Although pain is a prevalent nonmotor symptom in Parkinson’s disease (PD), it is undertreated, in part because of our limited understanding of the underlying mechanisms. Considering that the basal ganglia are implicated in pain sensation, and that their synaptic outputs are controlled by the subthalamic nucleus (STN), we hypothesized that...

One factor that contributes to the high prevalence of fetal alcohol spectrum disorder (FASD) is binge-like consumption of alcohol before pregnancy awareness. It is known that treatments are more effective with early recognition of FASD. Recent advances in retrospective motion correction for the reconstruction of three-dimensional (3D) fetal brain MRI...

Sleep pressure and sleep depth are key regulators of wake and sleep. Current methods of measuring these parameters in Drosophila melanogaster have low temporal resolution and/or require disrupting sleep. Here we report analysis tools for high-resolution, noninvasive measurement of sleep pressure and depth from movement data. Probability of initiating activity,...

Chronic pain is a highly prevalent disease with poorly understood pathophysiology. In particular, the brain mechanisms mediating the transition from acute to chronic pain remain largely unknown. Here, we identify a subcortical signature of back pain. Specifically, subacute back pain patients who are at risk for developing chronic pain exhibit...

Transcription factors (TFs) enact precise regulation of gene expression through site-specific, genome-wide binding. Common methods for TF-occupancy profiling, such as chromatin immunoprecipitation, are limited by requirement of TF-specific antibodies and provide only end-point snapshots of TF binding. Alternatively, TF-tagging techniques, in which a TF is fused to a DNA-modifying enzyme...

The initial response to an addictive substance can facilitate repeated use: That is, individuals experiencing more positive effects are more likely to use that drug again. Increasing evidence suggests that psychoactive cannabinoid use in adolescence enhances the behavioral effects of cocaine. However, despite the behavioral data, there is no neurobiological...

HIV-1 persists in cellular reservoirs that can reignite viremia if antiretroviral therapy (ART) is interrupted. Therefore, insight into the nature of those reservoirs may be revealed from the composition of recrudescing viremia following treatment cessation. A minor population of macrophage-tropic (M-tropic) viruses was identified in a library of recombinant viruses...

Isocitrate dehydrogenase (IDH) mutation is a common genetic abnormality in human malignancies characterized by remarkable metabolic reprogramming. Our present study demonstrated that IDH1-mutated cells showed elevated levels of reactive oxygen species and higher demands on Nrf2-guided glutathione de novo synthesis. Our findings showed that triptolide, a diterpenoid epoxide from Tripterygium...

Genetic polymorphisms in the region of the trimeric serine hydrolase high-temperature requirement 1 (HTRA1) are associated with increased risk of age-related macular degeneration (AMD) and disease progression, but the precise biological function of HtrA1 in the eye and its contribution to disease etiologies remain undefined. In this study, we have...

As the novel coronavirus spreads, communities across the United States are struggling to offer public testing. The need is urgent. Testing got off to a delayed start in the United States as a result of technical missteps and a slow response from government officials. Now cities across the country are...

Human activities and population growth have increased the natural burden of reactive nitrogen (N) in the environment. Excessive N deposition on Earth’s surface leads to adverse feedbacks on ecosystems and humans. Similar to that of air pollution, emission control is recognized as an efficient means to control acid deposition. Control...

Aerosol–radiation interaction (ARI) plays a significant role in the accumulation of fine particulate matter (PM2.5) by stabilizing the planetary boundary layer and thus deteriorating air quality during haze events. However, modification of photolysis by aerosol scattering or absorbing solar radiation (aerosol–photolysis interaction or API) alters the atmospheric oxidizing capacity, decreases...

Sub-Neptunes are common among the discovered exoplanets. However, lack of knowledge on the state of matter in H2O-rich setting at high pressures and temperatures (P−T) places important limitations on our understanding of this planet type. We have conducted experiments for reactions between SiO2 and H2O as archetypal materials for rock...

