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1.
JMIR Ment Health ; 11: e52369, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38728080

RESUMEN

BACKGROUND: The Feeling Good App is an automated stand-alone digital mobile mental health tool currently undergoing beta testing with the goal of providing evidence-informed self-help lessons and exercises to help individuals reduce depressive symptoms without guidance from a mental health provider. Users work through intensive basic training (IBT) and ongoing training models that provide education regarding cognitive behavioral therapy principles from a smartphone. OBJECTIVE: The key objective of this study was to perform a nonsponsored third-party academic assessment of an industry-generated data set; this data set focused on the safety, feasibility, and accessibility of a commercial automated digital mobile mental health app that was developed to reduce feelings associated with depression. METHODS: The Feeling Good App development team created a waitlist cohort crossover design and measured symptoms of depression and anxiety using the Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, and an app-specific measure of negative feelings called the 7 Dimension Emotion Slider (7-DES). The waitlist cohort crossover design divided the participants into 2 groups, where 48.6% (141/290) of the participants were given immediate access to the apps, while 51.4% (149/290) were placed on a 2-week waitlist before being given access to the app. Data collected by the Feeling Good App development team were deidentified and provided to the authors of this paper for analysis through a nonsponsored university data use agreement. All quantitative data were analyzed using SPSS Statistics (version 28.0; IBM Corp). Descriptive statistics were calculated for demographic variables. Feasibility and acceptability were descriptively assessed. All participants included in the quantitative data were given access to the Feeling Good App; this study did not include a control group. RESULTS: In terms of safety, there was no statistically significant change in suicidality from preintervention to postintervention time points (t288=0.0; P>.99), and there was a statistically significant decrease in hopelessness from preintervention to postintervention time points (F289=30.16; P<.01). In terms of acceptability, 72.2% (166/230) of the users who started the initial 2-day IBT went on to complete it, while 34.8% (80/230) of the users who started IBT completed the entirety of the apps' 4-week protocol (150/230, 65.22% dropout rate over 4 weeks). CONCLUSIONS: This study is the first reported proof-of-concept evaluation of the Feeling Good App in terms of safety, feasibility, and statistical trends within the data set. It demonstrates a feasible and novel approach to industry and academic collaboration in the process of developing a digital mental health technology translated from an existing evidence-informed treatment. The results support the prototype app as safe for a select nonclinical population. The app had acceptable levels of engagement and dropouts throughout the intervention. Those who stay engaged showed reductions in symptom severity of depression warranting further investigation of the app's efficacy.


Asunto(s)
Terapia Cognitivo-Conductual , Depresión , Estudios de Factibilidad , Aplicaciones Móviles , Humanos , Masculino , Femenino , Adulto , Terapia Cognitivo-Conductual/métodos , Depresión/terapia , Depresión/diagnóstico , Persona de Mediana Edad , Empatía , Aceptación de la Atención de Salud/psicología , Estudios Cruzados , Adulto Joven , Análisis de Datos Secundarios
2.
Islets ; 16(1): 2334044, 2024 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-38533763

RESUMEN

Pancreatic beta cells are among the slowest replicating cells in the human body and have not been observed to increase in number except during the fetal and neonatal period, in cases of obesity, during puberty, as well as during pregnancy. Pregnancy is associated with increased beta cell mass to meet heightened insulin demands. This phenomenon raises the intriguing possibility that factors present in the serum of pregnant individuals may stimulate beta cell proliferation and offer insights into expansion of the beta cell mass for treatment and prevention of diabetes. The primary objective of this study was to test the hypothesis that serum from pregnant donors contains bioactive factors capable of inducing human beta cell proliferation. An immortalized human beta cell line with protracted replication (EndoC-ßH1) was cultured in media supplemented with serum from pregnant and non-pregnant female and male donors and assessed for differences in proliferation. This experiment was followed by assessment of proliferation of primary human beta cells. Sera from five out of six pregnant donors induced a significant increase in the proliferation rate of EndoC-ßH1 cells. Pooled serum from the cohort of pregnant donors also increased the rate of proliferation in primary human beta cells. This study demonstrates that serum from pregnant donors stimulates human beta cell proliferation. These findings suggest the existence of pregnancy-associated factors that can offer novel avenues for beta cell regeneration and diabetes prevention strategies. Further research is warranted to elucidate the specific factors responsible for this effect.


