bluuebunny/crossref_metadata_2025 huggingface dataset:
LncRNA-encoded peptides: unveiling their significance in cardiovascular physiology and pathology—current research insights
Authors: Zhang Li , Tang Mi , Diao Haoyang , Xiong Liling , Yang Xiao , Xing Shasha
Published: July 2023

Long non-coding RNAs (lncRNAs), which are RNA transcripts exceeding 200 nucleotides were believed to lack any protein-coding capacity. But advancements in -omics technology have revealed that some lncRNAs have small open reading frames (sORFs) that can be translated by ribosomes to encode peptides, some of which have important biological functions. These encoded peptides subserve important biological functions by interacting with their targets to modulate transcriptional or signalling axes, thereby enhancing or suppressing cardiovascular disease (CVD) occurrence and progression. In this review, we summarize what is known about the research strategy of lncRNA-encoded peptides, mainly comprising predictive websites/tools and experimental methods that have been widely used for prediction, identification, and validation. More importantly, we have compiled a list of lncRNA- encoded peptides, with a focus on those that play significant roles in cardiovascular physiology and pathology, including ENSRNOT (RNO)-sORF6/RNO-sORF7/RNO-sORF8, dwarf open reading frame (DOWRF), myoregulin (NLN), etc. Additionally, we have outlined the functions and mechanisms of these peptides in cardiovascular physiology and pathology, such as cardiomyocyte hypertrophy, myocardial contraction, myocardial infarction, and vascular remodelling. Finally, an overview of the existing challenges and potential future developments in the realm of lncRNA-encoded peptides was provided, with consideration given to prospective avenues for further research. Given that many lncRNA-encoded peptides have not been functionally annotated yet, their application in CVD diagnosis and treatment still requires further research.
Donor circadian clock influences the long-term survival of heart transplantation by immunoregulation
Authors: Yim Wai Yen , Xiong Tixiusi , Geng Bingchuan , Xu Li , Feng Yu , Chi Jiangyang , Guo Ruikang , Li Chenghao , Chen Yuqi , Shi Jiawei , Wang Yixuan , Dong Nianguo
Published: July 2023

Aims

Circadian clocks play important role in immunoregulation. We aimed to investigate cardiac circadian clock specific pathways and compare cardiac grafts procured at different timing on survival after transplantation to explore novel criteria for donor selection.

Methods and results

In primate heart, phase set enrichment analysis (PSEA) showed rhythmic transcripts were enriched in antigen processing and presentation during activation of circadian rhythm. Digital sorting of immune cell composition and single-sample gene set enrichment analysis (ssGSEA) in unused donor transcriptomes showed the pathway, positive regulation of circadian rhythm significantly correlates with allograft rejection and antigen presentation pathways as well as with increased compositions of matured dendritic cell, CD4+ T cell, and naive B cell. Single-centre retrospective cohort of 390 adult heart transplants between 1 January 2015 and 31 December 2020 was used to generate a propensity score matching (PSM) cohort. Survival curve differed significantly showing inferior long-term survival when donor hearts were procured at activation group (12 pm to 12 am) compared to repression group (12 am to 12 pm) (6-year survival: 64.2% vs. 75.8%, P = 0.0065). Activation group was also associated with significantly higher rates of in-hospital death, cardiopulmonary resuscitation, and usage of mechanical circulatory support after heart transplantation compared to repression group. Furthermore, tendency for post-transplant free of rejection rates was higher in repression group compared to activation group (acute rejection, Gehan–Breslow P = 0.11 and 0.04; chronic rejection, Log rank P = 0.077 and 0.15, in full and PSM cohorts, respectively). Adjusted Cox regression analysis showed that activation group was associated with 2.20 times increased hazard of death (hazard ratio: 2.20; 95% confidence interval: 1.23–3.95; P = 0.008) compared to repression group.

Conclusions

Circadian immunity may represent donor-related risk factors for cardiac allograft rejection through activating genes related to antigen presentation pathway and immune cells oscillation at specific time of day. Molecular circadian clock should be considered during retrieval of cardiac allografts in order to maximize graft durability.
Immediate and sustained increases in the activity of vagal preganglionic neurons during exercise and after exercise training
Authors: Korsak Alla , Kellett Daniel O , Aziz Qadeer , Anderson Cali , D’Souza Alicia , Tinker Andrew , Ackland Gareth L , Gourine Alexander V
Published: July 2023

Aims

The brain controls the heart by dynamic recruitment and withdrawal of cardiac parasympathetic (vagal) and sympathetic activity. Autonomic control is essential for the development of cardiovascular responses during exercise, however, the patterns of changes in the activity of the two autonomic limbs, and their functional interactions in orchestrating physiological responses during exercise, are not fully understood. The aim of this study was to characterize changes in vagal parasympathetic drive in response to exercise and exercise training by directly recording the electrical activity of vagal preganglionic neurons in experimental animals (rats).

