bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Protein Intake on Visceral Abdominal Fat and Metabolic Biomarkers in Older Men With Functional Limitations: Results From a Randomized Clinical Trial
Authors: Huang Grace , Pencina Karol , Li Zhuoying , Apovian Caroline M , Travison Thomas G , Storer Thomas W , Gagliano-Jucá Thiago , Basaria Shehzad , Bhasin Shalender
Published: January 2021

Background

It remains controversial whether high protein diets improve cardiometabolic profile. We investigated whether increasing protein intake to 1.3 g/kg/day in functionally limited older adults with usual protein intake ≤RDA (0.8 g/kg/day) improves visceral fat accumulation and serum cardiovascular risk markers more than the recommended daily allowance (RDA).

Methods

The Optimizing Protein Intake in Older Men Trial was a placebo-controlled, randomized trial in which 92 functionally limited men, ≥65 years, with usual protein intake ≤RDA were randomized for 6 months to: 0.8 g/kg/day protein plus placebo; 1.3 g/kg/day protein plus placebo; 0.8 g/kg/day protein plus testosterone enanthate 100 mg weekly; or 1.3 g/kg/day protein plus testosterone enanthate 100 mg weekly. In this substudy, metabolic and inflammatory serum markers were measured in 77 men, and visceral adipose tissue (VAT) was assessed using dual-energy x-ray absorptiometry in 56 men.

Results

Treatment groups were similar in their baseline characteristics. Randomization to 1.3 g/kg/day protein group was associated with greater reduction in VAT compared to 0.8 g/kg/day group (between-group difference: −17.3 cm2, 95% confidence interval [CI]: −29.7 to −4.8 cm2, p = .008), regardless of whether they received testosterone or placebo. Changes in fasting glucose, fasting insulin, HOMA-IR, leptin, adiponectin, IL-6, and hs-CRP did not differ between the 0.8 versus 1.3 g/kg/day protein groups regardless of testosterone use.

Conclusions

Protein intake >RDA decreased VAT in functionally limited older men but did not improve cardiovascular disease risk markers.

Clinical Trials Registration Number

NCT01275365
Analysis of Global Oxidative Status Using Multimarker Scores Reveals a Specific Association Between Renal Dysfunction and Diuretic Therapy in Older Adults
Authors: Rodríguez-Sánchez Elena , Navarro-García José Alberto , Aceves-Ripoll Jennifer , González-Lafuente Laura , Corbacho-Alonso Nerea , Baldan-Martín Montserrat , Madruga Felipe , Alvarez-Llamas Gloria , Barderas María G , Ruilope Luis M , Ruiz-Hurtado Gema
Published: January 2021

Aging and chronic kidney disease (CKD) are important interrelated cardiovascular risk (CVR) factors linked to oxidative stress, but this relationship has not been well studied in older adults. We assessed the global oxidative status in an older population with normal to severely impaired renal function. We determined the oxidative status of 93 older adults (mean age 85 years) using multimarker scores. OxyScore was computed as index of systemic oxidative damage by analyzing carbonyl groups, oxidized low-density lipoprotein, 8-hydroxy-2′-deoxyguanosine, and xanthine oxidase activity. AntioxyScore was computed as index of antioxidant defense by analyzing catalase and superoxide dismutase (SOD) activity and total antioxidant capacity. OxyScore and AntioxyScore were higher in subjects with estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 than in peers with eGFR >60 mL/min/1.73 m2, with protein carbonyls, catalase, and SOD activity as major drivers. Older adults with a recent cardiovascular event had similar OxyScore and AntioxyScore as peers with eGFR >60 mL/min/1.73 m2. Multivariate linear regression analysis revealed that both indices were associated with decreased eGFR independently of traditional CVR factors. Interestingly, AntioxyScore was also associated with diuretic treatment, and a more pronounced increase was seen in subjects receiving combination therapy. The associations of AntioxyScore with diuretic treatment and eGFR were mutually independent. In conclusion, eGFR is the major contributor to the imbalance in oxidative stress in this older population. Given the association between oxidative stress, CKD, and CVR, the inclusion of renal function parameters in CVR estimators for older populations, such as the SCORE-OP, might improve their modest performance.
The reluctant preference: communities of enthusiasts and the diffusion of atypical innovation
Authors: Formilan Giovanni , Boari Cristina
Published: January 2021

Exploring the initial diffusion of innovation, this article investigates how early adopters reach a tipping point with a shared and emphatic preference for atypical products. In a community of enthusiasts where members mutually observes each other, we show that potential buyers are reluctant to express a preference for highly atypical products despite their vanguard positive attitude toward atypicality. We argue that such reluctance is driven by a membership-validating concern: while favoring highly atypical products, potential buyers still need to avoid atypical but low-quality alternatives that would undermine their sense of membership to the vanguard group. Consistently, we hypothesize that the endorsement granted by other community members to a basket of atypical products alleviates—and eventually removes—potential buyers’ reluctance. Between equally endorsed alternatives, potential buyers will then include the most atypical one in their displayed preference, thereby revealing their vanguard attitude and validating their membership to the in-group. We situate our analysis in a community of enthusiasts for electronic music recordings and find robust support to our hypotheses. By raising the bar of how a product must be to be distinctive, membership-seeking enthusiasts raise the threshold of atypicality. In so doing, they also expand the range of products deemed typical by the general consumer. These twined processes fuel the ongoing diffusion of innovation.
Catch up of complex products and systems: lessons from China’s high-speed rail sectoral system
Authors: Mei Liang , Zhang Nana
Published: January 2021

