bluuebunny/crossref_metadata_2025 huggingface dataset:
Disappearing thermal X-ray emission as a tell-tale signature of merging massive black hole binaries
Authors: Krauth Luke Major , Davelaar Jordy , Haiman Zoltán , Westernacher-Schneider John Ryan , Zrake Jonathan , MacFadyen Andrew
Published: October 2023

The upcoming Laser Interferometer Space Antenna (LISA) is expected to detect gravitational waves (GWs) from massive black hole binaries (MBHB). Finding the electromagnetic (EM) counterparts for these GW events will be crucial for understanding how and where MBHBs merge, measuring their redshifts, constraining the Hubble constant and the graviton mass, and for other novel science applications. However, due to poor GW sky localization, multiwavelength, time-dependent EM models are needed to identify the right host galaxy. We studied merging MBHBs embedded in a circumbinary disc (CBD) using high-resolution two-dimensional simulations, with a Γ-law equation of state, incorporating viscous heating, shock heating, and radiative cooling. We simulate the binary from large separation until after merger, allowing us to model the decoupling of the binary from the CBD. We compute the EM signatures and identify distinct features before, during, and after the merger. Our main result is a multiband EM signature: we find that the MBHB produces strong thermal X-ray emission until 1–2 d prior to the merger. However, as the binary decouples from the CBD, the X-ray-bright minidiscs rapidly shrink in size, become disrupted, and the accretion rate drops precipitously. As a result, the thermal X-ray luminosity drops by orders of magnitude, and the source remains X-ray dark for several days, regardless of any post-merger effects such as GW recoil or mass-loss. Looking for the abrupt spectral change where the thermal X-ray disappears is a tell-tale EM signature of LISA mergers that does not require extensive pre-merger monitoring.
An optically thin view of the flaring chromosphere: non-thermal widths in a chromospheric condensation during an X-class solar flare
Authors: Kerr Graham S , Kowalski Adam F , Allred Joel C , Daw Adrian N , Kane Melissa R
Published: October 2023

The bulk of solar flare energy is deposited in the chromosphere. Flare ribbons and footpoints in the chromosphere therefore offer great diagnostic potential of flare energy release and transport processes. High-quality observations from the Interface Region Imaging Spectrograph (IRIS) spacecraft have transformed our view of the Sun’s atmospheric response to flares. Since most of the chromospheric lines observed by IRIS are optically thick, forward modelling is required to fully appreciate and extract the information they carry. Reproducing certain aspects of the Mg ii lines remain frustratingly out of reach in state-of-the-art flare models, which are unable to satisfactorily reproduce the very broad-line profiles. A commonly proposed resolution to this is to assert that very large values of ‘microturbulence’ is present. We assess the validity of that approach by analysing optically thin lines in the flare chromosphere from the X-class flare SOL2014-10-25T17:08:00, using the derived value of non-thermal width as a constraint to our numerical models. A non-thermal width of the order 10 km s−1 was found within the short-lived red wing components of three spectral lines, with relatively narrow stationary components. Simulations of this flare were produced, and in the post-processing spectral synthesis we include within the downflows a microturbulence of 10 km s−1. While we can reproduce the O i 1355.598 Å line rather well, and we can capture the general shape and properties of the Mg ii line, the synthetic lines are still too narrow.
The Pristine survey – XXII. A serendipitous discovery of an extremely Li-rich very metal-poor giant and a new method of 6Li/7Li isotope measurement
Authors: Sitnova T M , Matsuno T , Yuan Z , Martin N F , Banerjee P , Sestito F , Venn K A , González Hernández J I
Published: October 2023

We report the serendipitous discovery of a very metal-poor (VMP) Li-rich giant star (Teff = 4690 ± 80 K, log g = 1.34 ± 0.13, [Fe/H] = −2.43 ± 0.07). We analyse the Li i 6103 and 6707 Å lines accounting for departures from local thermodynamic equilibrium (NLTE) and correcting for 3D effects using literature data, which yields a lithium abundance log εLi = 3.42 ± 0.07. Comparing lithium abundances from the two lines, in 1D NLTE we measure the isotope ratio 6Li/7Li = 1.64$^{+1.49}_{-1.08}$ per cent. When correcting for 3D effects, we detect the fragile 6Li isotope at 2-sigma level and the ratio 6Li/7Li = 5.65$^{+5.05}_{-2.51}$ per cent. To our knowledge, this is the first 6Li/7Li measurement in an extremely Li-rich VMP star. The Cameron–Fowler mechanism, which is proposed to produce Li-rich stars, does not imply 6Li production and is therefore inconsistent with our measurement when applying 3D corrections. We also derive NLTE abundances for 16 elements, most of which show similar abundances to those found in VMP stars. Sodium is an exception: [Na/Fe]NLTE1D = 0.07 ± 0.03, which is 0.5 dex higher than what is typical for VMP stars. This star joins the sample of rare Li-rich VMP stars, and we offer a novel way to constrain the source of lithium in such stars through isotope ratio measurements.
deep PACO: combining statistical models with deep learning for exoplanet detection and characterization in direct imaging at high contrast
Authors: Flasseur Olivier , Bodrito Théo , Mairal Julien , Ponce Jean , Langlois Maud , Lagrange Anne-Marie
Published: October 2023

