bluuebunny/crossref_metadata_2025 huggingface dataset:
Magnetic induction processes in hot Jupiters, application to KELT-9b
Authors: Dietrich Wieland , Kumar Sandeep , Poser Anna Julia , French Martin , Nettelmann Nadine , Redmer Ronald , Wicht Johannes
Published: October 2022

The small semimajor axes of hot Jupiters lead to high atmospheric temperatures of up to several thousand Kelvin. Under these conditions, thermally ionized metals provide a rich source of charged particles and thus build up a sizeable electrical conductivity. Subsequent electromagnetic effects, such as the induction of electric currents, Ohmic heating, magnetic drag, or the weakening of zonal winds have thus far been considered mainly in the framework of a linear, steady-state model of induction. For hot Jupiters with an equilibrium temperature Teq > 1500 K, the induction of atmospheric magnetic fields is a runaway process that can only be stopped by non-linear feedback. For example, the back-reaction of the magnetic field on to the flow via the Lorentz force or the occurrence of magnetic instabilities. Moreover, we discuss the possibility of self-excited atmospheric dynamos. Our results suggest that the induced atmospheric magnetic fields and electric currents become independent of the electrical conductivity and the internal field, but instead are limited by the planetary rotation rate and wind speed. As an explicit example, we characterize the induction process for the hottest exoplanet, KELT-9b, by calculating the electrical conductivity along atmospheric P–T profiles for the dayside and nightside. Despite the temperature varying between 3000 and 4500 K, the resulting electrical conductivity attains an elevated value of roughly 1 S m−1 throughout the atmosphere. The induced magnetic fields are predominately horizontal and might reach up to a saturation field strength of 400 mT, exceeding the internal field by two orders of magnitude.
Accuracy and precision of triaxial orbit models – II. Viewing angles, shape, and orbital structure
Authors: de Nicola Stefano , Neureiter Bianca , Thomas Jens , Saglia Roberto P , Bender Ralf
Published: October 2022

We explore the potential of our novel triaxial modelling machinery in recovering the viewing angles, the shape, and the orbit distribution of galaxies by using a high-resolution N-body merger simulation. Our modelling technique includes several recent advancements. (i) Our new triaxial deprojection algorithm shape3d is able to significantly shrink the range of possible orientations of a triaxial galaxy and therefore to constrain its shape relying only on photometric information. It also allows to probe degeneracies, i.e. to recover different deprojections at the same assumed orientation. With this method we can constrain the intrinsic shape of the N-body simulation, i.e. the axis ratios p = b/a and q = c/a, with Δp and Δq ≲ 0.1 using only photometric information. The typical accuracy of the viewing angles reconstruction is 15°–20°. (ii) Our new triaxial Schwarzschild code smart exploits the full kinematic information contained in the entire non-parametric line-of-sight velocity distributions along with a 5D orbital sampling in phase space. (iii) We use a new generalized Akaike information criterion AICp to optimize the smoothing and to select the best-fitting model, avoiding potential biases in purely χ2-based approaches. With our deprojected densities, we recover the correct orbital structure and anisotropy parameter β with Δβ ≲ 0.1. These results are valid regardless of the tested orientation of the simulation and suggest that even despite the known intrinsic photometric and kinematic degeneracies the above described advanced methods make it possible to recover the shape and the orbital structure of triaxial bodies with unprecedented accuracy.
Semi-analytical frameworks for subhaloes from the smallest to the largest scale
Authors: Hiroshima Nagisa , Ando Shin’ichiro , Ishiyama Tomoaki
Published: October 2022

Substructures of dark matter halo, called subhaloes, provide important clues to understand the nature of dark matter. We construct a useful model to describe the properties of subhalo mass functions based on the well-known analytical prescriptions, the extended Press–Schechter theory. The unevolved subhalo mass functions at arbitrary mass scales become describable without introducing free parameters. The different host halo evolution histories are directly recast to their subhalo mass functions. As applications, we quantify the effects from (i) the Poisson fluctuation, (ii) the host-mass scatter, and the (iii) different tidal evolution models on observables in the current Universe with this scheme. The Poisson fluctuation dominates in the number count of the mass ratio to the host of $\sim {\cal O}(10^{-2})$, where the intrinsic scatter is smaller by a factor of a few. The host-mass scatter around its mean does not affect the subhalo mass function. Different models of the tidal evolution predict a factor of ∼2 difference in numbers of subhaloes with $\lesssim {\cal O}(10^{-5})$, while the dependence of the Poisson fluctuation on the tidal evolution models is subtle. The scheme provides a new tool for investigating the smallest scale structures of our Universe which are to be observed in near future experiments.
Constraints on the Galactic Centre environment from Gaia hypervelocity stars II: The evolved population
Authors: Evans F A , Marchetti T , Rossi E M
Published: October 2022

