Conducting interfaces between band insulating oxides: the LaGaO3/SrTiO3

We show that the growth of the heterostructure LaGaO3/SrTiO3 yields the formation of a highly conductive interface. Our samples were carefully analyzed by high resolution electron microscopy, in order to assess their crystal perfection and to evaluate the abruptness of the interface. Their carrier density and sheet resistance are compared to the case of LaAlO3/SrTiO3 and a superconducting transition is found. The results open the route to widening the field of polar-non polar interfaces, pose some phenomenological constrains to their underlying physics and highlight the chance of tailoring their properties for future applications by adopting suitable polar materials.Comment: in press Appl. Phys. Lett. 97, 1 (2010

The N-fixing legume Periandra mediterranea constrains the invasion of an exotic grass (Melinis minutiflora P. Beauv) by altering soil N cycling

Melinis minutiflora is an invasive species that threatens the biodiversity of the endemic vegetation of the campo rupestre biome in Brazil, displacing the native vegetation and favouring fire spread. As M. minutiflora invasion has been associated with a high nitrogen (N) demand, we assessed changes in N cycle under four treatments: two treatments with contrasting invasion levels (above and below 50%) and two un-invaded control treatments with native vegetation, in the presence or absence of the leguminous species Periandra mediterranea. This latter species was considered to be the main N source in this site due to its ability to fix N2 in association with Bradyrhizobia species. Soil proteolytic activity was high in treatments with P. mediterranea and in those severely invaded, but not in the first steps of invasion. While ammonium was the N-chemical species dominant in plots with native species, including P.mediterranea, soil nitrate prevailed only in fully invaded plots due to the stimulation of the nitrifying bacterial (AOB) and archaeal (AOA) populations carrying the amoA gene. However, in the presence of P. mediterranea, either in the beginning of the invasion or in uninvaded plots, we observed an inhibition of the nitrifying microbial populations and nitrate formation, suggesting that this is a biotic resistance strategy elicited by P. mediterranea to compete with M. minutiflora. Therefore, the inhibition of proteolytic activity and the nitrification process were the strategies elicited by P.mediterranea to constrain M.munitiflora invasion

Experimental techniques for the study of angiogenesis in female reproductive diseases

El desarrollo vascular en el tracto reproductivo femenino es un proceso que se encuentra restringido a la formación del cuerpo lúteo y a la proliferación del endometrio uterino durante los ciclos menstruales. Se han identificado numerosos inductores de la angiogé- nesis, que incluyen, entre otros, los miembros del factor de crecimiento fibroblástico (FGF) y la familia del factor de crecimiento del endotelio vascular (VEGF), angiopoyetinas (ANGPT), factor de crecimiento transformante (TGF) y factor derivado de plaquetas (PDGF). Los defectos en la angiogénesis ovárica contribuyen a una variedad de desórdenes, incluyendo anovulación e infertilidad, pérdida de embarazo, síndrome de hiperestimulación ovárica (SHEO), síndrome de ovario poliquístico (SOP) y neoplasmas ováricos. Es decir, el endotelio es una fuente y un blanco de sustancias vasoactivas que son secretadas debido a las condiciones que se desencadenan durante los desórdenes ya mencionados. Para evaluar los mecanismos bioquímicos y moleculares que participan en la angiogénesis, se han desarrollado métodos in vitro (migración por herida, tubulogénesis, etc.) e in vivo (implante de Matrigel, membrana corionalantoide, etc.). Los ensayos in vitro pueden ser útiles para validar los primeros pasos de la angiogénesis pero deben ser confirmados por estudios in vivo. En particular, los ensayos in vitro e in vivo descriptos en este trabajo para evaluar el desarrollo de los vasos pueden ser aplicados para el estudio de desórdenes reproductivos con alteraciones en la angiogénesis (SHEO, SOP, cáncer de ovario, etc.) mediante la utilización del suero, líquido peritoneal, fluido folicular o de biopsias de distintos tejidos provenientes de las pacientesFil: Scotti, Leopoldina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Abramovich, Dalhia Nurit. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Irusta, Griselda. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Pazos Maidana, María Camila. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Pascuali, Natalia Marisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Haro Durand, Luis Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Tesone, Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Parborell, Maria Fernanda Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentin

Transcriptional dynamics of induced pluripotent stem cell differentiation into β cells reveals full endodermal commitment and homology with human islets.

