bluuebunny/crossref_metadata_2025 huggingface dataset:
Neutralizing antibody responses to an HIV envelope glycan hole are not easily broadened
Authors: Yang Yuhe R. , McCoy Laura E. , van Gils Marit J. , Andrabi Raiees , Turner Hannah L. , Yuan Meng , Cottrell Christopher A. , Ozorowski Gabriel , Voss James , Pauthner Matthias , Polveroni Thomas M. , Messmer Terrence , Wilson Ian A. , Sanders Rogier W. , Burton Dennis R. , Ward Andrew B.
Published: November 2019

Extensive studies with subtype A BG505-derived HIV envelope glycoprotein (Env) SOSIP immunogens have revealed that the dominant autologous neutralizing site in rabbits is located in an exposed region of the heavily glycosylated trimer that lacks potential N-linked glycosylation sites at positions 230, 241, and 289. The Env derived from B41, a subtype B virus, shares a glycan hole centered on positions 230 and 289. BG505 and B41 SOSIP immunogens were combined to test whether immunization in rabbits could induce broader Tier 2 neutralizing responses to the common glycan hole shared between BG505 and B41. Here we isolated autologous neutralizing antibodies (nAbs) that were induced by immunization with B41 SOSIP alone, as well as B41 and BG505 co-immunization, and describe their structure in complex with the B41 SOSIP trimer. Our data suggest that distinct autologous nAb lineages are induced by BG505 and B41 immunogens, even when both immunogens were administered together. In contrast to previously described BG505 glycan hole antibodies, the B41-specific nAbs accommodate the highly conserved N241 glycan (>97% conserved), which is present in B41. Single particle cryo-electron microscopy (cryoEM) studies confirmed that B41 and BG505-specific nAbs bind to overlapping glycan hole epitopes. In an attempt to broaden the reactivity of a B41-specific nAb, mutations in the BG505 glycan hole epitope guided by our high-resolution data only recovered partial binding. Overall, designing prime-boost immunogens to increase the breath of nAb responses directed at glycan holes epitopes remains challenging even when the typically immunodominant glycan holes despite overlap with different Envs.

IMPORTANCE

A glycan hole is one of the most dominant autologous neutralizing epitopes targeted on BG505 and B41 SOSIP trimer immunized rabbits. Our high-resolution cryoEM studies of B41 in complex with a B41-specific antibody complex elucidate the molecular basis of this strain-specific glycan hole response. We conclude that eliciting cross-reactive responses to this region would likely require hybrid immunogens that bridge between BG505 and B41.
Aggressive Periodontitis with Neutropenia Caused byMMD2Mutation
Authors: Mizuno Noriyoshi , Morino Hiroyuki , Mihara Keichiro , Iwata Tomoyuki , Ohno Yoshinori , Matsuda Shinji , Ouhara Kazuhisa , Kajiya Mikihito , Suzuki-Takedachi Kyoko , Sotomaru Yusuke , Takeda Katsuhiro , Sasaki Shinya , Okanobu Ai , Sakuma Tetsushi , Yamamoto Takashi , Matsuda Yukiko , Ohsawa Ryousuke , Fujita Tsuyoshi , Shiba Hideki , Kawakami Hideshi , Kurihara Hidemi
Published: November 2019

Aggressive periodontitis causes rapid periodontal tissue destruction and is a disease that occurs at a young age and runs in the patient’s family. Here, we revealed a heterozygous A116V missense mutation in the gene encoding monocyte to macrophage differentiation associated 2 (MMD2) protein in a Japanese family with aggressive periodontitis and neutropenia. Analyses of patients’ peripheral blood revealed a low number of neutrophils but abundant quantity of CD34+hematopoietic stem and progenitor cells (HSPCs). Moreover, mutantMmd2mice showed severe alveolar bone loss and neutropenia. In patients and mutantMmd2mice, differentiation of HSPCs into granulocytes was also impeded, and their granulocytes were functionally impaired. Taken together, A116V mutation inMMD2gene induced mild neutropenia and slightly limited the immune defense response. Our studies suggested that aggressive periodontitis in association with A116VMMD2mutation constitutes a new immune system defect that belongs to the same spectrum of severe congenital neutropenia.
Identification of Potential Dual-Targets Anti-Toxoplasma gondii Compounds Through Structure-Based Virtual Screening and In-Vitro Studies
Authors: Salin Nurul Hanim , Noordin Rahmah , Najjar Belal Omar Al , Kamarulzaman Ezatul Ezleen , Yunus Muhammad Hafiznur , Karim Izzati Zahidah Abdul , Nasim Nurul Nadieya Mohd , Zakaria Iffah Izzati , Wahab Habibah A.
Published: November 2019