A dynamical encounter between a stellar binary and Sgr A* in the Galactic Centre (GC) can tidally separate the binary and eject one member with a velocity beyond the escape speed of the Milky Way. These hypervelocity stars (HVSs) can offer insight into the stellar populations in the GC environment. In a previous work, our simulations showed that the lack of main sequence HVS candidates with precise astrometric uncertainties and radial velocities in current data releases from the Gaia space mission places a robust upper limit on the ejection rate of HVSs from the GC of $3\times 10^{-2} \, \mathrm{yr^{-1}}$. We improve this constraint in this work by additionally considering the absence of post-main sequence HVSs in Gaia Early Data Release 3 as well as the existence of the HVS candidate S5-HVS1. This evidence offers degenerate joint constraints on the HVS ejection rate and the stellar initial mass function (IMF) in the GC. For a top-heavy GC IMF as suggested by recent works, our modelling motivates an HVS ejection rate of $\eta =0.7_{-0.5}^{+1.5} \times 10^{-4} \, \mathrm{yr^{-1}}$. This preferred ejection rate can be as large as $10^{-2} \, \mathrm{yr^{-1}}$ for a very top-light IMF and as low as 10$^{-4.5} \, \mathrm{yr^{-1}}$ if the IMF is extremely top-heavy. Constraints will improve further with future Gaia data releases, regardless of how many HVS candidates are found therewithin.
Sustained FU Orionis-type outbursts from colliding discs in stellar flybys
Authors: Borchert Elisabeth M A , Price Daniel J , Pinte Christophe , Cuello Nicolás
Published: October 2022

We perform 3D hydrodynamic simulations of disc–disc stellar flybys with on-the-fly Monte Carlo radiative transfer. We show that pre-existing circumstellar discs around both stars result in fast rising (∼years) outbursts lasting two to five times longer than for a star–disc flyby. The perturber always goes into outburst ($\dot{M}\gt 10^{-5}~{\rm M_{\odot }~ yr^{-1}}$). Whereas we find that the primary goes into a decades long outburst only when the flyby is retrograde to the circumprimary disc rotation. High accretion rates during the outburst are triggered by angular momentum cancellation in misaligned material generated by the encounter. A large fraction of accreted material is alien.
The whisper of a whimper of a bang: 2400 d of the Type Ia SN 2011fe reveals the decay of 55Fe
Authors: Tucker M A , Shappee B J , Kochanek C S , Stanek K Z , Ashall C , Anand G S , Garnavich P
Published: October 2022

We analyse new multifilter Hubble Space Telescope (HST) photometry of the normal Type Ia supernova (SN Ia) 2011fe out to ≈2400 d after maximum light, the latest observations to date of a SN Ia. We model the pseudo-bolometric light curve with a simple radioactive decay model and find energy input from both 57Co and 55Fe are needed to power the late-time luminosity. This is the first detection of 55Fe in a SN Ia. We consider potential sources of contamination such as a surviving companion star or delaying the deposition time-scale for 56Co positrons but these scenarios are ultimately disfavored. The relative isotopic abundances place direct constraints on the burning conditions experienced by the white dwarf (WD). Additionally, we place a conservative upper limit of <10−3 M⊙ on the synthesized mass of 44Ti. Only two classes of explosion models are currently consistent with all observations of SN 2011fe: (1) the delayed detonation of a low-ρc, near-MCh (1.2–1.3 M⊙) WD, or (2) a sub-MCh (1.0–1.1 M⊙) WD experiencing a thin-shell double detonation.
Investigating the subchondral trabecular bone microstructure in patients with osteonecrosis of the femoral head using multi-detector row computed tomography
Authors: Inoue Tadashi , Shoji Takeshi , Kato Yuichi , Fujiwara Yusuke , Sumii Junichi , Shozen Hideki , Adachi Nobuo
Published: October 2022

Objectives

To analyse the microstructural changes of subchondral trabecular bone in patients with osteonecrosis of the femoral head (ONFH) using multi-detector row computed tomography (MDCT).

Methods

We retrospectively investigated 76 hips in 50 patients diagnosed with ONFH between 2017 and 2021. Groups 1, 2, 3, and 4 comprised hips without ONFH, ONFH without femoral head collapse (FHC), ONFH with mild collapse (<2 mm), and ONFH with severe collapse (>2 mm), respectively. All patients underwent MDCT, and the subchondral trabecular bone microstructure was assessed. Regions of interests were set at the lateral boundary of the femoral head necrotic lesion and centre of the acetabular weight-bearing portion.

Results

In both the femoral head and the acetabular regions, there were significant differences in Groups 2 and 3 compared to Group 1, with increased volumetric bone mineral density and apparent bone volume fraction, and more plate-like with increased connectivity, indicating that osteosclerotic changes were occurring.

Conclusions

In both the femoral head and the acetabular regions, osteosclerotic changes of subchondral trabecular bone microstructure were present before FHC.
A rare syndrome mimicking scleroderma: Werner syndrome
Authors: Okyar Burak , Akben Seçkin , Torun Bekir , Çetin Gözde Yıldırım
Published: October 2022

Werner syndrome (WS), also known as adult progeria, is a premature ageing syndrome that can manifest itself with grey hair, hair loss, diabetes mellitus, hyperlipidaemia, hypertension, skin disorders, ocular cataracts, myocardial infarction, osteoporosis, and stroke, especially after puberty. Physical examination findings similar to systemic sclerosis may be seen. Therefore, it may mimic this disease as misleading. A 43-year-old female patient was admitted to our clinic with a pre-diagnosis of systemic sclerosis complaint of skin hardening up to the ankle. In the first physical examination, there were wrinkles and thinning of the lip, suggesting systemic sclerosis in the facial appearance. On her capillaroscopy, there was tortuosity and an old focus of microhemorrhage. She had a history of diabetes mellitus and chronic osteomyelitis. When all symptoms, clinical findings, and antibody results were combined, it was thought that the patient might have WS. WS was diagnosed with homozygous c.2221 C>P p.R741*(rs763089663) positive in genetic analysis. It is known that WS creates a predisposition to malignancies, and most patients die secondary to malignancies. Therefore, early diagnosis becomes essential. Early diagnosis is of vital importance both to prevent complications and to delay treatment. In particular, systemic sclerosis-like findings of this syndrome may cause delays in diagnosis. For this reason, small clues suggesting WS in the clinic should be well known and well defined.
Total cortical interstitial inflammation predicts chronic kidney disease progression in patients with lupus nephritis
Authors: Duong Minh Dien , Wang Shudan , Schwartz Daniel , Mowrey Wenzhu B , Broder Anna , Goilav Beatrice
Published: October 2022

