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The high selectivity of the human blood-brain barrier (BBB) restricts delivery of many pharmaceuticals and therapeutic antibodies to the central nervous system. Here, we describe an in vitro microfluidic organ-on-a-chip BBB model lined by induced pluripotent stem cell-derived human brain microvascular endothelium interfaced with primary human brain astrocytes and pericytes that recapitulates the high level of barrier function of the in vivo human BBB for at least one week in culture. The endothelium expresses high levels of tight junction proteins and functional efflux pumps, and it displays selective transcytosis of peptides and antibodies previously observed in vivo. Increased barrier functionality was accomplished using a developmentally-inspired induction protocol that includes a period of differentiation under hypoxic conditions. This enhanced BBB Chip may therefore represent a new in vitro tool for development and validation of delivery systems that transport drugs and therapeutic antibodies across the human BBB. In vitro blood-brain barrier (BBB) models do not fully recapitulate the in vivo barrier function. Here the authors develop an organ-on-a-chip BBB model using iPS-derived human brain endothelial cells differentiated under hypoxia, primary human pericytes and astrocytes, which maintains in vivo-like BBB barrier and shuttling functions for a week.

The highly specialized endothelial cells in brain capillaries are a key component of the blood-brain barrier, forming a network of tight junctions that almost completely block paracellular transport. In contrast to vascular endothelial cells in other organs, we show that brain microvascular endothelial cells resist elongation in response to curvature and shear stress. Since the tight junction network is defined by endothelial cell morphology, these results suggest that there may be an evolutionary advantage to resisting elongation by minimizing the total length of cell-cell junctions per unit length of vessel.

The new potato variety INIA 333–CHUGAYNA, is the result of the joint work of the NGO Asociación Pataz, INIA and the International Potato Center, it was generated through traditional breeding and the use of the participatory varietal selection methodology, as a variety resilient to climate change with frost tolerance, resistance to late blight, compared to the improved variety INIA 302-Amarilis and the native varieties, Huevo de Indio. This new variety is also resilient to climate change, tolerant to frost, with field resistance to late blight, high tuber yield, low glycoalkaloid content and high quality for fresh consumption, adapted up to 4000 m above sea level. It was released in 2023 and officially registered in the national registry of commercial varieties of Peru. The new variety INIA 333-CHUGAYNA requires minimal use of fungicides and has a high economic profitability that will improve the living standards of small and medium-sized farmers in Peru. It can also be used as a parent in breeding programs in other countries in development, to confront climate change, especially frost.

Cases of iatrogenic prion disease have been reported from corneal transplants, yet the distribution and levels of prions throughout the eye remain unknown. This study probes the occurrence, level, and distribution of prions in the eyes of patients with sporadic Creutzfeldt-Jakob disease (sCJD). We tested the largest series of prion-infected eyes reported to date using an ultrasensitive technique to establish the prion seed levels in eight regions of the eye. All 11 cases had detectable prion seeds in the eye, and in some cases, the seed levels in the retina approached those in brain. In most cases, prion deposits could also be seen by immunohistochemical staining of retinal tissue; other ocular tissues were negative. Our results have implications for estimating the risk for iatrogenic transmission of sCJD as well as for the development of antemortem diagnostic tests for prion diseases. Sporadic Creutzfeldt-Jakob disease (sCJD) is the most common prion disease in humans and has been iatrogenically transmitted through corneal graft transplantation. Approximately 40% of sCJD patients develop visual or oculomotor symptoms and may seek ophthalmological consultation. Here we used the highly sensitive real-time quaking-induced conversion (RT-QuIC) assay to measure postmortem prion seeding activities in cornea, lens, ocular fluid, retina, choroid, sclera, optic nerve, and extraocular muscle in the largest series of sCJD patient eyes studied by any assay to date. We detected prion seeding activity in 100% of sCJD eyes, representing three common sCJD subtypes, with levels varying by up to 4 log-fold among individuals. The retina consistently showed the highest seed levels, which in some cases were only slightly lower than brain. Within the retina, prion deposits were detected by immunohistochemistry (IHC) in the retinal outer plexiform layer in most sCJD cases, and in some eyes the inner plexiform layer, consistent with synaptic prion deposition. Prions were not detected by IHC in any other eye region. With RT-QuIC, prion seed levels generally declined in eye tissues with increased distance from the brain, and yet all corneas had prion seeds detectable. Prion seeds were also present in the optic nerve, extraocular muscle, choroid, lens, vitreous, and sclera. Collectively, these results reveal that sCJD patients accumulate prion seeds throughout the eye, indicating the potential diagnostic utility as well as a possible biohazard. IMPORTANCE Cases of iatrogenic prion disease have been reported from corneal transplants, yet the distribution and levels of prions throughout the eye remain unknown. This study probes the occurrence, level, and distribution of prions in the eyes of patients with sporadic Creutzfeldt-Jakob disease (sCJD). We tested the largest series of prion-infected eyes reported to date using an ultrasensitive technique to establish the prion seed levels in eight regions of the eye. All 11 cases had detectable prion seeds in the eye, and in some cases, the seed levels in the retina approached those in brain. In most cases, prion deposits could also be seen by immunohistochemical staining of retinal tissue; other ocular tissues were negative. Our results have implications for estimating the risk for iatrogenic transmission of sCJD as well as for the development of antemortem diagnostic tests for prion diseases.

