RESUMO
Understanding signaling pathways that regulate pancreatic ß-cell function to produce, store, and release insulin, as well as pathways that control ß-cell proliferation, is vital to find new treatments for diabetes mellitus. Transforming growth factor-beta (TGF-ß) signaling is involved in a broad range of ß-cell functions. The canonical TGF-ß signaling pathway functions through intracellular smads, including smad2 and smad3, to regulate cell development, proliferation, differentiation, and function in many organs. Here, we demonstrate the role of TGF-ß/smad2 signaling in regulating mature ß-cell proliferation and function using ß-cell-specific smad2 null mutant mice. ß-cell-specific smad2-deficient mice exhibited improved glucose clearance as demonstrated by glucose tolerance testing, enhanced in vivo and ex vivo glucose-stimulated insulin secretion, and increased ß-cell mass and proliferation. Furthermore, when these mice were fed a high-fat diet to induce hyperglycemia, they again showed improved glucose tolerance, insulin secretion, and insulin sensitivity. In addition, ex vivo analysis of smad2-deficient islets showed that they displayed increased glucose-stimulated insulin secretion and upregulation of genes involved in insulin synthesis and insulin secretion. Thus, we conclude that smad2 could represent an attractive therapeutic target for type 2 diabetes mellitus.
Assuntos
Hiperglicemia/metabolismo , Secreção de Insulina , Células Secretoras de Insulina/metabolismo , Transdução de Sinais , Proteína Smad2/metabolismo , Animais , Dieta Hiperlipídica/efeitos adversos , Hiperglicemia/induzido quimicamente , Hiperglicemia/genética , Camundongos , Camundongos Knockout , Proteína Smad2/genéticaRESUMO
Despite the common use of fingerprints as a trusted means of identification, no method currently exists to reliably establish the time since deposition of latent fingerprints. A reproducible method of establishing latent fingerprint age would allow forensic personnel to determine if a latent fingerprint was relevant to a crime. This work investigates the ambient aging of triacylglycerols (TGs) and other lipids in latent fingerprint residue utilizing matrix-assisted laser desorption/ionization mass spectrometry imaging. Unsaturated TGs were found to undergo ambient ozonolysis resulting in a decrease over time. At the same time, two series of compounds related to the degradation of unsaturated TGs due to ambient ozonolysis emerged with time and were detectable within a single day of aging. Tracking the degradation of unsaturated TGs over time proved to be relatively reproducible in multiple individuals and is suggested as a means of establishing latent fingerprint age.
Assuntos
Ozônio/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Triglicerídeos/químicaRESUMO
Phosphate glasses containing Nd3+, Gd3+, and Yb3+ as lanthanide ions are attractive for applications in laser materials, phototherapy lamps, and solar spectral converters. The composition-structure-property relation in this type of glass system is thus of interest from fundamental and applied perspectives. In this work, the impact of the differing ionic radius of Nd3+, Gd3+, and Yb3+ and consequent field strength on the physical properties of phosphate glasses is investigated, focusing ultimately on thermal expansion effects. The glasses were made by melting with a fixed concentration of the lanthanide ions having 50P2O5-46BaO-4Ln2O3 nominal compositions (mol %) with Ln = Nd, Gd, and Yb. The investigation encompassed measurements by X-ray diffraction (XRD), optical spectroscopy, density, X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, and dilatometry. XRD supported the amorphous nature of the glasses, whereas absorption and photoluminescence spectra showed the optical features of the Nd3+, Gd3+, and Yb3+ ions in the glasses. Oxygen speciation by XPS indicated an increase in nonbridging oxygens for the larger radii Nd3+ and Gd3+ ions relative to the host, contrasting with Yb3+. Phosphorus XPS analysis further supported the hypothesis that the P 2p binding energies of the glasses increased with the cation field strength of the lanthanides. The Raman spectra were interpreted based on glass depolymerization effects and the impact of Ln3+ ions with high field strength. Particularly, the band position of the symmetric out-of-chain nonbridging oxygen stretch, νs(PO2-), shifted to higher frequencies correlating with the Ln3+ field strength. Dilatometry ultimately revealed a steady decrease in the coefficient of thermal expansion for the glasses, which correlated linearly with Ln3+ field strengths and thus indicated to sustain increased glass rigidities. The various analyses performed thus illuminated the structural foundation of the thermomechanical behavior of the glasses connected with changes in the Ln3+ field strengths.