Neural networks have become the method of choice in surrogate modeling because of their ability to characterize arbitrary, high-dimensional functions in a data-driven fashion. This paper advocates for the training of surrogates that are 1) consistent with the physical manifold, resulting in physically meaningful predictions, and 2) cyclically consistent with...

Active matter, both synthetic and biological, demonstrates complex spatiotemporal self-organization and the emergence of collective behavior. A coherent rotational motion, the vortex phase, is of great interest because of its ability to orchestrate well-organized motion of self-propelled particles over large distances. However, its generation without geometrical confinement has been a...

A ubiquitous structural feature in biological systems is texture in extracellular matrix that gains functions when hardened, for example, cell walls, insect scales, and diatom tests. Here, we develop patterned liquid crystal elastomer (LCE) particles by recapitulating the biophysical patterning mechanism that forms pollen grain surfaces. In pollen grains, a...

Legumes tend to be nodulated by competitive rhizobia that do not maximize nitrogen (N2) fixation, resulting in suboptimal yields. Rhizobial nodulation competitiveness and effectiveness at N2 fixation are independent traits, making their measurement extremely time-consuming with low experimental throughput. To transform the experimental assessment of rhizobial competitiveness and effectiveness, we...

The biological carbon pump (BCP) comprises wide-ranging processes that set carbon supply, consumption, and storage in the oceans’ interior. It is becoming increasingly evident that small changes in the efficiency of the BCP can significantly alter ocean carbon sequestration and, thus, atmospheric CO2 and climate, as well as the functioning...

Synaptic activity in neurons leads to the rapid activation of genes involved in mammalian behavior. ATP-dependent chromatin remodelers such as the BAF complex contribute to these responses and are generally thought to activate transcription. However, the mechanisms keeping such “early activation” genes silent have been a mystery. In the course...

Convection is buoyancy-driven flow resulting from unstable density stratification in the presence of a gravitational field. Beyond convection’s central role in myriad engineering heat transfer applications, it underlies many of nature’s dynamical designs on larger-than-human scales. For example, solar heating of Earth’s surface generates buoyancy forces that cause the winds...

At the pinnacle of the 17th century scientific revolution, René Descartes, the father of modern philosophy, published his monumental Meditations on First Philosophy (1), in which he proposed a division between soul and body—mind and brain—with the former in charge of our thoughts and conscious decisions (res cogitans) and the...

In 2006, the New York City-based Vilcek Foundation created an annual prize program for foreign-born biomedical scientists who have made major contributions to their fields while living and working in the United States. The founders, themselves immigrants from Czechoslovakia, established the program to raise public awareness of the indispensable role...

Our study in PNAS (1) applies a mathematically based framework to the study of reported emotional experience evoked by music in the United States and China. Germane to theoretical debate, our methods reveal how specific emotions such as “triumph” are more primary across cultures than valence and arousal, a finding...

Cowen et al. (1) leverage modern gains in data science to describe impressive cross-cultural similarities in the perception of musical affect and do so in unprecedented detail. Their approach is innovative and fundamentally empirical. As such, it should have important applications for prediction in the field of affective computing, which...

A growing literature at the intersection of personality psychology and behavioral economics investigates the interplay between personality and decision making in social dilemmas (1, 2). Engelmann et al. (3) extend prior research in this area by investigating the role of antisocial personality in the context of a trust game with...

Engelmann et al. ask whether “personality traits [can] help us better understand economic behavior across strategic contexts” (ref. 1, p. 12781), and, as an answer to this, identify “an antisocial personality profile” (APP) (ref. 1, p. 12785). There is much to like about this investigation; in particular, it illustrates “that...

