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1.
Sci Rep ; 9(1): 8957, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31222047

RESUMO

As the extent to which aquatic environments are polluted with nano-scale objects is becoming known, we are presented with an urgent need to study their effects on various forms of life and to clear and/or detoxify them. A range of methods exist to these ends, but a lack of inter-study comparability arising from an absence of experimental standardisation impedes progress. Here we present experiments that demonstrate measurement of orchestrated uptake and clearance of two environmentally-relevant nano- and micromaterials by a model aquatic microoraganism, Paramecium caudatum. Experiments were based on a simple, modular, multi-chamber platform that permits standardised control of organism behaviour and measurement of variables relevant to the study of nanotoxicology, including nanomaterial chemotaxis assays, bioaccumulation and deleterious effects on cell motility systems. Uptake of internalised materials may be estimated through the addition of a low-cost fluorescence spectrometer. P. caudatum cells can clear an estimated 0.7 fg of contaminant materials (or 161 of the particles used) per cell over a 5 mm distance per 6 hour experiment, whilst suffering few short-term adverse effects, suggesting that the organism and the platform used to investigate their properties are well-suited to a range of laboratory and field-based nanotoxicological studies.

2.
Diabetologia ; 62(6): 1036-1047, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30955045

RESUMO

AIMS/HYPOTHESIS: The molecular response and function of pancreatic islet cells during metabolic stress is a complex process. The anatomical location and small size of pancreatic islets coupled with current methodological limitations have prevented the achievement of a complete, coherent picture of the role that lipids and proteins play in cellular processes under normal conditions and in diseased states. Herein, we describe the development of untargeted tissue imaging mass spectrometry (IMS) technologies for the study of in situ protein and, more specifically, lipid distributions in murine and human pancreases. METHODS: We developed matrix-assisted laser desorption/ionisation (MALDI) IMS protocols to study metabolite, lipid and protein distributions in mouse (wild-type and ob/ob mouse models) and human pancreases. IMS allows for the facile discrimination of chemically similar lipid and metabolite isoforms that cannot be distinguished using standard immunohistochemical techniques. Co-registration of MS images with immunofluorescence images acquired from serial tissue sections allowed accurate cross-registration of cell types. By acquiring immunofluorescence images first, this serial section approach guides targeted high spatial resolution IMS analyses (down to 15 µm) of regions of interest and leads to reduced time requirements for data acquisition. RESULTS: MALDI IMS enabled the molecular identification of specific phospholipid and glycolipid isoforms in pancreatic islets with intra-islet spatial resolution. This technology shows that subtle differences in the chemical structure of phospholipids can dramatically affect their distribution patterns and, presumably, cellular function within the islet and exocrine compartments of the pancreas (e.g. 18:1 vs 18:2 fatty acyl groups in phosphatidylcholine lipids). We also observed the localisation of specific GM3 ganglioside lipids [GM3(d34:1), GM3(d36:1), GM3(d38:1) and GM3(d40:1)] within murine islet cells that were correlated with a higher level of GM3 synthase as verified by immunostaining. However, in human pancreas, GM3 gangliosides were equally distributed in both the endocrine and exocrine tissue, with only one GM3 isoform showing islet-specific localisation. CONCLUSIONS/INTERPRETATION: The development of more complete molecular profiles of pancreatic tissue will provide important insight into the molecular state of the pancreas during islet development, normal function, and diseased states. For example, this study demonstrates that these results can provide novel insight into the potential signalling mechanisms involving phospholipids and glycolipids that would be difficult to detect by targeted methods, and can help raise new hypotheses about the types of physiological control exerted on endocrine hormone-producing cells in islets. Importantly, the in situ measurements afforded by IMS do not require a priori knowledge of molecules of interest and are not susceptible to the limitations of immunohistochemistry, providing the opportunity for novel biomarker discovery. Notably, the presence of multiple GM3 isoforms in mouse islets and the differential localisation of lipids in human tissue underscore the important role these molecules play in regulating insulin modulation and suggest species, organ, and cell specificity. This approach demonstrates the importance of both high spatial resolution and high molecular specificity to accurately survey the molecular composition of complex, multi-functional tissues such as the pancreas.

