bluuebunny/crossref_metadata_2025 huggingface dataset:
Lending Relationships and the Collateral Channel
Authors: Anderson Gareth , Bahaj Saleem , Chavaz Matthieu , Foulis Angus , Pinter Gabor
Published: July 2022

This article shows that lending relationships insulate corporate investment from fluctuations in collateral values. The sensitivity of corporate investment to changes in real-estate collateral values is halved when the length of relationship between a bank and a firm, or its board of directors, doubles. Long relationships with board members dominate relationships with the firm in dampening the collateral channel. Moreover, lending relationships with directors in their personal capacity insulate corporate investment over and above corporate relationships. Our findings support theories where collateral and private information are substitutes in mitigating credit frictions over the cycle and show that lending relationships are more multi-faceted than previously thought.
Protectors as ‘mere toothless tigers’? Advocating in favour of the ‘Wider View’
Authors: Egan Sarah
Published: July 2022

The author considers the varying recent approaches of the High Court of England and Wales, the Royal Court of Jersey, and the Supreme Court of Bermuda in the construction of protectors’ powers to consent to or to veto a proposed distribution. These authorities have been instrumental in delineating the distinction between the ‘Narrower View’ and the ‘Wider View’. The Narrower View only permits the protectors a discretion to bless a valid and rational decision, but not to veto the exercise of powers of trustees. In contrast, the Wider View confers protectors as fiduciaries with an independent decision-making discretion when deciding whether to give their consent to the exercise of powers by the trustees. This article advances arguments in favour of the ‘Wider View’.
Bridge to Health/Puente a la Salud: a pilot randomized trial to address diabetes self-management and social needs among high-risk patients
Authors: Fitzpatrick Stephanie L , Papajorgji-Taylor Dea , Schneider Jennifer L , Lindberg Nangel , Francisco Melanie , Smith Ning , Vaughn Katie , Vrany Elizabeth A , Hill-Briggs Felicia
Published: July 2022

Social needs contribute to persistent diabetes disparities; thus, it is imperative to address social needs to optimize diabetes management. The purpose of this study was to determine determine the feasibility and acceptability of health system-based social care versus social care + behavioral intervention to address social needs and improve diabetes self-management among patients with type 2 diabetes. Black/African American, Hispanic/Latino, and low-income White patients with recent hemoglobin A1C (A1C) ≥ 8%, and ≥1 social need were recruited from an integrated health system. Patients were randomized to one-of-two 6-month interventions: (a) navigation to resources (NAV) facilitated by a Patient Navigator; or (b) NAV + evidence-based nine-session diabetes self-management support (DSMS) program facilitated by a community health worker (CHW). A1C was extracted from the electronic health record. We successfully recruited 110 eligible patients (54 NAV; 56 NAV + DSMS). During the trial, 78% NAV and 80% NAV + DSMS participants successfully connected to a navigator; 84% NAV + DSMS connected to a CHW. At 6-month follow-up, 33% of NAV and 34% of NAV + DSMS participants had an A1C < 8%. Mean reduction in A1C was clinically significant in NAV (−0.65%) and NAV + DSMS (−0.72%). By follow-up, 89% of NAV and 87% of NAV + DSMS were successfully connected to resources to address at least one need. Findings suggest that it is feasible to implement a health system-based social care intervention, separately or in combination, with a behavioral intervention to improve diabetes management among a high-risk, socially complex patient population. A larger, pragmatic trial is needed to test the comparative effectiveness of each approach on diabetes-related outcomes.
Meaning-Centered Psychotherapy for Cancer Caregivers: A pilot trial among caregivers of patients with glioblastoma multiforme
Authors: Applebaum Allison J , Baser Raymond E , Roberts Kailey E , Lynch Kathleen , Gebert Rebecca , Breitbart William S , Diamond Eli L
Published: July 2022

Caregivers of patients with glioblastoma multiforme (GBM) are at significant risk for existential distress. Such distress negatively impacts caregivers’ quality of life and capacity to serve in their role as healthcare proxies, and ultimately, contributes to poor bereavement outcomes. Our team developed Meaning-Centered Psychotherapy for Cancer Caregivers (MCP-C), the first targeted psychosocial intervention that directly addresses existential distress in caregivers. The purpose of this study was to evaluate the feasibility, acceptability, and preliminary effects of MCP-C among caregivers of patients with GBM via a mixed-method pilot trial. Caregivers were randomized to seven sessions of MCP-C or Enhanced Usual Care (EUC), which included distress screening and the provision of targeted referrals and completed quantitative assessments at baseline (T1), after completion of MCP-C (T2), and at 2-month follow-up (T3). A subset of participants engaged in semistructured interviews at T2. Of 60 caregivers randomized, 55 were evaluable for preliminary efficacy analysis. Constrained linear mixed models indicated the MCP-C arm had statistically significant improvement relative to the EUC arm in the primary outcome of personal meaning and multiple secondary outcomes, including benefit finding, depressive symptomatology, and spiritual wellbeing. MCP-C demonstrated preliminary efficacy in facilitating caregivers’ capacity to experience a sense of meaning and purpose despite the challenges and suffering associated with providing care to patients with GBM. Future studies are needed among more diverse samples of caregivers and should include the opportunity for concurrent patient enrollment to allow for a reciprocal and augmented experience of meaning among patient–caregiver dyads.
Prediction of tree sapwood and heartwood profiles using pipe model and branch thinning theory
Authors: Aye Tin Nwe , Brännström Åke , Carlsson Linus
Published: July 2022

