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1.
Sci Rep ; 14(1): 5271, 2024 03 04.
Article in English | MEDLINE | ID: mdl-38438511

ABSTRACT

Drinking water contaminated by pathogenic micro-organisms increases the risk of infectious gastrointestinal disease which could potentially lead to acute kidney injury and even death, particularly amongst the young and the elderly. Earlier studies have shown a substantial reduction in the incidence of diarrheal disease over a period of one year using a polysulfone membrane water gravity-powered water filtration device. The current report is a continuation of these studies to assess the long-term effects of the innovative method on diarrheal incidence rates over a 4-year follow-up period. This follow-up study monitored the trend of self-reported diarrheal events in all households in the previously studied villages for 5 months, in the last half of each study year, using the same questionnaire utilized in the earlier study. Three villages that had no device yet installed served as controls. We computed monthly diarrheal incidence rates for all study years (standardized to per 100 person-months) and compared these to the pre-device incidence rate in 2018 and in the control group, using the Wilcoxon rank sum exact test. The average diarrheal incidence rates of 1.5 p100pm in 2019, 2.19 p100pm in 2021, and 0.54p100pm in 2022 were significantly different from an earlier study that reported 17.8 p100pm rates before the devices were installed in 2018, (all p-values < 0.05). Concomitantly, self-reported diarrheal infections were substantially higher in the "control villages" not yet having the filtration device installed (80.9, 77.6, and 21.5 per 100 pm). The consistent and large reduction in diarrhea incidence documents the long-term efficacy of the use of the membrane filtration device. This simple water purification method using gravity flow improves public health in remote regions with limited resources.


Subject(s)
Diarrhea , Water , Aged , Humans , Ghana/epidemiology , Follow-Up Studies , Diarrhea/epidemiology , Diarrhea/prevention & control , Self Report
2.
J Orthop Res ; 42(6): 1170-1179, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38245849

ABSTRACT

A common animal model of muscle pathology following rotator cuff tear (RCT) is a tenotomy of the supraspinatus and infraspinatus, often combined with neurotomy of the suprascapular nerve, which induces a more robust atrophy response than tenotomy alone. However, the utility of this model depends on its similarity to human muscle pathology post-RCT, both in terms of the disease phenotype and mechanisms of muscle atrophy and fatty infiltration. Given the clinical prevalence of nerve injury is low and the muscular response to denervation is distinct from mechanical unloading in other models, an understanding of the biological influence of the nerve injury is critical for interpreting data from this RCT model. We evaluated the individual and combined effect of tenotomy and neurotomy across multiple biological scales, in a robust time-series in the mouse supraspinatus. Muscle composition, histological, and gene expression data related to muscle atrophy, degeneration-regeneration, fatty infiltration, and fibrosis were evaluated. Broadly, we found tenotomy alone caused small, transient changes in these pathological features, which resolved over the course of the study, while neurotomy alone caused a significant fatty atrophy phenotype. The dual injury group had a similar fatty atrophy phenotype to the neurotomy group, though the addition of tenotomy did marginally enhance the fat and connective tissue. Overall, these results suggest the most clinically relevant injury model, tenotomy alone, does not produce a clinically relevant phenotype. The dual injury model partially recapitulates the human condition, but it does so through a nerve injury, which is not well justified clinically.


Subject(s)
Disease Models, Animal , Mice, Inbred C57BL , Muscular Atrophy , Rotator Cuff Injuries , Tenotomy , Animals , Rotator Cuff Injuries/surgery , Rotator Cuff Injuries/pathology , Muscular Atrophy/etiology , Rotator Cuff/surgery , Rotator Cuff/pathology , Rotator Cuff/innervation , Male , Mice
3.
Brain Sci ; 13(8)2023 Aug 18.
Article in English | MEDLINE | ID: mdl-37626574

