An HIV feedback resistor: auto-regulatory circuit deactivator and noise buffer.

Animal viruses (e.g., lentiviruses and herpesviruses) use transcriptional positive feedback (i.e., transactivation) to regulate their gene expression. But positive-feedback circuits are inherently unstable when turned off, which presents a particular dilemma for latent viruses that lack transcriptional repressor motifs. Here we show that a dissipative feedback resistor, composed of enzymatic interconversion of the transactivator, converts transactivation circuits into excitable systems that generate transient pulses of expression, which decay to zero. We use HIV-1 as a model system and analyze single-cell expression kinetics to explore whether the HIV-1 transactivator of transcription (Tat) uses a resistor to shut off transactivation. The Tat feedback circuit was found to lack bi-stability and Tat self-cooperativity but exhibited a pulse of activity upon transactivation, all in agreement with the feedback resistor model. Guided by a mathematical model, biochemical and genetic perturbation of the suspected Tat feedback resistor altered the circuit's stability and reduced susceptibility to molecular noise, in agreement with model predictions. We propose that the feedback resistor is a necessary, but possibly not sufficient, condition for turning off noisy transactivation circuits lacking a repressor motif (e.g., HIV-1 Tat). Feedback resistors may be a paradigm for examining other auto-regulatory circuits and may inform upon how viral latency is established, maintained, and broken

Sub-concussive Hit Characteristics Predict Deviant Brain Metabolism in Football Athletes

Magnetic resonance spectroscopy and helmet telemetry were used to monitor the neural metabolic response to repetitive head collisions in 25 high school American football athletes. Specific hit characteristics were determined highly predictive of metabolic alterations, suggesting that sub-concussive blows can produce biochemical changes and potentially lead to neurological problems

Influence of grain size, shape and compaction on georadar waves: example of an Aeolian dune

Many Ground Penetrating Radar (GPR) profiles acquired in dry aeolian environment have shown good reflectivity inside present-day dunes. We show that the origin of this reflectivity is related to changes in grain size distribution, packing and/or grain shape in a sandy material. We integrate these three parameters into analytical models for bulk permittivity in order to predict the reflections and the velocity of GPR waves. We consider two GPR cross-sections acquired over Aeolian dunes in the Chadian desert. The 2D migration of GPR data suggests that dunes contain different kinds of bounding surfaces. We discuss and model three kinds of reflections using reasonable geological hypothesis about Aeolian sedimentation processes. The propagation and the reflection of radar waves are calculated using the 1D wavelet modelling method in spectral domain. The results of the forward modelling are in good accordance with real observed data

Robotic Habitat Technologies for Minimizing Crew Maintenance Requirements

NASA’s Lunar Gateway aims to be deployed later in the decade and will serve as an outpost orbiting the moon. This habitat will be utilized as a base for lunar operations as well as future missions to Mars. Unlike the International Space Station (ISS), which maintains three to six astronauts at any given time, the Lunar Gateway will be uncrewed for eleven months out of the year. Over 80% of crew time onboard the ISS is dedicated to logistics, repair, and maintenance, leaving minimal time for scientific research and experimentation. In order to maintain Gateway, robotic systems must be implemented to accomplish maintenance and operational tasks. This paper discusses our team’s proposed dexterous robotic system, which will address routine and contingency operational and maintenance tasks on Gateway. The project is experimentally-based, and split into three approaches: cataloging robotic capabilities via robot/taskboard interactions, logistics management of Cargo Transfer Bags (CTBs), and software development of an AprilTag situational development system. This research project utilizes the unique capabilities of the University of Maryland (UMD) Space Systems Laboratory (SSL), which houses various dexterous robotic manipulators, mock-ups of space habitats, and the Neutral Buoyancy Research Facility (NBRF), a 50-foot diameter, 25-foot deep water tank used to simulate microgravity conditions. By incorporating robotic systems into the architecture of the Lunar Gateway, it will allow for the lunar outpost to be continually operated and maintained while uncrewed, and will allow for astronauts, when present, to focus on maximizing scientific discoveries.NASA RASC-AL 202

Control of human adenovirus type 5 gene expression by cellular Daxx/ATRX chromatin-associated complexes

Death domain–associated protein (Daxx) cooperates with X-linked α-thalassaemia retardation syndrome protein (ATRX), a putative member of the sucrose non-fermentable 2 family of ATP-dependent chromatin-remodelling proteins, acting as the core ATPase subunit in this complex, whereas Daxx is the targeting factor, leading to histone deacetylase recruitment, H3.3 deposition and transcriptional repression of cellular promoters. Despite recent findings on the fundamental importance of chromatin modification in host-cell gene regulation, it remains unclear whether adenovirus type 5 (Ad5) transcription is regulated by cellular chromatin remodelling to allow efficient virus gene expression. Here, we focus on the repressive role of the Daxx/ATRX complex during Ad5 replication, which depends on intact protein–protein interaction, as negative regulation could be relieved with a Daxx mutant that is unable to interact with ATRX. To ensure efficient viral replication, Ad5 E1B-55K protein inhibits Daxx and targets ATRX for proteasomal degradation in cooperation with early region 4 open reading frame protein 6 and cellular components of a cullin-dependent E3-ubiquitin ligase. Our studies illustrate the importance and diversity of viral factors antagonizing Daxx/ATRX-mediated repression of viral gene expression and shed new light on the modulation of cellular chromatin remodelling factors by Ad5. We show for the first time that cellular Daxx/ATRX chromatin remodelling complexes play essential roles in Ad gene expression and illustrate the importance of early viral proteins to counteract cellular chromatin remodelling