The article uses a longitudinal case study of China’s high-speed rail from the sectoral system perspective to show how a latecomer achieves catch up in the context of complex products and systems (CoPS). Results indicate the coevolution among high-speed train CoPS, the complementary assets, and government engagement are important to the sectoral system’s catch up. To achieve catch up, a latecomer can choose a strategy in which the complementary assets take precedence over the CoPS, and the coordination of the two systems is maintained with government engagement. In addition, two elements involving the sectoral system’s knowledge base and government engagement play fundamental roles enabling the evolution of the competences of the CoPS and the leverage of complementary assets for catch up. The article contributes to the literature on catch up in the CoPS context using a sectoral system framework.
Left heart growth and biventricular repair after hybrid palliation
Authors: Sojak Vladimir , Bokenkamp Regina , Kuipers Irene , Schneider Adriaan , Hazekamp Mark
Published: January 2021

OBJECTIVES

We evaluated the outcomes of biventricular repair after initial hybrid palliation performed in small infants with various forms of left ventricle hypoplasia.

METHODS

Between September 2010 and January 2020, a total of 27 patients had biventricular repair after hybrid palliation at a median age of 11 days. Indications for the hybrid approach included growth promotion of the left ventricle outflow tract and/or the aortic valve in 14 patients and that of the left ventricle in 13 patients. Seven reinterventions and 7 reoperations were performed during the interstage period. Significant growth of left ventricle parameters was noted during the median interstage period of 62 days. Sixteen subjects had aortic arch repair, ventricular septal defect closure and relief of subaortic stenosis; 5 patients had the Ross–Konno procedure; 5 patients underwent the Yasui procedure; and 1 patient had unbalanced atrioventricular septal defect and aortic arch repair.

RESULTS

Twenty-three patients (85.2%) are alive at a median follow-up of 3.3 years. Two and 3 patients died early and late after achieving biventricular circulation, respectively. There were 22 reinterventions and 15 reoperations after biventricular repair.

CONCLUSIONS

Hybrid palliation can stimulate left heart growth in some patients with left ventricle hypoplasia. More patients may eventually achieve biventricular circulation than was initially thought. Additional interventions and operations are foreseeable. Despite ventricular rehabilitation, some patients with borderline left ventricles may develop restrictive physiology.
Does preoperative pulmonary rehabilitation/physiotherapy improve patient outcomes following lung resection?
Authors: Bibo Liam , Goldblatt Joshua , Merry Christopher
Published: January 2021

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was whether preoperative physiotherapy (pulmonary prehabilitation) is beneficial for patients undergoing lung resection. Altogether 177 papers were found using the reported search, of which 10 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. A meta-analysis by Li et al. showed that patients who received a preoperative rehabilitation programme (PRP) had reduced incidence of postoperative pulmonary complications (PPCs) (odds ratio 0.44, 95% CI 0.27–0.71), reduced length of stay (LOS) (−4.23 days, 95% CI −6.14 to −2.32 days) and improved 6-min walking distance (71.25 m, 95% CI 39.68–102.82) and peak oxygen uptake consumption (VO2 peak) (3.26, 95% CI 2.17–4.35). A meta-analysis by Steffens et al. showed that PPCs were reduced in patients with PRP (relative risk 0.49, 95% CI 0.33–0.73) and reduced LOS (−2.86 days, 95% CI −5.40 to −0.33). The results of 3 additional meta-analyses, 4 randomized controlled trials and 1 observational study all provide further support to PRP in enhanced recovery after surgery and the improvement in exercise capacity. We conclude that PRP improves exercise capacity in patients undergoing surgical resection for lung cancer. Moderate quality evidence supports preoperative exercise providing significant reduction in PPCs and hospital LOS. Referral to exercise programmes should be considered in patients awaiting lung resection, particularly those deemed borderline for suitability for surgical resection.
The impacts of subsidy policies and channel encroachment on the power battery recycling of new energy vehicles
Authors: Liu Kai , Wang Chuanxu
Published: January 2021

With the rapid development of new energy vehicles (NEVs), the recycling and reuse of retired power batteries has attracted extensive attention from the society and scholars. In this paper, we establish a closed-loop supply chain model composed of the government, one power battery supplier and one NEV manufacturer. Based on game theory, considering whether the battery supplier encroaches on the power battery recycling channel, we study the optimal decisions of the government and supply chain members under different government subsidy policies (no subsidy, subsidy for the NEV manufacturer and subsidy for consumers) and their impact on profits and social welfare. The results show that, whether the battery supplier encroaches on the recycling channel or not, compared with the no subsidy policy, subsidy for the NEV manufacturer is more conducive to the improvement of enterprise profits and social welfare. In addition, whether the battery collection quantity is constrained by the NEV sales quantity, when the recycling channel cost is lower than a certain threshold, the encroachment is always beneficial to the battery supplier. When the recycling channel cost is within a certain threshold range, the encroachment will achieve a win–win situation; otherwise, win–lose. When the recycling channel cost is higher than a certain threshold, the encroachment behavior has no impact on the NEV manufacturer and the battery supplier. Finally, we investigate the impact of key parameters on the enterprise profits and social welfare through numerical experiments. We also find that the environmental awareness of consumers have significant impacts on social welfare.
On the Stability of the Equator Map for Higher Order Energy Functionals
Authors: Fardoun A , Montaldo S , Ratto A
Published: January 2021

