may relate to pain reduction. Conclusion: In accordance with these results, we suggest that focusing on the movements of the hand and the elbow may be useful for understanding the condition of these patients, and that hand and elbow movements may be used as indices.

Gene therapy with viral vectors is one of the most promising strategies for sensorineural hearing loss. However, safe and effective administration of the viral vector into cochlear tissue is difficult because of the anatomical isolation of the cochlea. We investigated the efficiency and safety of round window membrane (RWM) application of Sendai virus, one of the most promising non-genotoxic vectors, after pretreatment with hyaluronic acid (HA) on the RWM to promote efficient viral translocation into the cochlea. Sendai virus expressing the green fluorescent protein reporter gene was detected throughout cochlear tissues following application combined with HA pretreatment. Quantitative analysis revealed that maximum expression was reached 3 days after treatment. The efficiency of transgene expression was several 100-fold greater with HA pretreatment than that without. Furthermore, unlike the conventional intracochlear delivery methods, this approach did not cause hearing loss. These findings reveal the potential utility of gene therapy with Sendai virus and HA for treatment of sensorineural hearing loss.