Direct imaging is an active research topic in astronomy for the detection and the characterization of young substellar objects. The very high contrast between the host star and its companions makes the observations particularly challenging. In this context, post-processing methods combining several images recorded with the pupil tracking mode of telescope are needed. In previous works, we have presented a data-driven algorithm, PACO, capturing locally the spatial correlations of the data with a multivariate Gaussian model. PACO delivers better detection sensitivity and confidence than the standard post-processing methods of the field. However, there is room for improvement due to the approximate fidelity of the PACO statistical model to the time evolving observations. In this paper, we propose to combine the statistical model of PACO with supervised deep learning. The data are first pre-processed with the PACO framework to improve the stationarity and the contrast. A convolutional neural network (CNN) is then trained in a supervised fashion to detect the residual signature of synthetic sources. Finally, the trained network delivers a detection map. The photometry of detected sources is estimated by a second CNN. We apply the proposed approach to several data sets from the VLT/SPHERE instrument. Our results show that its detection stage performs significantly better than baseline methods (cADI and PCA), and leads to a contrast improvement up to half a magnitude compared to PACO. The characterization stage of the proposed method performs on average on par with or better than the comparative algorithms (PCA and PACO) for angular separation above 0.5 arcsec.
On the natal kick of the black hole X-ray binary H 1705−250
Authors: Dashwood Brown Cordelia , Gandhi Poshak , Zhao Yue
Published: October 2023

When a compact object is formed, an impulse (kick) will be imparted to the system by the mass lost during the core-collapse supernova (SN). A number of other mechanisms may impart an additional kick on the system, although evidence for these natal kicks in black hole systems remains limited. Updated Gaia astrometry has recently identified a number of high peculiar velocity (in excess of Galactic motion) compact objects. Here, we focus on the black hole low-mass X-ray binary H 1705−250, which has a peculiar velocity $\upsilon _{\mathrm{pec}}\, =\, 221^{+101}_{-108}\, \,\mathrm{km}\, \mathrm{s}^{-1}$. Using population synthesis to reconstruct its evolutionary history (assuming formation via isolated binary evolution within the Galactic plane), we constrain the properties of the progenitor and pre-SN orbit. The magnitude of a kick solely due to mass-loss is found to be ∼30 km s−1, which cannot account for the high present-day peculiar motion. We therefore deduce that the black hole received an additional natal kick at formation, and place limits on its magnitude, finding it to be ∼295 km s−1 (minimum 90 km s−1). This furthers the argument that these kicks are not limited to neutron stars.
Quantitative assessment of painful diabetic peripheral neuropathy after high-frequency spinal cord stimulation: a pilot study
Authors: Kissoon Narayan R , LeMahieu Allison M , Stoltenberg Anita D , Bendel Markus A , Lamer Tim J , Watson James C , Sletten David M , Singer Wolfgang
Published: October 2023

Objective

Randomized trials have demonstrated efficacy of spinal cord stimulation (SCS) for treatment of painful diabetic neuropathy (PDN). Preliminary data suggested that treatment of PDN with high-frequency SCS resulted in improvements on neurological examination. The purpose of the present study was to explore whether patients with PDN treated with high-frequency SCS would have improvements in lower-extremity peripheral nerve function.

Design

Prospective cohort study in an outpatient clinical practice at a tertiary care center.

Methods

Patients with PDN were treated with high-frequency SCS and followed up for 12 months after SCS implantation with clinical outcomes assessments of pain intensity, neuropathic symptoms, and neurological function. Small-fiber sudomotor function was assessed with the quantitative sudomotor axon reflex test (QSART), and large-fiber function was assessed with nerve conduction studies (NCS). Lower-extremity perfusion was assessed with laser Doppler flowmetry.

Results

Nine patients completed 12-month follow-up visits and were observed to have improvements in lower-extremity pain, weakness, and positive sensory symptoms. Neuropathy impairment scores were improved, and 2 patients had recovery of sensory responses on NCS. A reduction in sweat volume on QSART was observed in the proximal leg but not at other sites. No significant differences were noted in lower-extremity perfusion or NCS as compared with baseline.

Conclusions

The improvement in pain relief was concordant with improvement in neuropathy symptoms. The findings from this study provide encouraging preliminary data in support of the hypothesis of a positive effect of SCS on peripheral neuropathy, but the findings are based on small numbers and require further evaluation.

Trial registration

ClinicalTrials.gov ID NCT03769675.
Use of spinal cord stimulation in treatment of intractable headache diseases
Authors: Towne Brooke V , Girgiss Carol B , Schuster Nathaniel M
Published: October 2023

Headache diseases remain one of the leading causes of disability in the world. With the development of neuromodulation strategies, high cervical spinal cord stimulation (hcSCS) targeting the trigeminocervical complex has been deployed to treat refractory headache diseases. In this article, we review the proposed mechanism behind hcSCS stimulation, and the various studies that have been described for the successful use of this treatment strategy in patients with chronic migraine, cluster headache, and other trigeminal autonomic cephalalgias.
Treatment of pain in length-dependent peripheral neuropathy with the use of spinal cord stimulation: a systematic review
Authors: D’Souza Ryan S , ElSaban Mariam , Martinez Alvarez Gabriel A , Jin Max Y , Kubrova Eva , Hassett Leslie C
Published: October 2023

Background

Chronic intractable pain from peripheral neuropathy is a debilitating condition that might not respond to conventional medical management and pharmacotherapy. The primary objective of this systematic review was to assess change (or reduction) in pain intensity in patients with length-dependent peripheral neuropathy after spinal cord stimulation (SCS) therapy.

