bluuebunny/crossref_metadata_2025 huggingface dataset:
Allochronic Divergence Driven by Spatial Asynchrony in Precipitation in Neotropical Frogs?
Authors: Guarnizo Carlos E. , Montoya Paola , Quintero Ignacio , Cadena Carlos Daniel
Published: May 2020

The role of geographic barriers in promoting reproductive isolation across space is well understood. Isolation by the time of breeding, however, may also promote population divergence when populations reproduce asynchronically in space, even in the absence of geographic barriers. Few examples exist of divergence due to breeding allochrony, particularly in vertebrates. We tested whether in Neotropical frogs’ asynchrony in precipitation patterns promotes intraspecific genetic divergence, speciation, and regional accumulation of diversity. We assessed the relationship between spatial asynchrony in precipitation and genetic divergence controlling for ecological connectivity across 48 Neotropical frog species. In addition, we examined whether regions within which precipitation regimes are more asynchronous across space have higher species richness and have experienced greater speciation rates. Beyond a generalized expected effect of ecological connectivity on intraspecific genetic divergence, we found that asynchrony in precipitation is positively associated with genetic differentiation in 31% of the species tested, resulting in a significantly positive cross-species effect of asynchrony in precipitation on genetic divergence in a meta-analysis. However, the effect of asynchrony in precipitation on population divergence seems not to scale to macroevolutionary patterns because spatial asynchrony in precipitation was not associated with geographical patterns of species richness or speciation rates. Our results indicate that genetic divergence can be promoted by asynchronous breeding lag in the absence of geographic barriers in species where breeding is associated with water availability, but such effects may not be stable enough through time to influence macroevolutionary patterns.
Towards understanding predictability in ecology: A forest gap model case study
Authors: Raiho Ann , Dietze Michael , Dawson Andria , Rollinson Christine R. , Tipton John , McLachlan Jason
Published: May 2020

Underestimation of uncertainty in ecology runs the risk of producing precise, but inaccurate predictions. Most predictions from ecological models account for only a subset of the various components of uncertainty, making it diffcult to determine which uncertainties drive inaccurate predictions. To address this issue, we leveraged the forecast-analysis cycle and created a new state data assimilation algorithm that accommodates non-normal datasets and incorporates a commonly left-out uncertainty, process error covariance. We evaluated this novel algorithm with a case study where we assimilated 50 years of tree-ring-estimated aboveground biomass data into a forest gap model. To test assumptions about which uncertainties dominate forecasts of forest community and carbon dynamics, we partitioned hindcast variance into five uncertainty components. Contrary to the assumption that demographic stochasticity dominates forest gap dynamics, we found that demographic stochasticity alone massively underestimated forecast uncertainty (0.09% of the total uncertainty) and resulted in overconfident, biased model predictions. Similarly, despite decades of reliance on unconstrained “spin-ups” to initialize models, initial condition uncertainty declined very little over the forecast period and constraining initial conditions with data led to large increases in prediction accuracy. Process uncertainty, which up until now had been diffcult to estimate in mechanistic ecosystem model projections, dominated the prediction uncertainty over the forecast time period (49.1%), followed by meteorological uncertainty (32.5%). Parameter uncertainty, a recent focus of the modeling community, contributed 18.3%. These findings call into question our conventional wisdom about how to improve forest community and carbon cycle projections. This foundation can be used to test long standing modeling assumptions across fields in global change biology and specifically challenges the conventional wisdom regarding which aspects dominate uncertainty in the forest gap models.
Effectiveness of 2ndSkull Products in Reducing Head Impact in Simulated Sports
Authors: Ritchie Marina , Lin Honghuang , Au Rhoda
Published: May 2020

Cumulative effects of repetitive head impact have been highly associated with short and long term neurological conditions. Despite high rates of head injuries, many people in the U.S. and around the world continue to participate in collision sports. As one approach to address this concern, 2ndSkull has developed supplemental protective headgears including a skull cap, scrum cap and headband that can be utilized in both helmet and non-helmet sports. To test the effectiveness of 2ndSkull products as an adjunctive tool to reduce the severity of head impact, data were extracted from a series of tests completed at four sites under laboratory conditions using linear, projectile and rotational impactor to simulate blows to the head in sports. The majority of test cases showed the same pattern of reduced impact severity with the addition of 2ndSkull padding. It remains to be seen if these laboratory results will translate to the field.
Mechano-Chemo Signaling Interactions Modulate Matrix Production by Cardiac Fibroblasts
Authors: Rogers Jesse D. , Holmes Jeffrey W. , Saucerman Jeffrey J. , Richardson William J.
Published: May 2020

Extracellular matrix remodeling after myocardial infarction occurs in a dynamic environment in which local mechanical stresses and biochemical signaling species stimulate the accumulation of collagen-rich scar tissue. It is well-known that cardiac fibroblasts regulate post-infarction matrix turnover by secreting matrix proteins, proteases, and protease inhibitors in response to both biochemical stimuli and mechanical stretch, but how these stimuli act together to dictate cellular responses is still unclear. We developed a screen of cardiac fibroblast-secreted proteins in response to combinations of biochemical agonists and cyclic uniaxial stretch in order to elucidate the relationships between stretch, biochemical signaling, and cardiac matrix turnover. We found that stretch significantly synergized with biochemical agonists to inhibit the secretion of matrix metalloproteinases, with stretch either amplifying protease suppression by individual agonists or antagonizing agonist-driven upregulation of protease expression. Stretch also modulated fibroblast sensitivity towards biochemical agonists by either sensitizing cells towards agonists that suppress protease secretion or de-sensitizing cells towards agonists that upregulate protease secretion. These findings suggest that the mechanical environment can significantly alter fibrosis-related signaling in cardiac fibroblasts, suggesting caution when extrapolatingin vitrodata to predict effects of fibrosis-related cytokines in situations like myocardial infarction where mechanical stretch occurs.
Skin Delivery of Modified Vaccinia Ankara Viral Vectors Generates Superior T Cell Immunity Against a Respiratory Viral Challenge
Authors: Pan Youdong , Liu Luzheng , Tian Tian , Zhao Jingxia , Park Chang Ook , Lofftus Serena Y. , Stingley Claire A. , Mei Shenglin , Liu Xing , Kupper Thomas S.
Published: May 2020