Toxoplasma gondiiis the etiologic agent of toxoplasmosis, a disease which can lead to morbidity and mortality of the fetus and immunocompromised individuals. Due to the limited effectiveness or side effects of existing drugs, the search for better drug can didates is still ongoing. In this study, we performed structure-based screening of potential dual-targets inhibitors of active sites ofT. gondiidrug targets such as uracil phosphoribosyltransferase (UPRTase) and adenosine kinase (AK). First screening of virtual compounds from the National Cancer Institute (NCI) was performedviamolecular docking. Subsequently, the hit compounds were testedin-vitrofor anti-T. gondiieffect using cell viability assay with Vero cells as host to determine cytotoxicity effects and drug selectivities. Clindamycin, as positive control, showed a selectivity index (SI) of 10.9, thus compounds with SI > 10.9 specifically targetT. gondiiproliferation with no significant effect on the host cells. Good anti-T. gondiieffects were observed with NSC77468 (7-ethoxy-4-methyl-6,7-dihydro-5H-thiopyrano[2,3-d] pyrimidin-2-amine) which showed SI values of 25. This study showed thatin-silicoselection can serve as an effective way to discover potentially potent and selective compounds againstT. gondii.
The complete mitochondrial genome of endangered Assam Roofed Turtle,Pangshura sylhetensis(Testudines: Geoemydidae): Genomic features and Phylogeny
Authors: Kundu Shantanu , Kumar Vikas , Tyagi Kaomud , Chandra Kailash
Published: November 2019

Assam Roofed Turtle,Pangshura sylhetensisis an endangered and least studied species endemic to India and Bangladesh. The genomic feature ofP. sylhetensismitogenome is still anonymous to the scientific community. The present study decodes the first complete mitochondrial genome ofP. sylhetensis(16,568 bp) by using next-generation sequencing. Thisde novoassembly encodes 13 Protein-coding genes (PCGs), 22 transfer RNAs (tRNAs), two ribosomal RNAs (rRNAs), and one control region (CR). Most of the genes were encoded on the majority strand, except NADH dehydrogenase subunit 6 (nad6) and eight tRNAs. Most of the PCGs were started with an ATG initiation codon, except for Cytochrome oxidase subunit 1 (cox1) and NADH dehydrogenase subunit 5 (nad5) with GTG. The study also found the typical cloverleaf secondary structure in most of the tRNA genes, except for serine (trnS1) with lack of conventional DHU arm and loop. Both, Bayesian and Maximum-likelihood topologies showed distinct clustering of all the Testudines species with their respective taxonomic ranks and congruent with the previous phylogenetic hypotheses (PangshuraandBatagursister taxa). Nevertheless, the mitogenomic phylogeny with other amniotes corroborated the sister relationship of Testudines with Archosaurians (Birds and Crocodilians). Additionally, the mitochondrial Gene Order (GO) analysis indicated that, most of the Testudines species showed plesiomorphy with typical vertebrate GO.
Inference of Population Genetic Structure and High Linkage Disequilibrium AmongAlternariaspp. Collected from Tomato and Potato Using Genotyping by Sequencing
Authors: Adhikari Tika B. , Knaus Brian J. , Grünwald Niklaus J. , Halterman Dennis , Louws Frank J.
Published: November 2019

Genotyping by sequencing (GBS) is considered a powerful tool to discover single nucleotide polymorphisms (SNPs), which are useful to characterize closely related genomes of plant species and plant pathogens. We applied GBS to determine genome-wide variations in a panel of 187 isolates of three closely relatedAlternariaspp. that cause diseases on tomato and potato in North Carolina (NC) and Wisconsin (WI). To compare genetic variations, reads were mapped to bothA. alternataandA. solanidraft reference genomes and detected dramatic differences in SNPs among them. Comparison ofA. linariaeandA. solanipopulations by principal component analysis revealed the first (83.8% of variation) and second (8.0% of variation) components containedA. linariaefrom tomato in NC andA. solanifrom potato in WI, respectively, providing evidence of population structure. Genetic differentiation (Hedrick’s G’ST) inA. linariaepopulations from Haywood, Macon, and Madison counties in NC were little or no differentiated (G’ST0.0 - 0.2). However,A. linariaepopulation from Swain county appeared to be highly differentiated (G’ST> 0.8). To measure the strength of the linkage disequilibrium (LD), we also calculated the allelic association between pairs of loci. Lewontin’sD(measures the fraction of allelic variations) and physical distances provided evidence of linkage throughout the entire genome, consistent with the hypothesis of non-random association of alleles among loci. Our findings provide new insights into the understanding of clonal populations on a genome-wide scale and microevolutionary factors that might play an important role in population structure. Although we found limited genetic diversity, the threeAlternariaspp. studied here are genetically distinct and each species is preferentially associated with one host.
Kinetic foundation of the zero-inflated negative binomial model for single-cell RNA sequencing data
Authors: Jia Chen
Published: November 2019

Single-cell RNA sequencing data have complex features such as dropout events, over-dispersion, and high-magnitude outliers, resulting in complicated probability distributions of mRNA abundances that are statistically characterized in terms of a zero-inflated negative binomial (ZINB) model. Here we provide a mesoscopic kinetic foundation of the widely used ZINB model based on the biochemical reaction kinetics underlying transcription. Using multiscale modeling and simplification techniques, we show that the ZINB distribution of mRNA abundance and the phenomenon of transcriptional bursting naturally emerge from a three-state stochastic transcription model. We further reveal a nontrivial quantitative relation between dropout events and transcriptional bursting, which provides novel insights into how and to what extent the burst size and burst frequency could reduce the dropout rate. Three different biophysical origins of over-dispersion are also clarified at the single-cell level.
Chromatin organization in early land plants reveals an ancestral association between H3K27me3, transposons, and constitutive heterochromatin
Authors: Montgomery Sean A. , Tanizawa Yasuhiro , Galik Bence , Wang Nan , Ito Tasuku , Mochizuki Takako , Akimcheva Svetlana , Bowman John , Cognat Valérie , Drouard Laurence , Ekker Heinz , Houng Syuan-Fei , Kohchi Takayuki , Lin Shih-Shun , Liu Li-Yu Daisy , Nakamura Yasukazu , Valeeva Lia R. , Shakirov Eugene V. , Shippen Dorothy E. , Wei Wei-Lun , Yagura Masaru , Yamaoka Shohei , Yamato Katsuyuki T. , Liu Chang , Berger Frédéric
Published: November 2019