ABSTRACT

Metabolic syndrome (MetS), which includes obesity, diabetes, hypertension, hyperlipidemia, and fatty-liver disease, affects more than two-thirds of the U.S. population. Surgical weight loss has been popularized in the last several decades as a means to produce significant weight loss and improvements in the comorbidities of MetS. Women are by far the most common recipients of these surgeries (more than 85%). Women of childbearing age are very likely to pursue surgical weight loss to improve their reproductive function and fertility for childbearing purposes. Significant research using pre-clinical models from our laboratory and clinical data from around the world suggest that surgical weight loss before pregnancy may have negative consequences for offspring. The present study investigates the metabolic endpoints in female-rodent offspring born to dams who had previously received vertical sleeve gastrectomy (VSG) before pregnancy. Comparisons were made to offspring from lean and obese dams. In the adult offspring of either maternal VSG or sham surgery, no differences in body weight, body fat, or lean body mass between groups were identified. The blood pressure measured in a subset of female offspring showed no differences between the VSG and the sham groups. Estrus cyclicity measured by lavage on serial days showed altered cycles in the VSG offspring compared to the controls. For animals that had previously only been exposed to chow, rats were fasted overnight and then given a 1 g meal of either chow or a novel high-fat diet (HFD). The animals were euthanized and paraformaldehyde (PFA)-perfused to perform brain immunohistochemistry for c-Fos, an immediate-early gene activated by novel stimuli. In the VSG rats exposed to either the chow or the HFD meal, the c-Fos-activated cells were significantly blunted in the nucleus of the solitary tract (p < 0.05), the paraventricular nucleus of the hypothalamus (PVN) (p < 0.05), and the dorsal medial nucleus of the hypothalamus (DMH) (p < 0.05) in comparison to the sham controls. These data suggest that the hypothalamic wiring within the brain that controls the response to nutrients and reproductive function was significantly altered in the VSG offspring compared to the offspring of the dams that did not receive weight-loss surgery.

4.
J Neurotrauma ; 40(11-12): 1216-1227, 2023 06.
Article in English | MEDLINE | ID: mdl-36680746

ABSTRACT

Abstract Traumatic brain injury (TBI) is one of the leading causes of death for children in the United States. Juveniles are more likely to sustain TBIs than most other age groups, and TBI has been shown to result in increased anxiety and stress behaviors. In addition, the hypothalamic-pituitary-adrenal (HPA) axis has previously been shown to become dysregulated after a TBI. Further, many children consume diets high in saturated fats and refined sugars, which are also connected to alterations in HPA axis function and behavior disorders. The goal of the current study was to identify a potential relationship between high-fat diet (HFD) consumption and TBI on HPA axis function in juvenile rats. In the present study, male juvenile Long-Evans rats were fed either a combination of an HFD with a high-fructose corn syrup solution or a standard chow diet. On post-natal Day 30, subjects sustained either a sham TBI or a TBI via the Closed-Head Injury Model of Engineered Rotational Acceleration (CHIMERA). Subjects participated in a trial of the open field test (OFT) following injury. In addition, some rats performed in an acute restraint stress test. All subjects were euthanized 7 days post-injury. Brain and blood plasma samples were collected for use in real-time polymerase chain reaction (RT-PCR), immunohistochemistry, and corticosterone or adrenocorticotropic hormone (ACTH) assays. Immediately following TBI, injured juveniles had increased time to righting and walking, with HFD-fed TBI rats having increased time to walking over Chow-fed TBI rats. HFD-fed TBI rats had a reduced number of entries to the center of the OFT, in addition to reduced time spent in the center compared with HFD Sham controls and Chow TBI rats. During the acute restraint stress test, HFD-fed TBI rats had elevated pre-stress ACTH and corticosterone and post-stress ACTH levels. Pre-stress ACTH levels were significantly elevated in HFD TBI compared with Chow TBI. Further, pre-stress ACTH:corticosterone ratios were elevated in HFD TBI compared with Chow TBI. cFos immunoreactivity in the paraventricular nucleus (PVN) of the hypothalamus following the acute restraint stress test was elevated in HFD-fed TBI rats. HFD TBI rats had greater activation of cFos in the PVN compared with Chow TBI. In addition, RT-PCR showed significantly reduced expression of relevant HPA axis genes, NR3C1, NR3C2, and CRHR2, in the hypothalamus of TBI subjects compared with Sham subjects. Further, AVP and CRHR2 in the hypothalamus were significantly reduced in HFD TBI compared with Chow TBI. These results offer evidence that TBI paired with high-fat diet consumption can cause HPA axis dysfunction, resulting in more anxiety-like behaviors.