Modified Vaccinia Ankara (MVA) was recently approved as a Smallpox vaccine. Transmission of Variola is by respiratory droplets, and MVA delivered by skin scarification (s.s.) protected mice far more effectively against lethal respiratory challenge with VACV than any other route of delivery, and at much lower doses. Comparisons of s.s. with intradermal, subcutaneous or intramuscular routes showed that MVAOVAs.s.-generated T cells were both more abundant and transcriptionally distinct. MVAOVAs.s. produced greater numbers of lung Ova-specific CD8+TRMand was superior in protecting mice against lethal VACVOVArespiratory challenge. Nearly as many lung TRMwere generated with MVAOVAs.s. compared to direct pulmonary immunization with MVAOVA, and both routes vaccination protected mice against lethal pulmonary challenge with VACVOVA. Strikingly, MVAOVAs.s.-generated effector T cells exhibited overlapping gene transcriptional profiles to those generated via direct pulmonary immunization. Overall, our data suggest that heterologous MVA vectors delivered via s.s. are uniquely well-suited as vaccine vectors for respiratory pathogens like COVID-19. In addition, MVA delivered via s.s. could represent a more effective dose-sparing smallpox vaccine.
Prokaryotic Argonaute fromArchaeoglobus fulgidusinteracts with DNA as a homodimer
Authors: Golovinas Edvardas , Rutkauskas Danielis , Manakova Elena , Jankunec Marija , Silanskas Arunas , Sasnauskas Giedrius , Zaremba Mindaugas
Published: May 2020

Background

Argonaute (Ago) proteins are found in all three domains of life. The best characterized group is eukaryotic Argonautes (eAgos), which are the core of RNA interference. The best understood prokaryotic Ago (pAgo) proteins are full-length pAgos. They are monomeric proteins, all composed of four major structural/functional domains (N, PAZ, MID and PIWI) and thereby closely resemble eAgos. It is believed that full-length pAgos function as prokaryotic antiviral systems, with the PIWI domain performing cleavage of invading nucleic acids. However, the majority of identified pAgos are shorter and catalytically inactive (encode just MID and inactive PIWI domains), thus their action mechanism and function remain unknown.

Results

In this work we focus on AfAgo, a short pAgo protein encoded by an archaeonArchaeoglobus fulgidus. We find that in all previously solved AfAgo structures, its two monomers form substantial dimerization interfaces involving the C-terminal β-sheets. Led by this finding, we have employed various biochemical and biophysical assays, including single-molecule FRET, SAXS and AFM, to test the possible dimerization of AfAgo. SAXS results confirm that WT AfAgo, but not the dimerization surface mutant AfAgoΔ, forms a homodimer both in the apo-form and when bound to a nucleic acid. Single molecule FRET and AFM studies demonstrate that the dimeric WT AfAgo binds two ends of a linear DNA fragment, forming a relatively stable DNA loop.

Conclusion

Our results show that contrary to other characterized Ago proteins, AfAgo is a stable homodimer in solution, which is capable of simultaneous interaction with two DNA molecules. This finding broadens the range of currently known Argonaute-nucleic acid interaction mechanisms.
Nighttime gibberellin biosynthesis is influenced by fluctuating environmental conditions and contributes to growth adjustments of Arabidopsis leaves
Authors: Prasetyaningrum Putri , Mariotti Lorenzo , Valeri Maria Cristina , Novi Giacomo , Dhondt Stijn , Inzé Dirk , Perata Pierdomenico , van Veen Hans
Published: May 2020

Optimal plant growth performance requires that the action of growth signals, such as gibberellins (GA), are coordinated with the availability of photo-assimilates. Here, we studied the links between gibberellin biosynthesis and carbon availability, and the subsequent effects on growth. The results presented here show that carbon availability, light and dark cues, and the clock ensure the timing and magnitude of gibberellin biosynthesis and that disruption of these mechanisms results in reduced gibberellin levels and expression of downstream genes. Carbon dependent nighttime induction of GIBBERELLIN 3-BETA-DIOXYGENASE 1 (GA3ox1) was severely hampered when preceded by a day of lowered light availability, leading specifically to reduced bioactive GA4 levels, and coinciding with a decline in leaf expansion rate during the night. We attribute this decline in leaf expansion mostly to reduced photo-assimilates. However, plants where gibberellin limitation was alleviated had significantly improved expansion demonstrating the relevance of gibberellins in growth control under varying carbon availability. Carbon dependent expression of upstream gibberellin biosynthesis genes (KAURENE SYNTHASE, KS and GIBBERELLIN 20 OXIDASE 1, GA20ox1) was not translated into metabolite changes within this short timeframe. We propose a model where the extent of nighttime biosynthesis of bioactive GA4 by GA3ox1 is determined by starch, as the nighttime carbon source, and so provides day-to-day adjustment of gibberellin responses.
Independent somatic evolution underlies clustered neuroendocrine tumors in the human small intestine
Authors: Elias Erik , Ardalan Arman , Lindberg Markus , Reinsbach Susanne , Muth Andreas , Nilsson Ola , Arvidsson Yvonne , Larsson Erik
Published: May 2020