With the discovery of the prion protein (PrP), immunodiagnostic procedures were applied to diagnose Creutzfeldt-Jakob disease (CJD). Before development of the conformation-dependent immunoassay (CDI), all immunoassays for the disease-causing PrP isoform ( PrPSc) used limited proteolysis to digest the precursor cellular PrP ( PrPC). Because the CDI is the only immunoassay that measures both the protease-resistant and protease-sensitive forms of PrPSc, we used the CDI to diagnose human prion disease. The CDI gave a positive signal for PrPScin all 10-24 brain regions (100%) examined from 28 CJD patients. A subset of 18 brain regions from 8 patients with sporadic CJD (sCJD) was examined by histology, immunohistochemistry (IHC), and the CDI. Three of the 18 regions (17%) were consistently positive by histology and 4 of 18 (22%) by IHC for the 8 sCJD patients. In contrast, the CDI was positive in all 18 regions (100%) for all 8 sCJD patients. In both gray and white matter, ≈90% of the total PrPScwas protease-sensitive and, thus, would have been degraded by procedures using proteases to eliminate PrPC. Our findings argue that the CDI should be used to establish or rule out the diagnosis of prion disease when a small number of samples is available as is the case with brain biopsy. Moreover, IHC should not be used as the standard against which all other immunodiagnostic techniques are compared because an immunoassay, such as the CDI, is substantially more sensitive.

Understanding the soil moisture behavior in relation to land use in tropical Andean mountain catchments is essential for comprehending water fluxes, ecohydrological relations and hydrological dynamics in this understudied ecosystem. Soils are a key factor of these ecosystems, especially in reference to water level regulation and anthropogenic activities that can alter the interactions, and generate physical, chemical and biological imbalances. In this study, we investigated the relationship between precipitation, soil water content (SWC) and the flow at different pedon scales, and hillslope and microcatchment scales subjected to different land uses. The results showed the relation between the soils uses, topographical conditions and soil moisture at the microcatchment scale. At the pedon scale, soil moisture is higher and with a low variability in depth; high soil moisture content throughout the study period was registered in forest > pasture > coffee agroforestry systems. The topographic wetness index (TWI), despite its adjusted interpretation of the behavior of humidity at the microcatchment scale, is a poor predictor of the behavior of soil humidity at the pedon scale. Pedon water content has a close relation with the precipitation behavior, especially in prolonged dry and humid periods. The soils studied tend to present udic moisture regimes with a dry period of approximately 67 accumulative days per year. The mean flow behavior responds to precipitation and soil moisture behavior at a monthly scale. Understanding the consequences of the land cover changes in relation to soil water behavior, as well as how soil water interacts with the different components of the hydric balance at different scales, allows an understanding of the complex interactions in natural microcatchments under different land use systems.

