Plasma membrane recovery kinetics of a microfluidic intracellular delivery platform

Intracellular delivery of materials is a challenge in research and therapeutic applications. Physical methods of plasma membrane disruption have recently emerged as an approach to facilitate the delivery of a variety of macromolecules to a range of cell types. We use the microfluidic CellSqueeze delivery platform to examine the kinetics of plasma membrane recovery after disruption and its dependence on the calcium content of the surrounding buffer (recovery time ~5 min without calcium vs. ~30 s with calcium). Moreover, we illustrate that manipulation of the membrane repair kinetics can yield up to 5× improvement in delivery efficiency without significantly impacting cell viability. Membrane repair characteristics initially observed in HeLa cells are shown to translate to primary naïve murine T cells. Subsequent manipulation of membrane repair kinetics also enables the delivery of larger materials, such as antibodies, to these difficult to manipulate cells. This work provides insight into the membrane repair process in response to mechanical delivery and could potentially enable the development of improved delivery methods.National Institutes of Health (U.S.) (Grant RC1 EB011187-02)National Institutes of Health (U.S.) (Grant R01GN101420-01A1)Kathy and Curt Marble Cancer Research FundNational Cancer Institute (U.S.) (Cancer Center Support (Core) Grant P30-CA14051)National Cancer Institute (U.S.) (Cancer Center Support (Core) Grant MPP-09Call-Langer-60

Determining Bathymetry of Shallow and Ephemeral Desert Lakes Using Satellite Imagery and Altimetry

©2020. American Geophysical Union. All Rights Reserved. Water volume estimates of shallow desert lakes are the basis for water balance calculations, important both for water resource management and paleohydrology/climatology. Water volumes are typically inferred from bathymetry mapping; however, being shallow, ephemeral, and remote, bathymetric surveys are scarce in such lakes. We propose a new, remote-sensing-based, method to derive the bathymetry of such lakes using the relation between water occurrence, during \u3e30 year of optical satellite data, and accurate elevation measurements from the new Ice, Cloud, and Land Elevation Satellite-2 (ICESat-2). We demonstrate our method at three locations where we map bathymetries with ~0.3 m error. This method complements other remotely sensed, bathymetry-mapping methods as it can be applied to: (a) complex lake systems with subbasins, (b) remote lakes with no in-situ records, and (c) flooded lakes. The proposed method can be easily implemented in other shallow lakes as it builds on publically accessible global data sets

Basal ganglia correlates of fatigue in young adults

Although the prevalence of chronic fatigue is approximately 20% in healthy individuals, there are no studies of brain structure that elucidate the neural correlates of fatigue outside of clinical subjects. We hypothesized that fatigue without evidence of disease might be related to changes in the basal ganglia and prefrontal cortex and be implicated in fatigue with disease. We aimed to identify the white matter structures of fatigue in young subjects without disease using magnetic resonance imaging (MRI). Healthy young adults (n = 883; 489 males and 394 females) were recruited. As expected, the degrees of fatigue and motivation were associated with larger mean diffusivity (MD) in the right putamen, pallidus and caudate. Furthermore, the degree of physical activity was associated with a larger MD only in the right putamen. Accordingly, motivation was the best candidate for widespread basal ganglia, whereas physical activity might be the best candidate for the putamen. A plausible mechanism of fatigue may involve abnormal function of the motor system, as well as areas of the dopaminergic system in the basal ganglia that are associated with motivation and reward

Synoptic-scale to mesoscale atmospheric circulation connects fluvial and coastal gravel conveyors and directional deposition of coastal landforms in the Dead Sea basin

Streams convey coarse-clastic sediments towards coasts, where interactions with deltaic and coastal processes determine their resultant sedimentology and geomorphology. Extracting hydroclimatic signals from such environments is a desired goal, and therefore studies commonly rely on interpreting available paleoclimatic proxy data, but the direct linking of depositional and geomorphic processes with the hydroclimate remains obscure. This is a consequence of the challenge of linking processes that are often studied separately and span across large spatial and temporal scales, including synoptic-scale hydroclimatic forcing, streamflows, water body hydrodynamics, fluvial and coastal sediment transport, and sedimentation. Here, we explore this chain of connected processes in the unique setting of the Dead Sea basin, where present-day hydroclimatology is closely tied with geomorphic evolution and sediment transport of streams and coasts that rapidly respond to lake-level fall. We use a 5-year (2018–2022) rich dataset of (i) high-resolution synoptic-scale circulation patterns, (ii) continuous wind-wave and rain–flood records, and (iii) storm-scale fluvial and coastal sediment transport of “smart” and marked boulders. We show the significance of Mediterranean cyclones in the concurrent activation of fluvial (floods) and coastal (wind waves) sediment conveyors. These synoptic-scale patterns drive the westerlies necessary for (i) delivering the moisture across the Judean desert, which is transformed into floods, and at the same time, (ii) the coeval, topographically funneled winds that turn into surface southerlies (&gt;10 m s−1) along the Dead Sea rift valley. During winter, these mesoscale southerlies generate 10–30 high-amplitude, northward-propagating storm waves, with &lt;4 m wave heights. Such waves transport cobbles for hundreds of meters alongshore, northward and away from the supplying channel mouths. Four to nine times per winter the rainfall generated by these atmospheric patterns is capable of generating floods that reach the stream mouths, delivering poorly sorted, coarse gravel. This usually occurs during the decay of the associated storm waves. This gravel is dispersed alongshore by waves during subsequent storms. As storm waves dominate and are &gt;5 times more frequent than flash floods, coarse-clastic beach berms and fan deltas are deposited preferentially north of the delivering channel mouths. This asymmetric depositional architecture, controlled by the regional hydroclimatology, is identified for both the modern and late Pleistocene coast and delta environments, implying that the dominance of present-day Mediterranean cyclones also persisted in the region during the late Pleistocene when Lake Lisan occupied the basin.</p

