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ATP-Binding Cassette A1 (ABCA1) is a key lipid transporter for cholesterol homeostasis. We recently reported that ABCA1 not only exports excess cholesterol in an apoA-I dependent manner, but that it also flops cholesterol from the inner to the outer leaflet of the plasma membrane. However, the relationship between these two activities of ABCA1 is still unclear. In this study, we analyzed the subcellular localization of ABCA1 by using a newly generated monoclonal antibody against its extracellular domain and the functions of eleven chimera proteins, in which the C-terminal domain of ABCA1 was replaced with those of the other ABCA subfamily members. We identified two motifs important for the functions of ABCA1. Three periodically repeated leucine residues were necessary for the cholesterol floppase activity but not the cholesterol efflux activity, while a VFVNFA motif was essential for both activities of ABCA1. These results suggest that the C-terminal of ABCA1 separately regulates the cholesterol floppase activity and the cholesterol efflux activity.

Host-microbe interactions within the gut are fundamental to all higher organisms. Caenorhabditis elegans has been in use as a surrogate model to understand the conserved mechanisms in host-microbe interactions. Morphological and functional similarities of C. elegans gut with the human have allowed the mechanistic investigation of gut microbes and their effects on metabolism, development, reproduction, behavior, pathogenesis, immune responses and lifespan. Recent reports suggest their suitability for functional investigations of human gut bacteria, such as gut microbiota of healthy and diseased individuals. Our knowledge on the gut microbial diversity of C. elegans in their natural environment and the effect of host genetics on their core gut microbiota is important. Caenorhabditis elegans, as a model, is continuously bridging the gap in our understanding the role of genetics, environment, and dietary factors on physiology of the host.

This study evaluated stereopsis and other visual functions in patients with idiopathic macular hole (MH), and sought to identify vision-related parameters that affect stereopsis. In this prospective, consecutive, comparative study, 39 eyes of 39 patients with unilateral idiopathic MH were included. At baseline and at 6 months after MH surgery, we evaluated stereopsis, with the Titmus stereo test (TST) and TNO stereotest (TNO), best-corrected visual acuity (BCVA), letter contrast sensitivity, severity of metamorphopsia, as assessed using M-CHARTS, and extent of aniseikonia, by the new aniseikonia test. Preoperative stereopsis (log) in patients with MH were 2.72 ± 0.53 (range 1.9-4.1) in the TST and 2.82 ± 0.65 (range 1.8-3.9) in the TNO. Preoperative TST was significantly correlated with letter contrast sensitivity (p < 0.05), but not with the other visual functions. TNO showed significant correlation with letter contrast sensitivity (p < 0.05) and aniseikonia (p < 0.005). Preoperative TNO was associated with aniseikonia by multivariate analysis (p < 0.005). MH surgery significantly improved stereopsis, BCVA, letter contrast sensitivity, metamorphopsia, and aniseikonia. Postoperative TST and TNO was significantly associated with BCVA by multivariate analysis. Deterioration of stereopsis in MH patients is associated with contrast sensitivity and the degree of aniseikonia.

Background: The aim of this study was to compare the surgical and oncological outcomes and complications of laparoscopic radical cystectomy (LRC) to those of open radical cystectomy (ORC) in patients with muscle-invasive bladder cancer (MIBC)., Methods: Our study focused on patients with histologically confirmed stage T2-T4a urothelial carcinoma of the bladder without distant metastases, who underwent LRC (LRC group) or ORC (ORC group). The primary endpoints in this study were the overall survival (OS) and recurrence-free survival (RFS) rates., Results: In this study, 59 patients, 17 underwent LRC and 42 underwent ORC, were enrolled. The 2-year OS rate was 100% in the LRC group and 88.0% in the ORC group (p = 0.85). The 2-year RFS rate was 63.5% in the LRC group and 69.5% in the ORC group (p = 0.321). On multivariate analysis, the histological type, positive lymph node, and positive resection margin were significantly associated with the OS rates., Conclusions: This study suggested that LRC may achieve similar oncological outcomes and fewer perioperative complications and less blood loss compared to ORC. Therefore, LRC should be considered as one of the treatment options for patients with MIBC., (© 2020 S. Karger AG, Basel.)

Animals demonstrate flexible behaviors through associative learning based on their experiences. Deciphering the neural mechanisms for sensing and integrating multiple types of sensory information is critical for understanding such behavioral controls. The soil nematode Caenorhabditis elegans avoids salt concentrations it has previously experienced under starvation conditions. Here, we identify a pair of sensory neurons, the ASG neuron pair, which in cooperation with the ASER salt-sensing neuron generate starvation-dependent salt avoidance. Animals whose sensory input is restricted to only ASER failed to show learned avoidance due to inappropriately directed navigation behaviors. However, their navigation through a salt concentration gradient was improved by allowing sensory inputs to ASG in addition to ASER. Detailed behavioral analyses of these animals revealed that input from ASG neurons is required not only for controlling the frequency of initiating a set of sharp turns (called pirouettes) based on detected ambient salt concentrations but also adjusting the migration direction during pirouettes. Optogenetic activation of ASER by ChR2 induced turning behaviors in a salt concentration-dependent manner where presence of intact ASG was important for the starvation-dependent responses. Calcium imaging of the activity of ASG neurons in freely moving worms revealed that ASG is activated upon turning behavior. Our results indicate that ASG neurons cooperate with the ASER neuron to generate destination-directed reorientation in starvation-associated salt concentration avoidance., Competing Interests: The authors declare no conflict of interest., (Copyright © 2019 the Author(s). Published by PNAS.)

Introduction: Enhance®Fitness is a low-cost group exercise program designed specifically for older adults (60+ years) to improve physical performance. The Hawai'i Healthy Aging Partnership, a statewide health promotion initiative, has continuously offered Enhance®Fitness to Hawai'i's multicultural population since 2007. This study examined 12-month participation in and impact of Enhance®Fitness on physical performance among older adults in Hawai'i., Method: Linear mixed-effects models were applied to analyze the physical performance measures (chair-stands, arm curls, and the up-and-go test) collected at baseline (month 0) and at 4, 8, and 12 months. We also compared the characteristics of participants who participated in the program for 12 months with those who dropped out in order to gain insights on participant retention., Results: Of 1,202 older adults with baseline data, 427 (35.5%) were continuously enrolled in Enhance®Fitness for 12 months and participated in follow-up data collection. On average, participants attended 63.7% of thrice-weekly classes each month. Participants' physical performance measures improved after 4 months, continued to improve until 8 months, and were maintained thereafter. Besides continuous attendance, performance-measure improvements were associated with younger age, male gender, living with others (vs. alone), and fewer chronic conditions. Compared to those who completed 12 months of the program, the 775 who left the program over the course of the year were more likely to be younger, to be Caucasian (vs. Asian or Pacific Islander), to self-report depression as a chronic condition, and to have lower levels of fitness at baseline. Common reasons for dropping out were illness, relocation, time conflicts, lost interest, and transportation issues., Conclusions: Long-term participants in Enhance®Fitness initially improved and then maintained physical performance. Future research is needed to identify strategies to maintain enrollment of older adults in the exercise programs over time., Competing Interests: All authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2019 Michiyo Tomioka et al.)