ROBOTIC TECHNOLOGIES FOR MINIMIZING CREW MAINTENANCE REQUIREMENTS IN SPACE HABITATS

Gemstone Team ASTROThe International Space Station (ISS) is crewed continuously by astronauts conducting scientifc research in microgravity. However, their work is not limited to scientifc research alone; in fact, logistics, maintenance, and repair tasks on the ISS require more than 80% of available crew time, severely limiting opportunities for performing scientifc experiments and technological development. NASA is planning a new project known as Gateway (also referred to as the Lunar Orbital Platform-Gateway). This station will orbit the Moon and be uncrewed for 11 months per year. Astronauts will only be present in the outpost for a limited period of time and will not always be available for continuous repairs and maintenance, as is required for Gateway to operate. Therefore, robotic system(s) are necessary to regularly accomplish these tasks both in the absence and presence of astronauts. Throughout this project, Team ASTRO (Assessment of Space Technologies for Robotic Operations) explored the feasibility of integrating dexterous robotic systems in space habitat architectures to perform routine and contingency operational and maintenance tasks. Ultimately, this allows for astronauts, when present, to focus on exploration and scientifc discoveries. The team conducted this research through three approaches: Gateway component analog taskboard development and end e˙ector assessment, Cargo Transfer Bag (CTB) manipulation and logistics, and AprilTag situational awareness simulation development. Based on analyses and experimental results gained from this research, the team found that robotic systems are feasible alternatives for space habitat operation. Team ASTRO also determined that AprilTags can be used for optimization of the Gateway design to facilitate uncrewed operations and robotic servicing to improve crew productivity when present

Intergenerational conflicts may help explain parental absence effects on reproductive timing: a model of age at first birth in humans.

Background. Parental absences in childhood are often associated with accelerated reproductive maturity in humans. These results are counterintuitive for evolutionary social scientists because reductions in parental investment should be detrimental for offspring, but earlier reproduction is generally associated with higher fitness. In this paper we discuss a neglected hypothesis that early reproduction is often associated with parental absence because it decreases the average relatedness of a developing child to her future siblings. Family members often help each other reproduce, meaning that parents and offspring may find themselves in competition over reproductive opportunities. In these intergenerational negotiations offspring will have less incentive to help the remaining parent rear future half-siblings relative to beginning reproduction themselves. Method. We illustrate this "intergenerational conflict hypothesis" with a formal game-theoretic model. Results. We show that when resources constrain reproductive opportunities within the family, parents will generally win reproductive conflicts with their offspring, i.e., they will produce more children of their own and therefore delay existing offsprings' reproduction. This is due to the asymmetric relatedness between grandparents and grandchildren (r = .25), compared to siblings (r = 0.5), resulting in greater incentives for older siblings to help rear younger siblings than for grandparents to help rear grandchildren. However, if a parent loses or replaces their partner, the conflict between the parent and offspring becomes symmetric since half siblings are as related to one another as grandparents are to grandchildren. This means that the offspring stand to gain more from earlier reproduction when their remaining parent would produce half, rather than full, siblings. We further show that if parents senesce in a way that decreases the quality of their infant relative to their offspring's infant, the intergenerational conflict can shift to favor the younger generation

Divergent Effects of Human Cytomegalovirus and Herpes Simplex Virus-1 on Cellular Metabolism

Viruses rely on the metabolic network of the host cell to provide energy and macromolecular precursors to fuel viral replication. Here we used mass spectrometry to examine the impact of two related herpesviruses, human cytomegalovirus (HCMV) and herpes simplex virus type-1 (HSV-1), on the metabolism of fibroblast and epithelial host cells. Each virus triggered strong metabolic changes that were conserved across different host cell types. The metabolic effects of the two viruses were, however, largely distinct. HCMV but not HSV-1 increased glycolytic flux. HCMV profoundly increased TCA compound levels and flow of two carbon units required for TCA cycle turning and fatty acid synthesis. HSV-1 increased anapleurotic influx to the TCA cycle through pyruvate carboxylase, feeding pyrimidine biosynthesis. Thus, these two related herpesviruses drive diverse host cells to execute distinct, virus-specific metabolic programs. Current drugs target nucleotide metabolism for treatment of both viruses. Although our results confirm that this is a robust target for HSV-1, therapeutic interventions at other points in metabolism might prove more effective for treatment of HCMV

Extent and Causes of Chesapeake Bay Warming

Coastal environments such as the Chesapeake Bay have long been impacted by eutrophication stressors resulting from human activities, and these impacts are now being compounded by global warming trends. However, there are few studies documenting long-term estuarine temperature change and the relative contributions of rivers, the atmosphere, and the ocean. In this study, Chesapeake Bay warming, since 1985, is quantified using a combination of cruise observations and model outputs, and the relative contributions to that warming are estimated via numerical sensitivity experiments with a watershed–estuarine modeling system. Throughout the Bay’s main stem, similar warming rates are found at the surface and bottom between the late 1980s and late 2010s (0.02 +/- 0.02C/year, mean +/- 1 standard error), with elevated summer rates (0.04 +/- 0.01C/year) and lower rates of winter warming (0.01 +/- 0.01C/year). Most (~85%) of this estuarine warming is driven by atmospheric effects. The secondary influence of ocean warming increases with proximity to the Bay mouth, where it accounts for more than half of summer warming in bottom waters. Sea level rise has slightly reduced summer warming, and the influence of riverine warming has been limited to the heads of tidal tributaries. Future rates of warming in Chesapeake Bay will depend not only on global atmospheric trends, but also on regional circulation patterns in mid-Atlantic waters, which are currently warming faster than the atmosphere. Supporting model data available at: https://doi.org/10.25773/c774-a36