Abstract Background aims Induced pluripotent stem cells (iPSCs) have the capacity to generate β cells in vitro, but the differentiation is incomplete and generates a variable percentage of off-target cells. Single-cell RNA sequencing offers the possibility of characterizing the transcriptional dynamics throughout differentiation and determining the identity of the final differentiation product. Methods Single-cell transcriptomics data were obtained from four stages across differentiation of iPSCs into β cells and from human donor islets. Results Clustering analysis revealed that iPSCs undertake a full endoderm commitment, and the obtained endocrine pancreatic cells have high homology with mature islets. The iPSC-derived β cells were devoid of pluripotent residual cells, and the differentiation was pancreas-specific, as it did not generate ectodermal or mesodermal cells. Pseudotime trajectory identified a dichotomic endocrine/non-endocrine cell fate and distinct subgroups in the endocrine branch. Conclusions Future efforts to produce β cells from iPSCs must aim not only to improve the resulting endocrine cell but also to avoid differentiation into non-pancreatic endoderm cells

Intercropping system of tropical leguminous species and Eucalyptus camaldulensis , inoculated with rhizobia and/or mycorrhizal fungi in semiarid Brazil

For the purpose of reforestation and wood supply the leguminous tree Anadenanthera peregrina, a native species, was intercropped with Eucalyptus camaldulensis in a degraded semiarid area of Brazil. Single and mixed stands of these species were inoculated with Rhizobium and/or arbuscular mycorrhizal fungi (AMF). The growth of all species in mixed stands did not differ from those cultivated in monoculture and land equivalent ratio (LER) exceeded unity in intercropped plots. Inoculated plants showed greater height and diameter growth and dry matter and nutrient concentration in plants of A. peregrina was higher in inoculated single plots. The distribution, composition and density of AMF species was related to the rhizosphere effect of plant species. The intercropped model where all the plants were inoculated achieved soil AMF diversity patterns similar to those of the preserved area and showed also higher soil organic matter, nutrient content as well as a reduction in soil macroporosity. This model of intercropping may be considered as an efficient system for reforestation under semiarid conditions.Facultad de Ciencias Naturales y Muse

Calcium biofortification of Rocha pears, tissues accumulation and physicochemical implications in fresh and heat-treated fruits

Low dietary intake of Ca in humans has been epidemiologically linked to various diseases, which can have serious health consequences over time. Accordingly, the development of an agronomic itinerary for Ca biofortification of Rocha pears and the assessment of physicochemical deviations prompted this study. Two orchards with contrasting soil and water characteristics were selected, characterized through orthophotomaping and, during fruits development, leaves were sprayed twice with Ca(NO3)2 (0.1, 0.3 and 0.6 kg ha - 1) or CaCl2 (0.4, 0.8 and 1.6 kg ha - 1), followed by pulverization only with CaCl2 (first once with 4 kg ha - 1 and then four times with 8 kg ha - 1). During fruits development net photosynthesis, stomatal conductance, transpiration rates, instantaneous and water use efficiency, only showed minor deviations, which indicated that the threshold of toxicity was not surpassed. Calcium contents varied during fruits development and at harvesting the average biofortification index varied between 47 %–63 % and 24 %–59 % in each of the orchards. Besides, the equatorial region of the fruits showed for all treatments (substantially in Ca treated samples) higher Ca contents in the epidermal and in the central regions. Fresh and heat-treated fruits (in a thermomix at 90 ◦C, during 10 min) biofortified with Ca only revealed minor differences and the sensory acceptability did not vary markedly. It is concluded that, although prevailing a heterogeneous distribution of Ca in fruit tissues, high indexes of biofortification in Rocha pears can be prompt in the orchards, without substantial physicochemical changes. Accordingly, agronomic biofortification with Ca can be used as a strategy for benefiting consumer’s healthinfo:eu-repo/semantics/publishedVersio

Neural stem cell transplantation in patients with progressive multiple sclerosis: an open-label, phase 1 study

