Dissociable Modulation of Overt Visual Attention in Valence and Arousal Revealed by Topology of Scan Path

Emotional stimuli have evolutionary significance for the survival of organisms; therefore, they are attention-grabbing and are processed preferentially. The neural underpinnings of two principle emotional dimensions in affective space, valence (degree of pleasantness) and arousal (intensity of evoked emotion), have been shown to be dissociable in the olfactory, gustatory and memory systems. However, the separable roles of valence and arousal in scene perception are poorly understood. In this study, we asked how these two emotional dimensions modulate overt visual attention. Twenty-two healthy volunteers freely viewed images from the International Affective Picture System (IAPS) that were graded for affective levels of valence and arousal (high, medium, and low). Subjects' heads were immobilized and eye movements were recorded by camera to track overt shifts of visual attention. Algebraic graph-based approaches were introduced to model scan paths as weighted undirected path graphs, generating global topology metrics that characterize the algebraic connectivity of scan paths. Our data suggest that human subjects show different scanning patterns to stimuli with different affective ratings. Valence salient stimuli (with neutral arousal) elicited faster and larger shifts of attention, while arousal salient stimuli (with neutral valence) elicited local scanning, dense attention allocation and deep processing. Furthermore, our model revealed that the modulatory effect of valence was linearly related to the valence level, whereas the relation between the modulatory effect and the level of arousal was nonlinear. Hence, visual attention seems to be modulated by mechanisms that are separate for valence and arousal

Novel Use of Surveillance Data to Detect HIV-Infected Persons with Sustained High Viral Load and Durable Virologic Suppression in New York City

Background: Monitoring of the uptake and efficacy of ART in a population often relies on cross-sectional data, providing limited information that could be used to design specific targeted intervention programs. Using repeated measures of viral load (VL) surveillance data, we aimed to estimate and characterize the proportion of persons living with HIV/AIDS (PLWHA) in New York City (NYC) with sustained high VL (SHVL) and durably suppressed VL (DSVL). Methods/Principal Findings: Retrospective cohort study of all persons reported to the NYC HIV Surveillance Registry who were alive and $12 years old by the end of 2005 and who had$2 VL tests in 2006 and 2007. SHVL and DSVL were defined as PLWHA with 2 consecutive VLs $100,000 copies/mL and PLWHA with all VLs #400 copies/mL, respectively. Logistic regression models using generalized estimating equations were used to model the association between SHVL and covariates. There were 56,836 PLWHA, of whom 7 % had SHVL and 38 % had DSVL. Compared to those without SHVL, persons with SHVL were more likely to be younger, black and have injection drug use (IDU) risk. PLWHA with SHVL were more likely to die by 2007 and be younger by nearly ten years, on average. Conclusions/Significance: Nearly 60 % of PLWHA in 2005 had multiple VLs, of whom almost 40 % had DSVL, suggesting successful ART uptake. A small proportion had SHVL, representing groups known to have suboptimal engagement in care. This group should be targeted for additional outreach to reduce morbidity and secondary transmission. Measures based o

A Cysteine Protease Is Critical for Babesia spp. Transmission in Haemaphysalis Ticks

Vector ticks possess a unique system that enables them to digest large amounts of host blood and to transmit various animal and human pathogens, suggesting the existence of evolutionally acquired proteolytic mechanisms. We report here the molecular and reverse genetic characterization of a multifunctional cysteine protease, longipain, from the babesial parasite vector tick Haemaphysalis longicornis. Longipain shares structural similarity with papain-family cysteine proteases obtained from invertebrates and vertebrates. Endogenous longipain was mainly expressed in the midgut epithelium and was specifically localized at lysosomal vacuoles and possibly released into the lumen. Its expression was up-regulated by host blood feeding. Enzymatic functional assays using in vitro and in vivo substrates revealed that longipain hydrolysis occurs over a broad range of pH and temperature. Haemoparasiticidal assays showed that longipain dose-dependently killed tick-borne Babesia parasites, and its babesiacidal effect occurred via specific adherence to the parasite membranes. Disruption of endogenous longipain by RNA interference revealed that longipain is involved in the digestion of the host blood meal. In addition, the knockdown ticks contained an increased number of parasites, suggesting that longipain exerts a killing effect against the midgut-stage Babesia parasites in ticks. Our results suggest that longipain is essential for tick survival, and may have a role in controlling the transmission of tick-transmittable Babesia parasites

The JWST Extragalactic Mock Catalog: Modeling Galaxy Populations from the UV through the Near-IR over 13 Billion Years of Cosmic History