RESUMO
Chronic pancreatitis is a debilitating disease affecting millions worldwide. These patients suffer from bouts of severe pain that are minimally relieved by pain medications and may necessitate major surgeries with high morbidity and mortality. Previously, we demonstrated that "chemical pancreatectomy," a pancreatic intraductal infusion of dilute acetic acid solution, ablated the exocrine pancreas while preserving the endocrine pancreas. Notably, chemical pancreatectomy resolved chronic inflammation, alleviated allodynia in the cerulein pancreatitis model, and improved glucose homeostasis. Herein, we extensively tested the feasibility of a chemical pancreatectomy in NHPs and validated our previously published pilot study. We did serial computed tomography (CT) scans of the abdomen and pelvis, analyzed dorsal root ganglia, measured serum enzymes, and performed histological and ultrastructural assessments and pancreatic endocrine function assays. â¯Based on serial CT scans, chemical pancreatectomy led to the loss of pancreatic volume. Immunohistochemistry and transmission electron microscopy demonstrated exocrine pancreatic ablation with endocrine islet preservation. Importantly, chemical pancreatectomy did not increase pro-nociceptive markers in harvested dorsal root ganglia. Also, chemical pancreatectomy improved insulin secretion to supranormal levels in vivo and in vitro. Thus, this study may provide a foundation for translating this procedure to patients with chronic pancreatitis or other conditions requiring a pancreatectomy.
RESUMO
Chronic pancreatitis is a debilitating disease affecting millions worldwide. These patients suffer from bouts of severe pain that are minimally relieved by pain medications and may necessitate major surgeries with high morbidity and mortality. Previously, we demonstrated that "chemical pancreatectomy," a pancreatic intraductal infusion of dilute acetic acid solution, ablated the exocrine pancreas while preserving the endocrine pancreas. Notably, chemical pancreatectomy resolved chronic inflammation, alleviated allodynia in the cerulein pancreatitis model, and improved glucose homeostasis. Herein, we extensively tested the feasibility of a chemical pancreatectomy in NHPs and validated our previously published pilot study. We did serial computed tomography (CT) scans of the abdomen and pelvis, analyzed dorsal root ganglia, measured serum enzymes, and performed histological and ultrastructural assessments and pancreatic endocrine function assays. Based on serial CT scans, chemical pancreatectomy led to the loss of pancreatic volume. Immunohistochemistry and transmission electron microscopy demonstrated exocrine pancreatic ablation with endocrine islet preservation. Importantly, chemical pancreatectomy did not increase pro-nociceptive markers in harvested dorsal root ganglia. Also, chemical pancreatectomy improved insulin secretion to supranormal levels in vivo and in vitro. Thus, this study may provide a foundation for translating this procedure to patients with chronic pancreatitis or other conditions requiring a pancreatectomy.
Assuntos
Pancreatectomia , Pancreatite Crônica , Animais , Pancreatectomia/métodos , Projetos Piloto , Pancreatite Crônica/cirurgia , Primatas , Dor , Doença CrônicaRESUMO
There is growing awareness of the need for mathematics and computing to quantitatively understand the complex dynamics and feedbacks in the life sciences. Although several institutions and research groups are conducting pioneering multidisciplinary research, communication and education across fields remain a bottleneck. The opportunity is ripe for using education research-supported mechanisms of cross-disciplinary training at the intersection of mathematics, computation, and biology. This case study uses the computational apprenticeship theoretical framework to describe the efforts of a computational biology lab to rapidly prototype, test, and refine a mentorship infrastructure for undergraduate research experiences. We describe the challenges, benefits, and lessons learned, as well as the utility of the computational apprenticeship framework in supporting computational/math students learning and contributing to biology, and biologists in learning computational methods. We also explore implications for undergraduate classroom instruction and cross-disciplinary scientific communication.
