Effects of polylinker uATGs on the function of grass HKT1 transporters expressed in yeast cells

HvHKT1 mediates K+ or Na+ uniport in yeast cells if the expression promoter is joined directly to the HvHKT1 cDNA, and Na+-K+ symport if a 59-nt polylinker is inserted. Our results show that three ATG triplets in the polylinker decreased the synthesis of the transporter and that the lower amount of transporter caused the functional change. With the rice HKT1 cDNA, the 59-nt polylinker changed the mode of Na+ uptake from K+-insensitive to K+-inhibitable. These two modes of Na+ uptake also occurred in rice plant

Surgery and radioembolization of liver tumors

Surgical resection is considered the curative treatment par excellence for patients with primary or metastatic liver tumors. However, less than 40% of them are candidates for surgery, either due to nonmodifiable factors (comorbidities, age, liver dysfunction. . .), or to the invasion or proximity of the tumor to the main vascular requirements, the lack of a future liver remnant (FLR) adequate to maintain postoperative liver function, or criteria oftumor size and number. In these lastfactors, hepatic radioembolization has been shown to play a role as a presurgical tool, either by hypertrophy of the FLR or by reducing tumor size that manages to reduce tumor staging (term known as downstaging ¨ ¨ ). To these is added a third factor, which is its ability to apply the test oftime, which makes it possible to identify those patients who present progression of the disease in a short period of time (both locally and at distance), avoiding a unnecessary surgery. This paper aims to review RE as a tool to facilitate liver surgery, both through the experience of our center and the available scientific evidence.La resección quirúrgica se considera eltratamiento curativo por excelencia para los pacientes con tumores hepáticos primarios o metastásicos. Sin embargo, menos del 40% de ellos son candidatos a cirugía, ya sea por factores no modificables (comorbilidades, edad, disfunción hepática. . .), como por la invasión o proximidad del tumor a los principales pedículos vasculares, la falta de un futuro remanente hepático (FRH) adecuado para mantener una función hepática postoperatoria, o criterios de tamano˜ y numero tumoral. En estos últimos factores, la radioembolización hepática ha mostrado tener un papel como herramienta prequirúrgica, ya sea mediante la hipertrofia del FRH o mediante la reducción del tamano˜ tumoral que consigue disminuir la estadificación tumoral (término conocido como “downstaging”). A estos se suma un tercer factor, que es su capacidad de aplicar el test del tiempo, que permite identificar aquellos pacientes que presenten en un plazo corto de tiempo progresión de la enfermedad (tanto a nivel local como a distancia), evitándoles una cirugía innecesaria. En este trabajo se pretende hacer una revisión de la RE como herramienta facilitadora de la cirugía hepática, tanto a través de la experiencia de nuestro centro como de la evidencia científica disponible

Impact of the dosimetry approach on the resulting 90Y radioembolization planned absorbed doses based on 99mTc-MAA SPEC T-CT: is there agreement between dosimetry methods?

Background: Prior radioembolization, a simulation using 99mTc-macroaggregated albumin as 90Y-microspheres surrogate is performed. Gamma scintigraphy images (planar, SPECT, or SPECT-CT) are acquired to evaluate intrahepatic 90Y-microspheres distribution and detect possible extrahepatic and lung shunting. These images may be used for pre-treatment dosimetry evaluation to calculate the 90Y activity that would get an optimal tumor response while sparing healthy tissues. Several dosimetry methods are available, but there is still no consensus on the best methodology to calculate absorbed doses. The goal of this study was to retrospectively evaluate the impact of using different dosimetry approaches on the resulting 90Y-radioembolization pre-treatment absorbed dose evaluation based on 99mTc-MAA images. Methods: Absorbed doses within volumes of interest resulting from partition model (PM) and 3D voxel dosimetry methods (3D-VDM) (dose-point kernel convolution and local deposition method) were evaluated. Additionally, a new “Multi-tumor Partition Model” (MTPM) was developed. The differences among dosimetry approaches were evaluated in terms of mean absorbed dose and dose volume histograms within the volumes of interest. Results: Differences in mean absorbed dose among dosimetry methods are higher in tumor volumes than in non-tumoral ones. The differences between MTPM and both 3D-VDM were substantially lower than those observed between PM and any 3D-VDM. A poor correlation and concordance were found between PM and the other studied dosimetry approaches. DVH obtained from either 3D-VDM are pretty similar in both healthy liver and individual tumors. Although no relevant global differences, in terms of absorbed dose in Gy, between both 3D-VDM were found, important voxel-by-voxel differences have been observed. Conclusions: Significant differences among the studied dosimetry approaches for 90Y-radioembolization treatments exist. Differences do not yield a substantial impact in treatment planning for healthy tissue but they do for tumoral liver. An individual segmentation and evaluation of the tumors is essential. In patients with multiple tumors, the application of PM is not optimal and the 3D-VDM or the new MTPM are suggested instead. If a 3D-VDM method is not available, MTPM is the best option. Furthermore, both 3D-VDM approaches may be indistinctly used