Genome packaging by nucleosomes is a hallmark of eukaryotes. Histones and the pathways that deposit, remove, and read histone modifications are deeply conserved. Yet, we lack information regarding chromatin landscapes in extant representatives of ancestors of the main groups of eukaryotes and our knowledge of the evolution of chromatin related processes is limited. We used the bryophyte Marchantia polymorpha, which diverged from vascular plants 400 Mya, to obtain a whole chromosome genome assembly and explore the chromatin landscape and three-dimensional organization of the genome of early land plants. Based on genomic profiles of ten chromatin marks, we conclude that the relationship between active marks and gene expression is conserved across land plants. In contrast, we observed distinctive features of transposons and repeats in Marchantia compared with flowering plants. Silenced transposons and repeats did not accumulate around centromeres, and a significant proportion of transposons were marked by H3K27me3, which is otherwise dedicated to the transcriptional repression of protein coding genes in flowering plants. Chromatin compartmentalization analyses of Hi-C data revealed that chromatin regions belonging to repressed heterochromatin were densely decorated with H3K27me3 but not H3K9 or DNA methylation as reported in flowering plants. We conclude that in early plants, H3K27me3 played an essential role in heterochromatin function, suggesting an ancestral role of this mark in transposon silencing.
IL-17A both initiates (via IFNγ suppression) and limits the pulmonary type-2 immune response to nematode infection
Authors: Ajendra Jesuthas , Chenery Alistair L. , Parkinson James E. , Chan Brian H. K. , Pearson Stella , Colombo Stefano A. P. , Boon Louis , Grencis Richard K. , Sutherland Tara E. , Allen Judith E.
Published: November 2019

Nippostrongylus brasiliensisis a well-defined model of type-2 immunity but the early lung-migrating phase is dominated by innate IL-17A production and neutrophilia. UsingN. brasiliensisinfection we confirm previous observations thatIl17a-KO mice exhibit an impaired type-2 immune response. Neutrophil depletion and reconstitution studies demonstrated that neutrophils contribute to the subsequent eosinophilia but are not responsible for the ability of IL-17A to promote type-2 cytokine responses. Transcriptional profiling of the lung on day 2 ofN. brasiliensisinfection revealed an increasedIfnγsignature in theIl17a-KO mice confirmed by enhanced IFNγ protein production. Depletion of early IFNγ rescued type-2 immune responses in theIl17a-KO mice demonstrating that IL-17A-mediated suppression of IFNγ promotes type-2 immunity. Notably, when IL-17A was blocked later in infection, the type-2 response increased. IL-17A regulation of type-2 immunity was lung-specific and infection withTrichuris muris,revealed that IL-17A promotes a type-2 immune response in the lung even when a parasite lifecycle is restricted to the intestine. Together our data reveal IL-17A as a major regulator of pulmonary type-2 immunity which supports the development of a protective type-2 immune response but subsequently limits the magnitude of that response.
MapGL: Inferring evolutionary gain and loss of short genomic sequence features by phylogenetic maximum parsimony
Authors: Diehl Adam G , Boyle Alan P
Published: November 2019

Comparative genomics studies are growing in number partly because of their unique ability to provide insight into shared and divergent biology between species. Of particular interest is the use of phylogenetic methods to infer the evolutionary history of cis-regulatory sequence features, which contribute strongly to phenotypic divergence and are frequently gained and lost in eutherian genomes. Understanding the mechanisms by which cis-regulatory element turnover generate emergent phenotypes is crucial to our understanding of adaptive evolution. Ancestral reconstruction methods can place species-specific cis-regulatory features in their evolutionary context, thus increasing our understanding of the process of regulatory sequence turnover. However, applying these methods to gain and loss of cis-regulatory features currently requires complex workflows which represent a potential barrier to widespread adoption by a broad scientific community. MapGL simplifies phylogenetic inference of the evolutionary history of short genomic sequence features by combining the necessary steps into a single piece of software with a simple set of inputs and outputs.
Biofilm rupture by laser-induced stress waves increases with loading amplitude, independent of location
Authors: Kearns Kaitlyn L. , Boyd James D. , Grady Martha E.
Published: November 2019

Integral to the production of safe and biocompatible medical devices is to determine the interfacial properties that affect or control strong biofilm adhesion. The laser spallation technique has recently emerged as an advantageous method to quantify biofilm adhesion across candidate biomedical surfaces. However, there is a possibility that membrane tension is a factor that contributes to the stress required to separate biofilm and substrate. In that case, the stress amplitude, controlled by laser fluence, that initiates biofilm rupture would vary systematically with location on the biofilm. Film rupture, also known as spallation, occurs when film material is ejected during stress wave loading. In order to determine effects of membrane tension, we present a protocol that measures spall size with increasing laser fluence (variable fluence) and with respect to distance from the biofilm centroid (iso-fluence).Streptococcus mutansbiofilms on titanium substrates serves as our model system. A total of 185 biofilm loading locations are analyzed in this study. We demonstrate that biofilm spall size increases monotonically with laser fluence and apply our procedure to failure of non-biological films. In iso-fluence experiments, no correlation is found between biofilm spall size and loading location, thus providing evidence that membrane tension does not play a dominant role in biofilm adhesion measurements. We recommend our procedure as a straightforward method to determine membrane effects in the measurement of adhesion of biological films on substrate surfaces via the laser spallation technique.