Asunto(s)
Diabetes Mellitus , Células Secretoras de Insulina , Recién Nacido , Humanos , Masculino , Femenino , Embarazo , Insulina/metabolismo , Células Secretoras de Insulina/metabolismo , Línea Celular , Diabetes Mellitus/metabolismo , Proliferación Celular
3.
Heliyon ; 10(3): e25126, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38333820

RESUMEN

The Old World Vultures (OWV), constituting 16 species primarily in Africa, Europe and Asia, are currently being driven to extinction mostly by anthropogenic activities, especially poisoning. The vulture losses from poisoning caused by human-related activities are en masse at a single mortality event-level and occur in complex social-ecological systems. There has been a growing body of knowledge on wildlife poisoning over the years. However, no review has been done to consolidate vulture poisoning studies in sub-Saharan Africa (SSA), with a social lens of conservation planning. Here we present a review of the vulture poisoning research by re-contextualizing the problem of vulture poisoning across SSA. We employed stepwise Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method to search for literature on vulture poisoning. The search yielded 211 studies which were trimmed to 55 after applying sets of eligibility criteria. Literature shows that efforts aimed at successful vulture conservation planning will require an understanding of the relational aspects of stakeholder social capital (assets) that are critical to the implementation of species recovery strategies. Strengthening relational social capital through multi-scale stakeholder evidence-based awareness creation and participation is necessary for addressing the African Vulture Crisis (AVC). Applying stakeholder social capital approaches to different vulture conservation scenarios at local, regional and international scales can enhance successful implementation of conservation strategies for the persistence of vultures in complex socio-ecological systems in African landscapes. Existing literature also showed the importance of stakeholder social capital as a countermeasure against vulture losses.

4.
J Anim Ecol ; 93(4): 417-427, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38311822

RESUMEN

Many African large carnivore populations are declining due to decline of the herbivore populations on which they depend. The densities of apex carnivores like the lion and spotted hyena correlate strongly with prey density, but competitively subordinate carnivores like the African wild dog benefit from competitive release when the density of apex carnivores is low, so the expected effect of a simultaneous decrease in resources and dominant competitors is not obvious. Wild dogs in Zambia's South Luangwa Valley Ecosystem occupy four ecologically similar areas with well-described differences in the densities of prey and dominant competitors due to spatial variation in illegal offtake. We used long-term monitoring data to fit a Bayesian integrated population model (IPM) of the demography and dynamics of wild dogs in these four regions. The IPM used Leslie projection to link a Cormack-Jolly-Seber model of area-specific survival (allowing for individual heterogeneity in detection), a zero-inflated Poisson model of area-specific fecundity and a state-space model of population size that used estimates from a closed mark-capture model as the counts from which (latent) population size was estimated. The IPM showed that both survival and reproduction were lowest in the region with the lowest density of preferred prey (puku, Kobus vardonii and impala, Aepyceros melampus), despite little use of this area by lions. Survival and reproduction were highest in the region with the highest prey density and intermediate in the two regions with intermediate prey density. The population growth rate ( λ ) was positive for the population as a whole, strongly positive in the region with the highest prey density and strongly negative in the region with the lowest prey density. It has long been thought that the benefits of competitive release protect African wild dogs from the costs of low prey density. Our results show that the costs of prey depletion overwhelm the benefits of competitive release and cause local population decline where anthropogenic prey depletion is strong. Because competition is important in many guilds and humans are affecting resources of many types, it is likely that similarly fundamental shifts in population limitation are arising in many systems.


Asunto(s)
Canidae , Carnívoros , Leones , Animales , Teorema de Bayes , Ecosistema , Densidad de Población , Dinámica Poblacional
5.
Biotechnol Bioeng ; 121(4): 1284-1297, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38240126