Estimates of tree heartwood and sapwood profiles are important in the pulp industry and for dynamic vegetation models, in which they determine tree biomechanical stability and hydraulic conductivity. Several phenomenological models of stem profiles have been developed for this purpose, based on assumptions on how tree crown and foliage distributions change over time. Here, we derive estimates of tree profiles by synthesizing a simple pipe model theory of plant form with a recently developed theory of branch thinning that from simple assumptions quantifies discarded branches and leaves. This allows us to develop a new trunk model of tree profiles from breast height up to the top of the tree. We postulate that leaves that are currently on the tree are connected by sapwood pipes, while pipes that previously connected discarded leaves or branches form the heartwood. By assuming that a fixed fraction of all pipes remain on the trunk after a branching event, as the trunk is traversed from the root system to the tips, this allows us to quantify trunk heartwood and sapwood profiles. We test the trunk model performance on empirical data from five tree species across three continents. We find that the trunk model accurately describes heartwood and sapwood profiles of all tested tree species (calibration; R2: 84–99%). Furthermore, once calibrated to a tree species, the trunk model predicts heartwood and sapwood profiles of conspecific trees in similar growing environments based only on the age and height of a tree (cross-validation/prediction; R2: 68–98%). The fewer and often contrasting parameters needed for the trunk model make it a potentially useful complementary tool for biologists and foresters.
The protein C pathways
Authors: Leon Gemma , Rehill Aisling M. , Preston Roger J.S.
Published: July 2022

Purpose of review

To provide an overview of the state-of-the-art in protein C (PC) pathway research.

Recent findings

The PC pathway is crucial for maintaining hemostasis to prevent venous thromboembolism. This is evident from genetic mutations that result in impaired PC pathway activity and contribute to increased venous thromboembolism risk in affected individuals. In addition to its anticoagulant role, activated PC (APC) also mediates a complex, pleiotropic role in the maintenance of vascular cell health, which it achieves via anti-inflammatory and antiapoptotic cell signaling on endothelial cells. Emerging data have demonstrated that cell signaling by APC, mediated by multiple receptor interactions on different cell types, also confers cytoprotective and anti-inflammatory benefits. Defects in both arms of the PC pathway are associated with increased susceptibility to thrombo-inflammatory disease in various preclinical thrombotic, proinflammatory and neurological disease models. Moreover, recent studies have identified attenuation of anticoagulant PC pathway activity as an exciting therapeutic opportunity to promote hemostasis in patients with inherited or acquired bleeding disorders.

In this review, we provide an overview of some recent developments in our understanding of the PC pathways.
Endoscopy in Infants With Gastrointestinal Bleeding Has Limited Diagnostic or Therapeutic Benefit
Authors: Bose Paroma , Jacobs Annalise S. , Cordova Jorge Gonzales , Gray Brian W. , Huff Katie A. , Molleston Jean P.
Published: July 2022

Objectives:

Pediatric gastroenterologists are often consulted to perform diagnostic and therapeutic endoscopy in infants with gastrointestinal bleeding (GIB). The value of endoscopy and risk of complications in this population are not well characterized. We aimed to describe findings and outcomes of infants with GIB who undergo endoscopy.

Methods:

Retrospective, single-center, cohort study of hospitalized infants ≤12 months who underwent esophagogastroduodenoscopy (EGD) and/or colonoscopy/flexible sigmoidoscopy (COL) for GIB. Current procedural technology codes, international classification of diseases codes, and quality control logs identified infants.

Results:

Fifty-six infants were identified from 2008 to 2019 (51.8% female; mean age 161.6 days). Seven endoscopies identified sources of GIB: gastric ulcers, a duodenal ulcer, gastric angiodysplasia, esophageal varices, and an anastomotic ulcer. Three infants underwent therapeutic interventions of banding/sclerotherapy of esophageal varices and triamcinolone injection of an anastomotic ulcer. Six infants underwent abdominal surgery for GIB or suspected intestinal perforation after endoscopy, where a gastric perforation, jejunal perforation at an anastomotic stricture, necrotizing enterocolitis totalis with perforation, Meckel’s diverticulum, and a duodenal ulcer were identified. No source of bleeding was identified surgically in 1 infant with GIB. Respiratory failure, use of vasopressors or octreotide, administration of blood products, and high blood urea nitrogen were associated with increased likelihood of requiring surgery (P < 0.05 for all).