Graphical Abstract
“Induction of pancreatic tumor-selective ferroptosis through modulation of cystine import”
Authors: Badgley Michael A. , Kremer Daniel , Maurer H. Carlo , DelGiorno Kathleen E. , Lee Ho-Joon , Purohit Vinee , Sagalovskiy Irina , Ma Alice , Kapillian Jonathan , Firl Christina E.M. , Decker Amanda R. , Sastra Steve A. , Palermo Carmine F. , Andrade Leonardo R. , Sajjakulnukit Peter , Zhang Li , Tolstyka Zachary P. , Hirschhorn Tal , Lamb Candice , Liu Tong , Gu Wei , Seeley E. Scott , Stone Everett , Georgiou George , Manor Uri , Iuga Alina , Wahl Geoffrey M. , Stockwell Brent R. , Lyssiotis Costas A. , Olive Kenneth P.
Published: November 2019

Pancreatic ductal adenocarcinoma (PDA) is the third-leading cause of cancer mortality in the US and is highly resistant to classical, targeted, and immune therapies. We show that human PDA cells are dependent on the provision of exogenous cystine to avert a catastrophic accumulation of lipid reactive oxygen species (ROS) that, left unchecked, leads to ferroptotic cell death, bothin vitroandin vivo. Using a dual-recombinase genetically engineered model, we found that acute deletion ofSlc7a11led to tumor-selective ferroptosis, tumor stabilizations/regressions, and extended overall survival. The mechanism of ferroptosis induction in PDA cells required the concerted depletion of both glutathione and coenzyme A, highlighting a novel branch of ferroptosis-relevant metabolism. Finally, we found that cystine depletionin vivousing the pre-IND agent cyst(e)inase phenocopiedSlc7a11deletion, inducing tumor-selective ferroptosis and disease stabilizations/regressions in the well-validated KPC model of PDA.

One Sentence Summary

Genetic and pharmacological targeting of cystine import induces pancreatic cancer-selective ferroptosisin vivo.
Divergent density feedback control of migratory predator recovery following sex-biased perturbations
Authors: Goto Daisuke , Hamel Martin J. , Pegg Mark A. , Hammen Jeremy J. , Rugg Matthew L. , Forbes Valery E.
Published: November 2019

Uncertainty in risks posed by emerging stressors such as synthetic hormones impedes conservation efforts for threatened vertebrate populations. Synthetic hormones often induce sex-biased perturbations in exposed animals by disrupting gonad development and early life-history stage transitions, potentially diminishing per capita reproductive output of depleted populations and, in turn, being manifest as Allee effects. We use a spatially-explicit biophysical model to evaluate how sex-biased perturbation in life history traits of individuals (maternal investment in egg production and male-skewed sex allocation in offspring) modulates density feedback control of year class strength and recovery trajectories of a long-lived, migratory fish–shovelnose sturgeon (Scaphirhynchus platorynchus)–under spatially and temporally dynamic synthetic androgen exposure and habitat conditions. Simulations show that reduced efficiency of maternal investment in gonad development prolonged maturation time, increased the probability of skipped spawning, and, in turn, gradually shrunk spawner abundance, weakening year class strength. However, positive density feedback quickly disappeared (no Allee effect) once the exposure ceased. By contrast, responses to the demographic perturbation manifested as strong positive density feedback; an abrupt shift in year class strength and spawner abundance followed after more than two decades owing to persistent negative population growth (a strong Allee effect), reaching an alternate state without any sign of recovery. When combined with the energetic perturbation, positive density feedback of the demographic perturbation was dampened as extended maturation time reduced the frequency of producing male-biased offspring, allowing the population to maintain positive growth rate (a weak Allee effect) and gradually recover. The emergent patterns in long-term population projections illustrate that sex-biased perturbation in life history traits of individuals can interactively regulate the strength of density feedback in depleted populations such asScaphirhynchussturgeon to further diminish reproductive capacity and abundance, posing increasingly greater conservation challenges in chemically altered riverscapes.
Heat stress induces ferroptosis in a photosynthetic prokaryote
Authors: Aguilera Anabella , Berdun Federico , Bartoli Carlos , Steelheart Charlotte , Alegre Matías , Salerno Graciela , Pagnussat Gabriela , Martin María Victoria
Published: November 2019

Ferroptosis is an oxidative iron-dependent form of cell death recently described in eukaryotic organisms like animals, plants and parasites. Here we report that a similar process takes place in the cyanobacteriumSynechocystissp. PCC 6803 in response to heat stress. After a heat shock,Synechocystiscells undergo a cell death pathway that can be suppressed by canonical ferroptosis inhibitors or by external addition of calcium, glutathione or ascorbic acid. Moreover, as described for eukaryotic cells ferroptosis, this pathway is characterized by an early depletion of antioxidants, and by lipid peroxidation. As in general prokaryotes membranes contain poorly oxidizable saturated or monounsaturated lipid molecules, it was thought that they were not susceptible to ferroptosis. Interestingly, cyanobacteria contain thylakoid membranes that are enriched in polyunsaturated-fatty-acid-containing phospholipids, which might explain their sensitivity to ferroptosis. These results indicate that all of the hallmarks described for eukaryotic ferroptosis are conserved in photosynthetic prokaryotes and suggest that ferroptosis might be an ancient cell death program.

