bluuebunny/crossref_metadata_2025 huggingface dataset:
Pathologic Response to Pretransplant Locoregional Therapy is Predictive of Patient Outcome After Liver Transplantation for Hepatocellular Carcinoma
Authors: DiNorcia Joseph , Florman Sander S. , Haydel Brandy , Tabrizian Parissa , Ruiz Richard M. , Klintmalm Goran B. , Senguttuvan Srinath , Lee David D. , Taner C. Burcin , Verna Elizabeth C. , Halazun Karim J. , Hoteit Maarouf , Levine Matthew H. , Chapman William C. , Vachharajani Neeta , Aucejo Federico , Nguyen Mindie H. , Melcher Marc L. , Tevar Amit D. , Humar Abhinav , Mobley Constance , Ghobrial Mark , Nydam Trevor L. , Amundsen Beth , Markmann James F. , Berumen Jennifer , Hemming Alan W. , Langnas Alan N. , Carney Carol A. , Sudan Debra L. , Hong Johnny C. , Kim Joohyun , Zimmerman Michael A. , Rana Abbas , Kueht Michael L. , Jones Christopher M. , Fishbein Thomas M. , Markovic Daniela , Busuttil Ronald W. , Agopian Vatche G.
Published: March 2019

Objective:

The aim of the study was to determine the rate, predictors, and impact of complete pathologic response (cPR) to pretransplant locoregional therapy (LRT) in a large, multicenter cohort of hepatocellular carcinoma (HCC) patients undergoing liver transplantation (LT).

Background:

LRT is used to mitigate waitlist dropout for patients with HCC awaiting LT. Degree of tumor necrosis found on explant has been associated with recurrence and overall survival, but has not been evaluated in a large, multicenter study.

Methods:

Comparisons were made among patients receiving pre-LT LRT with (n = 802) and without (n = 2637) cPR from the United States Multicenter HCC Transplant Consortium (UMHTC), and multivariable predictors of cPR were identified using logistic regression.

Results:

Of 3439 patients, 802 (23%) had cPR on explant. Compared with patients without cPR, cPR patients were younger; had lower Model for End-stage Liver Disease (MELD) scores, AFP levels, and neutrophil–lymphocyte ratios (NLR); were more likely to have tumors within Milan criteria and fewer LRT treatments; and had significantly lower 1-, 3-, and 5-year incidence of post-LT recurrence (1.3%, 3.5%, and 5.2% vs 6.2%, 13.5%, and 16.4%; P < 0.001) and superior overall survival (92%, 84%, and 75% vs 90%, 78%, and 68%; P < 0.001). Multivariable predictors of cPR included age, sex, liver disease diagnosis, MELD, AFP, NLR, radiographic Milan status, and number of LRT treatments (C-statistic 0.67).

Conclusions:

For LT recipients with HCC receiving pretransplant LRT, achieving cPR portends significantly lower posttransplant recurrence and superior survival. Factors predicting cPR are identified, which may help prioritize patients and guide LRT strategies to optimize posttransplant cancer outcomes.
The First Report of Laparoscopic Pancreaticoduodenectomy for Primary Duodenal Carcinoma in a Patient With Situs Inversus Totalis: Report of a Rare Case
Authors: Guo Cheng-Xiang , Chen Wei , Yao Wei-Yun , Li Guo-Gang , Zhang Qi , Chen Yi-Wen , Pan Yao , Shen Yi-Nan , Liang Ting-Bo , Bai Xue-Li
Published: March 2019

Background:

Situs inversus (SI) is a rare congenital anomaly characterized by the transposition of thoracic and abdominal viscera. Laparoscopic pancreaticoduodenectomy (LPD) is increasingly used in patients with periampullar and pancreatic carcinomas. For patients with SI, LPD can be more complicated because of reversed anatomy and possible other associated anomalies that have not been expected before surgery.

Case Presentation:

A female patient with SI totalis presented with inappetence, vomiting, and weight loss for 2 months. Imaging modalities and angiography revealed a mass in the periampullary region without obvious vascular abnormalities. The mass was successfully resected via LPD based on an elaborate preoperative plan. The surgical pathology report demonstrated adenocarcinoma of the duodenal papilla. The patient has been followed up for 4 months and no tumor recurrence or long-term complications were observed.

Conclusion:

LPD is technically difficult but feasible in patients with SI.
Network modularity influences plant reproduction in a mosaic tropical agroecosystem
Authors: Saunders Manu E. , Rader Romina
Published: March 2019