Methods and results

Single unit recordings were made using carbon-fibre microelectrodes from the populations of vagal preganglionic neurons of the nucleus ambiguus (NA) and the dorsal vagal motor nucleus of the brainstem. It was found that (i) vagal preganglionic neurons of the NA and the dorsal vagal motor nucleus are strongly activated during bouts of acute exercise, and (ii) exercise training markedly increases the resting activity of both populations of vagal preganglionic neurons and augments the excitatory responses of NA neurons during exercise.

Conclusions

These data show that central vagal drive increases during exercise and provide the first direct neurophysiological evidence that exercise training increases vagal tone. The data argue against the notion of exercise-induced central vagal withdrawal during exercise. We propose that robust increases in the activity of vagal preganglionic neurons during bouts of exercise underlie activity-dependent plasticity, leading to higher resting vagal tone that confers multiple health benefits associated with regular exercise.
Deaf and Hearing American Sign Language–English Bilinguals: Typical Bilingual Language Development
Authors: Goodwin Corina , Lillo-Martin Diane
Published: July 2023

Some studies have concluded that sign language hinders spoken language development for deaf and hard-of-hearing (DHH) children even though sign language exposure could protect DHH children from experiencing language deprivation. Furthermore, this research has rarely considered the bilingualism of children learning a signed and a spoken language. Here we compare spoken English development in 2–6-year-old deaf and hearing American Sign Language–English bilingual children to each other and to monolingual English speakers in a comparison database. Age predicted bilinguals’ language scores on all measures, whereas hearing status was only significant for one measure. Both bilingual groups tended to score below monolinguals. Deaf bilinguals’ scores differed more from monolinguals, potentially because of later age of and less total exposure to English, and/or to hearing through a cochlear implant. Overall, these results are consistent with typical early bilingual language development. Research and practice must treat signing-speaking children as bilinguals and consider the bilingual language development literature.
A reconsideration of the economic decline of the British aristocracy 1858–2018
Authors: Bond Matthew , Morton Julien
Published: July 2023

Historical accounts of the British aristocracy argue its economic decline was owed to anachronistic characteristics, declining land values, and inheritance taxes. We find disconfirming evidence based on the hereditary peerage's probates 1858 to 2018, showing: decline only began after World War I; no links between aristocratic wealth and farmland prices; and a greater role for tax avoidance with respect to inheritance taxes. Aristocrats also followed the rich with their share of wealth dwindling over the 20th century. Together, these arguments suggest the British aristocracy detached economic interests from status characteristics enabling them to persist more effectively than previously thought.
Unraveling the contributions of atmospheric rivers on Antarctica crustal deformation and its spatiotemporal distribution during the past decade
Authors: Li Jingming , Li Wenhao , Shum C K , Li Fei , Zhang Shengkai , Lei Jintao
Published: July 2023

Atmospheric rivers (ARs) are efficient mechanisms for transporting atmospheric moisture from low latitudes to the Antarctic continent. AR events induce intense snowfall episodes, which increase crustal deformation. Here, we used an AR detection algorithm, via a spatial matrix operation to quantify the contribution of AR-induced snowfall in the Antarctic continent, 2010–2019. Our results reveal that the AR snowfall contribution to Antarctica primarily ranged from 9.28 to 29.73 per cent from 2010 to 2019, and there was an evident increasing trend from 2015 to 2019 (20.66 per cent in 2015 to 29.30 per cent in 2019). AR-induced snowfall is one of the factors influencing the surface deformation of the Antarctic continent, based on the hourly AR snowfall deformation calculations for the Antarctic continent, both the average and maximum crustal deformation or displacement tends to be greatest near the coastline, while the displacement is less affected by AR further inland.
Hubris balancing: classical realism, self-deception and Putin's war against Ukraine
Authors: Ito Ryuta
Published: July 2023

Why did Putin decide to invade Ukraine in 2022? Structural realists regard it as a preventive war with a strategic rationale in response to NATO's eastward expansion. However, as many scholars suggest, Putin's decision-making is riddled with various irrationalities, which can be better framed as overbalancing and the classical realist concept of ‘hubris’. Lawrence Freedman and others argue that a key to explaining Putin's overbalancing is applying the concept of self-deception in evolutionary psychology, which can be the scientific foundation of hubris in classical realism. Thus, Freedman's argument of Putin's self-deception and others' general theses of self-deception as a cause of overconfidence led to the introduction of self-deception into classical realism to solve the puzzle of overbalancing in international affairs. Thereby, the novel balancing concept of ‘hubris balancing’ was developed: irrationally aggressive balancing that exceeds what is achievable in practice. There are three causal pathways (cognitive, emotional and social) to hubris balancing as ideal types: overconfidence, anger and nationalism. As a plausibility probe, hubris balancing is illustrated by analysing Putin's decision to wage war against Ukraine. The result shows that, as the logic of hubris balancing suggests, driven by overconfidence and anger towards western liberalism, Putin decided to invade Ukraine by driving exclusive nationalism.
Intralobular pulmonary sequestration of the right upper lobe supplied by ascending aorta
Authors: Wang Xiao-Xia , Zhang Hong-Sheng , Sui Yun-Xia , Liu Jie
Published: July 2023

