Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 311
Filtrar
1.
bioRxiv ; 2024 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-38766140

RESUMEN

Midbrain dopamine neurons (DNs) respond to a first exposure to addictive drugs and play key roles in chronic drug usage 1-3 . As the synaptic and transcriptional changes that follow an acute cocaine exposure are mostly resolved within a few days 4,5 , the molecular changes that encode the long-term cellular memory of the exposure within DNs remain unknown. To investigate whether a single cocaine exposure induces long-term changes in the 3D genome structure of DNs, we applied Genome Architecture Mapping and single nucleus transcriptomic analyses in the mouse midbrain. We found extensive rewiring of 3D genome architecture at 24 hours past exposure which remains or worsens by 14 days, outlasting transcriptional responses. The cocaine-induced chromatin rewiring occurs at all genomic scales and affects genes with major roles in cocaine-induced synaptic changes. A single cocaine exposure triggers extensive long-lasting changes in chromatin condensation in post-synaptic and post-transcriptional regulatory genes, for example the unfolding of Rbfox1 which becomes most prominent 14 days post exposure. Finally, structurally remodeled genes are most expressed in a specific DN sub-type characterized by low expression of the dopamine auto-receptor Drd2 , a key feature of highly cocaine-sensitive cells. These results reveal an important role for long-lasting 3D genome remodelling in the cellular memory of a single cocaine exposure, providing new hypotheses for understanding the inception of drug addiction and 3D genome plasticity.

2.
Nanotheranostics ; 8(2): 163-178, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38444740

RESUMEN

Background: Combining magnetic particle imaging (MPI) and magnetic fluid hyperthermia (MFH) offers the ability to perform localized hyperthermia and magnetic particle imaging-assisted thermometry of hyperthermia treatment. This allows precise regional selective heating inside the body without invasive interventions. In current MPI-MFH platforms, separate systems are used, which require object transfer from one system to another. Here, we present the design, development and evaluation process for integrable MFH platforms, which extends a commercial MPI scanner with the functionality of MFH. Methods: The biggest issue of integrating magnetic fluid hyperthermia platforms into a magnetic particle imaging system is the magnetic coupling of the devices, which induces high voltage in the imaging system, and is harming its components. In this paper, we use a self-compensation approach derived from heuristic algorithms to protect the magnetic particle imaging scanner. The integrable platforms are evaluated regarding electrical and magnetic characteristics, cooling capability, field strength, the magnetic coupling to a replica of the magnetic particle imaging system's main solenoid and particle heating. Results: The MFH platforms generate suitable magnetic fields for the magnetic heating of particles and are compatible with a commercial magnetic particle imaging scanner. In combination with the imaging system, selective heating with a gradient field and steerable heating positioning using the MPI focus fields are possible. Conclusion: The proposed MFH platforms serve as a therapeutic tool to unlock the MFH functionality of a commercial magnetic particle imaging scanner, enabling its use in future preclinical trials of MPI-guided, spatially selective magnetic hyperthermia therapy.


Asunto(s)
Hipertermia Inducida , Campos Magnéticos
3.
Theranostics ; 14(1): 324-340, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38164157

RESUMEN

Theranostic platforms, combining diagnostic and therapeutic approaches within one system, have garnered interest in augmenting invasive surgical, chemical, and ionizing interventions. Magnetic particle imaging (MPI) offers a quite recent alternative to established radiation-based diagnostic modalities with its versatile tracer material (superparamagnetic iron oxide nanoparticles, SPION). It also offers a bimodal theranostic framework that can combine tomographic imaging with therapeutic techniques using the very same SPION. Methods: We show the interleaved combination of MPI-based imaging, therapy (highly localized magnetic fluid hyperthermia (MFH)) and therapy safety control (MPI-based thermometry) within one theranostic platform in all three spatial dimensions using a commercial MPI system and a custom-made heating insert. The heating characteristics as well as theranostic applications of the platform were demonstrated by various phantom experiments using commercial SPION. Results: We have shown the feasibility of an MPI-MFH-based theranostic platform by demonstrating high spatial control of the therapeutic target, adequate MPI-based thermometry, and successful in situ interleaved MPI-MFH application. Conclusions: MPI-MFH-based theranostic platforms serve as valuable tools that enable the synergistic integration of diagnostic and therapeutic approaches. The transition into in vivo studies will be essential to further validate their potential, and it holds promising prospects for future advancements.