Philophthalmid eyeflukes are cosmopolitan parasites of birds and occasionally of mammals, including humans. A gravid adult of Philophthalmus sp. was found from the bulbar conjunctiva of a 64-yr-old woman in Japan, who was diagnosed with acute conjunctivitis. The parasite was morphologically most similar to Philophthalmus hegeneri , but distinctive in lacking an esophagus and in having clearly lobed testes. The DNA sequence analysis of genes for nuclear 28S ribosomal RNA and mitochondrial cytochrome c oxidase subunit 1 supported the identification at generic level. The morphological and molecular analyses strongly suggest that the eyefluke from a human in Japan should be treated as an undescribed species of Philophthalmus . The occurrence of human philophthalmosis is very rare. As far as we know, a total of 11 human cases have been reported worldwide to date.

The avoidance of starvation is critical for the survival of most organisms, thus animals change behavior based on past nutritional conditions. Insulin signaling is important for nutritional state-dependent behavioral plasticity, yet the underlying regulatory mechanism at the cellular level remains unclear. Previous studies showed that insulin-like signaling is required for taste avoidance learning, in which the nematode Caenorhabditis elegans avoids salt concentrations encountered under starvation conditions. DAF-2c, a splice isoform of the DAF-2 insulin receptor, functions in the axon of the ASER sensory neuron, which senses changes in salt concentrations. In addition, mutants of a major downstream factor of DAF-2, the forkhead transcription factor O (FOXO) homolog DAF-16, show defects in taste avoidance learning. Interestingly, the defect of the daf-2 mutant is not suppressed by daf-16 mutations in the learning, unlike those in other phenomena, such as longevity and development. Here we show that multiple DAF-16 isoforms function in ASER. By epistasis analysis using a DAF-2c isoform-specific mutant and an activated form of DAF-16, we found that DAF-16 acts in the nucleus in parallel with the DAF-2c-dependent pathway in the axon, indicating that insulin-like signaling acts both in the cell body and axon of a single neuron, ASER. Starvation conditioning induces nuclear translocation of DAF-16 in ASER and degradation of DAF-16 before starvation conditioning causes defects in taste avoidance learning. Forced nuclear localization of DAF-16 in ASER biased chemotaxis towards lower salt concentrtions and this effect required the Gq/PKC pathway and neuropeptide processing enzymes. These data imply that DAF-16/FOXO transmits starvation signals and modulates neuropeptide transmission in the learning., Competing Interests: The authors have declared that no competing interests exist.

The purpose of this study was to investigate the clinical and radiological features of osteoporotic burst fractures affecting levels below the second lumbar (middle-low lumbar) vertebrae, and to clarify the appropriate surgical procedure to avoid postoperative complications. Thirty-eight consecutive patients (nine male, 29 female; mean age: 74.8 years; range: 60-86 years) with burst fractures affecting the middle-low lumbar vertebrae who underwent posterior-instrumented fusion were included. Using the Magerl classification system, these fractures were classified into three types: 16 patients with superior incomplete burst fracture (superior-type), 11 patients with inferior incomplete burst fracture (inferior-type) and 11 patients with complete burst fracture (complete-type). The clinical features were investigated for each type, and postoperative complications such as postoperative vertebral collapse (PVC) and instrumentation failure were assessed after a mean follow-up period of 3.1 years (range: 1-8.1 years). All patients suffered from severe leg pain by radiculopathy, except one with superior-type fracture who exhibited cauda equina syndrome. Nineteen of 27 patients with superior- or inferior-type fracture were found to have spondylolisthesis due to segmental instability. Although postoperative neurological status improved significantly, lumbar lordosis and segmental lordosis at the fused level deteriorated from the postoperative period to the final follow-up due to postoperative complications caused mainly by PVC (29%) and instrument failure (37%). Posterior-instrumented fusion led to a good clinical outcome; however, a higher incidence of postoperative complications due to bone fragility was inevitable. Therefore, short-segment instrument and fusion with some augumentation techniqus, together with strong osteoporotic medications may be required to avoid such complications.

Bovine leukemia virus (BLV) is the etiological agent of enzootic bovine leukosis (EBL), which causes enormous economic losses in the livestock industry worldwide. To reduce the economic loss caused by BLV infection, it is important to clarify the characters associated with BLV transmissibility and pathogenesis in cattle. In this study, we focused on viral characters and examined spontaneous mutations in the virus and viral properties by analyses of whole genome sequences and BLV molecular clones derived from cows with and without EBL. Genomic analysis indicated that all 28 strains harbored limited genetic variations but no deletion mutations that allowed classification into three groups (A, B, and C), except for one strain. Some nucleotide/amino acid substitutions were specific to a particular group. On the other hand, these genetic variations were not associated with the host bovine leukocyte antigen-DRB3 allele, which is known to be related to BLV pathogenesis. The viral replication activity in vitro was high, moderate, and low in groups A, B, and C, respectively. In addition, the proviral load, which is related to BLV transmissibility and pathogenesis, was high in cows infected with group A strains and low in those infected with group B/C strains. Therefore, these results suggest that limited genetic variations could affect viral properties relating to BLV transmissibility and pathogenesis., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Aspiration of oral debris, containing dense oral bacteria, is a major cause of pneumonia in elderly adults. This study investigated the relationship between tongue microbiota composition and incidence of pneumonia-related deaths, in nursing home residents., Methods: The subjects were assessed for health conditions, including their tongue microbiota, at baseline. We determined tongue microbiota profiles by 16S ribosomal RNA gene sequencing and clustering approach. All subjects (n = 173) were followed prospectively for a median of 19 months to assess the incidence of all-cause death, including pneumonia-related death. We evaluated risk estimates of microbiota effects on death using multivariate Cox proportional hazards regression analysis., Results: Tongue microbiota were classified into two community types: type I was dominated by Prevotella and Veillonella species, while type II was dominated by Neisseria and Fusobacterium species. The subjects with type I microbiota exhibited a significantly greater risk of all-cause death (adjusted hazard ratio [aHR] = 3.79, 95% confidence interval [CI] = 1.38-10.39) and pneumonia-related death (aHR = 13.88, 95% CI = 1.64-117.21), than those with type II microbiota. There was no significant association between microbiota type and other-cause death., Conclusions: The tongue microbiota type was significantly associated with an increased mortality risk from pneumonia in nursing home residents.

Introduction: The abrupt onset of sensorimotor deficits is a neurologic emergency that requires immediate management. Acute spontaneous spinal cord infarction (SCI) is rare, but can cause the sudden onset of quadriplegia or quadriparesis. Magnetic resonance imaging (MRI) is an essential imaging modality to diagnose SCI., Case Presentation: A 75-year-old man with a history of diabetes mellitus type 2, hypertension, and dyslipidemia was transferred to our facility for further workup of the sudden onset of quadriplegia. Diffusion-weighted contrast MRI (DWI) on hospital day 8 revealed hyperintense signals predominantly at the grey matter, and a contrast T2 signal abnormality with a decreased apparent diffusion coefficient (ADC). Steroid pulse therapy was initiated because myelitis could not be completely ruled out, but this did not improve the neurological deficits. Spontaneous SCI was finally diagnosed as an exclusion diagnosis. Symptoms were gradually recovered with rehabilitation, and he was transferred to a rehabilitation facility on hospital day 40., Conclusion: MRI with DWI of the spine should be considered for an early diagnosis of SCI. A combination of DWI with ADC maps is recommended to distinguish SCI from other differential disorders.