Background

End-stage kidney disease (ESKD) from lupus nephritis (LN) is a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Kidney biopsy is the gold standard for diagnosis and prognostication of LN. While interstitial fibrosis and tubular atrophy (IFTA) predict progression to ESKD, the National Institutes of Health (NIH) classification of interstitial inflammation in unscarred cortical parenchyma is not predictive of chronic kidney disease (CKD) progression. The objective of this study was to determine whether total cortical interstitial inflammation that accounts for inflammation in the entire cortical parenchyma could predict CKD progression in patients with LN. Early identification of at-risk patients may improve outcomes.

Methods

This retrospective cohort study included 125 SLE patients with LN class III, IV, V or mixed (III/V, IV/V) on the index biopsy (2005–2018). Kidney biopsies were reviewed and assigned based on the 2018 NIH Activity Index (AI) and tubulointerstitial lesion categories. Total interstitial inflammation in the entire cortical parenchyma was graded as 0, 1, 2 or 3, corresponding to <10%, 10–25%, 26–50% and >50%, respectively, of the total cortical parenchyma containing an inflammatory infiltrate (similar to the definition used in the Banff total inflammation score). CKD progression was defined as an estimated glomerular filtration rate decrease of ≥30% within 5 years after the index biopsy. Kaplan–Meier survival curves and Cox proportional hazards models were performed to compare the two scoring systems, the total cortical intestinal inflammation score and the NIH interstitial inflammation score as predictors of CKD progression.

Results

Of 125 patients, 46 experienced CKD progression; 21 of 46 subsequently developed ESKD, 28 (22.4%) had moderate–severe total cortical interstitial inflammation and 8 (6.4%) had moderate–severe NIH interstitial inflammation. There were no differences in baseline characteristics between progressors and nonprogressors. Total cortical interstitial inflammation was associated with CKD progression in time-dependent analyses [hazard ratio 2.45 (95% confidence interval 1.2–4.97)] adjusted for age at biopsy, race, sex, LN class and hypertensive vascular change on kidney biopsy. The NIH interstitial inflammation was not associated with CKD progression.

Conclusions

In contrast to the current NIH interstitial inflammation classification, accounting for interstitial inflammation in the entire cortical parenchyma allows identification of patients at risk for CKD progression in LN.
A Primer on Home Infusion Administration Methods
Authors: Loriaux Alain , Desmond Michael , Li Peng Cheng
Published: October 2022

Home infusion therapy is a rapidly growing field in healthcare, allowing patients to receive postacute care at home at a fraction of the cost of an inpatient stay. Understanding the various drug delivery systems can facilitate a more seamless discharge to home with improved patient outcomes. Herein we review several home infusion methods of administration utilized to transition patients from hospital to home care for a variety of therapies.
Reducing substrate inhibition of malate dehydrogenase from Geobacillus stearothermophilus by C-terminal truncation
Authors: Shimozawa Yuya , Matsuhisa Hinano , Nakamura Tsutomu , Himiyama Tomoki , Nishiya Yoshiaki
Published: October 2022

Malate dehydrogenase (MDH) catalyzes the reduction of oxaloacetate to L-malate. Geobacillus stearothermophilus MDH (gs-MDH) is used as a diagnostic reagent; however, gs-MDH is robustly inhibited at high substrate concentrations, which limits its reaction rate. Here, we reduced substrate inhibition of gs-MDH by deleting its C-terminal residues. Computational analysis showed that C-terminal residues regulate the position of the active site loop. C-terminal deletions of gs-MDH successfully increased Ki values by 5- to 8-fold with maintained thermal stability (>90% of the wild-type enzyme), although kcat/Km values were decreased by <2-fold. The structure of the mutant showed a shift in the location of the active site loop and a decrease in its volume, suggesting that substrate inhibition was reduced by eliminating the putative substrate binding site causing inhibition. Our results provide an effective method to reduce substrate inhibition of the enzyme without loss of other parameters, including binding and stability constants.
Co-creating end-user roles. Understanding the new variety of user involvement in public sector innovation
Authors: Lipp Benjamin , Baudrin Mathieu , Cuevas-Garcia Carlos , Pepponi Federica , Rozwadowska Magdalena , Tsui Shelly
Published: October 2022

Co-creation has become a major concern in science and public policy. It aims to give a more central role to end users in producing (public sector) innovation outcomes. This leads to a new variety of end user roles in innovation activities and poses challenges for both practitioners and policy makers. We offer an in-depth, comparative analysis of such end user roles in three cases of co-creative public sector innovation across Europe. We argue that the definition of particular end user roles is crucial in shaping both the inclusiveness and outcomes of co-creative innovation. We offer a typology of end user roles and their respective limits and potentials with regard to co-creation. Our analysis suggests that, for co-creation to produce useful and legitimate outcomes, the process by which roles are assigned to and negotiated with end users must be part of the co-creative process itself.
Accurate characterization of dynamic microbial gene expression and growth rate profiles
Authors: Vidal Gonzalo , Vitalis Carolus , Muñoz Silva Macarena , Castillo-Passi Carlos , Yáñez Feliú Guillermo , Federici Fernán , Rudge Timothy J
Published: October 2022

