Causes of Higher Climate Sensitivity in CMIP6 Models

Equilibrium climate sensitivity, the global surface temperature response to CO urn:x-wiley:grl:media:grl60047:grl60047-math-0001 doubling, has been persistently uncertain. Recent consensus places it likely within 1.5–4.5 K. Global climate models (GCMs), which attempt to represent all relevant physical processes, provide the most direct means of estimating climate sensitivity via CO urn:x-wiley:grl:media:grl60047:grl60047-math-0002 quadrupling experiments. Here we show that the closely related effective climate sensitivity has increased substantially in Coupled Model Intercomparison Project phase 6 (CMIP6), with values spanning 1.8–5.6 K across 27 GCMs and exceeding 4.5 K in 10 of them. This (statistically insignificant) increase is primarily due to stronger positive cloud feedbacks from decreasing extratropical low cloud coverage and albedo. Both of these are tied to the physical representation of clouds which in CMIP6 models lead to weaker responses of extratropical low cloud cover and water content to unforced variations in surface temperature. Establishing the plausibility of these higher sensitivity models is imperative given their implied societal ramifications

A Methodology for Risk Assessment to Improve the Resilience and Sustainability of Critical Infrastructure with Case Studies from the United States Army

Reliable performance of energy and water infrastructure is central to the mission readiness of the United States Army. These systems are vulnerable to coordinated attacks from an adversary as well as disruption from natural events. The objectives of this work were to investigate Army installations in North America, identify best practices for improving the resilience and sustainability of critical energy and water infrastructure, and develop a framework and methodology for analyzing the resilience of an installation under varying outage scenarios. This work was accomplished using a multi-layered decision process to identify unique case studies from the 117 active-duty domestic Army installations. A framework for analyzing and assessing the resilience of an installation was then developed to help inform stakeholders. Metered energy and water data from buildings across Fort Benning, GA were curated to inform the modeling framework, including a discrete-event simulation of the supply and demand for energy and water on the installation using ProModel. This simulation was used to study the scale of solutions required to address outage events of varying frequency, duration, and magnitude, the combination of which is described as the severity of outages at a given site. This project helps develop a framework to inform how installations might meet Army Directive 2020-03, which states that installations must be able to sustain mission requirements for a minimum of 14 days after a disruption has occurred

Serum Müllerian inhibiting substance levels are lower in premenopausal women with breast precancer and cancer

<p>Abstract</p> <p>Background</p> <p>In preclinical studies, müllerian inhibiting substance (MIS) has a protective affect against breast cancer. Our objective was to determine whether serum MIS concentrations were associated with cancerous or precancerous lesions. Blood from 30 premenopausal women was collected and serum extracted prior to their undergoing breast biopsy to assess a suspicious lesion found on imaging or physical examination. Based on biopsy results, the serum specimens were grouped as cancer (invasive or ductal carcinoma <it>in situ</it>), precancer (atypical hyperplasia or lobular carcinoma <it>in situ</it>), or benign.</p> <p>Findings</p> <p>Serum from women with cancer and precancer (p = .0009) had lower MIS levels than serum from women with benign disease.</p> <p>Conclusion</p> <p>Our findings provide preliminary evidence for MIS being associated with current breast cancer risk, which should be validated in a larger population.</p

Control of substrate access to the active site in methane monooxygenase

Methanotrophs consume methane as their major carbon source and have an essential role in the global carbon cycle by limiting escape of this greenhouse gas to the atmosphere. These bacteria oxidize methane to methanol by soluble and particulate methane monooxygenases (MMOs). Soluble MMO contains three protein components, a 251-kilodalton hydroxylase (MMOH), a 38.6-kilodalton reductase (MMOR), and a 15.9-kilodalton regulatory protein (MMOB), required to couple electron consumption with substrate hydroxylation at the catalytic diiron centre of MMOH. Until now, the role of MMOB has remained ambiguous owing to a lack of atomic-level information about the MMOH–MMOB (hereafter termed H–B) complex. Here we remedy this deficiency by providing a crystal structure of H–B, which reveals the manner by which MMOB controls the conformation of residues in MMOH crucial for substrate access to the active site. MMOB docks at the α[subscript 2]β[subscript 2] interface of α[subscript 2]β[subscript 2]γ[subscript 2] MMOH, and triggers simultaneous conformational changes in the α-subunit that modulate oxygen and methane access as well as proton delivery to the diiron centre. Without such careful control by MMOB of these substrate routes to the diiron active site, the enzyme operates as an NADH oxidase rather than a monooxygenase. Biological catalysis involving small substrates is often accomplished in nature by large proteins and protein complexes. The structure presented in this work provides an elegant example of this principle.National Institute of General Medical Sciences (U.S.) (Grant GM 32114