Asunto(s)
Hipertermia Inducida , Nanopartículas de Magnetita , Termometría , Medicina de Precisión , Diagnóstico por Imagen/métodos , Nanopartículas de Magnetita/uso terapéutico , Campos Magnéticos
4.
bioRxiv ; 2023 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-37745570

RESUMEN

Vitamin D deficiency is a common deficiency worldwide, particularly among women of reproductive age. During pregnancy, it increases the risk of immune-related diseases in offspring later in life. However, exactly how the body remembers exposure to an adverse environment during development is poorly understood. Herein, we explore the effects of prenatal vitamin D deficiency on immune cell proportions in offspring using vitamin D deficient mice established by dietary manipulation. We show that prenatal vitamin D deficiency alters immune cell proportions in offspring by changing the transcriptional properties of genes downstream of vitamin D receptor signaling in hematopoietic stem and progenitor cells of both the fetus and adults. Further investigations of the associations between maternal vitamin D levels and cord blood immune cell profiles from 75 healthy pregnant women and their term babies also confirm that maternal vitamin D levels significantly affect immune cell proportions in the babies. Thus, lack of prenatal vitamin D, particularly at the time of hematopoietic stem cell migration from the liver to the bone marrow, has long-lasting effects on immune cell proportions. This highlights the importance of providing vitamin D supplementation at specific stages of pregnancy.

5.
PLoS One ; 18(7): e0289146, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37494382

RESUMEN

Mycetosoritis hartmanni is a rarely collected fungus-farming ant of North America. We describe life history and nest architecture for a M. hartmanni population in central Texas, USA. Colonies are monogynous with typically less than 100 workers (average 47.6 workers, maximum 148 workers). Nests occur always in sand and have a uniform architecture with 1-3 underground garden chambers arranged along a vertical tunnel, with the deepest gardens 50-70 cm deep. Foragers are active primarily between April and October. After reduced activity between November and February, egg laying by queens resumes in April, and the first worker pupae develop in early June. Reproductive females and males are reared primarily in July and August, with proportionally more females produced early in summer (protogyny). Mating flights and founding of new nests by mated females occur in late June to August, but may extend through September. For a cohort of 150 established nests (nests that had survived at least one year after nest founding), the estimated mortality rate was 0.41-0.53, the estimated average lifespan for these nests was 1.9-2.5 years, and the longest-living nests were observed to live for 6 years. These life-history parameters for M. hartmanni in central Texas are consistent with information from additional M. hartmanni nests observed throughout the range of this species from eastern Louisiana to southern Texas. Throughout its range in the USA, M. hartmanni can be locally very abundant in sun-exposed, sandy soil. Abundance of M. hartmanni seems so far relatively unaffected by invasive fire ants, and at present M. hartmanni does not appear to be an endangered species.


Asunto(s)
Hormigas , Animales , Femenino , Masculino , Longevidad , Razón de Masculinidad , Comportamiento de Nidificación , Hongos , Arena , Texas
6.
PLoS One ; 18(7): e0284317, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37478076

RESUMEN

A total of 24 chromosome-specific fluorescence in situ hybridization probes for interphase nucleus analysis were developed to determine the chromosomal content of individual human invasive cytotrophoblasts derived from in vitro cultured assays. At least 75% of invasive cytotrophoblasts were hyperdiploid and the total number of chromosomes ranged from 47 to 61. The results also demonstrated that these hyperdiploid invasive cytotrophoblasts showed significant heterogeneity. The most copy number gains were observed for chromosomes 13, 14, 15, 19, 21, and 22 with average copy number greater than 2.3. A parallel study using primary invasive cytotrophoblasts also showed a similar trend of copy number changes. Conclusively, 24-chromosome analysis of human non-proliferating cytotrophoblasts (interphase nuclei) was achieved. Hyperdiploidy and chromosomal heterogeneity without endoduplication in invasive cytotrophoblasts may suggest a selective advantage for invasion and short lifespan during normal placental development.