Genetic circuits are subject to variability due to cellular and compositional contexts. Cells face changing internal states and environments, the cellular context, to which they sense and respond by changing their gene expression and growth rates. Furthermore, each gene in a genetic circuit operates in a compositional context of genes which may interact with each other and the host cell in complex ways. The context of genetic circuits can, therefore, change gene expression and growth rates, and measuring their dynamics is essential to understanding natural and synthetic regulatory networks that give rise to functional phenotypes. However, reconstruction of microbial gene expression and growth rate profiles from typical noisy measurements of cell populations is difficult due to the effects of noise at low cell densities among other factors. We present here a method for the estimation of dynamic microbial gene expression rates and growth rates from noisy measurement data. Compared to the current state-of-the-art, our method significantly reduced the mean squared error of reconstructions from simulated data of growth and gene expression rates, improving the estimation of timing and magnitude of relevant shapes of profiles. We applied our method to characterize a triple-reporter plasmid library combining multiple transcription units in different compositional and cellular contexts in Escherichia coli. Our analysis reveals cellular and compositional context effects on microbial growth and gene expression rate dynamics and suggests a method for the dynamic ratiometric characterization of constitutive promoters relative to an in vivo reference.

Graphical Abstract
A randomized feasibility trial of the Midlife Black Women’s Stress and Wellness intervention (B-SWELL); a community participatory intervention to increase adoption of Life’s Simple 7 healthy lifestyle behaviors
Authors: Jones Holly J , Butsch Kovacic Melinda , Lambert Joshua , Almallah Wala’a R , Becker Richard , de las Fuentes Lisa , Bakas Tamilyn
Published: October 2022

Background

Black women have a disproportionately higher incidence of cardiovascular disease-related mortality than other groups, yet they are less likely to receive culturally proficient education and competent preventive care.

Purpose

The purpose of this study was to determine feasibility of the Midlife Black Women’s Stress and Wellness intervention (B-SWELL); a culturally adapted, 8-week group intervention leveraging stress reduction and goal setting to increase awareness and adoption of Life’s Simple 7 (LS7) healthy lifestyle behaviors.

Methods

A randomized feasibility trial was conducted. Participants (N = 48, mean age = 55 years) were randomized to the B-SWELL or a group wellness (WE) intervention that lacked stress reduction and goal setting instruction. We hypothesized that B-SWELL participants would achieve a lower perceived stress, greater self-efficacy, improved LS7 scores, fewer symptoms (depression and unhealthy days), and greater perceived general health compared to WE participants. Survey data were collected at three timepoints: baseline, 8 weeks, and 12 weeks.

Results

Both B-SWELL and WE groups had low attrition and navigated the online platform well. Further, both groups experienced lower perceived stress, improved LS7 scores, reduced depressive symptoms, and greater perceived general health from baseline to 8 weeks. Based on data trends, participants in the B-SWELL had more improvement in perceived stress, self-efficacy, and mental and physical unhealthy days compared to WE participants.

Conclusion

The B-SWELL is a feasible intervention for midlife Black women. Positive data trends were found for both B-SWELL and WE groups. Based on observations from the feasibility study, a larger outcomes-based study is planned.
The mitochondrial complex I proteins of Candida albicans moderate phagocytosis and the production of pro‐inflammatory cytokines in murine macrophages and dendritic cells
Authors: She Xiaodong , Zhang Pengyi , Shi Dongmei , Peng Jingwen , Wang Qiong , Meng Xiangjing , Jiang Yong , Calderone Richard , Bellanti Joseph A. , Liu Weida , Li Dongmei
Published: October 2022

Loss of respiratory functions impairs Candida albicans colonization of host tissues and virulence in a murine model of candidiasis. Furthermore, it is known that respiratory inhibitors decrease mannan synthesis and glucan exposure and thereby promotes phagocytosis. To understand the impact of respiratory proteins of C. albicans on host innate immunity, we characterized cell wall defects in three mitochondrial complex I (CI) null mutants (nuo1Δ, nuo2Δ and ndh51Δ) and in one CI regulator mutant (goa1Δ), and we studied the corresponding effects of these mutants on phagocytosis, neutrophil killing and cytokine production by dendritic cells (DCs). We find that reductions of phosphopeptidomannan (PPM) in goa1Δ, nuo1Δ and phospholipomannan (PLM) in nuo2Δ lead to reductions of IL‐2, IL‐4, and IL‐10 but increase of TNF‐α in infected DCs. While PPM loss is a consequence of a reduced phospho‐Cek1/2 MAPK that failed to promote phagocytosis and IL‐22 production in goa1Δ and nuo1Δ, a 30% glucan reduction and a defective Mek1 MAPK response in ndh51Δ lead to only minor changes in phagocytosis and cytokine production. Glucan exposure and PLM abundance seem to remain sufficient to opsonize neutrophil killing perhaps via humoral immunity. The diversity of immune phenotypes in these mutants possessing divergent cell wall defects is further supported by their transcriptional profiles in each infected murine macrophage scenario. Since metabolic processes, oxidative stress‐induced senescence, and apoptosis are differently affected in these scenarios, we speculate that during the early stages of infection, host immune cells coordinate their bioactivities based upon a mixture of signals generated during host‐fungi interactions.
Zebrafishcox17modulates primitive erythropoiesis via regulation of mitochondrial metabolism to facilitate hypoxia tolerance
Authors: Li LingYa , Chen MingYue , Liu WenYe , Tai PengZhi , Liu Xingguo , Liu Jing‐Xia
Published: October 2022

