Imaging the Neutrophil Phagosome and Cytoplasm Using a Ratiometric pH Indicator.

Neutrophils are crucial to host innate defense and, consequently, constitute an important area of medical research. The phagosome, the intracellular compartment where the killing and digestion of engulfed particles take place, is the main arena for neutrophil pathogen killing that requires tight regulation. Phagosomal pH is one aspect that is carefully controlled, in turn regulating antimicrobial protease activity. Many fluorescent pH-sensitive dyes have been used to visualize the phagosomal environment. S-1 has several advantages over other pH-sensitive dyes, including its dual emission spectra, its resistance to photo-bleaching, and its high pKa. Using this method, we have demonstrated that the neutrophil phagosome is unusually alkaline in comparison to other phagocytes. By using different biochemical conjugations of the dye, the phagosome can be delineated from the cytoplasm so that changes in the size and shape of the phagosome can be assessed. This allows for further monitoring of ionic movement

Would I be helped? Cross-national CCTV footage shows that intervention is the norm in public conflicts

This is the author accepted manuscript. The final version is available from APS via the DOI in this record.Replication data, statistical scripts, and video coding procedures are made available on the Open Science Framework - https://osf.io/xzjsgHalf a century of research on bystander behavior concludes that individuals are less likely to intervene during an emergency when in the presence of others than when alone. By contrast, little is known regarding the aggregated likelihood that at least someone present at an emergency will do something to help. The importance of establishing this aggregated intervention baseline is not only of scholarly interest but is also the most pressing question for actual public victims-will I receive help if needed? The current article describes the largest systematic study of real-life bystander intervention in actual public conflicts captured by surveillance cameras. Using a unique cross-national video dataset from the United Kingdom, the Netherlands, and South Africa (N = 219), we show that in 9 of 10 public conflicts, at least 1 bystander, but typically several, will do something to help. We record similar likelihoods of intervention across the 3 national contexts, which differ greatly in levels of perceived public safety. Finally, we find that increased bystander presence is related to a greater likelihood that someone will intervene. Taken together these findings allay the widespread fear that bystanders rarely intervene to help. We argue that it is time for psychology to change the narrative away from an absence of help and toward a new understanding of what makes intervention successful or unsuccessful. (PsycINFO Database Record (c) 2019 APA, all rights reserved)

Sorafenib dose escalation is not uniformly associated with blood pressure elevations in normotensive patients with advanced malignancies.

Hypertension after treatment with vascular endothelial growth factor (VEGF) receptor inhibitors is associated with superior treatment outcomes for advanced cancer patients. To determine whether increased sorafenib doses cause incremental increases in blood pressure (BP), we measured 12-h ambulatory BP in 41 normotensive advanced solid tumor patients in a randomized dose-escalation study. After 7 days' treatment (400 mg b.i.d.), mean diastolic BP (DBP) increased in both study groups. After dose escalation, group A (400 mg t.i.d.) had marginally significant further increase in 12-h mean DBP (P = 0.053), but group B (600 mg b.i.d.) did not achieve statistically significant increases (P = 0.25). Within groups, individuals varied in BP response to sorafenib dose escalation, but these differences did not correlate with changes in steady-state plasma sorafenib concentrations. These findings in normotensive patients suggest BP is a complex pharmacodynamic biomarker of VEGF inhibition. Patients have intrinsic differences in sensitivity to sorafenib's BP-elevating effects

Cross-national CCTV footage shows low victimization risk for bystander interveners in public conflicts

This is the author accepted manuscript. The final version is available from the American Psychological Association via the DOI in this record Objective: Accumulating evidence shows that bystanders witnessing public disputes frequently intervene to help. However, little is known regarding the risks entailed for those bystanders who enter the fray to stop conflicts. This study systematically examined the prevalence of bystander victimizations and the associated risk factors. Method: Data were a cross-national sample of 93 surveillance camera recordings of real-life public disputes, capturing the potential victimizations of 417 intervening and 636 nonintervening bystanders. Results: Data showed that interveners were rarely physically harmed-at a rate of 3.6%-and noninterveners were virtually never victimized. Confirmatory regression results showed that conflict party affiliation was a moderately robust predictor of bystander victimization. The gender of the intervener was a highly fragile risk factor. More severe conflicts were not associated with a higher victimization likelihood. Conclusions: Our findings highlight the value of naturalistic observation for bystander research and emphasize the need for evidence-based bystander intervention recommendations. Data, materials, and postprint are available at osf.io/vyutj

A harmonized atlas of mouse spinal cord cell types and their spatial organization