Innovative pro-regenerative treatment strategies for progressive multiple sclerosis (PMS), combining neuroprotection and immunomodulation, represent an unmet need. Neural precursor cells (NPCs) transplanted in animal models of multiple sclerosis have shown preclinical efficacy by promoting neuroprotection and remyelination by releasing molecules sustaining trophic support and neural plasticity. Here we present the results of STEMS, a prospective, therapeutic exploratory, non-randomized, open-label, single-dose-finding phase 1 clinical trial (NCT03269071, EudraCT 2016-002020-86), performed at San Raffaele Hospital in Milan, Italy, evaluating the feasibility, safety and tolerability of intrathecally transplanted human fetal NPCs (hfNPCs) in 12 patients with PMS (with evidence of disease progression, Expanded Disability Status Scale >= 6.5, age 18-55 years, disease duration 2-20 years, without any alternative approved therapy). The safety primary outcome was reached, with no severe adverse reactions related to hfNPCs at 2-year follow-up, clearly demonstrating that hfNPC therapy in PMS is feasible, safe and tolerable. Exploratory secondary analyses showed a lower rate of brain atrophy in patients receiving the highest dosage of hfNPCs and increased cerebrospinal fluid levels of anti-inflammatory and neuroprotective molecules. Although preliminary, these results support the rationale and value of future clinical studies with the highest dose of hfNPCs in a larger cohort of patients

Outcomes of COVID-19 patients treated with continuous positive airway pressure outside ICU

Aim We aim at characterizing a large population of Coronavirus 19 (COVID-19) patients with moderate-to-severe hypoxemic acute respiratory failure (ARF) receiving CPAP outside intensive care unit (ICU), and ascertaining whether the duration of CPAP application increased the risk of mortality for patients requiring intubation. Methods In this retrospective, multicentre cohort study, we included COVID-19 adult patients, treated with CPAP outside ICU for hypoxemic ARF from March 1 st to April 15th, 2020. We collected demographic and clinical data, including CPAP therapeutic goal, hospital length of stay (LOS), and 60- day in-hospital mortality. Results The study includes 537 patients with a median age of 69 (IQR, 60-76) years. Males were 391 (73%). According to predefined CPAP therapeutic goal, 397 (74%) patients were included in full treatment subgroup, and 140 (26%) in the do-not intubate (DNI) subgroup. Median CPAP duration was 4 (IQR, 1-8) days, while hospital LOS 16 (IQR, 9-27) days. Sixty-day in-hospital mortality was overall 34% (95%CI, 0.304-0.384), and 21% (95%CI, 0.169-0.249) and 73% (95%CI, 0.648-0.787) for full treatment and DNI subgroups, respectively. In the full treatment subgroup, in-hospital mortality was 42% (95%CI, 0.345-0.488) for 180 (45%) CPAP failures requiring intubation, while 2% (95%CI, 0.008- 0.035) for the remaining 217 (55%) patients who succeeded. Delaying intubation was associated with increased mortality [HR, 1.093 (95%CI, 1.010-1.184)]. Conclusions We described a large population of COVID-19 patients treated with CPAP outside ICU. Intubation delay represents a risk factor for mortality. Further investigation is needed for early identification of CPAP failures

Regulation of polarized morphogenesis by protein kinase C iota in oncogenic epithelial spheroids.

Protein kinase C iota (PKCι), a serine/threonine kinase required for cell polarity, proliferation and migration, is commonly up- or downregulated in cancer. PKCι is a human oncogene but whether this is related to its role in cell polarity and what repertoire of oncogenes acts in concert with PKCι is not known. We developed a panel of candidate oncogene expressing Madin-Darby canine kidney (MDCK) cells and demonstrated that H-Ras, ErbB2 and phosphatidylinositol 3-kinase transformation led to non-polar spheroid morphogenesis (dysplasia), whereas MDCK spheroids expressing c-Raf or v-Src were largely polarized. We show that small interfering RNA (siRNA)-targeting PKCι decreased the size of all spheroids tested and partially reversed the aberrant polarity phenotype in H-Ras and ErbB2 spheroids only. This indicates distinct requirements for PKCι and moreover that different thresholds of PKCι activity are required for these phenotypes. By manipulating PKCι function using mutant constructs, siRNA depletion or chemical inhibition, we have demonstrated that PKCι is required for polarization of parental MDCK epithelial cysts in a 3D matrix and that there is a threshold of PKCι activity above and below which, disorganized epithelial morphogenesis results. Furthermore, treatment with a novel PKCι inhibitor, CRT0066854, was able to restore polarized morphogenesis in the dysplastic H-Ras spheroids. These results show that tightly regulated PKCι is required for normal-polarized morphogenesis in mammalian cells and that H-Ras and ErbB2 cooperate with PKCι for loss of polarization and dysplasia. The identification of a PKCι inhibitor that can restore polarized morphogenesis has implications for the treatment of Ras and ErbB2 driven malignancies.Cancer Research UK; Royal Marsden/Institute of Cancer Research National Institute for Health Research Biomedical Research Centre (M.L.)