Noun and verb knowledge in monolingual preschool children across 17 languages: Data from cross-linguistic lexical tasks (LITMUS-CLT)

This article investigates the cross-linguistic comparability of the newly developed lexical assessment tool Cross-linguistic Lexical Tasks (LITMUS-CLT). LITMUS-CLT is a part the Language Impairment Testing in Multilingual Settings (LITMUS) battery (Armon-Lotem, de Jong & Meir, 2015). Here we analyse results on receptive and expressive word knowledge tasks for nouns and verbs across 17 languages from eight different language families: Baltic (Lithuanian), Bantu (isiXhosa), Finnic (Finnish), Germanic (Afrikaans, British English, South African English, German, Luxembourgish, Norwegian, Swedish), Romance (Catalan, Italian), Semitic (Hebrew), Slavic (Polish, Serbian, Slovak) and Turkic (Turkish). The participants were 639 monolingual children aged 3;0-6;11 living in 15 different countries. Differences in vocabulary size were small between 16 of the languages; but isiXhosa-speaking children knew significantly fewer words than speakers of the other languages. There was a robust effect of word class: accuracy was higher for nouns than verbs. Furthermore, comprehension was more advanced than production. Results are discussed in the context of cross-linguistic comparisons of lexical development in monolingual and bilingual populations

PARP inhibitors and the treatment of breast cancer: beyond BRCA1/2?

Poly(ADP-ribose) polymerase (PARP) inhibitors have been explored as therapeutic agents for the treatment of hereditary breast and ovarian cancers harboring mutations in BRCA1 or BRCA2. In a new study, Inbar-Rozensal and colleagues show that phenanthridine-derived PARP inhibitors promote cell cycle arrest and cell death in breast cancer cells lacking BRCA1 and BRCA2 mutations and prevent the growth of tumors from xenografts of these cells in immunocompromised mice. These results suggest a potential broader utility of PARP-1 inhibitors in the treatment of breast cancer, although further mechanistic studies are needed

Foldable structures made of hydrogel bilayers

We discuss self-folding of a thin sheet by using patterned hydrogel bilayers, which act as hinges connecting flat faces. Folding is actuated by heterogeneous swelling due to different crosslinking densities of the polymer network in the two layers. Our analysis is based on a dimensionally reduced plate model, obtained by applying a recently developed theory [1], which provides us with an explicit connection between (three-dimensional) material properties and the curvatures induced at the hinges. This connection offers a recipe for the fabrication and design of the bilayers, by providing the values of the cross-linking density of each layer that need to be imprinted during polymerization in order to produce a desired folded shape upon swelling

Guidelines on acute gastroenteritis in children: a critical appraisal of their quality and applicability in primary care

<p>Abstract</p> <p>Background</p> <p>Reasons for poor guideline adherence in acute gastroenteritis (AGE) in children in high-income countries are unclear, but may be due to inconsistency between guideline recommendations, lack of evidence, and lack of generalizability of the recommendations to general practice. The aim of this study was to assess the quality of international guidelines on AGE in children and investigate the generalizability of the recommendations to general practice.</p> <p>Methods</p> <p>Guidelines were retrieved from websites of professional medical organisations and websites of institutes involved in guideline development. In addition, a systematic search of the literature was performed. Articles were selected if they were a guideline, consensus statement or care protocol.</p> <p>Results</p> <p>Eight guidelines met the inclusion criteria, the quality of the guidelines varied. 242 recommendations on diagnosis and management were found, of which 138 (57%) were based on evidence.</p> <p>There is a large variety in the classification of symptoms to different categories of dehydration. No signs are generalizable to general practice.</p> <p>It is consistently recommended to use hypo-osmolar ORS, however, the recommendations on ORS-dosage are not evidence based and are inconsistent. One of 14 evidence based recommendations on therapy of AGE is based on outpatient research and is therefore generalizable to general practice.</p> <p>Conclusions</p> <p>The present study shows considerable variation in the quality of guidelines on AGE in children, as well as inconsistencies between the recommendations. It remains unclear how to asses the extent of dehydration and determine the preferred treatment or referral of a young child with AGE presenting in general practice.</p