3.
Soft Matter ; 15(17): 3541-3551, 2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-30945723

RESUMO

Liquid marbles (LMs) have many promising roles in the ongoing development of microfluidics, microreactors, bioreactors, and unconventional computing. In many of these applications, the coalescence of two LMs is either required or actively discouraged, therefore it is important to study liquid marble collisions and establish parameters which enable the desired collision outcome. Recent reports on LM coalescence have focused on either two mobile LMs colliding, or an accelerating LM hitting a sessile LM with a backstop. A further possible scenario is the impact of a mobile LM against a non-supported static LM. This paper investigates such a collision, using high-speed videography for single-frame analysis. Multiple collisions were undertaken whilst varying the modified Weber number (We*) and offset ratios (X*). Parameter ranges of 1.0 < We* < 1.4 and 0.0 < X* < 0.1, resulted in a coalescence rate of approximately 50%. Whereas, parameter ranges X* > 0.25, and We* < 0.95 or We* > 1.55 resulted in 100% non-coalescence. Additionally, observations of LMs moving above a threshold velocity of 0.6 m s-1 have revealed a new and unusual deformation. Comparisons of the outcome of collisions whilst varying both the LM volume and the powder grain size have also been made, revealing a strong link. The results of this work provide a deeper understanding of LM coalescence, allowing improved control when designing future collision experiments.

4.
Cell Metab ; 2018 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-30449685

RESUMO

Identification of cell-surface markers specific to human pancreatic ß cells would allow in vivo analysis and imaging. Here we introduce a biomarker, ectonucleoside triphosphate diphosphohydrolase-3 (NTPDase3), that is expressed on the cell surface of essentially all adult human ß cells, including those from individuals with type 1 or type 2 diabetes. NTPDase3 is expressed dynamically during postnatal human pancreas development, appearing first in acinar cells at birth, but several months later its expression declines in acinar cells while concurrently emerging in islet ß cells. Given its specificity and membrane localization, we utilized an NTPDase3 antibody for purification of live human ß cells as confirmed by transcriptional profiling, and, in addition, for in vivo imaging of transplanted human ß cells. Thus, NTPDase3 is a cell-surface biomarker of adult human ß cells, and the antibody directed to this protein should be a useful new reagent for ß cell sorting, in vivo imaging, and targeting.

5.
Sci Rep ; 8(1): 14153, 2018 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-30237417

RESUMO

A mechanical flip-flop actuator has been developed that allows for the facile re-routing and distribution of liquid marbles (LMs) in digital microfluidic devices. Shaped loosely like a triangle, the actuating switch pivots from one bistable position to another, being actuated by the very low mass and momentum of a LM rolling under gravity (~4 × 10-6 kg ms-1). The actuator was laser-cut from cast acrylic, held on a PTFE coated pivot, and used a PTFE washer. Due to the rocking motion of the switch, sequential LMs are distributed along different channels, allowing for sequential LMs to traverse parallel paths. This distributing effect can be easily cascaded, for example to evenly divide sequential LMs down four different paths. This lightweight, cheap and versatile actuator has been demonstrated in the design and construction of a LM-operated mechanical multiplication device - establishing its effectiveness. The actuator can be operated solely by gravity, giving it potential use in point-of-care devices in low resource areas.

6.
Phys Rev E ; 98(1-1): 012306, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30110822

RESUMO

Belousov-Zhabotinsky (BZ) thin layer solution is a fruitful substrate for designing unconventional computing devices. A range of logical circuits, wet electronic devices, and neuromorphic prototypes have been constructed. Information processing in BZ computing devices is based on interaction of oxidation (excitation) wave fronts. Dynamics of the wave fronts propagation is programed by geometrical constraints and interaction of colliding wave fronts is tuned by illumination. We apply the principles of BZ computing to explore a geometry of street networks. We use two-variable Oregonator equations, the most widely accepted and verified in laboratory experiments BZ models, to study propagation of excitation wave fronts for a range of excitability parameters, with gradual transition from excitable to subexcitable to nonexcitable. We demonstrate a pruning strategy adopted by the medium with decreasing excitability when wider and ballistically appropriate streets are selected. We explain mechanics of streets selection and pruning. The results of the paper will be used in future studies of studying dynamics of cities and characterizing geometry of street networks.

