bluuebunny/crossref_metadata_2025 huggingface dataset:
Lactate Metabolism and Signaling in Tuberculosis and Cancer: A Comparative Review
Authors: Kiran Dilara , Basaraba Randall J.
Published: February 2021

Infection with Mycobacterium tuberculosis (Mtb) leading to tuberculosis (TB) disease continues to be a major global health challenge. Critical barriers, including but not limited to the development of multi-drug resistance, lack of diagnostic assays that detect patients with latent TB, an effective vaccine that prevents Mtb infection, and infectious and non-infectious comorbidities that complicate active TB, continue to hinder progress toward a TB cure. To complement the ongoing development of new antimicrobial drugs, investigators in the field are exploring the value of host-directed therapies (HDTs). This therapeutic strategy targets the host, rather than Mtb, and is intended to augment host responses to infection such that the host is better equipped to prevent or clear infection and resolve chronic inflammation. Metabolic pathways of immune cells have been identified as promising HDT targets as more metabolites and metabolic pathways have shown to play a role in TB pathogenesis and disease progression. Specifically, this review highlights the potential role of lactate as both an immunomodulatory metabolite and a potentially important signaling molecule during the host response to Mtb infection. While long thought to be an inert end product of primarily glucose metabolism, the cancer research field has discovered the importance of lactate in carcinogenesis and resistance to chemotherapeutic drug treatment. Herein, we discuss similarities between the TB granuloma and tumor microenvironments in the context of lactate metabolism and identify key metabolic and signaling pathways that have been shown to play a role in tumor progression but have yet to be explored within the context of TB. Ultimately, lactate metabolism and signaling could be viable HDT targets for TB; however, critical additional research is needed to better understand the role of lactate at the host-pathogen interface during Mtb infection before adopting this HDT strategy.
Molecular Epidemiology and Clone Transmission of Carbapenem-Resistant Acinetobacter baumannii in ICU Rooms
Authors: Zhang Xiufeng , Li Fangping , Awan Furqan , Jiang Hongye , Zeng Zhenling , Lv Weibiao
Published: February 2021

Carbapenem-resistant Acinetobacter baumannii (CRAB) is a major cause of nosocomial infections and hospital outbreaks worldwide, remaining a critical clinical concern. Here we characterized and investigated the phylogenetic relationships of 105 CRAB isolates from an intensive care unit from one hospital in China collected over six years. All strains carried blaOXA-23, blaOXA-66 genes for carbapenem resistance, also had high resistance gene, virulence factor, and insertion sequence burdens. Whole-genome sequencing revealed all strains belonged to ST2, the global clone CC2. The phylogenetic analysis based on the core genome showed all isolates were dominated by a single lineage of three clusters and eight different clones. Two clones were popular during the collection time. Using chi-square test to identify the epidemiologically meaningful groupings, we found the significant difference in community structure only existed in strains from separation time. The haplotype and median-joining network analysis revealed genetic differences appeared among clusters and changes occurred overtime in the dominating cluster. Our results highlighted substantial multidrug-resistant CRAB burden in the hospital ICU environment demonstrating potential clone outbreak in the hospital.
Biochemical and Virulence Characterization of Vibrio vulnificus Isolates From Clinical and Environmental Sources
Authors: Lydon Keri A. , Kinsey Thomas , Le Chinh , Gulig Paul A. , Jones Jessica L.
Published: February 2021

Vibrio vulnificus is a deadly human pathogen for which infections occur via seafood consumption (foodborne) or direct contact with wounds. Virulence is not fully characterized for this organism; however, there is evidence of biochemical and genotypic correlations with virulence potential. In this study, biochemical profiles and virulence genotype, based on 16S rRNA gene (rrn) and virulence correlated gene (vcg) types, were determined for 30 clinical and 39 oyster isolates. Oyster isolates were more biochemically diverse than the clinical isolates, with four of the 20 tests producing variable (defined as 20–80% of isolates) results. Whereas, for clinical isolates only mannitol fermentation, which has previously been associated with virulence potential, varied among the isolates. Nearly half (43%) of clinical isolates were the more virulent genotype (rrnB/vcgC); this trend was consistent when only looking at clinical isolates from blood. The majority (64%) of oyster isolates were the less virulent genotype (rrnA or AB/vcgE). These data were used to select a sub-set of 27 isolates for virulence testing with a subcutaneously inoculated, iron-dextran treated mouse model. Based on the mouse model data, 11 isolates were non-lethal, whereas 16 isolates were lethal, indicating a potential for human infection. Within the non-lethal group there were eight oyster and three clinical isolates. Six of the non-lethal isolates were the less virulent genotype (rrnA/vcgE or rrnAB/vcgE) and two were rrnB/vcgC with the remaining two of mixed genotype (rrnAB/vcgC and rrnB/vcgE). Of the lethal isolates, five were oysters and 11 were clinical. Eight of the lethal isolates were the less virulent genotype and seven the more virulent genotype, with the remaining isolate a mixed genotype (rrnA/vcgC). A discordance between virulence genotype and individual mouse virulence parameters (liver infection, skin infection, skin lesion score, and body temperature) was observed; the variable most strongly associated with mouse virulence parameters was season (warm or cold conditions at time of strain isolation), with more virulent strains isolated from cold conditions. These results indicate that biochemical profiles and genotype are not significantly associated with virulence potential, as determined by a mouse model. However, a relationship with virulence potential and seasonality was observed.
The Psychophysiological Experience of Solving Moral Dilemmas Together: An Interdisciplinary Comparison Between Participants With and Without Depression
Authors: Koskinen Emmi , Tuhkanen Samuel , Järvensivu Milla , Savander Enikö , Valkeapää Taina , Valkia Kaisa , Weiste Elina , Stevanovic Melisa
Published: February 2021