Methods

This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The primary outcome was change (or reduction) in pain intensity after 12 months of SCS therapy compared with baseline in participants with length-dependent peripheral neuropathy. Secondary outcomes included change in pain intensity after 6 months and change in opioid consumption after 12 months. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guidelines were used to appraise the quality of evidence.

Results

Nineteen studies consisting of 376 participants who underwent SCS implantation met the inclusion criteria. Qualitative synthesis revealed that all eligible studies reported a significant improvement in pain intensity after 12 months of SCS therapy as compared with baseline. Mean differences with 95% confidence intervals were calculated for 4 studies, all of which achieved the minimal clinically important difference for change in pain intensity at 12 months. The GRADE quality of evidence for this outcome was appraised as very low quality.

Conclusion

This systematic review highlights that SCS could lead to significant improvement in pain intensity for length-dependent peripheral neuropathy, although future well-powered randomized controlled trials are warranted to increase the certainty of evidence in this finding.

Study registration

PROSPERO (https://www.crd.york.ac.uk/PROSPERO/) ID: CRD42022377572.
Arrhythmia-associated calmodulin variants interact with KCNQ1 to confer aberrant membrane trafficking and function
Authors: Kang Po wei , Woodbury Lucy , Angsutararux Paweorn , Sambare Namit , Shi Jingyi , Marras Martina , Abella Carlota , Bedi Anish , Zinn DeShawn , Cui Jianmin , Silva Jonathan R
Published: October 2023

Missense variants in calmodulin (CaM) predispose patients to arrhythmias associated with high mortality rates (“calmodulinopathy”). As CaM regulates many key cardiac ion channels, an understanding of disease mechanism associated with CaM variant arrhythmias requires elucidating individual CaM variant effects on distinct channels. One key CaM regulatory target is the KCNQ1 (KV7.1) voltage-gated potassium channel that carries the IKs current. Yet, relatively little is known as to how CaM variants interact with KCNQ1 or affect its function. Here, we take a multipronged approach employing a live-cell fluorescence resonance energy transfer binding assay, fluorescence trafficking assay, and functional electrophysiology to characterize >10 arrhythmia-associated CaM variants for effect on KCNQ1 CaM binding, membrane trafficking, and channel function. We identify one variant (G114W) that exhibits severely weakened binding to KCNQ1 but find that most other CaM variants interact with similar binding affinity to KCNQ1 when compared with CaM wild-type over physiological Ca2+ ranges. We further identify several CaM variants that affect KCNQ1 and IKs membrane trafficking and/or baseline current activation kinetics, thereby delineating KCNQ1 dysfunction in calmodulinopathy. Lastly, we identify CaM variants with no effect on KCNQ1 function. This study provides extensive functional data that reveal how CaM variants contribute to creating a proarrhythmic substrate by causing abnormal KCNQ1 membrane trafficking and current conduction. We find that CaM variant regulation of KCNQ1 is not uniform with effects varying from benign to significant loss of function, suggesting how CaM variants predispose patients to arrhythmia via the dysregulation of multiple cardiac ion channels.

Classification: Biological, Health, and Medical Sciences, Physiology
Extending aquatic spectral information with the first radiometric IR-B field observations
Authors: Houskeeper Henry F , Hooker Stanford B
Published: October 2023

Planetary radiometric observations enable remote sensing of biogeochemical parameters to describe spatiotemporal variability in aquatic ecosystems. For approximately the last half century, the science of aquatic radiometry has established a knowledge base using primarily, but not exclusively, visible wavelengths. Scientific subdisciplines supporting aquatic radiometry have evolved hardware, software, and procedures to maximize competency for exploiting visible wavelength information. This perspective culminates with the science requirement that visible spectral resolution must be continually increased to extract more information. Other sources of information, meanwhile, remain underexploited, particularly information from nonvisible wavelengths. Herein, absolute radiometry is used to evaluate spectral limits for deriving and exploiting aquatic data products, specifically the normalized water-leaving radiance, Γ(λ), and its derivative products. Radiometric observations presented herein are quality assured for individual wavebands, and spectral verification is conducted by analyzing celestial radiometric results, comparing agreement of above- and in-water observations at applicable wavelengths, and evaluating consistency with bio-optical models and optical theory. The results presented include the first absolute radiometric field observations of Γ(λ) within the IR-B spectral domain (i.e. spanning 1400–3000 nm), which indicate that IR-B signals confer greater and more variable flux than formerly ascribed. Black-pixel processing, a routine correction in satellite and in situ aquatic radiometry wherein a spectrum is offset corrected relative to a nonvisible waveband (often IR-B or a shorter legacy waveband) set to a null value, is shown to degrade aquatic spectra and derived biogeochemical parameters.
Recruitment, deployment, promotion, and attrition of female officers: The impact on staffing and perceptions of police practice
Authors: Miles-Johnson Toby , Fay Suzanna
Published: October 2023

There is little research examining (collectively) recruitment, deployment, promotion, and attrition of female constables in policing, and how these issues affect organizational staffing, police practice. Presenting findings from semi-structured interviews with 46 male and female constables working in an Australian State and Territories police organization, this paper argues that exclusionary staffing practices start from the onset of recruitment because female applicants are singled-out by their sex. It argues that exclusionary staffing practices for female constables occur throughout initial recruit training, during placement within a police station or area of command, whilst being deployed or not deployed to police work, and during consideration or application of promotion related processes, which increases the probability that attrition rates of female constables will be high. Unless police organizations address these issues, it is likely that the number of female constables transitioning into senior roles will remain small; thereby reducing the likelihood that police organizations will implement or achieve equitable staffing principles. It will also diminish appropriate resources needed to run an organization and have a negative impact on staffing.
Corticolimbic structural connectivity encapsulates real-world emotional reactivity and happiness
Authors: Kim Mijin , Shin Sunghyun , Jyung Mina , Choi Jong-An , Choi Incheol , Kim M. Justin , Sul Sunhae
Published: October 2023