7.
Artigo em Inglês | MEDLINE | ID: mdl-29994029

RESUMO

An accurate modelling of bio-electrochemical processes that govern Microbial Fuel Cells (MFCs) and mapping their behaviour according to several parameters will enhance the development of MFC technology and enable their successful implementation in well defined applications. The geometry of the electrodes is among key parameters determining efficiency of MFCs due to the formation of a biofilm of anodophilic bacteria on the anode electrode, which is a decisive factor for the functionality of the device. We simulate the bio-electrochemical processes in an MFC while taking into account the geometry of the electrodes. Namely, lattice Boltzmann methods are used to simulate the fluid dynamics and the advection-diffusion phenomena in the anode compartment. The model is verified on voltage and current outputs of a single MFC derived from laboratory experiments under continuous flow. Conclusions can be obtained from a parametric analysis of the model concerning the design of the geometry of the anode compartment, the positioning and microstructure of the anode electrode, in order to achieve more efficient overall performance of the system. An example of such a parametric analysis is presented here, taking into account the positioning of the electrode in the anode compartment.

8.
Langmuir ; 34(7): 2573-2580, 2018 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-29359941

RESUMO

Liquid marbles (LMs) have recently attracted interest for use as cargo carriers in digital microfluidics and have successfully been implemented as signal carriers in collision-based unconventional computing circuits. Both application domains require LMs to roll over substantial distances and to survive a certain number of collisions without degrading. To evaluate the lifetime of LMs being subjected to movement and impact stresses, we have selected four types of coating to investigate: polytetrafluoroethylene (PTFE), ultrahigh density polyethylene (PE), Ni, and a mixture of Ni with PE (Ni-PE). Hierarchies of robustness have been constructed which showed that pure PE LMs survived the longest when stationary and in motion. Pure PTFE LMs were shown to be the least resilient to multiple impacts. The PTFE coating provided minimal protection against evaporative losses for small LM volumes (2 and 5 µL) however, larger LMs (10 µL) were shown to have good evaporative stabilities when stationary. Conversely, PE LMs showed a remarkable ability to withstand multiple impacts and were also stable when considering just passive evaporation. Hybrid Ni-PE LMs exhibited more resilience to multiple impacts compared to Ni LMs. Thus, when designing LM devices, it is paramount to determine impact pathways and select appropriate coating materials.

9.
Diabetes ; 67(1): 26-35, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28931519

RESUMO

ß-Cells derived from stem cells hold great promise for cell replacement therapy for diabetes. Here we examine the ability of nuclear transfer embryonic stem cells (NT-ESs) derived from a patient with type 1 diabetes to differentiate into ß-cells and provide a source of autologous islets for cell replacement. NT-ESs differentiate in vitro with an average efficiency of 55% into C-peptide-positive cells, expressing markers of mature ß-cells, including MAFA and NKX6.1. Upon transplantation in immunodeficient mice, grafted cells form vascularized islet-like structures containing MAFA/C-peptide-positive cells. These ß-cells adapt insulin secretion to ambient metabolite status and show normal insulin processing. Importantly, NT-ES-ß-cells maintain normal blood glucose levels after ablation of the mouse endogenous ß-cells. Cystic structures, but no teratomas, were observed in NT-ES-ß-cell grafts. Isogenic induced pluripotent stem cell lines showed greater variability in ß-cell differentiation. Even though different methods of somatic cell reprogramming result in stem cell lines that are molecularly indistinguishable, full differentiation competence is more common in ES cell lines than in induced pluripotent stem cell lines. These results demonstrate the suitability of NT-ES-ß-cells for cell replacement for type 1 diabetes and provide proof of principle for therapeutic cloning combined with cell therapy.


Assuntos
Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/terapia , Células-Tronco Embrionárias/citologia , Células Secretoras de Insulina/citologia , Animais , Glicemia/metabolismo , Diferenciação Celular/fisiologia , Linhagem Celular , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/imunologia , Células-Tronco Embrionárias/fisiologia , Feminino , Citometria de Fluxo , Glucose/farmacologia , Proteínas de Homeodomínio/metabolismo , Humanos , Hospedeiro Imunocomprometido , Imuno-Histoquímica , Insulina/metabolismo , Células Secretoras de Insulina/fisiologia , Fatores de Transcrição Maf Maior/metabolismo , Masculino , Camundongos
11.
J Clin Invest ; 127(10): 3835-3844, 2017 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-28920919