Dyads with a depressed and a non-depressed participant (N = 15) and two non-depressed participants (N = 15) discussed a moral dilemma, during which the participants’ gaze direction and skin conductance (SC) were measured. Partner gazing occurred most frequently when a speaker took a strong stance toward saving a person in the dilemma, depressed participants however looking at their co-participants less often than non-depressed participants. The participants’ SC response rates were higher during responsive utterances expressing disagreement (vs. agreement) with co-participant ideas or suggesting that a person be sacrificed (vs. saved). We argue that a better understanding of the affective corollaries of human social interaction necessitates a balanced consideration of both contents of talk and behavioral patterns.
Multiscale Dynamics of Blood Pressure Fluctuation Is Associated With White Matter Lesion Burden in Older Adults With and Without Hypertension: Observations From a Pilot Study
Authors: Jiang Xin , Guo Yi , Zhao Yue , Gao Xia , Peng Dan , Zhang Hui , Deng Wuhong , Fu Wen , Qin Na , Chang Ruizhen , Manor Brad , Lipsitz Lewis A. , Zhou Junhong
Published: February 2021

Background: White matter lesions (WMLs) are highly prevalent in older adults, and hypertension is one of the main contributors to WMLs. The blood pressure (BP) is regulated by complex underlying mechanisms over multiple time scales, thus the continuous beat-to-beat BP fluctuation is complex. The association between WMLs and hypertension may be manifested as diminished complexity of BP fluctuations. The aim of this pilot study is to explore the relationships between hypertension, BP complexity, and WMLs in older adults.

Method: Fifty-three older adults with clinically diagnosed hypertension and 47 age-matched older adults without hypertension completed one MRI scan and one BP recording of 10–15 min when sitting quietly. Their cerebral WMLs were assessed by two neurologists using the Fazekas scale based on brain structural MRI of each of their own. Greater score reflected higher WML grade. The complexity of continuous systolic (SBP) and diastolic (DBP) BP series was quantified using multiscale entropy (MSE). Lower MSE reflected lower complexity.

Results: Compared to the non-hypertensive group, hypertensives had significantly greater Fazekas scores (F > 5.3, p < 0.02) and lower SBP and DBP complexity (F > 8.6, p < 0.004). Both within each group (β < −0.42, p < 0.01) and across groups (β < −0.47, p < 0.003), those with lower BP complexity had higher Fazekas score. Moreover, complexity of both SBP and DBP mediated the influence of hypertension on WMLs (indirect effects > 0.25, 95% confidence intervals = 0.06 – 0.50).

Conclusion: These results suggest that diminished BP complexity is associated with WMLs and may mediate the influence of hypertension on WMLs. Future longitudinal studies are needed to examine the causal relationship between BP complexity and WMLs.
The Role of Crystal Accumulation and Cumulate Remobilization in the Formation of Large Zoned Ignimbrites: Insights From the Aso-4 Caldera-forming Eruption, Kyushu, Japan
Authors: Keller Franziska , Bachmann Olivier , Geshi Nobuo , Miyakawa Ayumu
Published: February 2021

The Aso-4 caldera-forming event (86.4 ± 1.1 ka, VEI-8) is the second largest volcanic eruption Earth experienced in the past 100 ka. The ignimbrite sheets produced during this event are some of the first ever described compositionally zoned pyroclastic flow deposits exhibiting clear compositional, mineralogical and thermal gradients with stratigraphic position. Large quantities of the deposits are composed of crystal-poor, highly evolved juvenile pumices, while late-erupted pyroclastic flows are in many cases dominated by crystal-rich and less silicic scoria. These petrological gradients in the Aso-4 deposits have been linked to extensive magma mixing of two compositionally distinct magmas in a complex upper crustal reservoir. However, new studies on several other zoned ignimbrites suggest that magma mixing alone is not sufficient to fully explain such strong compositional gradients in the deposits. These gradients are expected to be dominantly caused by the recharge-induced reactivation of extracted melt caps and their complementary cumulate in the upper crust. Here, we investigate bulk rock and matrix glass data with detailed analyses of mineral chemistry in order to re-evaluate the Aso-4 deposits in light of these latest developments. Reverse chemical zoning in phenocrysts, Sr enrichment in euhedral rims of plagioclase and the presence of mafic minerals (clinopyroxene, olivine) indicate recharge of hot, mafic magmas shortly prior to eruption, inducing a mixing signature. However, the marked enrichment in some elements in bulk-rock analyses and the presence of highly evolved minerals (some in the form of glomerocrysts) in the late-erupted, crystal-rich units, provide clear evidence for crystal accumulation in these scoria. Mass balance modeling of P2O5, Sr and SiO2 supports the extraction of melt-rich lenses within an upper crustal mush zone, leaving a partly cumulative evolved crystal residue. We therefore propose an origin of the compositionally zoned Aso-4 ignimbrite largely by erupting a heterogeneous upper crustal reservoir, consisting of crystal-poor rhyodacitic melt caps within its associated cumulate mush. This complex reservoir was reactivated by mafic recharge shortly prior to eruption, imparting an additional mixing signature to the deposits.
Stable Strontium Isotopic Compositions of River Water, Groundwater and Sediments From the Ganges–Brahmaputra–Meghna River System in Bangladesh
Authors: Yoshimura Toshihiro , Wakaki Shigeyuki , Kawahata Hodaka , Hossain H. M. Zakir , Manaka Takuya , Suzuki Atsushi , Ishikawa Tsuyoshi , Ohkouchi Naohiko
Published: February 2021