The statistical neuroanatomy of frontal networks in the macaque

We were interested in gaining insight into the functional properties of frontal networks based upon their anatomical inputs. We took a neuroinformatics approach, carrying out maximum likelihood hierarchical cluster analysis on 25 frontal cortical areas based upon their anatomical connections, with 68 input areas representing exterosensory, chemosensory, motor, limbic, and other frontal inputs. The analysis revealed a set of statistically robust clusters. We used these clusters to divide the frontal areas into 5 groups, including ventral-lateral, ventral-medial, dorsal-medial, dorsal-lateral, and caudal-orbital groups. Each of these groups was defined by a unique set of inputs. This organization provides insight into the differential roles of each group of areas and suggests a gradient by which orbital and ventral-medial areas may be responsible for decision-making processes based on emotion and primary reinforcers, and lateral frontal areas are more involved in integrating affective and rational information into a common framework

Structure of the stationary phase survival protein YuiC from B.subtilis

- Background: Stationary phase survival proteins (Sps) were found in Firmicutes as having analogous domain compositions, and in some cases genome context, as the resuscitation promoting factors of Actinobacteria, but with a different putative peptidoglycan cleaving domain. - Results: The first structure of a Firmicute Sps protein YuiC from B. subtilis, is found to be a stripped down version of the cell-wall peptidoglycan hydrolase MltA. The YuiC structures are of a domain swapped dimer, although some monomer is also found in solution. The protein crystallised in the presence of pentasaccharide shows a 1,6-anhydrodisaccharide sugar product, indicating that YuiC cleaves the sugar backbone to form an anhydro product at least on lengthy incubation during crystallisation. - Conclusions: The structural simplification of MltA in Sps proteins is analogous to that of the resuscitation promoting factor domains of Actinobacteria, which are stripped down versions of lysozyme and soluble lytic transglycosylase proteins

Emergent global patterns of ecosystem structure and function from a mechanistic general ecosystem model

Anthropogenic activities are causing widespread degradation of ecosystems worldwide, threatening the ecosystem services upon which all human life depends. Improved understanding of this degradation is urgently needed to improve avoidance and mitigation measures. One tool to assist these efforts is predictive models of ecosystem structure and function that are mechanistic: based on fundamental ecological principles. Here we present the first mechanistic General Ecosystem Model (GEM) of ecosystem structure and function that is both global and applies in all terrestrial and marine environments. Functional forms and parameter values were derived from the theoretical and empirical literature where possible. Simulations of the fate of all organisms with body masses between 10 µg and 150,000 kg (a range of 14 orders of magnitude) across the globe led to emergent properties at individual (e.g., growth rate), community (e.g., biomass turnover rates), ecosystem (e.g., trophic pyramids), and macroecological scales (e.g., global patterns of trophic structure) that are in general agreement with current data and theory. These properties emerged from our encoding of the biology of, and interactions among, individual organisms without any direct constraints on the properties themselves. Our results indicate that ecologists have gathered sufficient information to begin to build realistic, global, and mechanistic models of ecosystems, capable of predicting a diverse range of ecosystem properties and their response to human pressures

An Allograft Glioma Model Reveals the Dependence of Aquaporin-4 Expression on the Brain Microenvironment

Aquaporin-4 (AQP4), the main water channel of the brain, is highly expressed in animal glioma and human glioblastoma in situ. In contrast, most cultivated glioma cell lines don’t express AQP4, and primary cell cultures of human glioblastoma lose it during the first passages. Accordingly, in C6 cells and RG2 cells, two glioma cell lines of the rat, and in SMA mouse glioma cell lines, we found no AQP4 expression. We confirmed an AQP4 loss in primary human glioblastoma cell cultures after a few passages. RG-2 glioma cells if grafted into the brain developed AQP4 expression. This led us consider the possibility of AQP4 expression depends on brain microenvironment. In previous studies, we observed that the typical morphological conformation of AQP4 as orthogonal arrays of particles (OAP) depended on the extracellular matrix component agrin. In this study, we showed for the first time implanted AQP4 negative glioma cells in animal brain or flank to express AQP4 specifically in the intracerebral gliomas but neither in the extracranial nor in the flank gliomas. AQP4 expression in intracerebral gliomas went along with an OAP loss, compared to normal brain tissue. AQP4 staining in vivo normally is polarized in the astrocytic endfoot membranes at the glia limitans superficialis and perivascularis, but in C6 and RG2 tumors the AQP4 staining is redistributed over the whole glioma cell as in human glioblastoma. In contrast, primary rat or mouse astrocytes in culture did not lose their ability to express AQP4, and they were able to form few OAPs