Biodiversity influences ecosystem function, but there is limited understanding of the mechanisms that support this relationship across different land use types in mosaic agroecosystems. Network approaches can help to understand how community structure influences ecosystem function across landscapes; however, in ecology, network analyses have largely focused on species–species interactions. Here, we use bipartite network analysis in a novel way: to link pollinator communities to sites in a tropical agricultural landscape. We used sentinel plants ofBrassica rapato examine how the structure of the community network influences plant reproduction. Diptera was the most common order of flower visitors at every site. Syrphidae visits were the strongest contributor to the number of fertilized pods, while visits by Syrphidae, Hymenoptera and Lepidoptera had the strongest effect on the number of seeds per pod. Sentinel pots at forest sites were visited by more unique species (i.e. species with higherd′) than sites in other land uses, and dairy sites had more visitors that were common across the network. Participation coefficients, which indicate how connected a single node is across network modules, were strong predictors of ecosystem function: plant reproduction increased at sites with higher participation coefficients. Flower visitor taxa with higher participation coefficients also had the strongest effect on plant reproduction. Hymenoptera visits were the best predictor for participation coefficients but anAllograptasp. (Diptera: Syrphidae) was the most influential flower visitor species in the landscape network. A diverse insect community contributed to plant reproduction and connection among nodes in this system. Identifying the ‘keystone’ flower visitor species and sites that have a strong influence on network structure is a significant step forward to inform conservation priorities and decision-making in diverse agroecosystems.
Digging the optimum pit: antlions, spirals and spontaneous stratification
Authors: Franks Nigel R. , Worley Alan , Falkenberg Max , Sendova-Franks Ana B. , Christensen Kim
Published: March 2019

Most animal traps are constructed from self-secreted silk, so antlions are rare among trap builders because they use only materials found in the environment. We show how antlions exploit the properties of the substrate to produce very effective structures in the minimum amount of time. Our modelling demonstrates how antlions: (i) exploit self-stratification in granular media differentially to expose deleterious large grains at the bottom of the construction trench where they can be ejected preferentially, and (ii) minimize completion time by spiral rather than central digging. Both phenomena are confirmed by our experiments. Spiral digging saves time because it enables the antlion to eject material initially from the periphery of the pit where it is less likely to topple back into the centre. As a result, antlions can produce their pits—lined almost exclusively with small slippery grains to maximize powerful avalanches and hence prey capture—much more quickly than if they simply dig at the pit's centre. Our demonstration, for the first time to our knowledge, of an animal using self-stratification in granular media exemplifies the sophistication of extended phenotypes even if they are only formed from material found in the animal's environment.
Effect of Cytoplasmic Viscosity on Red Blood Cell Migration in Small Arteriole-level Confinements
Authors: Saadat Amir , Guido Christopher J. , Shaqfeh Eric S. G.
Published: March 2019

The dynamics of red blood cells in small arterioles are important as these dynamics affect many physiological processes such as hemostasis and thrombosis. However, studying red blood cell flows via computer simulations is challenging due to the complex shapes and the non-trivial viscosity contrast of a red blood cell. To date, little progress has been made studying small arteriole flows (20-40μm) with a hematocrit (red blood cell volume fraction) of 10-20% and a physiological viscosity contrast. In this work, we present the results of large-scale simulations that show how the channel size, viscosity contrast of the red blood cells, and hematocrit affect cell distributions and the cell-free layer in these systems. We utilize a massively-parallel immersed boundary code coupled to a finite volume solver to capture the particle resolved physics. We show that channel size qualitatively changes how the cells distribute in the channel. Our results also indicate that at a hematocrit of 10% that the viscosity contrast is not negligible when calculating the cell free layer thickness. We explain this result by comparing lift and collision trajectories of cells at different viscosity contrasts.
Evidence for the F200Y (TAC) mutation conferring benzimidazole resistance in a southern USA cattle population of Haemonchus placei spreading from a single emergence
Authors: Chaudhry Umer , Redman E. M. , Kaplan Ray , Yazwinski Thomas , Sargison Neil , Gilleard John S.
Published: March 2019

The benzimidazoles are one of the most important broad-spectrum anthelmintic drug classes for the control of parasitic nematodes of domestic animals and humans. They have been widely used in the livestock sector, particularly in small ruminants for over 40 years. This has resulted in the development and wide spread of resistance in small ruminant gastrointestinal nematode parasite species, including Haemonchus contortus. Recently, resistance to benzimidazole drugs has been reported in Haemonchus placei, but there is relatively little information on its prevalence. It is important to develop a molecular tools to identify resistance mutations in H. placei early in their development in order to understand the emergence and spread. Our previous study demonstrated the F200Y (TAC) mutation at their early stage in 6/9 H. placei populations derived from southern USA, albeit at low frequencies between 2 and 10%. The present study analysis the phylogenetics of the isotype-1 β-tubulin locus to suggest that F200Y (TAC) mutation has been spread from a single emergence in H. placei; likely by the anthroprogenic movement of ruminant livestock in southern USA. Population genetic data of H. placei using a panel of microsatellite markers revealed little genetic sub-structure, consistent with a high level of gene flow in this region. Overall, these results provide clear genetic evidence for the spread of F200Y (TAC) benzimidazoles resistance mutation to multiple different locations from a single emergence in H. placei.
Hierarchical representation of multi-step tasks in multiple-demand and default mode networks
Authors: Wen Tanya , Duncan John , Mitchell Daniel J
Published: March 2019