Pulmonary sequestration (PS) is a rare congenital lung malformation that is more common in the left lower lobe. In 95% of cases, the artery supplying the sequestration usually originates from the thoracic and abdominal aorta. We report a rare intralobular PS case for a feeding artery from the ascending aorta. Angio-computed tomography should be performed for diagnosis once PS is suspected.
Uniform stabilization of a Schrödinger equation with partial Dirichlet delayed control
Authors: Wang Xiaorui , Li Yanfang
Published: July 2023

In this paper, the uniform stabilization of a multi-dimensional Schrödinger equation with partial Dirichlet delayed control is concerned. The control input is suffered from time delay. Herein a new feedback controller is adopted in the investigation. Firstly, we rewrite the delayed system under consideration into a cascaded system of a transport equation and a Schrödinger equation, and construct an exponentially stable target system. Then by defining a bounded invertible linear transformation and choosing some appropriate kernel functions, we establish the equivalence between the closed-loop system and the target system. Finally, the exponential stability of the closed-loop system is obtained.
The effects of BPA-BNCT on normal bone: determination of the CBE value in mice
Authors: Iwasaki Ryota , Yoshikawa Ryutaro , Umeno Ryo , Seki Azusa , Matsukawa Takehisa , Takeno Satoshi , Yokoyama Kazuhito , Mori Takashi , Suzuki Minoru , Ono Koji
Published: July 2023

Boron neutron capture therapy (BNCT) with p-boronophenylalanine (BPA) is expected to have less effect on the decrease in normal bone strength than X-ray therapy. However, the compound biological effectiveness (CBE) value necessary to convert the boron neutron capture reaction (BNCR) dose into a bioequivalent X-ray dose has not been determined yet. The purpose of this study was to evaluate the influence of BNCT on normal bone in mice and to elucidate the CBE factor. We first searched the distribution of BPA in the normal bone of C3H/He mice and then measured the changes in bone strength after irradiation. The CBE value was determined when the decrease in bone strength was set as an index of the BNCT effect. The 10B concentrations in the tibia after subcutaneous injection of 125, 250 and 500 mg/kg BPA were measured by prompt gamma-ray spectroscopy and inductively coupled plasma (ICP)-atomic emission spectrometry. The 10B mapping in the tibia was examined by alpha-track autoradiography and laser ablation-ICP-mass spectrometry. The 10B concentration increased dose-dependently; moreover, the concentrations were maintained until 120 min after BPA administration. The administered 10B in the tibia was abundantly accumulated in the growth cartilage, trabecular bone and bone marrow. The bone strength was analyzed by a three-point bending test 12 weeks after irradiation. The bending strength of the tibia decreased dose-dependently after the irradiation of X-ray, neutron and BNCR. The CBE factor was obtained as 2.27 by comparing these dose-effect curves; the value determined in this study will enable an accurate dosimetry of normal bone.
Hybrid staged approach to subclavian artery aneurysm repair with aberrant dominant left vertebral artery
Authors: Clausen David J , Kanitra John , Bendix Scott
Published: July 2023

Intrathoracic subclavian aneurysms are a rare entity, accounting for only a small percentage of all repaired aneurysms. These are repaired to alleviate symptoms and prevent complications of rupture, thrombosis and distal embolization. Most of these are amenable to thoracic endovascular aneurysm repair (TEVAR), which has resulted in an associated reduction in operative mortality. When there is a proximal involvement of the artery, revascularization is recommended prior to TEVAR. Herein, we present the case of a proximal subclavian aneurysm with an aberrant left vertebral artery that originated off the aortic arch. This was repaired using a two staged approach; carotid-subclavian bypass with vertebral artery-transposition followed by TEVAR.
An inguinal hernia ‘hard to stomach’
Authors: Liechty Shawn , Eiref Andrew D , Vengatesan Keerthivasan , Barasch Samuel P , Dong Xiang D , Zimmerman Patrick W , Nicoara Michael , Patel Krishan , Walden Heath , Eiref Simon D
Published: July 2023

Inguinal hernias containing the stomach are extremely rare, and have never been described in females. We are reporting the case of a 79 year old female who presented in septic shock with a left inguinal hernia containing the stomach, resulting in gastric perforation and loss of abdominal domain. She underwent emergency exploratory laparotomy with manual reduction of the hernia, wedge resection of the perforated gastric segment, abdominal washout, and closure of the abdominal fascia using biological mesh. She had a complicated but successful postoperative course, and was discharged to a rehabilitation center three weeks after hospital admission.
The dire consequences of multiple failed hypospadias repairs: a case report of a cavernosal reconstruction with mesh and malleable prosthesis
Authors: Tozzi Marco , Gobbo Andrea , Yebes Alvaro , Spiridonescu Bogdan , Djinovic Rados
Published: July 2023

