bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recipient and Graft Outcomes in Simultaneous Kidney and Pancreas Transplantation With Steroid Avoidance in the United States
Authors: Cerise Adam , Shaker Tamer , LeNguyen Phuoc , Dinesh Anant , Jackson Scott , Kandaswamy Raja , Riad Samy 
Published: October 2022

Background.
Steroid avoidance in kidney transplantation has been proven noninferior. Long-term outcome data on steroid avoidance in simultaneous pancreas-kidney (SPK) remains scant.

Methods.
Utilizing the Scientific Registry of Transplant Recipients between 2000 and 2020, we studied all primary crossmatch negative SPK recipients (N = 5683) who received antithymocyte globulin induction and were discharged alive with functioning grafts on tacrolimus and mycophenolate ± steroid maintenance. Recipients were grouped according to steroid use into 2 groups: steroid maintenance (n = 4191) and steroid avoidance (n = 1492). Kaplan-Meier curves censored at 10 y were generated for recipient and allograft survival by steroid maintenance. Predictors for recipient and graft survival were examined using Cox Proportional Hazards. Models were adjusted for age, body mass index, ethnicity, diabetes type, human leukocyte-antigen mismatches, cold ischemia time, transplant era, preemptive transplantation, and pancreas donor risk index with the transplant center included as a random effect.

Results.
Steroid avoidance gained popularity over time, accounting for over one-fourth of the studied cohort. One-year acute rejection rates by steroid avoidance were comparable for kidney (8.6% versus 9%, P = 0.783); however, the pancreas rejection rate was lower in the steroid avoidance group (7.9% versus 10%; P = 0.035). After adjustment, steroid avoidance did not influence recipient survival (lower level of confidence interval, adjusted hazard ratio, upper level of confidence interval: 0.94, 1.15, 1.39), pancreas (0.75, 0.93, 1.16), or kidney (0.95, 1.18, 1.45) death-censored survival, compared with steroid maintenance.

Conclusions.
Accounting for the recipient and graft characteristics, steroid avoidance is associated with similar recipient, pancreas, and kidney graft outcomes compared with steroid maintenance in SPK recipients after antithymocyte globulin induction with tacrolimus and mycophenolate maintenance.
Local IL-17 orchestrates skin aging
Authors: Solá Paloma , Mereu Elisabetta , Bonjoch Júlia , Casado Marta , Reina Oscar , Blanco Enrique , Esteller Manel , DiCroce Luciano , Heyn Holger , Solanas Guiomar , Benitah Salvador Aznar 
Published: October 2022

Abstract
Skin aging is characterized by structural and functional changes that lead
to slower wound healing and higher rate of infections, which contribute to
age-associated frailty. This likely depends on synergy between alterations in
the local microenvironment and stem cell–intrinsic changes, underscored by
pro-inflammatory microenvironments that drive pleotropic changes. To date,
little is known about the precise nature and origin of the proposed
age-associated inflammatory cues, or how they affect different tissue resident
cell types. Based on deep single-cell RNA-sequencing of the entire dermal
compartment, we now provide a comprehensive understanding of the age-associated
changes in all skin cell types. We show a previously unreported skew towards an
IL-17–expressing phenotype of Th cells, γδ T cells and innate lymphoid cells in
aged skin. Aberrant IL-17 signaling is common to many autoimmune (e.g.,
rheumatoid arthritis and psoriasis) and chronic inflammatory diseases.
Importantly, in vivo blockade of IL-17–triggered
signaling during the aging process reduces the pro-inflammatory state by
affecting immune and non-immune skin cells of both dermis and epidermis.
Strikingly, IL-17 neutralization significantly delays the appearance of
age-related traits, such as decreased epidermal thickness, increased cornified
layer thickness and ameliorated hair follicle stem cell activation and hair
shaft regeneration. Our results indicate that the aged skin shows chronic and
persistent signs of inflammation, and that age-associated increased IL-17
signaling could be targeted as a strategy to prevent age-associated skin
ailments in elderly.
Mutual inhibition of airway epithelial responses supports viral and fungal
co-pathogenesis during coinfection
Authors: Dancer Patrick , Pickard Adam , Potocka Wiktoria , Earle Kayleigh , Fortune-Grant Rachael , Kadler Karl , Bertuzzi Margherita , Gago Sara 
Published: October 2022