Asunto(s)
Placenta , Trofoblastos , Humanos , Femenino , Embarazo , Hibridación Fluorescente in Situ/métodos , Aneuploidia , Núcleo Celular , Interfase/genética
7.
J Neural Eng ; 20(3)2023 06 22.
Artículo en Inglés | MEDLINE | ID: mdl-37307808

RESUMEN

Objective.Current-controlled neurostimulation is increasingly used in the clinical treatment of neurological disorders and widely applied in neural prostheses such as cochlear implants. Despite its importance, time-dependent potential traces of electrodes during microsecond-scale current pulses, especially with respect to a reference electrode (RE), are not precisely understood. However, this knowledge is critical to predict contributions of chemical reactions at the electrodes, and ultimately electrode stability, biocompatibility, and stimulation safety and efficacy.Approach.We assessed the electrochemistry of neurostimulation protocolsin vitrowith Pt microelectrodes from millisecond (classical electroanalysis) to microsecond (neurostimulation) timescales. We developed a dual-channel instrumentation amplifier to include a RE in neurostimulation setups. Uniquely, we combined potential measurements with potentiostatic prepolarization to control and investigate the surface status, which is not possible in typical stimulation setups.Main results.We thoroughly validated the instrumentation and highlighted the importance of monitoring individual electrochemical electrode potentials in different configurations of neurostimulation. We investigated electrode processes such as oxide formation and oxygen reduction by chronopotentiometry, bridging the gap between milli- and microsecond timescales. Our results demonstrate how much impact on potential traces the electrode's initial surface state and electrochemical surface processes have, even on a microsecond scale.Significance.Our unique use of preconditioning in combination with stimulation reveals that interpreting potential traces with respect to electrode processes is misleading without rigorous control of the electrode's surface state. Especiallyin vivo, where the microenvironment is unknown, simply measuring the voltage between two electrodes cannot accurately reflect the electrode's state and processes. Potential boundaries determine charge transfer, corrosion, and alterations of the electrode/tissue interface such as pH and oxygenation, particularly in long-termin vivouse. Our findings are relevant for all use-cases of constant-current stimulation, strongly advocating for electrochemicalin situinvestigations in many applications like the development of new electrode materials and stimulation methods.


Asunto(s)
Implantación Coclear , Implantes Cocleares , Prótesis Neurales , Electrodos , Microelectrodos , Electroquímica/métodos , Platino (Metal)
8.
Front Hum Neurosci ; 17: 1162712, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37351363

RESUMEN

Near-infrared spectroscopy (NIRS) is a promising research tool that found its way into the field of brain-computer interfacing (BCI). BCI is crucially dependent on maximized usability thus demanding lightweight, compact, and low-cost hardware. We designed, built, and validated a hybrid BCI system incorporating one optical and two electrical modalities ameliorating usability issues. The novel hardware consisted of a NIRS device integrated with an electroencephalography (EEG) system that used two different types of electrodes: Regular gelled gold disk electrodes and tri-polar concentric ring electrodes (TCRE). BCI experiments with 16 volunteers implemented a two-dimensional motor imagery paradigm in off- and online sessions. Various non-canonical signal processing methods were used to extract and classify useful features from EEG, tEEG (EEG through TCRE electrodes), and NIRS. Our analysis demonstrated evidence of improvement in classification accuracy when using the TCRE electrodes compared to disk electrodes and the NIRS system. Based on our synchronous hybrid recording system, we could show that the combination of NIRS-EEG-tEEG performed significantly better than either single modality only.