The management of hypospadias during the neonatal period should be carried out exclusively in specialized medical centers because of the potential dire complications that may arise. In this report, we present a case of a 22-year-old male who underwent thirteen unsuccessful surgical procedures for his penoscrotal hypospadias in various hospitals. The purpose of this case report is to describe the surgical correction of severe corporal fibrosis and penile curvature that ensued from the multiple failed hypospadias corrections. We implanted an extra cavernosal malleable penile prosthesis and reconstructed the tunica albuginea defect with surgical meshes used in hernia repairs.
On identity, indiscernibility and (non-)individuality in the quantum domain
Authors: Krause Décio
Published: July 2023

The topics of identity, individuality and indiscernibility had already entered the domain of the philosophy of physics, mainly in what respects the philosophy of quantum theories. In this paper, I present the main ideas of an underlying metaphysics that considers the basic entities of quantum physics as non-individuals, that is, as entities to which the standard theory of identity of classical logic and standard mathematics (set theory) does not apply. Two things must be emphasized: the first is that we pursue Erwin Schrödinger’s ideas that the notion of identity (orsameness) does not apply to quantum things; the second is to follow Heinz Post’s claim that the non-individuality of quantum entities ‘must be introduced right at the start’ and not by takingindividualsand making them pretend to be non-individuals ‘by hand’, say by confining them to non-rigid structures. Thus, this paper should be regarded as an attempt to justify the metaphysics of non-individuals and the logical systems that cope with them, although these systems are here only referred to. We also answer some criticisms that have been directed to such a view. The paper is directed to an audience of both physicists interested in foundations and philosophers of physics.

This article is part of the theme issue ‘Identity, individuality and indistinguishability in physics and mathematics’.
A no-individuals account of quantum mechanics
Authors: Arenhart Jonas Rafael Becker
Published: July 2023

One of the most famous metaphysical problems in the philosophy of quantum mechanics concerns the individuality status of quantum entities: are they individuals, or non-individuals? The typical approach to the problem consists in defending one of the options by appealing directly to features of quantum mechanics with the addition, eventually, of theoretical virtues the favoured proposal may have. In this paper, we argue that this strategy is inappropriate, because the problem of individuality is ill formulated in the case of quantum mechanics. In a nutshell, our point is that considerations exclusively from quantum mechanics are too general and generic to grant the level of particularity required for providing for a principle of individuality. Problems of individuality appear only at the level of particular applications of the theory in specific contexts, and in these cases, we shall argue, search for a metaphysical notion of individuality may be substituted by an epistemic notion of individuation. The approach also has the benefits of dissolving the problems created by metaphysical underdetermination on this front.

This article is part of the theme issue 'Identity, individuality and indistinguishability in physics and mathematics'.
Ontological indistinguishability as a central tenet of quantum theory
Authors: de Barros J. A. , Holik F.
Published: July 2023

Quantum indistinguishability directly relates to the philosophical debate on the notions of identity and individuality. They are crucial for our understanding of multipartite quantum systems. Furthermore, the correct interpretation of this feature of quantum theory has implications that transcend fundamental science and philosophy, given that quantum indistinguishability is a resource in quantum information theory. Most of the conceptual analysis of quantum indistinguishability is restricted to studying the permutational invariance of quantum states, the concomitant quantum statistics and their entanglement. Here, we analyse the role of indistinguishability and non-individuality in other areas of quantum theory. We start by analysing how a very peculiar use of indistinguishability underlies Feynman’s rules for summing amplitudes in interference phenomena. Next, we study how quantum indistinguishability is underestimated in several topics of debate in the quantum physics literature, such as the Einstein–Podolsky–Rosen argument, Bell’s inequalities and the Bell–Kochen–Specker theorem. Finally, we argue that an ontology of truly indistinguishable entities can serve as a basis for a quantum ontology that can give interesting answers to the interpretational problems of quantum mechanics. We claim that, in addition to superposition, contextuality and entanglement, indistinguishability (understood in a robust ontological sense) is one of the central features of quantum physics.

This article is part of the theme issue ‘Identity, individuality and indistinguishability in physics and mathematics’.
Aristotle on identity: close enough!
Authors: Muller F. A.
Published: July 2023

We present what Aristotle wrote on identity in a leisurely manner, which is much more than is generally known, save among the
cognoscenti
(Aristotle scholars), and
mutatis mutandis
about the introduction of the identity-symbol

(
=
)

. We add two codas, one on the so-called Leibniz’ Law, which is different (but resembles) what passes for it in logic and philosophy, and one on the status of identity, as accepted by mathematicians and logicians, in physics.

This article is part of the theme issue ‘Identity, individuality and indistinguishability in physics and mathematics’.
Abstraction, equality and univalence
Authors: Catren Gabriel
Published: July 2023

We shall propose a conceptual-oriented discussion of the so-called Univalent Foundations Program, that is, of Martin–Löf type theory enriched with a homotopic interpretation, together with the univalence axiom proposed by Voevodsky. We shall argue that the type-theoretic notion of
propositional equality
encodes the notion of
indiscernibility
, we shall address the homotopic interpretation of Martin–Löf type theory, and we shall analyse whether Leibniz’s principle of the identity of indiscernibles holds or not in Univalent Foundations. We shall finally argue that univalence can be understood as a particular implementation of a constructive notion of abstraction that resolves Fregean abstraction.