Cox17 is required in the assembly of mitochondrial intermembrane space (IMS) and Cu metallization of cytochrome C oxidase (CcO) in mitochondria as well as Cu homeostasis in cells. Cox deficiency is associated with hematopoietic diseases such as tubulopathy and leukodystrophy, but whether and howcox17functions in hematopoiesis are still unknown. Here, we report the effects of zebrafishcox17deficiency on primitive erythropoiesis, mitochondrial metabolism, and hypoxia tolerance.Cox17−/−larvae were sensitive to hypoxia stress, with reduced primitive erythropoiesis. Meanwhile,cox17−/−mutants showed a significant reduction in the expression of pivotal transcriptional regulators in erythropoiesis, such asscl,lmo2, andgata1aat 14 h post fertilization (hpf), with expression remaining downregulated forsclbut upregulated forlmo2andgata1aat 24 hpf. Mechanistically,cox17−/−mutants showed impaired mitochondrial metabolism, coupled with a significant decrease in the mitochondrial membrane potential, ATP and SAM content, and the ratio of SAM and SAH. Additionally, disrupting mitochondrial metabolism in wild type (WT) larvae treated with carbonyl cyanide 3‐chlorophenylhydrazone (CCCP) could mimic the primitive erythropoiesis defects observed incox17−/−mutants. Moreover,cox17−/−mutants exhibited significantly downregulated WNT signaling and upregulated ER stress, with a significant reduction of beta‐Catenin ingata1a+cells and of binding enrichment in bothsclandlmo2promoters of the WNT transcriptional factor TCF4. This is the first report on the novel linkage ofcox17deficiency with defective primitive erythropoiesis and reduced hypoxia tolerance. This study has shed light on the potential mechanism by which Cox deficiency, especiallycox17deficiency, induces Cu homeostasis imbalance, leading to hematopoietic diseases.
Knockdown of circHIPK3 promotes the osteogenic differentiation of human bone marrow mesenchymal stem cells through activating the autophagy flux
Authors: Zhuang Ziyao , Jin Chanyuan , Li Xiaobei , Han Yineng , Yang Qiaolin , Huang Yiping , Zheng Yunfei , Li Weiran
Published: October 2022

Many circular RNAs (circRNAs) involved in the osteogenesis of human bone marrow mesenchymal stem cells (hBMSCs) have recently been discovered. The role of circHIPK3 in osteogenesis has yet to be determined. Cell transfection was conducted using small‐interfering RNAs (siRNAs). Expression of osteogenic markers were detected by quantitative reverse transcription‐polymerase chain reaction, western blotting analysis, and immunofluorescence staining. Ectopic bone formation models in nude mice were used to examined the bone formation ability in vivo. The autophagy flux was examined via western blotting analysis, immunofluorescence staining and transmission electron microscopy analysis. RNA immunoprecipitation (RIP) analysis was carried out to analyze the binding between human antigen R (HUR) and circHIPK3 or autophagy‐related 16‐like 1 (ATG16L1). Actinomycin D was used to determine the mRNA stability. Our results demonstrated that silencing circHIPK3 promoted the osteogenesis of hBMSCs while silencing the linear mHIPK3 did not affect osteogenic differentiation, both in vivo and in vitro. Moreover, we found that knockdown of circHIPK3 activated autophagy flux. Activation of autophagy enhanced the osteogenesis of hBMSCs and inhibition of autophagy reduced the osteogenesis through using autophagy regulators chloroquine and rapamycin. We also discovered that circHIPK3 and ATG16L1 both bound to HUR. Knockdown of circHIPK3 released the binding sites of HUR to ATG16L1, which stabilized the mRNA expression of ATG16L1, resulting in the upregulation of ATG16L1 and autophagy activation. CircHIPK3 functions as an osteogenesis and autophagy regulator and has the potential for clinical application in the future.
Telomere-to-Telomere and Haplotype-Phased Genome Assemblies of the Heterozygous Octoploid ‘Florida Brilliance’ Strawberry (Fragaria × ananassa)
Authors: Han Hyeondae , Barbey Christopher R , Fan Zhen , Verma Sujeet , Whitaker Vance M. , Lee Seonghee
Published: October 2022