RESUMEN

Product association of host-cell proteins (HCPs) to monoclonal antibodies (mAbs) is widely regarded as a mechanism that can enable HCP persistence through multiple purification steps and even into the final drug substance. Discussion of this mechanism often implies that the existence or extent of persistence is directly related to the strength of binding but actual measurements of the binding affinity of such interactions remain sparse. Two separate avenues of investigation of HCP-mAb binding are reported here. One is the measurement of the affinity of binding of individual, commonly persistent Chinese hamster ovary (CHO) HCPs to each of a set of mAbs, and the other uses quantitative proteomic measurements to assess binding of HCPs in a null CHO harvested cell culture fluid (HCCF) to mAbs produced in the same cell line. The individual HCP measurements show that the binding affinities of individual HCPs to different mAbs can vary appreciably but are rarely very high, with only weak pH dependence. The measurements on the null HCCF allow estimation of individual HCP-mAb affinities; these are typically weaker than those seen in affinity measurements on isolated HCPs. Instead, the extent of binding appears correlated with the initial abundance of individual HCPs in the HCCF and the forms of the HCPs in the solution, i.e., whether HCPs are present as free molecules or as parts of large aggregates. Separate protein A chromatography experiments performed by feeding different fractions of a mAb-containing HCCF obtained by size-exclusion chromatography (SEC) showed clear differences in the number and identity of HCPs found in the protein A eluate. These results indicate a significant role for HCP-mAb association in determining HCP persistence through protein A chromatography, presumably through binding of HCP-mAb complexes to the resin. Overall, the results illustrate the importance of considering more fully the biophysical context of HCP-product association in assessing the factors that may affect the phenomenon and determine its implications. Knowledge of the abundances and the forms of individual or aggregated HCPs in HCCF are particularly significant, emphasizing the integration of upstream and downstream bioprocessing and the importance of understanding the collective properties of HCPs in addition to just the biophysical properties of individual HCPs.


Asunto(s)
Anticuerpos Monoclonales , Proteómica , Cricetinae , Animales , Cricetulus , Proteómica/métodos , Células CHO , Anticuerpos Monoclonales/química , Cromatografía en Gel , Proteína Estafilocócica A/química
6.
Nat Commun ; 14(1): 7299, 2023 11 11.
Artículo en Inglés | MEDLINE | ID: mdl-37949871

RESUMEN

Resorbable, implantable bioelectronic devices are emerging as powerful tools to reliably monitor critical physiological parameters in real time over extended periods. While degradable magnesium-based electronics have pioneered this effort, relatively short functional lifetimes have slowed clinical translation. Barrier films that are both flexible and resorbable over predictable timelines would enable tunability in device lifetime and expand the viability of these devices. Herein, we present a library of stereocontrolled succinate-based copolyesters which leverage copolymer composition and processing method to afford tunability over thermomechanical, crystalline, and barrier properties. One copolymer composition within this library has extended the functional lifetime of transient bioelectronic prototypes over existing systems by several weeks-representing a considerable step towards translational devices.


Asunto(s)
Electrónica , Polímeros , Polímeros/química
7.
Anal Chim Acta ; 1283: 341963, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-37977787

RESUMEN

Polymer thin films are often used in transdermal patches as a method of continuous drug administration for patients with chronic illness. Understanding the drug segregation and distribution within these films is important for monitoring proper drug release over time. Surface-layer matrix-assisted laser desorption/ionization mass spectrometry imaging (SL-MALDI-MSI) is a unique analytical technique that provides an optical representation of chemical compositions that exist at the surface of polymeric materials. Solvent-free sublimation is employed for application of matrix to the sample surface, so that only molecules in direct contact with the matrix layer are detected. Here, these methodologies are utilized to visualize variations in drug concentration at both the air and substrate interface in pharmaceutical-loaded polymer films.


Asunto(s)
Polímeros , Urea , Humanos , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Preparaciones Farmacéuticas , Rayos Láser
8.
Nat Commun ; 14(1): 4838, 2023 08 10.
Artículo en Inglés | MEDLINE | ID: mdl-37563117

RESUMEN

Polymers are ubiquitous to almost every aspect of modern society and their use in medical products is similarly pervasive. Despite this, the diversity in commercial polymers used in medicine is stunningly low. Considerable time and resources have been extended over the years towards the development of new polymeric biomaterials which address unmet needs left by the current generation of medical-grade polymers. Machine learning (ML) presents an unprecedented opportunity in this field to bypass the need for trial-and-error synthesis, thus reducing the time and resources invested into new discoveries critical for advancing medical treatments. Current efforts pioneering applied ML in polymer design have employed combinatorial and high throughput experimental design to address data availability concerns. However, the lack of available and standardized characterization of parameters relevant to medicine, including degradation time and biocompatibility, represents a nearly insurmountable obstacle to ML-aided design of biomaterials. Herein, we identify a gap at the intersection of applied ML and biomedical polymer design, highlight current works at this junction more broadly and provide an outlook on challenges and future directions.