This article is part of the theme issue ‘Identity, individuality and indistinguishability in physics and mathematics’.
Generating indistinguishability within identical particle systems: spatial deformations as quantum resource activators
Authors: Piccolini Matteo , Nosrati Farzam , Adesso Gerardo , Morandotti Roberto , Lo Franco Rosario
Published: July 2023

Identical quantum subsystems can possess a property which does not have any classical counterpart: indistinguishability. As a long-debated phenomenon, identical particles’ indistinguishability has been shown to be at the heart of various fundamental physical results. When concerned with the spatial degree of freedom, identical constituents can be made indistinguishable by overlapping their spatial wave functions via appropriately definedspatial deformations. By the laws of quantum mechanics, any measurement designed to resolve a quantity which depends on the spatial degree of freedom only and performed on the regions of overlap is not able to assign the measured outcome to one specific particle within the system. The result is an entangled state where the measured property issharedbetween the identical constituents. In this work, we present a coherent formalization of the concept of deformation in a generalN-particle scenario, together with a suitable measure of the degree of indistinguishability. We highlight the basic differences with non-identical particles scenarios and discuss the inherent role of spatial deformations as entanglement activators within thespatially localized operations and classical communicationoperational framework.

This article is part of the theme issue ‘Identity, individuality and indistinguishability in physics and mathematics’.
Identity, individuality and indistinguishability in physics and mathematics
Authors: Catren Gabriel
Published: July 2023

In this brief survey, we discuss some of the scientific and philosophical problems and debates that underlie the notions ofidentity,individualityandindistinguishabilityin physics and mathematics. We critically analyse the different positions for or against the existence of indistinguishable objects in different scientific theories, notably quantum mechanics and gauge theories in physics and homotopy type theory in mathematics. We argue that the different forms of indistinguishability that occur in many areas of physics and mathematics—far from being a problem to be eradicated—exhibit a rich formal structure that plays a key role in the corresponding theories that needs to be properly understood.

This article is part of the theme issue ‘Identity, individuality and indistinguishability in physics and mathematics’.
Effects of online tDCS and hf-tRNS on reading performance in children and adolescents with developmental dyslexia: a study protocol for a within-subject, randomized, double-blind, and sham-controlled trial
Authors: Battisti Andrea , Lazzaro Giulia , Varuzza Cristiana , Vicari Stefano , Menghini Deny
Published: July 2023

Background

Developmental Dyslexia (DD) is a brain-based developmental disorder characterized by severe impairments in the acquisition of fluent and/or accurate reading. The extensive data on the neurobiology of DD have increased interest inbrain-directedapproaches. Transcranial direct current stimulation (tDCS) has been proposed as a non-invasive method to address reading difficulties in individuals with DD. While overall positive outcomes have been observed, the results remain heterogeneous. To enhance the current findings, various modalities have been employed, including manipulation of electrode montages, experimental designs, and targeting different brain regions. However, no studies have yet investigated the comparative effects of two different types of transcranial electrical stimulation, namely tDCS and transcranial random noise stimulation (tRNS), on reading abilities in children and adolescents with DD.

Methods

The present study will apply a within-subject, randomized, double-blind, and sham-controlled design. The aim of the present study is to investigate the effects of tDCS and tRNS on reading abilities in children and adolescents with DD. Participants will undergo three conditions, each separated by a one-week interval: (A) a single session of active tDCS; (B) a single session of active tRNS; and (C) a single session of sham (tDCS or sham tRNS). The order of the sessions will be counter-matched among participants. Left anodal/right cathodal tDCS and bilateral tRNS will be applied over the temporo-parietal regions for a duration of 20 minutes. The assessment of text, word, and non-word reading measures will be conducted immediately before and during each stimulation sessions. Safety, tolerability and blinding parameters will be assessed using a questionnaire.

Results

Our hypothesis is that tRNS will demonstrate comparable effectiveness to tDCS in improving text, word, and non-word reading measures compared to the sham conditions. Additionally, we anticipate that tRNS will exhibit a similar safety profile to tDCS.

Conclusion

This study has the potential to contribute novel insights into the effectiveness of tRNS, a newly-wave tES method that has not yet been explored in children and adolescents with DD. Furthermore, findings may lay the groundwork for further investigations involving multiple tRNS sessions.