BACKGROUND:Assisted coughing via mechanical in-exsufflation (MI-E) is a first-line treatment for secretion management in patients with amyotrophic lateral sclerosis (ALS) with unassisted CPF < 4.25 L/s. Some devices enable oscillations to be added to MI-E (MI-E+O). We sought to determine whether adding oscillations to MI-E enables a reduction in the use of invasive secretion management procedures (ie, bronchoscopy or tracheostomy) in subjects with ALS.METHODS:We conducted a 12-month, prospective, randomized follow-up study of subjects with ALS for whom assisted coughing techniques were indicated. One group was treated with oscillations in addition to MI-E (MI-E+O), and the other group was treated with conventional MI-E.RESULTS:29 subjects were included in the MI-E group and 27 subjects were included in the MI-E+O group. Five subjects (8.9%) required invasive techniques for secretion management (3 in the MI-E group and 2 in the MI-E+O group, P = .70). Treatment with MI-E+O did not alter the risk of invasive procedures (odds ratio 0.69, 95% CI 0.10–4.50, P = .70). The mean number of respiratory infections was 0.58 ± 0.16 in the MI-E group and 0.025 ± 0.08 in the MI-E+O group (P = .10). Survival was 8.96 ± 0.18 months in the MI-E group and 7.70 ± 0.70 months in the MI-E+O group (P = .10).CONCLUSION:Adding oscillations to MI-E did not enable a reduction in the need to perform invasive procedures for secretion management in subjects with ALS.

Elizabeth J. Lawrence, Marija Zanic, and Luke M. Rice

CLIP-associating proteins (CLASPs) form an evolutionarily conserved family of regulatory factors that control microtubule dynamics and the organization of microtubule networks. The importance of CLASP activity has been appreciated for some time, but until recently our understanding of the underlying molecular mechanisms remained basic. Over the past few years, studies of, for example, migrating cells, neuronal development, and microtubule reorganization in plants, along with in vitro reconstitutions, have provided new insights into the cellular roles and molecular basis of CLASP activity. In this Cell Science at a Glance article and the accompanying poster, we will summarize some of these recent advances, emphasizing how they impact our current understanding of CLASP-mediated microtubule regulation.

A multidisciplinary endocrinologist-led shared medical appointment (SMA) model showed statistically significant reductions in A1C from baseline over 3 years that were not significantly different from appointments with endocrinologists or primary care providers alone within a resource-poor population. Similarly, the SMA model achieved clinical outcomes on par with endocrinologist-only visits with the added benefit of improving endocrine provider productivity and specialty access for patients. Greater patient engagement with the SMA model was associated with significantly lower A1C.

ABSTRACT

Academics in non-tenure-track positions encounter a unique set of challenges on the road toward tenure. Institutionalized policies and lack of mentors are additional burdens for foreign scientists, resulting in representation differences. Becoming a scientist has been a personal and moving journey in which my multiple selves intersect and clash every now and again. My identity as a scientist is a life project and has intersected with my other identities: a young Latina immigrant in Western Europe. This crossroad has molded, and at times, challenged my participation in science.

The type VI secretion system (T6SS) is a weapon for delivering effectors into target cells that is widespread in Gram-negative bacteria. The T6SS is a highly versatile machine, as it can target both eukaryotic and prokaryotic cells, and it has been proposed that T6SSs are adapted to the specific needs of each bacterium. The expression of T6SS gene clusters and the activation of the secretion apparatus are therefore tightly controlled. In enteroaggregative Escherichia coli (EAEC), the sci1 T6SS gene cluster is subject to a complex regulation involving both the ferric uptake regulator (Fur) and DNA adenine methylase (Dam)-dependent DNA methylation. In this study, an additional, internal, promoter was identified within the sci1 gene cluster using +1 transcriptional mapping. Further analyses demonstrated that this internal promoter is controlled by a mechanism strictly identical to that of the main promoter. The Fur binding box overlaps the –10 transcriptional element and a Dam methylation site, GATC-32. Hence, the expression of the distal sci1 genes is repressed and the GATC-32 site is protected from methylation in iron-rich conditions. The Fur-dependent protection of GATC-32 was confirmed by an in vitro methylation assay. In addition, the methylation of GATC-32 negatively impacted Fur binding. The expression of the sci1 internal promoter is therefore controlled by iron availability through Fur regulation, whereas Dam-dependent methylation maintains a stable ON expression in iron-limited conditions.