Conclusions:

There was limited utility to performing endoscopy in infants ≤12 months old with clinical GIB. Endoscopy in these sick infants carries risk, and 3 infants in this series presented with a gastrointestinal (GI) perforation shortly after the procedure. These limitations and risks should influence clinical decision-making regarding endoscopy in infants with GIB.
Appraising scattering theories for polycrystals of any symmetry using finite elements
Authors: Huang Ming , Rokhlin Stanislav I. , Lowe Michael J. S.
Published: July 2022

This paper uses three-dimensional grain-scale finite-element (FE) simulations to appraise the classical scattering theory of plane longitudinal wave propagation in untextured polycrystals with statistically equiaxed grains belonging to the seven crystal symmetries. As revealed from the results of 10 390 materials, the classical theory has a linear relationship with the elastic scattering factor at the quasi-static velocity limit, whereas the reference FE and self-consistent (SC) results generally exhibit a quadratic relationship. As supported by the results of 90 materials, such order difference also extends to the attenuation and phase velocity, leading to larger differences between the classical theory and the FE results for more strongly scattering materials. Alternatively, two approximate models are proposed to achieve more accurate calculations by including an additional quadratic term. One model uses quadratic coefficients from quasi-static SC velocity fits and is thus symmetry-specific, while the other uses theoretically determined coefficients and is valid for any individual material. These simple models generally deliver more accurate attenuation and phase velocity (particularly the second model) than the classical theory, especially for strongly scattering materials. However, the models are invalid for the attenuation of materials with negative quadratic coefficients.

This article is part of the theme issue 'Wave generation and transmission in multi-scale complex media and structured metamaterials (part 1)'.
A Poisson scaling approach to backward wave propagation in a tube
Authors: Chapman C. J. , Sorokin S. V.
Published: July 2022

A mathematical analysis of wave propagation along an elastic cylindrical tube is presented, with the aim of determining the range of Poisson’s ratio for which backward wave propagation (i.e. at negative group velocity) can occur near the ring frequency. This range includes zero Poisson’s ratio and a surrounding interval of positive and negative values, whose width depends on the thickness of the tube. The whole range of Poisson’s ratio is considered, so that the work applies to modern materials, e.g. composites. All results are presented in simple analytic form by means of a dominant balance in parameter space. The identification of this balance, which is unique, is a main new result in the paper, which makes possible a new type of shell theory based on ‘Poisson scaling’. The mathematical approach is deductive from the equations of motion, rather than being based on kinematic hypotheses. A key finding, accessible via the Poisson scaling, is that the regime of negative group velocities extends to high wavenumbers, while being confined to a narrow band of frequencies. Thus responses localized in space are possible for near-monochromatic forcing, an important fact for nonlinear theories of tube dynamics near the ring frequency.

This article is part of the theme issue ‘Wave generation and transmission in multi-scale complex media and structured metamaterials (part 1)’.
Tensile material instabilities in elastic beam lattices lead to a bounded stability domain
Authors: Bordiga Giovanni , Bigoni Davide , Piccolroaz Andrea
Published: July 2022

Homogenization of the incremental response of grids made up of
preloaded
elastic rods leads to homogeneous effective continua which may suffer macroscopic instability, occurring at the same time in both the grid and the effective continuum. This instability corresponds to the loss of ellipticity in the effective material and the formation of localized responses as, for instance, shear bands. Using lattice models of elastic rods, loss of ellipticity has always been found to occur for stress states involving compression of the rods, as
usually
these structural elements buckle only under compression. In this way, the locus of material stability for the effective solid is unbounded in tension, i.e. the material is always stable for a tensile prestress. A rigorous application of homogenization theory is proposed to show that the inclusion of sliders (constraints imposing axial and rotational continuity, but allowing shear jumps) in the grid of rods leads to loss of ellipticity in tension so that the locus for material instability becomes
bounded
. This result explains (i) how to design elastic materials subject to localization of deformation and shear banding for all radial stress paths; and (ii) how for all these paths a material may fail by developing strain localization and without involving cracking.

This article is part of the theme issue ‘Wave generation and transmission in multi-scale complex media and structured metamaterials (part 1)’.
Modelling of seismic assessment for large geological systems
Authors: Movchan Igor B. , Yakovleva Alexandra A. , Frid Vladimir , Movchan Alexander B. , Shaygallyamova Zilya I.
Published: July 2022

A new approach to seismic analysis has been introduced and demonstrated for a sequence of recent seismic events recorded in the Blackpool region of Lancashire, UK. The seismic activity, induced by an industrial hydraulic fracturing at a depth exceeding 2 km, had the extent of registered surface elastic vibrations reaching a distance exceeding 15 km. The analysis is based on the study of elastic fields, three-dimensional extrapolations of the landscape and the novel reconstruction of a three-dimensional digital model of seismic map boundaries and vertical profiles. The verification of the proposed approach is carried out via the comparison with published data of the Blackpool seismic events, combined with the new spectral analysis linked to the identified regions of seismic activity. The latter was accompanied by a finite-element simulation of vibrations for an elastic layer of variable thickness, approximating the test region. The analysis and numerical modelling have demonstrated consistency with the dynamic nature of structural stratification of the geological systems, and in addition, the predictive nature of the modelling work was demonstrated by the comparison of the model eigenmodes with the published parameters of registered earthquakes in the Blackpool area.