Emotional reactivity to everyday events predicts happiness, but the neural circuits underlying this relationship remain incompletely understood. Here, we combined experience sampling methods and diffusion magnetic resonance imaging to examine the association among corticolimbic structural connectivity, real-world emotional reactivity and daily experiences of happiness from 79 young adults (35 females). Participants recorded momentary assessments of emotional and happiness experiences five times a day for a week, approximately 2 weeks after brain scanning. Model-based emotional reactivity scores, which index the degree to which moment-to-moment affective state varies with the occurrence of positive or negative events, were computed. Results showed that stronger microstructural integrity of the uncinate fasciculus and the external capsule was associated with both greater positive and negative emotional reactivity scores. The relationship between these fiber tracts and experienced happiness was explained by emotional reactivity. Importantly, this indirect effect was observed for emotional reactivity to positive but not negative real-world events. Our findings suggest that the corticolimbic circuits supporting socioemotional functions are associated with emotional reactivity and happiness in the real world.
Neural correlates of successful emotion recognition in healthy elderly: a multimodal imaging study
Authors: Orlando Isabella , Ricci Carlo , Griffanti Ludovica , Filippini Nicola
Published: October 2023

The ageing process is associated with reduced emotional recognition (ER) performance. The ER ability is an essential part of non-verbal communication, and its role is crucial for proper social functioning. Here, using the ‘Cambridge Centre for Ageing and Neuroscience cohort sample’, we investigated when ER, measured using a facial emotion recognition test, begins to consistently decrease along the lifespan. Moreover, using structural and functional MRI data, we identified the neural correlates associated with ER maintenance in the age groups showing early signs of ER decline (N = 283; age range: 58–89 years). The ER performance was positively correlated with greater volume in the superior parietal lobule, higher white matter integrity in the corpus callosum and greater functional connectivity in the mid-cingulate area. Our results suggest that higher ER accuracy in older people is associated with preserved gray and white matter volumes in cognitive or interconnecting areas, subserving brain regions directly involved in emotional processing.
Role of medial prefrontal cortex and primary somatosensory cortex in self and other-directed vicarious social touch: a TMS study
Authors: Bellard Ashleigh , Trotter Paula D , McGlone Francis L , Cazzato Valentina
Published: October 2023

Conflicting evidence points to the contribution of several key nodes of the ‘social brain’ to the processing of both discriminatory and affective qualities of interpersonal touch. Whether the primary somatosensory cortex (S1) and the medial prefrontal cortex (mPFC), two brain areas vital for tactile mirroring and affective mentalizing, play a functional role in shared representations of C-tactile (CT) targeted affective touch is still a matter of debate. Here, we used offline continuous theta-burst transcranial magnetic stimulation (cTBS) to mPFC, S1 and vertex (control) prior to participants providing ratings of vicarious touch pleasantness for self and others delivered across several body sites at CT-targeted velocities. We found that S1-cTBS led to a significant increase in touch ratings to the self, with this effect being positively associated to levels of interoceptive awareness. Conversely, mPFC-cTBS reduced pleasantness ratings for touch to another person. These effects were not specific for CT-optimal (slow) stroking velocities, but rather they applied to all types of social touch. Overall, our findings challenge the causal role of the S1 and mPFC in vicarious affective touch and suggest that self- vs other-directed vicarious touch responses might crucially depend on the specific involvement of key social networks in gentle tactile interactions.
Forgotten Concepts of Korea’s Welfare State: Productivist Welfare Capitalism and Confucianism Revisited in Family Policy Change
Authors: Gurín Martin
Published: October 2023

Understanding the dominant principle(s) of a welfare regime has been the “higher-level” objective of welfare state analysis. East Asian welfare states are no exception, and thus many contributions have sought to understand the welfare state order of these countries. In this article, we consider the development and current architecture of family policies at the center of welfare regime debate for the case of South Korea. Through this analysis we aim to critically assess current assumptions that both original foundations—productivist welfare capitalism and Confucianism—are theoretically useless for understanding the current welfare state and its development. Instead, this article argues that productivism remains at the heart of family policy in South Korea. The repositioning of productivism, however, and the related focus on social reproduction in the welfare state project, have led to most of the changes introduced to the detriment of Confucianism.
Divergent hepaciviruses, delta-like viruses, and a chu-like virus in Australian marsupial carnivores (dasyurids)
Authors: Harvey Erin , Mifsud Jonathon C O , Holmes Edward C , Mahar Jackie E
Published: October 2023