RESUMO
We present the longest available dataset (by 15 years) of estuarine zooplankton abundance worldwide. Zooplankton have been monitored throughout the upper San Francisco Estuary from 1972 -present due to its status as a central hub of California water delivery and home to commercially important and endangered fishes. We integrated data from five monitoring programs, including over 300 locations, three size-classes of zooplankton targeted with different gears, over 80,000 samples, and over two billion sampled organisms. Over the duration of this dataset, species invasions have driven community turnover, periodic droughts have occurred, and important fishes have declined, likely due in part to reduced food supply from zooplankton. Data from the individual surveys have been used in prior studies on issues related to species invasions, flows, fish diets and population dynamics, zooplankton population dynamics, and community ecology. Our integrated dataset offers unparalleled spatio-temporal scope to address these and other fundamental ecological questions.
Assuntos
Estuários , Zooplâncton , Animais , Ecossistema , Peixes , São FranciscoRESUMO
The mycobacteriophages JeTaime (E cluster) and Luna22 (Q cluster) were isolated from soil in Providence, Rhode Island, and Charleston, South Carolina, respectively, using a Mycobacterium smegmatis mc2 155 host. The genome of JeTaime is 75,099 bp (142 predicted genes), and that of Luna22 is 53,730 bp (87 predicted genes). Both phages exhibit Siphoviridae morphology.
RESUMO
We developed a new age-structured deterministic model for the transmission dynamics of chikungunya virus. The model is analyzed to gain insights into the qualitative features of its associated equilibria. Some of the theoretical and epidemiological findings indicate that the stable disease-free equilibrium is globally asymptotically stable when the associated reproduction number is less than unity. Furthermore, the model undergoes, in the presence of disease induced mortality, the phenomenon of backward bifurcation, where the stable disease-free equilibrium of the model coexists with a stable endemic equilibrium when the associated reproduction number is less than unity. Further analysis of the model indicates that the qualitative dynamics of the model are not altered by the inclusion of age structure. This is further emphasized by the sensitivity analysis results, which shows that the dominant parameters of the model are not altered by the inclusion of age structure. However, the numerical simulations show the flaw of the exclusion of age in the transmission dynamics of chikungunya with regard to control implementations. The exclusion of age structure fails to show the age distribution needed for an effective age based control strategy, leading to a one size fits all blanket control for the entire population.
Assuntos
Febre de Chikungunya/diagnóstico , Febre de Chikungunya/transmissão , Vírus Chikungunya , Algoritmos , Animais , Número Básico de Reprodução , Febre de Chikungunya/virologia , Simulação por Computador , Culicidae , Surtos de Doenças , Humanos , Modelos Biológicos , Sensibilidade e EspecificidadeRESUMO
By prohibiting fishing, marine protected areas (MPAs) provide a refuge for harvested species. Humans are often perceived as predators by prey and therefore respond fearfully to humans. Thus, fish responses to humans inside and outside of an MPA can provide insights into their perception of humans as a predatory threat. Previous studies have found differences in the distance that harvested species of fish initiate flight (flight initiation distance-FID) from humans inside and outside an MPA, but less is known about unharvested species. We focused on whether the lined bristletooth Ctenochaetus striatus, an unharvested surgeonfish, can discriminate between a snorkeler and a snorkeler with a spear gun inside and outside of a no-take MPA in Mo'orea, French Polynesia. Additionally, we incorporated starting distance (the distance between the person and prey at the start of an experimental approach), a variable that has been found to be important in assessing prey escape decisions in terrestrial species, but that has not been extensively studied in aquatic systems. Lined bristletooth FID was significantly greater in the presence of a spear gun and varied depending on if the spear gun encounter was inside or outside of the MPA. These results imply a degree of sophistication of fish antipredator behavior, generate questions as to how a nontargeted species of fish could acquire fear of humans, and demonstrate that behavioral surveys can provide insights about antipredator behavior.