9.
J Diabetes Metab Disord ; 22(1): 827-833, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37255826

RESUMEN

Background: There is a need for a non-pharmacological approach to reduce pain and plantar pressure in diabetic peripheral neuropathy (DPN). Matrix Rhythm Therapy (MaRhyThe®) is a therapeutic modality that works on the principle of physiologic rhythmic oscillations of the body cells. This study aimed to evaluate the effect of MaRhyThe® on neuropathic pain and maximum plantar pressure distribution among type 2 diabetes mellitus patients with peripheral neuropathy. Materials and methods: A total of 33 participants with DPN were recruited for the study based on inclusion criteria. Maximum plantar pressure was recorded using Win-Track 11K005, and the pain score was obtained using a visual analogue scale. Ten sessions of MaRhyThe® were given to all the participants. Outcome measures were evaluated at the baseline and after 10th session. Paired t-test was performed to analyze the changes in outcome measures. Results: Participants of DPN were recruited with the average age of 64 ± 9 years, and an average duration of diabetes was 14 ± 9 years were included. Results of the present study found significant improvement in neuropathic pain and plantar pressure in post intervention assessment. (p < 0.05). Conclusion: In the present study, we found that MaRhyThe® is effective in reducing neuropathic pain and maximum plantar pressure in type 2 diabetes mellitus with peripheral neuropathy.

10.
J Cancer Surviv ; 17(1): 160-173, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-33595753

RESUMEN

PURPOSE: Physical activity is associated with improved health outcomes for cancer survivors and their romantic partners, yet it is unclear if joint exercise programs for survivor-partner dyads are acceptable. This study examined demographic, relationship, exercise, and cancer history correlates of survivors' and their romantic partners' couples-based exercise beliefs and their preferences for program designs. METHODS: All participants (survivors n=209, partners n=155, couples n=143) completed an online survey. Correlations and linear regression analyses were used to examine correlates of participants' importance of and interest in couples-based exercise and their likelihood of joining a couples-based exercise program. Intraclass correlations estimated shared variance at the couple level. RESULTS: Most participants believed that couples-based exercise was highly important (51.8%) and were interested in a couples-based exercise program (61.5%), but fewer survivors believed their partner would be interested or would likely join a couples-based program. Across all outcomes, partner support for exercise was most strongly associated with participants' couples-based exercise beliefs (r = 0.19-0.54, p<.05), and couples were significantly aligned in their beliefs (ρ=0.20-0.31, p<.01). Participants were interested in exercise programs involving exercising together (67.3%) as well as exercising separately while sharing activity data on an app or website (48.0%). CONCLUSIONS: This novel understanding of couples-based exercise beliefs provides a strong foundation upon which future exercise programs may be designed for survivors and their romantic partners. IMPACT FOR CANCER SURVIVORS: Survivors' adoption and maintenance of exercise may be enhanced by the inclusion of romantic partners in exercise programs, and partners' inclusion is appealing to couples.


Asunto(s)
Supervivientes de Cáncer , Neoplasias , Humanos , Ejercicio Físico , Sobrevivientes , Encuestas y Cuestionarios , Parejas Sexuales
12.
Annu Int Conf IEEE Eng Med Biol Soc ; 2022: 2190-2193, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-36086080

RESUMEN

Magnetic Particle imaging (MPI) allows to measure and quantify background-free tracer distribution with a high temporal resolution. Anatomical structures are not displayed in MPI, rendering orientation within a sample error-prone and necessitating co-registration with other imaging modalities such as MRI. To support this challenge, defined external landmarks (fiducials) made from materials visible in each of the imaging modalities respectively were used in this work. Resulting signals can be aligned with the merged image containing both anatomical data and information about the tracer distribution. Defining the optimal fiducial placement is demanding and can drastically impact the 3D MPI-MRI image presentation. Here we present an adaptable 3D-printed fiducial system for preclinical co-registration of MRI and MPI data designed for easy visualisation. Clinical relevance- MPI is a promising imaging modality with many conceivable clinical applications. Simple and reliable co-registration with other imaging modalities will be crucial for a seamless transition into the clinic.