The present article has the purpose of measuring the organizational development of the associative organizations in the south of Colombia through members' and associates' perception regarding the intellectual capital developed in the components of human, structural and relational capital. The study was of a quantitative and descriptive type, in which the survey technique was used through a Likert-scale applied to members and associates of 27 associative organizations. Faced with the results, organizations were obtained with an organizational advance that exceeds 60% in the components of human and structural capital, which implies that the organizations developed aspects of human capital such as the knowledge of its members, the professional relevance, the processes of improvement and the antiquity of the association, while in the structural capital aspects such as standards and values, certifications and brands stand out and the revolving fund among others. Nevertheless, relational capital has not yet reached its development, especially in its marketing and business relations components.

The voluntary control of gaze implies the ability to make saccadic eye movements specified by abstract instructions, as well as the ability to repress unwanted orientating to sudden stimuli. Both of these abilities are challenged in the antisaccade task, because it requires subjects to look at an unmarked location opposite to a flashed stimulus, without glancing at it 1 , 2 . Performance on this task depends on the frontal/prefrontal cortex and related structures 3 , 4 , 5 , 6 , 7 , 8 , but the neuronal operations underlying antisaccades are not understood. It is not known, for example, how excited visual neurons that normally trigger a saccade to a target (a prosaccade) can activate oculomotor neurons directing gaze in the opposite direction. Visual neurons might, perhaps, alter their receptive fields depending on whether they receive a pro- or antisaccade instruction. If the receptive field is not altered, the antisaccade goal must be computed and imposed from the top down to the appropriate oculomotor neurons. Here we show, using recordings from the supplementary eye field (a frontal cortex oculomotor centre) in monkeys, that visual and movement neurons retain the same spatial selectivity across randomly mixed pro- and antisaccade trials. However, these neurons consistently fire more before antisaccades than prosaccades with the same trajectories, suggesting a mechanism through which voluntary antisaccade commands can override reflexive glances.

Despite shared colonization histories between the United States and Latin America, research examining racial disparities in health in the United States has often neglected Latinos. Additionally, descendants from Latin America residing in the United States are often categorized under the pan-ethnic label of Hispanic or Latino. This categorization obscures the group's heterogeneity, which is illuminated by research showing consistent differences in health for the three largest segments of the Latino population-Mexicans, Puerto Ricans, and Cubans. We examine whether the patterns of infant mortality associated with race in the non-Latino population also follow for Latinos. We also examine whether we can attribute patterns of infant mortality between the three largest Latino sub-groups to a process we term segmented racialization. We find that race operates for Latinos the same way it does for the non-Latino population and that there seems to be some evidence to support our segmented racialization hypothesis. The results point to the need to abandon the practices of combining Latino sub-groups as well as ignoring the racial diversity within the Latino population in health research. Adapted from the source document.

The subcellular organization of proteins carries important information on cellular state and gene function, yet currently there are no technologies that enable accurate measurement of subcellular protein localizations at scale. Here we develop an approach for pooled endogenous protein tagging using prime editing, which coupled with an optical readout and sequencing, provides a snapshot of proteome organization in a manner akin to perturbation-based CRISPR screens. We constructed a pooled library of 17,280 pegRNAs designed to exhaustively tag 60 endogenous proteins spanning diverse localization patterns and explore a large space of genomic and pegRNA design parameters. Pooled measurements of tagging efficiency uncovered both genomic and pegRNA features associated with increased efficiency, including epigenetic states and interactions with transcription. We integrate pegRNA features into a computational model with predictive value for tagging efficiency to constrain the design space of pegRNAs for large-scale peptide knock-in. Lastly, we show that combining in-situ pegRNA sequencing with high-throughput deep learning image analysis, enables exploration of subcellular protein localization patterns for many proteins in parallel following a single pooled lentiviral transduction, setting the stage for scalable studies of proteome dynamics across cell types and environmental perturbations.