The Sr isotopic composition of rivers and groundwaters in the Bengal Plain is a major contributor to the global oceanic Sr inventory. The stable strontium isotope ratios (δ88Sr) provide a new tool to identify chemical weathering reactions in terrestrial water. In this study, we investigated the spatiotemporal variations of δ88Sr in samples of river water, bedload sediment, and groundwater collected from the Ganges–Brahmaputra–Meghna drainage basin in Bangladesh, which is known to strongly influence the 87Sr/86Sr ratio in seawater. The average δ88Sr values of waters of the Ganges, Brahmaputra, and Meghna rivers were 0.269, 0.316, and 0.278‰, respectively. Our data showed little difference between seasons of high and low discharge. The δ88Sr values measured in sequential leaching fractions of sediments varied from –0.258 to 0.516‰ and were highest in the silicate fraction, followed in turn by the carbonate fraction and the exchangeable fraction. Both 87Sr/86Sr and δ88Sr of these waters are primarily controlled by the inputs of Sr in weathering products from the Bengal Plain and Sr from the Himalayan rivers (Ganges and Brahmaputra). Values of δ88Sr and Sr/Ca were higher in the Brahmaputra River than in the Ganges River, a difference we attribute to greater input from silicate weathering. The variations of δ88Sr and 87Sr/86Sr were greater in groundwater than in river waters. Mineral sorting effects and dissolution kinetics can account for the large scatter in 87Sr/86Sr and δ88Sr values. The depth profile of δ88Sr showed wide variation at shallow depths and convergence to a narrow range of about 0.31‰ at depths greater than 70 m, which reflects more complete equilibration of chemical interactions between groundwater and ambient sediments owing to the longer residence time of deeper groundwater. We found that δ88Sr values in the groundwater of Bangladesh were almost identical to those of river water from the lower Meghna River downstream of its confluence with the Ganges–Brahmaputra river system, thus confirming that the δ88Sr composition of the groundwater discharge to the Bay of Bengal is very similar to that of the river discharge.
The Early Upper Paleolithic Site Crvenka-At, Serbia–The First Aurignacian Lowland Occupation Site in the Southern Carpathian Basin
Authors: Nett Janina J. , Chu Wei , Fischer Peter , Hambach Ulrich , Klasen Nicole , Zeeden Christian , Obreht Igor , Obrocki Lea , Pötter Stephan , Gavrilov Milivoj B. , Vött Andreas , Mihailović Dušan , Marković Slobodan B. , Lehmkuhl Frank
Published: February 2021

The Carpathian Basin is a key region for understanding modern human expansion into western Eurasia during the Late Pleistocene because of numerous early hominid fossil find spots. However, the corresponding archeological record remains less understood due to a paucity of well dated, contextualized sites. To help rectify this, we excavated and sampled Crvenka-At (Serbia), one of the largest Upper Paleolithic sites in the region to obtain radiometric ages for the archeological artifacts and evaluate their depositional context and subsequent site formation processes. Our results confirm that this locality represents a multiple-occupation Aurignacian site that dates to 36.4 ± 2.8 ka based on modeling of luminescence ages. Electrical resistivity tomography measurements indicate that the site formed on a sandy-gravelly fill terrace covered by overbank deposits. Complex grain size distributions further suggest site formation in contrasting depositional environments typically occurring alongside fluvial channels, at lakeshores, in alluvial fan or delta settings. The site is thus the closest (ca. 50 km) known Aurignacian site to the earliest undisputed modern human remains in Europe at the Peştera cu oase and some intervals of the occupation may therefore have been contemporaneous with them. This suggests that modern humans, during their initial settlement of Europe, exploited a wider range of topographic and ecological settings than previously posited. Our findings indicate that lowland areas of the Carpathian Basin are an important part of understanding the early settlement patterns of modern humans in Europe.
QQuake, a QGIS Plugin for Loading Seismological Data From Web Services
Authors: Locati Mario , Vallone Roberto , Ghetta Matteo , Dawson Nyall
Published: February 2021