Although Australian marsupials are characterised by unique biology and geographic isolation, little is known about the viruses present in these iconic wildlife species. The Dasyuromorphia are an order of marsupial carnivores found only in Australia that include both the extinct Tasmanian tiger (thylacine) and the highly threatened Tasmanian devil. Several other members of the order are similarly under threat of extinction due to habitat loss, hunting, disease, and competition and predation by introduced species such as feral cats. We utilised publicly available RNA-seq data from the National Center for Biotechnology Information (NCBI) Sequence Read Archive (SRA) database to document the viral diversity within four Dasyuromorph species. Accordingly, we identified fifteen novel virus sequences from five DNA virus families (Adenoviridae, Anelloviridae, Gammaherpesvirinae, Papillomaviridae, and Polyomaviridae) and three RNA virus taxa: the order Jingchuvirales, the genus Hepacivirus, and the delta-like virus group. Of particular note was the identification of a marsupial-specific clade of delta-like viruses that may indicate an association of deltaviruses with marsupial species. In addition, we identified a highly divergent hepacivirus in a numbat liver transcriptome that falls outside of the larger mammalian clade. We also detect what may be the first Jingchuvirales virus in a mammalian host—a chu-like virus in Tasmanian devils—thereby expanding the host range beyond invertebrates and ectothermic vertebrates. As many of these Dasyuromorphia species are currently being used in translocation efforts to reseed populations across Australia, understanding their virome is of key importance to prevent the spread of viruses to naive populations.
Computational Design of a Highly-Specific HVEM-Based Inhibitor of LIGHT Protein
Authors: Ciura Piotr , Smardz Pamela , Krupa Magdalena A. , Spodzieja Marta , Krupa Pawel , Sieradzan Adam K.
Published: October 2023

Motivation

HVEM-LIGHT binding regulates the immune system response in various ways: it co-stimulates T cell proliferation; promotes B cell differentiation and secretion of immunoglobulins; and enhances dendritic cell maturation. Strong and prolonged stimulation of T cells to proliferate causes high levels of IFN–γ, which leads to chronic inflammation and is the reason for various autoimmune diseases. Therefore, blocking HVEM-LIGHT interaction may be a way to cure these diseases and prevent adverse reaction in organ and tissue transplantation.

Results

In this work, we designed 62 peptides based on the CRDs of the HVEM structure, differentiating in the number and combination of disulfide bonds present. Based on extensive all-atom MD simulations in state-of-the-art force fields, followed by MM-GBSA binding energy estimation, we selected the most promising CRD2 variants interacting with LIGHT. Several point mutations of these variants provided us with the most strongly binding moiety: the CRD2 with a single disulfide bond (C58-C73) and K54E substitution. This result was supprased only by the truncated variants of CRD2(39-73) with the same disulfide bond present. The binding mechanism was investigated by the use of steered MD simulations, which showed the increased binding affinity of the abovementioned variants, while experimental circular dichroism was used to determine their structural properties.

Availability and Implementation

Three PDB models of the LIGHT inhibitors: PM0084527, PM0084528, and PM0084592.

Contact

pkrupa@ifpan.edu.pl

Supplementary information

Online supplementary data is available at: .
CCR5 promotes the migration of CD8+T cells to the leishmanial lesions
Authors: Sacramento Laís Amorim , Amorim Camila Farias , Lombana Claudia G. , Beiting Daniel , Novais Fernanda , Carvalho Lucas P. , Carvalho Edgar M. , Scott Phillip
Published: October 2023

Cytolytic CD8+T cells mediate immunopathology in cutaneous leishmaniasis without controlling parasites. Here, we identify factors involved in CD8+T cell migration to the lesion that could be targeted to ameliorate disease severity. CCR5 was the most highly expressed chemokine receptor in patient lesions, and the high expression of CCL3 and CCL4, CCR5 ligands, was associated with delayed healing of lesions. To test the requirement for CCR5,Leishmania-infected Rag1-/-mice were reconstituted with CCR5-/-CD8+T cells. We found that these mice developed smaller lesions accompanied by a reduction in CD8+T cell numbers compared to controls. We confirmed these findings by showing that the inhibition of CCR5 with maraviroc, a selective inhibitor of CCR5, reduced lesion development without affecting the parasite burden. Together, these results reveal that CD8+T cells migrate to leishmanial lesions in a CCR5-dependent manner and that blocking CCR5 prevents CD8+T cell-mediated pathology.
DeMixSC: a deconvolution framework that uses single-cell sequencing plus a small benchmark dataset for improved analysis of cell-type ratios in complex tissue samples
Authors: Guo Shuai , Liu Xiaoqian , Cheng Xuesen , Jiang Yujie , Ji Shuangxi , Liang Qingnan , Koval Andrew , Li Yumei , Owen Leah A. , Kim Ivana K. , Aparicio Ana , Shen John Paul , Kopetz Scott , Weinstein John N. , DeAngelis Margaret M. , Chen Rui , Wang Wenyi
Published: October 2023

Bulk deconvolution with single-cell/nucleus RNA-seq data is critical for understanding heterogeneity in complex biological samples, yet the technological discrepancy across sequencing platforms limits deconvolution accuracy. To address this, we introduce an experimental design to match inter-platform biological signals, hence revealing the technological discrepancy, and then develop a deconvolution framework called DeMixSC using the better-matched, i.e., benchmark, data. Built upon a novel weighted nonnegative least-squares framework, DeMixSC identifies and adjusts genes with high technological discrepancy and aligns the benchmark data with large patient cohorts of matched-tissue-type for large-scale deconvolution. Our results using a benchmark dataset of healthy retinas suggest much-improved deconvolution accuracy. Further analysis of a cohort of 453 patients with age-related macular degeneration supports the broad applicability of DeMixSC. Our findings reveal the impact of technological discrepancy on deconvolution performance and underscore the importance of a well-matched dataset to resolve this challenge. The developed DeMixSC framework is generally applicable for deconvolving large cohorts of disease tissues, and potentially cancer.
sincFold: end-to-end learning of short- and long-range interactions in RNA secondary structure
Authors: Bugnon Leandro A. , Di Persia Leandro , Gerard Matias , Raad Jonathan , Prochetto Santiago , Fenoy Emilio , Chorostecki Uciel , Ariel Federico , Stegmayer Georgina , Milone Diego H.
Published: October 2023