Aguilera et al, show that ferroptosis, an oxidative and iron-dependent form of regulated cell death, plays an important role in the cyanobacteriumSynechocystissp. PCC 6803 in response to heat stress.
Chchd10 or Chchd2 are not Required for Human Motor Neuron Differentiation In Vitro but Modify Synaptic Transcriptomes
Authors: Harjuhaahto Sandra , Rasila Tiina S , Molchanova Svetlana M , Woldegebriel Rosa , Kvist Jouni , Konovalova Svetlana , Sainio Markus T , Pennonen Jana , Ibrahim Hazem , Otonkoski Timo , Taira Tomi , Ylikallio Emil , Tyynismaa Henna
Published: November 2019

Mitochondrial intermembrane space proteins CHCHD2 and CHCHD10 have roles in diseases affecting motor neurons such as amyotrophic lateral sclerosis, spinal muscular atrophy and axonal neuropathy and in Parkinson’s disease, and form a complex of unknown function. Here we address the importance of these two proteins in human motor neurons. We show that gene edited human induced pluripotent stem cells (iPSC) lacking either CHCHD2 or CHCHD10 are viable and can be differentiated into functional motor neurons that fire spontaneous and evoked action potentials. Knockout iPSC and motor neurons sustain mitochondrial ultrastructure and show reciprocal compensatory increases in CHCHD2 or CHCHD10. Knockout motor neurons have largely overlapping transcriptome profiles compared to isogenic control line, in particular for synaptic gene expression. Our results show that absence of CHCHD2 or CHCHD10 does not disrupt functionality, but induces similar modifications in human motor neurons. Thus pathogenic mechanisms may involve loss of synaptic function.
Inferring punctuated evolution in the learned songs of African sunbirds
Authors: McEntee Jay P. , Zhelezov Gleb , Werema Chacha , Najar Nadje , Peñalba Joshua V. , Mulungu Elia , Mbilinyi Maneno , Karimi Sylvester , Chumakova Lyubov , Burleigh J. Gordon , Bowie Rauri C.K.
Published: November 2019

Signals used in animal communication, especially those that are learned, are thought to be prone to rapid and/or regular evolution. It has been hypothesized that the evolution of song learning in birds has resulted in elevated diversification rates, as learned song may be subject to especially rapid evolution, and song is involved in mate choice. However, we know little about the evolutionary modes of learned song divergence over timescales relevant to speciation. Here we provide evidence that aspects of the territorial songs of Eastern Afromontane sky island sunbirdsCinnyrisevolve in a punctuated fashion, with periods of stasis, on the order of hundreds of thousands of years or more, broken up by strong evolutionary pulses. Stasis in learned songs is inconsistent with learned traits being subject to constant or frequent change, as would be expected if selection does not constrain song phenotypes, or if novel phenotypes are frequently advantageous. Learned song may instead follow a process resembling peak shifts on adaptive landscapes. While much research has focused on the potential for rapid evolution in bird song, our results suggest that selection can tightly constrain the evolution of learned songs over fairly long timescales. More broadly, these results demonstrate that some aspects of highly variable, plastic traits can exhibit punctuated evolution, with stasis over fairly long time periods.
Urbanization reshapes a food web
Authors: Start Denon , Barbour Matthew A. , Bonner Colin
Published: November 2019

Cities represent humanity's most intense impact on our planet, with more than half of all humans now residing in urban areas. Indeed, urbanization has well‐understood impacts on both individual species and general patterns of biodiversity. However, species do not exist in isolation, but are instead members of complex interaction networks that shape patterns of diversity and influence ecosystem services.

Despite the importance of species interaction for creating patterns of diversity, we do not understand how urbanization alters these interactions. Here, we investigate how an interaction network (food web) is reshaped by urbanization.

We show that, consistent with theory, cities tend to support less diverse ecological communities, and rare species that interact with few species are particularly sensitive to urbanization. As a result, remnant urban food webs tend to have more interactions per species and greater connectance, creating more integrated interaction networks.

We discuss the implications of this food web reshaping for ecological stability, eco‐evolutionary dynamics, and the joining of interaction networks and conservation planning. The role of cities in reshaping interaction networks provides an interesting study of food web (dis)assembly, while also shedding light on new approaches to applied conservation issues.
Spatial disturbance synchrony alters the association of food chain length and ecosystem size
Authors: Terui Akira , Nishijima Shota
Published: November 2019

The origin of variation in food chain length (FCL) has long been a central topic of ecology due to its influences on trophic control, energy flow and bioaccumulation of environmental contaminants. The positive association of FCL and ecosystem size has been consistently supported in natural systems. Recent studies, however, have begun to report no effects of ecosystem size on FCL. The emerging inconsistency among previous studies implies the existence of overlooked factors that can modulate the relationship between FCL and ecosystem size. Here, we developed a mathematical model describing metacommunity dynamics to show that large ecosystems do not necessarily support long food chains in the presence of spatially correlated disturbance. Our simple model predicted that the effect of ecosystem size was strongly dependent on the spatial extent of disturbance synchrony. When the spatial correlation of disturbance was weak, the positive association between FCL and ecosystem size appeared. However, the relationship of FCL and ecosystem size became more complex, including hump‐shaped and multimodal forms, as the spatial extent of disturbance synchrony increases. This pattern emerged because larger ecosystems have wider aerial coverage, so more chances exist that an episodic disturbance hits some of the habitat patches and spreads across the landscape. Our finding highlights the important role of spatial disturbance synchrony in driving FCL, providing insights into why ecosystem size effects are variable across systems.
‘Every single minute and hour is scrutinised’: neoliberalism and Australian private mental health care
Authors: Dawson Lisa , River Jo , McCloughen Andrea , Buus Niels
Published: November 2019