The available haplotype-resolved allo-octoploid strawberry (Fragaria×ananassaDuch.) (2n= 8x= 56) genomes were assembled with the trio-binning pipeline, supplied with parental short-reads. We report here a high-quality, haplotype-phased genome assembly of a short-day cultivar, ‘Florida Brilliance’ (FaFB2) without the use of parental sequences. Using Pacific Biosciences (PacBio) long reads and high-throughput chromatic capture (Hi-C) data, we completed telomere-to-telomere phased genome assemblies of both haplotypes. The N50 continuity of the two haploid assemblies were 23.7 Mb and 26.6 Mb before scaffolding and gap-filling. All 56 pseudochromosomes from the phased-1 and phased-2 assemblies contained putative telomere sequences at the 5’ and/or 3’ ends. A high level of collinearity between the haplotypes was confirmed by high-density genetic linkage mapping with 10,269 SNPs, and a high level of collinearity with the ‘Royal Royce’ FaRR1 reference genome was observed. Genome completeness was further confirmed by consensus quality. The LTR assembly Index score for entire genome assembly was 19.72. Moreover, the BUSCO analysis detected over 99% of conserved genes in the combined phased-1 and phased-2 assembly. Both haploid assemblies were annotated using Iso-Seq data from six different ‘Florida Brilliance’ tissues and RNA-Seq data representing variousF. ×ananassatissues from the NCBI sequence read archive, resulting in a total of 104,099 genes. This telomere-to-telomere reference genome of ‘Florida Brilliance’ will advance our knowledge of strawberry genome evolution and gene functions, and facilitate the development of new breeding tools and approaches.
Triangulation reduces the polygon of error for the history of Transeurasian
Authors: Robbeets Martine , Hudson Mark , Ning Chao , Bouckaert Remco , Savelyev Alexander , Kim Geonyoung , Li Tao , Oskolskaya Sofia , Gruntov Ilya , Mazo Olga , Rhee Seongha , Ahn Kyou-Dong , Fernandes Ricardo , Shinoda Ken-ichi , Kanzawa-Kiriyama Hideaki , Bjørn Rasmus , Deng Bingcong , An Deog-im , Bentley John , Kawashima Takamune , Dolińska Joanna
Published: October 2022

In a recent study we used an interdisciplinary approach combining linguistics, archaeology and genetics to analyse the Transeurasian languages1. Our analysis concluded that the early dispersals of these languages were driven by agriculture. A preprint published on this server presents objections to the Transeurasian hypothesis and its association with farming dispersals2. However, close inspection of that text reveals numerous misinterpretations and inconsistencies. In the interest of furthering scientific debate over Transeurasian language and population history, we address the critiques, revising datasets and fine-tuning approaches. The linguistic critique questions the quantity and quality of our datasets. Here we show that the number of surviving cognate sets for Transeurasian is in line with that for well-established language families. In addition, we find that Tian et al.’s failure to reject a core of regularly corresponding cognates in the basic vocabulary creates ground for a consensus about the genealogical relatability of the Transeurasian languages. The archaeological critique attempts a re-analysis of one Bayesian test using re-scored data only for northern China. Over half of the suggested re-scorings contain inconsistencies and it is not explained why the re-analysis retains the original data for sites outside northern China, comprising almost 60% of the total. More importantly, the sweeping claim that there is no evidence supporting the prehistoric migrations analysed in our study is not backed by any discussion of the archaeological record. With respect to genetics, the preprint claims a re-analysis showing that the data ‘do not conclusively support the farming-driven dispersal of Turkic, Mongolian, and Tungusic, nor the two-wave spread of farming to Korea.’ In fact, the only genetic re-analysis presented is limited to samples from Korea and Japan and does not contradict our original conservative modelling of Neolithic individuals with Hongshan and our Bronze Age ones with Upper Xiajiadian. In sum, in bringing multiple lines of evidence together through triangulation, we gained a more balanced and richer understanding of Transeurasian dispersals than each discipline could provide individually. Our research doubtless leaves room for improvement but we remain confident that triangulation did not ‘fail’, but rather brought us a step closer to understanding the history of the Transeurasian languages.
Disk-Drive-Like Operations in the Hippocampus
Authors: Nicola Wilten , Dupret David , Clopath Claudia
Published: October 2022

The rapid computation of re-playable memories within the hippocampus in the form of spike sequences is a near computer-like operation. Information can be encoded once during the initial experience, and replayed numerous times after in a compressed-time representation [1–8]. Theta oscillations, sharp-wave ripples, and attractor dynamics have been posited to collectively play a role in the formation and replay of memories. However, the precise interplay between these dynamical states remains elusive. Here, we show that the memory formation dynamics and operations of the hippocampus are not just computer-like, but map directly onto the dynamics and operations of a disk-drive. We constructed a tripartite spiking neural network model where the hippocampus is explicitly described as a disk drive with a rotating disk, an actuator arm, and a read/write head. In this Neural Disk Drive (NDD) model, hippocampal oscillations map to disk rotations in the rotating disk network while attractor dynamics in the actuator arm network point to “tracks” (spike assemblies) on the disk. The read/write head then writes information onto these tracks, which have temporally-structured spikes. Tracks can be replayed during hippocampal ripples for consolidation. We confirmed the existence of interneuron-ring-sequences, predicted by the rotating disk network, in experimental data. Our results establish the hippocampus as a brain region displaying explicit, computer-like operations. Based on the known interactions between the hippocampus and other brain areas, we anticipate that our results may lead to additional models that revisit the hypothesis that the brain performs explicit, computer-like operations.
M1 selective muscarinic allosteric modulation enhances cognitive flexibility and effective salience in nonhuman primates
Authors: Hassani Seyed A. , Neumann Adam , Russell Jason , Jones Carrie K. , Womelsdorf Thilo
Published: October 2022