Subject(s)
Brain Injuries, Traumatic , Diet, High-Fat , Rats , Male , Animals , Diet, High-Fat/adverse effects , Hypothalamo-Hypophyseal System/metabolism , Corticosterone , Rats, Long-Evans , Pituitary-Adrenal System , Adrenocorticotropic Hormone , Brain Injuries, Traumatic/metabolism
5.
J Orthop Res ; 40(5): 1016-1025, 2022 05.
Article in English | MEDLINE | ID: mdl-34392563

ABSTRACT

Rotator cuff (RC) tears present a treatment challenge due to muscle atrophy and degeneration, fatty infiltration, and fibrosis. The purpose of this study was to generate a high time-resolution model of RC tear in rabbits and to characterize the progression of architectural and histological changes. Thirty-five female New Zealand White rabbits (age: 6 months) underwent left supraspinatus tenotomy. Five rabbits were used to evaluate immediate muscle architectural changes. The remaining 30 rabbits underwent right shoulder sham surgery and sacrifice at 1, 2, 4, 8, or 16 weeks. Histology was used to quantify muscle fiber cross-sectional area (CSA), muscle degeneration and regeneration, and fat localized to inter- versus intrafascicular regions. Muscle fiber CSA decreased by 26.5% compared to sham at 16 weeks (effect of treatment, p < 0.0001). Muscle degeneration increased after tenotomy (effect of treatment, p = 0.0006) without any change in regeneration. Collagen and fat content increased by 4 weeks and persisted through 16 weeks. Interfascicular fat was increased at all time points, but intrafascicular fat was increased only at 1, 4, and 16 weeks posttenotomy. Intrafascicular fat adjacent to degenerating muscle fibers increased as well (effect of treatment, p < 0.0001; effect of time, p = 0.0102). Statement of clinical relevance: Rabbit supraspinatus tenotomy recapitulates key features of the pathophysiology of human RC tears, including muscle atrophy and degeneration, lack of regeneration, fat accumulation, and fibrosis.


Subject(s)
Rotator Cuff Injuries , Adipose Tissue/pathology , Animals , Female , Fibrosis , Muscular Atrophy/pathology , Rabbits , Rotator Cuff/pathology , Rotator Cuff Injuries/pathology
6.
Neural Dev ; 15(1): 11, 2020 08 02.
Article in English | MEDLINE | ID: mdl-32741370

ABSTRACT

Synapses are the sites of neuron-to-neuron communication and form the basis of the neural circuits that underlie all animal cognition and behavior. Chemical synapses are specialized asymmetric junctions between a presynaptic neuron and a postsynaptic target that form through a series of diverse cellular and subcellular events under the control of complex signaling networks. Once established, the synapse facilitates neurotransmission by mediating the organization and fusion of synaptic vesicles and must also retain the ability to undergo plastic changes. In recent years, synaptic genes have been implicated in a wide array of neurodevelopmental disorders; the individual and societal burdens imposed by these disorders, as well as the lack of effective therapies, motivates continued work on fundamental synapse biology. The properties and functions of the nervous system are remarkably conserved across animal phyla, and many insights into the synapses of the vertebrate central nervous system have been derived from studies of invertebrate models. A prominent model synapse is the Drosophila melanogaster larval neuromuscular junction, which bears striking similarities to the glutamatergic synapses of the vertebrate brain and spine; further advantages include the simplicity and experimental versatility of the fly, as well as its century-long history as a model organism. Here, we survey findings on the major events in synaptogenesis, including target specification, morphogenesis, and the assembly and maturation of synaptic specializations, with a emphasis on work conducted at the Drosophila neuromuscular junction.


Subject(s)
Drosophila Proteins/genetics , Drosophila melanogaster/growth & development , Gene Expression Regulation/genetics , Neuromuscular Junction/growth & development , Synapses/physiology , Animals
7.
Sci Rep ; 10(1): 11101, 2020 07 06.
Article in English | MEDLINE | ID: mdl-32632178

ABSTRACT

In rural regions with limited resources, the provision of clean water remains challenging. The resulting high incidence of diarrhea can lead to acute kidney injury and death, particularly in the young and the old. Membrane filtration using recycled hemodialyzers allows water purification. This study quantifies the public health effects. Between 02/2018 and 12/2018, 4 villages in rural Ghana were provided with a high-volume membrane filtration device (NuFiltration). Household surveys were collected monthly with approval from Ghana Health Services. Incidence rates of diarrhea for 5-month periods before and after implementation of the device were collected and compared to corresponding rates in 4 neighboring villages not yet equipped. Data of 1,130 villagers over 10 months from the studied communities were studied. Incidence rates showed a decline following the implementation of the device from 0.18 to 0.05 cases per person-month (ppm) compared to the control villages (0.11 to 0.08 ppm). The rate ratio of 0.27 for the study villages is revised to 0.38 when considering the non-significant rate reduction in the control villages. Provision of a repurposed hemodialyzer membrane filtration device markedly improves health outcomes as measured by diarrhea incidence within rural communities.