Trial registration

The study has been registered withClinicalTrials.govunder the identifierNCT05832060.
Does larval ability to modulate body buoyancy explain successful colonization of freshwater environments by diadromous gobies?
Authors: Oto Yumeki , Watanabe Katsutoshi
Published: July 2023

Salinity is an environmental factor that strongly characterizes the habitat use patterns of aquatic organisms. However, knowledge is biased toward the effect of differences in osmotic pressure among salinity habitats; how ambient specific gravity (SG) differences determine species distribution is scarcely understood. Diadromous fish, which migrate between marine and freshwater habitats, may encounter this SG problem when they are unexpectedly landlocked in or colonize freshwater areas with low environmental SG. This is particularly serious for planktonic larval fish, which must maintain neutral buoyancy for foraging and passive locomotion, although their swimbladders are generally underdeveloped. Then, we hypothesized that the SG problem limits the establishment of freshwater resident populations in marine-originated diadromous fishes. To test this hypothesis, the SG modulation ability of newly hatched larvae was compared among three closely related diadromous goby species inGymnogobius, one of which has freshwater resident populations. The aquarium experimental results did not support that only the species deriving freshwater residents can maintain neutral buoyancy even in freshwater conditions; that is, all three species could modulate their body SG almost equally to those of both fresh and sea waters. This suggests that the ability to maintain neutral buoyancy in freshwater had been pre-adaptively acquired prior to larval freshwater colonization. On the other hand, it is highly noteworthy that the early larvae of the target group maintained neutral buoyancy in various SG environments using swimbladders, which is the first such evidence in teleosts.
Computational prediction of protein interactions on single cells by proximity sequencing
Authors: Xia Junjie , Van Phan Hoang , Vistain Luke , Chen Mengjie , Khan Aly A. , Tay Savaş
Published: July 2023

Proximity sequencing (Prox-seq) measures gene expression, protein expression, and protein complexes at the single cell level, using information from dual-antibody binding events and a single cell sequencing readout. Prox-seq provides multi-dimensional phenotyping of single cells and was recently used to track the formation of receptor complexes during inflammatory signaling in macrophages and to discover a new interaction between CD9/CD8 proteins on naïve T cells. The distribution of protein abundance affects identification of protein complexes in a complicated manner in dual-binding assays like Prox-seq. These effects are difficult to explore with experiments, yet important for accurate quantification of protein complexes. Here, we introduce a physical model for protein dimer formation on single cells and computationally evaluate several different methods for reducing background noise when quantifying protein complexes. Furthermore, we developed an improved method for analysis of Prox-seq single-cell data, which resulted in more accurate and robust quantification of protein complexes. Finally, our model offers a simple way to investigate the behavior of Prox-seq under various biological conditions and guide users toward selecting the best analysis method for their data.
Evolutionary signatures of human cancers revealed via genomic analysis of over 35,000 patients
Authors: Fontana Diletta , Crespiatico Ilaria , Crippa Valentina , Malighetti Federica , Villa Matteo , Angaroni Fabrizio , Sano Luca De , Aroldi Andrea , Antoniotti Marco , Caravagna Giulio , Piazza Rocco , Graudenzi Alex , Mologni Luca , Ramazzotti Daniele
Published: July 2023

By leveraging the ever-increasing availability of cancer omics data and the continuous advances in cancer data science and machine learning, we have discovered the existence of cancer type-specificevolutionary signaturesassociated with different disease outcomes. These signatures represent “favored trajectories” of acquisition of driver mutations that are repeatedly detected in patients with similar prognosis. In this work, we present a novel framework named ASCETIC (Agony-baSedCancerEvoluTion InferenCe) that extracts such signatures from NGS experiments generated by different technologies such as bulk and single-cell sequencing data. In our study, we applied ASCETIC to (i) single-cell sequencing data from 146 patients with distinct myeloid malignancies and bulk whole-exome sequencing data from 366 acute myeloid leukemia patients, (ii) multi-region sequencing data from 100 early-stage lung cancer patients from the TRACERx project, (iii) whole-exome/genome sequencing data from more than 10,000 Pan-Cancer Atlas samples, and (iv) targeted bulk sequencing data from more than 25,000 MSK-MET metastatic patients (both datasets including multiple cancer types). As a result, we extracted different cancer (sub)type-specific single-nucleotide variants evolutionary signatures associated with clusters of patients with statistically significant different prognoses. In addition, we conducted several validations using diverse and previously unexplored datasets to evaluate the reliability and applicability of the evolutionary signatures extracted by ASCETIC. Such analyses provided evidence of the robustness and generalizability of the identified evolutionary patterns.
An Optimized Pipeline for Detection of Salmonella Sequences in Shotgun Metagenomics Datasets
Authors: Bradford Lauren M. , Carrillo Catherine , Wong Alex
Published: July 2023

Background

Culture-independent diagnostic tests (CIDTs) are gaining popularity as tools for detecting pathogens in food. Shotgun sequencing holds substantial promise for food testing as it provides abundant information on microbial communities, but the challenge is in analyzing large and complex sequencing datasets with a high degree of both sensitivity and specificity. Falsely classifying sequencing reads as originating from pathogens can lead to unnecessary food recalls or production shutdowns, while low sensitivity resulting in false negatives could lead to preventable illness.