Let $B^n\subset \mathbb{R} ^{n}$ and $\mathbb{S} ^n\subset \mathbb{R} ^{n+1}$ denote the Euclidean $n$-dimensional unit ball and sphere, respectively. The extrinsic $k$-energy functional is defined on the Sobolev space $W^{k,2}\left (B^n,\mathbb{S} ^n \right )$ as follows: $E_{k}^{{\textrm{ext}}}(u)=\int _{B^n}|\Delta ^s u|^2\ dx$ when $k=2s$, and $E_{k}^{{\textrm{ext}}}(u)=\int _{B^n}|\nabla \Delta ^s u|^2\ dx$ when $k=2s+1$. These energy functionals are a natural higher order version of the classical extrinsic bienergy, also called Hessian energy. The equator map $u^*: B^n \to \mathbb{S} ^n$, defined by $u^*(x)=(x/|x|,0)$, is a critical point of $E_{k}^{{\textrm{ext}}}(u)$ provided that $n \geq 2k+1$. The main aim of this paper is to establish necessary and sufficient conditions on $k$ and $n$ under which $u^*: B^n \to \mathbb{S} ^n$ is minimizing or unstable for the extrinsic $k$-energy.
Multipeptide Assays for Sensitive and Differential Detection of Anti-Chlamydia Trachomatis Antibodies
Authors: Rahman Kh Shamsur , Kaltenboeck Bernhard
Published: January 2021

Detection of anti-Chlamydia trachomatis (Ctr) antibodies is compromised by cross-reactivity and poor sensitivity of classic Ctr-antigens. We discovered 48 strongly reactive peptide antigens of Ctr-specific B-cell epitopes from 21 immunodominant proteins. In this study, we review the utility of peptide assays for diagnosis of Ctr infections. By combining many of these Ctr-specific B-cell epitopes from several proteins in separate or mixed multipeptide assays, they achieved vastly superior assay sensitivity and specificity over standard enzyme-linked immunosorbent assays. Such multipeptide assays eliminate cross-reactivities (false positives) and correct for stochastic gaps in antibody responses (false negatives). More importantly, we developed and validated a novel microarray platform in which hundreds of peptides from many proteins are spotted in a single reaction well. This offers the possibility of high-throughput screening of many candidate peptides for routine serological fingerprinting of Ctr infections. Discovery of optimal sets of antibody responses that associate with clinical pelvic inflammatory disease (PID) may identify diagnostically useful PID biomarker antigens.
Growth of tumor emboli within a vessel model reveals dependence on the magnitude of mechanical constraint
Authors: Kulwatno Jonathan , Gearhart Jamie , Gong Xiangyu , Herzog Nora , Getzin Matthew , Skobe Mihaela , Mills Kristen L
Published: January 2021

Tumor emboli—aggregates of tumor cells within vessels—pose a clinical challenge as they are associated with increased metastasis and tumor recurrence. When growing within a vessel, tumor emboli are subject to a unique mechanical constraint provided by the tubular geometry of the vessel. Current models of tumor emboli use unconstrained multicellular tumor spheroids, which neglect this mechanical interplay. Here, we modeled a lymphatic vessel as a 200 μm-diameter channel in either a stiff or soft, bioinert agarose matrix to create a vessel-like constraint model (VLCM), and we modeled colon or breast cancer tumor emboli with aggregates of HCT116 or SUM149PT cells, respectively. The stiff matrix VLCM constrained the tumor emboli to the cylindrical channel, which led to continuous growth of the emboli, in contrast to the growth rate reduction that unconstrained spheroids exhibit. Emboli morphology in the soft matrix VLCM, however, was dependent on the magnitude of mechanical mismatch between the matrix and the cell aggregates. In general, when the elastic modulus of the matrix of the VLCM was greater than the emboli (EVLCM/Eemb > 1), the emboli were constrained to grow within the channel, and when the elastic modulus of the matrix was less than the emboli (0 < EVLCM/Eemb < 1), the emboli bulged into the matrix. Due to a large difference in myosin II expression between the cell lines, we hypothesized that tumor cell aggregate stiffness is an indicator of cellular force-generating capability. Inhibitors of myosin-related force generation decreased the elastic modulus and/or increased the stress relaxation of the tumor cell aggregates, effectively increasing the mechanical mismatch. The increased mechanical mismatch after drug treatment was correlated with increased confinement of tumor emboli growth along the channel, which may translate to increased tumor burden due to the increased tumor volume within the diffusion distance of nutrients and oxygen.
On the Impact of Interpretability Methods in Active Image Augmentation Method
Authors: Arthur Oliveira Santos Flávio , Zanchettin Cleber , Nogueira Matos Leonardo , Novais Paulo
Published: January 2021