Subject(s)
Diarrhea/prevention & control , Health Services/statistics & numerical data , Hemodiafiltration/instrumentation , Hemodiafiltration/methods , Public Health , Rural Population/statistics & numerical data , Water Purification/methods , Adolescent , Adult , Child , Child, Preschool , Developing Countries , Diarrhea/epidemiology , Female , Ghana/epidemiology , Humans , Incidence , Kidneys, Artificial/statistics & numerical data , Male , Membranes, Artificial , Middle Aged , Recycling , Young Adult
8.
IEEE Trans Vis Comput Graph ; 26(1): 492-502, 2020 01.
Article in English | MEDLINE | ID: mdl-31403430

ABSTRACT

We introduce Artifact-Based Rendering (ABR), a framework of tools, algorithms, and processes that makes it possible to produce real, data-driven 3D scientific visualizations with a visual language derived entirely from colors, lines, textures, and forms created using traditional physical media or found in nature. A theory and process for ABR is presented to address three current needs: (i) designing better visualizations by making it possible for non-programmers to rapidly design and critique many alternative data-to-visual mappings; (ii) expanding the visual vocabulary used in scientific visualizations to depict increasingly complex multivariate data; (iii) bringing a more engaging, natural, and human-relatable handcrafted aesthetic to data visualization. New tools and algorithms to support ABR include front-end applets for constructing artifact-based colormaps, optimizing 3D scanned meshes for use in data visualization, and synthesizing textures from artifacts. These are complemented by an interactive rendering engine with custom algorithms and interfaces that demonstrate multiple new visual styles for depicting point, line, surface, and volume data. A within-the-research-team design study provides early evidence of the shift in visualization design processes that ABR is believed to enable when compared to traditional scientific visualization systems. Qualitative user feedback on applications to climate science and brain imaging support the utility of ABR for scientific discovery and public communication.


Subject(s)
Computer Graphics , Imaging, Three-Dimensional/methods , Algorithms , Artifacts , Brain/diagnostic imaging , Gulf of Mexico , Humans , Seaweed , Software
9.
Cytoskeleton (Hoboken) ; 77(1-2): 4-15, 2020 01.
Article in English | MEDLINE | ID: mdl-31702858

ABSTRACT

Regulation of the synaptic cytoskeleton is essential to proper neuronal development and wiring. Perturbations in neuronal microtubules (MTs) are associated with numerous pathologies, yet it remains unclear how changes in MTs may be coupled to synapse morphogenesis. Studies have identified many MT regulators that promote synapse growth. However, less is known about the factors that restrict growth, despite the potential links of synaptic overgrowth to severe neurological conditions. Here, we report that dTACC, which is implicated in MT assembly and stability, prevents synapse overgrowth at the Drosophila neuromuscular junction by restricting addition of new boutons throughout larval development. dTACC localizes to the axonal MT lattice and is required to maintain tubulin levels and the integrity of higher-order MT structures in motor axon terminals. While previous reports have demonstrated the roles of MT-stabilizing proteins in promoting synapse growth, our findings suggest that in certain contexts, MT stabilization may correlate with restricted growth.


Subject(s)
Drosophila Proteins/metabolism , Microtubule-Associated Proteins/metabolism , Microtubules/metabolism , Neuromuscular Junction/metabolism , Animals , Drosophila
10.
BMC Musculoskelet Disord ; 20(1): 290, 2019 Jun 18.
Article in English | MEDLINE | ID: mdl-31208400

