Association between First Trimester Pregnancy Associated Plasma Protein–A (PAPP-A) and Gestational Diabetes Mellitus Development

Background: Gestational diabetes (GDM) is a common pregnancy complication with significant cardiometabolic consequences for mothers and offspring. Previous research from our group suggests that adipose tissue IGFBP-5 and its unique metalloprotease PAPP-A (Pregnancy Associated Plasma Protein-A) may play mechanistic roles in GDM development by regulating functional IGF-1 levels and lipid storage and metabolism. Aim: To examine the relationship between circulating PAPP-A levels and GDM development. We hypothesized that high first trimester PAPP-A levels would be associated with decreased GDM risk. Methods: A retrospective cohort of women delivering singleton gestations at UMass Memorial Healthcare (2009, 2010, 2014, 2015) was assembled by abstracting electronic medical records. PAPP-A was measured in first trimester (11-14 weeks), and reported as quartiles of multiples of the mean (MoM) based on gestational age and adjusted for maternal weight and race/ethnicity. GDM diagnosis based on standard 2-step protocol (~24-28 weeks; failed 50g 1hr glucola screen then ≥2 abnormal values per Carpenter-Coustan criteria on 100g 3hr glucose tolerance test). Crude and multivariable-adjusted logistic regression models estimated the association between PAPP-A MoM quartiles and GDM. Results: Women (N=1,251) were 29.7 (SD:5.7) years old and 12.5 (SD:0.6) weeks gestation at PAPP-A measurement. 7.6% (n=95) developed GDM. Median PAPP-A MoM were 0.7 (inter-quartile range [IQR]=0.5-1.0) among women with GDM and 0.9 (IQR=0.6-1.3) among controls; 39% versus 23% were in the 1st quartile, respectively. After adjusting for pre-pregnancy body mass index, nuchal translucency, crown rump length, smoking status, and parity, women with PAPP-A MoM in 2nd, 3rd, and 4th quartiles had 52% (OR=0.48, 95%CI=0.26-0.88), 45% (OR=0.55, 95%CI=0.30-0.99) and 73% (OR=0.27, 95%CI=0.13-0.53) lower odds of GDM compared to women in the 1st quartile. Conclusion: Higher PAPP-A MoM levels were associated with lower GDM risk. Future studies will assess whether higher PAPP-A levels are associated with enhanced IGF-1 signaling and improved pregnancy metabolic homeostasis

Association between First Trimester Pregnancy Associated Plasma Protein–A and the Development of Gestational Diabetes Mellitus

Background: Gestational diabetes (GDM) is a common pregnancy complication with significant cardiometabolic consequences for mothers and offspring. Previous research from our group suggests that adipose tissue IGFBP-5 and its unique metalloprotease PAPP-A (Pregnancy Associated Plasma Protein-A) may play mechanistic roles in GDM development by regulating functional IGF-1 levels and lipid storage and metabolism. Aim: To examine the relationship between circulating PAPP-A levels and GDM development. We hypothesized that high first trimester PAPP-A levels would be associated with decreased GDM risk. Methods: A retrospective cohort of women delivering singleton gestations at UMass Memorial Healthcare (2009, 2010, 2014, 2015) was assembled by abstracting electronic medical records. PAPP-A was measured in first trimester (11-14 weeks), and reported as quartiles of multiples of the mean (MoM) based on gestational age and adjusted for maternal weight and race/ethnicity. GDM diagnosis based on standard 2-step protocol (~24-28 weeks; failed 50g 1hr glucola screen then ≥2 abnormal values per Carpenter-Coustan criteria on 100g 3hr glucose tolerance test). Crude and multivariable-adjusted logistic regression models estimated the association between PAPP-A MoM quartiles and GDM. Results: Women (N=1,251) were 29.7 (SD:5.7) years old and 12.5 (SD:0.6) weeks gestation at PAPP-A measurement. 7.6% (n=95) developed GDM. Median PAPP-A MoM were 0.7 (inter-quartile range [IQR]=0.5-1.0) among women with GDM and 0.9 (IQR=0.6-1.3) among controls; 39% versus 23% were in the 1st quartile, respectively. After adjusting for pre-pregnancy body mass index, nuchal translucency, crown rump length, smoking status, and parity, women with PAPP-A MoM in 2nd, 3rd, and 4th quartiles had 52% (OR=0.48, 95%CI=0.26-0.88), 45% (OR=0.55, 95%CI=0.30-0.99) and 73% (OR=0.27, 95%CI=0.13-0.53) lower odds of GDM compared to women in the 1st quartile. Conclusion: Higher PAPP-A MoM levels were associated with lower GDM risk. Future studies will assess whether higher PAPP-A levels are associated with enhanced IGF-1 signaling and improved pregnancy metabolic homeostasis