Cellular translation should be precisely controlled in response to extracellular cues. However, knowledge is limited concerning signal transduction-regulated translation. In the present study, phosphorylation was identified in the 40S small subunit ribosomal protein uS7 (Yjr123w/previously called as Rps5) by Ypk1 and Pkc1, AGC family protein kinases in yeast Saccharomyces cerevisiae. Serine residue 223 (Ser223) of uS7 in the conserved C-terminal region was crucial for this phosphorylation event. S223A mutant uS7 caused severe reduction of small ribosomal subunit production, likely due to compromised interaction with Rio2, resulting in both reduced translation and reduced cellular proliferation. Contrary to optimal culture conditions, heat stressed S223A mutant cells exhibited increased heat resistance and induced heat shock proteins. Taken together, an intracellular signal transduction pathway involving Ypk1/Pkc1 seemed to play an important role in ribosome biogenesis and subsequent cellular translation, utilizing uS7 as a substrate.

The ATP-binding cassette transporter A7 (ABCA7), which is highly expressed in the brain, is associated with the pathogenesis of Alzheimer's disease (AD). However, the physiological function of ABCA7 and its transport substrates remain unclear. Immunohistochemical analyses of human brain sections from AD and non-AD subjects revealed that ABCA7 is expressed in neuron and microglia cells in the cerebral cortex. The transport substrates and acceptors were identified in BHK/ABCA7 cells and compared with those of ABCA1. Like ABCA1, ABCA7 exported choline phospholipids in the presence of apoA-I and apoE; however, unlike ABCA1, cholesterol efflux was marginal. Lipid efflux by ABCA7 was saturated by 5μg/ml apoA-I and was not dependent on apoE isoforms, whereas efflux by ABCA1 was dependent on apoA-I up to 20μg/ml and apoE isoforms. Liquid chromatography-tandem mass spectrometry analyses revealed that the two proteins had different preferences for phospholipid export: ABCA7 preferred phosphatidylcholine (PC)≥lysoPC>sphingomyelin (SM)=phosphatidylethanolamine (PE), whereas ABCA1 preferred PC>>SM>PE=lysoPC. The major difference in the pattern of lipid peaks between ABCA7 and ABCA1 was the high lysoPC/PC ratio of ABCA7. These results suggest that lysoPC is one of the major transport substrates for ABCA7 and that lysoPC export may be a physiologically important function of ABCA7 in the brain., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Several types of associative learning are dependent upon the presence or absence of food, and are crucial for the survival of most animals. Target of rapamycin (TOR), a kinase which exists as a component of two complexes, TOR complex 1 (TORC1) and TOR complex 2 (TORC2), is known to act as a nutrient sensor in numerous organisms. However, the in vivo roles of TOR signaling in the nervous system remain largely unclear, partly because its multifunctionality and requirement for survival make it difficult to investigate. Here, using pharmacological inhibitors and genetic analyses, we show that TORC1 and TORC2 contribute to associative learning between salt and food availability in the nematode Caenorhabditis elegans in a process called taste associative learning. Worms migrate to salt concentrations experienced previously during feeding, but they avoid salt concentrations experienced under starvation conditions. Administration of the TOR inhibitor rapamycin causes a behavioral defect after starvation conditioning. Worms lacking either RICT-1 or SINH-1, two TORC2 components, show defects in migration to high salt levels after learning under both fed and starved conditions. We also analyzed the behavioral phenotypes of mutants of the putative TORC1 substrate RSKS-1 (the C. elegans homolog of the mammalian S6 kinase S6K) and the putative TORC2 substrates SGK-1 and PKC-2 (homologs of the serum and glucocorticoid-induced kinase 1, SGK1, and protein kinase C-α, PKC-α, respectively) and found that neuronal RSKS-1 and PKC-2, as well as intestinal SGK-1, are involved in taste associative learning. Our findings shed light on the functions of TOR signaling in behavioral plasticity and provide insight into the mechanisms by which information sensed in the intestine affects the nervous system to modulate food-searching behaviors.

Background: Rotational acetabular osteotomy (RAO) is an effective joint-preserving surgical treatment for adulthood hip dysplasia (AHD). Despite sufficient correction of acetabular dysplasia, some patients still experience osteoarthritis (OA) progression and require total hip arthroplasty (THA). The purposes of the current study were to investigate the survival rate and the risk factors for OA progression or THA requirement after RAO and to explore whether acetabular overcorrection relates to OA progression., Methods: Fifty-six patients (65 hips, mean age: 36.5 ± 11.7 years) with AHD who underwent RAO and were followed up for >10 years (mean: 15.0 ± 3.2 years) were enrolled in this study. A Kaplan-Meier survival analysis was performed to assess the non-OA progression rate and THA-free survival rate of RAO during the 10-year follow-up. To analyze the risk factors for OA progression and THA requirement, the Cox proportional hazards regression analysis was performed., Results: No OA progression was found in 76.7% of the patients, and THA was not required in 92.3% during the 10-year follow-up. By multivariate regression analysis, older age at the time of surgery was a risk factor for both OA progression (hazard ratio [HR] = 1.047, 95% confidence interval [CI] = 1.005-1.091) and THA requirement (HR = 1.293, 95% CI = 1.041-1.606)., Conclusion: RAO is an effective surgical procedure for symptomatic patients with AHD that prevents OA progression and protects the hips from undergoing THA. However, older patients have a higher risk for both OA progression and THA requirement.

With increased life expectancy, people need more education about healthy aging. This paper examines older adult perceptions regarding various factors impacting longevity, including genetics, lifestyle, and the environment. Data were collected from 733 Hawai'i adults age 50 years and older (39% Caucasian, 27% Japanese, 19% Native Hawaiian and Pacific Islander (NHOPI), 9% Chinese, and 7% Filipino) through randomized telephone interviews. Participants were asked to rate a variety of factors as having "great impact," "some impact," or "no impact" on lifespan. Regardless of ethnicity, more than half of the participants felt that eating habits, exercise, health information, health care, and the environment had great impact on lifespan. Less than half felt that economic status and community had great impact. Compared to the all ethnic groups, Filipino respondents were significantly less likely to feel that smoking (44%, compared with an average across all race/ethnicities of 64%) and stress (48%, average 62%) had great impact. Chinese participants were more likely to feel that drinking alcohol (64%) had great impact (average 38%). Filipinos and Chinese were more likely to perceive that working conditions have great impact (65% and 56%, respectively; average 45%), and NHOPI and Filipinos were more likely to perceive the natural environment as having great impact (59% and 54%, respectively; average 46%). Findings suggest that cultural values and experiences may shape older adults' perceptions of factors associated with lifespan, providing guidance for health professionals on how to tailor health messages to older adults in different ethnic groups.