We present an original phenomenological model to describe the evolution of galaxy number counts, morphologies, and spectral energy distributions across a wide range of redshifts ($0.2\lt z\lt 15$) and stellar masses $[\mathrm{log}(M/{M}_{\odot })\geqslant 6]$. Our model follows observed mass and luminosity functions of both star-forming and quiescent galaxies, and reproduces the redshift evolution of colors, sizes, star formation, and chemical properties of the observed galaxy population. Unlike other existing approaches, our model includes a self-consistent treatment of stellar and photoionized gas emission and dust attenuation based on the beagle tool. The mock galaxy catalogs generated with our new model can be used to simulate and optimize extragalactic surveys with future facilities such as the James Webb Space Telescope (JWST), and to enable critical assessments of analysis procedures, interpretation tools, and measurement systematics for both photometric and spectroscopic data. As a first application of this work, we make predictions for the upcoming JWST Advanced Deep Extragalactic Survey (JADES), a joint program of the JWST/NIRCam and NIRSpec Guaranteed Time Observations teams. We show that JADES will detect, with NIRCam imaging, 1000s of galaxies at z gsim 6, and 10s at z gsim 10 at ${m}_{{AB}}\lesssim 30$ (5σ) within the 236 arcmin2 of the survey. The JADES data will enable accurate constraints on the evolution of the UV luminosity function at z > 8, and resolve the current debate about the rate of evolution of galaxies at z gsim 8. Ready-to-use mock catalogs and software to generate new realizations are publicly available as the JAdes extraGalactic Ultradeep Artificial Realizations (JAGUAR) package

The macrophage in HIV-1 infection: From activation to deactivation?

Macrophages play a crucial role in innate and adaptative immunity in response to microorganisms and are an important cellular target during HIV-1 infection. Recently, the heterogeneity of the macrophage population has been highlighted. Classically activated or type 1 macrophages (M1) induced in particular by IFN-γ display a pro-inflammatory profile. The alternatively activated or type 2 macrophages (M2) induced by Th-2 cytokines, such as IL-4 and IL-13 express anti-inflammatory and tissue repair properties. Finally IL-10 has been described as the prototypic cytokine involved in the deactivation of macrophages (dM). Since the capacity of macrophages to support productive HIV-1 infection is known to be modulated by cytokines, this review shows how modulation of macrophage activation by cytokines impacts the capacity to support productive HIV-1 infection. Based on the activation status of macrophages we propose a model starting with M1 classically activated macrophages with accelerated formation of viral reservoirs in a context of Th1 and proinflammatory cytokines. Then IL-4/IL-13 alternatively activated M2 macrophages will enter into the game that will stop the expansion of the HIV-1 reservoir. Finally IL-10 deactivation of macrophages will lead to immune failure observed at the very late stages of the HIV-1 disease

JEMS: A Deep Medium-band Imaging Survey in the Hubble Ultra Deep Field with JWST NIRCam and NIRISS

We present JWST Extragalactic Medium-band Survey, the first public medium-band imaging survey carried out using JWST/NIRCam and NIRISS. These observations use ∼2 and ∼4 μm medium-band filters (NIRCam F182M, F210M, F430M, F460M, F480M; and NIRISS F430M and F480M in parallel) over 15.6 arcmin2 in the Hubble Ultra Deep Field (UDF), thereby building on the deepest multiwavelength public data sets available anywhere on the sky. We describe our science goals, survey design, NIRCam and NIRISS image reduction methods, and describe our first data release of the science-ready mosaics, which reach 5σ point-source limits (AB mag) of ∼29.3-29.4 in 2 μm filters and ∼28.2-28.7 at 4 μm. Our chosen filters create a JWST imaging survey in the UDF that enables novel analysis of a range of spectral features potentially across the redshift range of 0.3 1 mag) across redshifts 1.5 < z < 9.3, most prominently Hα+[N ii] and [O iii]+Hβ. We present our first data release including science-ready mosaics of each medium-band image available to the community, adding to the legacy value of past and future surveys in the UDF. This survey demonstrates the power of medium-band imaging with JWST, informing future extragalactic survey strategies using JWST observations

Cancer Biomarker Discovery: The Entropic Hallmark

Background: It is a commonly accepted belief that cancer cells modify their transcriptional state during the progression of the disease. We propose that the progression of cancer cells towards malignant phenotypes can be efficiently tracked using high-throughput technologies that follow the gradual changes observed in the gene expression profiles by employing Shannon's mathematical theory of communication. Methods based on Information Theory can then quantify the divergence of cancer cells' transcriptional profiles from those of normally appearing cells of the originating tissues. The relevance of the proposed methods can be evaluated using microarray datasets available in the public domain but the method is in principle applicable to other high-throughput methods. Methodology/Principal Findings: Using melanoma and prostate cancer datasets we illustrate how it is possible to employ Shannon Entropy and the Jensen-Shannon divergence to trace the transcriptional changes progression of the disease. We establish how the variations of these two measures correlate with established biomarkers of cancer progression. The Information Theory measures allow us to identify novel biomarkers for both progressive and relatively more sudden transcriptional changes leading to malignant phenotypes. At the same time, the methodology was able to validate a large number of genes and processes that seem to be implicated in the progression of melanoma and prostate cancer. Conclusions/Significance: We thus present a quantitative guiding rule, a new unifying hallmark of cancer: the cancer cell's transcriptome changes lead to measurable observed transitions of Normalized Shannon Entropy values (as measured by high-throughput technologies). At the same time, tumor cells increment their divergence from the normal tissue profile increasing their disorder via creation of states that we might not directly measure. This unifying hallmark allows, via the the Jensen-Shannon divergence, to identify the arrow of time of the processes from the gene expression profiles, and helps to map the phenotypical and molecular hallmarks of specific cancer subtypes. The deep mathematical basis of the approach allows us to suggest that this principle is, hopefully, of general applicability for other diseases