Mode-coupling approach to non-Newtonian Hele-Shaw flow

The Saffman-Taylor viscous fingering problem is investigated for the displacement of a non-Newtonian fluid by a Newtonian one in a radial Hele-Shaw cell. We execute a mode-coupling approach to the problem and examine the morphology of the fluid-fluid interface in the weak shear limit. A differential equation describing the early nonlinear evolution of the interface modes is derived in detail. Owing to vorticity arising from our modified Darcy's law, we introduce a vector potential for the velocity in contrast to the conventional scalar potential. Our analytical results address how mode-coupling dynamics relates to tip-splitting and side branching in both shear thinning and shear thickening cases. The development of non-Newtonian interfacial patterns in rectangular Hele-Shaw cells is also analyzed.Comment: 14 pages, 5 ps figures, Revtex4, accepted for publication in Phys. Rev.

Viscous fingering in liquid crystals: Anisotropy and morphological transitions

We show that a minimal model for viscous fingering with a nematic liquid crystal in which anisotropy is considered to enter through two different viscosities in two perpendicular directions can be mapped to a two-fold anisotropy in the surface tension. We numerically integrate the dynamics of the resulting problem with the phase-field approach to find and characterize a transition between tip-splitting and side-branching as a function of both anisotropy and dimensionless surface tension. This anisotropy dependence could explain the experimentally observed (reentrant) transition as temperature and applied pressure are varied. Our observations are also consistent with previous experimental evidence in viscous fingering within an etched cell and simulations of solidification.Comment: 12 pages, 3 figures. Submitted to PR

A phase-field model of Hele-Shaw flows in the high viscosity contrast regime

A one-sided phase-field model is proposed to study the dynamics of unstable interfaces of Hele-Shaw flows in the high viscosity contrast regime. The corresponding macroscopic equations are obtained by means of an asymptotic expansion from the phase-field model. Numerical integrations of the phase-field model in a rectangular Hele-Shaw cell reproduce finger competition with the final evolution to a steady state finger the width of which goes to one half of the channel width as the velocity increases

Sorting of EGF and transferrin at the plasma membrane and by cargo-specific signaling to EEA1-enriched endosomes

The biological function of receptors is determined by their appropriate trafficking through the endosomal pathway. Following internalization, the transferrin (Tf) receptor quantitatively recycles to the plasma membrane, whereas the epidermal growth factor (EGF) receptor undergoes degradation. To determine how Tf and EGF engage these two different pathways we imaged their binding and early endocytic pathway in live cells using total internal reflection fluorescence microscopy (TIRF-M). We find that EGF and Tf bind to distinct plasma membrane regions and are incorporated into different endocytic vesicles. After internalization, both EGF-enriched and Tf-enriched vesicles interact with endosomes containing early endosome antigen 1 (EEA1). EGF is incorporated and retained in these endosomes, while Tf-containing vesicles rapidly dissociate and move to a juxtanuclear compartment. Endocytic vesicles carrying EGF recruit more Rab5 GTPase than those carrying Tf, which, by strengthening their association with EEA1-enriched endosomes, may provide a mechanism for the observed cargo-specific sorting. These results reveal pre-endocytic sorting of Tf and EGF, a specialized role for EEA1-enriched endosomes in EGF trafficking, and a potential mechanism for cargo-specified sorting of endocytic vesicles by these endosomes

Dynamic Characterization of Permeabilities and Flows in Microchannels

We make an analytical study of the nonsteady flow of Newtonian fluids in microchannels. We consider the slip boundary condition at the solid walls with Navier hypothesis and calculate the dynamic permeability, which gives the system's response to dynamic pressure gradients. We find a scaling relation in the absence of slip that is broken in its presence. We discuss how this might be useful to experimentally determine by means of microparticle image velocimetry technology whether slip exists or not in a system, the value of the slip length, and the validity of Navier hypothesis in dynamic situations

NTFP harvesters as citizen scientists: Validating traditional and crowdsourced knowledge on seed production of Brazil nut trees in the Peruvian Amazon.