ABSTRACT

BACKGROUND: Muscle atrophy and fatty infiltration of the lumbar extensors is associated with LBP. Exercise-based rehabilitation targets strengthening these muscles, but few studies show consistent changes in muscle quality with standard-of-care rehabilitation. The goal of this study was to assess the effect of high-intensity resistance exercise on lumbar extensor muscle size (cross sectional area) and quality (fat fraction) in individuals with low back pain (LBP). METHODS: Fourteen patients with LBP were recruited from a local rehabilitation clinic. Patients underwent MRI scanning before and after a standardized 10-week high-intensity machine-based, resistance exercise program. Patient pain, disability, anxiety/depression, satisfaction, strength, and range of motion was compared pre- and post-rehabilitation using analysis of covariance (covariates: age, gender). Exercise-induced changes in MRI, and patient functional outcome measures were correlated using Pearson's correlation test. RESULTS: No significant differences were found in muscle size or fatty infiltration of the lumbar extensors over the course of rehabilitation (p > 0.31). However, patients reported reduced pain (p = 0.002) and were stronger (p = 0.03) at the conclusion of the program. Improvements in muscle size and quality for both multifidus and erector spinae correlated with improvements in disability, anxiety/depression, and strength. CONCLUSION: While average muscle size and fatty infiltration levels did not change with high-intensity exercise, the results suggest that a subgroup of patients who demonstrate improvements in muscle health demonstrate the largest functional improvements. Future research is needed to identify which patients are most likely to respond to this type of treatment.


Subject(s)
Exercise Therapy/methods , Low Back Pain/therapy , Muscular Atrophy/therapy , Paraspinal Muscles/physiopathology , Resistance Training , Adult , Aged , Cohort Studies , Female , Humans , Low Back Pain/etiology , Magnetic Resonance Imaging , Male , Middle Aged , Muscular Atrophy/complications , Muscular Atrophy/physiopathology , Paraspinal Muscles/diagnostic imaging , Standard of Care , Treatment Outcome
11.
Front Robot AI ; 6: 61, 2019.
Article in English | MEDLINE | ID: mdl-33501076

ABSTRACT

We present Bento Box, a virtual reality data visualization technique and bimanual 3D user interface for exploratory analysis of 4D data ensembles. Bento Box helps scientists and engineers make detailed comparative judgments about multiple time-varying data instances that make up a data ensemble (e.g., a group of 10 parameterized simulation runs). The approach is to present an organized set of complementary volume visualizations juxtaposed in a grid arrangement, where each column visualizes a single data instance and each row provides a new view of the volume from a different perspective and/or scale. A novel bimanual interface enables users to select a sub-volume of interest to create a new row on-the-fly, scrub through time, and quickly navigate through the resulting virtual "bento box." The technique is evaluated through a real-world case study, supporting a team of medical device engineers and computational scientists using in-silico testing (supercomputer simulations) to redesign cardiac leads. The engineers confirmed hypotheses and developed new insights using a Bento Box visualization. An evaluation of the technical performance demonstrates that the proposed combination of data sampling strategies and clipped volume rendering is successful in displaying a juxtaposed visualization of fluid-structure-interaction simulation data (39 GB of raw data) at interactive VR frame rates.

12.
Zebrafish ; 15(6): 652-655, 2018 12.
Article in English | MEDLINE | ID: mdl-30183545

ABSTRACT

Zebrafish and other aquatic organisms depend on careful monitoring and adjustment of water quality for health and survival. This ideally includes continuous monitoring of several water parameters, including temperature, pH, conductivity, and dissolved oxygen. However, manual readings can be laborious, and commercially available monitors are cost-prohibitive for many installations, especially in small laboratories and classrooms. To address these issues, we have created ZeMo, a high-end open-source water monitoring system that includes a touchscreen, web interface, and email alerts-making continuous water quality monitoring attainable for a wide range of aquarium installations.


Subject(s)
Animal Welfare , Aquaculture/methods , Oxygen/analysis , Water Pollutants, Chemical/analysis , Water Quality , Web Browser , Zebrafish/physiology , Animals , Aquaculture/instrumentation , Environmental Monitoring
13.
BMC Musculoskelet Disord ; 19(1): 135, 2018 May 07.
Article in English | MEDLINE | ID: mdl-29734942