ABSTRACT
Awareness that fungal coinfection complicates viral respiratory infections
causing worse disease outcome has recently emerged. The environmental fungus
Aspergillus fumigatus
(Af) has been reported as the main driver of
fungal coinfection in patients suffering from viral infections caused by
Cytomegalovirus, Influenza or more recently SARS-CoV2. The airway epithelium is
the first common point of contact between inhaled pathogens and the host.
Aberrant airway epithelial cell (AEC) responses against fungal challenge have
been described in patients susceptible to aspergillosis. Therefore, it is likely
that a dysregulation of AEC responses during fungal-viral coinfection represents
a potent driver for the development of fungal disease. Here we used an
in vitro model of
Af-viral infection of AECs to determine outcomes of
spore internalisation, killing and viral replication during coinfection. Our
data indicate that viral stimulation, while boosting
Af uptake by AECs, limits
Af spore killing by those cells, favouring fungal
persistence and growth. Type I viral-induced interferon release was
significantly decreased in the presence of Af hyphal
forms suggesting a possible role of Af secreted
factors in modulating viral pathogenicity. We next explored the impact of
Af challenge in SARS-CoV2 replication within
airway epithelial cells using nano-luciferase as a measure of viral replication.
We found that Af increased SARS-CoV2 pathogenicity in
a strain-dependent manner. Collectively, our findings demonstrate a mutual
inhibition of antifungal and antiviral AEC responses during
Af-viral coinfection and also suggest that some
fungal factors might be key regulators of co-pathogenicity during in lung
infection.
A di-arginine additive for dissociation of gold nanoparticle aggregates: A matrix-insensitive approach with applications in protease detection
Authors: Retout Maurice , Jin Zhicheng , Tsujimoto Jason , Mantri Yash , Borum Raina , Creyer Matthew N. , Yim Wonjun , He Tengyu , Chang Yu-Ci , Jokerst Jesse V. 
Published: October 2022

ABSTRACTWe report the reversible aggregation of gold nanoparticle (AuNPs) assemblies via a diarginine peptide additive and thiolated PEGs (HS-PEGs). The AuNPs were first aggregated by attractive forces between the citrate-capped surface and the arginine side chains. We found that HS-PEG thiol group has higher affinity for the AuNPs surface, thus leading to redispersion and colloidal stability. In turn, there was a robust and obvious color change due to on/off plasmonic coupling. The assemblies’ dissociation was directly related to the HS-PEG structural properties such as their size or charge. As an example, HS-PEGs with a molecular weight below 1 kDa could dissociate 100% of the assemblies and restore the exact optical properties of the initial AuNPs suspension (prior to the assembly). Surprisingly, the dissociation capacity of HS-PEGs was not affected by the composition of the operating medium and could be performed in complex matrices such as plasma, saliva, bile, urine, cell lysates or even sea water. The high affinity of thiols for the gold surface encompasses by far the one of endogenous molecules and is thus favorized. Moreover, starting with AuNPs already aggregated ensured the absence of background signal as the dissociation of the assemblies was far from spontaneous. Remarkably, it was possible to dry the AuNPs assemblies and to solubilize them back with HS-PEGs, improving the colorimetric signal generation. We used this system for protease sensing in biological fluid. Trypsin was chosen as model enzyme and highly positively charged peptides were conjugated to HS-PEG molecules as cleavage substrate. The increase of positive charge of the HS-PEG-peptide conjugate quenched the dissociation capacity of the HS-PEG molecules which could only be restored by the proteolytic cleavage. Picomolar limit of detection was obtained as well as the detection in saliva or urine.TOC
Emulating clinical pressure waveforms in cell culture using an Arduino-controlled 3D-printed platform for 96-well plates
Authors: Szmelter Adam H. , Venturini Giulia , Abbed Rana J. , Acheampong Manny O. , Eddington David T. 
Published: October 2022

AbstractHigh blood pressure is the primary risk factor for heart disease, the leading cause of death globally. Despite this, current methods to replicate physiological pressures in-vitro remain limited in sophistication and throughput. Single-chamber exposure systems allow for only one pressure condition to be studied at a time and the application of dynamic pressure waveforms is currently limited to simple sine, triangular, or square waves. Here, we introduce a high-throughput hydrostatic pressure exposure system for 96-well plates. The platform can deliver a fully-customizable pressure waveform to each column of the plate, for a total of 12 simultaneous conditions. Using clinical waveform data, we are able to replicate real patients’ blood pressures as well as other medically-relevant pressures within the body and have assembled a small patient-derived waveform library of some key physiological locations. As a proof of concept, human umbilical vein endothelial cells (HUVECs) survived and proliferated under pressure for 3 days under a wide range of static and dynamic blood pressures ranging from 10 mm Hg to 400 mm Hg. Interestingly, pathologic and supraphysiologic pressure exposures did not inhibit cell proliferation. By integrating with, rather than replacing, ubiquitous lab cultureware it is our hope that this device will facilitate the incorporation of hydrostatic pressure into standard cell culture practice.
Effect of victim relatedness on cannibalistic behaviour of ladybird beetle,Menochilus sexmaculatusFabricius (Coleoptera: Coccinellidae)
Authors: Yadav Tripti , Omkar  , Mishra Geetanjali 
Published: October 2022