Robustness is a significant constraint in machine learning models. The performance of the algorithms must not deteriorate when training and testing with slightly different data. Deep neural network models achieve awe-inspiring results in a wide range of applications of computer vision. Still, in the presence of noise or region occlusion, some models exhibit inaccurate performance even with data handled in training. Besides, some experiments suggest deep learning models sometimes use incorrect parts of the input information to perform inference. Active image augmentation (ADA) is an augmentation method that uses interpretability methods to augment the training data and improve its robustness to face the described problems. Although ADA presented interesting results, its original version only used the vanilla backpropagation interpretability to train the U-Net model. In this work, we propose an extensive experimental analysis of the interpretability method’s impact on ADA. We use five interpretability methods: vanilla backpropagation, guided backpropagation, gradient-weighted class activation mapping (GradCam), guided GradCam and InputXGradient. The results show that all methods achieve similar performance at the ending of training, but when combining ADA with GradCam, the U-Net model presented an impressive fast convergence.
Available drugs and supplements for rapid deployment for treatment of COVID-19
Authors: Cicka Danielle , Sukhatme Vikas P
Published: January 2021

Effective treatment for COVID-19 remains elusive, though urgently needed in the current pandemic. Repurposing marketed therapies may be an effective strategy for finding treatments quickly and, recently, in vitro and clinical testing of such therapies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has skyrocketed. However, not all marketed drugs showing in vitro efficacy could achieve therapeutic concentrations in humans and discernment of drugs that have favorable pharmacokinetic properties can save time and resources for future studies. Here, we compile marketed therapies, including supplements, having anti-viral activity with in vitro, in vivo, and/or clinical data against α and β coronaviruses into tables, alongside their pharmacokinetic properties. We point to several drugs or supplements available for immediate repurposing because they have achievable blood concentrations in humans well above their inhibitory concentrations against coronaviruses. This compilation may contribute to the implementation of rapid future studies by narrowing the vast number of marketed drugs reported for potential efficacy against SARS-CoV-2 on the basis of their pharmacokinetic properties and published coronavirus data.
Variation in regrowth ability in relation to land-use intensity in three common grassland herbs
Authors: Kirschbaum Anna , Bossdorf Oliver , Scheepens J F
Published: January 2021

Aims

Plant populations in managed grasslands are subject to strong selection exerted by grazing, mowing and fertilization. Many previous studies showed that this can cause evolutionary changes in mean trait values, but little is known about the evolution of phenotypic plasticity in response to land use. In this study, we aimed to elucidate the relationships between phenotypic plasticity—specifically, regrowth ability after biomass removal—and the intensity of grassland management and levels of temporal variation therein.

Methods

We conducted an outdoor common garden experiment to test if plants from more intensively mown and grazed sites showed an increased ability to regrow after biomass removal. We used three common plant species from temperate European grasslands, with seed material from 58 to 68 populations along gradients of land-use intensity, ranging from extensive (only light grazing) to very intensive management (up to four cuts per year).

Important Findings

In two out of three species, we found significant population differentiation in regrowth ability after clipping. While variation in regrowth ability was unrelated to the mean land-use intensity of populations of origin, we found a relationship with its temporal variation in Plantago lanceolata, where plants experiencing less variable environmental conditions over the last 11 years showed stronger regrowth in reproductive biomass after clipping. Therefore, while mean grazing and mowing intensity may not select for regrowth ability, the temporal stability of the environmental heterogeneity created by land use may have caused its evolution in some species.
Drivers of understorey biomass: tree species identity is more important than richness in a young forest
Authors: Germany Markus S , Bruelheide Helge , Erfmeier Alexandra
Published: January 2021

Aims

Positive biodiversity–ecosystem functioning relationships have been widely reported, predominately from grassland ecosystems. However, this does not necessarily have to apply accordingly in more complex situations such as in forests across different vertical strata. For instance, overstorey tree species richness has been shown to be associated with a lower understorey productivity. Whether or not tree species richness effects add to understorey productivity by increasing (i.e. due to habitat heterogeneity) or reducing resource availability (i.e. through increasing competition) and whether understorey productivity is indeed being governed more strongly by tree species identity are likely to change over time. Moreover, studies also suggested that richness–productivity relationships change with the environmental context. Using an experimental forest plantation with manipulated tree species richness, this study examined these temporal and environmental dynamics across strata.

Methods

In the context of the Biodiversity-Ecosystem Functioning project in subtropical China (BEF-China), we made use of understorey biomass samples repeatedly collected over a time period of 3 years along a tree species richness gradient. The effects of tree species richness, tree species identities and time were studied across different environmental treatments for their impact on understorey biomass.

Important Findings

While we found significant and consistent tree layer identity effects on understorey biomass, no such effect was encountered for tree species richness. Our results also indicate that among structural layers in forests, there might not be a single, generalizable overstorey species richness–understorey productivity relationship, and that the extent as to which overstorey-related environmental factors such as light transmittance contribute to understorey productivity change with time. Overall, we demonstrate that temporal dynamics should be considered when studying relationship among structural layers in forests.
Effects of nitrogen addition and mowing on nitrogen- and water-use efficiency of Artemisia frigida in a grassland restored from an abandoned cropland
Authors: Diao Huajie , Kardol Paul , Dong Kuanhu , Wang Changhui
Published: January 2021

Aims

Competition among plants in a community usually depends on their nitrogen (N)-use efficiency (NUE) and water-use efficiency (WUE) in arid and semi-arid regions. Artemisia frigida is an indicator species in heavily degraded grassland, however, how its NUE and WUE respond to N addition in different successional stages is still unclear, especially with mowing, a common management practice in semi-arid grasslands.

