Generation of Human Female Reproductive Tract Epithelium from Human Embryonic Stem Cells

BACKGROUND: Recent studies have identified stem/progenitor cells in human and mouse uterine epithelium, which are postulated to be responsible for tissue regeneration and proliferative disorders of human endometrium. These progenitor cells are thought to be derived from Müllerian duct (MD), the primordial female reproductive tract (FRT). METHODOLOGY/PRINCIPAL FINDINGS: We have developed a model of human reproductive tract development in which inductive neonatal mouse uterine mesenchyme (nMUM) is recombined with green fluorescent protein (GFP)-tagged human embryonic stem cells (hESCs); GFP-hESC (ENVY). We demonstrate for the first time that hESCs can be differentiated into cells with a human FRT epithelial cell phenotype. hESC derived FRT epithelial cells emerged from cultures containing MIXL1(+) mesendodermal precursors, paralleling events occurring during normal organogenesis. Following transplantation, nMUM treated embryoid bodies (EBs) generated epithelial structures with a typical MD phenotype that expressed the MD markers PAX2, HOXA10. Functionally, the hESCs derived FRT epithelium responded to exogenous estrogen by proliferating and secreting uterine-specific glycodelin A (GdA). CONCLUSIONS/SIGNIFICANCE: These data show nMUM can induce differentiation of hESC to form the FRT epithelium. This may provide a model to study early developmental events of the human FRT

Rational Passivation of Sulfur Vacancy Defects in Two-Dimensional Transition Metal Dichalcogenides.

Structural defects vary the optoelectronic properties of monolayer transition metal dichalcogenides, leading to concerted efforts to control defect type and density via materials growth or postgrowth passivation. Here, we explore a simple chemical treatment that allows on-off switching of low-lying, defect-localized exciton states, leading to tunable emission properties. Using steady-state and ultrafast optical spectroscopy, supported by ab initio calculations, we show that passivation of sulfur vacancy defects, which act as exciton traps in monolayer MoS2 and WS2, allows for controllable and improved mobilities and an increase in photoluminescence up to 275-fold, more than twice the value achieved by other chemical treatments. Our findings suggest a route for simple and rational defect engineering strategies for tunable and switchable electronic and excitonic properties through passivation

Rational Passivation of Sulfur Vacancy Defects in Two-Dimensional Transition Metal Dichalcogenides.

Structural defects vary the optoelectronic properties of monolayer transition metal dichalcogenides, leading to concerted efforts to control defect type and density via materials growth or postgrowth passivation. Here, we explore a simple chemical treatment that allows on-off switching of low-lying, defect-localized exciton states, leading to tunable emission properties. Using steady-state and ultrafast optical spectroscopy, supported by ab initio calculations, we show that passivation of sulfur vacancy defects, which act as exciton traps in monolayer MoS2 and WS2, allows for controllable and improved mobilities and an increase in photoluminescence up to 275-fold, more than twice the value achieved by other chemical treatments. Our findings suggest a route for simple and rational defect engineering strategies for tunable and switchable electronic and excitonic properties through passivation

Electronic properties of guanine-based nanowires

We present a first-principle study of the electronic and conduction properties of a few classes of nanowires constituted of guanine (G) molecules, self-assembled in different geometries. We first analyze the effect of the vertical $\pi$-$\pi$ interaction in model G-stack columns. Then, we exploit the results obtained from those models to interpret the features of realistic stacked and hydrogen-bonded structures, namely the guanine quadruple helices and the planar ribbons. With respect to natural DNA, the different structures as well as the inclusion of metal cations, drastically affect the bonding pattern among the bases, introducing novel features in the electronic properties of the systems. These supramolecular G-aggregates, alternative to DNA, are expected to show intersting properties for molecular elec tronics applications.Comment: 30 pages (preprint format), 8 figures. To appear in Solid State Communications - Special Issue on "New advances on collective phenomena in one-dimensional systems

Quantifying osmotic membrane fouling to enable comparisons across diverse processes