Acetylcholine (ACh) in cortical neural circuits mediates how selective attention is sustained in the presence of distractors and how flexible cognition adjusts to changing task demands. The cognitive domains of attention and cognitive flexibility might be differentially supported by the M1 muscarinic cholinergic sub-receptor. Understanding how M1 mechanisms support these cognitive subdomains is of highest importance for advancing novel drug treatments for conditions with altered attention and reduced cognitive control including Alzheimer’s disease or schizophrenia. Here, we tested this question by assessing how the subtype selective M1-receptor specific positive allosteric modulator (M1 PAM VU0453595) affects visual search and flexible reward-learning in nonhuman primates. We found that allosteric potentiation of the M1 receptor enhanced flexible learning performance by improving extra-dimensional set shifting, by reducing latent inhibition of previously experienced distractors, and by reducing response perseveration in the absence of adverse side effects. These pro-cognitive effects occurred in the absence of apparent changes of attentional performance during visual search. In contrast, non-selective ACh modulation using the acetylcholinesterase inhibitor donepezil improved attention during visual search at doses that did not alter cognitive flexibility and that already triggered gastrointestinal cholinergic side effects. These findings illustrate that M1 positive allosteric modulation enhances cognitive flexibility without affecting attentional filtering of distraction, consistent with M1 activity boosting the effective salience of relevant over irrelevant objects. These results suggest that M1 PAMs are versatile compounds for enhancing cognitive flexibility in disorders spanning schizophrenia and Alzheimer’s diseases.

Statement of significance

Muscarinic receptors mediate the pro-cognitive effects of acetylcholine, but it has remained unclear whether they differentially affect the cognitive subfunctions of attentional filtering, set shifting, and learning. To clarify the functional specificity of M1 receptors, we assessed these diverse functions using a recently developed, highly selective M1 PAM. This M1 PAM caused domain-specific cognitive improvement of flexible learning and extra-dimensional set shifting, reduced perseverations and enhanced target recognition during learning without altering attentional filtering functions. These domain-specific improvement contrasted to effects of a non-selective acetylcholinesterase inhibitor that primarily enhanced attention and caused dose limiting adverse side effects. These results demonstrate domain-specific improvements of cognitive flexibility suggesting M1 PAMs are versatile compounds for treating cognitive deficits in schizophrenia and Alzheimer’s disease.
Second-generation dual-channel visible light optical coherence tomography enables wide-field, full-range, and shot-noise limited retinal imaging
Authors: Wang Jingyu , Nolen Stephanie , Song Weiye , Shao Wenjun , Yi Wei , Yi Ji
Published: October 2022

Visible light optical coherence tomography (VIS-OCT) is an emerging ophthalmic imaging method uniquely featured by ultrahigh depth resolution, retinal microvascular oximetry, and distinct scattering contrast in the visible spectral range. However, the clinical utility of VIS-OCT is impeded by the fundamental trade-off between the imaging depth range and axial resolution, determined by the spectral resolution and bandwidth respectively. While the full potential of VIS-OCT is leveraged by a broad bandwidth, the imaging depth is inversely sacrificed. The effective depth range is further limited by the wavelength-dependent roll-off that the signal-to-noise ratio (SNR) reduces in the deeper imaging range, more so in shorter wavelength. To address this trade-off, we developed a second-generation dual-channel VIS-OCT system including the first linear-in-k VIS-OCT spectrometer, reference pathlength modulation, and per A-line noise cancellation. All combined, we have achieved 7.2dB roll-off over the full 1.74 mm depth range (water) with shot-noise limited performance. The system uniquely enables >60° wide-field imaging over large retinal curvature at peripheral retina and optic nerve head, as well as high-definition imaging at ultrahigh 1.3 um depth resolution (water). The dual-channel design includes a conventional near infrared (NIR) channel, compatible with Doppler OCT and OCT angiography (OCTA). The comprehensive structure-function measurement by 2nd-Gen VIS-OCT system is a significant advance towards broader adaptation of VIS-OCT in clinical applications.
Efficient Multi-Label Attribute Classification and Recognition of Microbiological Bacteria Based on Deep Learning and model fine-tuning
Authors: Wu Duidi , Huang Haiqing , Zhang Shuo , Qi Jin , Wang Dong , Hu Jie
Published: October 2022

Bacterial vaginosis (BV) is the most common gynecological complaint affecting health of a large percentage of women worldwide. Traditional manual microscopy methods are expensive and time-consuming, to improve accuracy and efficiency, automated bacterial identification devices with detection intelligence algorithms are urgently needed. We propose a Fine-tuned SmallerVGG (FTS-VGG) deep convolutional network model based multi-label classification method for bacteria. Comparison experiments were deployed on several advanced backbone networks, including transfer learning on pre-trained VGG19, demonstrating that the proposed method achieves the advantages of being lighter, faster, more accurate and more efficient. Due to the high cost of time and expertise of experienced clinicians, we use random erasing for data augmentation to address the challenge of dataset collection and annotation, experiments demonstrate its robustness to occlusion. The proposed method has theoretical and practical implications, as well as the potential to be widely extended to other microscopic imaging applications.
Free-water volume fraction increases non-linearly with age in the white matter of the healthy human brain
Authors: Pieciak Tomasz , París Guillem , Beck Dani , Maximov Ivan I. , Tristán-Vega Antonio , de Luis-García Rodrigo , Westlye Lars T. , Aja-Fernández Santiago
Published: October 2022