This article is part of the theme issue ‘Wave generation and transmission in multi-scale complex media and structured metamaterials (part 1)’.
On the Bövik–Benveniste methodology and related approaches for modelling thin layers
Authors: Baranova S. , Mogilevskaya S. G.
Published: July 2022

This paper reviews several leading approaches for asymptotic modelling of thin layers in elastostatics and wave propagation phenomena. The issues related to applications of the so-called ‘equivalent’ or ‘effective’ boundary conditions and their interpretations are highlighted. Comparative analysis of asymptotic models is performed for a two-dimensional elastostatic case using a novel complex variables-based modelling tool. Its implementation allows for straightforward derivations of higher order boundary conditions for problems with layers of arbitrary sufficiently smooth curvatures. Explicit expressions for the conditions up to the third order are provided. All models are tested using available benchmark solutions and the solutions for the limiting cases of the layer parameters.

This article is part of the theme issue ‘Wave generation and transmission in multi-scale complex media and structured metamaterials (part 1)’.
Lineage-specific, fast-evolving GATA-like gene regulates zygotic gene activation to promote endoderm specification and pattern formation in the Theridiidae spider
Authors: Iwasaki-Yokozawa Sawa , Nanjo Ryota , Akiyama-Oda Yasuko , Oda Hiroki
Published: July 2022

Background

The process of early development varies across the species-rich phylum Arthropoda. Owing to the limited research strategies for dissecting lineage-specific processes of development in arthropods, little is known about the variations in early arthropod development at molecular resolution. The Theridiidae spider, Parasteatoda tepidariorum, has its genome sequenced and could potentially to contribute to dissecting early embryonic processes.

Results

We present genome-wide identification of candidate genes that exhibit locally restricted expression in germ-disc forming stage embryos of P. tepidariorum, based on comparative transcriptomes of isolated cells from different regions of the embryo. A subsequent pilot screen by parental RNA interference identifies three genes required for body axis formation. One of them is a GATA-like gene that has been fast evolving after duplication and divergence from a canonical GATA family gene. This gene is designated fuchi nashi (fuchi) after its knockdown phenotypes, where the cell movement toward the formation of a germ disc was reversed. fuchi expression occurs in cells outside a forming germ disc and persists in the endoderm. Transcriptome and chromatin accessibility analyses of fuchi pRNAi embryos suggest that early fuchi activity regulates chromatin state and zygotic gene activation to promote endoderm specification and pattern formation. We also show that there are many uncharacterized genes regulated by fuchi.

Conclusions

Our genome-based research using an arthropod phylogenetically distant from Drosophila identifies a lineage-specific, fast-evolving gene with key developmental roles in one of the earliest, genome-wide regulatory events, and allows for molecular exploration of the developmental variations in early arthropod embryos.
Atypical Polycystic Kidney Disease in Individuals Heterozygous for ALG8 Protein-truncating variants
Authors: Apple Benjamin , Sartori Gino , Moore Bryn , Chintam Kiran , Singh Gurmukteshwar , Mohan Anand Prince , Strande Natasha , Mirshahi Tooraj , Triffo William , Chang Alex
Published: July 2022

Background

Heterozygous ALG8 variants have previously been associated with polycystic liver disease (PLD) with or without kidney cysts. A clear-cut relationship between application of PKD diagnostic criteria and kidney manifestations of ALG8 variants remains to be described. We therefore sought to determine whether ALG8 protein-truncating variant (PTV) heterozygotes are at increased risk of polycystic kidney disease (PKD).

Methods

We identified participants heterozygous for pathogenic (P) and likely pathogenic (LP) ALG8 (NM_024079.5) PTVs described in ClinVar from the Geisinger-Regeneron DiscovEHR MyCode study, an unselected health system-based cohort linked to electronic health records. ALG8 PTV heterozygotes were matched 1:1 to non-heterozygote family members by age at time of imaging (within 10 years) and sex. Phenotypes were assessed by International Classification of Disease (ICD) codes, chart review, and imaging, which was reviewed by a blinded radiologist. Imaging diagnosis of PKD was defined as ≥4 kidney cysts on an abdominal ultrasound or computed tomography. Secondary outcomes included bilateral renal cysts, and ≥1 liver cyst.

Results

Out of 174,418 participants in MyCode,103 participants (mean age 56.7 years) were heterozygous for an ALG8 P/LP variant: p.Arg364Ter (n=86), p.Arg41Ter (n=7), p.Arg179Ter (n=9), and c.368+2T>G (n=2). None of the ALG8 P/LP variant heterozygotes had an ICD diagnosis of PKD or PLD. Out of 51 participants ≥40 years of age with available imaging, 51% had ≥4 renal cysts and 14% had ≥1 liver cyst. After matching 23 ALG8 P/LP variant heterozygotes with 23 related non-heterozygotes by age and imaging modality, ALG8 P/LP heterozygotes had higher prevalence of 4+ kidney cysts (48% versus 9% in non-heterozygotes; p=0.007) and bilateral kidney cysts (61% vs. 17%; p=0.006).