Asunto(s)
Imagenología Tridimensional , Imagen por Resonancia Magnética , Imagen por Resonancia Magnética/métodos , Registros
13.
Annu Int Conf IEEE Eng Med Biol Soc ; 2022: 3530-3533, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-36086280

RESUMEN

Identifying different functional regions during a brain surgery is a challenging task usually performed by highly specialized neurophysiologists. Progress in this field may be used to improve in situ brain navigation and will serve as an important building block to minimize the number of animals in preclinical brain research required by properly positioning implants intraoperatively. The study at hand aims to correlate recorded extracellular signals with the volume of origin by deep learning methods. Our work establishes connections between the position in the brain and recorded high-density neural signals. This was achieved by evaluating the performance of BLSTM, BGRU, QRNN and CNN neural network architectures on multisite electrophysiological data sets. All networks were able to successfully distinguish cortical and thalamic brain regions according to their respective neural signals. The BGRU provides the best results with an accuracy of 88.6 % and demonstrates that this classification task might be solved in higher detail while minimizing complex preprocessing steps.


Asunto(s)
Aprendizaje Automático , Roedores , Animales , Encéfalo/fisiología , Redes Neurales de la Computación
14.
Elife ; 112022 08 30.
Artículo en Inglés | MEDLINE | ID: mdl-36040792

RESUMEN

Background: Mutations in the SF3B1 splicing factor are commonly seen in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), yet the specific oncogenic pathways activated by mis-splicing have not been fully elucidated. Inflammatory immune pathways have been shown to play roles in the pathogenesis of MDS, though the exact mechanisms of their activation in splicing mutant cases are not well understood. Methods: RNA-seq data from SF3B1 mutant samples was analyzed and functional roles of interleukin-1 receptor-associated kinase 4 (IRAK4) isoforms were determined. Efficacy of IRAK4 inhibition was evaluated in preclinical models of MDS/AML. Results: RNA-seq splicing analysis of SF3B1 mutant MDS samples revealed retention of full-length exon 6 of IRAK4, a critical downstream mediator that links the Myddosome to inflammatory NF-kB activation. Exon 6 retention leads to a longer isoform, encoding a protein (IRAK4-long) that contains the entire death domain and kinase domain, leading to maximal activation of NF-kB. Cells with wild-type SF3B1 contain smaller IRAK4 isoforms that are targeted for proteasomal degradation. Expression of IRAK4-long in SF3B1 mutant cells induces TRAF6 activation leading to K63-linked ubiquitination of CDK2, associated with a block in hematopoietic differentiation. Inhibition of IRAK4 with CA-4948, leads to reduction in NF-kB activation, inflammatory cytokine production, enhanced myeloid differentiation in vitro and reduced leukemic growth in xenograft models. Conclusions: SF3B1 mutation leads to expression of a therapeutically targetable, longer, oncogenic IRAK4 isoform in AML/MDS models. Funding: This work was supported by Cincinnati Children's Hospital Research Foundation, Leukemia Lymphoma Society, and National Institute of Health (R35HL135787, RO1HL111103, RO1DK102759, RO1HL114582), Gabrielle's Angel Foundation for Cancer Research, and Edward P. Evans Foundation grants to DTS. AV is supported by Edward P. Evans Foundation, National Institute of Health (R01HL150832, R01HL139487, R01CA275007), Leukemia and Lymphoma Society, Curis and a gift from the Jane and Myles P. Dempsey family. AP and JB are supported by Blood Cancer UK (grants 13042 and 19004). GC is supported by a training grant from NYSTEM. We acknowledge support of this research from The Einstein Training Program in Stem Cell Research from the Empire State Stem Cell Fund through New York State Department of Health Contract C34874GG. MS is supported by a National Institute of Health Research Training and Career Development Grant (F31HL132420).