Methods

Based on a long-term controlled experiment with N addition and mowing in an abandoned cropland from 2006 to 2013, we investigated the NUE and WUE of A. frigida in two patches (i.e. grass and herb patches) in 2013 which represented two potential successional stages from herb to grass communities. The coverage of A. frigida was higher (about 50%) in the herb patch than in the grass patch (about 10%). Stable isotopic C (δ 13C) and N (δ 15N) as well as C and N pools were measured in plants and soils. NUE was calculated as leaf C/N, and leaf δ 13C values were used as a proxy for WUE.

Important Findings

N addition did not affect WUE of A. frigida, but significantly decreased NUE by 42.9% and 26.6% in grass and herb patches, respectively. The response of NUE to N addition was related to altering utilization of different N sources (NH4+vs. NO3−) by A. frigida according to the changed relationship between leaf δ 15N/soil δ 15N and NUE. Mowing had no effect on NUE regardless of N addition, but significantly increased WUE by 2.3% for A. frigida without N addition in the grass patch. The addition of N reduced the positive effect of mowing on its WUE in grass patch. Our results suggested that decreased NUE and/or WUE of A. frigida under mowing and N addition could reduce its competition, and further accelerate restoration succession from the abandoned cropland to natural grassland in the semi-arid region.
Quantifying the transmission advantage associated with N501Y substitution of SARS-CoV-2 in the UK: an early data-driven analysis
Authors: Zhao Shi , Lou Jingzhi , Cao Lirong , Zheng Hong , Chong Marc K C , Chen Zigui , Chan Renee W Y , Zee Benny C Y , Chan Paul K S , Wang Maggie H
Published: January 2021

The emerging N501Y mutation in severe acute respiratory syndrome coronavirus 2, which becomes prevalent in the UK rapidly, is one of the major challenges of COVID-19 control. To explore the transmission advantage, we estimate that the N501Y substitution increases the infectivity by 52% (95% confidence interval: 46, 58) in terms of the reproduction number.
Molecular responses of legumes to abiotic stress: post-translational modifications of proteins and redox signaling
Authors: Matamoros Manuel A , Becana Manuel
Published: January 2021

Legumes include several major crops that can fix atmospheric nitrogen in symbiotic root nodules, thus reducing the demand for nitrogen fertilizers and contributing to sustainable agriculture. Global change models predict increases in temperature and extreme weather conditions. This scenario might increase plant exposure to abiotic stresses and negatively affect crop production. Regulation of whole plant physiology and nitrogen fixation in legumes during abiotic stress is complex, and only a few mechanisms have been elucidated. Reactive oxygen species (ROS), reactive nitrogen species (RNS), and reactive sulfur species (RSS) are key players in the acclimation and stress tolerance mechanisms of plants. However, the specific redox-dependent signaling pathways are far from understood. One mechanism by which ROS, RNS, and RSS fulfil their signaling role is the post-translational modification (PTM) of proteins. Redox-based PTMs occur in the cysteine thiol group (oxidation, S-nitrosylation, S-glutathionylation, persulfidation), and also in methionine (oxidation), tyrosine (nitration), and lysine and arginine (carbonylation/glycation) residues. Unraveling PTM patterns under different types of stress and establishing the functional implications may give insight into the underlying mechanisms by which the plant and nodule respond to adverse conditions. Here, we review current knowledge on redox-based PTMs and their possible consequences in legume and nodule biology.
Evolution of disc thickness in simulated high-redshift galaxies
Authors: Meng Xi , Gnedin Oleg Y
Published: January 2021

We study the growth of stellar discs of Milky Way-sized galaxies using a suite of cosmological simulations. We calculate the half-mass axis lengths and axis ratios of stellar populations split by age in galaxies with stellar mass $M_{*}=10^7\!-\!10^{10}\, \mathrm{M}_{\odot }$ at redshifts z > 1.5. We find that in our simulations stars always form in relatively thin discs, and at ages below 100 Myr are contained within half-mass height z1/2 ∼ 0.1 kpc and short-to-long axial ratio z1/2/x1/2 ∼ 0.15. Disc thickness increases with the age of stellar population, reaching median z1/2 ∼ 0.8 kpc and z1/2/x1/2 ∼ 0.6 for stars older than 500 Myr. We trace the same group of stars over the simulation snapshots and show explicitly that their intrinsic shape grows more spheroidal over time. We identify a new mechanism that contributes to the observed disc thickness: rapid changes in the orientation of the galactic plane mix the configuration of young stars. The frequently mentioned ‘upside-down’ formation scenario of galactic discs, which posits that young stars form in already thick discs at high redshift, may be missing this additional mechanism of quick disc inflation. The actual formation of stars within a fairly thin plane is consistent with the correspondingly flat configuration of dense molecular gas that fuels star formation.
Optical and near-infrared observations of the SPT2349-56 proto-cluster core at z = 4.3
Authors: Rotermund K M , Chapman S C , Phadke K A , Hill R , Pass E , Aravena M , Ashby M L N , Babul A , Béthermin M , Canning R , de Breuck C , Dong C , Gonzalez A H , Hayward C C , Jarugula S , Marrone D P , Narayanan D , Reuter C , Scott D , Spilker J S , Vieira J D , Wang G , Weiss A
Published: January 2021