An increasing number of web services providing convenient access to seismological data have become available in recent years. A huge effort at multiple levels was required to achieve this goal and the seismological community was engaged in the standardization of both data formats and web services. Although access to seismological data is much easier than in the past, users encounter problems because of the large number of web services, and due to the complexity of the discipline-specific data encodings. In addition, instead of adopting cross-disciplinary standards such as those by the Open Geospatial Consortium (OGC), most seismological web services created their own standards, primarily those by the International Federation of Digital Seismograph Networks (FDSN). This article introduces “QQuake,” a plugin for QGIS—the Open Source Geographic Information System—that aims at making access to seismological data easier. The plugin is based on an Open Source code available on GitHub, and it is designed in a modular and customizable way, allowing users to easily include new web services.
Upstream Regulators of Fibroblast Growth Factor 23
Authors: Ratsma Danielle M. A. , Zillikens M. Carola , van der Eerden Bram C. J.
Published: February 2021

Fibroblast growth factor 23 (FGF23) has been described as an important regulator of mineral homeostasis, but has lately also been linked to iron deficiency, inflammation, and erythropoiesis. FGF23 is essential for the maintenance of phosphate homeostasis in the body and activating mutations in the gene itself or inactivating mutations in its upstream regulators can result in severe chronic hypophosphatemia, where an unbalanced mineral homeostasis often leads to rickets in children and osteomalacia in adults. FGF23 can be regulated by changes in transcriptional activity or by changes at the post-translational level. The balance between O-glycosylation and phosphorylation is an important determinant of how much active intact or inactive cleaved FGF23 will be released in the circulation. In the past years, it has become evident that iron deficiency and inflammation regulate FGF23 in a way that is not associated with its classical role in mineral metabolism. These conditions will not only result in an upregulation of FGF23 transcription, but also in increased cleavage, leaving the levels of active intact FGF23 unchanged. The exact mechanisms behind and function of this process are still unclear. However, a deeper understanding of FGF23 regulation in both the classical and non-classical way is important to develop better treatment options for diseases associated with disturbed FGF23 biology. In this review, we describe how the currently known upstream regulators of FGF23 change FGF23 transcription and affect its post-translational modifications at the molecular level.
Stem Cell-Based Clinical Trials for Diabetes Mellitus
Authors: de Klerk Eleonora , Hebrok Matthias
Published: February 2021

Since its introduction more than twenty years ago, intraportal allogeneic cadaveric islet transplantation has been shown to be a promising therapy for patients with Type I Diabetes (T1D). Despite its positive outcome, the impact of islet transplantation has been limited due to a number of confounding issues, including the limited availability of cadaveric islets, the typically lifelong dependence of immunosuppressive drugs, and the lack of coverage of transplant costs by health insurance companies in some countries. Despite improvements in the immunosuppressive regimen, the number of required islets remains high, with two or more donors per patient often needed. Insulin independence is typically achieved upon islet transplantation, but on average just 25% of patients do not require exogenous insulin injections five years after. For these reasons, implementation of islet transplantation has been restricted almost exclusively to patients with brittle T1D who cannot avoid hypoglycemic events despite optimized insulin therapy. To improve C-peptide levels in patients with both T1 and T2 Diabetes, numerous clinical trials have explored the efficacy of mesenchymal stem cells (MSCs), both as supporting cells to protect existing β cells, and as source for newly generated β cells. Transplantation of MSCs is found to be effective for T2D patients, but its efficacy in T1D is controversial, as the ability of MSCs to differentiate into functional β cells in vitro is poor, and transdifferentiation in vivo does not seem to occur. Instead, to address limitations related to supply, human embryonic stem cell (hESC)-derived β cells are being explored as surrogates for cadaveric islets. Transplantation of allogeneic hESC-derived insulin-producing organoids has recently entered Phase I and Phase II clinical trials. Stem cell replacement therapies overcome the barrier of finite availability, but they still face immune rejection. Immune protective strategies, including coupling hESC-derived insulin-producing organoids with macroencapsulation devices and microencapsulation technologies, are being tested to balance the necessity of immune protection with the need for vascularization. Here, we compare the diverse human stem cell approaches and outcomes of recently completed and ongoing clinical trials, and discuss innovative strategies developed to overcome the most significant challenges remaining for transplanting stem cell-derived β cells.
A Real-Time Electricity Price Decision Model for Demand Side Management in Wind Power Heating Mode
Authors: Li Qiang , Li Jian , Huang Zhengyong , Fan Fulin , Teng Weijun
Published: February 2021

The problem of wind power curtailment (WPC) during winter heating periods in China’s “Three-North regions” is becoming worse. Wind power heating, though being an effective way to increase wind power consumptions, is constrained by high electric heating costs under a peak-to-valley electricity price pattern. This study develops a real-time price (RTP) decision model which adjusts the time-varying RTPs within an acceptable range of heating users based on the WPC distribution over a particular dispatch day. The lower RTPs accompanying the higher WPC can guide the electric heating user side equipped with regenerative electric boilers (REBs) to actively increase REB imports to absorb additional wind generation. Then, the demand side response using REBs under the RTP scheme is optimized to minimize the total heating cost met by electric heating users while assisting in the large-scale wind generation accommodation. The total heating costs and WPC reductions under different heating scenarios are compared and discussed alongside the effectiveness of the RTP-based demand side management in terms of reducing the WPC and heating costs and increasing the feasibility of wind power heating during winter heating periods.
Coffee and Potato Agroecosystems: Social Construction of Spaces as a Concept to Analyse Nature's Contributions to People
Authors: Bravo-Monroy Liliana
Published: February 2021