ABSTRACT

BACKGROUND: Magnetic Resonance Imaging (MRI) is commonly used to assess the health of the lumbar spine and supporting structures. Studies have suggested that fatty infiltration of the posterior lumbar muscles is important in predicting responses to treatment for low back pain. However, methodological differences exist in defining the region of interest (ROI) of a muscle, which limits the ability to compare data between studies. The purpose of this study was to determine reliability and systematic differences within and between two commonly utilized methodologies for ROI definitions of lumbar paraspinal muscle. METHODS: T2-weighted MRIs of the mid-L4 vertebrae from 37 patients with low back pain who were scheduled for lumbar spine surgery were included from a hospital database. Fatty infiltration for these patients ranged from low to high, based on Kjaer criteria. Two methods were used to define ROI: 1) segmentation of the multifidus and erector spinae based on fascial planes including epimuscular fat, and 2) segmentation of the multifidus and erector spinae based on visible muscle boundaries, which did not include epimuscular fat. Total cross sectional area (tCSA), fat signal fraction (FSF), muscle cross sectional area, and fat cross sectional area were measured. Degree of agreement between raters for each parameter was assessed using intra-class correlation coefficients (ICC) and area fraction of overlapping voxels. RESULTS: Excellent inter-rater agreement (ICC > 0.75) was observed for all measures for both methods. There was no significant difference between area fraction overlap of ROIs between methods. Method 1 demonstrated a greater tCSA for both the erector spinae (14-15%, p < 0.001) and multifidus (4%, p < 0.016) but a greater FSF only for the erector spinae (11-13%, p < 0.001). CONCLUSION: The two methods of defining lumbar spine muscle ROIs demonstrated excellent inter-rater reliability, although significant differences exist as method 1 showed larger CSA and FSF values compared to method 2. The results of this study confirm the validity of using either method to measure lumbar paraspinal musculature, and that method should be selected based on the primary outcome variables of interest.


Subject(s)
Lumbar Vertebrae/diagnostic imaging , Magnetic Resonance Imaging/methods , Magnetic Resonance Imaging/standards , Paraspinal Muscles/diagnostic imaging , Cohort Studies , Female , Humans , Low Back Pain/diagnostic imaging , Male
14.
Int J Insect Sci ; 10: 1179543317751909, 2018.
Article in English | MEDLINE | ID: mdl-29371784

ABSTRACT

The morphology of the female Cyrtobagous salviniae Calder and Sands reproductive system is similar to other weevil species being meroistic and telotrophic. The reproductive system is composed of 2 ovaries each containing 2 ovarioles where the follicles mature. A physiological age grading system was developed where the continuum of ovarium development was divided into 2 nulliparous and 3 parous classes. This was based on the differentiation of the ovarioles, presence, and appearance of follicular relics, cuticle hardness/coloration, and fat body quantity/appearance. High correlation occurred between the parous classes and number of eggs produced where the P3 class had over 9-fold higher number of eggs in comparison with the P1 class. Mean number of eggs produced for each parous class was significantly different, however, overlap occurred. Such a system enables a determination of the past, present, and future reproductive status of field populations and mass-rearing colonies.

15.
PLoS One ; 11(10): e0165300, 2016.
Article in English | MEDLINE | ID: mdl-27788193

ABSTRACT

The fatty acid composition of membrane glycerolipids is a major determinant of Staphylococcus aureus membrane biophysical properties that impacts key factors in cell physiology including susceptibility to membrane active antimicrobials, pathogenesis, and response to environmental stress. The fatty acids of S. aureus are considered to be a mixture of branched-chain fatty acids (BCFAs), which increase membrane fluidity, and straight-chain fatty acids (SCFAs) that decrease it. The balance of BCFAs and SCFAs in USA300 strain JE2 and strain SH1000 was affected considerably by differences in the conventional laboratory medium in which the strains were grown with media such as Mueller-Hinton broth and Luria broth resulting in high BCFAs and low SCFAs, whereas growth in Tryptic Soy Broth and Brain-Heart Infusion broth led to reduction in BCFAs and an increase in SCFAs. Straight-chain unsaturated fatty acids (SCUFAs) were not detected. However, when S. aureus was grown ex vivo in serum, the fatty acid composition was radically different with SCUFAs, which increase membrane fluidity, making up a substantial proportion of the total (<25%) with SCFAs (>37%) and BCFAs (>36%) making up the rest. Staphyloxanthin, an additional major membrane lipid component unique to S. aureus, tended to be greater in content in cells with high BCFAs or SCUFAs. Cells with high staphyloxanthin content had a lower membrane fluidity that was attributed to increased production of staphyloxanthin. S. aureus saves energy and carbon by utilizing host fatty acids for part of its total fatty acids when growing in serum, which may impact biophysical properties and pathogenesis given the role of SCUFAs in virulence. The nutritional environment in which S. aureus is grown in vitro or in vivo in an infection is likely to be a major determinant of membrane fatty acid composition.