Conclusions

Our study demonstrates that patients heterozygous for ALG8 P/LP variants are at increased risk of PKD on imaging but not by ICD diagnosis codes. Additional studies are needed to determine whether ALG8 P/LP heterozygotes are at increased risk of kidney failure.
Defining the lipidome of Arabidopsis leaf mitochondria: Specific lipid complement and lipid biosynthesis capacity
Authors: Liu Yi-Tse , Senkler Jennifer , Herrfurth Cornelia , Braun Hans-Peter , Feussner Ivo
Published: July 2022

Mitochondria are often considered the power stations of the cell, playing critical roles in various biological processes such as cellular respiration, photosynthesis, stress responses and programmed cell death. To maintain the structural and functional integrities of mitochondria, it is crucial to achieve a defined membrane lipid composition between different lipid classes wherein specific proportions of individual lipid species are present. Although mitochondria are capable of self-synthesizing a few lipid classes, many phospholipids are synthesized in the endoplasmic reticulum and transferred to mitochondria via membrane contact sites, as mitochondria are excluded from the vesicular transportation pathway. However, knowledge on the capability of lipid biosynthesis in mitochondria and the precise mechanism of maintaining the homeostasis of mitochondrial lipids is still scarce. Here we describe the lipidome of mitochondria isolated fromArabidopsisleaves, including the molecular species of glycerolipids, sphingolipids and sterols to depict the lipid landscape of mitochondrial membranes. In addition, we define proteins involved in lipid metabolism by proteomic analysis and compare our data with mitochondria from cell cultures since they still serve as model system. Proteins putatively localized to the membrane contact sites are proposed based on the proteomic results and online databases. Collectively, our results suggest that leaf mitochondria are capable - with the assistance of membrane contact site-localised proteins - of generating several lipid classes including phosphatidylethanolamines, cardiolipins, diacylgalactosylglycerols and free sterols. We anticipate our work to be a foundation to further investigate the functional roles of lipids and their involvement in biochemical reactions in plant mitochondria.

One sentence summary

The lipid landscape of plant mitochondria suggests that they are capable in generating several phospholipid classes with the assistant of membrane contact site-localized proteins.
Single-cell transcriptomics reveals immune suppression and cell states predictive of patient outcomes in rhabdomyosarcoma
Authors: DeMartino Jeff , Meister Michael T. , Visser Lindy , Brok Mariël , Groot Koerkamp Marian J. A. , Hiemcke-Jiwa Laura S. , de Souza Terezinha , Merks Johannes H. M. , Holstege Frank C. P. , Margaritis Thanasis , Drost Jarno
Published: July 2022

Paediatric rhabdomyosarcoma (RMS) is a soft tissue malignancy of mesenchymal origin which is thought to arise as a consequence of derailed myogenic differentiation. Despite intensive treatment regimens, the prognosis for high-risk patients remains dismal. The cellular differentiation states underlying RMS and how these relate to patient outcomes remain largely elusive. Here, we used single-cell mRNA-sequencing to generate a transcriptomic atlas of RMS. Analysis of the RMS tumour niche revealed evidence of an immunosuppressive microenvironment. We also identified an interaction between NECTIN3 and TIGIT, specific to the more aggressive fusion-positive (FP) RMS subtype, as a putative cause of tumour-induced T-cell dysfunction. In malignant RMS cells we defined transcriptional programs reflective of normal myogenic differentiation. Furthermore, we showed that these cellular differentiation states are predictive of patient outcomes in both FP RMS and the more clinically homogenous fusion-negative subtype. Our study reveals the potential of therapies targeting the immune microenvironment of RMS and suggests that assessing tumour differentiation states may enable a more refined risk stratification.
Hippocampal Place-like Signal in Latent Space
Authors: Schafer Matthew , Kamilar-Britt Philip , Sahani Vyoma , Bachi Keren , Schiller Daniela
Published: July 2022

During navigation, the hippocampus represents physical places like coordinates on a map; similar location-like signals have been seen in sensory and concept spaces. It is unclear just how general this hippocampal place code is, however: does it map places in wholly non-perceivable spaces, without locations being instructed or reinforced and during navigation-like behavior? To search for such a signal, we imaged participants’ brains while they played a naturalistic, narrativebased social interaction game, and modeled their relationships as a kind of navigation through social space. Two independent samples showed hippocampal place-like signals in both region-based and whole-brain representational similarity analyses, as well as decoding and average pattern similarity analyses; the effects were not explained by other measures of the behavior or task information. These results are the first demonstration of complete domain generality in hippocampal place representation.

One-Sentence Summary

hippocampal place-like signal in non-perceivable and unreinforced space during naturalistic navigational behavior.

Significance statement

The hippocampus is a brain structure known to encode maps of physical spaces; this study shows that it also maps fully abstract, latent and uninstructed spaces. People played a naturalistic social interaction game while their brains were scanned. Hippocampal brain activity correlated with the fictional characters’ locations in an abstract social space framed by axes of affiliation and power, despite the participants never being exposed to a perceivable spatial representation. This mapping was present across multiple analyses and two samples, demonstrating that the brain system responsible for spatial mapping maps our social interactions too.
Dietary non-starch polysaccharides impair immunity to enteric nematode infection
Authors: Valente Angela H. , Jensen Karen M.R. , Myhill Laura J. , Zhu Ling , Mentzel Caroline M.J. , Krych Lukasz , Simonsen Henrik T. , Castro-Mejía Josue L. , Gobbi Alex , Bach Knudsen Knud Erik , Nielsen Dennis S. , Thamsborg Stig M. , Williams Andrew R.
Published: July 2022