IMPORTANCE Bacteria use weapons to deliver effectors into target cells. One of these weapons, the type VI secretion system (T6SS), assembles a contractile tail acting as a spring to propel a toxin-loaded needle. Its expression and activation therefore need to be tightly regulated. Here, we identified an internal promoter within the sci1 T6SS gene cluster in enteroaggregative E. coli. We show that this internal promoter is controlled by Fur and Dam-dependent methylation. We further demonstrate that Fur and Dam compete at the –10 transcriptional element to finely tune the expression of T6SS genes. We propose that this elegant regulatory mechanism allows the optimum production of the T6SS in conditions where enteroaggregative E. coli encounters competing species.

Background:

Previous studies examining potential sex and gender bias in the Canadian Resident Matching Service (CaRMS) match have had conflicting results. We examined the results of the CaRMS match over the period 2013–2019 to determine the potential association between applicants’ gender and the outcome of matching to their first-choice discipline.

Developer Mirari & Co. announced the science-fiction action platformer Dark Light for Windows PC via Steam Early Access on May 8 and later for the Nintendo Switch when the game leaves Steam Early Access. 

Mirari & Co. is looking to release the game within one year of the Steam Early Access release, however, it depends "on how we are taking players suggestions and advice to shaping the game."

View the latest trailer of the game below:

Here is an overview of the game:

Dark Light is a science-fiction action-platformer with unique gameplay. Explore an apocalyptic cyberpunk world full of supernatural beings. Encounter and defeat creatures of darkness invisible to the naked eye, detected only with the light source from your drone. Experience the horror and feel their presence as they surround you.

As a Dark Hunter you were dropped into a wreaked world. To survive, you need to equip yourself, fight your way through, and collect ‘shards’ from killing supernatural creatures to reinforce your energy. Through survival, you will explore the mysterious dark zones of the apocalypse world.

Key Features:

• Cinematic quality graphic, detailed characters and environment design, and vivid animation with lush visual effect.
• A variety of range, melee, and throwable weapons; unique items; and multiple ways to upgrade weapons, special equipment, and the player to shape your own character skills.
• Non-linear map structure for you to choose your own path to explore the dark zones. Encounter horrifying supernatural enemies, fearsome bosses, and friendly NPCs, and fight with invisible creatures that can only be seen in a special light source.
• Detect invisible enemies and reveal hidden paths with the special light source from your drone.

A life-long and avid gamer, William D'Angelo was first introduced to VGChartz in 2007. After years of supporting the site, he was brought on in 2010 as a junior analyst, working his way up to lead analyst in 2012. He has expanded his involvement in the gaming community by producing content on his own YouTube channel and Twitch channel dedicated to gaming Let's Plays and tutorials. You can contact the author at wdangelo@vgchartz.com or on Twitter @TrunksWD.

Full Article - https://www.vgchartz.com/article/443411/sci-fi-action-platformer-dark-light-launches-may-8-for-steam-early-access-later-for-switch/

As part of its eventual launch on Steam, daunting simulation Dwarf Fortress has been planning a big visual overhaul. “Now with graphics!” Bay 12 proclaim on the store page. In a new little update, they’re giving us a look at what the generated world maps will look like with these non-ASCII pixels—though, yes, you’ll still […]

A new movie reimagines H.G. Wells's novel The Invisible Man. We still can't make people invisible, but it is possible to make tiny objects completely disappear

Flying car hopefuls were meant to take off at a competition on a NASA airbase, but no team claimed the prize after a string of crashes and no-shows

Pandemics of the past can teach us about the current one, says John Troyer, who studies how we use technology to alter the experience of death

Is our love affair with AI really about building a new kind of deity to meet human needs no amount of rationality can fill? Max Barry's disturbing novel Providence lays out the case, says Sally Adee

In TV series Devs, a tech company has built an extremely powerful quantum computer. The show is both beautiful and captivating, says Rowan Hooper

"This government has failed to show any self-criticism whatsoever, when it is glaringly obvious to everybody that big mistakes have been made."

X-37B? Sorry, I thought you said your name was X Æ A-12.

Whether it was driverless cars, lab-grown meat or faster-than-light neutrinos, some things just didn't live up to the hype in the 2010s