Subject(s)
Fatty Acids, Unsaturated/chemistry , Fatty Acids, Unsaturated/metabolism , Staphylococcus aureus/metabolism , Culture Media , Membrane Fluidity , Staphylococcus aureus/cytology , Staphylococcus aureus/physiology
16.
Mol Biol Cell ; 27(18): 2857-66, 2016 09 15.
Article in English | MEDLINE | ID: mdl-27466320

ABSTRACT

The Notch signaling pathway plays essential roles in both animal development and human disease. Regulation of Notch receptor levels in membrane compartments has been shown to affect signaling in a variety of contexts. Here we used steady-state and pulse-labeling techniques to follow Notch receptors in sensory organ precursor cells in Drosophila. We find that the endosomal adaptor protein Numb regulates levels of Notch receptor trafficking to Rab7-labeled late endosomes but not early endosomes. Using an assay we developed that labels different pools of Notch receptors as they move through the endocytic system, we show that Numb specifically suppresses a recycled Notch receptor subpopulation and that excess Notch signaling in numb mutants requires the recycling endosome GTPase Rab11 activity. Our data therefore suggest that Numb controls the balance between Notch receptor recycling and receptor targeting to late endosomes to regulate signaling output after asymmetric cell division in Drosophila neural progenitors.


Subject(s)
Drosophila Proteins/metabolism , Juvenile Hormones/metabolism , Neural Stem Cells/metabolism , Receptors, Notch/metabolism , Animals , Cell Differentiation/physiology , Cell Membrane/metabolism , Drosophila melanogaster/metabolism , Endocytosis/physiology , Endosomes/metabolism , Endosomes/physiology , Protein Transport , Receptors, Notch/physiology , Signal Transduction , rab GTP-Binding Proteins/metabolism , rab7 GTP-Binding Proteins
17.
Psychopharmacology (Berl) ; 233(15-16): 2973-84, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27318989

ABSTRACT

BACKGROUND: In previous studies, female monkeys self-administered more oral phencyclidine (PCP) than males, and PCP intake differed by phase of menstrual cycle. OBJECTIVES: The purpose of this study was to examine sex and hormonal influences on oral cocaine self-administration in male and female rhesus monkeys in the follicular vs. luteal phases of the menstrual cycle, with concurrent access to an alternative nondrug reward, saccharin (SACC) vs. water. MATERIALS AND METHODS: Concurrent access to cocaine (0.2, 0.4, and 0.8 mg/ml) and SACC or water was available from two drinking spouts under concurrent fixed-ratio (FR) 2, 4, and 8 schedules during daily 3-h sessions. RESULTS: Cocaine deliveries were similar in males and females in the females' luteal phase, but cocaine deliveries were higher in females during the follicular phase than the luteal phase and compared to males. When SACC was available, cocaine deliveries were reduced in females in the follicular phase of the cycle, and cocaine intake (mg/kg) was reduced in males and in females' follicular and luteal phases. CONCLUSIONS: Access to concurrent SACC (vs. water) reduced cocaine intake (mg/kg) in males and in females during both menstrual phases, and the magnitude of the reduction in cocaine intake was greatest during the females' follicular phase. Thus, a nondrug alternative reward, SACC, is a viable alternative treatment for reducing cocaine's rewarding effects on male and female monkeys, and reductions in cocaine seeking were optimal in the females' luteal phase.


Subject(s)
Cocaine/administration & dosage , Dopamine Uptake Inhibitors/administration & dosage , Drug-Seeking Behavior/physiology , Menstrual Cycle/physiology , Saccharin/administration & dosage , Sweetening Agents/administration & dosage , Administration, Oral , Animals , Female , Follicular Phase , Luteal Phase , Macaca mulatta , Male , Phencyclidine/pharmacology , Reward , Self Administration , Sex Factors
18.
PLoS One ; 9(7): e101239, 2014.
Article in English | MEDLINE | ID: mdl-25010047

ABSTRACT

Validation of clinical biomarkers and response to therapy is a challenging topic in cancer research. An important source of information for virtual validation is the datasets generated from multi-center cancer research projects such as The Cancer Genome Atlas project (TCGA). These data enable investigation of genetic and epigenetic changes responsible for cancer onset and progression, response to cancer therapies, and discovery of the molecular profiles of various cancers. However, these analyses often require bulk download of data and substantial bioinformatics expertise, which can be intimidating for investigators. Here, we report on the development of a new resource available to scientists: a data base called Glioblastoma Bio Discovery Portal (GBM-BioDP). GBM-BioDP is a free web-accessible resource that hosts a subset of the glioblastoma TCGA data and enables an intuitive query and interactive display of the resultant data. This resource provides visualization tools for the exploration of gene, miRNA, and protein expression, differential expression within the subtypes of GBM, and potential associations with clinical outcome, which are useful for virtual biological validation. The tool may also enable generation of hypotheses on how therapies impact GBM molecular profiles, which can help in personalization of treatment for optimal outcome. The resource can be accessed freely at http://gbm-biodp.nci.nih.gov (a tutorial is included).