Achieving goals for conservation and sustainability using nature, decision-making, and policy planning requires accurate modes of description to understand the relationship between society and the environment. Despite most planning strategies being constrained by policy objectives, planning is expected to be more participatory and inclusive of the plurality of values and all types of socio-spatial relationships. Based on Lefebvre's social theory, the objectives of this work are to propose a triad of spaces as a helpful framework to analyse nature's contributions to people (NCP), describe different spaces socially constructed by coffee and potato farmer communities in Colombia, and explore the implications for various kinds of decision-making. Using qualitative research methods, this manuscript describes three spaces:lived spacesas intangible spaces based on local, religious, and ceremonial values of NCP;perceived spacesinclude farmer spatial organization according to the ties of kinship and the downward course of streams, the incidence of negative NCP, such as plant diseases, and types of management crops; andconceived spacesas the overlapping of different spatial views of territorial planning. Given that NCP has great potential to integrate diversity of values about nature and cultural contexts into decision-making, the triad of social spaces offers a spatial dimension to the analyses of NCP. Lived spaces make non-material NCP and non-instrumental values more visible. Perceived spaces highlight material NCP and regulating NCP with the view that maintenance of NCP in the future is essential for relational and instrumental values, e.g., how material NCP and regulating NCP of landscapes are perceived and by whom. Conceived spaces emphasize the predominance of the intrinsic biophysical values of NCP. Thus, the triad of social spaces as a conceptual framework can be useful in the operationalization of NCP in environmental management, the governance of schemes, and the implementation of land-use plans at the local scale. By thinking of these spaces relationally, such insight can inform and enhance decisions and policymaking about the value of places toward the priorities of meeting management. The results of the study emphasize the important policy implications of recognizinglivedandperceivedspaces in decision-making and highlight the role of NCP in facilitating the communication of these spaces to support spatial management of land use.
Next-Generation Camera Trapping: Systematic Review of Historic Trends Suggests Keys to Expanded Research Applications in Ecology and Conservation
Authors: Delisle Zackary J. , Flaherty Elizabeth A. , Nobbe Mackenzie R. , Wzientek Cole M. , Swihart Robert K.
Published: February 2021

Camera trapping is an effective non-invasive method for collecting data on wildlife species to address questions of ecological and conservation interest. We reviewed 2,167 camera trap (CT) articles from 1994 to 2020. Through the lens of technological diffusion, we assessed trends in: (1) CT adoption measured by published research output, (2) topic, taxonomic, and geographic diversification and composition of CT applications, and (3) sampling effort, spatial extent, and temporal duration of CT studies. Annual publications of CT articles have grown 81-fold since 1994, increasing at a rate of 1.26 (SE = 0.068) per year since 2005, but with decelerating growth since 2017. Topic, taxonomic, and geographic richness of CT studies increased to encompass 100% of topics, 59.4% of ecoregions, and 6.4% of terrestrial vertebrates. However, declines in per article rates of accretion and plateaus in Shannon'sHfor topics and major taxa studied suggest upper limits to further diversification of CT research as currently practiced. Notable compositional changes of topics included a decrease in capture-recapture, recent decrease in spatial-capture-recapture, and increases in occupancy, interspecific interactions, and automated image classification. Mammals were the dominant taxon studied; within mammalian orders carnivores exhibited a unimodal peak whereas primates, rodents and lagomorphs steadily increased. Among biogeographic realms we observed decreases in Oceania and Nearctic, increases in Afrotropic and Palearctic, and unimodal peaks for Indomalayan and Neotropic. Camera days, temporal extent, and area sampled increased, with much greater rates for the 0.90 quantile of CT studies compared to the median. Next-generation CT studies are poised to expand knowledge valuable to wildlife ecology and conservation by posing previously infeasible questions at unprecedented spatiotemporal scales, on a greater array of species, and in a wider variety of environments. Converting potential into broad-based application will require transferable models of automated image classification, and data sharing among users across multiple platforms in a coordinated manner. Further taxonomic diversification likely will require technological modifications that permit more efficient sampling of smaller species and adoption of recent improvements in modeling of unmarked populations. Environmental diversification can benefit from engineering solutions that expand ease of CT sampling in traditionally challenging sites.
Testing Equid Body Mass Estimate Equations on Modern Zebras—With Implications to Understanding the Relationship of Body Size, Diet, and Habitats of Equus in the Pleistocene of Europe
Authors: Saarinen Juha , Cirilli Omar , Strani Flavia , Meshida Keiko , Bernor Raymond L.
Published: February 2021