Task episodes consist of sequences of steps that are performed to achieve a goal. We used fMRI to examine neural representation of task identity, component items, and sequential position, focusing on two major cortical systems – the multiple-demand (MD) and default mode networks (DMN). Human participants (20 male, 22 female) learned six tasks each consisting of four steps. Inside the scanner, participants were cued which task to perform and then sequentially identified the target item of each step in the correct order. Univariate time-course analyses indicated that intra-episode progress was tracked by a tonically increasing global response, plus an increasing phasic step response specific to MD regions. Inter-episode boundaries evoked a widespread response at episode onset, plus a marked offset response specific to DMN regions. Representational similarity analysis was used to examine encoding of task identity and component steps. Both networks represented the content and position of individual steps, but the DMN preferentially represented task identity while the MD network preferentially represented step-level information. Thus, although both DMN and MD networks are sensitive to step-level and episode-level information in the context of hierarchical task performance, they exhibit dissociable profiles in terms of both temporal dynamics and representational content. The results suggest collaboration of multiple brain regions in control of multi-step behavior, with MD regions particularly involved in processing the detail of individual steps, and DMN adding representation of broad task context.

Significance Statement

Achieving one’s goals requires knowing what to do and when. Tasks are typically hierarchical, with smaller steps nested within overarching goals. For effective, flexible behavior, the brain must represent both levels. We contrast response time-courses and information content of two major cortical systems – the multiple-demand (MD) and default mode networks (DMN) – during multi-step task episodes. Both networks are sensitive to step-level and episode-level information, but with dissociable profiles. Intra-episode progress is tracked by tonically increasing global responses, plus MD-specific increasing phasic step responses. Inter-episode boundaries evoke widespread responses at episode onset, plus DMN-specific offset responses. Both networks encode content and position of individual steps, but the DMN and MD networks favor task identity and step-level information respectively.
Neuro-genetic plasticity ofCaenorhabditis elegansbehavioral thermal tolerance
Authors: Stegeman Gregory W. , Medina Denise , Cutter Asher D. , Ryu William S.
Published: March 2019

Background

Animal responses to thermal stimuli involve intricate contributions of genetics, neurobiology and physiology, with temperature variation providing a pervasive environmental factor for natural selection. Thermal behavior thus exemplifies a dynamic trait that requires non-trivial phenotypic summaries to appropriately capture the trait in response to a changing environment. To characterize the deterministic and plastic components of thermal responses, we developed a novel micro-droplet assay of nematode behavior that permits information-dense summaries of dynamic behavioral phenotypes as reaction norms in response to increasing temperature (thermal tolerance curves, TTC).

Results

We found thatC. elegansTTCs shift predictably with rearing conditions and developmental stage, with significant differences between distinct wildtype genetic backgrounds. Moreover, after screening TTCs for 58C. elegansgenetic mutant strains, we determined that genes affecting thermosensation, includingcmk-1andtax-4, potentially play important roles in the behavioral control of locomotion at high temperature, implicating neural decision-making in TTC shape rather than just generalized physiological limits. However, expression of the transient receptor potential ion channel TRPA-1 in the nervous system is not sufficient to rescue rearing-dependent plasticity in TTCs conferred by normal expression of this gene, indicating instead a role for intestinal signaling involving TRPA-1 in the adaptive plasticity of thermal performance.

Conclusions

These results implicate nervous system and non-nervous system contributions to behavior, in addition to basic cellular physiology, as key mediators of evolutionary responses to selection from temperature variation in nature.
Live-cell Imaging Analysis of Antimycin-Type Depsipeptides via Bioorthogonal Stimulated Raman Scattering Microscopy
Authors: Seidel Jeremy , Miao Yupeng , Porterfield William , Cai Wenlong , Zhu Xuejun , Kim Seong-Jong , Hu Fanghao , Bhattarai-Kline Santi , Min Wei , Zhang Wenjun
Published: March 2019

Small-molecule natural products have been an essential source of pharmaceuticals to treat human diseases, but very little is known about their behavior inside dynamic, living human cells. Here, we demonstrate the first structure-activity-distribution study of complex natural products, the anti-cancer antimycin-type depsipeptides, using the emerging bioorthogonal Stimulated Raman Scattering (SRS) Microscopy. Our results show that the intracellular enrichment and distribution of these compounds are driven by their potency and specific protein targets, as well as the lipophilic nature of compounds.
Improving the accuracy of single turnover active fluorometry (STAF) for the estimation of phytoplankton primary productivity (PhytoPP)
Authors: Boatman Tobias G. , Geider Richard J. , Oxborough Kevin
Published: March 2019

Photosystem II (PSII) photochemistry is the ultimate source of reducing power for phytoplankton primary productivity (PhytoPP). Single turnover active chlorophyll fluorometry (STAF) provides a non-intrusive method that has the potential to measure PhytoPP on much wider spatiotemporal scales than is possible with more direct methods such as 14C fixation and O2 evolved through water oxidation. Application of a STAF-derived absorption coefficient for PSII light-harvesting (aLHII) provides a method for estimating PSII photochemical flux on a unit volume basis (JVPII). Within this study, we assess potential errors in the calculation of JVPII arising from sources other than photochemically active PSII complexes (baseline fluorescence) and the package effect. Although our data show that such errors can be significant, we identify fluorescence-based correction procedures that can be used to minimize their impact. For baseline fluorescence, the correction incorporates an assumed consensus PSII photochemical efficiency for dark-adapted material. The error generated by the package effect can be minimized through the ratio of variable fluorescence measured within narrow wavebands centered at 730 nm, where the re-absorption of PSII fluorescence emission is minimal, and at 680 nm, where re-absorption of PSII fluorescence emission is maximal. We conclude that, with incorporation of these corrective steps, STAF can provide a reliable estimate of JVPII and, if used in conjunction with simultaneous satellite measurements of ocean color, could take us significantly closer to achieving the objective of obtaining reliable autonomous estimates of PhytoPP.
Immune and environment-driven gene expression during invasion: An eco-immunological application of RNA-Seq
Authors: Selechnik D , Richardson MF , Shine R , Brown GP , Rollins LA
Published: March 2019