We present Gemini-S and Spitzer-IRAC optical-through-near-IR observations in the field of the SPT2349-56 proto-cluster at z = 4.3. We detect optical/IR counterparts for only 9 of the 14 submillimetre galaxies (SMGs) previously identified by ALMA in the core of SPT2349-56. In addition, we detect four z ∼ 4 Lyman-break galaxies (LBGs) in the 30 arcsec-diameter region surrounding this proto-cluster core. Three of the four LBGs are new systems, while one appears to be a counterpart of one of the nine observed SMGs. We identify a candidate brightest cluster galaxy (BCG) with a stellar mass of $(3.2^{+2.3}_{-1.4})\times 10^{11}$ M⊙. The stellar masses of the eight other SMGs place them on, above, and below the main sequence of star formation at z ≈ 4.5. The cumulative stellar mass for the SPT2349-56 core is at least (12.2 ± 2.8) × 1011 M⊙, a sizeable fraction of the stellar mass in local BCGs, and close to the universal baryon fraction (0.19) relative to the virial mass of the core (1013 M⊙). As all 14 of these SMGs are destined to quickly merge, we conclude that the proto-cluster core has already developed a significant stellar mass at this early stage, comparable to z = 1 BCGs. Importantly, we also find that the SPT2349-56 core structure would be difficult to uncover in optical surveys, with none of the ALMA sources being easily identifiable or constrained through g, r, and i colour selection in deep optical surveys and only a modest overdensity of LBGs over the more extended structure. SPT2349-56 therefore represents a truly dust-obscured phase of a massive cluster core under formation.
The T414G mitochondrial DNA mutation: a biomarker of ageing in human eye
Authors: Gary Anne-Sophie , Dorr Marie M , Rochette Patrick J
Published: January 2021

The mitochondrial mutation T414G (mtDNAT414G) has been shown to accumulate in aged and sun-exposed skin. The human eye is also exposed to solar harmful rays. More precisely, the anterior structures of the eye (cornea, iris) filter UV rays and the posterior portion of the eye (retina) is exposed to visible light. These rays can catalyse mutations in mitochondrial DNA such as the mtDNAT414G, but the latter has never been investigated in the human ocular structures. In this study, we have developed a technique to precisely assess the occurrence of mtDNAT414G. Using this technique, we have quantified mtDNAT414G in different human ocular structures. We found an age-dependent accumulation of mtDNAT414G in the corneal stroma, the cellular layer conferring transparency and rigidity to the human cornea, and in the iris. Since cornea and iris are two anterior ocular structures exposed to solar UV rays, this suggests that the mtDNAT414G mutation is resulting from cumulative solar exposure and this could make the mtDNAT414G a good marker of solar exposure. We have previously shown that the mtDNACD4977 and mtDNA3895 deletions accumulate over time in photo-exposed ocular structures. With the addition of mtDNAT414G mutation, it becomes feasible to combine the levels of these different mtDNA mutations to obtain an accurate assessment of the solar exposure that an individual has accumulated during his/her lifetime.
Genetic damage in lymphocytes of lung cancer patients is correlated to the composition of the respiratory tract microbiome
Authors: Druzhinin V G , Matskova L V , Demenkov P S , Baranova E D , Volobaev V P , Minina V I , Larionov A V , Titov V A , Fucic A
Published: January 2021

Recent findings indicate that the microbiome may have significant impact on the development of lung cancer by its effects on inflammation, dysbiosis or genome damage. The aim of this study was to compare the sputum microbiome of lung cancer (LC) patients with the chromosomal aberration (CA) and micronuclei (MN) frequency in peripheral blood lymphocytes. In the study, the taxonomic composition of the sputum microbiome of 66 men with untreated LC were compared with 62 control subjects with respect to CA and MN frequency and centromere fluorescence in situ hybridisation analysis. Results showed a significant increase in CA (4.11 ± 2.48% versus 2.08 ± 1.18%) and MN (1.53 ± 0.67% versus 0.87 ± 0.49%) frequencies, respectively, in LC patients as compared to control subjects. The higher frequency of centromeric positive MN of LC patients was mainly due to aneuploidy. A significant increase in Streptococcus, Bacillus, Gemella and Haemophilus in LC patients was detected, in comparison to the control subjects while 18 bacterial genera were significantly reduced, which indicates a decrease in the beta diversity in the microbiome of LC patients. Although, the CA frequency in LC patients is significantly associated with an increased presence of the genera Bacteroides, Lachnoanaerobaculum, Porphyromonas, Mycoplasma and Fusobacterium in their sputum, and a decrease for the genus Granulicatella after application of false discovery rate correction, significance was not any more present. The decrease of MN frequency of LC patients is significantly associated with an increase in Megasphaera genera and Selenomonas bovis. In conclusion, a significant difference in beta diversity of microbiome between LC and control subjects and association between the sputum microbiome composition and genome damage of LC patients was detected, thus supporting previous studies suggesting an etiological connection between the airway microbiome and LC.
The solution structures of higher-order human telomere G-quadruplex multimers
Authors: Monsen Robert C , Chakravarthy Srinivas , Dean William L , Chaires Jonathan B , Trent John O
Published: January 2021