Animals show various behaviors in response to environmental chemicals. These behaviors are often plastic depending on previous experiences. Caenorhabditis elegans , which has highly developed chemosensory system with a limited number of sensory neurons, is an ideal model for analyzing the role of each neuron in innate and learned behaviors. Here, we report a new type of memory-dependent behavioral plasticity in Na + chemotaxis generated by the left member of bilateral gustatory neuron pair ASE (ASEL neuron). When worms were cultivated in the presence of Na + , they showed positive chemotaxis toward Na + , but when cultivated under Na + -free conditions, they showed no preference regarding Na + concentration. Both channelrhodopsin-2 (ChR2) activation with blue light and up-steps of Na + concentration activated ASEL only after cultivation with Na + , as judged by increase in intracellular Ca 2+ Under cultivation conditions with Na + , photoactivation of ASEL caused activation of its downstream interneurons AIY and AIA, which stimulate forward locomotion, and inhibition of its downstream interneuron AIB, which inhibits the turning/reversal behavior, and overall drove worms toward higher Na + concentrations. We also found that the Gq signaling pathway and the neurotransmitter glutamate are both involved in the behavioral response generated by ASEL. SIGNIFICANCE STATEMENT Animals have acquired various types of behavioral plasticity during their long evolutionary history. Caenorhabditis elegans prefers odors associated with food, but plastically changes its behavioral response according to previous experience. Here, we report a new type of behavioral response generated by a single gustatory sensory neuron, the ASE-left (ASEL) neuron. ASEL did not respond to photostimulation or upsteps of Na + concentration when worms were cultivated in Na + -free conditions; however, when worms were cultivated with Na + , ASEL responded and inhibited AIB to avoid turning and stimulated AIY and AIA to promote forward locomotion, which collectively drove worms toward higher Na + concentrations. Glutamate and the Gq signaling pathway are essential for driving worms toward higher Na + concentrations., (Copyright © 2017 the authors 0270-6474/17/372097-15$15.00/0.)

Strangulated intestinal obstruction is one of the most common types of acute abdomen and requires urgent surgical treatment. Herein, we report a very rare case of strangulated intestinal obstruction caused by an ileo-ileal knot. An 80-year-old woman was admitted to our hospital with suspicion of strangulation ileus and underwent emergency laparotomy after investigation by exploratory single-port laparoscopy. During surgery, a small bowel gangrene caused by an ileo-ileal knot was found. The gangrenous segment was resected, and primary anastomosis was performed. Post-operative recovery was uneventful except for a minor wound infection. Our extensive search of the literature found only 7 case reports of ileo-ileal knot including ours. An ileo-ileal knot should be considered in the differential diagnosis of acute intestinal obstruction, because this rare phenomenon requires urgent surgical treatment; and some complications should be considered during or after surgery.

There is a popular belief that the lunar cycle influences spontaneous delivery in both humans and cattle. To assess this relationship, we investigated the synodic distribution of spontaneous deliveries in domestic Holstein cows. We used retrospective data from 428 spontaneous, full-term deliveries within a three-year period derived from the calving records of a private farm in Hokkaido, Japan. Spontaneous birth frequency increased uniformly from the new moon to the full moon phase and decreased until the waning crescent phase. There was a statistically significant peak between the waxing gibbous and full moon phases compared with those between the last quarter and the waning crescent. These changes were clearly observed in deliveries among multiparous cows, whereas they were not evident in deliveries among nulliparous cows. These data suggest the utility of dairy cows as models for bio-meteorological studies, and indicate that monitoring lunar phases may facilitate comprehensive understanding of parturition., Competing Interests: The authors have declared that no competing interests exist.

Alternative splicing generates protein diversity essential for neuronal properties. However, the precise mechanisms underlying this process and its relevance to physiological and behavioural functions are poorly understood. To address these issues, we focused on a cassette exon of the Caenorhabditis elegans insulin receptor gene daf-2, whose proper variant expression in the taste receptor neuron ASER is critical for taste-avoidance learning. We show that inclusion of daf-2 exon 11.5 is restricted to specific neuron types, including ASER, and is controlled by a combinatorial action of evolutionarily conserved alternative splicing factors, RBFOX, CELF and PTB families of proteins. Mutations of these factors cause a learning defect, and this defect is relieved by DAF-2c (exon 11.5+) isoform expression only in a single neuron ASER. Our results provide evidence that alternative splicing regulation of a single critical gene in a single critical neuron is essential for learning ability in an organism.

Purposes: To evaluate the effects of axial length and age on the circumpapillary retinal nerve fiber layer (cpRNFL) and the inner macular parameters measured using 3 spectral-domain optical coherence tomography (OCT) instruments., Methods: A total of 102 normal eyes (1 eye per subject) were imaged using Cirrus, RTVue, and 3D-OCT. The cpRNFL and the macular retinal nerve fiber layer (mRNFL), the ganglion cell layer+inner plexiform layer (GCLIPL), and the mRNFL+GCLIPL ganglion cell complex, GCC thicknesses were analyzed. The correlations between these values and the axial length or age were evaluated using a partial correlation analysis. These correlations were corrected using the axial length-related magnification effect., Results: All but the nasal quadrant cpRNFL thicknesses and GCC thicknesses obtained using the 3 OCT instruments were significantly correlated with age. The average cpRNFL thickness and GCC thickness measured using the Cirrus and RTVue, but not by the 3D-OCT, had a negative correlation with the axial length. The temporal quadrant cpRNFL thickness measured using the 3 instruments was positively correlated with the axial length. The magnification correction made the most correlations positive., Conclusions: The average cpRNFL and GCC thicknesses measured using these 3 instruments decreased with age. The axial length affected the cpRNFL and GCC thicknesses as measured using the Cirrus and RTVue; this effect likely depended on the fundus area of analyses.

In 2006, funds were received to replicate Stanford's Chronic Disease Self-Management Program (CDSMP) among eldercare providers in Honolulu. This case study, conducted 1 year after the close of the initial 3-year replication grant, explored factors for sustaining the delivery of CDSMP, with an aim to create guidelines for cultivating sustainability. Face-to-face semi-structured interviews were conducted with one representative from each of eight eldercare agencies, with the representative specified by the agency. Representatives discussed the presence and strength (low, medium, or high) of sustainability factors, including readiness, champions, technical assistance, perceived fit of CDSMP with their agency, CDSMP modifiability, perceived benefits of CDSMP, and other. Only three of the eight agencies (38%) were still offering CDSMP by the end of 2010. Agencies who sustained CDSMP rated higher on all sustainability factors compared to those that did not sustain the program. Additional factors identified by representatives as important were funding and ongoing access to pools of elders from which to recruit program participants. When replicating evidence-based programs, sustainability factors must be consciously nurtured. For example, readiness must be cultivated, multiple champions must be developed, agencies must be helped to modify the program to best fit their clientele, evaluation findings demonstrating program benefit should be shared, and linkages to funding may be needed.