RESUMO

Inadequate pancreatic ß cell function underlies type 1 and type 2 diabetes mellitus. Strategies to expand functional cells have focused on discovering and controlling mechanisms that limit the proliferation of human ß cells. Here, we developed an engraftment strategy to examine age-associated human islet cell replication competence and reveal mechanisms underlying age-dependent decline of ß cell proliferation in human islets. We found that exendin-4 (Ex-4), an agonist of the glucagon-like peptide 1 receptor (GLP-1R), stimulates human ß cell proliferation in juvenile but not adult islets. This age-dependent responsiveness does not reflect loss of GLP-1R signaling in adult islets, since Ex-4 treatment stimulated insulin secretion by both juvenile and adult human ß cells. We show that the mitogenic effect of Ex-4 requires calcineurin/nuclear factor of activated T cells (NFAT) signaling. In juvenile islets, Ex-4 induced expression of calcineurin/NFAT signaling components as well as target genes for proliferation-promoting factors, including NFATC1, FOXM1, and CCNA1. By contrast, expression of these factors in adult islet ß cells was not affected by Ex-4 exposure. These studies reveal age-dependent signaling mechanisms regulating human ß cell proliferation, and identify elements that could be adapted for therapeutic expansion of human ß cells.


Assuntos
Envelhecimento/metabolismo , Calcineurina/metabolismo , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Células Secretoras de Insulina/metabolismo , Transdução de Sinais , Adulto , Animais , Ciclina A1/metabolismo , Exenatida , Feminino , Proteína Forkhead Box M1/metabolismo , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Humanos , Insulina/metabolismo , Masculino , Camundongos Endogâmicos NOD , Pessoa de Meia-Idade , Fatores de Transcrição NFATC/metabolismo , Peptídeos/farmacologia , Peçonhas/farmacologia
12.
Cell Metab ; 25(6): 1362-1373.e5, 2017 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-28591638

RESUMO

Decreasing glucagon action lowers the blood glucose and may be useful therapeutically for diabetes. However, interrupted glucagon signaling leads to α cell proliferation. To identify postulated hepatic-derived circulating factor(s) responsible for α cell proliferation, we used transcriptomics/proteomics/metabolomics in three models of interrupted glucagon signaling and found that proliferation of mouse, zebrafish, and human α cells was mTOR and FoxP transcription factor dependent. Changes in hepatic amino acid (AA) catabolism gene expression predicted the observed increase in circulating AAs. Mimicking these AA levels stimulated α cell proliferation in a newly developed in vitro assay with L-glutamine being a critical AA. α cell expression of the AA transporter Slc38a5 was markedly increased in mice with interrupted glucagon signaling and played a role in α cell proliferation. These results indicate a hepatic α islet cell axis where glucagon regulates serum AA availability and AAs, especially L-glutamine, regulate α cell proliferation and mass via mTOR-dependent nutrient sensing.


Assuntos
Proliferação de Células , Glucagon/metabolismo , Glutamina/metabolismo , Fígado/metabolismo , Transdução de Sinais , Sistemas de Transporte de Aminoácidos Neutros/genética , Sistemas de Transporte de Aminoácidos Neutros/metabolismo , Animais , Glucagon/genética , Glutamina/genética , Camundongos , Camundongos Knockout , Peixe-Zebra , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo
13.
J Neurosurg Spine ; 27(2): 215-226, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28598292