Single-cell RNA sequencing data can unveil the molecular diversity of cell types. Cell type atlases of the mouse spinal cord have been published in recent years but have not been integrated together. Here, we generate an atlas of spinal cell types based on single-cell transcriptomic data, unifying the available datasets into a common reference framework. We report a hierarchical structure of postnatal cell type relationships, with location providing the highest level of organization, then neurotransmitter status, family, and finally, dozens of refined populations. We validate a combinatorial marker code for each neuronal cell type and map their spatial distributions in the adult spinal cord. We also show complex lineage relationships among postnatal cell types. Additionally, we develop an open-source cell type classifier, SeqSeek, to facilitate the standardization of cell type identification. This work provides an integrated view of spinal cell types, their gene expression signatures, and their molecular organization

Strong Water Absorption in the Dayside Emission Spectrum of the Planet HD 189733b

Recent observations of the extrasolar planet HD 189733b did not reveal the presence of water in the emission spectrum of the planet. Yet models of such 'Hot Jupiter' planets predict an abundance of atmospheric water vapour. Validating and constraining these models is crucial for understanding the physics and chemistry of planetary atmospheres in extreme environments. Indications of the presence of water in the atmosphere of HD 189733b have recently been found in transmission spectra, where the planet's atmosphere selectively absorbs the light of the parent star, and in broadband photometry. Here we report on the detection of strong water absorption in a high signal-to-noise, mid-infrared emission spectrum of the planet itself. We find both a strong downturn in the flux ratio below 10 microns and discrete spectral features that are characteristic of strong absorption by water vapour. The differences between these and previous observations are significant and admit the possibility that predicted planetary-scale dynamical weather structures might alter the emission spectrum over time. Models that match the observed spectrum and the broadband photometry suggest that heat distribution from the dayside to the night side is weak. Reconciling this with the high night side temperature will require a better understanding of atmospheric circulation or possible additional energy sources.Comment: 11 pages, 1 figure, published in Natur

Consolation in the aftermath of robberies resembles post-aggression consolation in chimpanzees

This is the final version. Available on open access from Public Library of Science via the DOI in this record. Data Availability: We fully respect and endorse the philosophy and derived data and computer code availability policy of PLOS, and would in fact welcome and encourage replications and extensions of our work. Access to the raw CCTV footage data will be granted by signing an agreement stating that the applicant (1) will use the data only for scientific purposes, (2) will not make the data accessible to third parties, and (3) will not publish results that will disclose the identity of the subjects in the data. To request access to the raw footage files or inquire about the conditions, please contact Ho-Young Wisselink, datamanager at the Netherlands Institute for the Study of Crime and Law Enforcement (NSCR), at email address [email protected]. The analyzed data file with coded observations of the video footage and the code descriptions are added as supplementary files (S1 File and S2 File) to the manuscript submission. This allows readers to replicate the analytical parts of our research.Post-aggression consolation is assumed to occur in humans as well as in chimpanzees. While consolation following peer aggression has been observed in children, systematic evidence of consolation in human adults is rare. We used surveillance camera footage of the immediate aftermath of nonfatal robberies to observe the behaviors and characteristics of victims and bystanders. Consistent with empathy explanations, we found that consolation was linked to social closeness rather than physical closeness. While females were more likely to console than males, males and females were equally likely to be consoled. Furthermore, we show that high levels of threat during the robbery increased the likelihood of receiving consolation afterwards. These patterns resemble post-aggression consolation in chimpanzees and suggest that emotions of empathic concern are involved in consolation across humans and chimpanzees.Netherlands National Polic

Wall-Crossing from Boltzmann Black Hole Halos

A key question in the study of N=2 supersymmetric string or field theories is to understand the decay of BPS bound states across walls of marginal stability in the space of parameters or vacua. By representing the potentially unstable bound states as multi-centered black hole solutions in N=2 supergravity, we provide two fully general and explicit formulae for the change in the (refined) index across the wall. The first, "Higgs branch" formula relies on Reineke's results for invariants of quivers without oriented loops, specialized to the Abelian case. The second, "Coulomb branch" formula results from evaluating the symplectic volume of the classical phase space of multi-centered solutions by localization. We provide extensive evidence that these new formulae agree with each other and with the mathematical results of Kontsevich and Soibelman (KS) and Joyce and Song (JS). The main physical insight behind our results is that the Bose-Fermi statistics of individual black holes participating in the bound state can be traded for Maxwell-Boltzmann statistics, provided the (integer) index \Omega(\gamma) of the internal degrees of freedom carried by each black hole is replaced by an effective (rational) index \bar\Omega(\gamma)= \sum_{m|\gamma} \Omega(\gamma/m)/m^2. A similar map also exists for the refined index. This observation provides a physical rationale for the appearance of the rational Donaldson-Thomas invariant \bar\Omega(\gamma) in the works of KS and JS. The simplicity of the wall crossing formula for rational invariants allows us to generalize the "semi-primitive wall-crossing formula" to arbitrary decays of the type \gamma\to M\gamma_1+N\gamma_2 with M=2,3.Comment: 71 pages, 1 figure; v3: changed normalisation of symplectic form 3.22, corrected 3.35, other cosmetic change