Background

Small intestine neuroendocrine tumor (SI-NET), the most common cancer of the small bowel, often displays a curious multifocal phenotype with several intestinal tumors centered around a regional lymph node metastasis. Although SI-NET patients often present with metastatic disease at the time of diagnosis, there is an unusual absence of somatic driver mutations explaining tumor initiation and metastatic spread. The evolutionary trajectories that underlie multifocal SI-NET lesions could provide insight into the underlying tumor biology, but this question remains unresolved. Here, we determined the complete genome sequences of 65 tumor and tissue samples from 11 patients with multifocal SI-NET, allowing for elucidation of phylogenetic relationships between tumors within individual patients. Intra-individual comparisons of whole genome sequences revealed a lack of shared somatic single-nucleotide variants and copy number alterations among the sampled intestinal lesions, supporting that they were of independent clonal origin. Furthermore, each metastasis originated from a single intestinal tumor, and in three of the patients, two independent tumors had metastasized. We conclude that primary multifocal SI-NETs generally arise from clonally independent cells, suggesting a contribution from of a cancer-priming local factor.
Role ofDrosophilaRap/Fzr (DCdh1) in Retinal Axon Targeting and its Interactions with Loco and Liprin-alpha
Authors: Grońska-Pęski Marta , Venkatesh Tadmiri R.
Published: May 2020

The development of the wild typeDrosophilacompound eye involves stereotypical targeting of photoreceptor axons to the specific layers of the optic ganglion, medulla and lamina, in the third instar larvae. To test the hypothesis that ubiquitin ligases play an important role during retinal axon targeting we have examined the patterns of axon targeting in the developing eye of theretina aberrant in pattern (rap/fzr)mutants. Rap/Fzr is a homolog of mammalian Cdh1, an activator of anaphase promoting complex (APC), a multi-subunit E3 ubiquitin ligase, regulating the cell cycle progression. Previous work has shown that Rap/Fzr is required during eye development for proper cell cycle regulation, glia differentiation and pattern formation. It was also necessary for proper neuromuscular junction development and circadian rhythms. Our results show that Rap/Fzr is required for proper retinal axon targeting in the developing eye. Usingro-tau-lacZ, we show that the R2-R5 axons fail to stop in the lamina and mis-target to the medulla levels. Also, mosaic analyses experiments using FLP-FRT and GAL4-UAS techniques show that Rap/Fzr functions in a cell autonomous manner. To test for possible role of other signalling molecules and interactions with Rap/Fzr, we have examinedrap/fzraxon projection phenotypes in double mutant combinations with the RGS protein,locomotion defective(loco) mutants and a scaffolding protein, Liprin-α. Our studies suggest that Rap/Fzr is required for proper axon targeting duringDrosophilavisual system development, and the phenotype is enhanced in double mutants with eitherlocoor Liprin-α. These results are consistent with other mammalian studies reporting a role of Cdh1 in axon growth and targeting and provides further insights into neuronal functions of the ubiquitin ligase APC/CCdh1.

Highlights

Loss ofrap/fzrin the third instar Drosophila eye disc leads to photoreceptor axon overgrowth

Overexpression ofrap/fzrleads to photoreceptor axon leads to axon shortening and clumping

Loss ofLocoP452leads to photoreceptor overgrowth

Double mutants ofrapandlocoorrapandLiprin-αshow axon enhancement of the axon targeting defects in theDrosophilathird instar larvae eye imaginal discs.
The contribution of hippocampal subfields to the progression of neurodegeneration
Authors: Kwak Kichang , Niethammer Marc , Giovanello Kelly S. , Styner Martin , Dayan Eran ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: May 2020

Mild cognitive impairment (MCI) is often considered the precursor of Alzheimer’s disease. However, MCI is associated with substantially variable progression rates, which are not well understood. Attempts to identify the mechanisms that underlie MCI progression have often focused on the hippocampus, but have mostly overlooked its intricate structure and subdivisions. Here, we utilized deep learning to delineate the contribution of hippocampal subfields to MCI progression using a total sample of 1157 subjects (349 in the training set, 427 in a validation set and 381 in the testing set). We propose a dense convolutional neural network architecture that differentiates stable and progressive MCI based on hippocampal morphometry. The proposed deep learning model predicted MCI progression with an accuracy of 75.85%. A novel implementation of occlusion analysis revealed marked differences in the contribution of hippocampal subfields to the performance of the model, with presubiculum, CA1, subiculum, and molecular layer showing the most central role. Moreover, the analysis reveals that 10.5% of the volume of the hippocampus was redundant in the differentiation between stable and progressive MCI. Our predictive model uncovers pronounced differences in the contribution of hippocampal subfields to the progression of MCI. The results may reflect the sparing of hippocampal structure in individuals with a slower progression of neurodegeneration.
Carbohydrate binding domains facilitate efficient oligosaccharides synthesis by enhancing mutant catalytic domain transglycosylation activity
Authors: Bandi Chandra Kanth , Goncalves Antonio , Pingali Sai Venkatesh , Chundawat Shishir P. S.
Published: May 2020