Motivation

Coding and non-coding RNA molecules participate in many important biological processes. Non-coding RNAs fold into well-defined secondary structures to exert their functions. However, the computational prediction of the secondary structure from a raw RNA sequence is a long-standing unsolved problem, which after decades of almost unchanged performance has now re-emerged thanks to deep learning. Traditional RNA secondary structure prediction algorithms have been mostly based on thermodynamic models and dynamic programming for free energy minimization. More recently deep learning methods have shown competitive performance compared with the classical ones, but still leaving a wide margin for improvement.

Results

In this work we present sincFold an end-to-end deep learning approach that predicts the nucleotides contact matrix using only the RNA sequence as input. The model is based on 1D and 2D residual neural networks that can learn short- and long-range interaction patterns. We show that structures can be accurately predicted with minimal physical assumptions. Extensive experiments were conducted on several benchmark datasets, considering sequence homology and cross-family validation. sincFold was compared against classical methods and recent deep learning models, showing that it can outperform state-of-the-art methods.

Availability

The source code is available athttps://github.com/sinc-lab/sincFold(v0.16) and the web access is provided athttps://sinc.unl.edu.ar/web-demo/sincFold

Contact

lbugnon@sinc.unl.edu.ar
Chlorophyll to Zeaxanthin Energy Transfer in Non-Photochemical Quenching: An Exciton Annihilation-free Transient Absorption Study
Authors: Lee Tsung-Yen , Lam Lam , Patel-Tupper Dhruv , Roy Partha Pratim , Ma Sophia A. , Lucas-DeMott Aviva , Karavolias Nicholas G. , Niyogi Krishna K. , Fleming Graham R.
Published: October 2023

Zeaxanthin (Zea) is a key component in the energy-dependent, rapidly reversible, non-photochemical quenching process (qE) that regulates photosynthetic light harvesting. Previous transient absorption (TA) studies suggested that Zea can participate in direct quenching via Chlorophyll (Chl) to Zea energy transfer. However, the contamination of intrinsic exciton-exciton annihilation (EEA) makes the assignment of TA signal ambiguous. In this study, we present EEA-free TA data usingNicotiana benthamianathylakoid membranes, including wild type and three NPQ mutants (npq1,npq4, andlut2) generated by CRISPR/Cas9 mutagenesis. Results show a strong correlation between excitation energy transfer from excited Chl Qyto Zea S1and the xanthophyll cycle during qE activation. Notably, a Lut S1signal is absent in thenpq1thylakoids which lack zeaxanthin. Additionally, the fifth-order response analysis shows a reduction in the exciton diffusion length (LD) from 55 ± 5 nm to 38 ± 3 nm under high light illumination, consistent with the reduced range of exciton motion being a key aspect of plants’ response to excess light.
Optoelectronic enhancement of photocurrent by cyanobacteria on sustainable AP-VPP-fabricated PEDOT electrodes
Authors: Wey Laura T. , Yewale Rahul , Hautala Emilia , Hannonen Jenna , Katavisto Kalle , Kvarnström Carita , Allahverdiyeva Yagut , Damlin Pia
Published: October 2023

Photosynthetic microrganisms, including cyanobacteria, can be interfaced with electrodes in biophotovoltaic devices (BPVs) for solar energy conversion. Effective BPV electrodes need to be conductive, transparent, flexible, biocompatible and environmentally friendly, while also being cost-effective, abundant in material and lightweight. The utilization of electrically conducting polymers (CPs), particularly poly(3,4-ethylenedioxythiophene) (PEDOT) fabricated by an atmospheric pressure vapor phase polymerization (AP-VPP) technique, is a promising avenue for BPV applications. However, challenges remain in optimising their performance as CPs are dynamic optoelectronic materials, and their interaction with photosynthetic biocatalysts under a range of conditions has not been explored thoroughly. Here we show that AP-VPP-PEDOT electrodes hold promise for interfacing with cyanobacteria in BPVs to generate green electricity under red and blue light and moderate applied potentials with exogenous electron mediators. The highest non-mediated photocurrent achieved was 0.48 µA cm−2, with a two-layer PEDOT electrode at 0.5 V applied potential and blue light. The highest mediated photocurrent achieved was 2.73 µA cm−2, with a one-layer PEDOT electrode at 0.3 V applied potential and blue light and the exogenous electron mediator 2,6-dichloro-1,4-benzoquinone (DCBQ). The proposed approach to fabricating PEDOT electrodes offers a new pathway for developing sustainable electrodes for BPVs and pinpoints strategies for future optimisation for achieving high-performance outcomes.