The monodactyl horses of the genusEquusoriginated in North America during the Pliocene, and from the beginning of the Pleistocene, they have been an essential part of the large ungulate communities of Europe, North America and Africa. Understanding how body size ofEquusspecies evolved and varied in relation to changes in environments and diet thus forms an important part of understanding the dynamics of ungulate body size variation in relation to Pleistocene paleoenvironmental changes. Here we test previously published body mass estimation equations for the family Equidae by investigating how accurately different skeletal and dental measurements estimate the mean body mass (and body mass range) reported for extant Grevy's zebra (Equus grevyi) and Burchell's zebra (Equus quagga). Based on these tests and information on how frequently skeletal elements occur in the fossil record, we construct a hierarchy of best practices for the selection of body mass estimation equations inEquus. As a case study, we explore body size variation in Pleistocene EuropeanEquuspaleopopulations in relation to diet and vegetation structure in their paleoenvironments. We show a relationship between diet and body size inEquus: very large-sized species tend to have more browse-dominated diets than small and medium-sized species, and paleovegetation proxies indicate on average more open and grass-rich paleoenvironments for small-sized, grazing species ofEquus. When more than one species ofEquusco-occur sympatrically, the larger species tend to be less abundant and have more browse-dominated diets than the smaller species. We suggest that body size variation in PleistoceneEquuswas driven by a combined effect of resource quality and availability, partitioning of habitats and resources between species, and the effect of environmental openness and group size on the body size of individuals.
Conservation Across Aquatic-Terrestrial Boundaries: Linking Continental-Scale Water Quality to Emergent Aquatic Insects and Declining Aerial Insectivorous Birds
Authors: Manning David W. P. , Sullivan S. Mažeika P.
Published: February 2021

Larval aquatic insects are used to assess water quality, but less attention is paid to their adult, terrestrial life stage, which is an important food resource for declining aerial insectivorous birds. We used open-access water-quality, aquatic-invertebrate, and bird-survey data to study how impaired water quality can emanate from streams and lakes through changes in aquatic insect communities across the contiguous United States. Emergent insect relative abundance was highest across the West, in northern New England, and the Carolinas in streams, and highest near the Great Lakes, parts of the Southwest, and northern New England for lakes. Emergent insects declined with sedimentation, roads, and elevated ammonium concentrations in streams, but not lakes. The odds that a given taxon would be non-emergent increased by up to 2.0× as a function of pollution tolerance, underscoring the sensitivity of emergent aquatic insects to water-quality impairment. However, relationships between bird populations and emergent insects were generally weak for both streams and lakes. For streams, we observed the strongest positive relationships for a mixture of upland and riparian aerial insectivorous birds such as Western Wood-Pewee, Olive-sided Flycatcher, and Acadian Flycatcher and the strongest negative association for Purple Martin. Different avian insectivores responded to emergent insect abundances in lakes (e.g., Barn Swallow, Chimney Swift, Eastern Wood-Pewee, Common Nighthawk). In both streams and lakes, we observed stronger, but opposing, relationships between several aerial insectivores and the relative abundance of sensitive insect orders (E)phemeroptera, (P)lecoptera, and (T)richoptera (positive), and pollution tolerant individuals (negative). Overall, our findings indicate that emergent insects are negatively correlated with pollution tolerance, suggesting a large-scale loss of this nutritional subsidy to terrestrial environments from impaired aquatic ecosystems. While some bird populations tracked scarcities of emergent aquatic insects, especially EPT taxa, responses varied among species, suggesting that unique habitat and foraging behaviors likely complicated these relationships. Strengthening spatial and temporal concordance between emergent-insect and bird-survey data will improve our ability to interpret species-level responses over time. Thus, our analysis highlights the need for developing conservation and biomonitoring strategies that consider the cross-ecosystem effects of water quality declines for threatened insectivorous avifauna and other terrestrial wildlife.
Short-Term Increase in Abundance of Foliage-Gleaning Insectivorous Birds Following Experimental Ice Storms in a Northern Hardwood Forest
Authors: Leuenberger Wendy , Cohen Jonathan B. , Rustad Lindsey , Wallin Kimberly F. , Parry Dylan
Published: February 2021

Large-scale disturbances such as ice storms may increase in frequency and intensity as climate changes. While disturbances are a natural component of forest ecosystems, climatically driven alteration to historical patterns may impart fundamental change to ecosystem function. At Hubbard Brook Experimental Forest, NH, experimental ice storms of varying severity were applied to replicate plots of mature northern hardwoods to quantify their effects on forested ecosystems. We assessed ice storm treatment effects on insectivorous foliage-gleaning birds and evaluated insectivore predation on model caterpillars in the understory vegetation. These birds are charismatic, of conservation concern, and are major predators of caterpillars. In turn, lepidopterans are the dominant herbivores in temperate forests and are integral to ecosystem function. We predicted that avian abundance would increase due to additional structural heterogeneity caused by ice treatments, with a concomitant increase in caterpillar predation. Point counts were used to measure insectivorous bird activity in the ice storm experiment plots and additional control plots before and after treatments. We deployed and retrieved plasticine model caterpillars and estimated predation from characteristic marks to these surrogates. Abundance of foliage-gleaning birds was higher in the ice storm plots and birds responded to treatments as a single diffuse disturbance rather than on an individual plot level. All species except one were observed both before and after the ice treatments. Surprisingly, predation on caterpillar models was unaffected by ice storm treatments but rather was a function of caterpillar density. The increase in avian abundance in the ice storm treatment plots corroborates other studies of bird responses to relatively small-scale disturbances in forests and the limited change in species composition was expected given the plot size. We conclude that ice storms may provide beneficial changes for foliage-gleaning birds in the growing season following the disturbance.
The Novel Key Genes of Non-obstructive Azoospermia Affect Spermatogenesis: Transcriptomic Analysis Based on RNA-Seq and scRNA-Seq Data
Authors: He Haihong , Yu Fan , Shen Wang , Chen Keyan , Zhang Lijun , Lou Shuang , Zhang Qiaomin , Chen Siping , Yuan Xinhua , Jia Xingwang , Zhou Yiwen
Published: February 2021