Subject(s)
Brain Neoplasms/genetics , Databases, Factual , Genomics/methods , Glioblastoma/genetics , Brain Neoplasms/diagnosis , Brain Neoplasms/pathology , Gene Expression Profiling , Genes, Neoplasm/genetics , Glioblastoma/diagnosis , Glioblastoma/pathology , Humans , MicroRNAs/genetics , Prognosis , Survival Analysis
19.
Clin Ther ; 36(6): 953-60, 2014 Jun 01.
Article in English | MEDLINE | ID: mdl-24835558

ABSTRACT

BACKGROUND: Mupirocin has been used topically for treating skin and skin structure infections and for nasal decolonization before surgical interventions. Pleuromutilin compounds, including retapamulin, provide similar treatment/interventional options. Rates of resistance of Staphylococcus aureus to mupirocin and other agents used to treat skin and skin structure infections vary between countries and medical centers, including those in the United States. These resistance rates may be associated with higher usage and/or improper epidemiologic practices. OBJECTIVE: This study aimed to determine rates of resistance to topical and other class agents against S aureus isolates collected from SSSIs. METHODS: Isolates were obtained from outpatients at 6 US dermatology centers in 5 states. Demographic data were collected from medical records, and each patient completed a study questionnaire on recent history of skin infections, antibiotic use, and hospitalization. Each isolate was tested against cephalothin, clindamycin, erythromycin, gentamicin, mupirocin, tetracycline, retapamulin, and trimethoprim/sulfamethoxazole. RESULTS: Although methicillin-resistance rates varied between centers (range, 15.8%-35.5%), macrolide resistance was ~50% at all of the sites in this study. Mupirocin-resistant isolates were observed much more frequently from 1 center (33.9%), and nearly all demonstrated high-level resistance. Only 1 retapamulin-resistant isolate (0.5%) was observed, with a minimum inhibitory concentration of 16 µg/mL. The other agents had relatively low resistance rates, which varied between centers and were dependent on susceptibility to methicillin. CONCLUSIONS: Although the rate of mupirocin-resistant S aureus isolates collected in this investigation was >10%, retapamulin resistance was infrequent. Surveillance of topical agents to determine resistance rates against targeted bacteria is necessary.


Subject(s)
Mupirocin/pharmacology , Staphylococcal Skin Infections/drug therapy , Staphylococcus aureus/drug effects , Administration, Topical , Anti-Bacterial Agents/pharmacology , Bridged Bicyclo Compounds, Heterocyclic/therapeutic use , Clindamycin , Diterpenes , Humans , Methicillin-Resistant Staphylococcus aureus/drug effects , Microbial Sensitivity Tests , Mupirocin/therapeutic use , Staphylococcal Skin Infections/microbiology , Staphylococcus aureus/isolation & purification , Surgical Wound Infection/prevention & control , United States
20.
PLoS One ; 7(12): e51693, 2012.
Article in English | MEDLINE | ID: mdl-23284744

ABSTRACT

The increasing availability and maturity of DNA microarray technology has led to an explosion of cancer profiling studies for identifying cancer biomarkers, and predicting treatment response. Uncovering complex relationships, however, remains the most challenging task as it requires compiling and efficiently querying data from various sources. Here, we describe the Stress Response Array Profiler (StRAP), an open-source, web-based resource for storage, profiling, visualization, and sharing of cancer genomic data. StRAP houses multi-cancer microarray data with major emphasis on radiotherapy studies, and takes a systems biology approach towards the integration, comparison, and cross-validation of multiple cancer profiling studies. The database is a comprehensive platform for comparative analysis of gene expression data. For effective use of arrays, we provide user-friendly and interactive visualization tools that can display the data and query results. StRAP is web-based, platform-independent, and freely accessible at http://strap.nci.nih.gov/.


Subject(s)
Biomarkers, Tumor/genetics , Database Management Systems , Gene Expression Profiling , Genomics , Neoplasms/genetics , Software , Stress, Physiological/genetics , High-Throughput Nucleotide Sequencing , Humans , Oligonucleotide Array Sequence Analysis
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