Chemoenzymatic approaches using carbohydrate-active enzymes (CAZymes) offer a promising avenue for synthesis of glycans like oligosaccharides. Here, we report a novel chemoenzymatic route for cellodextrins synthesis employed by chimeric CAZymes, akin to native glycosyltransferases, involving the unprecedented participation of a ‘non-catalytic’ lectin-like or carbohydrate-binding domains (CBMs) in the catalytic step for glycosidic bond synthesis using β-cellobiosyl donor sugars as activated substrates. CBMs are often thought to play a passive substrate targeting role in enzymatic glycosylation reactions mostly via overcoming substrate diffusion limitations for tethered catalytic domains (CDs) but are not known to participate directly in any nucleophilic substitution mechanisms that impact the actual glycosyl transfer step. Our study provides evidence for the direct participation of CBMs in the catalytic reaction step for β-glucan glycosidic bonds synthesis enhancing activity for CBM-based CAZyme chimeras by >140-fold over CDs alone. Dynamic intra-domain interactions that facilitate this poorly understood reaction mechanism were further revealed by small-angle X-ray scattering structural analysis along with detailed mutagenesis studies to shed light on our current limited understanding of similar transglycosylation-type reaction mechanisms. In summary, our study provides a novel strategy for engineering similar CBM-based CAZyme chimeras for synthesis of bespoke oligosaccharides using simple activated sugar monomers.
A hybrid open-top light-sheet microscope for multi-scale imaging of cleared tissues
Authors: Glaser Adam K. , Bishop Kevin W. , Barner Lindsey A. , Susaki Etsuo A. , Kubota Shimpei I. , Gao Gan , Serafin Robert B. , Balaram Pooja , Turschak Emily , Nicovich Philip R. , Lai Hoyin , Lucas Luciano A.G. , Yi Yating , Nichols Eva K. , Huang Hongyi , Reder Nicholas P. , Wilson Jasmine J. , Sivakumar Ramya , Shamskhou Elya , Stoltzfus Caleb R. , Wei Xing , Hempton Andrew K. , Pende Marko , Murawala Prayag , Dodt Hans U. , Imaizumi Takato , Shendure Jay , Beliveau Brian J. , Gerner Michael Y. , Xin Li , Zhao Hu , True Lawrence D. , Reid R. Clay , Chandrashekar Jayaram , Ueda Hiroki R. , Svoboda Karel , Liu Jonathan T.C.
Published: May 2020

Light-sheet microscopy has emerged as the preferred means for high-throughput volumetric imaging of cleared tissues. However, there is a need for a user-friendly system that can address imaging applications with varied requirements in terms of resolution (mesoscopic to sub-micrometer), sample geometry (size, shape, and number), and compatibility with tissue-clearing protocols and sample holders of various refractive indices. We present a ‘hybrid’ system that combines a novel non-orthogonal dual-objective and conventional (orthogonal) open-top light-sheet architecture for versatile multi-scale volumetric imaging.
Endophilin A1 promotes Actin Polymerization in response to Ca2+/calmodulin to Initiate Structural Plasticity of Dendritic Spines
Authors: Yang Yanrui , Chen Jiang , Chen Xue , Li Di , He Jianfeng , Zhao Shun , Yang Xiaoyu , Deng Shikung , Wang Dou , Guo Zhenzhen , Zhu Shaoxia , Li Dong , Ma Cong , Liang Xin , Shi Yun S. , Liu Jia-Jia
Published: May 2020

Dendritic spines of excitatory neurons undergo activity-dependent structural and functional plasticity, which are cellular correlates of learning and memory. However, mechanisms underlying the rapid morphological changes immediately after NMDAR-mediated Ca2+influx into spines remain poorly understood. Here we report that endophilin A1, a neuronal N-BAR protein, orchestrates membrane dynamics with actin polymerization to initiate spine enlargement in the induction phase of long-term potentiation (LTP). Upon LTP induction, Ca2+/calmodulin enhances its binding to both membrane and p140Cap, a cytoskeleton regulator. As a result, endophilin A1 rapidly associates with the relaxed plasma membrane and promotes actin polymerization, leading to acute expansion of spine head. Moreover, not only the p140Cap-binding, but also calmodulin- and membrane-binding capacities of endophilin A1 are required for LTP and long-term memory. Thus, endophilin A1 functions as calmodulin effector to drive spine enlargement in response to Ca2+influx in the initial phase of structural plasticity.
High-Dimensional Immunophenotyping of Murine T-cell and B-cell Subsets
Authors: Mincham Kyle T. , Young Jacob D. , Strickland Deborah H.
Published: May 2020

Purpose and appropriate sample types

This 19-parameter, 18-colour flow cytometry panel was designed and optimised to enable the comprehensive and simultaneous immunophenotyping of distinct T-cell and B-cell subsets within murine lymphoid tissues (Table 1). Cellular populations identified by employing this OMIP include 4 major subsets of B-cells (memory, activated, plasma cells and plasmablasts) and 7 major subsets of CD4+T-cells (naïve, central memory, effector memory, helper, regulatory, follicular helper and follicular regulatory). Staining was performed on freshly isolated splenocytes from 21-day-old neonatal BALB/c mice, however due to the omission of mouse strain-specific markers, this OMIP can be implemented across a range of murine models where in-depth immunophenotyping of the diverse repertoire of T-cell and B-cell populations localised within lymphoid tissues is required.
Transcriptional comparison of Testicular Adrenal Rest Tumors with fetal and adult tissues
Authors: Schröder Mariska A.M. , Sweep Fred C.G.J. , van Herwaarden Antonius E. , Rowan Alan E. , Korbie Darren , Mitchell Rod T. , Stikkelbroeck Nike M.M.L. , Claahsen – van der Grinten Hedi L. , Span Paul N.
Published: May 2020