Non-obstructive azoospermia (NOA) is one of the most important causes of male infertility. It is mainly characterized by the absence of sperm in semen repeatedly or the number of sperm is small and not fully developed. At present, its pathogenesis remains largely unknown. The goal of this study is to identify hub genes that might affect biomarkers related to spermatogenesis. Using the clinically significant transcriptome and single-cell sequencing data sets on the Gene Expression Omnibus (GEO) database, we identified candidate hub genes related to spermatogenesis. Based on them, we performed Gene Ontology (GO) functional enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway analyses, protein-protein interaction (PPI) network analysis, principal component analysis (PCA), cell cluster analysis, and pseudo-chronological analysis. We identified a total of 430 differentially expressed genes, of which three have not been reported related to spermatogenesis (C22orf23, TSACC, and TTC25), and the expression of these three hub genes was different in each type of sperm cells. The results of the pseudo-chronological analysis of the three hub genes indicated that TTC25 was in a low expression state during the whole process of sperm development, while the expression of C22orf23 had two fluctuations in the differentiating spermatogonia and late primary spermatocyte stages, and TSACC showed an upward trend from the spermatogonial stem cell stage to the spermatogenesis stage. Our research found that the three hub genes were different in the trajectory of sperm development, indicating that they might play important roles in different sperm cells. This result is of great significance for revealing the pathogenic mechanism of NOA and further research.
Construction of circRNA-Based ceRNA Network to Reveal the Role of circRNAs in the Progression and Prognosis of Hepatocellular Carcinoma
Authors: Deng Rong , Cui Xiaohan , Dong Yuxiang , Tang Yanqiu , Tao Xuewen , Wang Shuyu , Wang Jincheng , Chen Lin
Published: February 2021

Background

Circular RNAs (circRNAs) are now under hot discussion as novel promising biomarkers for patients with hepatocellular carcinoma (HCC). The purpose of our study is to identify several competing endogenous RNA (ceRNA) networks related to the prognosis and progression of HCC and to further investigate the mechanism of their influence on tumor progression.

Methods

First, we obtained gene expression data related to liver cancer from The Cancer Genome Atlas (TCGA) database (http://www.portal.gdc.cancer.gov/), including microRNA (miRNA) sequence, RNA sequence, and clinical information. A co-expression network was constructed through the Weighted Correlation Network Analysis (WGCNA) software package in R software. The differentially expressed messenger RNAs (DEmRNAs) in the key module were analyzed with the Database for Annotation Visualization and Integrated Discovery (DAVID) (https://david.ncifcrf.gov/summary.jsp) to perform functional enrichment analysis including Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO). The data of miRNA expression and clinical information downloaded from TCGA were utilized for survival analysis to detach the prognostic value of the DEmiRNAs of the key module.

Results

The 201 differentially expressed miRNAs (DEmiRNAs) and 3,783 DEmRNAs were preliminarily identified through differential expression analysis. The co-expression networks of DEmiRNAs and DEmRNAs were constructed with WGCNA. Further analysis confirmed four miRNAs in the most significant module (blue module) were associated with the overall survival (OS) of patients with liver cancer, including hsa-miR-92b-3p, hsa-miR-122-3p, hsa-miR-139-5p, and hsa-miR-7850-5p. DAVID was used for functional enrichment analysis of 286 co-expressed mRNAs. The GO analysis results showed that the top enriched GO terms were oxidation–reduction process, extracellular exosome, and iron ion binding. In KEGG pathway analysis, the top three enriched terms included metabolic pathways, fatty acid degradation, and valine, leucine, and isoleucine degradation. In addition, we intersected the miRNA–mRNA interaction prediction results with the differentially expressed and prognostic mRNAs. We found that hsa-miR-92b-3p can be related to CPEB3 and ACADL. By overlapping the data of predicted circRNAs by circBank and differentially expressed circRNAs of GSE94508, we screened has_circ_0077210 as the upstream regulatory molecule of hsa-miR-92b-3p. Hsa_circ_0077210/hsa-miR-92b-3p/cytoplasmic polyadenylation element binding protein-3 (CPEB3) and acyl-Coenzyme A dehydrogenase, long chain (ACADL) were validated in HCC tissue.