The influence of diet on immune function and resistance to enteric infection and disease is becoming ever more established. Highly processed, refined diets can lead to inflammation and gut microbiome dysbiosis, whilst health-promoting dietary components such as phytonutrients and fermentable fibres are thought to promote a healthy microbiome and balanced mucosal immunity. Chicory (Cichorium intybus) is a leafy green vegetable rich in fibres and bioactive compounds that may promote gut health. Unexpectedly, we here show that incorporation of chicory into semisynthetic AIN93G diets renders mice susceptible to infection with enteric helminths. Mice fed a high level of chicory leaves (10% dry matter) had a more diverse gut microbiota, but a diminished type-2 immune response to infection with the intestinal roundworm Heligmosomoides polygyrus. Furthermore, the chicory-supplemented diet significantly increased burdens of the caecum-dwelling whipworm Trichuris muris, concomitant with a highly skewed type-1 immune environment in caecal tissue. The chicory-supplemented diet was rich in non-starch polysaccharides, particularly uronic acids (the monomeric constituents of pectin). In accordance, mice fed pectin-supplemented AIN93G diets had higher T. muris burdens and reduced IgE production and expression of genes involved in type-2 immunity. Importantly, treatment of pectin-fed mice with exogenous IL-25 restored type-2 responses and was sufficient to allow T. muris expulsion. Collectively, our data suggest that increasing levels of fermentable, non-starch polysaccharides in refined diets compromises immunity to helminth infection in mice. This diet-infection interaction may inform new strategies for manipulating the gut environment to promote resistance to enteric parasites.
Exploring DTI-derived metrics to non-invasively track recellularisation in vascular tissue engineering
Authors: Tornifoglio B , Stone A. J. , Mathieu P. , Fitzpatrick E. , Kerskens C. , Lally C.
Published: July 2022

Despite significant growth in the field of tissue engineering over the past decades, non-invasive, non-destructive methods to characterise recellularisation of grafts are lacking. Here, we investigate a non-invasive magnetic resonance imaging technique, diffusion tensor imaging (DTI), within acellular and recellularised vascular grafts. Using two decellularised porcine carotid grafts, smooth muscle cells were cultured dynamically for two weeks with terminal time points at day 3, 7, and 14. Grafts were fixed at each time point and investigated by DTI in anex vivoset up. Semi-quantitative histology was carried out to investigate collagen, elastin, and cell density changes over time. DTI-derived metrics, namely the fractional anisotropy, mean diffusivity and tractography, not only were significantly different between day 3 and day 7 grafts, but also distinguished between acellular and recellularised grafts. Specifically, within the wet decellularised grafts, increasing fractional anisotropy was strongly correlated to increasing cell density. The results from this study show, for the first time, DTI’s place in the field of tissue engineering, offering non-invasive, non-destructive insight into graft recellularisation.
Diverse strategies for tracking seasonal environmental niches at hemispheric scale
Authors: Cohen Jeremy , Jetz Walter
Published: July 2022

Species depend upon a constrained set of environmental conditions, or niches, for survival and reproduction that are increasingly lost under climatic change. Seasonal environments require species to either track their niches via movement or undergo physiological or behavioral changes to survive. Here we identify the tracking of both environmental niche position and breadth across 619 New World bird species and assess their phylogenetic and functional underpinning. Partitioning niche position and breadth tracking can inform whether climatic means or extremes limit seasonal distributions. We uncover diverse strategies, including the tracking of niche position, breadth, both, or neither, suggesting highly variable sensitivity to ongoing climatic change. There was limited phylogenetic determinism to this variation, but a strong association with functional attributes that differed between niche position and breadth tracking. Our findings imply significant functional consequences for communities and ecosystems as impending climate change affects some niche tracking strategies more than others.
Pollen accumulation on hawkmoths varies substantially among moth-pollinated flowers
Authors: Smith Gordon , Kim Christine , Raguso Robert
Published: July 2022

Using the pollen loads carried by floral visitors to infer their floral visitation behavior is a powerful technique to explore the foraging of wild pollinators. Interpreting these pollen records, however, requires assumptions about the underlying pollen dynamics. To compare visitor foraging across flower species, the most important assumption is that pollen is picked up and retained on the visitor at similar rates. Given differences in pollen presentation traits such as grain number or stickiness even among flowers with similar morphologies, however, the generality of this assumption is unclear. We investigated pollen accumulation on the hawkmoth Manduca sexta, testing the degree to which accumulation differed among flower species and how pollen stickiness affected this accumulation. In no-choice floral visitation assays to six plant species visited by long-tongued hawkmoths in the wild, M. sexta individuals were allowed to visit flowers 1, 2, or 5 times, after which the pollen on their proboscises was removed and counted. We found that the six plant species varied orders of magnitude in the number of pollen grains deposited on the moths, with some placing thousands of grains after a single visit and other placing none after five. Plant species with sticky pollen adhesion mechanisms placed more pollen on the moths and had relatively less pollen accumulation over successive visits than non-sticky plants. Intriguingly, moths carried fewer pollen grains after 5 visits than after 2 visits, suggesting that both sticky and non-sticky pollen was lost during foraging. Together, our results suggest that interpretation of pollen load data should be made cautiously, especially when comparing across plant species.
Choice-Induced Preference Change under a Sequential Sampling Model Framework
Authors: Lee Douglas G. , Pezzulo Giovanni
Published: July 2022