Testicular Adrenal Rest Tumors (TART) are a common complication of unknown origin in patients with Congenital Adrenal Hyperplasia. These benign tumors may derive from cells of adrenal origin or from pluripotent progenitor cells from the fetal adrenogonadal primordium. By comparing the transcriptome of TART with fetal- and adult-testis and adrenal tissues, this study aims to unravel the origin of TART. Targeted transcriptome sequencing was followed by unsupervised clustering-, differential expression-, functional enrichment- and pathway analyses. Immunohistochemistry demonstrated co-expression of adrenal-specific CYP11B1 and testis-specific HSD17B3 in TART, indicating the existence of a distinct TART cell exhibiting both adrenal- and testicular characteristics. Principal component analysis indicated that the TART transcriptome was distinct from either adrenal or testis fetal tissue, making a progenitor-like phenotype of TART unlikely. Rather, TART appears to originate from -or differentiate into-a mature cell type, with both adrenal- and testicular characteristics. The present study, the first to describe the TART transcriptome, expands knowledge about the identity and functional characteristics of TART and identifies clinically targetable pathways associated with fibrosis.
Teacher-student neural coupling during teaching and learning
Authors: Nguyen Mai , Chang Ashley , Micciche Emily , Meshulam Meir , Nastase Samuel A. , Hasson Uri
Published: May 2020

Human communication is remarkably versatile, enabling teachers to share highly abstracted and novel information with their students. What neural processes enable such transfer of information across brains during naturalistic teaching and learning? Here, we show that during lectures, wherein information transmission is unidirectional and flows from the teacher to the student, the student’s brain mirrors the teacher’s brain and that this neural coupling is correlated with learning outcomes. A teacher was scanned in fMRI giving an oral lecture with slides on a scientific topic followed by a review lecture. Students were then scanned watching either the intact lecture and review (N= 20) or a temporally scrambled version of the lecture (N= 20). Using intersubject correlation (ISC), we observed widespread teacher-student neural coupling spanning sensory cortex and language regions along the superior temporal sulcus as well as higher-level regions including posterior medial cortex (PMC), superior parietal lobule (SPL), and dorsolateral and dorsomedial prefrontal cortex. Teacher-student alignment in higher-level areas was not observed when learning was disrupted by temporally scrambling the lecture. Moreover, teacher-student coupling in PMC was significantly correlated with learning outcomes: the more closely the student’s brain mirrored the teacher’s brain, the more the student improved between behavioral pre-learning and post-learning assessments. Together, these results suggest that the alignment of neural responses between teacher and students may underlie effective communication of complex information across brains in classroom settings.

Significance statement

How is technical, non-narrative information communicated from one brain to another during teaching and learning? In this fMRI study, we show that the DMN activity of teachers and students are coupled during naturalistic teaching. This teacher-student neural coupling emerges only during intact learning and is correlated with learning outcomes. Together, these findings suggest that teacher-student neural alignment underlies effective communication during teaching.
Soil and root nutrient chemistry structure root‐associated fungal assemblages in temperate forests
Authors: Nguyen Dung Quang , Schneider Dominik , Brinkmann Nicole , Song Bin , Janz Dennis , Schöning Ingo , Daniel Rolf , Pena Rodica , Polle Andrea
Published: May 2020

Root‐associated fungi (RAF) link nutrient fluxes between soil and roots and thus play important roles in ecosystem functioning. To enhance our understanding of the factors that control RAF, we fitted statistical models to explain variation in RAF community structure using data from 150 temperate forest sites covering a broad range of environmental conditions and chemical root traits. We found that variation in RAF communities was related to both root traits (e.g., cations, carbohydrates, NO3−) and soil properties (pH, cations, moisture, C/N). The identified drivers were the combined result of distinct response patterns of fungal taxa (determined at the rank of orders) to biotic and abiotic factors. Our results support that RAF community variation is related to evolutionary adaptedness of fungal lineages and consequently, drivers of RAF communities are context‐dependent.
Genomic characterization of closely related species in the Rumoiensis clade infers ecogenomic signatures to non‐marine environments
Authors: Tanaka Mami , Kumakura Daiki , Mino Sayaka , Doi Hidetaka , Ogura Yoshitoshi , Hayashi Tetsuya , Yumoto Isao , Cai Man , Zhou Yu‐Guang , Gomez‐Gil Bruno , Araki Toshiyoshi , Sawabe Tomoo
Published: May 2020

Members of the family Vibrionaceae are generally found in marine and brackish environments, playing important roles in nutrient cycling. The Rumoiensis clade is an unconventional group in the genus Vibrio, currently comprising six species from different origins including two species isolated from non‐marine environments. In this study, we performed comparative genome analysis of all six species in the clade using their complete genome sequences. We found that two non‐marine species, Vibrio casei and Vibrio gangliei, lacked the genes responsible for algal polysaccharide degradation, while a number of glycoside hydrolase genes were enriched in these two species. Expansion of insertion sequences was observed in V. casei and Vibrio rumoiensis, which suggests ongoing genomic changes associated with niche adaptations. The genes responsible for the metabolism of glucosylglycerate, a compound known to play a role as compatible solutes under nitrogen limitation, were conserved across the clade. These characteristics, along with genes encoding species‐specific functions, may reflect the habit expansion which has led to the current distribution of Rumoiensis clade species. Genome analysis of all species in a single clade give us valuable insights into the genomic background of the Rumoiensis clade species and emphasize the genomic diversity and versatility of Vibrionaceae.
The Real Estate Frontier
Authors: Gillespie Tom
Published: May 2020

