Paper Session III-B - Life Support Research & Development for the Department of Energy Space Exploration Initiative

Long-term, manned space missions of the future will require an approach to life support systems in which most of the waste materials must be processed and recycled and/or local resources are utilized. The requirement for a reliable life support system has been recognized as an important component of the Space Exploration Initiative, and the Department of Energy (DOE), in conjunction with the National Aeronautics and Space Agency, is organizing a program in support of the development of this type of technology. It is quite likely that bioprocesses will be important components of the integrated system, and this will be the primary area of research and development (R&D) within the DOE national laboratories. Microbial, enzymatic, and thermochemical processing of wastes will be investigated in the initial research studies. Other research areas of interest include water and air purification by plants, microbial detection systems, biophotochemical CO2 recycle, tissue cultures for food, single-cell protein, bioadsorbents for pollutant removal, and several others. The resulting innovative technology developed for space exploration could also serve as the basis for new approaches for the processing and recycle of waste materials on Earth

CMBPol Mission Concept Study: Probing Inflation with CMB Polarization

We summarize the utility of precise cosmic microwave background (CMB) polarization measurements as probes of the physics of inflation. We focus on the prospects for using CMB measurements to differentiate various inflationary mechanisms. In particular, a detection of primordial B-mode polarization would demonstrate that inflation occurred at a very high energy scale, and that the inflaton traversed a super-Planckian distance in field space. We explain how such a detection or constraint would illuminate aspects of physics at the Planck scale. Moreover, CMB measurements can constrain the scale-dependence and non-Gaussianity of the primordial fluctuations and limit the possibility of a significant isocurvature contribution. Each such limit provides crucial information on the underlying inflationary dynamics. Finally, we quantify these considerations by presenting forecasts for the sensitivities of a future satellite experiment to the inflationary parameters.Comment: 107 pages, 14 figures, 17 tables; Inflation Working Group contribution to the CMBPol Mission Concept Study; v2: typos fixed and references adde

Differentiating Prodromal Dementia with Lewy Bodies from Prodromal Alzheimer’s Disease: A Pragmatic Review for Clinicians

\ua9 The Author(s) 2024.This pragmatic review synthesises the current understanding of prodromal dementia with Lewy bodies (pDLB) and prodromal Alzheimer’s disease (pAD), including clinical presentations, neuropsychological profiles, neuropsychiatric symptoms, biomarkers, and indications for disease management. The core clinical features of dementia with Lewy bodies (DLB)—parkinsonism, complex visual hallucinations, cognitive fluctuations, and REM sleep behaviour disorder are common prodromal symptoms. Supportive clinical features of pDLB include severe neuroleptic sensitivity, as well as autonomic and neuropsychiatric symptoms. The neuropsychological profile in mild cognitive impairment attributable to Lewy body pathology (MCI-LB) tends to include impairment in visuospatial skills and executive functioning, distinguishing it from MCI due to AD, which typically presents with impairment in memory. pDLB may present with cognitive impairment, psychiatric symptoms, and/or recurrent episodes of delirium, indicating that it is not necessarily synonymous with MCI-LB. Imaging, fluid and other biomarkers may play a crucial role in differentiating pDLB from pAD. The current MCI-LB criteria recognise low dopamine transporter uptake using positron emission tomography or single photon emission computed tomography (SPECT), loss of REM atonia on polysomnography, and sympathetic cardiac denervation using meta-iodobenzylguanidine SPECT as indicative biomarkers with slowing of dominant frequency on EEG among others as supportive biomarkers. This review also highlights the emergence of fluid and skin-based biomarkers. There is little research evidence for the treatment of pDLB, but pharmacological and non-pharmacological treatments for DLB may be discussed with patients. Non-pharmacological interventions such as diet, exercise, and cognitive stimulation may provide benefit, while evaluation and management of contributing factors like medications and sleep disturbances are vital. There is a need to expand research across diverse patient populations to address existing disparities in clinical trial participation. In conclusion, an early and accurate diagnosis of pDLB or pAD presents an opportunity for tailored interventions, improved healthcare outcomes, and enhanced quality of life for patients and care partners

Nontemplated Nucleotide Additions Distinguish the Small RNA Composition in Cells from Exosomes

Functional biomolecules, including small noncoding RNAs (ncRNAs), are released and transmitted between mammalian cells via extracellular vesicles (EVs), including endosome-derived exosomes. The small RNA composition in cells differs from exosomes, but underlying mechanisms have not been established. We generated small RNA profiles by RNA sequencing (RNA-seq) from a panel of human B cells and their secreted exosomes. A comprehensive bioinformatics and statistical analysis revealed nonrandomly distributed subsets of microRNA (miRNA) species between B cells and exosomes. Unexpectedly, 3′ end adenylated miRNAs are relatively enriched in cells, whereas 3′ end uridylated isoforms appear overrepresented in exosomes, as validated in naturally occurring EVs isolated from human urine samples. Collectively, our findings suggest that posttranscriptional modifications, notably 3′ end adenylation and uridylation, exert opposing effects that may contribute, at least in part, to direct ncRNA sorting into EVs.T.W. is supported by VIDI 91711366. D.M.P. is supported by personal Dutch Cancer Society research award (KWF-5510). This work was funded by AICR grant 11-0157 and NWO-VENI 91696087 awarded to D.M.P