Host-pathogen dynamics change rapidly during a biological invasion and are predicted to impose strong selection on immune function. The invader may experience an abrupt reduction in pathogen-mediated selection (‘enemy release’), thereby favoring decreased investment into ‘costly’ immune responses, and the extent of this reduction may depend on factors such as propagule size. Across plants and animals, there is mixed support for this prediction. Pathogens are not the only form of selection imposed on invaders; differences in abiotic environmental conditions between native and introduced ranges are also expected to drive rapid evolution. Here, we assess the expression patterns of immune and environmentally-associated genes in the cane toad (Rhinella marina) across its invasive Australian range. Transcripts encoding mediators of costly immune responses (inflammation, cytotoxicity) showed a curvilinear relationship with invasion history, with highest expression in toads from oldest and newest colonized areas. This pattern is surprising given theoretical expectations of density dynamics in invasive species, and may be because density influences both intraspecific competition and parasite transmission, generating conflicting effects on the strength of immune responses. Alternatively, this expression pattern may be the result of other evolutionary forces, such as spatial sorting and genetic drift, working simultaneously with natural selection. Our findings do not support predictions about immune function based on the enemy release hypothesis, and suggest instead that the effects of enemy release are difficult to isolate in wild populations. Additionally, expression patterns of genes underlying putatively environmentally-associated traits are consistent with previous genetic studies, providing further support that Australian cane toads have adapted to novel abiotic challenges.
Superlets: time-frequency super-resolution using wavelet sets
Authors: Moca Vasile V. , Nagy-Dăbâcan Adriana , Bârzan Harald , Mureşan Raul C.
Published: March 2019

Time-frequency analysis is ubiquitous in many fields of science. Due to the Heisenberg-Gabor uncertainty principle, a single measurement cannot estimate precisely the location of a finite oscillation in both time and frequency. Classical spectral estimators, like the short-time Fourier transform (STFT) or the continuous-wavelet transform (CWT) optimize either temporal or frequency resolution, or find a tradeoff that is suboptimal in both dimensions. Following concepts from optical super-resolution, we introduce a new spectral estimator enabling time-frequency super-resolution. Sets of wavelets with increasing bandwidth are combined geometrically in asuperletto maintain the good temporal resolution of wavelets and gain frequency resolution in the upper bands.Superletsoutperform the STFT, CWT, and other super-resolution methods on synthetic data and brain signals recorded in humans and rodents, resolving time-frequency details with unprecedented precision. Importantly,superletscan reveal transient oscillation events that are hidden in the averaged time-frequency spectrum by other methods.
Genetic architecture constrains exploitation of siderophore cooperation inBurkholderia cenocepacia
Authors: Sathe Santosh , Mathew Anugraha , Agnoli Kirsty , Eberl Leo , Kümmerli Rolf
Published: March 2019

Explaining how cooperation can persist in the presence of cheaters, exploiting the cooperative acts, is a challenge for evolutionary biology. While microbial systems have proved extremely useful to test evolutionary theory and identify mechanisms maintaining cooperation, our knowledge is often limited to insights gained from a few model organisms. Here, we introduce siderophore secretion by the bacteriumBurkholderia cenocepaciaas a novel study system. Using a combination of phenotypic and competition assays we found that ornibactin, the main siderophore used for iron scavenging in this species, is secreted into the media, can be shared as public good between cells, but cannot be exploited by ornibactin-defective mutants. Molecular analysis revealed that cheating is compromised because the ornibactin receptor gene and genes involved in ornibactin synthesis are co-expressed from the same operon, such that disruptive mutations in the upstream synthesis genes compromise receptor availability. To prove that it is the genetic architecture of the siderophore locus that prevents cheating, we broke the linked traits by expressing the ornibactin receptor from a plasmid, a measure that turned the ornibactin mutant into a functional cheater. A literature survey acrossBurkholderiaspecies suggests that the genetic linkage independently broke over evolutionary time scales in several lineages, indicating that cheating and countermeasures might be under selection. Altogether, our results highlight that expanding our repertoire of microbial study systems leads to new discoveries and reinforce the view that social interactions shape evolutionary dynamics in microbial communities.
Confidence reports in decision-making with multiple alternatives violate the Bayesian confidence hypothesis
Authors: Li Hsin-Hung , Ma Wei Ji
Published: March 2019