AbstractCannibalism is taxonomically widespread and has a large impact on the individuals’ fitness and population dynamics. Thus, identifying how the rates of cannibalism are affected by different ecological cues is crucial for predicting species evolution and population dynamics. In current experiment, we investigated how victim relatedness affects the cannibalistic tendencies of different life stages of ladybird,Menochilus sexmaculatus, which is highly cannibalistic. We provided larval instars and newly emerged adults ofM. sexmaculatuswith a choice of sibling, half-sibling and non-sibling conspecific eggs as victim of cannibalism. First victim cannibalised and latency to cannibalise were observed along with total number of victims cannibalised after 24 hours. First preference of victim did not differ with life stages of the cannibals though the number of victims cannibalized did increase with advancement in stage. Percentage of total eggs cannibalised also varied significantly with life stage and victim relatedness. First and second instars tend to cannibalise more percentage of siblings and non-sibling eggs while third instars cannibalised more percentage of non-sibling eggs; fourth instars and adults on the other hand cannibalised highest percentage of eggs irrespective of their relatedness. Insignificant effect of victim relatedness was observed on latency to cannibalise eggs, though it varied significantly with the cannibal’s life stage. Shortest latency to cannibalise was recorded for first instars and longest for adults and second instars. In conclusion, kin recognition and its avoidance is stage-specific, with fourth instar and newly emerged adults being less discriminatory as compared to early stages owing to increased evolutionary survival pressure.
Minor intron containing genes: Achilles’ heel of viruses?
Authors: Wuchty Stefan , White Alisa K. , Olthof Anouk M. , Drake Kyle , Hume Adam J. , Olejnik Judith , Mühlberger Elke , Aguiar-Pulido Vanessa , Kanadia Rahul N. 
Published: October 2022

AbstractThe pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) revealed the world’s unpreparedness to deal with the emergence of novel pathogenic viruses, pointing to the urgent need to identify targets for broad-spectrum antiviral strategies. Here, we report that proteins encoded by Minor Intron-containing Genes (MIGs) are significantly enriched in datasets of cellular proteins that are leveraged by SARS-CoV-2 and other viruses. Pointing to a general gateway for viruses to tap cellular machinery, MIG-encoded proteins (MIG-Ps) that react to the disruption of the minor spliceosome are most important points of viral attack, suggesting that MIG-Ps may pan-viral drug targets. While contemporary anti-viral drugs shun MIG-Ps, we surprisingly found that anti-cancer drugs that have been repurposed to combat SARS-CoV-2, indeed target MIG-Ps, suggesting that such genes can potentially be tapped to efficiently fight viruses.
Defective neuritogenesis inAbcd1/2deficient rat neurons due to intrinsic and astrocyte-dependent mechanisms
Authors: Golbano Arantxa , Pardo Luis , Menacho Carmen M. , Rierola Marina , Claro Enrique , Wood Levi B. , Masgrau Roser , Galea Elena 
Published: October 2022