Genes contain blocks of code that tell cells how to make each part of a protein. Between these blocks are sections of linking DNA, which cells remove when they are preparing to use their genes. Scientists call this process 'splicing'. Cells can splice some genes in more than one way, allowing them to make different proteins from the same genetic code. Mutations that affect the splicing process can change the way cells make their proteins, leading to disease. For example, the myelodysplastic syndromes are a group of blood cancers often caused by mutations in splicing proteins, such as SF3B1. The disorder stops blood cells from maturing and causes abnormal inflammation. So far, the link between splicing, blood cell immaturity, inflammation and cancer is not clear. To find out more, Choudhary, Pellagatti et al. looked at the spliced genetic code from people with myelodysplastic syndromes. Mutations in the splicing protein SF3B1 changed the way cells spliced an important signalling molecule known as IRAK4. Affected cells cut out less genetic code and made a longer version of this signalling protein, named IRAK4-Long. This altered protein activated inflammation and stopped blood cells from maturing. Blocking IRAK4-Long reversed the effects. It also reduced tumour formation in mice carrying affected human cells. The molecule used to block IRAK4, CA-4948 ­ also known as Emavusertib ­ is currently being evaluated in clinical trials for myelodysplastic syndromes and other types of blood cancer. The work of Choudhary, Pellagatti et al. could help scientists to design genetic tests to predict which patients might benefit from this treatment.


Asunto(s)
Leucemia Mieloide Aguda , Síndromes Mielodisplásicos , Fosfoproteínas/metabolismo , Factores de Empalme de ARN/metabolismo , Niño , Humanos , Quinasas Asociadas a Receptores de Interleucina-1/genética , Quinasas Asociadas a Receptores de Interleucina-1/metabolismo , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , Mutación , Síndromes Mielodisplásicos/metabolismo , FN-kappa B/genética , FN-kappa B/metabolismo , Isoformas de Proteínas/metabolismo , Empalme del ARN
15.
Bioinformatics ; 38(16): 4036-4038, 2022 08 10.
Artículo en Inglés | MEDLINE | ID: mdl-35771633

RESUMEN

SUMMARY: The functional sub-string(s) of a biopolymer sequence defines the specificity of its interaction with other biomolecules and is often referred to as motifs. Computational algorithms and software have been broadly developed for finding such motifs in sequences in which the individual elements are single characters, such as those in DNA and protein sequences. However, there are more complex scenarios where the motifs exist in non-single-letter contexts, e.g. preferred patterns of chemical modifications on proteins, DNAs, RNAs or polysaccharides. To search for those motifs, we describe a new method that converts the modified sequence elements to representative single-letter codes and then uses a modified Gibbs-sampling algorithm to define the position specific scoring matrix representing the motif(s). As a proof of principle, we describe the implementation and application of an R package for discovering heparan sulfate (HS) motifs in glycan sequences, which are important in regulating protein-protein interactions. This software can be valuable for analyzing high-throughput glycoprotein binding data using microarrays with HS oligosaccharides or other biological polymers. AVAILABILITY AND IMPLEMENTATION: HSMotifDiscover is freely available as an open source R package released under an MIT license at https://github.com/bioinfoDZ/HSMotifDiscover and also available in the form of an app at https://hsmotifdiscover.shinyapps.io/HSMotifDiscover_ShinyApp/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Asunto(s)
Algoritmos , Programas Informáticos , Proteínas/química , Secuencia de Aminoácidos , ADN/química
16.
Cancer Cell ; 40(6): 639-655.e13, 2022 06 13.
Artículo en Inglés | MEDLINE | ID: mdl-35700707