Asunto(s)
Materiales Biocompatibles , Polímeros
9.
Adv Mater ; 35(41): e2302163, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37399511

RESUMEN

Most elastomers undergo strain-induced crystallization (SIC) under tension; as individual chains are held rigidly in a fixed position by an applied strain, their alignment along the strain field results in a shift from strain-hardening (SH) to SIC. A similar degree of stretching is associated with the tension necessary to accelerate mechanically coupled, covalent chemical responses of mechanophores in overstretched chains, raising the possibility of an interplay between the macroscopic response of SIC and the molecular response of mechanophore activation. Here, thiol-yne-derived stereoelastomers doped covalently with a dipropiolate-derivatized spiropyran (SP) mechanophore (0.25-0.38 mol%) are reported. The material properties of SP-containing films are consistent with undoped controls, indicating that the SP is a reporter of the mechanical state of the polymer. Uniaxial tensile tests reveal correlations between mechanochromism and SIC, which are strain-rate-dependent. When mechanochromic films are stretched slowly to the point of mechanophore activation, the covalently tethered mechanophore remains trapped in a force-activated state, even after the applied stress is removed. Mechanophore reversion kinetics correlate with the applied strain rate, resulting in highly tunable decoloration rates. Because these polymers are not covalently crosslinked, they are recyclable by melt-pressing into new films, increasing their potential range of strain-sensing, morphology-sensing, and shape-memory applications.

10.
J Funct Biomater ; 14(7)2023 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-37504845

RESUMEN

The objective of this research was to create and appraise biodegradable polymer-based nanofibers containing distinct concentrations of calcium trimetaphosphate (Ca-TMP) for periodontal tissue engineering. Poly(ester urea) (PEU) (5% w/v) solutions containing Ca-TMP (15%, 30%, 45% w/w) were electrospun into fibrous scaffolds. The fibers were evaluated using SEM, EDS, TGA, FTIR, XRD, and mechanical tests. Degradation rate, swelling ratio, and calcium release were also evaluated. Cell/Ca-TMP and cell/scaffold interaction were assessed using stem cells from human exfoliated deciduous teeth (SHEDs) for cell viability, adhesion, and alkaline phosphatase (ALP) activity. Analysis of variance (ANOVA) and post-hoc tests were used (α = 0.05). The PEU and PEU/Ca-TMP-based membranes presented fiber diameters at 469 nm and 414-672 nm, respectively. Chemical characterization attested to the Ca-TMP incorporation into the fibers. Adding Ca-TMP led to higher degradation stability and lower dimensional variation than the pure PEU fibers; however, similar mechanical characteristics were observed. Minimal calcium was released after 21 days of incubation in a lipase-enriched solution. Ca-TMP extracts enhanced cell viability and ALP activity, although no differences were found between the scaffold groups. Overall, Ca-TMP was effectively incorporated into the PEU fibers without compromising the morphological properties but did not promote significant cell function.

11.
Sci Adv ; 9(22): eadg1082, 2023 06 02.
Artículo en Inglés | MEDLINE | ID: mdl-37267353

RESUMEN

Extracellular vesicles (EVs) can affect immune responses through antigen presentation and costimulation or coinhibition. We generated designer EVs to modulate T cells in the context of type 1 diabetes, a T cell-mediated autoimmune disease, by engineering a lymphoblast cell line, K562, to express HLA-A*02 (HLA-A2) alongside costimulatory CD80 and/or coinhibitory programmed death ligand 1 (PD-L1). EVs presenting HLA-A2 and CD80 activated CD8+ T cells in a dose, antigen, and HLA-specific manner. Adding PD-L1 to these EVs produced an immunoregulatory response, reducing CD8+ T cell activation and cytotoxicity in vitro. EVs alone could not stimulate T cells without antigen-presenting cells. EVs lacking CD80 were ineffective at modulating CD8+ T cell activation, suggesting that both peptide-HLA complex and costimulation are required for EV-mediated immune modulation. These results provide mechanistic insight into the rational design of EVs as a cell-free approach to immunotherapy that can be tailored to promote inflammatory or tolerogenic immune responses.