RESUMO

OBJECTIVE Chordoma is a slow-growing, locally aggressive cancer that is minimally responsive to conventional chemotherapy and radiotherapy and has high local recurrence rates after resection. Currently, there are no rodent models of spinal chordoma. In the present study, the authors sought to develop and characterize an orthotopic model of human chordoma in an immunocompromised rat. METHODS Thirty-four immunocompromised rats were randomly allocated to 4 study groups; 22 of the 34 rats were engrafted in the lumbar spine with human chordoma. The groups were as follows: UCH1 tumor-engrafted (n = 11), JHC7 tumor-engrafted (n = 11), sham surgery (n = 6), and intact control (n = 6) rats. Neurological impairment of rats due to tumor growth was evaluated using open field and locomotion gait analysis; pain response was evaluated using mechanical or thermal paw stimulation. Cone beam CT (CBCT), MRI, and nanoScan PET/CT were performed to evaluate bony changes due to tumor growth. On Day 550, rats were killed and spines were processed for H & E-based histological examination and immunohistochemistry for brachyury, S100ß, and cytokeratin. RESULTS The spine tumors displayed typical chordoma morphology, that is, physaliferous cells filled with vacuolated cytoplasm of mucoid matrix. Brachyury immunoreactivity was confirmed by immunostaining, in which samples from tumor-engrafted rats showed a strong nuclear signal. Sclerotic lesions in the vertebral body of rats in the UCH1 and JHC7 groups were observed on CBCT. Tumor growth was confirmed using contrast-enhanced MRI. In UCH1 rats, large tumors were observed growing from the vertebral body. JHC7 chordoma-engrafted rats showed smaller tumors confined to the bone periphery compared with UCH1 chordoma-engrafted rats. Locomotion analysis showed a disruption in the normal gait pattern, with an increase in the step length and duration of the gait in tumor-engrafted rats. The distance traveled and the speed of rats in the open field test was significantly reduced in the UCH1 and JHC7 tumor-engrafted rats compared with controls. Nociceptive response to a mechanical stimulus showed a significant (p < 0.001) increase in the paw withdrawal threshold (mechanical hypalgesia). In contrast, the paw withdrawal response to a thermal stimulus decreased significantly (p < 0.05) in tumor-engrafted rats. CONCLUSIONS The authors developed an orthotopic human chordoma model in rats. Rats were followed for 550 days using imaging techniques, including MRI, CBCT, and nanoScan PET/CT, to evaluate lesion progression and bony integrity. Nociceptive evaluations and locomotion analysis were performed during follow-up. This model reproduces cardinal signs, such as locomotor and sensory deficits, similar to those observed clinically in human patients. To the authors' knowledge, this is the first spine rodent model of human chordoma. Its use and further study will be essential for pathophysiology research and the development of new therapeutic strategies.


Assuntos
Cordoma/fisiopatologia , Modelos Animais de Doenças , Membro Posterior/fisiopatologia , Atividade Motora , Nociceptividade , Neoplasias da Coluna Vertebral/fisiopatologia , Animais , Linhagem Celular Tumoral , Cordoma/diagnóstico por imagem , Cordoma/patologia , Feminino , Marcha/fisiologia , Humanos , Hospedeiro Imunocomprometido , Atividade Motora/fisiologia , Recidiva Local de Neoplasia/fisiopatologia , Transplante de Neoplasias , Nociceptividade/fisiologia , Distribuição Aleatória , Ratos , Sacro , Medula Espinal/diagnóstico por imagem , Medula Espinal/patologia , Medula Espinal/fisiopatologia , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Neoplasias da Coluna Vertebral/patologia
14.
Biosystems ; 156-157: 53-62, 2017 Jun - Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28428117

RESUMO

A cellular non-linear network (CNN) is a uniform regular array of locally connected continuous-state machines, or nodes, which update their states simultaneously in discrete time. A microbial fuel cell (MFC) is an electro-chemical reactor using the metabolism of bacteria to drive an electrical current. In a CNN model of the MFC, each node takes a vector of states which represent geometrical characteristics of the cell, like the electrodes or impermeable borders, and quantify measurable properties like bacterial population, charges produced and hydrogen ion concentrations. The model allows the study of integral reaction of the MFC, including temporal outputs, to spatial disturbances of the bacterial population and supply of nutrients. The model can also be used to evaluate inhomogeneous configurations of bacterial populations attached on the electrode biofilms.


Assuntos
Fontes de Energia Bioelétrica , Bactérias , Biofilmes , Eletrodos , Concentração de Íons de Hidrogênio
15.
Spine J ; 17(9): 1325-1334, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28412561