Women with psychotic episodes during pregnancy show increased markers of placental damage with Tenney-Parker changes

y. Psychosis is a hazardous and functionally disruptive psychiatric condition which may affect women in pregnancy, entailing negative consequences for maternofetal well-being. The precise pathophysiological basis and consequences of a psychotic episode in pregnancy remain to be further elucidated. The placenta is a pivotal tissue with many functions in the gestational period, critically influencing the fate and development of pregnancy. Although detrimental alterations have been observed in women undergoing severe psychiatric disorders in pregnancy, there are little studies evaluating the consequences of suffering from a psychotic episode in the placental tissue In this work, we have evaluated the histopathological consequences of a first episode of psychosis in pregnancy (FE-PW; N=22) and compare them with healthy pregnant women (HC-PW; N=20) by using histological, immunohistochemical and gene expression techniques. Our results define that the placental tissue of FE-PW display an increase in the number of placental villi, bridges, syncytial knots and syncytial knots/villi. Besides, we have also observed an enhanced gene and protein expression in FE-PW of the hypoxic marker HIF-1α, together with the apoptotic markers BAX and Bcl-2. To our knowledge, this is the first study demonstrating significant histopathological changes in the placenta of women suffering a new-onset psychotic episode in pregnancy. Further studies should be aimed at deepening the knowledge about the pernicious effects of psychosis in the maternofetal tissues, as well as the potential implications of these alterations

Monoubiquitination of syntaxin 3 leads to retrieval from the basolateral plasma membrane and facilitates cargo recruitment to exosomes

Syntaxin 3 (Stx3), a SNARE protein located and functioning at the apical plasma membrane of epithelial cells, is required for epithelial polarity. A fraction of Stx3 is localized to late endosomes/lysosomes, although how it traffics there and its function in these organelles is unknown. Here we report that Stx3 undergoes monoubiquitination in a conserved polybasic domain. Stx3 present at the basolateral—but not the apical—plasma membrane is rapidly endocytosed, targeted to endosomes, internalized into intraluminal vesicles (ILVs), and excreted in exosomes. A nonubiquitinatable mutant of Stx3 (Stx3-5R) fails to enter this pathway and leads to the inability of the apical exosomal cargo protein GPRC5B to enter the ILV/exosomal pathway. This suggests that ubiquitination of Stx3 leads to removal from the basolateral membrane to achieve apical polarity, that Stx3 plays a role in the recruitment of cargo to exosomes, and that the Stx3-5R mutant acts as a dominant-negative inhibitor. Human cytomegalovirus (HCMV) acquires its membrane in an intracellular compartment and we show that Stx3-5R strongly reduces the number of excreted infectious viral particles. Altogether these results suggest that Stx3 functions in the transport of specific proteins to apical exosomes and that HCMV exploits this pathway for virion excretion

Permalloy thin films exchange coupled to arrays of cobalt islands

Periodic arrays of elongated cobalt islands exchange coupled to continuous Permalloy thin films were fabricated using silicon nitride stencil masks and the magnetic spin configurations during magnetization reversal were studied with photoemission electron microscopy. The presence of cobalt islands results in a spatial modulation of the magnetic properties of the Permalloy films and domain walls positioned at the island boundaries. While magneto-optical Kerr effect measurements indicate differences depending on film thickness, the direct observations reveal two reversal mechanisms: formation of domains running between the islands and coherent rotation followed by propagation of a large domain

Evolution of metabolic risk factors over a two-year period in a cohort of first episodes of psychosis

Patients with a first episode of psychosis (FEP) display a broad range of metabolic risk factors related to the development of diverse medical comorbidities. Initial stages of these disorders are essential in understanding the increased vulnerability of developing cardiometabolic disturbances, associated with a reduced life expectancy. This study aimed to evaluate the metabolic profile of a cohort of patients with a FEP and its evolution during a two year follow-up, as well as the factors that influence the changes in their metabolic status. 16 participating centers from the PEPs Project recruited 335 subjects with a FEP and 253 matched healthy controls, aged 9–35 years. We investigated a set of anthropometric measures, vital signs and laboratory data obtained from each participant over two years in a prospective, naturalistic study. From the beginning of the study the FEP group showed differences in the metabolic profile compared to the control group, together with a progressive worsening in the major part of the analyzed variables during the follow-up period, with higher rates of obesity and metabolic syndrome. Certain risk factors were related to determinate clinical variables such as male gender, the presence of affective symptoms or an early onset or to treatment variables such as the use of antipsychotic polypharmacy, antidepressants or mood stabilizers. Our results highlight the extremely high risk of patients at early phases of schizophrenia and other psychotic disorders of developing cardiovascular comorbidity and the fast worsening of the metabolic profile during the first two years

Combining scanning probe microscopy and x-ray spectroscopy

A new versatile tool, combining Shear Force Microscopy and X-Ray Spectroscopy was designed and constructed to obtain simultaneously surface topography and chemical mapping. Using a sharp optical fiber as microscope probe, it is possible to collect locally the visible luminescence of the sample. Results of tests on ZnO and on ZnWO4 thin layers are in perfect agreement with that obtained with other conventional techniques. Twin images obtained by simultaneous acquisition in near field of surface topography and of local visible light emitted by the sample under X-Ray irradiation in synchrotron environment are shown. Replacing the optical fibre by an X-ray capillary, it is possible to collect local X-ray fluorescence of the sample. Preliminary results on Co-Ti sample analysis are presented