Asunto(s)
Diabetes Mellitus Tipo 1 , Vesículas Extracelulares , Humanos , Antígeno B7-H1/metabolismo , Linfocitos T CD8-positivos/metabolismo , Antígeno HLA-A2/metabolismo , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 1/metabolismo , Vesículas Extracelulares/metabolismo
12.
bioRxiv ; 2023 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-37131658

RESUMEN

Pancreatic beta cells are among the slowest replicating cells in the human body. Human beta cells usually do not increase in number with exceptions being during the neonatal period, in cases of obesity, and during pregnancy. This project explored maternal serum for stimulatory potential on human beta cell proliferation and insulin output. Gravid, full-term women who were scheduled to undergo cesarean delivery were recruited for this study. A human beta cell line was cultured in media supplemented with serum from pregnant and non-pregnant donors and assessed for differences in proliferation and insulin secretion. A subset of pregnant donor sera induced significant increases in beta cell proliferation and insulin secretion. Pooled serum from pregnant donors also increased proliferation in primary human beta cells but not primary human hepatocytes indicating a cell-type specific effect. This study suggests stimulatory factors in human serum during pregnancy could provide a novel approach for human beta cell expansion.

13.
Front Cell Dev Biol ; 11: 1155882, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37255596

RESUMEN

Cell migration plays an essential role in physiological and pathological states, such as immune response, tissue generation and tumor development. This phenomenon can occur spontaneously or it can be triggered by an external stimuli, including biochemical, mechanical, or electrical cues that induce or direct cells to migrate. The migratory response to these cues is foundational to several fields including neuroscience, cancer and regenerative medicine. Various platforms are available to qualitatively and quantitatively measure cell migration, making the measurements of cell motility straight-forward. Migratory behavior must be analyzed by multiple metrics and then models to connect the measurements to physiological meaning. This review will focus on describing and quantifying cell movement for individual cell migration.

14.
Nat Neurosci ; 26(6): 1068-1079, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37248339

RESUMEN

The cerebellum is hypothesized to refine movement through online adjustments. We examined how such predictive control may be generated using a mouse reach paradigm, testing whether the cerebellum uses within-reach information as a predictor to adjust reach kinematics. We first identified a population-level response in Purkinje cells that scales inversely with reach velocity, pointing to the cerebellar cortex as a potential site linking kinematic predictors and anticipatory control. Next, we showed that mice can learn to compensate for a predictable reach perturbation caused by repeated, closed-loop optogenetic stimulation of pontocerebellar mossy fiber inputs. Both neural and behavioral readouts showed adaptation to position-locked mossy fiber perturbations and exhibited aftereffects when stimulation was removed. Surprisingly, position-randomized stimulation schedules drove partial adaptation but no opposing aftereffects. A model that recapitulated these findings suggests that the cerebellum may decipher cause-and-effect relationships through time-dependent generalization mechanisms.


Asunto(s)
Cerebelo , Células de Purkinje , Cerebelo/fisiología , Movimiento/fisiología , Aprendizaje , Condicionamiento Clásico
15.
Biotechnol Bioeng ; 120(4): 1068-1080, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36585356

RESUMEN

In the production of biopharmaceuticals such as monoclonal antibodies (mAbs) and vaccines, the residual amounts of host-cell proteins (HCPs) are among the critical quality attributes. In addition to overall HCP levels, individual HCPs may elude purification, potentially causing issues in product stability or patient safety. Such HCP persistence has been attributed mainly to biophysical interactions between individual HCPs and the product, resin media, or residual chromatin particles. Based on measurements on process streams from seven mAb processes, we have found that HCPs in aggregates, not necessarily chromatin-derived, may play a significant role in the persistence of many HCPs. Such aggregates may also hinder accurate detection of HCPs using existing proteomics methods. The findings also highlight that certain HCPs may be difficult to remove because of their functional complementarity to the product; specifically, chaperones and other proteins involved in the unfolded protein response (UPR) are disproportionately present in the aggregates. The methods and findings described here expand our understanding of the origins and potential behavior of HCPs in cell-based biopharmaceutical processes and may be instrumental in improving existing techniques for HCP detection and clearance.