Abstract Figure
Autophagosome development and chloroplast segmentation occur synchronously for piecemeal degradation of chloroplasts
Authors: Izumi Masanori , Nakamura Sakuya , Otomo Kohei , Ishida Hiroyuki , Hidema Jun , Nemoto Tomomi , Hagihara Shinya
Published: October 2023

Plants distribute many nutrients to chloroplasts during leaf development and maturation. When leaves senesce or experience sugar starvation, the autophagy machinery degrades chloroplast proteins to facilitate efficient nutrient reuse. Here, we report on the intracellular dynamics of an autophagy pathway responsible for piecemeal degradation of chloroplast components. Through live-cell monitoring of chloroplast morphology, we observed the formation of chloroplast budding structures in sugar-starved leaves. These buds were then released and incorporated into the vacuolar lumen as an autophagic cargo termed a Rubisco-containing body. The budding structures did not accumulate in mutants of core autophagy machinery, suggesting that autophagosome creation is required for forming chloroplast buds. Simultaneous tracking of chloroplast morphology and autophagosome development revealed that the isolation membranes of autophagosomes interact closely with part of the chloroplast surface before forming chloroplast buds. Chloroplasts then protrude at the site associated with the isolation membranes, which divide synchronously with autophagosome maturation. This autophagy-related division does not require DYNAMIN-RELATED PROTEIN 5B, which constitutes the division ring for chloroplast proliferation in growing leaves. An unidentified division machinery may thus fragment chloroplasts for degradation in coordination with the development of the chloroplast-associated isolation membrane.
Gap-free X and Y chromosomes ofSalix arbutifoliareveal an evolutionary change from male to female heterogamety in willows, without a change in the sex-determining region
Authors: Wang Yi , Gong Guangnan , Zhang Rengang , Hörandl Elvira , Zhang Zhixiang , Charlesworth Deborah , He Li
Published: October 2023

In theVetrixclade ofSalix, a genus of woody flowering plants, sex determination involves chromosome 15, but an XY system has changed to a ZW system. We used genome sequencing (with chromosome conformation capture (Hi-C) and PacBio HiFi high-fidelity reads) to study the evolutionary history of the sex-linked regions before and after the transition. We assembled chromosome level gap-free X and Y chromosomes ofSalix arbutifolia, and distinguished the haplotypes in the 15X- and 15Y-linked regions. This revealed “micro-heteromorphism” differentiating the haplotypes of the Y- and X-linked regions, including insertions, deletions and duplications. Unusually, the X-linked region is considerably larger than the corresponding Y region, and we show that this primarily reflects extensive accumulation of repetitive sequences and gene duplications. The phylogenies of single-copy orthogroups within the sex-linked regions ofS. arbutifolia(X and Y) andS. purpurea(Z and W) indicate that they possess a common ancestral sex-linked region that is physically small and located in a repeat-rich region near the chromosome 15 centromere. During the change in heterogamety, the W-linked region was derived from the X-linked one and the Z from the Y. The W may subsequently have evolved a region in which recombination became suppressed. We also detected accumulation of genes with opposite sex-biases in the sex-linked regions.
Interleukin 11-induced microRNAs as functional mediators and circulating biomarkers of cardiac fibrosis
Authors: Tikhomirov Roman , Reilly-O’Donnell Benedict , Lucarelli Carla , Srivastava Prashant Kumar , Anwar Maryam , Yiu Chi Him Kendrick , Dielesen Julia , Piella Santiago Nicolas , Kwan Zoe , Zaccagnini Germana , Mansfield Catherine , Tessari Maddalena , Menicanti Lorenzo , Greco Simona , Leszek Przemysław , Faggian Giuseppe , Emanueli Costanza , Martelli Fabio , Gorelik Julia
Published: October 2023

Background

Cardiac fibrosis can be triggered by several pathologies, including ischemic heart disease and aortic stenosis (AS). Cardiac fibrosis is brought about by uncontrolled extracellular matrix (ECM) deposition by myofibroblasts. Interleukin-11 (IL-11) has been firmly demonstrated to be a major trigger of multi-organ fibrosis. However, the molecular mechanisms underpinning IL-11-induced fibrosis requires further characterisation. Recent studies indicate that microRNA (miRNA) dysregulation contributes to the pathogenesis of cardiac fibrosis and can be targeted therapeutically. In this study, we explored the hypothesis that miRNAs act as downstream effectors of IL-11-induced cardiac fibrosis. Moreover, we investigated the translational potential of IL-11-regulated miRNAs as circulating biomarkers of cardiac fibrosis in AS patients.

Methods and Results

Using computational approaches, we identified miRNA-497-5p and miRNA-27b-5p as potential new downstream profibrotic effectors of IL-11 in fibroblasts. We next confirmed that both miRNAs increased in healthy rat CF stimulated with IL-11 and in CF derived from post-infarction failing hearts. At the functional level, miRNA-497-5p and miRNA-27b-5p inhibition indirectly reduced the mRNA expression of collagen 1 (Col1a1). Conversely, transfection of CFs with mimics for each of the two miRNAs promoted fibroblast-to-myofibroblast transition and increased Col1a1 levels. We provided evidences that miRNA-27b-5p and miRNA-497-5p converge to promote hypoxia-inducible factor 1 signalling, by targeting its regulator EGLN (PHD) family members. The clinical relevance of our findings was confirmed using left ventricle (LV) specimens obtained from surgical patients with AS. The miRNA-27b-5p and miRNA-497-5p measured in the LV, peripheral plasma and plasma extracellular vesicles correlated with the severity of LV fibrosis, indicating these miRNAs’ potential as new circulating biomarkers of cardiac fibrosis.