ABSTRACTX-linked adrenoleukodystrophy (X-ALD) is a rare neurometabolic and demyelinating disorder caused by loss of function mutations of the ABCD1 transporter that imports very-long-chain fatty acids (VLCFA) into the peroxisome for beta-oxidation. Impaired ABCD1 function results in VLCFA accumulation, which ultimately causes lethal forms of X-ALD in children (CCALD) and adults (CAMN). Because X-ALD is a genetic disorder, we looked for signs of altered neurodevelopmental pathways in the transcriptomes of brain cortical tissues free of pathology from patients that died of CALD or CAMN. Several categories related to brain development, axonal growth, synaptic signaling and synaptic compartments were significantly dysregulated in both CALD and CAMN, suggesting that congenital circuit abnormalities might be structural in brains of mutated ABCD1 carriers. We partially dissected the cellular origin of dysregulated pathways using rat neuronal and astrocytic cultures in which X-ALD was modeled by silencing of Abcd1 and Abcd2 by RNA interference. Abcd2 was silenced lest it compensated for Abcd1 loss. Abcd1/2 deficient neurons presented higher rates of death, reduced sizes and defective formation of spines, dendrites and axons. The aberrant neuron development was caused by cell-autonomous and astrocyte-dependent mechanisms, and involved Wnt signaling, as suggested by the rescue of the expression of a synaptic gene upon pharmacological activation of the Wnt pathway. As recently proposed for neurogenetic disorders such as Huntington’s disease, our data suggest that X-ALD has a neurodevelopmental component that may cause psychiatric alterations and prime neural circuits for neurodegeneration. If this is the case, therapies aimed at restoring neural-circuit function in neurodevelopmental disorders may be reprofiled for X-ALD therapeutics.
READemption 2: Multi-species RNA-Seq made easy
Authors: Sauerwein Till , Bischler Thorsten , Förstner Konrad U. 
Published: October 2022

AbstractDual or Multi RNA-seq simultaneously analyze the transcriptomes of two or more interacting species to gain insights about their interplay. The RNA of the interacting species is collected and sequenced together and only separated in silico by mapping the reads to the corresponding genomes. We developed READemption 2.0, to our knowledge the first tool that performs all necessary steps to handle RNA-seq data from any number of species. These steps comprise basic quality filtering and adapter trimming of raw reads, aligning the reads to reference genomes, generating nucleotide-wise coverage files, creating gene-wise read counts and performing differential gene expression analysis. These results can be visualized by additional subcommands of the software. READemption 2.0 allows users to produce meaningful results with default settings that follow conventional standards. Furthermore, many parameters can be adjusted to meet the users’ specific needs, e.g. keeping or discarding species cross-mapped reads or normalizing the data.
Semi-supervised machine learning for sensitive open modification spectral library searching
Authors: Arab Issar , Fondrie William E. , Laukens Kris , Bittremieux Wout 
Published: October 2022

AbstractA key analysis task in mass spectrometry proteomics is matching the acquired tandem mass spectra to their originating peptides by sequence database searching or spectral library searching. Machine learning is an increasingly popular post-processing approach to maximize the number of confident spectrum identifications that can be obtained at a given false discovery rate threshold. Here, we have integrated semi-supervised machine learning in the ANN-SoLo tool, an efficient spectral library search engine that is optimized for open modification searching to identify peptides with any type of post-translational modification. We show that machine learning rescoring boosts the number of spectra that can be identified for both standard searching and open searching, and we provide insights into relevant spectrum characteristics harnessed by the machine learning model. The semi-supervised machine learning functionality has now been fully integrated into ANN-SoLo, which is available as open source under the permissive Apache 2.0 license on GitHub athttps://github.com/bittremieux/ANN-SoLo.
Two new “Incertae sedis” syllids (Annelida: Syllidae) from Brazilian oceanic islands
Authors: Nascimento Rodolfo Leandro , Fukuda Marcelo Veronesi , De Paiva Paulo Cesar 
Published: October 2022

AbstractOceanic islands present very interesting environments, known by possessing relatively distinct fauna and flora. However, taxonomic accounts from Brazilian oceanic islands focused on important groups, such as the family Syllidae, began to be published only in recent years. In this paper we provide descriptions and illustrations of two new species,Brevicirrosyllissp. nov. from Trindade Islands andWestheidesyllissp. nov. from Rocas Atoll, two incertae sedis genera previously included in the Eusyllinae subfamily. We also provide updated identification keys for both genera.
A novel micro-ECoG recording method for recording multisensory neural activity from the parietal to temporal cortices in mice
Authors: Setogawa Susumu , Kanda Ryota , Tada Shuto , Hikima Takuya , Saitoh Yoshito , Ishikawa Mikiko , Nakada Satoshi , Seki Fumiko , Hikishima Keigo , Matsumoto Hideyuki , Mizuseki Kenji , Fukayama Osamu , Osanai Makoto , Sekiguchi Hiroto , Ohkawa Noriaki 
Published: October 2022