The term free-water volume fraction (FWVF) refers to the cerebrospinal and interstitial fluids in the extracellular space of the white matter (WM) of the brain, which has been demonstrated as a sensitive biomarker that correlates with the cognitive performance and the neuropathological processes modifying the interstitial extracellular spaces. It can be quantified by properly fitting the isotropic compartment of the magnetic resonance (MR) signal in diffusion-sensitized sequences. UsingN= 287 healthy subjects aged 25-94, this study examines in detail the evolution of the FWVF in the human brain WM across the adult lifespan, which has been previously reported to exhibit a positive trend. We found evidence of a noticeably non-linear gain after the sixth decade of life, with a region-specific variate and varying change rate of the FWVF parameter with age, at the same time a heteroskedastic pattern across the adult lifespan is suggested. On the other hand, the FW-compensated MR signal leads to a region-dependent flattened age-related evolution of the mean diffusivity (MD) and fractional anisotropy (FA), along with a considerable reduction in their variability, as compared to standard studies conducted over the raw MR signal. This way, our study provides a new perspective on the trajectory-based assessment of the brain and explains the source of the variations observed in FA and MD parameters across the lifespan with previous studies with the standard diffusion tensor imaging.
Reactive fungal insoles
Authors: Nikolaidou Anna , Phillips Neil , Tsompanas Michail-Antisthenis , Adamatzky Andrew
Published: October 2022

Mycelium bound composites are promising materials for a diverse range of applications including wearables and building elements. Their functionality surpasses some of the capabilities of traditionally passive materials, such as synthetic fibres, reconstituted cellulose fibres and natural fibres. Thereby, creating novel propositions including augmented functionality (sensory) and aesthetic (personal fashion). Biomaterials can offer multiple modal sensing capability such as mechanical loading (compressive and tensile) and moisture content. To assess the sensing potential of fungal insoles we undertook laboratory experiments on electrical response of bespoke insoles made from capillary matting colonised with oyster fungi Pleurotus ostreatus to compressive stress which mimics human loading when standing and walking. We have shown changes in electrical activity with compressive loading. The results advance the development of intelligent sensing insoles which are a building block towards more generic reactive fungal wearables. Using FitzhHugh-Nagumo model we numerically illustrated how excitation wave-fronts behave in a mycelium network colonising an insole and shown that it may be possible to discern pressure points from the mycelium electrical activity.
Investigation of mutated in colorectal cancer evolution history indicate a putative role in Th17/Treg differentiation
Authors: Kubick Norwin , Bieńkowska Irmina , Horbańczuk Jarosław Olav , Sacharczuk Mariusz , Mickael Michel Edwar
Published: October 2022

The MCC family of genes plays a role in colorectal cancer development through various immunological pathways, including the Th17/Treg axis. We have previously shown that MCC1 and not MCC2 play a role in Treg differentiation. Our understanding of the genetic divergence patterns and evolutionary history of the MCC family in relation to its function, in general, and the Th17/Treg axis, in particular, remains incomplete. In this investigation, we explored 12 species’ genomes to study the phylogenetic origin, structure, and functional specificity of this family. In vertebrates, both MCC1 and MCC2 homologs have been discovered, while invertebrates have a single MCC homolog. We found MCC homologs as early as Cnidarians and Trichoplax, suggesting that the MCC family first appeared 741 million years ago (Ma), whereas MCC divergence into MCC1 and MCC2 families occurred at 540 Ma. In general, we did not detect significant positive selection regulating MCC evolution. Our investigation, based on MCC1 structural similarity, suggests that they may play a role in the evolutionary changes in Tregs’ emergence towards complexity, including the ability to utilize calcium for differentiation through the use of the EFH calcium-binding domain. We also found that the motif NPSTGE was highly conserved in MCC1 but not in MCC2. The NPSTGE motif binds KEAP1 with high affinity, suggesting an Nrf2-mediated function for Nrf2. In the case of MCC2, we found that the “Modifier of rudimentary” motif is highly conserved. This motif contributes to the regulation of alternative splicing. Overall, our study sheds light on how the evolution of the MCC family is connected to its function in regulating the Th17/Treg axis.
Investigating the attentional focus to workplace-related soundscapes in a complex audio-visual-motor task using EEG
Authors: Rosenkranz Marc , Cetin Timur , Uslar Verena , Bleichner Martin G.
Published: October 2022

In demanding work situations (e.g., during a surgery) the processing of complex soundscapes varies over time and can be a burden for medical personnel. Here we study, using mobile electroencephalography (EEG), how humans process workplace-related soundscapes while performing a complex audio-visual-motor task (3D Tetris). Specifically, we wanted to know how the attentional focus changes the processing of the soundscape as a whole. Participants played a game of 3D Tetris in which they had to use both hands to control falling blocks. At the same time, participants listened to a complex soundscape, similar to what is found in an operating room (i.e., sound of machinery, people talking in the background, alarm sounds, and instructions). In this within-subject design, participants had to react to instructions (e.g., “place the next Block in the upper left corner”) and to sounds depending on the experimental condition, either to a specific alarm sound originating from a fixed location or to a beep sound that originated from varying locations. Attention to the alarm reflected a narrow attentional focus, as it was easy to detect and most of the soundscape could be ignored. Attention to the beep reflected a wide attentional focus, as it required the participants to monitor multiple different sound streams. Results show the robustness of the N1 and P3 event related potential response during this dynamic task with a complex auditory soundscape. Furthermore, we used temporal response functions to study auditory processing to the whole soundscape. This work is a step towards studying workplace-related sound processing in the operating room using mobile EEG.