In this study, a method of in situ membrane fouling quantification is developed that enables comparisons of foulant accumulation between desalination processes with different membranes, driving forces, and feed solutions. Unlike the conventional metric of flux decline, which measures the response of a process to fouling, the proposed method quantifies the foulant accumulation. Foulant accumulation is parameterized by two variables, cake structural parameter and hydraulic diameter, that are calculated from flux measurements using a model for salt and water transport through fouled reverse osmosis (RO) and forward osmosis (FO) membranes, including dispersive mass transfer in the FO membrane support layer. Model results show that pressure declines through the foulant layer and can, in FO, reach negative absolute values at the membrane. Experimental alginate gel fouling rates are measured within a range of feed ionic compositions where cake hydraulic resistance is negligible. Using both flux decline and cake structural parameter as metrics, the effect of feed salinity on RO fouling is tested and RO is compared to FO. When RO is fouled with alginate, feed salinity and membrane permeability affect flux decline but not foulant accumulation rate. Between FO and RO, the initial rates of foulant accumulation are similar; however, FO exhibits slower flux decline, which causes greater foulant accumulation over time. The new methodology enables meaningful quantification and comparison of fouling rates with the aim of improving fundamental understanding of fouling processes.Center for Clean Water and Clean Energy at MIT and KFUPM (Project R4-CW-11)MIT Martin Family Society of Fellows for SustainabilityNational Science Foundation (U.S.). Graduate Research Fellowship (Grant 1122374

Matrix assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) for direct visualization of plant metabolites in situ

Direct visualization of plant tissues by matrix assisted laser desorption ionization-mass spectrometry imaging (MALDI-MSI) has revealed key insights into the localization of metabolites in situ. Recent efforts have determined the spatial distribution of primary and secondary metabolites in plant tissues and cells. Strategies have been applied in many areas of metabolism including isotope flux analyses, plant interactions, and transcriptional regulation of metabolite accumulation. Technological advances have pushed achievable spatial resolution to subcellular levels and increased instrument sensitivity by several orders of magnitude. It is anticipated that MALDI-MSI and other MSI approaches will bring a new level of understanding to metabolomics as scientists will be encouraged to consider spatial heterogeneity of metabolites in descriptions of metabolic pathway regulatio

MMP-15 Is Upregulated in Preeclampsia, but Does Not Cleave Endoglin to Produce Soluble Endoglin

Preeclampsia is a major pregnancy complication, characterized by severe endothelial dysfunction, hypertension and maternal end-organ damage. Soluble endoglin is an anti-angiogenic protein released from placenta and thought to play a central role in causing the endothelial dysfunction and maternal organ injury seen in severe preeclampsia. We recently reported MMP-14 was the protease producing placentally-derived soluble endoglin by cleaving full-length endoglin present on the syncytiotrophoblast surface. This find identifies a specific drug target for severe preeclampsia; interfering with MMP-14 mediated cleavage of endoglin could decrease soluble endoglin production, ameliorating clinical disease. However, experimental MMP-14 inhibition alone only partially repressed soluble endoglin production, implying other proteases might have a role in producing soluble endoglin. Here we investigated whether MMP-15–phylogenetically the closest MMP relative to MMP-14 with 66% sequence similarity–also cleaves endoglin to produce soluble endoglin. MMP-15 was localized to the syncytiotrophoblast layer of the placenta, the same site where endoglin was localized. Interestingly, it was significantly (p = 0.03) up-regulated in placentas from severe early-onset preeclamptic pregnancies (n = 8) compared to gestationally matched preterm controls (n = 8). However, siRNA knockdown of MMP-15 yielded no significant decrease of soluble endoglin production from either HUVECs or syncytialised BeWo cells in vitro. Importantly, concurrent siRNA knockdown of both MMP-14 and MMP-15 in HUVECS did not yield further decrease in soluble endoglin production compared to MMP-14 siRNA alone. We conclude MMP-15 is up-regulated in preeclampsia, but does not cleave endoglin to produce soluble endoglin