Sequential sampling models of choice, such as the drift-diffusion model (DDM), are frequently fit to empirical data to account for a variety of effects related to accuracy/consistency, response time (RT), and sometimes confidence. However, no model in this class can account for the phenomenon known aschoice-induced preference change, where decision makers tend to rate options higher after they choose them and lower after they reject them. Studies have reported choice-induced preference change for many decades, and the principal findings are robust. The resultingspreading of alternatives(SoA) in terms of their subjective value ratings is incompatible with traditional sequential sampling models, which consider the rated values of the options to be stationary throughout choice deliberation. Here, we propose an extension of the basic DDM that allows the drift rate to vary across deliberation time depending on which attributes are attended to at which points in time. Critically, the model assumes that choice deliberation commences based only on the more salient attributes of the options, and that additional attributes eventually come into consideration when the decision cannot be resolved based on the initial attributes alone. We show that this model can account for SoA (in addition to choice consistency and RT), as well as all previously reported relationships between SoA and choice difficulty, attribute disparity, and RT.
Mixed selectivity coding of content-temporal detail by dorsomedial posterior parietal neurons
Authors: Wang Lei , Zhou Xufeng , Zeng Fu , Cao Mingfeng , Zuo Shuzhen , Yang Jie , Kusunoki Makoto , Wang Huimin , Zhou Yong-di , Chen Aihua , Kwok Sze Chai
Published: July 2022

The dorsomedial posterior parietal cortex is part of a higher-cognition network implicated in elaborate processes underpinning memory formation, recollection, episodes reconstruction, and temporal information processing. Neural coding for complex episodic processing is however under-documented. Here we revealed a set of neural codes of ‘neuroethogram’ in the primate parietal cortex. Analyzing neural responses in macaque dmPPC to naturalistic videos, we discovered several groups of neurons that are sensitive to different categories of ethogram-items and to low-level sensory features, and saccadic eye movement. We also discovered that the processing of category and feature information by these neurons is sustained by accumulation of temporal information over a long timescale up to 30 s, corroborating its reported long temporal receptive windows. We performed an additional behavioral experiment and found that saccade-related activities could not account for the mixed neuronal responses elicited by the video stimuli. We further observed monkeys’ scan-paths and gaze consistency are modulated by video content. Taken altogether, these neural findings explain how dorsomedial PPC weaves fabrics of ongoing experiences together in real-time. The high dimensionality of neural representations should motivate us to shift the focus of attention from pure selectivity neurons to mixed selectivity neurons, especially in increasingly complex naturalistic task designs.

HIGHLIGHTS

Neural codes for “neuroethogram” in macaque dorsomedial parietal cortex

Parietal neural codes exhibit mixed selectivity of event features

Dorsomedial PPC neurons support a long temporal receptive window for episodes

Saccadic movement could not explain away mixed neuronal responses

Consistency in scan-path and gaze shown across viewing repetitions
A Joint Distribution Approach on Non-linear Functional Connectivity
Authors: Yang Huzheng , Gu Shi
Published: July 2022

This report summarizes experiments on exploring non-linear functional connectivity. Using resting-state functional MRI data from the HCP1200 dataset, we define nodes as 17 functional networks and edges as the joint distribution between times series pairs. Linear dependence is removed before taking the joint distribution. We then employ a test for normality on the joint distribution to find non-normal distribution patterns. However, the result from an experimental run of 10 subjects shows that: only less than 1% of edges is non-normal distributed, and the location of such edges is not consistent across subjects. From this point of view, the non-linear part seems to be governed by random noise.
Translational regulation by RACK1 in astrocytes represses KIR4.1 expression and regulates neuronal activity
Authors: Oudart Marc , Avila-Gutierrez Katia , Moch Clara , Dossi Elena , Milior Giampaolo , Boulay Anne-Cécile , Gaudey Mathis , Moulard Julien , Lombard Bérangère , Loew Damarys , Bemelmans Alexis-Pierre , Rouach Nathalie , Chapat Clément , Cohen-Salmon Martine
Published: July 2022

The regulation of translation in astrocytes, the main glial cells in the brain, remains poorly characterized. We developed a high-throughput proteomic screen for polysome-associated proteins in astrocytes and focused on the ribosomal protein receptor of activated protein C kinase 1 (RACK1), a critical factor in translational regulation. In astrocyte somata and perisynaptic astrocytic processes (PAPs), RACK1 preferentially bound to a number of mRNAs, includingKcnj10, encoding the inward rectifying potassium (K+) channel KIR4.1, a critical astrocytic regulator of neurotransmission. By developing an astrocyte-specific, conditional RACK1 knock-out mouse model, we showed that RACK1 repressed the production of KIR4.1 in hippocampal astrocytes and PAPs. Reporter-based assays revealed that RACK1 controlledKcnj10translation through the transcript’s 5’ untranslated region. Upregulation of KIR4.1 in the absence of RACK1 modified the astrocyte territory volume and neuronal activity attenuatin burst frequency and duration in the hippocampus. Hence, astrocytic RACK1 represses KIR4.1 translation and influences neuronal activity.
Comparative Analysis of Commercially Available Typhoid Point of Care Tests: Results of a Prospective and Hybrid Retrospective Multicenter Diagnostic Accuracy Study in Kenya and Pakistan
Authors: Sapkota Jyotshna , Hasan Rumina , Onsare Robert , Arafah Sonia , Kariuki Sam , Shakoor Sadia , Qamar Farah , Mundalo Sheillah , Njeru Frida , Too Rael , Ndegwa Elizabeth , Andrews Jason R , Dittrich Sabine
Published: July 2022