Africa's major cities are experiencing dramatic transformation as a result of growing real estate investment. This article explores whether existing theories can explain the dynamics of urban redevelopment in an African context, and how African cases can inform new theorizations of real estate driven urban transformation. Examining the utility of theories of gentrification and speculative urbanism for understanding urban redevelopment in Accra, Ghana, it argues that urban redevelopment in this city has been shaped by its particular (post)colonial history of state land acquisition and urban planning. Rather than simply identifying empirical variation on established theories, however, the article draws on recent research on commodity frontiers to propose an original theorization of urban redevelopment in Accra in terms of the production of a ‘real estate frontier’. This real estate frontier is characterized by the incremental and contested commodification of state land to enable the growth of the real estate sector in the city. The article concludes by calling for a comparative research agenda to better understand real estate frontiers globally.
OUT IN SPACE: Difference and Abstraction in Planetary Urbanization
Authors: Angelo Hillary , Goh Kian
Published: May 2020

A common thread has emerged in recent critiques of planetary urbanization. Whether on empirical, epistemological or theoretical grounds, critics tend to posit ‘difference against abstraction’, arguing that planetary urbanization—as an abstract theory of large‐scale phenomena—occludes ‘everyday’ embodied, small‐scale and place‐based forms of social difference in its production and/or application. Here we engage with this critique as two queer, feminist scholars sympathetic both to critics’ arguments about the politics of knowledge production and to the planetary urbanization framework. While we agree that the theory's most visible adherents have not systematically engaged with questions of difference, especially at smaller scales of social analysis, we reject the suggestion that planetary urbanization is inherently incompatible with such concerns. Rather, we argue that the opposite is true. Using examples from our own research, we show how the planetary urbanization framework—by enforcing a multiscalar and non‐city‐centric view of apparently local phenomena—can be central to theorizing and understanding social difference at the level of everyday life in empirical research.
The impact of housing conditions on health outcomes
Authors: Palacios Juan , Eichholtz Piet , Kok Nils , Aydin Erdal
Published: May 2020

We investigate the relationship between housing conditions and health outcomes using a data set that tracks 25,000 German households over 25 years. We document that individuals exposed to poor housing conditions report worse mental and physical health, and experience an 11% increase in doctor visits, increasing to 20% for age groups over 64. The analysis controls for individual, dwelling, and temporal fixed effects, and is robust to changes in socioeconomic status, lifestyle choices, and neighborhood conditions. As a robustness check, we use home renovations as major a trigger of changes in housing conditions. Restricting the analysis to tenants, whose renovations are paid by landlords, we document that home renovations significantly reduce doctor visits, corroborating the findings on home conditions and health outcomes.
Ultrafiltration volume by once‐weekly hemodialysis is a predictor of technique survival of combination therapy with peritoneal dialysis and hemodialysis
Authors: Tanaka Mototsugu , Ishibashi Yoshitaka , Hamasaki Yoshifumi , Kamijo Yuka , Idei Mayumi , Nishi Takahiro , Takeda Michio , Nonaka Hiroshi , Nangaku Masaomi , Mise Naobumi
Published: May 2020

Overhydration is a major cause of technique failure of peritoneal dialysis (PD). Hence, we investigated the impact of ultrafiltration (UF) volume by once‐weekly hemodialysis (HD), excess volume beyond their dry weight, on technique survival of PD and HD combination therapy (PD+HD). Forty‐six anuric PD+HD patients were divided into three groups according to baseline UF volume by HD: low‐UF (<mean − 1SD), middle‐UF (≥mean − 1SD and <mean + 1SD), and high‐UF (≥mean + 1SD). High‐UF group showed larger extracellular water normalized to height (P = .038) and longer HD sessions (P < .001) compared with low‐UF group, whereas low‐UF group was older than middle‐UF group (P = .001). Technique survival rate was significantly lower in high‐UF group than in low and middle‐UF groups (P < .001), and the rates at 44 months were 80%, 90%, 20% in low, middle, and high‐UF groups, respectively. Chronic overhydration was the leading cause of technique failure for all. This study suggests that fluid overload remains a major cause of technique failure of PD even after once‐weekly HD is added.
Incidental findings detected on cone beam computed tomography in an older population for pre‐implant assessment
Authors: Nguyen P‐N , Kruger E , Huang T , Koong B
Published: May 2020

Objectives

The aim of this retrospective study was to record incidental findings in CBCT scans taken in an older population for pre‐implant assessment, and to examine whether these findings would influence the intended dental implant placement.

Methods

300 consecutive CBCT scans over the age of 40 years was carried out. The incidental findings were grouped into regions as follows: dentoalveolar structures, maxilla and mandible, paranasal sinuses, temporomandibular joint (TMJ), naso/oral‐pharyngeal airway, cervical spine and neurovascular canals. The incidental findings are further categories into their significance towards the intended treatment plan.