Decision confidence reflects our ability to evaluate the quality of decisions and guides subsequent behaviors. Experiments on confidence reports have almost exclusively focused on two-alternative decision-making. In this realm, the leading theory is that confidence reflects the probability that a decision is correct (the posterior probability of the chosen option). There is, however, another possibility, namely that people are less confident if thebest twooptions are closer to each other in posterior probability, regardless of how probable they are inabsoluteterms. This possibility has not previously been considered because in two-alternative decisions, it reduces to the leading theory. Here, we test this alternative theory in a three alternative visual categorization task. We found that confidence reports are best explained by the difference between the posterior probabilities of the best and the next-best options, rather than by the posterior probability of the chosen (best) option alone, or by the overall uncertainty (entropy) of the posterior distribution. Our results upend the leading notion of decision confidence and instead suggest that confidence reflects the observer’s subjective probability that they made the best possible decision.
Transcriptomics supports that pleuropodia of insect embryos function in degradation of the serosal cuticle to enable hatching
Authors: Konopová Barbora , Buchberger Elisa , Crisp Alastair
Published: March 2019

Pleuropodia are limb-derived vesicular organs that transiently appear on the first abdominal segment of embryos from the majority of insect “orders”. They are missing in the modelDrosophilaand little is known about them. Experiments carried out on orthopteran insects eighty years ago indicated that the pleuropodia secrete a “hatching enzyme” that at the end of embryogenesis digests the serosal cuticle to enable the larva to hatch. This hypothesis contradicts the view that insect cuticle is digested by enzymes produced by the tissue that deposited it. We studied the development of the pleuropodia in embryos of the locustSchistocerca gregaria(Orthoptera) using transmission electron microscopy. RNA-seq was applied to generate a comprehensive embryonic reference transcriptome that was used to study genome-wide gene expression of ten stages of pleuropodia development. We show that the mature and secretion releasing pleuropodia are primarily enriched in transcripts associated with transport functions. They express genes encoding enzymes capable of digesting cuticular protein and chitin. These include the potent cuticulo-lytic Chitinase 5, whose transcript rises just before hatching. The pleuropodia are also enriched in transcripts for immunity-related enzymes, including the Toll signaling pathway, melanization cascade and lysozymes. These data provide transcriptomic evidence that the pleuropodia of orthopterans produce the “hatching enzyme”, whose important component is the Chitinase 5. They also indicate that the organs facilitate epithelial immunity and may function in embryonic immune defense. Based on their gene expression the pleuropodia appear to be an essential part of insect physiology.
Characterization of genes and alleles involved in the control of flowering time in grapevine
Authors: Kamal Nadia , Ochßner Iris , Schwandner Anna , Viehöver Prisca , Hausmann Ludger , Töpfer Reinhard , Weisshaar Bernd , Holtgräwe Daniela
Published: March 2019

Grapevine (Vitis vinifera) is one of the most important perennial crop plants in worldwide. Understanding of developmental processes like flowering, which impact quality and quantity of yield in this species is therefore of high interest. This gets even more important when considering some of the expected consequences of climate change. Earlier bud burst and flowering, for example, may result in yield loss due to spring frost. Berry ripening under higher temperatures will impact wine quality. Knowledge of interactions between a genotype or allele combination and the environment can be used for the breeding of genotypes that are better adapted to new climatic conditions. To this end, we have generated a list of more than 500 candidate genes that may play a role in the timing of flowering. The grapevine genome was exploited for flowering time control gene homologs on the basis of functional data from model organisms likeA. thaliana. In a previous study, a mapping population derived from early flowering GF.GA-47-42 and late flowering ‘Villard Blanc’ was analyzed for flowering time QTLs. In a second step we have now established a workflow combining amplicon sequencing and bioinformatics to follow alleles of selected candidate genes in the F1individuals and the parental genotypes. Allele combinations of these genes in individuals of the mapping population were correlated with early or late flowering phenotypes. Specific allele combinations of flowering time candidate genes within and outside of the QTL regions for flowering time on chromosome 1, 4, 14, 17, and 18 were found to be associated with an early flowering phenotype. In addition, expression of many of the flowering candidate genes was analyzed over consecutive stages of bud and inflorescence development indicating functional roles of these genes in the flowering control network.
Dynamics of functional networks for syllable and word-level processing
Authors: Rimmele J.M. , Sun Y. , Michalareas G. , Ghitza O. , Poeppel D.
Published: March 2019

Speech comprehension requires the ability to temporally segment the acoustic input for higher-level linguistic analysis. Oscillation-based approaches suggest that low-frequency auditory cortex oscillations track syllable-sized acoustic information and therefore emphasize the relevance of syllabic-level processing for speech segmentation. Most linguistic approaches, however, focus on mapping from acoustic-phonemic representations to the lexical level. How syllabic processing interacts with higher levels of speech processing, beyond segmentation, including the anatomical and neurophysiological characteristics of the networks involved, is debated. Here we investigate the effects of lexical processing and the interactions with (acoustic) syllable processing by examining MEG data recorded in two experiments using a frequency-tagging paradigm. Participants listened to disyllabic words presented at a rate of 4 syllables/sec. Two conjectures were evaluated: (i) lexical processing of words activates a network that interacts with syllable processing; and (ii) syllable transitions contribute to word-level processing. We show that lexical content activated a left-lateralized frontal and superior and middle temporal network and increased the interaction between left middle temporal areas and auditory cortex (phase-phase coupling). Mere syllable-transition information, in contrast, activated a bilateral superior-, middle temporal and inferior frontal network and increased the interaction between those areas. Word and syllable processing interacted in superior and middle temporal areas (cross-frequency coupling), whereas syllable tracking (cerebro-acoustic coherence) decreased when word-level information was present. The data provide a new perspective on speech comprehension by demonstrating a contribution of an acoustic-syllabic to lexical processing route.