The phosphatidylinositol 3-kinase (PI3K) pathway regulates many cellular functions, but its roles in the nervous system are still poorly understood. We found that a newly discovered insulin receptor isoform, DAF-2c, is translocated from the cell body to the synaptic region of the chemosensory neuron in Caenorhabditis elegans by a conditioning stimulus that induces taste avoidance learning. This translocation is essential for learning and is dependent on the mitogen-activated protein kinase-regulated interaction of CASY-1 (the calsyntenin ortholog) and kinesin-1. The PI3K pathway is required downstream of the receptor. Light-regulated activation of PI3K in the synaptic region, but not in other parts of the cell, switched taste-attractive behavior to taste avoidance, mimicking the effect of conditioning. Thus, synaptic PI3K is crucial for the behavioral switch caused by learning., (Copyright © 2014, American Association for the Advancement of Science.)

Aims: This project tested the six-month impact of Stanford's Diabetes Self-Management Program (DSMP), adapted for Asians and Pacific Islanders (APIs), on behavioral and clinical indicators., Methods: Participants attended DSMP workshops at a community health center. Employing a one-group, pre-post-test design, data were collected at baseline and six-months. Ninety-six eligible API adults were enrolled. All attended four or more of the six weekly sessions, and 82 completed data collection. Measures included body mass index, blood pressure, blood lipids, blood glucose, HbA1c, as well as health behaviors. Data were analyzed by descriptive statistics and paired t-tests., Results: Adaptations to DSMP were minimal, but critical to the local acceptance of the program. At six-months, significant behavioral improvements included: (1) increased minutes in stretching and aerobic exercise per week (p<0.001); (2) reduced symptoms of hypoglycemia and hyperglycemia (p<0.001); (3) increased self-efficacy (p<0.001); and (4) increased number of days and times testing blood sugar levels (p<0.001). Significant clinical improvements included: (1) lower BMI (p<0.001); (2) lower HbA1c (p<0.001); (3) lower total cholesterol, triglycerides, and LDL (p<0.001); and (4) lower blood pressure (p<0.001)., Conclusions: Findings suggest that the DSMP can be successfully adapted to API populations and can improve clinical measures as well as health behaviors., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

A small-molecule fluorescent probe specific for human pluripotent stem cells would serve as a useful tool for basic cell biology research and stem cell therapy. Screening of fluorescent chemical libraries with human induced pluripotent stem cells (iPSCs) and subsequent evaluation of hit molecules identified a fluorescent compound (Kyoto probe 1 [KP-1]) that selectively labels human pluripotent stem cells. Our analyses indicated that the selectivity results primarily from a distinct expression pattern of ABC transporters in human pluripotent stem cells and from the transporter selectivity of KP-1. Expression of ABCB1 (MDR1) and ABCG2 (BCRP), both of which cause the efflux of KP-1, is repressed in human pluripotent stem cells. Although KP-1, like other pluripotent markers, is not absolutely specific for pluripotent stem cells, the identified chemical probe may be used in conjunction with other reagents., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

Health care providers are challenged to replicate evidence-based programs in their communities. These programs may be adapted to fit new communities, but the key components must be delivered with fidelity. This article describes a four-step fidelity assurance protocol developed by the Hawai'i's Healthy Aging Partnership as it adapted and replicated evidence-based health promotion programs for Hawai'i's older adults. The four steps are the following: (a) deconstruct the program into its components and prepare a step-by-step plan for program replication; (b) identify agencies ready to replicate the program, and sponsor excellent training to local staff who will deliver and coordinate it; (c) monitor the fidelity of program delivery using standardized checklists; and (d) track participant outcomes to assure achievement of expected outcomes. The protocol is illustrated with examples from Hawai'i's Healthy Aging Partnership's experience replicating EnhanceFitness, a senior exercise program. This protocol is transferrable to other communities wanting to adapt and replicate evidence-based, public health programs.

It is known that baldness caused by androgenetic alopecia is involved with androgen and the androgen receptor. Furthermore, it has been reported that testosterone secretion follows a circadian rhythm. Therefore, we hypothesized that a relationship exists between androgen-induced alopecia and biological rhythm. The mammalian circadian rhythm is controlled by several clock genes. Brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein-1 (BMAL1), one of the clock genes, is a transcription factor that plays central roles in the regulation of circadian rhythms. In this study, we investigated the influence of BMAL1 on hair follicle functions and hair growth. Mice deficient in BMAL1 expression exhibited a delay in hair regrowth after shaving. In hair follicles of mouse vibrissa, expression of Bmal1 and other clock genes was found to be rhythmic. Knockdown of BMAL1 in human follicle dermal papilla cells resulted in modulation of expression of several hair growth-related genes. Therefore, we concluded that expression of clock genes in hair follicles is linked to the circadian rhythm and that BMAL1 can regulate hair growth.

Signal-regulatory protein-α (SIRPα) is a transmembrane protein that contains tyrosine phosphorylation sites in its cytoplasmic region; two tyrosine phosphatases, SHP-1 and SHP-2, bind to these sites in a phosphorylation-dependent manner and transduce multiple intracellular signals. Recently, SIRPα was identified as one of the major tyrosine-phosphorylated proteins in the glomeruli and found to be expressed in podocytes. In the present study, we examined the role of SIRPα expression in podocytes using knockin mice (C57BL/6 background) expressing mutant SIRPα that lacks a cytoplasmic region (SIRPα-mutant mice). Light microscopic examination revealed no apparent morphological abnormalities in the kidneys of the SIRPα-mutant mice. On the other hand, electron microscopic examination revealed abnormal podocytes with irregular major processes and wider and flattened foot processes in the SIRPα-mutant mice compared with their wild-type counterparts. Significantly impaired renal functions and slight albuminuria were demonstrated in the SIRPα-mutant mice. In addition, adriamycin injection induced massive albuminuria together with focal glomerulosclerosis in the SIRPα-mutant mice, while their wild-type counterparts were resistant to adriamycin-induced nephropathy. These data demonstrate that SIRPα is involved in the regulation of podocyte structure and function as a filtration barrier under both physiological and pathological conditions.

In sexually reproducing animals, mating is essential for transmitting genetic information to the next generation and therefore animals have evolved mechanisms for optimizing the chance of successful mate location. In the soil nematode C. elegans, males approach hermaphrodites via the ascaroside pheromones, recognize hermaphrodites when their tails contact the hermaphrodites' body, and eventually mate with them. These processes are mediated by sensory signals specialized for sexual communication, but other mechanisms may also be used to optimize mate location. Here we describe associative learning whereby males use sodium chloride as a cue for hermaphrodite location. Both males and hermaphrodites normally avoid sodium chloride after associative conditioning with salt and starvation. However, we found that males become attracted to sodium chloride after conditioning with salt and starvation if hermaphrodites are present during conditioning. For this conditioning, which we call sexual conditioning, hermaphrodites are detected by males through pheromonal signaling and additional cue(s). Sex transformation experiments suggest that neuronal sex of males is essential for sexual conditioning. Altogether, these results suggest that C. elegans males integrate environmental, internal and social signals to determine the optimal strategy for mate location.