Result

Incidental findings were noted on all of the scans. 555 incidental findings (1.85 findings/scan) were identified. The highest number of incidental findings was in the sinuses (34%), followed by dentoalveolar structures (31%), nasal/oral‐pharyngeal airway (12%), maxilla and mandible (10%), TMJ (6%), cervical spine (4%) and neurovascular canals (3%). A total of 37% of findings required follow‐up. In 12% of cases detection of the incidental findings lead to amendment or abortion of the intended implant treatment plan.

Conclusion

Incidental findings within and beyond the region of interest are common in CBCT scans. The numbers of incidental findings per scan in an older population is higher than in a younger population.
Receptive anal sex contributes substantially to heterosexually acquired HIV infections among at‐risk women in twenty US cities: Results from a modelling analysis
Authors: Elmes Jocelyn , Silhol Romain , Hess Kristen L. , Gedge Lukyn M. , Nordsletten Ashley , Staunton Roisin , Anton Peter , Shacklett Barbara , McGowan Ian , Dang Que , Adimora Adaora A. , Dimitrov Dobromir T. , Aral Sevgi , Handanagic Senad , Paz‐Bailey Gabriela , Boily Marie‐Claude
Published: May 2020

Problem

Receptive anal intercourse (RAI) is more efficient than receptive vaginal intercourse (RVI) at transmitting HIV, but its contribution to heterosexually acquired HIV infections among at‐risk women in the USA is unclear.

Method of study

We analysed sexual behaviour data from surveys of 9152 low‐income heterosexual women living in 20 cities with high rates of HIV conducted in 2010 and 2013 as part of US National HIV Behavioral Surveillance. We estimated RAI prevalence (past‐year RAI) and RAI fraction (fraction of all sex acts (RVI and RAI) at the last sexual episode that were RAI among those reporting past‐year RAI) overall and by key demographic characteristics. These results and HIV incidence were used to calibrate a risk equation model to estimate the population attributable fraction of new HIV infections due to RAI (PAFRAI) accounting for uncertainty in parameter assumptions.

Results

Receptive anal intercourse prevalence (overall: 32%, city range: 19%‐60%) and RAI fraction (overall: 27%, city range: 18%‐34%) were high overall and across cities, and positively associated with exchange sex. RAI accounted for an estimated 41% (uncertainty range: 18%‐55%) of new infections overall (city range: 21%‐57%). Variability in PAFRAI estimates was most influenced by uncertainty in the estimate of the per‐act increased risk of RAI relative to RVI and the number of sex acts.

Conclusion

Receptive anal intercourse may contribute disproportionately to new heterosexually acquired HIV infections among at‐risk low‐income women in the USA, meaning that tools to prevent HIV transmission during RAI are warranted. The number of RVI and RAI acts should also be collected to monitor heterosexually acquired HIV infections.
Timely surgical intervention for ureteric complications ensures adequate graft function in renal transplantation: a 10‐year review
Authors: Salter Sherry , Lee Alice , Jaya Joseph , Suh Nancy , Yii Ming Kon , Saunder Alan
Published: May 2020

Background

Ureteric complications can cause significant morbidity in renal and simultaneous pancreas–kidney (SPK) transplantation. This 10‐year review identified transplant patients with ureteric complications necessitating surgical intervention in an Australian tertiary centre.

Methods

The hospital records were scrutinized in detail to identify all patients who underwent renal or SPK transplantation from 1 June 2009 to 31 May 2019 with subsequent surgical management of ureteric complications. A case series of patients with ureteric complications was generated and findings were analysed.

Results

A total of 893 renal and SPK transplants were performed over the 10‐year period. Ten of these (1.12%; seven renal and three SPK) had ureteric complications. All were managed surgically. Five of the 10 had ureteric leaks (0.56%); three had ureteric strictures (0.34%), one had ureteric obstruction from extraluminal compression (0.11%) and one had both leak and stricture (0.11%). All 10 patients underwent ureteric reimplantation. Two patients required more than one operation for their ureteric complication. No graft loss or surgical mortality occurred. All 10 patients currently have functioning kidney transplants and none require maintenance dialysis.

Conclusion

We report a low rate (1.12%) of ureteric complications in our renal and SPK transplants. Our standard practice of definitive correction by ureteric reimplantation is proving successful. The authors confirm that appropriate surgery is a viable and durable option in renal transplant patients with excellent graft outcomes.
Review article: the emerging role of genetics in precision medicine for patients with non‐alcoholic steatohepatitis
Authors: Carlsson Björn , Lindén Daniel , Brolén Gabriella , Liljeblad Mathias , Bjursell Mikael , Romeo Stefano , Loomba Rohit
Published: May 2020

Background

Non‐alcoholic steatohepatitis (NASH) is a severe form of non‐alcoholic fatty liver disease (NAFLD) characterised by liver fat accumulation, inflammation and progressive fibrosis. Emerging data indicate that genetic susceptibility increases risks of NAFLD, NASH and NASH‐related cirrhosis.

Aims

To review NASH genetics and discuss the potential for precision medicine approaches to treatment.

Method

PubMed search and inclusion of relevant literature.