RESUMO

BACKGROUND CONTEXT: Metastases to the spine are a common source of severe pain in cancer patients. The secondary effects of spinal metastases include pain, bone fractures, hypercalcemia, and neurological deficits. As the disease progresses, pain severity can increase until it becomes refractory to medical treatments and leads to a decreased quality of life for patients. A key obstacle in the study of pain-induced spinal cancer is the lack of reliable and reproducible spine cancer animal models. In the present study, we developed a reproducible and reliable rat model of spinal cancer using human-derived tumor tissue to evaluate neurological decline using imaging and behavioral techniques. PURPOSE: The present study outlines the development and characterization of an orthotopic model of human breast cancer to the spine in immunocompromised rats. STUDY DESIGN/SETTING: This is a basic science study. METHODS: Female immunocompromised rats were randomized into three groups: tumor (n=8), RBC3 mammary adenocarcinoma tissue engrafted in the L5 vertebra body; sham (n=6), surgery performed but not tumor engrafted; and control (n=6), naive rats, no surgery performed. To evaluate the neurological impairment due to tumor invasion, functional assessment was done in all rodents at day 40 after tumor engraftment using locomotion gait analysis and pain response to a mechanical stimulus (Randall-Selitto test). Bioluminescence (BLI) was used to evaluate tumor growth in vivo and cone beam computed tomography (CBCT) was performed to evaluate bone changes due to tumor invasion. The animals were euthanized at day 45 and their spines were harvested and processed for hematoxylin and eosin (H&E) staining. RESULTS: Tumor growth in the spine was confirmed by BLI imaging and corroborated by histological analysis. Cone beam computed tomography images were characterized by a decrease in the bone intensity in the lumbar spine consistent with tumor location on BLI. On H&E staining of tumor-engrafted animals, there was a near-complete ablation of the ventral and posterior elements of the L5 vertebra with severe tumor invasion in the bony components displacing the spinal cord. Locomotion gait analysis of tumor-engrafted rats showed a disruption in the normal gait pattern with asignificant reduction in length (p=.02), duration (p=.002), and velocity (p=.002) of right leg strides and only in duration (p=.0006) and velocity (p=.001) of left leg strides, as compared with control and sham rats. Tumor-engrafted animals were hypersensitive to pain stimulus shown as a significantly reduced response in time (p=.02) and pressure (p=.01) applied when compared with control groups. CONCLUSIONS: We developed a system for the quantitative analysis of pain and locomotion in an animal model of metastatic human breast cancer of the spine. Tumor-engrafted animals showed locomotor and sensory deficits that are in accordance with clinical manifestation in patients with spine metastasis. Pain response and locomotion gait analysis were performed during follow-up. The Randall-Selitto test was a sensitive method to evaluate pain in the rat's spine. We present a model for the study of bone-associated cancer pain secondary to cancer metastasis to the spine, as well as for the study of new therapies and treatments to lessen pain from metastatic cancer to the neuroaxis.


Assuntos
Adenocarcinoma/patologia , Marcha , Hiperalgesia/etiologia , Neoplasias Mamárias Experimentais/patologia , Neoplasias da Coluna Vertebral/patologia , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Hiperalgesia/patologia , Hiperalgesia/fisiopatologia , Ratos , Medula Espinal/patologia , Medula Espinal/fisiopatologia , Neoplasias da Coluna Vertebral/secundário
16.
Biosystems ; 153-154: 1-5, 2017 Mar - Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28167098

RESUMO

Living architectures and green energy are hot topics of the applied sciences. They aim to develop buildings that co-live with their environment and co-habit with people they house. An ultimate goal would be to make every block in a building capable of producing energy. We present results of scoping, and somewhat illustrative, experiments on generating electrical energy in modified aerated concrete blocks. These blocks are commonly used in modern building industry and therefore make an ideal candidate for 'inbuilt' microbial bio-reactors. We fill the blocks with milk to evaluate electro-generation potential of a pasteurised milk and to study power generating potential of the medium nutrient rich for micro-organisms. We assess the practicality of using bio-reactors which become colonised by local micro-flora.


Assuntos
Reatores Biológicos , Leite , Animais , Bactérias , Fontes de Energia Bioelétrica , Eletrodos , Meio Ambiente , Desenho de Equipamento
17.
Blood Adv ; 1(17): 1324-1334, 2017 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-29296775