Conclusion

Our research provides a mechanistic elucidation of the unknown ceRNA regulatory network in HCC. Hsa_circ_0077210 might serve a momentous therapeutic role to restrain the occurrence and development of HCC.
An Efficient Computational Model for Large-Scale Prediction of Protein–Protein Interactions Based on Accurate and Scalable Graph Embedding
Authors: Su Xiao-Rui , You Zhu-Hong , Hu Lun , Huang Yu-An , Wang Yi , Yi Hai-Cheng
Published: February 2021

Protein–protein interaction (PPI) is the basis of the whole molecular mechanisms of living cells. Although traditional experiments are able to detect PPIs accurately, they often encounter high cost and require more time. As a result, computational methods have been used to predict PPIs to avoid these problems. Graph structure, as the important and pervasive data carriers, is considered as the most suitable structure to present biomedical entities and relationships. Although graph embedding is the most popular approach for graph representation learning, it usually suffers from high computational and space cost, especially in large-scale graphs. Therefore, developing a framework, which can accelerate graph embedding and improve the accuracy of embedding results, is important to large-scale PPIs prediction. In this paper, we propose a multi-level model LPPI to improve both the quality and speed of large-scale PPIs prediction. Firstly, protein basic information is collected as its attribute, including positional gene sets, motif gene sets, and immunological signatures. Secondly, we construct a weighted graph by using protein attributes to calculate node similarity. Then GraphZoom is used to accelerate the embedding process by reducing the size of the weighted graph. Next, graph embedding methods are used to learn graph topology features from the reconstructed graph. Finally, the linear Logistic Regression (LR) model is used to predict the probability of interactions of two proteins. LPPI achieved a high accuracy of 0.99997 and 0.9979 on the PPI network dataset and GraphSAGE-PPI dataset, respectively. Our further results show that the LPPI is promising for large-scale PPI prediction in both accuracy and efficiency, which is beneficial to other large-scale biomedical molecules interactions detection.
Case Report: Identification of a Novel ODAD3 Variant in a Patient With Primary Ciliary Dyskinesia
Authors: Wang Rongchun , Yang Danhui , Guo Ting , Lei Cheng , Chen Xu , Kang Xi , Qing Jie , Luo Hong
Published: February 2021

Background:ODAD3 encodes a protein of 595 amino acids and contain three highly conserved coiled-coil domains, which is essential for cilia axoneme dynein arm assembly and docking. Primary ciliary dyskinesia (PCD) of ODAD3 deficiency are rarely reported. Female infertility in PCD related to ODAD3 variants has not been reported.

Methods: Whole-exome and Sanger sequencing were used to identify the disease-related gene of the patient with PCD in a consanguineous Chinese family. Domain analysis was applied to predict the impact of the variant on ODAD3 protein.

Results: The 35 year-old female patient exhibited chronic sinusitis, diffuse bronchiectasis, dextrocardia and infertility. We identified a novel homozygous variant in ODAD3, c.1166_1169dupAGAC, p.(Leu391Aspfs*105) in the PCD patient by exome sequencing and Sanger sequencing. This frameshift variant was predicted to be disease causing by bioinformatics analysis and was also not presented in the current authorized large genetic databases.

Conclusions: Our study enriches the genetic spectrum and clinical phenotypes of ODAD3 variants in PCD and provide more evidence for future genetic counseling and gene-targeted therapy for this disease.
Disrupted Service Delivery? The Impact of Conflict on Antenatal Care Quality in Kenya
Authors: Chukwuma Adanna , Wong Kerry L. M. , Ekhator-Mobayode Uche Eseosa
Published: February 2021

Introduction: African countries facing conflict have higher levels of maternal mortality. Understanding the gaps in the utilization of high-quality maternal health care is essential to improving maternal survival in these states. Few studies have estimated the impact of conflict on the quality of health care. In this study, we estimated the impact of conflict on the quality of health care in Kenya, a country with multiple overlapping conflicts and significant disparities in maternal survival.

Materials and Methods: We drew on data on the observed quality of 553 antenatal care (ANC) visits between January and April 2010. Process quality was measured as the percentage of elements of client–provider interactions performed in these visits. For structural quality, we measured the percentage of required components of equipment and infrastructure and the management and supervision in the facility on the day of the visit. We spatially linked the analytical sample to conflict events from January to April 2010. We modeled the quality of ANC as a function of exposure to conflict using spatial difference-in-difference models.

Results: ANC visits that occurred in facilities within 10,000 m of any conflict event in a high-conflict month received 18–21 percentage points fewer components of process quality on average and had a mean management and supervision score that was 12.8–13.5 percentage points higher. There was no significant difference in the mean equipment and infrastructure score at the 5% level. The positive impact of conflict exposure on the quality of management and supervision was driven by rural facilities. The quality of management and supervision and equipment and infrastructure did not modify the impact of conflict on process quality.

Discussion: Our study demonstrates the importance of designing maternal health policy based on the context-specific evidence on the mechanisms through which conflict affects health care. In Kenya, deterioration of equipment and infrastructure does not appear to be the main mechanism through which conflict has affected ANC quality. Further research should focus on better understanding the determinants of the gaps in process quality in conflict-affected settings, including provider motivation, competence, and incentives.