RESUMEN

Glioblastomas are malignant tumors of the central nervous system hallmarked by subclonal diversity and dynamic adaptation amid developmental hierarchies. The source of dynamic reorganization within the spatial context of these tumors remains elusive. Here, we characterized glioblastomas by spatially resolved transcriptomics, metabolomics, and proteomics. By deciphering regionally shared transcriptional programs across patients, we infer that glioblastoma is organized by spatial segregation of lineage states and adapts to inflammatory and/or metabolic stimuli, reminiscent of the reactive transformation in mature astrocytes. Integration of metabolic imaging and imaging mass cytometry uncovered locoregional tumor-host interdependence, resulting in spatially exclusive adaptive transcriptional programs. Inferring copy-number alterations emphasizes a spatially cohesive organization of subclones associated with reactive transcriptional programs, confirming that environmental stress gives rise to selection pressure. A model of glioblastoma stem cells implanted into human and rodent neocortical tissue mimicking various environments confirmed that transcriptional states originate from dynamic adaptation to various environments.


Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Neoplasias Encefálicas/patología , Glioblastoma/patología , Humanos , Metabolómica/métodos
17.
Trends Microbiol ; 30(10): 997-1011, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35595643

RESUMEN

Microbiome breeding is a new artificial selection technique that seeks to change the genetic composition of microbiomes in order to benefit plant or animal hosts. Recent experimental and theoretical analyses have shown that microbiome breeding is possible whenever microbiome-encoded genetic factors affect host traits (e.g., health) and microbiomes are transmissible between hosts with sufficient fidelity, such as during natural microbiome transmission between individuals of social animals, or during experimental microbiome transplanting between plants. To address misunderstandings that stymie microbiome-breeding programs, we (i) clarify and visualize the corresponding elements of microbiome selection and standard selection; (ii) elucidate the eco-evolutionary processes underlying microbiome selection within a quantitative genetic framework to summarize practical guidelines that optimize microbiome breeding; and (iii) characterize the kinds of host species most amenable to microbiome breeding.


Asunto(s)
Microbiota , Fitomejoramiento , Animales , Evolución Biológica , Especificidad del Huésped , Microbiota/genética , Plantas
18.
Nat Commun ; 13(1): 925, 2022 02 17.
Artículo en Inglés | MEDLINE | ID: mdl-35177622

RESUMEN

Despite recent advances in cancer immunotherapy, certain tumor types, such as Glioblastomas, are highly resistant due to their tumor microenvironment disabling the anti-tumor immune response. Here we show, by applying an in-silico multidimensional model integrating spatially resolved and single-cell gene expression data of 45,615 immune cells from 12 tumor samples, that a subset of Interleukin-10-releasing HMOX1+ myeloid cells, spatially localizing to mesenchymal-like tumor regions, drive T-cell exhaustion and thus contribute to the immunosuppressive tumor microenvironment. These findings are validated using a human ex-vivo neocortical glioblastoma model inoculated with patient derived peripheral T-cells to simulate the immune compartment. This model recapitulates the dysfunctional transformation of tumor infiltrating T-cells. Inhibition of the JAK/STAT pathway rescues T-cell functionality both in our model and in-vivo, providing further evidence of IL-10 release being an important driving force of tumor immune escape. Our results thus show that integrative modelling of single cell and spatial transcriptomics data is a valuable tool to interrogate the tumor immune microenvironment and might contribute to the development of successful immunotherapies.


Asunto(s)
Neoplasias Encefálicas/inmunología , Glioblastoma/inmunología , Interleucina-10/metabolismo , Células Mieloides/metabolismo , Linfocitos T/inmunología , Adulto , Anciano , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/patología , Comunicación Celular/inmunología , Línea Celular Tumoral , Femenino , Glioblastoma/tratamiento farmacológico , Glioblastoma/patología , Voluntarios Sanos , Hemo-Oxigenasa 1/metabolismo , Humanos , Inmunoterapia/métodos , Inhibidores de las Cinasas Janus/farmacología , Inhibidores de las Cinasas Janus/uso terapéutico , Quinasas Janus/antagonistas & inhibidores , Quinasas Janus/metabolismo , Masculino , Persona de Mediana Edad , Neocórtex/citología , Neocórtex/inmunología , Neocórtex/patología , Cultivo Primario de Células , RNA-Seq , Factores de Transcripción STAT/metabolismo , Transducción de Señal/efectos de los fármacos , Transducción de Señal/inmunología , Análisis de la Célula Individual , Linfocitos T/efectos de los fármacos , Linfocitos T/metabolismo , Técnicas de Cultivo de Tejidos , Escape del Tumor , Microambiente Tumoral/inmunología
19.
J Colloid Interface Sci ; 606(Pt 1): 57-66, 2022 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-34388573