RESUMO

Classical Hodgkin lymphoma (CHL) is a neoplasm characterized by robust inflammatory infiltrates and heightened expression of the immunosuppressive PD-1/PD-L1 pathway. Although anti-PD-1 therapy can be effective in >60% of patients with refractory CHL, improved treatment options are needed for CHLs which are resistant to anti-PD-1 or relapse after this form of immunotherapy. A deeper understanding of immunologic factors in the CHL microenvironment might support the design of more effective treatment combinations based on anti-PD-1. In addition, because the Epstein-Barr virus (EBV) residing in some CHL tumors is strongly immunogenic, we hypothesized that characteristics of the tumor immune microenvironment in EBV+ CHL would be distinct from EBV- CHL, with specific implications for designing combination treatment regimens. Employing immunohistochemistry for immune cell subsets and checkpoint molecules, as well as gene expression profiling, we characterized 32 CHLs from the Johns Hopkins archives, including 12 EBV+ and 20 EBV- tumors. Our results revealed a dichotomous cellular and cytokine immune milieu in EBV+ vs EBV- CHL. EBV+ tumors displayed a T helper 1 (Th1) profile typical of effective antitumor immunity, with increased infiltration of CD8+ T cells and coordinate expression of the canonical Th1 transcription factor Tbet (TBX21), interferon-γ (IFNG), and the IFN-γ-inducible immunosuppressive enzyme indoleamine 2,3-dioxygenase. In contrast, EBV- tumors manifested a pathogenic Th17 profile and ongoing engagement of the interleukin-23 (IL-23)/IL-17 axis, with heightened phosphorylated signal transducer and activator of transcription 3 expression in infiltrating lymphocytes. These findings suggest that drugs blocking the IL-23/IL-17 axis, which are already in the clinic for treating certain autoimmune disorders, may enhance the therapeutic impact of anti-PD-1 therapy in EBV- CHL.

18.
Transplantation ; 99(7): 1396-402, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25675195

RESUMO

BACKGROUND: Solid organ transplantation reduces both morbidity and mortality. Donation rates have increased by more than 60% in the last 6 years in the United Kingdom, largely through improved identification and management of potential donors. However, the next of kin (NoK) decline to consent in 43% of cases-the second highest rate in Europe. We aimed to define factors that influence decisions to consent for organ donation. METHODS: This is an online survey of 1549 adult residents of England with results weighted to national demographics. RESULTS: Eighty percent would consider donating some or all of their organs. Religion, age, and ethnicity influenced this support. Concerns over body integrity, religion, and effects on the quality of care received reduce support. Only 48% recognized that NoK consent would be sought before any donation. Previous discussion and Organ Donor Register (ODR) enrollment both correlate with NoK consent: 87% would consent after discussion and ODR enrollment, 79% would consent after discussion alone, 55% would consent with ODR registration alone, and 29% would consent without either. Reported misconceptions inhibiting consent included a perceived inability to deregister from the ODR and that individuals were too old to donate. Those who did not wish to donate their own organs were more likely to overrule others' expressed wishes to donate. CONCLUSIONS: To ensure that organ donation occurs wherever appropriate, attention should focus primarily on determining an individual's wishes before death, ensuring that any misconceptions are corrected before a decision is made, promotion of ODR enrollment, and challenging those NoK who wish to overrule others' wishes.


Assuntos
Comportamento de Escolha , Conhecimentos, Atitudes e Prática em Saúde , Consentimento Livre e Esclarecido , Doadores de Tecidos/psicologia , Obtenção de Tecidos e Órgãos , Adolescente , Adulto , Fatores Etários , Idoso , Altruísmo , Atitude Frente a Morte , Inglaterra , Grupos Étnicos , Feminino , Doações , Humanos , Masculino , Pessoa de Meia-Idade , Percepção , Qualidade da Assistência à Saúde , Religião e Medicina , Inquéritos e Questionários , Doadores de Tecidos/provisão & distribução , Adulto Jovem
19.
J Physiol ; 593(3): 739-52; discussion 753, 2015 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-25433073