Significance statement

The comprehension of speech requires integrating information at multiple time scales, including phonemic, syllabic, and word scales. Typically, we think of decoding speech in the service of recognizing words as a process that maps from phonemic units to words. Recent neurophysiological evidence, however, has highlighted the relevance of syllable-sized chunks for segmenting speech. Is there more to recognizing spoken language? We provide neural evidence for brain network dynamics that support an interaction of lexical with syllable-level processing. We identify cortical networks that differ depending on whether lexical-semantic information versus low-level syllable-transition information is processed. Word- and syllable-level processing interact within MTG and STG. The data enrich our understanding of comprehension by implicating a mapping from syllabic to lexical representations.
Assays for monitoringToxoplasma gondiiinfectivity in the laboratory mouse
Authors: Wang Qiuling , David Sibley L.
Published: March 2019

Toxoplasmais a widespread parasite of animals including many rodents that are a natural part of the transmission cycle between cats, which serve as the definitive host. Although wild rodents, including house mice, are relatively resistant, laboratory mice are highly susceptible to infection. As such, laboratory mice and have been used to compare pathogenesis of natural variants, and to evaluate the contributions of both host and parasite genes to infection. Protocols are provided here for evaluating acute and chronic infection with different parasite strains in laboratory mice. These protocols should provide uniform standards for evaluating natural variants and attenuated mutants and for comparing outcomes across different studies and between different laboratories.
Population productivity of wedgefishes, guitarfishes, and banjo rays: inferring the potential for recovery
Authors: D’Alberto Brooke M. , Carlson John K. , Pardo Sebastián A. , Simpfendorfer Colin A.
Published: March 2019

Recent evidence of widespread and rapid declines of wedgefishes, guitarfishes, and banjo ray populations (Order Rhinopristiformes), driven by a high demand for their fins in Asian markets and the quality of their flesh, raises concern about their risk of over-exploitation and extinction. Using life history theory and incorporating uncertainty into a modified Euler-Lotka model, maximum intrinsic rates of population increase (rmax) were estimated for nine species from the four families of rhinopristiforms. Estimates of medianrmaxvaried from −0.04 to 0.60 year−1among the nine species, but generally increased with increasing maximum size. In comparison to 115 other species of chondrichthyans for whichrmaxvalues were available, the families Rhinidae and Glaucostegidae are relatively productive, while most species from Rhinobatidae and Trygonorrhinidae had relatively lowrmaxvalues. If the demand for their high value products can be addressed, then population recovery for this species is likely possible but will vary depending on the species.
Profiling Gene Specific Changes to RNA Editome in Preeclampsia
Authors: Hasan Saam , Robbani Shahriyar Mahdi , Afroze Tamanna , Ahsan Gias U , Hossain Muhammad Maqsud
Published: March 2019

RNA editing is a form of post-transcriptional modification that results in changes to the messenger RNA sequence. At the onset of the study we focused on detecting the changes in RNA editing patterns in cell lines exposed to hypoxic conditions followed by the detection of changes in RNA editing patterns in the fetuses of preeclamptic mothers using publicly available RNA sequence data from the NCBI SRA database. The results showed an increase in RNA editing activity in hypoxic cell lines and a decrease in RNA editing activity in the fetuses with preeclamptic mothers. A total of 85 genes common in the cell lines and 33 in the fetus disease models and not present in controls were identified as harboring editing sites in exonic, downstream, upstream or splicing regions. Subsequently we focused on unique editing sites in genes and categorized in order of relevance to Preeclampsia as A, B and C (A being most closely related to the disease and C the least). The genes implicated ones involved in respiration chains, blood cell growth, cytokine and complement activation. Among the most significant of the genes were CTSB, GSR, CASP10, and MAPK13. Total number of common editing sites were found in different conditions and these were 667 for cell lines and 23 for fetuses. Validation of these variations in a larger samples size determines refined editing sites which could be used as potential diagnostic markers for intervention.
Lineage does not regulate the connectivity of projection neurons in the mouse olfactory bulb
Authors: Sánchez-Guardado Luis , Lois Carlos
Published: March 2019