Human telomeres contain the repeat DNA sequence 5′-d(TTAGGG), with duplex regions that are several kilobases long terminating in a 3′ single-stranded overhang. The structure of the single-stranded overhang is not known with certainty, with disparate models proposed in the literature. We report here the results of an integrated structural biology approach that combines small-angle X-ray scattering, circular dichroism (CD), analytical ultracentrifugation, size-exclusion column chromatography and molecular dynamics simulations that provide the most detailed characterization to date of the structure of the telomeric overhang. We find that the single-stranded sequences 5′-d(TTAGGG)n, with n = 8, 12 and 16, fold into multimeric structures containing the maximal number (2, 3 and 4, respectively) of contiguous G4 units with no long gaps between units. The G4 units are a mixture of hybrid-1 and hybrid-2 conformers. In the multimeric structures, G4 units interact, at least transiently, at the interfaces between units to produce distinctive CD signatures. Global fitting of our hydrodynamic and scattering data to a worm-like chain (WLC) model indicates that these multimeric G4 structures are semi-flexible, with a persistence length of ∼34 Å. Investigations of its flexibility using MD simulations reveal stacking, unstacking, and coiling movements, which yield unique sites for drug targeting.
Lamin B1 acetylation slows the G1 to S cell cycle transition through inhibition of DNA repair
Authors: Murray-Nerger Laura A , Justice Joshua L , Rekapalli Pranav , Hutton Josiah E , Cristea Ileana M
Published: January 2021

The integrity and regulation of the nuclear lamina is essential for nuclear organization and chromatin stability, with its dysregulation being linked to laminopathy diseases and cancer. Although numerous posttranslational modifications have been identified on lamins, few have been ascribed a regulatory function. Here, we establish that lamin B1 (LMNB1) acetylation at K134 is a molecular toggle that controls nuclear periphery stability, cell cycle progression, and DNA repair. LMNB1 acetylation prevents lamina disruption during herpesvirus type 1 (HSV-1) infection, thereby inhibiting virus production. We also demonstrate the broad impact of this site on laminar processes in uninfected cells. LMNB1 acetylation negatively regulates canonical nonhomologous end joining by impairing the recruitment of 53BP1 to damaged DNA. This defect causes a delay in DNA damage resolution and a persistent activation of the G1/S checkpoint. Altogether, we reveal LMNB1 acetylation as a mechanism for controlling DNA repair pathway choice and stabilizing the nuclear periphery.
Spetzler-Martin Grade III Arteriovenous Malformations: A Comparison of Modified and Supplemented Spetzler-Martin Grading Systems
Authors: Frisoli Fabio A , Catapano Joshua S , Farhadi Dara S , Cadigan Megan S , Nguyen Candice L , Labib Mohamed A , Srinivasan Visish M , Lawton Michael T
Published: January 2021

BACKGROUND

The modified Spetzler-Martin (SM) grading system proposes that grade III arteriovenous malformation (AVM) subtypes are associated with variable microsurgical risks, with small AVMs (III−) having lower risk and medium/eloquent AVMs (III+) having higher risk. Adding patient age and AVM bleeding status and compactness to the SM grade produces a score – the supplemented SM (Supp-SM) grade – to more accurately assess preoperative risk.

OBJECTIVE

To compare the predictive power of the modified SM and Supp-SM grades for risk assessment in patients with grade III AVMs.

METHODS

Patients with SM grade III AVMs treated between 2011 and 2018 were retrospectively reviewed. Good outcomes were defined as modified Rankin Scale (mRS) scores ≤ 2 or unchanged/improved mRS scores (pre- vs postsurgery).

RESULTS

Of 102 patients with SM grade III AVMs, 59% had grade III− and 24% had grade III+ AVMs. Supp SM grade 6 and grade 7 AVMs accounted for 44% and 24%, respectively. Overall, 33% of patients worsened but outcomes did not significantly differ by SM III subtype. Neurological outcomes were associated with Supp-SM grade, with proportions of patients with worsening increasing from 0% with Supp-SM grade 4 AVMs to 54% with Supp-SM grade 7 AVMs. Analyses of factors associated with neurological worsening identified age > 60 yr and Supp-SM grade 7 as significant.

CONCLUSION

Supp-SM grades were more predictive of microsurgical outcomes than modified SM grades for grade III AVMs, with a hard cutoff for acceptable surgical risk at Supp-SM grade 6. Supp-SM grading is a better decision-making tool than subtyping with the modified SM scale.
A Citrus Phosphate Starvation Response Factor CsPHL3 Negatively Regulates Carotenoid Metabolism
Authors: Lu Suwen , Ye Junli , Zhu Kaijie , Zhang Yin , Zhang Mengwei , Xu Qiang , Deng Xiuxin
Published: January 2021

Carotenoids provide precursors for the biosynthesis of strigolactones, which are a new class of hormones that are essential in phosphate (Pi) signaling during plant development. Carotenoid metabolism is a finely tuned pathway, but our understanding of the regulation mechanisms is still limited. In this study, we isolated a protein designated as CsPHL3 from citrus. CsPHL3 belonged to the Pi starvation response factor (PHR)-like subclade and was upregulated by low Pi. Acting as a nucleus-localized protein with transactivation activity, CsPHL3 bound directly to activate the promoter of a key metabolic gene, lycopene β-cyclase1 (LCYb1). Transgenic analysis revealed that the CsPHL3-overexpressing tomato plants exhibited abnormal growth, like the plants grew under limited Pi conditions. The transgenic lines showed reduced carotenoid contents and elevated expression of LCYb genes but downregulation of other key carotenogenic genes, including phytoene synthase (PSY). Moreover, CsPHL3 induced anthocyanin biosynthesis and affected Pi signaling in the transgenic plants. We further demonstrated that the expression of PSY was negatively regulated by CsPHL3 and high Pi. It is concluded that CsPHL3 is a Pi starvation response factor that negatively regulates carotenoid metabolism by modulating the expression of carotenogenic genes. Establishment of the CsPHL3-CsLCYb1 network provides new valuable knowledge of the function and underlying mechanism of PHR transcription factors and expands our understanding of the complex regulation mechanisms of carotenoid biosynthesis.
Posttranslational Modifications: Regulation of Nitrogen Utilization and Signaling
Authors: Wang Wei , Li Aifu , Zhang Zhihua , Chu Chengcai
Published: January 2021