Asunto(s)
Productos Biológicos , Agregado de Proteínas , Cricetinae , Animales , Humanos , Cricetulus , Anticuerpos Monoclonales , Proteómica/métodos , Células CHO
16.
Biomaterials ; 292: 121940, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36493714

RESUMEN

Intraperitoneal adhesions (IAs) are a major complication arising from abdominal repair surgeries, including hernia repair procedures. Herein, we fabricated a composite mesh device using a macroporous monofilament polypropylene mesh and a degradable elastomer coating designed to meet the requirements of this clinical application. The degradable elastomer was synthesized using an organo-base catalyzed thiol-yne addition polymerization that affords independent control of degradation rate and mechanical properties. The elastomeric coating was further enhanced by the covalent tethering of antifouling zwitterion molecules. Mechanical testing demonstrated the elastomer forms a robust coating on the polypropylene mesh does not exhibit micro-fractures, cracks or mechanical delamination under cyclic fatigue testing that exceeds peak abdominal loads (50 N/cm). Quartz crystal microbalance measurements showed the zwitterionic functionalized elastomer further reduced fibrinogen adsorption by 73% in vitro when compared to unfunctionalized elastomer controls. The elastomer exhibited degradation with limited tissue response in a 10-week murine subcutaneous implantation model. We also evaluated the composite mesh in an 84-day study in a rabbit cecal abrasion hernia adhesion model. The zwitterionic composite mesh significantly reduced the extent and tenacity of IAs by 94% and 90% respectively with respect to uncoated polypropylene mesh. The resulting composite mesh device is an excellent candidate to reduce complications related to abdominal repair through suppressed fouling and adhesion formation, reduced tissue inflammation, and appropriate degradation rate.


Asunto(s)
Polipropilenos , Mallas Quirúrgicas , Conejos , Ratones , Animales , Mallas Quirúrgicas/efectos adversos , Adhesivos , Elastómeros , Implantes Absorbibles , Adherencias Tisulares/prevención & control , Adherencias Tisulares/etiología , Hernia/prevención & control
17.
Front Endocrinol (Lausanne) ; 13: 989815, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36506044

RESUMEN

There is a critical need for therapeutic approaches that combine renewable sources of replacement beta cells with localized immunomodulation to counter recurrence of autoimmunity in type 1 diabetes (T1D). However, there are few examples of animal models to study such approaches that incorporate spontaneous autoimmunity directed against human beta cells rather than allogenic rejection. Here, we address this critical limitation by demonstrating rejection and survival of transplanted human stem cell-derived beta-like cells clusters (sBCs) in a fully immune competent mouse model with matching human HLA class I and spontaneous diabetes development. We engineered localized immune tolerance toward transplanted sBCs via inducible cell surface overexpression of PD-L1 (iP-sBCs) with and without deletion of all HLA class I surface molecules via beta-2 microglobulin knockout (iP-BKO sBCs). NOD.HLA-A2.1 mice, which lack classical murine MHC I and instead express human HLA-A*02:01, underwent transplantation of 1,000 human HLA-A*02:01 sBCs under the kidney capsule and were separated into HLA-A2 positive iP-sBC and HLA-class I negative iP-BKO sBC groups, each with +/- doxycycline (DOX) induced PD-L1 expression. IVIS imaging showed significantly improved graft survival in mice transplanted with PD-L1 expressing iP-sBC at day 3 post transplantation compared to controls. However, luciferase signal dropped below in vivo detection limits by day 14 for all groups in this aggressive immune competent diabetes model. Nonetheless, histological examination revealed significant numbers of surviving insulin+/PD-L1+ sBCs cells for DOX-treated mice at day 16 post-transplant despite extensive infiltration with high numbers of CD3+ and CD45+ immune cells. These results show that T cells rapidly infiltrate and attack sBC grafts in this model but that significant numbers of PD-L1 expressing sBCs manage to survive in this harsh immunological environment. This investigation represents one of the first in vivo studies recapitulating key aspects of human autoimmune diabetes to test immune tolerance approaches with renewable sources of beta cells.


Asunto(s)
Diabetes Mellitus Tipo 1 , Supervivencia de Injerto , Humanos , Ratones , Animales , Ratones Endogámicos NOD , Antígeno B7-H1/genética , Antígeno HLA-A2 , Células Madre , Diabetes Mellitus Tipo 1/cirugía
18.
Nanoscale ; 14(45): 16845-16856, 2022 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-36331392