Results

We have developed a bioinformatic pipeline for identifyingSalmonellaas a model pathogen in metagenomic datasets with very high sensitivity and specificity. We tested this pipeline on mock communities of closely related bacteria and with simulatedSalmonellareads added to published metagenomic datasets.Salmonella-derived reads could be found at very low abundances (high sensitivity) without false positives (high specificity). Carefully considering software parameters and database choices is essential to avoiding false positive sample calls. With well-chosen parameters plus additional steps to confirm the taxonomic origin of reads, it is possible to detect pathogens with very high specificity and sensitivity.
Emergence of selectivity and specificity in a coarse-grained model of the nuclear pore complex with sequence-agnostic FG-Nups
Authors: Patel Manoj Kumar , Chakrabarti Buddhapriya , Panwar Ajay Singh
Published: July 2023

The role of hydrophobicity of phenylalanine-glycine nucleoporins (FG-Nups) in determining transport of receptor-bound cargo across the nuclear pore complex (NPC) is investigated using Langevin dynamics simulations. A coarse-grained, minimal model of the NPC, comprising a cylindrical pore and hydrophobic-hydrophilic random copolymers for FG-Nups was employed. Karyopherin-bound receptor-cargo complexes (Kaps) were modeled as rigid, coarse-grained spheres without (inert) and with (patchy) FG-binding hydrophobic domains. With a sequence-agnostic description of FG-Nups and the absence of any anisotropies associated with either NPC or cargo, the model described tracer transport only as a function of FG-Nup hydrophobicity,f. The simulations showed the emergence of two important features of cargo transport, namely, NPC selectivity and specificity. NPC selectivity to patchy tracers emerged due to hydrophobic Kap-FG interactions and despite the sequence-agnostic description of FG-Nups. Further, NPC selectivity was observed only in a specific range of FG-hydrophobic fraction, 0.05 ≤f≤ 0.20, resulting in specificity of NPC transport with respect tof. Significantly, this range corresponded to the number fraction of FG-repeats observed in bothS. cerevisiaeandH. sapiensNPCs. This established the centrality of FG-hydrophobic fraction in determining NPC transport, and provided a biophysical basis for conservation of FG-Nup hydrophobic fraction across evolutionarily distant NPCs. Specificity in NPC transport emerged from the formation of a hydrogel-like network inside the pore with a characteristic mesh size dependent onf. This network rejected cargo forf> 0.2 based on size exclusion which resulted in an enhanced translocation probability for 0.05 ≤f≤ 0.20. Thus, the NPC model provides a template for designing synthetic, biomimetic nanopores for macromolecular separations with high degrees of selectivity and specificity.
einprot: flexible, easy-to-use, reproducible workflows for statistical analysis of quantitative proteomics data
Authors: Soneson Charlotte , Iesmantavicius Vytautas , Hess Daniel , Stadler Michael B , Seebacher Jan
Published: July 2023

We describe einprot, an R package providing easy-to-use reproducible workflows for quality control, statistical analysis and visualization of quantitative proteomics data. einprot is applicable to tabular output from MaxQuant, Proteome Discoverer and FragPipe, and a single function call generates an html report that describes the full analysis pipeline applied to the data and contains static and interactive figures and tables for further exploration. This has the potential to facilitate routine analyses as well as to provide a standardized, yet comprehensive way to communicate results to collaborators and the broader community. The source file underlying the report is also returned, giving the user full flexibility to further modify the workflow according to their needs.
Extended Similarity Methods for Efficient Data Mining in Imaging Mass Spectrometry
Authors: Ellin Nicholas R. , Miranda-Quintana Ramón Alain , Prentice Boone M.
Published: July 2023

Imaging mass spectrometry is a label-free imaging modality that allows for the spatial mapping of many compounds directly in tissues. In an imaging mass spectrometry experiment, a raster of the tissue surface produces a mass spectrum at each sampledx,yposition, resulting in thousands of individual mass spectra, each comprising a pixel in the resulting ion images. However, efficient analysis of imaging mass spectrometry datasets can be challenging due to the hyperspectral characteristics of the data. Each spectrum contains several thousand unique compounds at discretem/zvalues that result in unique ion images, which demands robust and efficient algorithms for searching, statistical analysis, and visualization. Some traditional post-processing techniques are fundamentally ill-equipped to dissect these types of data. For example, while principal component analysis (PCA) has long served as a useful tool for mining imaging mass spectrometry datasets to identify correlated analytes and biological regions of interest, the interpretation of the PCA scores and loadings can be non-trivial. The loadings often containing negative peaks in the PCA-derived pseudo-spectra, which are difficult to ascribe to underlying tissue biology. Herein, we have utilized extended similarity indices to streamline the interpretation of imaging mass spectrometry data. This novel workflow uses PCA as a pixel-selection method to parse out the most and least correlated pixels, which are then compared using the extended similarity indices. The extended similarity indices complement PCA by removing all non-physical artifacts and streamlining the interpretation of large volumes of IMS spectra simultaneously. The linear complexity, O(N), of these indices suggests that large imaging mass spectrometry datasets can be analyzed in a 1:1 scale of time and space with respect to the size of the input data. The extended similarity indices algorithmic workflow is exemplified here by identifying discrete biological regions of mouse brain tissue.
Modeling time-varying phytoplankton subsidy reveals at-risk species in a Chilean intertidal ecosystem
Authors: Duckwall Casey S. , Largier John L. , Wieters Evie A. , Valdovinos Fernanda S.
Published: July 2023