Nitrogen is the most important macroelement required for the composition of key molecules, such as nucleic acids, proteins and other organic compounds. As sessile organisms, plants have evolved sophisticated mechanisms to acquire nitrogen for their normal growth and development. Besides the transcriptional and translational regulation of nitrogen uptake, assimilation, remobilization and signal transduction, posttranslational modifications (PTMs) are shown to participate in these processes in plants. In addition to alterations in protein abundance, PTMs may dramatically increase the complexity of the proteome without the concomitant changes in gene transcription and have emerged as an important type of protein regulation in terms of protein function, subcellular localization and protein activity and stability. Herein, we briefly summarize recent advances on the posttranslational regulation of nitrogen uptake, assimilation, remobilization and nitrogen signaling and discuss the underlying mechanisms of PTMs as well as the signal output of such PTMs. Understanding these regulation mechanisms will provide novel insights for improving the nitrogen use efficiency of plants.
Structural insights into the multivalent binding of the Arabidopsis FLOWERING LOCUS T promoter by the CO–NF–Y master transcription factor complex
Authors: Lv Xinchen , Zeng Xiaolin , Hu Hongmiao , Chen Lixian , Zhang Fan , Liu Rui , Liu Yue , Zhou Xuelin , Wang Changshi , Wu Zhe , Kim Chanhong , He Yuehui , Du Jiamu
Published: January 2021

Flowering plants sense various environmental and endogenous signals to trigger the floral transition and start the reproductive growth cycle. CONSTANS (CO) is a master transcription factor in the photoperiod floral pathway that integrates upstream signals and activates the florigen gene FLOWERING LOCUS T (FT). Here, we performed comprehensive structural and biochemical analyses to study the molecular mechanism underlying the regulation of FT by CO in Arabidopsis thaliana. We show that the four previously characterized cis-elements in the FT promoter proximal region, CORE1, CORE2, P1, and P2, are all direct CO binding sites. Structural analysis of CO in complex with NUCLEAR FACTOR-YB/YC (NF–YB/YC) and the CORE2 or CORE1 elements revealed the molecular basis for the specific recognition of the shared TGTG motifs. Biochemical analysis suggested that CO might form a homomultimeric assembly via its N-terminal B-Box domain and simultaneously occupy multiple cis-elements within the FT promoter. We suggest that this multivalent binding gives the CO–NF–Y complex high affinity and specificity for FT promoter binding. Overall, our data provide a detailed molecular model for the regulation of FT by the master transcription factor complex CO–NF–Y during the floral transition.
Changes in dietary fat intake and associations with mental health in a UK public sample during the COVID-19 pandemic
Authors: Wilson Jason J , McMullan Ilona , Blackburn Nicole E , Klempel Natalie , Yakkundi Anita , Armstrong Nicola C , Brolly Colette , Butler Laurie T , Barnett Yvonne , Jacob Louis , Koyanagi Ai , Smith Lee , Tully Mark A
Published: January 2021

Background

Consumption of unhealthy foods may have changed during the COVID-19 pandemic. This study explored how dietary fat intake was impacted in a sample of the UK public who were social distancing during the COVID-19 pandemic.

Methods

Data were collected from a UK COVID-19 online survey. Fat intake was measured using the Dietary Instrument for Nutrition Education questionnaire. Anxiety and depressive symptoms were assessed using Becks’ Anxiety and Depression Inventories, while the short-form Warwick-Edinburgh Mental Well-being Scale assessed mental well-being. Differences between individuals who increased versus decreased fat intake were explored using chi-square or independent sample t-tests. Association between fat intake and mental health was explored using adjusted linear regression models.

Results

Eight hundred and eighty-seven adults were included. Approximately, 34% recorded medium-to-high levels of fat consumption during social distancing. Around 48% reported decreased fat intake during social distancing compared to usual levels, while 41.3% documented increased fat intake. Fat intake was not significantly associated (P > 0.05) with any measures of mental health.

Conclusions

A higher proportion of a sample of UK adults social distancing during the COVID-19 pandemic recorded decreased fat intake when compared to levels prior to social distancing. There appeared to be no associations between fat intake and mental health.
When a Master Dies: Speculation and Asset Float
Authors: Pénasse Julien , Renneboog Luc , Scheinkman José A
Published: January 2021

An artist’s death constitutes a negative shock to his future production; death permanently decreases the artist’s float. We use this shock to test predictions of speculative trading models with short-selling constraints. As predicted in our model, we find that an artist’s premature death leads to a permanent increase in prices and turnover; this effect being larger for more famous artists. We document that premature death increases prices (by 54.7%) and secondary market volume (by 63.2%).