Most of the metabolic diseases of dairy cows occur within the first 2 wk after calving, and cows with a metabolic disease are prone to infectious diseases. Although metabolic diseases are generally recognized as a risk factor for infectious diseases owing to the associated decrease in immune function, the difference in immune status between cows with milk fever (MF) or displaced abomasum (DA) during the lactation period has not been clarified. Therefore, the peripheral blood leukocyte populations in 38 multiparous Holstein cows from 1 herd were analyzed after calving. The cows were divided into 3 groups according to health: 21 cows that remained clinically healthy throughout the experimental period (control group), 9 cows that had MF on the day of calving, and 8 cows with an onset of DA within 4 wk after calving. The T- and B-cell numbers were lowest at week 0, and they increased gradually after calving. There was no significant difference between the 3 groups in the number of each subset of leukocytes on the day of calving, but the number of CD8⁺ T-cells was significantly lower in the MF and DA groups than in the control group at week 1. The numbers of CD4⁺, CD8⁺, and WC1⁺ T-cells tended to be lower in the DA group than in control group from weeks 4 to 12, a tendency not observed in the MF group. These data suggest that when cows have DA around the time of calving, their lymphocyte numbers remain lower until 12 wk after calving.

Purpose: To compare the relationships of parapapillary retinal nerve fibre layer (RNFL) thickness among three spectral-domain optical coherence tomography (SD-OCT) instruments with visual field sensitivity (VFS)., Methods: One hundred and thirteen eyes of 113 Japanese subjects with glaucoma (mean deviation in standard automated perimetry = -8.9 ± 6.7 dB) were imaged by Cirrus, RTVue and 3D OCT. The average hemi-superior and hemi-inferior RNFL thicknesses were obtained. In addition, the structure-function relationship using two retinotopic maps that consisted of six or nine sectors was also evaluated. Decibel (dB) scale and 1/Lamert (1/L) were used to express VFS. RNFL thickness correlation with corresponding VFS in visual field sectors was compared among the three instruments. Background RNFL thickness (non-neuronal tissue) for each instrument was estimated using a linear regression model at 1/L = 0., Results: The correlation between the average hemi-superior and hemi-inferior RNFL thickness in the three SD-OCT instruments with corresponding VFS was similar. In the analysis of retinotopic maps, 3D OCT showed a higher correlation in superotemporal sectors than RTVue, whereas RTVue had a stronger relationship in the nasal sector than Cirrus. The background RNFL thickness extrapolated was approximately 60% that of normal eyes in all the instruments., Conclusions: The three SD-OCT showed similar overall correspondence with VFS with a partially discordant retinotopic relationship. RNFL measured with any SD-OCT devices likely contains non-neuronal tissue, comprising 60% of its thickness., (© 2013 The Authors. Acta Ophthalmologica © 2013 Acta Ophthalmologica Scandinavica Foundation.)

T helper (Th) cells play a central role in immune responses and new Th1/Th2/Th17 and regulatory T (Treg)-cell paradigm in pregnancy has developed. Progesterone (P(4)) is essential for the maintenance of pregnancy; however the effect of P(4) on Th1/Th2/Th17 and Treg paradigm is unclear in cows. We evaluated the effect of P(4) on the expression of Th1/Th2/Th17 and Treg-related cytokines, transcription factors, and P(4) receptors in the peripheral blood mononuclear cells (PBMCs) from 8 pregnant (163.1 ± 16.9 days of gestation) and 8 non-pregnant luteal phase cows. PBMCs were stimulated with P(4) at 0, 0.1, 1 or 10 μg/ml, and the mRNA expression of Th1, Th2, Th17 and Treg-related cytokines (IFN-γ, IL-4, IL-17 and TGF-β), transcription factors (T-bet, GATA-3, RORC and Foxp3) and P(4) receptors (PGR, PGRMC1 and PGRMC2) were analyzed by real time RT-PCR. In both pregnant and non-pregnant cows, P(4) significantly inhibited the expression of IFN-γ and IL-17 dose-dependently, whereas P(4) did not affect the expression of TGF-β and Foxp3. In addition, P(4) significantly decreased the expression of T-bet and RORC, and enhanced the expression of IL-4 in the pregnant cows, but this reaction was not found in the non-pregnant cows. P(4) tended to increase PGRMC1 in the pregnant cows but not in the non-pregnant cows, indicating that PGRMC1 may be involved in the regulation of the effect of P(4) during bovine pregnancy. These results indicate that P(4) is an important regulator of Th1/Th2/Th17 and Treg immunity, and higher Th2 immunity is characteristic in the pregnant cows.

Japanese Black cattle occasionally demonstrate growth retardation despite sufficient nutrient intake. To clarify hormonal and transcriptional characteristics, we investigated differences in blood components, including hormones, and differences in exhaustive gene expressions in the liver and peripheral lymphocytes of six cattle with growth retardation (GR cattle) and eight control cattle of the same age and pedigree with normal growth. Hematocrit values and concentrations of hemoglobin, serum albumin, total cholesterol, insulin-like growth factor 1 (IGF-1), thyroxine and insulin in GR cattle were significantly lower than those in controls. GR cattle also excreted higher levels of GH. We used three GR and three control cattle for a microarray analysis in the liver and found that 279 gene expressions were significantly different. However, gene expressions related to the GH-IGF-1 axis, such as the GH receptor and IGF-1, were not significantly different from those of controls. Immune-related gene expressions were significantly lower. To clarify these gene expression levels, peripheral lymphocytes were used for real-time RT-PCR. The expression rates of genes that were significantly lower in the liver, such as chemokine ligand 8, interferon gamma receptor 1 and immunoglobulin light chain VJ region were also significantly lower in three GR cattle than those in the three control cattle. These results suggest that the cause of growth retardation in the present study was due to other factors, not abnormal gene expressions of factors related to the GH-IGF-1 axis in the liver, and that GR cattle were susceptible to infectious disease.

Alprostadil (lipo-PGE1) is a drug delivery system preparation. This preparation is applied to treat refractory skin ulcers and arteriosclerosis obliterans. We investigated the effects of alprostadil by using the earflap ischemic model. The following results were obtained: 1) Treatment with alprostadil significantly increased the VEGF contents in an ischemic ear; 2) Treatment with alprostadil resulted in strongly expressed VEGF levels only in the ischemic region; 3) Image analysis revealed a significant increase in the number of vessel bypasses and paths after flap creation with alprostadil administration compared to the vehicle-treated ears. The results suggest that it may be possible to apply alprostadil as one device for regenerative medical technology.

The loading of antigenic peptides onto major histocompatibility complex class I (MHC I) molecules is an essential step in the adaptive immune response against virally or malignantly transformed cells. The ER-resident peptide-loading complex (PLC) consists of the transporter associated with antigen processing (TAP1 and TAP2), assembled with the auxiliary factors tapasin and MHC I. Here, we demonstrated that the N-terminal extension of each TAP subunit represents an autonomous domain, named TMD(0), which is correctly targeted to and inserted into the ER membrane. In the absence of coreTAP, each TMD(0) recruits tapasin in a 1:1 stoichiometry. Although the TMD(0)s lack known ER retention/retrieval signals, they are localized to the ER membrane even in tapasin-deficient cells. We conclude that the TMD(0)s of TAP form autonomous interaction hubs linking antigen translocation into the ER with peptide loading onto MHC I, hence ensuring a major function in the integrity of the antigen-processing machinery.