Lineage regulates the synaptic connections between neurons in some regions of the invertebrate nervous system. In mammals recent experiments suggest that cell lineage determines the connectivity of pyramidal neurons in the neocortex, but the functional relevance of this phenomenon and whether it occurs in other neuronal types remains controversial. We investigated whether lineage plays a role in the connectivity of mitral and tufted cells, the projection neurons in the mouse olfactory bulb. We used transgenic mice to label neuronal progenitors sparsely and observed that clonally related neurons receive synaptic input from olfactory sensory neurons expressing different olfactory receptors. These results indicate that lineage does not determine the connectivity between olfactory sensory neurons and olfactory bulb projection neurons.
Islet macrophages drive islet vascular remodeling and compensatory hyperinsulinemia in the early stages of diabetes
Authors: Chittezhath Manesh , Gunaseelan Divya , Zheng Xiaofeng , Hasan Riasat , Tay Vanessa SY , Lim Seok Ting , Wang Xiaomeng , Bornstein Stefan , Berggren Per-Olof , Boehm Bernhard , Ruedl Christiane , Ali Yusuf
Published: March 2019

β-cells respond to peripheral insulin resistance by increasing circulating insulin in early type-2 diabetes (T2D). Islet remodeling supports this compensation but the drivers of this process remain poorly understood. Infiltrating macrophages have been implicated in late stage T2D but relatively little is known on islet resident macrophages, especially in early T2D. We hypothesize that islet resident macrophages contribute to islet vascular remodeling and hyperinsulinemia, the failure of which results in a rapid progression to T2D. Using genetic and diet-induced models of compensatory hyperinsulinemia we show that its depletion significantly compromises islet remodeling in terms of size, vascular density and insulin secretion capacity. Depletion of islet macrophages reduces VEGF-A secretion from both human and mouse islets ex vivo and the impact of reduced VEGF-A functionally translates to delayed re-vascularization upon transplantation in vivo. Hence, we show a new role of islet resident macrophages in the context of early T2D and suggest that there is considerable utility in harnessing islet macrophages to promote islet remodeling and islet insulin secretion capacity.

Highlights

The compensatory hyperinsulinemic phase of type-2 diabetes is accompanied with significant pancreatic islet remodeling.

Bona fideislet resident macrophages are increased during the diabetic compensation phase by largelyin situproliferation.

Ablating macrophages severely compromises the islet remodeling process and exacerbates glycemic controlin vivo.

Mouse and human islet macrophages contribute VEGF-A to the islet environment.

Specific removal of islet macrophages delays islet vascularization in compensatory hyperinsulinemic mice.
Genomics of expanded avian sex chromosomes shows that certain chromosomes are predisposed towards sex-linkage in vertebrates
Authors: Sigeman Hanna , Ponnikas Suvi , Chauhan Pallavi , Dierickx Elisa , de L. Brooke M. , Hansson Bengt
Published: March 2019

Sex chromosomes have evolved from the same autosomes multiple times across vertebrates, suggesting that certain genomic regions are predisposed towards sex-linkage. However, to test this hypothesis detailed studies of independently originated sex-linked regions and their gene content are needed. Here we address this problem through comparative genomics of birds where multiple chromosomes appear to have formed neo-sex chromosomes: larks (Alaudidae; Sylvioidea). We detected the largest known avian sex chromosome (195.3 Mbp) and show that it originates from fusions between (parts of) four avian chromosomes (Z, 3, 4A and 5). We found evidence of five evolutionary strata where recombination has been suppressed at different time points, and that these time points correlate with the level of Z–W gametolog differentiation. We show that there is extensive homology to sex chromosomes in other vertebrate lineages: three of the fused chromosomes (Z, 4A, 5) have independently evolved into sex chromosomes in fish (Z), turtles (Z, 5), lizards (Z, 4A) and mammals (Z, 4A). Moreover, we found that the fourth chromosome, chromosome 3, was significantly enriched for genes with predicted sex-specific functions. These results support a key role of chromosome content in the evolution of sex chromosomes in vertebrates.
WAT’s up!? – Organ-on-a-chip integrating human mature white adipose tissues for mechanistic research and pharmaceutical applications
Authors: Rogal Julia , Binder Carina , Kromidas Elena , Probst Christopher , Schneider Stefan , Schenke-Layland Katja , Loskill Peter
Published: March 2019

Obesity and its numerous adverse health consequences have taken on global, pandemic proportions. White adipose tissue (WAT) – a key contributor in many metabolic diseases – contributes about one fourth of a healthy human’s body mass. Despite its significance, many WAT-related pathophysiogical mechanisms in humans are still not understood, largely due to the reliance on non-human animal models. In recent years, Organ-on-a-chip (OoC) platforms have developed into promising alternatives for animal models; these systems integrate engineered human tissues into physiological microenvironment supplied by a vasculature-like microfluidic perfusion. Here, we report the development of a novel OoC that integrates functional mature human WAT. The WAT-on-a-chip is a multilayer device that features tissue chambers tailored specifically for the maintenance of 3D tissues based on human primary adipocytes, with supporting nourishment provided through perfused media channels. The platform’s capability to maintain long-term viability and functionality of WAT was confirmed by real-time monitoring of fatty acid uptake, by quantification of metabolite release into the effluent media as well as by an intact responsiveness to a therapeutic compound. The novel system provides a promising tool for wide-ranging applications in mechanistic research of WAT-related biology, in studying of pathophysiological mechanisms in obesity and diabetes, and in R&D of pharmaceutical industry.
Relationship between cardiac cycle and the timing of actions during action execution and observation
Authors: Palser E. R. , Glass J. , Fotopoulou A. , Kilner J. M.
Published: March 2019