Conclusions

In this study, we have newly identified the potential value of miRNA-27b-5p and miRNA-497-5p as actionable biomarkers of the profibrotic response to IL-11 in the heart. Future studies should validate the translational potential of the miRNAs as new clinical biomarkers and therapeutic targets.
Antibodies utilizing VL6-57 light chains target a convergent cryptic epitope on SARS-CoV-2 spike protein driving the genesis of Omicron variants
Authors: Yan Qihong , Gao Xijie , Liu Banghui , Hou Ruitian , He Ping , Ma Yong , Zhang Yudi , Zhang Yanjun , Li Zimu , Chen Qiuluan , Wang Jingjing , Huang Xiaohan , Liang Huan , Chen Xianying , Niu Xuefeng , He Jun , Chen Ling , Zhao Jincun , Xiong Xiaoli
Published: October 2023

Continued evolution of SARS-CoV-2 generates variants to challenge antibody immunity established by infection and vaccination. A connection between population immunity and genesis of virus variants has long been suggested but its molecular basis remains poorly understood. Here, we identify a class of SARS-CoV-2 neutralising public antibodies defined by their shared usage of VL6-57 light chains. Although heavy chains of diverse genotypes are utilized, convergent HCDR3 rearrangements have been observed among these public antibodies to cooperate with germline VL6-57 LCDRs to target a convergent epitope defined by RBD residues S371-S373-S375. Antibody repertoire analysis identifies that this class of VL6-57 antibodies is present in SARS-CoV-2-naïve individuals and is clonally expanded in most COVID-19 patients. We confirm that Omicron specific substitutions at S371, S373 and S375 mediate escape of antibodies of the VL6-57 class. These findings support that this class of public antibodies constitutes immune pressure promoting the introduction of S371L/F-S373P-S375F in Omicron variants. The results provide further molecular evidences to support that antigenic evolution of SARS-CoV-2 is driven by antibody mediated population immunity.
Arabidopsis AGO1 N-terminal Poly-Q domain promotes phase separation and association with stress granules during heat stress
Authors: Blagojevic Aleksandar , Baldrich Patricia , Schiaffini Marlene , Lechner Esther , Baumberger Nicolas , Hammann Philippe , Elmayan Taline , Garcia Damien , Vaucheret Hervé , Meyers Blake C. , Genschik Pascal
Published: October 2023

InArabidopsis thaliana, ARGONAUTE1 (AGO1) plays a central role in microRNA (miRNA) and small interfering RNA (siRNA)-mediated silencing. Nuclear AGO1 is loaded with miRNAs and exported to the cytosol where it associates to the rough ER to conduct miRNA-mediated translational repression, mRNA cleavage and biogenesis of phased siRNAs. These latter, as well as other cytosolic siRNAs, are loaded into cytosolic AGO1, but in which compartment this happens is not known. Moreover, the effect of stress on AGO1 localization is still unclear. Here, we show that a 37°C heat stress (HS) promotes AGO1 protein accumulation in cytosolic condensates where it co-localizes with components of siRNA bodies and of stress granules (SGs). AGO1 contains a prion-like domain in its poorly characterized N-terminal Poly-Q domain, which, is sufficient to undergo phase separation, independent of the presence or absence of SGS3. HS only moderately affects the small RNA repertoire, the loading of AGO1 by miRNAs and the signatures of target cleavage, suggesting that its localization in condensates protects AGO1 rather than promotes or impairs its activity in reprograming gene expressing during stress. Collectively, our work shed new light on the impact of high temperature on a main effector of RNA silencing in plants.
The human microglia responsome: a resource to better understand microglia states in health and disease
Authors: Snijders Gijsje J.L.J. , de Paiva Lopes Katia , Sneeboer Marjolein A.M. , Muller Benjamin Z. , Gigase Frederieke A.J. , Vialle Ricardo A. , Missall Roy , Kubler Raphael , Raj Towfique , Humphrey Jack , de Witte Lot D.
Published: October 2023

Microglia, the immune cells of the brain, are increasingly implicated in neurodegenerative disorders through genetic studies. However, how genetic risk factors for these diseases are related to microglial gene expression, microglial function, and ultimately disease, is still largely unknown. Microglia change rapidly in response to alterations in their cellular environment, which is regulated through changes in transcriptional programs, which are as yet poorly understood. Here, we compared the effects of a set of inflammatory and restorative stimuli (lipopolysaccharide, interferon-gamma, resiquimod, tumor necrosis factor-alpha, adenosine triphosphate, dexamethasone, and interleukin-4) on human microglial cells from 67 different donors (N = 398 samples) at the gene and transcript level. We show that microglia from different anatomical brain regions show distinct responses to inflammatory stimuli. We observed a greater overlap between human stimulated microglia and human monocytes than with mouse microglia. We define specific microglial signatures across conditions which are highly relevant for a wide range of biological functions and complex human diseases. Finally, we used our stimulation signatures to interpret associations from Alzheimer’s disease (AD) genetic studies and microglia by integrating our inflammatory gene expression profiles with common genetic variants to mapcis-expression QTLs (eQTLs). Together, we provide the most comprehensive transcriptomic database of the human microglia responsome.

Highlights

RNA-sequencing of 398 human microglial samples exposed to six different triggers.

Microglia from different anatomical regions show distinct stimulation responses.

Responses in human microglia show a greater overlap with human monocytes than murine microglia.

Mapping of response Quantitative Trait Loci identifies interactions between genotype and effect of stimulation on gene expression.

Our atlas provides a reference map for interpreting microglia signatures in health and disease.