Results

Single‐nucleotide polymorphisms in PNPLA3, TM6SF2, GCKR, MBOAT7 and HSD17B13 are clearly associated with NASH development or progression. These genetic variants are common and have moderate‐to‐large effect sizes for development of NAFLD, NASH and hepatocellular carcinoma (HCC). The genes play roles in lipid remodelling in lipid droplets, hepatic very low‐density lipoprotein (VLDL) secretion and de novo lipogenesis. The PNPLA3 I148M variant (rs738409) has large effects, with approximately twofold increased odds of NAFLD and threefold increased odds of NASH and HCC per allele. Obesity interacts with PNPLA3 I148M to elevate liver fat content and increase rates of NASH. Although the isoleucine‐to‐methionine substitution at amino acid position 148 of the PNPLA3 enzyme inactivates its lipid remodelling activity, the effect of PNPLA3 I148M results from trans‐repression of another lipase (ATGL/PNPLA2) by sequestration of a shared cofactor (CGI‐58/ABHD5), leading to decreased hepatic lipolysis and VLDL secretion. In homozygous Pnpla3 I148M knock‐in rodent models of NAFLD, targeted PNPLA3 mRNA knockdown reduces hepatic steatosis, inflammation and fibrosis.

Conclusion

The emerging genetic and molecular understanding of NASH paves the way for novel interventions, including precision medicines that can modulate the activity of specific genes associated with NASH.
Stone projectiles from the siege of Alcalá la Vieja (Spain) and likely trebuchet placement
Authors: Galán M. Ramírez , Galán M. Benítez
Published: May 2020

Investigations of the siege of Islamic Alcalá la Vieja (Madrid, Spain) by Christian forces in the 12th centurycehave depended on secondary sources proven to be unreliable and error‐laden. In a search for possible locations of trebuchets used by the Christian attackers, the option was for an interdisciplinary approach combining elements from archaeology, physics and spatial analysis. The discovery of stone projectiles near the Islamic fortress allowed for the application of projectile physics to the calculation of several effective firing ranges for each stone. Those outcomes, in combination with geographical information system (GIS) data, have revealed a possible location where Christian forces could have effectively deployed hybrid trebuchets as siege engines.
A novel rat model of ocular hypertension by a single intracameral injection of cross‐linked hyaluronic acid hydrogel (Healaflow®)
Authors: Liu Ying , Wang Jichen , Jin Xin , Xin Zhiyuan , Wu Xing , Tong Xu , Tao Ye , Wang Dajiang
Published: May 2020

To create a novel animal model of ocular hypertension via the intracameral injection of Healaflow. Unilateral chronic ocular hypertension model of rats was created by the intracameral injection of 3 μL Healaflow. The IOP of subjects was monitored. Dynamic morphological changes were evaluated by fundus imaging, OCT and histological examination. Visual function changes were measured by electroretinography and flash visual‐evoked potentials. 24 and 72 hours after injection, the retinal tissue was collected for transcriptome analysis. The expression levels of related genes and proteins were further evaluated by qRT‐PCR and Western blotting. The IOP peaked within 1 day after a single intracameral injection of Healaflow and then decreased gradually within 4 weeks. Furthermore, the persistently degenerating retinal ganglion cells occurred within 4 weeks. The visual function of these rats was also impaired. The results of transcriptome analyses, qRT‐PCR and Western blotting showed that the expression levels of B2m, Ikzf1 and Stat3 were up‐regulated, while the expression levels of Six3 and Prss56 were down‐regulated in the retinal tissues. Intracameral injection of Healaflow is an effective approach to induce glaucomatous neurodegeneration in rats. Six3 and Prss56 may be involved in the pathogenesis of progressive glaucomatous damage.
Challenges, applications and future directions of precision medicine in prostate cancer – the role of organoids and patient‐derived xenografts
Authors: Joshi Andre , Roberts Matthew J. , Alinezhad Saeid , Williams Elizabeth D. , Vela Ian
Published: May 2020

Objective

To provide a clinically relevant outline of various current precision medicine principles and available evidence on the application and potential for a precision medicine approach in prostate cancer.

Methods

Narrative review of the current literature in the field.

Conclusion

Precision medicine is the concept of individualising patient management based on specific tumour characteristics and biology, rather than traditional histological subtypes. The overall aim is to personalise management to individual patients, to provide the right cancer treatment, to the right patient, at the right time. While the approach aims to improve clinical outcomes, decrease morbidity and improve survival in men with advanced prostate cancer, its clinical application is in its infancy. It does however show great promise in this and other cancers, and will continue to be an area of active research and clinical investigation.
Utilization rate of uncontrolled donors after circulatory death‐a 3‐year single‐center investigation
Authors: Lazzeri Chiara , Bonizzoli Manuela , Fulceri Giorgio Enzo , Guetti Cristiana , Ghinolfi Davide , Li Marzi Vincenzo , Migliaccio Maria Luisa , Peris Adriano
Published: May 2020

Background

Effectiveness of uncontrolled donation after circulatory death (uDCD) has been recently reported to be 75% according to data coming from some European countries in 2016, but few data are to date available on this topic.

Methods

We assessed the utilization rate (as the percentage of donors who were converted into actual donors) in 37 uDCDs consecutively enrolled at our Center (Careggi Teaching Hospital) from June 2016 to June 2019.

Results

In three cases, the family did not give consent for donation (3/37, 8.1%). Among the 37 potential uDCDs, 22 became actual donors (22/37, 59%), with 10 livers and 38 kidneys being transplanted, respectively. Fifteen livers were recovered (15/37, 68%), and 10 livers were transplanted (10/15, 67%). Forty‐two kidneys were procured and 38 organs transplanted. The overall effectiveness was 78%.

Conclusions

According to our 3‐year experience, uncontrolled DCDs do represent an additional means of increasing the number of transplanted organs (kidneys and livers) with an acceptable utilization rate. Research on organ viability assessment (for both livers and kidneys from uDCDs) is still in its infancy, and there is probably space for a further wider use of organs from uDCDs.