Crystal structures and binding dynamics of Odorant-Binding Protein 3 from two aphid species Megoura viciae and Nasonovia ribisnigri

Aphids use chemical cues to locate hosts and find mates. The vetch aphid Megoura viciae feeds exclusively on the Fabaceae, whereas the currant-lettuce aphid Nasonovia ribisnigri alternates hosts between the Grossulariaceae and Asteraceae. Both species use alarm pheromones to warn of dangers. For N. ribisnigri this pheromone is a single component (E)-β-farnesene but M. viciae uses a mixture of (E)-β-farnesene, (-)-α- pinene, β-pinene, and limonene. Odorant-binding proteins (OBP) are believed to capture and transport such semiochemicals to their receptors. Here, we report the first aphid OBP crystal structures and examine their molecular interactions with the alarm pheromone components. Our study reveals some unique structural features: 1) the lack of internal ligand binding site; 2) a striking groove in the surface of the proteins as a putative binding site; 3) the N-terminus rather than the C-terminus occupies the site closing off the conventional OBP pocket. The results from fluorescent binding assays, molecular docking and dynamics demonstrate that OBP3 from M. viciae can bind to all four alarm pheromone components and the differential ligand binding between these very similar OBP3s from the two aphid species is determined mainly by the direct π-π interactions between ligands and the aromatic residues of OBP3s in the binding pocket

The human resource for health situation in Zambia: deficit and maldistribution

<p>Abstract</p> <p>Introduction</p> <p>Current health policy directions in Zambia are formulated in the National Health Strategic Plan. The Plan focuses on national health priorities, which include the human resources (HR) crisis. In this paper we describe the way the HRH establishment is distributed in the different provinces of Zambia, with a view to assess the dimension of shortages and of imbalances in the distribution of health workers by province and by level of care.</p> <p>Population and methods</p> <p>We used secondary data from the "March 2008 payroll data base", which lists all the public servants on the payroll of the Ministry of Health and of the National Health Service facilities. We computed rates and ratios and compared them.</p> <p>Results</p> <p>The highest relative concentration of all categories of workers was observed in Northern, Eastern, Lusaka, Western and Luapula provinces (in decreasing order of number of health workers).</p> <p>The ratio of clinical officers (mid-level clinical practitioners) to general medical officer (doctors with university training) varied from 3.77 in the Lusaka to 19.33 in the Northwestern provinces. For registered nurses (3 to 4 years of mid-level training), the ratio went from 3.54 in the Western to 15.00 in Eastern provinces and for enrolled nurses (two years of basic training) from 4.91 in the Luapula to 36.18 in the Southern provinces.</p> <p>This unequal distribution was reflected in the ratio of population per cadre. The provincial distribution of personnel showed a skewed staff distribution in favour of urbanized provinces, e.g. in Lusaka's doctor: population ratio was 1: 6,247 compared to Northern Province's ratio of 1: 65,763.</p> <p>In the whole country, the data set showed only 109 staff in health posts: 1 clinical officer, 3 environmental health technologists, 2 registered nurses, 12 enrolled midwives, 32 enrolled nurses, and 59 other.</p> <p>The vacancy rates for level 3 facilities(central hospitals, national level) varied from 5% in Lusaka to 38% in Copperbelt Province; for level 2 facilities (provincial level hospitals), from 30% for Western to 70% for Copperbelt Province; for level 1 facilities (district level hospitals), from 54% for the Southern to 80% for the Western provinces; for rural health centres, vacancies varied from 15% to 63% (for Lusaka and Luapula provinces respectively); for urban health centres the observed vacancy rates varied from 13% for the Lusaka to 96% for the Western provinces. We observed significant shortages in most staff categories, except for support staff, which had a significant surplus.</p> <p>Discussion and Conclusions</p> <p>This case study documents how a peaceful, politically stable African country with a longstanding tradition of strategic management of the health sector and with a track record of innovative approaches dealt with its HRH problems, but still remains with a major absolute and relative shortage of health workers. The case of Zambia reinforces the idea that training more staff is necessary to address the human resources crisis, but it is not sufficient and has to be completed with measures to mitigate attrition and to increase productivity.</p