The allometric trophic network (ATN) framework for modeling population dynamics has provided numerous insights into ecosystem functioning in recent years. Herein we extend ATN modeling of the intertidal ecosystem off the central coast of Chile to include empirical data on pelagic chlorophyll-a concentration. This intertidal community requires subsidy of primary productivity to support its rich ecosystem. Previous work models this subsidy using a constant rate of phytoplankton input to the system. However, data shows pelagic subsidies exhibit short-term, highly variable, pulse-like behavior. Incorporating this variable input into ATN modeling is the primary contribution of this work and provides several new insights into this ecosystem’s response to pulses of offshore phytoplankton, including: (1) closely related sea snails show differential responses to pulses of phytoplankton that are explained by underlying network structure; (2) increasing the rate of pelagic-intertidal mixing increases fluctuations in species’ biomasses that may increase the risk of local extirpation; (3) predators are the most sensitive species to phytoplankton biomass fluctuations, putting these species at greater risk of extirpation than others. Finally, our work provides a straightforward way to incorporate empirical, time-series data into the ATN framework that will expand this powerful methodology to new applications.
Accounting for genetic effect heterogeneity in fine-mapping and improving power to detect gene-environment interactions with SharePro
Authors: Zhang Wenmin , Sladek Robert , Li Yue , Najafabadi Hamed S. , Dupuis Josée
Published: July 2023

Background

Characterizing genetic effect heterogeneity across subpopulations with different environmental exposures is useful for identifying exposure-specific pathways, understanding biological mechanisms underlying disease heterogeneity and further pinpointing modifiable risk factors for disease prevention and management. Classical gene-by-environment interaction (GxE) analysis can be used to characterize genetic effect heterogeneity. However, it can have a high multiple testing burden in the context of genome-wide association studies (GWAS) and requires a large sample size to achieve sufficient power.

Methods

We adapt a colocalization method, SharePro, to account for effect heterogeneity in finemapping and subsequently improve power for GxE analysis. Through joint fine-mapping of exposure stratified GWAS summary statistics, SharePro can greatly reduce multiple testing burden in GxE analysis.

Results

Through extensive simulation studies, we demonstrated that accounting for effect heterogeneity can improve power for fine-mapping. With efficient joint fine-mapping of exposure stratified GWAS summary statistics, SharePro alleviated multiple testing burden in GxE analysis and demonstrated improved power with well-controlled false discovery rate. Through analyses of smoking status stratified GWAS summary statistics, we identified genetic effects on lung function modulated by smoking status mapped to the genesCHRNA3,ADAM19andUBR1. Additionally, using sex stratified GWAS summary statistics, we characterized sex differentiated genetic effects on fat distribution and provided biologically plausible candidates for functional follow-up studies.

Conclusions

We have developed an analytical framework to account for effect heterogeneity in finemapping and subsequently improve power for GxE analysis. The SharePro software for GxE analysis is openly available athttps://github.com/zhwm/SharePro_gxe.
Functional traits fail to predict long-term responses to climate change
Authors: Ash Jeremy D. , Li Daijiang , Johnson Sarah E. , Rogers David A. , Waller Donald M.
Published: July 2023

Aim

Environmental conditions strongly affect the distribution and abundance of species via complex forces. Shifts in environmental conditions and differences in the speed and scale of these effects complicate our efforts to infer how species will respond to future environmental change. We test how 18 functional traits affect plant species responses to gradients in environmental conditions and 50-year shifts in climate.

Location

We analyzed 50-year shifts in the distribution and abundance of 153 plant species distributed across 284 sites in Wisconsin, USA.

Time period

1950s to 2000s.

Major taxa studied

Vascular plants (much of the flora of NE North America).

Methods

We used random forest and integrated hierarchical mixed models to test how plant abundances (and 50-year changes in abundance) track gradients in overstory, soil, and climatic conditions.

Results

Within study periods, plant abundances reflect gradients in environmental conditions. Leaf traits affected local abundance (both directly and via trait-environment interactions) in the 1950s and 2000s. Strong soil and temperature effects in the 1950s have weakened while precipitation effects have strengthened. Although we expected these models to also predict how plants would respond to shifts in climate, they did not.

Main conclusions

Lags in species’ responses, increases in the stochastic forces affecting community assembly, and other forces limit the ability of models fitted to static data (e.g., space-for-time substitutions) to predict how plant species will respond to long-term shifts in environmental conditions. We must therefore be cautious about applying trait-based species distribution models to predict how climate change will affect species distributions and community structure.