AbstractCharacterization of inter-regional interactions in brain is essential for understanding the mechanism relevant to normal brain function and neurological disease. The recently developed flexible micro (μ)-electrocorticography (μECoG) device is one prominent method used to examine large-scale cortical activity across multiple regions. The sheet-shaped μECoG electrodes arrays can be placed on a relatively wide area of cortical surface beneath the skull by inserting the device into the space between skull and brain. Although rats and mice are useful tools for neuroscience, current μECoG recording methods in these animals are limited to the parietal region of cerebral cortex. Recording cortical activity from the temporal region of cortex in mice has proven difficult because of surgical barriers created by the skull and surrounding temporalis muscle anatomy. Here, we developed a sheet-shaped 64-channel μECoG device that allows access to the mouse temporal cortex, and we determined the factor determining the appropriate bending stiffness for the μECoG electrode array. We also established a surgical technique to implant the electrode arrays into the epidural space over a wide area of cerebral cortex covering from the barrel field to olfactory (piriform) cortex, which is the deepest region of the cerebral cortex. Using histology and computed tomography (CT) images, we confirmed that the tip of the μECoG device reached to the most ventral part of cerebral cortex without causing noticeable damage to the brain surface. Moreover, the device simultaneously recorded somatosensory and odor stimulus-evoked neural activity from dorsal and ventral parts of cerebral cortex in awake and anesthetized mice. These data indicate that our μECoG device and surgical techniques enable the recording of large-scale cortical activity from the parietal to temporal cortex in mice, including somatosensory and olfactory cortices. This system will provide more opportunities for the investigation of physiological functions from wider areas of the mouse cerebral cortex than those currently available with existing ECoG techniques.
Insulin receptor substrate 4 deficiency mediates the insulin effect on the epithelial magnesium channel TRPM6 and causes hypomagnesemia
Authors: Zhang Jing , An Sung Wan , Neelam Sudha , Bhatta Anuja , Nie Mingzhu , Duran Claudia , Bal Manjot , Latta Femke , Hou Jianghui , Otto Joseph J. , Kozlitina Julia , Lemoff Andrew , Hoenderop Joost , Baum Michel , Wolf Matthias T 
Published: October 2022

ABSTRACTThe kidney is the key regulator of magnesium (Mg2+) homeostasis in the human body. In the distal convoluted tubule (DCT), the apical epithelial magnesium (Mg2+) channel TRPM6, determines how much Mg2+is excreted in the urine. To better understand the regulation of human renal Mg2+absorption we identified novel, potential interaction partners of TRPM6 by pursuing a liquid chromatography – tandem mass spectrometry (LC-MS/MS) proteomics approach.We found insulin receptor substrate 4 (IRS4) enriched with TRPM6 tagged to glutathione S-transferase (TRPM6-GST) but not GST control. Physical interaction between IRS4 and TRPM6 was confirmed by co-immunoprecipitation. Applying microdissection of mouse tubules, we detectedIrs4mRNA expression mostly in the DCT and to a lower degree in the proximal tubule and thick ascending limb of Henle. Given the overall low abundance ofIrs4mRNA along the tubule we investigated the phenotype ofIrs4knockout mice (Irs4-/-). TheseIrs4-/-mice displayed significantly higher urinary and fecal Mg2+losses and lower blood Mg2+levels than wild-type (WT) mice. Claudin-16, claudin-19, and Hnf1b mRNA and Claudin-16 and Trpm6 protein expression was significantly higher in kidneys of 3 month oldIrs4-/-mice consistent with a compensatory mechanism to conserve Mg2+. Applying whole-cell patch-clamp recording we confirmed the stimulatory role of insulin on TRPM6 channel activity and showed that IRS4 targets the two TRPM6 phosphorylation sites T1391 and S1583 to enhance TRPM6 current density. To test the effect of Mg2+deficiency on metabolism, we performed glucose and insulin tolerance studies, which were mildly abnormal inIrs4-/-mice.SIGNIFICANCE STATEMENTMagnesium (Mg2+) is the second most abundant intracellular cation but the regulation of Mg2+homeostasis is not well understood. The kidney is the key organ for regulating Mg2+homeostasis. Insulin is a known stimulator of the apical epithelial Mg2+channel TRPM6. We present a novel modifier of Mg2+absorption with insulin receptor substrate 4 (IRS4) which illuminates further, how insulin activates the TRPM6 channel and modifies Mg2+homeostasis. Applying protein biochemistry, tubular microdissection, whole mouse physiology, and patch-clamp recording, we demonstrate that IRS4 mediates the stimulatory effect of insulin by enhancing phosphorylation of two specific TRPM6 residues.Irs4-/-mice develop increased urinary and stool Mg2+losses, lower serum Mg2+concentration, and display mild impairment in glucose and insulin tolerance.