Previous research suggests that there may be a relationship between the timing of motor events and phases of the cardiac cycle. However, this relationship has thus far only been researched using simple isolated movements such as key-presses in reaction-time tasks and only in a single subject acting alone. Other research has shown both movement and cardiac coordination among interacting individuals. Here, we investigated how the cardiac cycle relates to ongoing self-paced movements in both action execution and observation using a novel dyadic paradigm. We recorded electrocardiography (ECG) in 26 healthy adult subjects who formed 19 dyads (7 comprised of two subjects and 12 subjects paired with an experimenter). Each dyad contained an action executioner and observer as they performed a self-paced sequence of movements. We demonstrated that heartbeats are timed to movements during both action execution and observation. Specifically, movements were less likely to culminate synchronously with the heartbeat, around the time of the R-peak of the ECG. The same pattern was observed for action observation, with the observers’ heartbeats occurring off-phase with movement culmination. These findings demonstrate that there is coordination between an action executioner’s cardiac cycle and the timing of their movements, and that the same relationship is mirrored in an observer. This suggests that previous findings of interpersonal coordination may be caused by the mirroring of a phasic relationship between movement and the heart.
N-linked glycans confer protein stability and modulate multidrug efflux pump assemblyin Campylobacter jejuni
Authors: Abouelhadid Sherif , Raynes John , Bui Tam T.T. , Cuccui Jon , Wren Brendan W.
Published: March 2019

It is now apparent that nearly all bacteria species have at least a single glycosylation system, but the direct effect(s) of these protein post translational modifications are unresolved. In this study, we used the generalN-linked glycosylation pathway fromCampylobacter jejunito investigate the biophysical roles of protein modification on the CmeABC multidrug efflux pump complex. The study reveals the multifunctional role ofN-linked glycans in enhancing protein thermostability, stabilising protein complexes and the promotion of protein-protein interaction. Our findings demonstrate, for the first time, that regardless of glycan diversification among domains of life,N-linked glycans confer a common evolutionary intrinsic role.
Beta secretase 1-dependent amyloid precursor protein processing promotes excessive vascular sprouting through NOTCH3 signaling
Authors: Durrant Claire S. , Ruscher Karsten , Sheppard Olivia , Coleman Michael P. , Özen Ilknur
Published: March 2019

Amyloid beta peptides (Aβ) proteins play a key role in vascular pathology in Alzheimer’s Disease (AD) including impairment of the blood brain barrier and aberrant angiogenesis. Although previous work has demonstrated a pro-angiogenic role of Aβ, the exact mechanisms by which amyloid precursor protein (APP) processing and endothelial angiogenic signalling cascades interact in AD remain a largely unsolved problem. Here, we report that increased endothelial sprouting in human-APP transgenic mouse (TgCRND8) tissue is dependent on β-secretase (BACE1) processing of APP. Higher levels of Aβ processing in TgCRND8 tissue coincides with decreased NOTCH3/JAG1 signalling, over-production of endothelial filopodia and increased numbers of vascular pericytes. Using a novel in vitro approach to study sprouting angiogenesis in TgCRND8 organotypic brain slice cultures (OBSCs), we find that BACE1 inhibition normalises excessive endothelial filopodia formation and restores NOTCH3 signalling. These data present the first evidence for the potential of BACE1 inhibition as an effective therapeutic target for aberrant angiogenesis in AD.

Significance

In this study, we show that targeting amyloid beta processing provides an opportunity to selectively target tip cell filopodia-driven angiogenesis and develop therapeutic targets for vascular dysfunction related to aberrant angiogenesis in AD. Our data provide the first evidence for a safe level of BACE1 inhibition that can normalize excess angiogenesis in AD, without inducing vascular deficits in healthy tissue. Our findings may pave the way for the development of new angiogenesis dependent therapeutic strategies in Alzheimer’s Disease.
Uncovering the gene machinery of the Amazon River microbiome to degrade rainforest organic matter
Authors: Santos Célio Dias , Sarmento Hugo , de Miranda Fernando Pellon , Henrique-Silva Flávio , Logares Ramiro
Published: March 2019

The Amazon River receives, from the surrounding rainforest, huge amounts of terrestrial organic matter (TeOM), which is typically resistant to microbial degradation. However, only a small fraction of the TeOM ends up in the ocean, indicating that most of it is degraded in the river. So far, the nature of the genes involved in TeOM degradation and their spatial distributions are barely known. Here, we examined the Amazon River microbiome gene repertoire and found that it contains a substantial gene-novelty, compared to other environments (rivers and rainforest soil). We predicted ~3.7 million non-redundant genes, affiliating mostly to bacteria. The gene-functions involved in TeOM degradation revealed that lignin degradation correlated to tricarboxylates and hemicellulose processing, pointing to higher lignin degradation rates under consumption of labile compounds. We describe the biochemical machinery that could be speeding up the decomposition of recalcitrant compounds in Amazonian waters, previously reported only in incubation experiments.