Backgrounds/aims: To evaluate the agreement of parapapillary retinal nerve fibre layer (RNFL) thickness among three spectral-domain optical coherence tomography (OCT) instruments., Methods: Two hundred and three glaucomatous eyes and 88 normal eyes were imaged by Cirrus, RTVue and 3D OCT. The average and the four quadrant RNFL thicknesses were evaluated. Agreement among RNFL measurements was evaluated using Bland-Altman analysis and linear regression analysis. The percentage of each quadrant in the average RNFL thickness value was compared among the three instruments., Results: Cirrus showed significantly smaller thickness values than RTVue (difference=8.8 μm, p<0.0001) and 3D OCT (difference=8.1 μm, p<0.0001). Although RNFL measurements among the instruments were highly correlated, the Bland-Altman analysis revealed proportional biases for most of the pair-wise agreements. Additionally, 3D OCT showed strong proportional biases with RTVue and 3D OCT. RTVue had a smaller occupied proportion of nasal quadrants (30.2%) and a larger proportion of inferior quadrants (32.4%) compared with Cirrus and 3D OCT., Conclusions: RNFL measurements among the instruments were well correlated but had different values for thickness. The measurement circle of RTVue might be more superior-temporally located compared with the other instruments. Differences in the measurement protocols might be affected by the disagreements. These instruments should not be used interchangeably.

Escherichia coli(E. coli) isolated from the uterus of a Thoroughbred mare with bacterial endometritis was used to evaluate the effect of progesterone (P(4)) on the immune response of mares. Peripheral blood mononuclear cells (PBMCs) were collected from 10 nonpregnant clinically healthy adult mares (range, 4-12 years) during diestrus, four Thoroughbreds and six Hokkaido native horses. Cell proliferation and expression of cytokine mRNA, including interferon (IFN)-γ, tumor necrosis factor (TNF)-α and interleukin (IL)-10, of PBMCs stimulated with E. coli and P(4) were examined in vitro. P(4) was shown to have significantly inhibited E. coli induced proliferation and expression of IFN-γ in PBMCs. These results indicate that P(4) inhibits the immune response to E. coli in mares.

Purpose of the Study: Stanford's Chronic Disease Self-Management Program (CDSMP) has been proven to increase patients' ability to manage distress. We describe how we replicated CDSMP in Asian and Pacific Islander (API) communities., Design and Methods: We used the "track changes" tool to deconstruct CDSMP into its various components (e.g., recruitment and staffing) and the "adaptation traffic light" to identify allowable modifications to the original program. We monitored local leaders' fidelity of delivery of CDSMP and tracked participants' attendance, satisfaction, and 6-month outcomes., Results: Between July 2007 and February 2010, 584 completed a CDSMP workshop. Baseline and 6-month data were available for 422 (72%), including 53 Caucasians, 177 Asians, and 194 Pacific Islanders. All 3 groups realized significant decreases in social and role activity limitations and significant increases in communication with physicians. Asians and Pacific Islanders also realized significant increases in self-rated health and time spent engaging in stretching/strengthening exercise. Asians also reported significant reductions in health distress and self-reported physician visits and increases in time spent in aerobic exercise, ability to cope with symptoms, and self-efficacy., Implications: Our experience suggests that CDSMP can be modified for increased cultural appropriateness for API communities while maintaining the key components responsible for behavior change.

In this study, we studied the relationship between fracture patterns and motor function recovery in 70 consecutive patients with cervical spinal cord injury. Fractures were categorized into 6 fracture types and subdivided into stages according to the Allen-Ferguson classification system:compressive flexion (CF), distractive flexion (DF), compressive extension (CE), distractive extension (DE), vertical compression (VC) and lateral flexion (LF). Paralysis was evaluated using the American Spinal Injury Association (ASIA) impairment scale at the time of injury and 3 months afterwards. The residual rate of complete motor palsy (ASIA grade A or B) at the final examination was higher in those patients with DE fractures than those with CF, DF or CE. The final outcomes were as follows. Of the 14 patients who were classified with CF fractures, residual palsy was frequently seen in patients who had stage 5 injury. Of the 27 patients with DF fractures, residual palsy occurred in about half of the patients who had stage 4 or 5 injury. Of the 18 patients with CE fractures, residual palsy occurred in half of the patients with stage 3 injury or higher. Finally, of the 7 patients with DE fractures, the rate of residual palsy was high even for the stage 1 and 2 cases;indeed, all DE patients who had complete motor palsy at the first examination had residual palsy at the final examination. Accordingly, we conclude that motor recovery may be related to fracture pattern.

Rare coding variants of ATP-binding cassette protein A13 (ABCA13) contribute to the risk of neurological disorders, but little is known about the physiological function of ABCA13 and how single nucleotide polymorphisms (SNPs) affect it. Here, we examined the effects of neurological disorder-related SNPs ABCA13, T4031A and R4843C in the context of ABCA1, and found that the former SNP (T1088A in ABCA1) severely impaired the ABCA1 functions of apolipoprotein A-I (apoA-I) binding and cholesterol efflux. The antibody against mouse ABCA13 reacted with neurons in the cerebral cortex, hippocampus, and cerebellum. These results suggest that the T4031A replacement affects the function of ABCA13 in the brain.

Somatic (adult) stem cells are thought to have pluripotency, just as do embryotic stem (ES) cells. We investigated the possibility that grafted epithelial keratinocytes could induce spinal cord regeneration in an animal model of spinal cord injury (SCI). Normal human keratinocytes were cultured by the routine technique, and normal human dermal fibroblasts were cultured by a similar method as a control group. SCI model was prepared by dropping a 10-g weight onto the exposed spinal cord of rats from a height of 25 mm, and 8 days later, the cultured cells were grafted into the injury site. Motor function was significantly improved in the cultured-keratinocyte-grafted group compared with that in the fibroblast-grafted group. After functional observation, human nestin- and nuclei-positive cells were found at the grafted spinal cord. Grafted cultured keratinocytes induced in vitro morphological changes in the neural induction medium. These results indicated one possibility that some of the grafted cultured keratinocytes survived and could have contributed to neural regeneration. On the other hand, it should be noted that the grafted cultured keratinocytes secreted a large amount of enzymes and/or growth factors. Therefore, another possibility is that the grafted-keratinocyte-derived factors could induce survived cell growth and endogenous neural differentiation of spinal-nerve-derived stem cells surrounding the injured spinal cord, leading to functional recovery. Epithelial stem cell therapy may be applied clinically in the near future to treat SCI.

Enteral tube feeding is widely used to maintain nutrition for elderly adults with eating difficulties, but its long-term use alters the environment of the oral ecosystem. This study characterized the tongue microbiota of tube-fed elderly adults by analyzing the 16S rRNA gene. The terminal restriction fragment length polymorphism (T-RFLP) profiles of 44 tube-fed subjects were compared with those of 54 subjects fed orally (average age, 86.4 ± 6.9 years). Bar-coded pyrosequencing data were also obtained for a subset of the subjects from each group (15 tube-fed subjects and 16 subjects fed orally). The T-RFLP profiles demonstrated that the microbiota of the tube-fed subjects was distinct from that of the subjects fed orally (permutational multivariate analysis of variance [perMANOVA], P < 0.001). The pyrosequencing data revealed that 22 bacterial genera, including Corynebacterium, Peptostreptococcus, and Fusobacterium, were significantly more predominant in tube-fed subjects, whereas the dominant genera in the subjects fed orally, such as Streptococcus and Veillonella, were present in much lower proportions. Opportunistic pathogens rarely detected in the normal oral microbiota, such as Corynebacterium striatum and Streptococcus agalactiae, were often found in high proportions in tube-fed subjects. The oral indigenous microbiota is disrupted by the use of enteral feeding, allowing health-threatening bacteria to thrive.