There is little understanding of how recovery‐oriented approaches fit within contemporary mental healthcare systems, which emphasise biomedical approaches to care, increased efficiency and cost‐cutting. This article examines the established models of service delivery in a private, youth, mental health service and the impacts of the current system on staff. It explores whether the service is prepared or capable of adopting recovery‐oriented approaches to care. Qualitative interviews were undertaken with staff and thematically analysed to understand the everyday practices on the unit. Data suggest that economic efficiencies and biomedical dominance largely shaped how health care was organised and delivered, which was perceived by staff as inflexible to change. Additionally, findings suggest that market‐oriented principles associated with neoliberalism restricted the capacity of individuals to transform services in line with alternative models of care and lowered staff morale. These finding suggest that, while neoliberal ideologies and biomedical approaches remain dominant in organisations, there will be challenges to adopting alternative recovery‐oriented models of care and promoting healthcare systems that understand mental health issues in broader socio‐political contexts and can flexibly respond to the needs of service users.
Development of the FAST‐M maternal sepsis bundle for use in low‐resource settings: a modified Delphi process
Authors: Lissauer D , Cheshire J , Dunlop C , Taki F , Wilson A , Smith JM , Daniels R , Kissoon N , Malata A , Chirwa T , Lwesha VM , Mhango C , Mhango E , Makwenda C , Banda L , Munthali L , Nambiar B , Hussein J , Williams HM , Devall AJ , Gallos I , Merriel A , Bonet M , Souza JP , Coomarasamy A
Published: November 2019

Objective

To develop a sepsis care bundle for the initial management of maternal sepsis in low resource settings.

Design

Modified Delphi process.

Setting

Participants from 34 countries.

Population

Healthcare practitioners working in low resource settings (n = 143; 34 countries), members of an expert panel (n = 11) and consultation with the World Health Organization Global Maternal and Neonatal Sepsis Initiative technical working group.

Methods

We reviewed the literature to identify all potential interventions and practices around the initial management of sepsis that could be bundled together. A modified Delphi process, using an online questionnaire and in‐person meetings, was then undertaken to gain consensus on bundle items. Participants ranked potential bundle items in terms of perceived importance and feasibility, considering their use in both hospitals and health centres. Findings from the healthcare practitioners were then triangulated with those of the experts.

Main outcome measure

Consensus on bundle items.

Results

Consensus was reached after three consultation rounds, with the same items deemed most important and feasible by both the healthcare practitioners and expert panel. Final bundle items selected were: (1) Fluids, (2) Antibiotics, (3) Source identification and control, (4) Transfer (to appropriate higher‐level care) and (5) Monitoring (of both mother and neonate as appropriate). The bundle was given the acronym ‘FAST‐M’.

Conclusion

A clinically relevant maternal sepsis bundle for low resource settings has been developed by international consensus.

Tweetable abstract

A maternal sepsis bundle for low resource settings has been developed by international consensus.
Deleterious effects of electron beam irradiation on development and reproduction of tomato/potato psyllids, Bactericera cockerelli
Authors: Lei Jiaxin , Meng Jia , Chen Ivy W. , Cheng Weining , Beam Andrea L. , Islam Md‐Sajedul , Bailey Woodward D. , Pillai Suresh , Zhu‐Salzman Keyan
Published: November 2019

The potato/tomato psyllid Bactericera cockerelli causes serious damage to several solanaceous crops by direct feeding and vectoring Candidatus Liberibacter solanacearum, a bacterial pathogen. Electron beam (eBeam) irradiation is an environmentally friendly, chemical‐free alternative method that is increasing in use for disinfestation of insect pests. We hypothesize that this irradiation technology will have detrimental effects on potato psyllid and thus impede its disease vectoring. To this end, we explored the effects of eBeam treatment ranging from 50 to 500 Gy on survival, development and reproduction of this pest. Impact on psyllids was apparently dose‐dependent. When irradiated at 350 Gy, eggs could not hatch, 1st instar nymphs failed to emerge, and although a small portion of irradiated 5th instar nymphs survived, the emerged adults were mostly deformed. Abnormality in eclosed adults suggests harmful effects of eBeam on metamorphosis. Reproduction was seriously impaired when female psyllids were exposed to eBeam at the 5th instar nymphal or young adult stage, presumably due to inability to form oocytes. In addition, reciprocal crosses between irradiated and untreated psyllids indicated that female psyllids were more radiosensitive than males to eBeam. Taken together, these findings indicate that eBeam negatively impacted potato psyllid development and reproduction, which would inevitably compromise its disease transmission capacity. A dose of 350 Gy can be considered as a reference dose for effective control of potato psyllids.
Inferring competitive outcomes, ranks and intransitivity from empirical data: A comparison of different methods
Authors: Feng Yanhao , Soliveres Santiago , Allan Eric , Rosenbaum Benjamin , Wagg Cameron , Tabi Andrea , De Luca Enrica , Eisenhauer Nico , Schmid Bernhard , Weigelt Alexandra , Weisser Wolfgang W. , Roscher Christiane , Fischer Markus
Published: November 2019

The inference of pairwise competitive outcomes (PCO) and multispecies competitive ranks and intransitivity from empirical data is essential to evaluate how competition shapes plant communities. Three categories of methods, differing in theoretical background and data requirements, have been used: (a) theoretically sound coexistence theory‐based methods, (b) index‐based methods, and (c) ‘process‐from‐pattern’ methods. However, how they are related is largely unknown.