RESUMEN

Printed carbon nanotube thin-film transistors (CNT-TFTs) are candidates for flexible electronics with printability on a wide range of substrates. Among the layers comprising a CNT-TFT, the gate dielectric has proven most difficult to additively print owing to challenges in film uniformity, thickness, and post-processing requirements. Printed ionic dielectrics show promise for addressing these issues and yielding devices that operate at low voltages thanks to their high-capacitance electric double layers. However, the printing of ionic dielectrics in their various compositions is not well understood, nor is the impact of certain stresses on these materials. In this work, we studied three compositionally distinct ionic dielectrics in fully printed CNT-TFTs: the polar-fluorinated polymer elastomer PVDF-HFP; an ion gel consisting of triblock polymer PS-PMMA-PS and ionic liquid EMIM-TFSI; and crystalline nanocellulose (CNC) with a salt concentration of 0.05%. Although ion gel has been thoroughly studied, e-PVDF-HFP and CNC printing are relatively new and this study provides insights into their ink formulation, print processing, and performance as gate dielectrics. Using a consistent aerosol jet printing approach, each ionic dielectric was printed into similar CNT-TFTs, allowing for direct comparison through extensive characterization, including mechanical and electrical stress tests. The ionic dielectrics were found to have distinct operational dependencies based on their compositional and ionic attributes. Overall, the results reveal a number of trade-offs that must be managed when selecting a printable ionic dielectric, with CNC showing the strongest performance for low-voltage operation but the ion gel and elastomer exhibiting better stability under bias and mechanical stresses.

19.
Nat Commun ; 13(1): 6518, 2022 10 31.
Artículo en Inglés | MEDLINE | ID: mdl-36316354

RESUMEN

Physically transient forms of electronics enable unique classes of technologies, ranging from biomedical implants that disappear through processes of bioresorption after serving a clinical need to internet-of-things devices that harmlessly dissolve into the environment following a relevant period of use. Here, we develop a sustainable manufacturing pathway, based on ultrafast pulsed laser ablation, that can support high-volume, cost-effective manipulation of a diverse collection of organic and inorganic materials, each designed to degrade by hydrolysis or enzymatic activity, into patterned, multi-layered architectures with high resolution and accurate overlay registration. The technology can operate in patterning, thinning and/or cutting modes with (ultra)thin eco/bioresorbable materials of different types of semiconductors, dielectrics, and conductors on flexible substrates. Component-level demonstrations span passive and active devices, including diodes and field-effect transistors. Patterning these devices into interconnected layouts yields functional systems, as illustrated in examples that range from wireless implants as monitors of neural and cardiac activity, to thermal probes of microvascular flow, and multi-electrode arrays for biopotential sensing. These advances create important processing options for eco/bioresorbable materials and associated electronic systems, with immediate applicability across nearly all types of bioelectronic studies.


Asunto(s)
Implantes Absorbibles , Electrónica , Semiconductores , Electrodos , Rayos Láser
20.
Ecol Evol ; 12(10): e9414, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36262265

RESUMEN

Large herbivore migrations are imperiled globally; however the factors limiting a population across its migratory range are typically poorly understood. Zambia's Greater Liuwa Ecosystem (GLE) contains one of the largest remaining blue wildebeest (Connochaetes taurinus taurinus) migrations, yet the population structure, vital rates, and limiting factors are virtually unknown. We conducted a long-term demographic study of GLE wildebeest from 2012 to 2019 of 107 collared adult females and their calves, 7352 herd observations, 12 aerial population surveys, and concurrent carnivore studies. We applied methods of vital rate estimation and survival analysis within a Bayesian estimation framework. From herd composition observations, we estimated rates of fecundity, first-year survival, and recruitment as 68%, 56%, and 38% respectively, with pronounced interannual variation. Similar rates were estimated from calf-detections with collared cows. Adult survival rates declined steadily from 91% at age 2 years to 61% at age 10 years thereafter dropping more sharply to 2% at age 16 years. Predation, particularly by spotted hyena, was the predominant cause of death for all wildebeest ages and focused on older animals. Starvation only accounted for 0.8% of all unbiased known natural causes of death. Mortality risk differed substantially between wet and dry season ranges, reflecting strong spatio-temporal differences in habitat and predator densities. There was substantial evidence that mortality risk to adults was 27% higher in the wet season, and strong evidence that it was 45% higher in the migratory range where predator density was highest. The estimated vital rates were internally consistent, predicting a stable population trajectory consistent with aerial estimates. From essentially zero knowledge of GLE wildebeest dynamics, this work provides vital rates, age structure, limiting factors, and a plausible mechanism for the migratory tendency, and a robust model-based foundation to evaluate the effects of potential restrictions in migratory range, climate change, predator-prey dynamics, and poaching.

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