The ATP-binding cassette protein A1 (ABCA1) mediates the secretion of cellular-free cholesterol and phospholipids to an extracellular acceptor, apolipoprotein A-I, to form high-density lipoprotein. Because ABCA1 is a key factor in cholesterol homeostasis, elaborate transcriptional and post-transcriptional regulations of ABCA1 have evolved to maintain cholesterol homeostasis. Recent studies suggest that ABCA1 moves lipids not only between membranes but also within membranes to organize and reorganize membrane meso-domains to modulate cell proliferation and immunity., (© 2011 The Authors Journal compilation © 2011 FEBS.)

Quantification of neuronal plasticity in a living animal is essential for understanding learning and memory. Caenorhabditis elegans shows a chemotactic behavior toward NaCl. However, it learns to avoid NaCl after prolonged exposure to NaCl under starvation conditions, which is called salt chemotaxis learning. Insulin-like signaling is important for this behavioral plasticity and functions in one of the salt-sensing sensory neurons, ASE right (ASER). However, how neurons including ASER show neuronal plasticity is unknown. To determine the neuronal plasticity related to salt chemotaxis learning, we measured Ca(2+) response and synaptic release of individual neurons by using in vivo imaging techniques. We found that response of ASER increased whereas its synaptic release decreased after prolonged exposure to NaCl without food. These changes in the opposite directions were abolished in insulin-like signaling mutants, suggesting that insulin-like signaling regulates these plasticities in ASER. The response of one of the downstream interneurons, AIB, decreased profoundly after NaCl conditioning. This alteration in AIB response was independent of the insulin-like signaling pathway. Our results suggest that information on NaCl is modulated at the level of both sensory neurons and interneurons in salt chemotaxis learning.

The elderly consume a disproportionate amount of health care resources, and the recent trend in obesity will only escalate costs. EnhanceFitness® (EF) is an exercise program designed to increase the strength, flexibility, and balance of older adults. A comprehensive controlled study in Washington state of an elderly population has shown that participants who attend at least one EF class per week reduce healthcare costs by 20% per year. The present study reports the costs and potential benefits of replicating EF on Kaua'i. For Kaua'i the annual cost of an EF pilot program for 132 clients would be $204,735. Attendance records of the Kaua'i program showed that 96 (73%) of those enrolled attended at least weekly. Based on national reports of healthcare costs for the elderly, averting 20% of the costs for these 96 elderly would save $344,256 per year. The expected investment to return ratio, I-R ratio, for EF on Kaua'i is about 1-1.8. On economic grounds, a case can be made to support and expand these types of programs. In these times of budget cuts, cost-benefit analysis provides a common economic "language" to prioritize among different programs.

Aim: Transforming growth factor-β (TGF-β) is involved in renal tubulointerstitial fibrosis. Recently, the ubiquitin proteasome system was shown to participate in the TGF-β signalling pathway. The aim of this study was to examine the effects of proteasome inhibitors on TGF-β-induced transformation of renal fibroblasts and tubular epithelial cells in vitro and on unilateral ureteral obstruction (UUO) in vivo., Methods: Rat renal fibroblasts NRK-49F cells and tubular epithelial cells, NRK-52E, were treated with TGF-β in the presence or absence of a proteasome inhibitor, MG132 or lactacystin. Rats were subjected to UUO and received MG132 i.p. for 7 days., Results: In cultured renal cells, both MG132 and lactacystin inhibited TGF-β-induced α-smooth muscle actin (α-SMA) protein expression according to both western blotting and immunofluorescent study results. MG132 also suppressed TGF-β-induced mRNA expression of α-SMA and upregulation of Smad-response element reporter activity. However, MG132 did not inhibit TGF-β-induced phosphorylation and nuclear translocation of Smad2. In contrast, MG132 increased the protein level of Smad co-repressor SnoN, demonstrating that SnoN is one of the target molecules by which MG132 blocks the TGF-β signalling pathway. Although the proteasome inhibitor suppressed TGF-β-induced transformation of cultured fibroblasts and tubular epithelial cells, MG132 treatment did not ameliorate tubulointerstitial fibrosis in the rat UUO model., Conclusion: Proteasome inhibitors attenuate TGF-β signalling by blocking Smad signal transduction in vitro, but do not inhibit renal interstitial fibrosis in vivo., (© 2011 The Authors. Nephrology © 2011 Asian Pacific Society of Nephrology.)

Animals search for foods and decide their behaviors according to previous experience. Caenorhabditis elegans detects chemicals with a limited number of sensory neurons, allowing us to dissect roles of each neuron for innate and learned behaviors. C. elegans is attracted to salt after exposure to the salt (NaCl) with food. In contrast, it learns to avoid the salt after exposure to the salt without food. In salt-attraction behavior, it is known that the ASE taste sensory neurons (ASEL and ASER) play a major role. However, little is known about mechanisms for learned salt avoidance. Here, through dissecting contributions of ASE neurons for salt chemotaxis, we show that both ASEL and ASER generate salt chemotaxis plasticity. In ASER, we have previously shown that the insulin/PI 3-kinase signaling acts for starvation-induced salt chemotaxis plasticity. This study shows that the PI 3-kinase signaling promotes aversive drive of ASER but not of ASEL. Furthermore, the Gq signaling pathway composed of Gqα EGL-30, diacylglycerol, and nPKC (novel protein kinase C) TTX-4 promotes attractive drive of ASER but not of ASEL. A putative salt receptor GCY-22 guanylyl cyclase is required in ASER for both salt attraction and avoidance. Our results suggest that ASEL and ASER use distinct molecular mechanisms to regulate salt chemotaxis plasticity.

We used a navigation system to insert 128 pedicle screws into 69 vertebrae (L1 to L3) of 49 consecutive patients. We assessed the pedicle isthmic width and the permission angle for pedicle screw insertion. The permission angle is the angle defined by the greatest medial and lateral trajectories allowable when placing the screw through the center of the pedicle. The rate of narrow-width pedicles (isthmic width less than 5 mm) was 5 of 60 pedicles (8%) at L1, 4 of 60 pedicles (7%) at L2, and none (0%) at L3, L4 and L5. The rate of narrow-angle pedicles (a permission angle less than 15 degrees) was 21 of 60 pedicles (35%) at L1, 7 of 60 (12%) at L2, 3 of 60 (5%) at L3, and none (0%) at L4 and L5. Of 128 pedicle screws inserted into 69 vertebrae from L1 to L3, 125 (97.7%) were classified as Grade 1 (no pedicle perforation). In general, the upper lumbar vertebrae have more narrow-width and -angle pedicles. However, we could reduce the rate of pedicle screw misplacement in upper lumbar vertebra using a three-dimensional fluoroscopy and navigation system.