RESUMEN

HYPOTHESIS: Weakly bound, physisorbed hydrocarbons could in principle provide a similar water-repellency as obtained by chemisorption of strongly bound hydrophobic molecules at surfaces. EXPERIMENTS: Here we present experiments and computer simulations on the wetting behaviour of water on molecularly thin, self-assembled alkane carpets of dotriacontane (n-C32H66 or C32) physisorbed on the hydrophilic native oxide layer of silicon surfaces during dip-coating from a binary alkane solution. By changing the dip-coating velocity we control the initial C32 surface coverage and achieve distinct film morphologies, encompassing homogeneous coatings with self-organised nanopatterns that range from dendritic nano-islands to stripes. FINDINGS: These patterns exhibit a good water wettability even though the carpets are initially prepared with a high coverage of hydrophobic alkane molecules. Using in-liquid atomic force microscopy, along with molecular dynamics simulations, we trace this to a rearrangement of the alkane layers upon contact with water. This restructuring is correlated to the morphology of the C32 coatings, i.e. their fractal dimension. Water molecules displace to a large extent the first adsorbed alkane monolayer and thereby reduce the hydrophobic C32 surface coverage. Thus, our experiments evidence that water molecules can very effectively hydrophilize initially hydrophobic surfaces that consist of weakly bound hydrocarbon carpets.


Asunto(s)
Silicio , Agua , Interacciones Hidrofóbicas e Hidrofílicas , Propiedades de Superficie , Humectabilidad
20.
J Interprof Care ; 36(1): 4-14, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-33685327

RESUMEN

As in other areas of healthcare, the quality of patient care in the field of sport science and sports medicine (SSSM) could benefit from interprofessional collaboration between the professions involved. As a prerequisite, healthcare providers in the SSSM field should be equipped with positive attitudes and perceptions toward interprofessional collaboration (IPC) and interprofessional education (IPE), however detailed investigations are lacking. This study aimed to collect and compare socio-demographic data as well as interprofessional attitudes of SSSM professionals from an international perspective. Subjects were invited via professional SSSM organizations, personal networks and social media to participate in a cross-sectional online survey. Three-hundred and twenty complete datasets of SSSM professionals from the regions USA (n = 83), Canada (n = 179) and Europe (n = 58) were evaluated. In this survey, socio-demographic data as well as attitudes toward IPC and IPE using the 4 subscales of the University of West of England interprofessional Questionnaire (UWE-IP) were collected and analyzed with descriptive and inferential statistics. In the socio-demographic data, there was a diversity of participants representing different regional healthcare, sports and educational framing conditions. On average, in all regions clear positive attitudes were shown in the UWE-IP subscales communication & teamwork, interprofessional learning and interprofessional relationship, whereas in the subscale interprofessional interaction negative perceptions were observed on average across all regions. Significant effects of participants' demographic variables region, age and gender on some of the subscales were detected. Practitioners in the SSSM field have a high willingness and a beneficial preparedness for IPC and IPE, however, the framing conditions and the systems the respondents surveyed are working in do not support IPC. Interprofessional settings in learning and in workplace (e.g., theme-centred workshops, patient-centred case studies, health promotion activities) may help to improve interprofessional interactions in SSSM.


Asunto(s)
Relaciones Interprofesionales , Medicina Deportiva , Actitud del Personal de Salud , Conducta Cooperativa , Estudios Transversales , Personal de Salud/educación , Humanos
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...