Blood and bone marrow cultures are considered the gold standard for the diagnosis of typhoid, but those methods require infrastructure and skilled manpower that are not always available in low- and middle-income countries where typhoid is endemic. The objective of the study is to evaluate the sensitivity and specificity of nine commercially available Salmonella Typhi rapid diagnostic tests (RDTs) using blood culture as reference standard in a multicenter study. This was a prospective and retrospective multicenter diagnostic accuracy study conducted in two geographically distant typhoid-endemic areas (Pakistan and Kenya; NCT04801602). 9 RDTs were evaluated were including Widal test. Point estimates for sensitivity and specificity were calculated using the Wilson method. Latent class analyses were performed using R to address the imperfect gold standard. 531 serum samples were evaluated (264 blood-culture positive; 267 blood-culture negative). The sensitivity of RDTs varied widely (range 0–78.8%), with the best overall performance shown by Enterocheck WB (72.7% sensitivity: 86.5% specificity). In latent class modeling, CTK IgG was found to have the highest sensitivity (79.1%), while the highest overall accuracy was observed with Enterocheck (73.8% sensitivity and 94.5% specificity). All commercially available Salmonella Typhi RDTs evaluated in the study had sensitivity and specificity values that fell below the required levels to be recommended for an accurate diagnosis. There were minimal differences in RDT performances between endemic regions. These findings highlight the clear need for new, more accurate Salmonella Typhi tests.
MAIT cells have a negative impact on glioblastoma
Authors: Keretsu Seketoulie , Hana Taijun , Lee Alexander , Kedei Noemi , Malik Nargis , Kim Hye , Spurgeon Jo , Khayrullina Guzal , Ruf Benjamin , Hara Ayaka , Coombs Morgan , Watowich Matthew , Hari Ananth , Ford Michael K.B. , Sahinalp Cenk , Watanabe Masashi , Zaki George , Gilbert Mark R. , Cimino Patrick. J. , Prins Robert , Terabe Masaki
Published: July 2022

Glioblastoma (GBM) is the most aggressive primary brain cancer in adults and remains incurable. Our study revealed an immunosuppressive role of mucosal-associated invariant T (MAIT) cells in GBM. In bulk RNA sequencing data analysis of GBM tissues, MAIT cell gene signature significantly correlated with poor patient survival. A scRNA-seq of CD45+cells from 23 GBM tissue samples showed 15 (65.2%) were positive for MAIT cells and the enrichment of MAIT17. The MAIT cell signature significantly correlated with the activity of tumor-associated neutrophils (TANs) and myeloid-derived suppressor cells (MDSCs). Multiple immune suppressive genes known to be used by TANs/MDSCs were upregulated in MAIT-positive tumors. Spatial imaging analysis of GBM tissues showed that all specimens were positive for both MAIT cells and TANs and localized enrichment of TANs. These findings highlight the MAIT-TAN/MDSC axis as a novel therapeutic target to modulate GBM’s immunosuppressive tumor microenvironment.
The snapdragon genomes reveal the evolutionary dynamics of theSlocus supergene
Authors: Zhu Sihui , Zhang Yu’e , Copsy Lucy , Han Qianqian , Zheng Dongfeng , Coen Enrico , Xue Yongbiao
Published: July 2022

The multi-allelicS-locus, containing a pistilS-RNaseand dozens ofS-locus F-box (SLF), underlies genetic control of self-incompatibility (SI) inAntirrhinum hispanicum. The genusAntirrhinum, harboring such a SI system has been used as a model to study self-incompatibility extensively. However, there have been limited studies on the genomic organization of theS-locus supergene due to a lack of high-quality genomic data. Here, we present the chromosome-level reference and haplotype-resolved genome assemblies of a self-incompatibleAntirrhinum hispanicumline,AhS7S8. Alongside with the draft genome ofMisopates orontium, comparative genomics reveals thatA.hispanicumdiverged from its self-compatible cousin 12.3 million years ago (Mya). Expanded gene families enriched in distinct functional terms implied different evolutionary trajectories of outcrossing and selfing species. For the first time, two completeA.hispanicum S-haplotypes spanning ∼1.2Mb and containing 32SLFswere reconstructed, while most of theSLFsderived from retroelement-mediated proximal or tandem duplication approximately 122 Mya. Moreover, we detected a candidatecis-transcription factor associated with regulatingSLFs expression, and two miRNAs may control the expression of this transcription factor. Inter-specificS-locus and intra-specificS-haplotype comparisons revealed the dynamic nature and polymorphism of theS-locus supergene mediated by continuous gene duplication, segmental translocation or loss, and TE-involved transposition events. Our data provides an excellent resource for future research on the evolutionary studies onS-RNase-based self-incompatibility system.