Understanding the factors that underlie the production of non-timber forest products (NTFPs), as well as regularly monitoring production levels, are key to allow sustainability assessments of NTFP extractive economies. Brazil nut (Bertholletia excelsa, Lecythidaceae) seed harvesting from natural forests is one of the cornerstone NTFP economies in Amazonia. In the Peruvian Amazon it is organized in a concession system. Drawing on seed production estimates of >135,000 individual Brazil nut trees from >400 concessions and ethno-ecological interviews with >80 concession holders, here we aimed to (i) assess the accuracy of seed production estimates by Brazil nut seed harvesters, and (ii) validate their traditional ecological knowledge (TEK) about the variables that influence Brazil nut production. We compared productivity estimates with actual field measurements carried out in the study area and found a positive correlation between them. Furthermore, we compared the relationships between seed production and a number of phenotypic, phytosanitary and environmental variables described in literature with those obtained for the seed production estimates and found high consistency between them, justifying the use of the dataset for validating TEK and innovative hypothesis testing. As expected, nearly all TEK on Brazil nut productivity was corroborated by our data. This is reassuring as Brazil nut concession holders, and NTFP harvesters at large, rely on their knowledge to guide the management of the trees upon which their extractive economies are based. Our findings suggest that productivity estimates of Brazil nut trees and possibly other NTFP-producing species could replace or complement actual measurements, which are very expensive and labour intensive, at least in areas where harvesters have a tradition of collecting NTFPs from the same trees over multiple years or decades. Productivity estimates might even be sourced from harvesters through registers on an annual basis, thus allowing a more cost-efficient and robust monitoring of productivity levels

Forestry performance of Bertholletia excelsa Humn. & Bonpl Lecythidaceae under different fertilizers after two years of planting.

A espécie Bertholletia excelsa é frequentemente utilizada em reflorestamentos pelo alto grau de adaptabilidade e seu ótimo crescimento inicial. Com isso, esse trabalho objetivou estudar o crescimento de B. excelsa de acordo com diferentes tipos e concentrações de adubação, buscando contribuir para o desenvolvimento silvicultural dessa espécie. Para isso, foram plantadas mudas de Bertholletia excelsa na região de Madre de Dios em uma propriedade próxima a província de Puerto Maldonado no Peru. As mudas foram selecionadas quando apresentaram altura média de 22 cm para todos os tratamentos, sendo T1: Dolomita + SPT; T2: Dolomita + NPK; T3: Dolomita + SPT + Gesso agrícola; T4: Dolomita + NPK + Gesso agrícola e o tratamento controle sem modificações por adubação. O delineamento experimental utilizado foi em blocos ao acaso com cinco tratamentos e quatro repetições de 6 plântulas cada. Uma vez atendidos os pressupostos da ANOVA, os dados foram submetidos à análise de variância, havendo diferenças significativas entre os dados, as médias foram comparadas pelo teste de Tukey (p <0,05). A sobrevivência (%) foi avaliada a partir do número de indivíduos vivos em dois anos de medição. O tratamento T4 apresentou grande potencial silvicultural pelo que a adubação proporcionou ao desenvolvimento em altura e em diâmetro. Os tratamentos T1 e T3 não obtiveram um bom desempenho quando comparado ao controle, apresentando as menores taxas de crescimento em altura e em diâmetro, e as menores taxa de sobrevivência. O tratamento controle obteve um bom resultado não diferindo estatisticamente de T4, assim concluindo que não é necessário a adubação pré-plantio de B. excelsa