In this study, we explored the relations between the three categories by explicitly comparing three representatives of them: (a) relative fitness difference (RFD), (b) relative yield (RY), and (c) a reverse‐engineering approach (RE). Specifically, we first conducted theoretical analyses with Lotka–Volterra competition models to explore their theoretical linkages. Second, we used data from a long‐term field experiment and a short‐term greenhouse experiment with eight herbaceous perennials to validate the theoretical findings.

The theoretical analyses showed that RY or RE applied with equilibrium data indicated equivalent, or very similar, PCO respectively to RFD, but these relations became weaker or absent with data further from equilibrium. In line with this, both RY and RE converged with RFD in indicating PCO over time in the field experiment as the communities became closer to equilibrium. Moreover, the greenhouse PCO (far from equilibrium) were only similar to the field PCO of earlier rather than later years. Intransitivity was more challenging to infer because it could be reshuffled by even a small competitive shift among similar competitors. For example, the field intransitivity inferred by three methods differed greatly: no intransitivity was detected with RFD; intransitivity detected with RY and RE was poorly correlated, changed substantially over time (even after equilibrium) and failed to explain coexistence.

Our findings greatly help the comparison and generalization of studies using different methods. For future studies, if equilibrium data are available, one can infer PCO and multispecies competitive ranks with RY or RE. If not, one should apply RFD with density gradient or time‐series data. Equilibria could be evaluated with T tests or standard deviations. To reliably infer intransitivity, one needs high quality data for a given method to first accurately infer PCO, especially among similar competitors.
Machine learning algorithms to infer trait‐matching and predict species interactions in ecological networks
Authors: Pichler Maximilian , Boreux Virginie , Klein Alexandra‐Maria , Schleuning Matthias , Hartig Florian
Published: November 2019

Ecologists have long suspected that species are more likely to interact if their traits match in a particular way. For example, a pollination interaction may be more likely if the proportions of a bee's tongue fit a plant's flower shape. Empirical estimates of the importance of trait‐matching for determining species interactions, however, vary significantly among different types of ecological networks.

Here, we show that ambiguity among empirical trait‐matching studies may have arisen at least in parts from using overly simple statistical models. Using simulated and real data, we contrast conventional generalized linear models (GLM) with more flexible Machine Learning (ML) models (Random Forest, Boosted Regression Trees, Deep Neural Networks, Convolutional Neural Networks, Support Vector Machines, naïve Bayes, and k‐Nearest‐Neighbor), testing their ability to predict species interactions based on traits, and infer trait combinations causally responsible for species interactions.

We found that the best ML models can successfully predict species interactions in plant–pollinator networks, outperforming GLMs by a substantial margin. Our results also demonstrate that ML models can better identify the causally responsible trait‐matching combinations than GLMs. In two case studies, the best ML models successfully predicted species interactions in a global plant–pollinator database and inferred ecologically plausible trait‐matching rules for a plant–hummingbird network from Costa Rica, without any prior assumptions about the system.

We conclude that flexible ML models offer many advantages over traditional regression models for understanding interaction networks. We anticipate that these results extrapolate to other ecological network types. More generally, our results highlight the potential of machine learning and artificial intelligence for inference in ecology, beyond standard tasks such as image or pattern recognition.
Maternal plasma proteomics in a rat model of pregnancy complications reveals immune and pro‐coagulant gene pathway activation
Authors: Sanchez Tino W. , Li Bo , Molinaro Christine , Casiano Carlos A. , Bellinger Denise L. , Mata‐Greenwood Eugenia
Published: November 2019

Problem

The Brown Norway (BN) rat is a model of T‐helper 2 immune diseases, and also a model of pregnancy disorders that include placental insufficiency, fetal loss, and pre‐eclampsia‐like symptoms. The aim of this study was to investigate the plasma proteomic/cytokine profile of pregnant BN rats in comparison to that of the Lewis (LEW) rat strain.

Method of study

Plasma proteomics differences were studied at day 13 of pregnancy in pooled plasma samples by differential in‐gel electrophoresis, and protein identification was performed by mass spectrometry. Key protein findings and predicted cytokine differences were validated by ELISA using plasma from rats at various pregnancy stages. Proteomics data were used for ingenuity pathway analysis (IPA).

Results

In‐gel analysis revealed 74 proteins with differential expression between BN and LEW pregnant dams. ELISA studies confirmed increased maternal plasma levels of complement 4, prothrombin, and C‐reactive protein in BN compared to LEW pregnancies. LEW pregnancies showed higher maternal plasma levels of transthyretin and haptoglobin than BN pregnancies. Ingenuity pathway analysis revealed that BN pregnancies are characterized by activation of pro‐coagulant, reactive oxygen species, and immune‐mediated chronic inflammation pathways, and suggested increased interleukin 6 and decreased transforming growth factor‐β1 as potential upstream events. Plasma cytokine analysis revealed that pregnant BN dams have a switch from anti‐ to pro‐inflammatory cytokines with the opposite switch observed in pregnant LEW dams.