RESUMO

KEY POINTS: Heat stroke afflicts thousands of humans each year, worldwide. The immune system responds to hyperthermia exposure resulting in heat stroke by producing an array of immunological proteins, such as interleukin-6 (IL-6). However, the physiological functions of IL-6 and other cytokines in hyperthermia are poorly understood. We hypothesized that IL-6 plays a protective role in conditions of heat stroke. To test this, we gave small IL-6 supplements to mice prior to exposing them to hot environments sufficient to induce conditions of heat stroke. Pretreatment with IL-6 resulted in improved ability to withstand heat exposure in anaesthetized mice, it protected the intestine from injury, reducing the permeability of the intestinal barrier, and it attenuated the release of other cytokines involved in inflammation. The results support the hypothesis that IL-6 is a 'physiological stress hormone' that plays an important role in survival during acute life-threatening conditions such as heat stroke. ABSTRACT: The role of interleukin-6 (IL-6) in hyperthermia and heat stroke is poorly understood. Plasma IL-6 is elevated following hyperthermia in animals and humans, and IL-6 knockout mice are more intolerant of severe hyperthermia. We evaluated the effect of IL-6 supplementation on organ injury following severe hyperthermia exposure in anaesthetized mice. Two hours prior to hyperthermia, mice were treated with 0.6 µg intraperitoneal IL-6, or identical volumes of saline in controls. Mice were anaesthetized, gavaged with FITC-dextran for measures of gastrointestinal permeability, and exposed to incremental (0.5°C every 30 min) increases in temperature. Heating stopped when maximum core temperature (Tc) of 42.4°C was attained (Tc,max). The mice recovered at room temperature (≈22°C) for 30 or 120 min, at which time plasma and tissues were collected. IL-6-treated mice, on average, required ≈25 min longer to attain Tc,max . Injury and swelling of the villi in the duodenum was present in untreated mice after 30 min of recovery. These changes were blocked by IL-6 treatment. IL-6 also reduced gastrointestinal permeability, assayed by the accumulation of FITC-dextran in plasma. Plasma cytokines were also attenuated in IL-6-treated animals, including significant reductions in TNFα, MCP-1 (CXCL2), RANTES (CCL5) and KC (CCL5). The results demonstrate that IL-6 has a protective influence on the pattern of physiological responses to severe hyperthermia, suggesting that early endogenous expression of IL-6 may provide a protection from the development of organ damage and inflammation.


Assuntos
Golpe de Calor/tratamento farmacológico , Interleucina-6/uso terapêutico , Mucosa Intestinal/metabolismo , Animais , Quimiocina CCL2/sangue , Quimiocina CCL5/sangue , Suplementos Nutricionais , Golpe de Calor/prevenção & controle , Interleucina-6/administração & dosagem , Absorção Intestinal , Intestinos/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fator de Necrose Tumoral alfa/sangue
20.
PLoS One ; 9(9): e106693, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25198535

RESUMO

BACKGROUND: Type 2 diabetes results from failure of the ß-cells to compensate for increased insulin demand due to abnormal levels of metabolic factors. The ob/ob(lep-/-) mouse has been extensively studied as an animal model of type 2 diabetes. Previous studies have shown a correlation between ß-cell function and bioluminescent imaging in lean genetically engineered mice. The ability to noninvasively monitor ß-cell function in ob/ob mice could provide new information on ß-cell regulation in type 2 diabetes. METHODS: To create the B6 Albino ob/ob MIP-luc mice (ob/ob-luc), the ob/ob mouse was crossed with the CD1 MIP-luc mouse. All mice were backcrossed over multiple generations to ensure the genetic background of the transgenic mice was over 96% similar to the background of the original ob/ob mouse. Animal weight, blood glucose levels, insulin in plasma, and in vivo bioluminescence (BLI) were monitored weekly or biweekly for up to 70 weeks of age. BL imaging was performed using IVIS Spectrum (Perkin Elmer) and calculated by integrating the bioluminescence signal between 5 and 10 min after i.v. injection of D-luciferin. Insulin immunohistochemistry determined islet beta cell count and insulin secretion assay determined islet insulin function. RESULTS: There were significant increases in BLI and insulin levels as the ob/ob-luc mice aged while glucose levels gradually decreased. Ob/ob-luc were sacrificed at different time points to determine ex vivo BLI, islet function and total ß-cell numbers using a cell counting training algorithm developed for the Vectra image analysis system (Perkin Elmer). The number of ß-cells increased as the mice aged and all three ex vivo measurements correlated with BLI. CONCLUSIONS: The ob/ob-luc mice can serve as a model of metabolic stress, similar to human type 2 diabetes using BLI as a surrogate marker for ß-cell function.


Assuntos
Hiperglicemia/fisiopatologia , Ilhotas Pancreáticas/fisiopatologia , Obesidade/fisiopatologia , Animais , Diabetes Mellitus Tipo 2/fisiopatologia , Luminescência , Camundongos
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