Observing the Evolution of the Universe

How did the universe evolve? The fine angular scale (l>1000) temperature and polarization anisotropies in the CMB are a Rosetta stone for understanding the evolution of the universe. Through detailed measurements one may address everything from the physics of the birth of the universe to the history of star formation and the process by which galaxies formed. One may in addition track the evolution of the dark energy and discover the net neutrino mass. We are at the dawn of a new era in which hundreds of square degrees of sky can be mapped with arcminute resolution and sensitivities measured in microKelvin. Acquiring these data requires the use of special purpose telescopes such as the Atacama Cosmology Telescope (ACT), located in Chile, and the South Pole Telescope (SPT). These new telescopes are outfitted with a new generation of custom mm-wave kilo-pixel arrays. Additional instruments are in the planning stages.Comment: Science White Paper submitted to the US Astro2010 Decadal Survey. Full list of 177 author available at http://cmbpol.uchicago.ed

Metabolic Syndrome Mediates ROS-miR-193b-NFYA–Dependent Downregulation of Soluble Guanylate Cyclase and Contributes to Exercise-Induced Pulmonary Hypertension in Heart Failure With Preserved Ejection Fraction

BackgroundMany patients with heart failure with preserved ejection fraction have metabolic syndrome and develop exercise-induced pulmonary hypertension (EIPH). Increases in pulmonary vascular resistance in patients with heart failure with preserved ejection fraction portend a poor prognosis; this phenotype is referred to as combined precapillary and postcapillary pulmonary hypertension (CpcPH). Therapeutic trials for EIPH and CpcPH have been disappointing, suggesting the need for strategies that target upstream mechanisms of disease. This work reports novel rat EIPH models and mechanisms of pulmonary vascular dysfunction centered around the transcriptional repression of the soluble guanylate cyclase (sGC) enzyme in pulmonary artery (PA) smooth muscle cells.MethodsWe used obese ZSF-1 leptin-receptor knockout rats (heart failure with preserved ejection fraction model), obese ZSF-1 rats treated with SU5416 to stimulate resting pulmonary hypertension (obese+sugen, CpcPH model), and lean ZSF-1 rats (controls). Right and left ventricular hemodynamics were evaluated using implanted catheters during treadmill exercise. PA function was evaluated with magnetic resonance imaging and myography. Overexpression of nuclear factor Y α subunit (NFYA), a transcriptional enhancer of sGC β1 subunit (sGCβ1), was performed by PA delivery of adeno-associated virus 6. Treatment groups received the SGLT2 inhibitor empagliflozin in drinking water. PA smooth muscle cells from rats and humans were cultured with palmitic acid, glucose, and insulin to induce metabolic stress.ResultsObese rats showed normal resting right ventricular systolic pressures, which significantly increased during exercise, modeling EIPH. Obese+sugen rats showed anatomic PA remodeling and developed elevated right ventricular systolic pressure at rest, which was exacerbated with exercise, modeling CpcPH. Myography and magnetic resonance imaging during dobutamine challenge revealed PA functional impairment of both obese groups. PAs of obese rats produced reactive oxygen species and decreased sGCβ1 expression. Mechanistically, cultured PA smooth muscle cells from obese rats and humans with diabetes or treated with palmitic acid, glucose, and insulin showed increased mitochondrial reactive oxygen species, which enhanced miR-193b-dependent RNA degradation of nuclear factor Y α subunit (NFYA), resulting in decreased sGCβ1-cGMP signaling. Forced NYFA expression by adeno-associated virus 6 delivery increased sGCβ1 levels and improved exercise pulmonary hypertension in obese+sugen rats. Treatment of obese+sugen rats with empagliflozin improved metabolic syndrome, reduced mitochondrial reactive oxygen species and miR-193b levels, restored NFYA/sGC activity, and prevented EIPH.ConclusionsIn heart failure with preserved ejection fraction and CpcPH models, metabolic syndrome contributes to pulmonary vascular dysfunction and EIPH through enhanced reactive oxygen species and miR-193b expression, which downregulates NFYA-dependent sGCβ1 expression. Adeno-associated virus-mediated NFYA overexpression and SGLT2 inhibition restore NFYA-sGCβ1-cGMP signaling and ameliorate EIPH

Imagining renewable energy: towards a Social Energy Systems approach to community renewable energy projects in the Global South

Rural community energy projects in the Global South have too frequently been framed within a top-down technologically-driven framework that limits their ability to provide sustainable solutions to energy poverty and improving livelihoods. This framing is linked to how energy interventions are being imagined and constructed by key actors in the sector, via particular sociotechnical imaginaries through which a set of increasingly universalised energy futures for rural communities is prescribed. Projects are too frequently reverse-engineered through the lens of particular combinations of technologies, financial models and delivery mechanisms, rather than by attending to the particular energy needs/aspirations of individual communities. Assumptions over the association between energy access and livelihood enhancement have also reinforced a technocratic determination of appropriate system scale and a search for universalised ‘scaleable’ delivery models. There is, however, no necessary causation between scaleability and outcomes – appropriate implementation scales are not purely determined by technical or financial considerations, rather it is the social scale via which optimum forms of local participation and ownership can be achieved. To operationalise this concern for social space we propose a Social Energy Systems (SES) approach that is advanced via exploration of the interactions between three distinct but mutually edifying variants of energy literacy – energy systems literacy, project community literacy and political literacy

The evolution of gene expression and the transcriptome–phenotype relationship

Changes in gene expression underlie the adaptive evolution in many complex phenotypes, and the recent increase in the availability of multi-species comparative transcriptome data has made it possible to scan whole transcriptomes for loci that have experienced adaptive changes in expression. However, despite the increase in data availability, current models of gene expression evolution often do not account for the complexities and inherent noise associated with transcriptome data. Additionally, in contrast to current models of gene sequence evolution, models of transcriptome evolution often lack the sophistication to effectively determine whether transcriptional differences between species or within a clade are the result of neutral or adaptive processes. In this review, we discuss the tools, methods and models that define our current understanding of the relationship between gene expression and complex phenotype evolution. Our goal is to summarize what we know about the evolution of global gene expression patterns underlying complex traits, as well to identify some of the questions that remain to be answered