Conclusion

Brown Norway rats show a maternal pro‐inflammatory response to pregnancy that likely contributes to the reproductive outcomes observed in this rat strain.
Ontogenetic pattern, morphological sexual and side dimorphism in the saccular otolith of a scaleless killifish Aphanius furcatus (Teleostei: Aphaniidae)
Authors: Motamedi Mina , Teimori Azad , Iranmanesh Atefeh
Published: November 2019

The relationships between ontogenetic and sexual factors with otolith morphology are poorly studied in killifish genus Aphanius Nardo, 1827. We studied the ontogeny, morphological sexual and side dimorphism in the saccular otolith of a scaleless killifish Aphanius furcatus inhabiting a high‐salinity environment in Southern Iran. The results highlighted growth‐dependent variability in the otolith of A. furcatus, which might be useful to define its certain developmental stages. We underlined those characters that were consistent during fish development, which could be valuable to identify the species. Considering the ontogenetic pattern of otolith in A. furcatus, it was found that the otoliths of young individuals have largely been influenced by sexes and that it was reduced during the fish development. Morphological side dimorphism in the otolith of A. furcatus tends to be increased during fish development. The outcomes of this study are essential since they have provided new information on ontogenetic changes and the sexual and side dimorphism of Aphanius otolith.
Immunolabelling for RhoV and actin in early regenerating tail of the lizard Podarcis muralis suggests involvement in epithelial and mesenchymal cell motility
Authors: Alibardi Lorenzo , Borsetti Francesca
Published: November 2019

Immunolabelling for RhoV and actin in early regenerating tail of the lizard Podarcis muralis suggests involvement in epithelial and mesenchymal cell motility. Acta Zoologica, Stockolm. Immunolabelling for RhoV and α‐smooth muscle actin, genes that are highly expressed in the regenerating tail of lizards, shows that a main protein band immunolabelled for RhoV is seen at 65–70 kDa and only a weak band at 22–24 kDa. This suggests that alteration occurred during extraction or is due to biochemical processing of the protein. RhoV immunolabelled cells are present in apical and proximal regenerating epidermis during scale neogenesis. The apical ependyma is labelled but labelling fades and disappears in medial‐proximal regions, near the original spinal cord. Differentiating muscles and cartilage show low labelling. Ultrastructural immunolocalization of RhoV in wound keratinocytes shows labelling in regions containing actin filaments that associate with tonofilaments and desmosomes while a low labelling is present in mesenchymal cells. Filamentous regions of the nucleus, nuclear membrane and the nucleolus are immune‐labelled for RhoV. Similar localization is seen for actin that is present along the perimeters of keratinocytes associated with tonofilaments, in elongations of mesenchymal cells, in muscle satellite cells, endothelial and pericytes of blood vessels. It is suggested that RhoV and actin are associated in the dynamic cytoskeleton needed for the movements of epidermal and mesenchymal cells and in endothelial cells forming new blood vessels.
Immunological features of a lung cancer patient achieving an objective response with anti‐programmed death‐1 blockade therapy
Authors: Kamata Toshiko , Yoshida Shigetoshi , Takami Mariko , Ihara Fumie , Yoshizawa Hiroko , Toyoda Takahide , Takeshita Yuichiro , Nobuyama Seiichi , Kanetsuna Yukiko , Sato Tetsuo , Yoshino Ichiro , Motohashi Shinichiro
Published: November 2019

The role of immune checkpoint inhibitors in metastatic lung cancer has been established in recent years and the pretherapeutic profiles of the tumor microenvironment in responders have been increasingly reported. The role of salvage surgery and the immune profiles of the posttherapeutic specimens in patients achieving an objective response have rarely been studied. We report a case of metastatic lung cancer treated by anti‐programmed death‐1 Ab followed by surgical resection. The immune status of the tumor was assessed, showing germinal center formation, memory B cell infiltration, and a high frequency of interferon gamma ‐secreting T cells.
Women's preferences for communication with the cervical screening programme: A qualitative study
Authors: Ravindran Roshini , Cotton Seonaidh , Cruickshank Margaret
Published: November 2019

Background

In Scotland, invitations and results for cervical screening are sent by post. We ask the question: is this an effective means of communication in the 21st century? Consideration of other ways of communicating with women may help to increase acceptability of the cervical screening programme.

Objective

To explore perspectives of screening‐eligible women, regarding methods for communication of invitations and results from the cervical screening programme to improve acceptability.

Methods

A qualitative study design using semi‐structured face‐to‐face or telephone interviews with women aged 25‐65 years. Thirty interviews were directed using visual cues to generate discussion. Interviews were audio‐recorded and transcribed verbatim. Thematic analysis of the data was conducted using a Framework approach.

Results

The main advantage of the postal system is its perceived formality; however, its lack of speed was a concern. Advantages of e‐communication included speed and convenience; however, concerns such as lack of confidentiality and access were mentioned. Telephone communication was deemed impractical, while face‐to‐face communication was highly regarded. Furthermore, the majority of participants felt screening appointments set at a specific date and time may improve uptake. Overall, participants believed there is no universal solution regarding the issue of communication.

Conclusion

At present, the postal system may be an appropriate method for invitation and results for cervical screening; however, there may be greater scope for preference of communication to improve the acceptability of the screening programme to women.