bluuebunny/crossref_metadata_2025 huggingface dataset:
SPECTRAL INEQUALITIES FOR COMBINATIONS OF HERMITE FUNCTIONS AND NULL-CONTROLLABILITY FOR EVOLUTION EQUATIONS ENJOYING GELFAND–SHILOV SMOOTHING EFFECTS
Authors: Martin Jérémy , Pravda-Starov Karel
Published: March 2022

This work is devoted to the study of uncertainty principles for finite combinations of Hermite functions. We establish some spectral inequalities for control subsets that are thick with respect to some unbounded densities growing almost linearly at infinity, and provide quantitative estimates, with respect to the energy level of the Hermite functions seen as eigenfunctions of the harmonic oscillator, for the constants appearing in these spectral estimates. These spectral inequalities allow us to derive the null-controllability in any positive time for evolution equations enjoying specific regularizing effects. More precisely, for a given index$\frac {1}{2} \leq \mu <1$, we deduce sufficient geometric conditions on control subsets to ensure the null-controllability of evolution equations enjoying regularizing effects in the symmetric Gelfand–Shilov space$S^{\mu }_{\mu }(\mathbb {R}^{n})$. These results apply in particular to derive the null-controllability in any positive time for evolution equations associated to certain classes of hypoelliptic non-self-adjoint quadratic operators, or to fractional harmonic oscillators.
The Challenge of Gafcon to the Unity of the Anglican Communion
Authors: Joseph Keith
Published: March 2022

Since 2008 the Global Anglican Futures Conference (Gafcon) has emerged as a powerful force within the Anglican Communion. It had the potential to reform some of the issues facing the Anglican Communion. However, its Jerusalem Declaration has become a standard of Anglican orthodoxy to the exclusion of many orthodox Anglicans who cannot assent to its extra-doctrinal material. This lends Gafcon to schismatic ends.
Sensitivity to sublethal rates of dicamba for selected mid-Atlantic vegetable crops
Authors: Wasacz Maggie H. , Ward Daniel L. , VanGessel Mark J. , Besançon Thierry E.
Published: March 2022

Dicamba is a synthetic auxin herbicide that may be applied over the top of transgenic dicamba-tolerant crops. The increasing prevalence of herbicide-resistant weeds has resulted in increased reliance on dicamba-based herbicides in soybean production systems. Because of the high volatility of dicamba it is prone to off-target movement, and therefore concern exists regarding its drift onto nearby specialty crops. The present study evaluates 12 mid-Atlantic vegetable crops species for sensitivity to sublethal rates of dicamba. Soybean, snap bean, lima bean, tomato, eggplant, bell pepper, cucumber, summer squash, watermelon, pumpkin, sweet basil, lettuce, and kale were grown in a greenhouse and exposed to dicamba at 0, 0.056, 0.11, 0.28, 0.56, 1.12, 2.24 g ae ha−1, which is, respectively, 0, 1/10,000, 1/5,000, 1/2,000, 1/1,000, 1/500, and 1/250 of the maximum recommended label rate for soybean application (560 g ae ha−1). Vegetable crop injury was evaluated 4 wk after treatment using visual rating methods and leaf deformation index measurements. Overall, snap bean was the most sensitive crop, with dicamba rates as low as 0.11 g ae ha−1 resulting in significantly higher leaf deformation levels compared with the nontreated control. Other Fabaceae and Solanaceae species also demonstrated high sensitivity to sublethal rates of dicamba with rates ranging 0.28 to 0.56 g ae ha−1 causing higher leaf deformation compared with the nontreated control. While cucumber, pumpkin, and summer squash were no or moderately sensitive to dicamba, watermelon showed greater sensitivity with unique symptoms at rates as low as 0.056 g ae ha−1 based on visual evaluation. Within the range of tested dicamba rates, sweet basil, lettuce, and kale demonstrated tolerance to dicamba with no injury observed at the maximum rate of 2.24 g ae ha−1.
Effects of shrimp oil on cardio-metabolic risk factors in children and adolescents
Authors: Aref Maryam , Movahedi Ariyo , Heidari-Beni Motahar , Kelishadi Roya
Published: March 2022

Abstract. Background: Antioxidants have beneficial effects on health. Shrimp oil has Astaxanthin and omega 3 that act as powerful antioxidants and might have anti-inflammatory effects on cardiovascular diseases. This study aims to investigate the effects of shrimp oil supplementation on cardio-metabolic risk factors in overweight and obese children and adolescents. Methods: This randomized, triple-blind, placebo-controlled clinical trial was conducted on 64 overweight and obese participants with 10–18 years of age. They were randomly assigned to receive either 500 mg shrimp oil or identical placebo that contained medium-chain triglycerides once per day for eight weeks. Dietary intake was obtained using food record questionnaire for three days at baseline and at the end of the study. Fasting blood samples were obtained at baseline and after eight weeks of intervention. Results: Overall, 53 participants completed the study; 30 subjects received shrimp oil and 23 subjects received placebo. There were no significant effects of shrimp oil on total cholesterol, triglyceride, HDL-C, LDL-C and blood pressure compared with the placebo group (p>0.05). Shrimp oil had no significant effects on body mass index, waist circumference and hip circumference compared with the placebo group (p>0.05). Conclusions: Supplementation with shrimp oil had no significant effects on improving the anthropometric measures and cardio-metabolic risk factors. Future clinical trials are needed to investigate the beneficial effects of higher doses of shrimp oil on cardio-metabolic risk factors in the pediatric age groups.
Representing Socio‐Economic Uncertainty in Human System Models
Authors: Morris Jennifer , Reilly John , Paltsev Sergey , Sokolov Andrei , Cox Kenneth
Published: March 2022

Socio‐economic development pathways and their implications for the environment are highly uncertain, and energy transitions will involve complex interactions among sectors. Here, traditional Monte Carlo analysis is paired with scenario discovery techniques to provide a richer portrait of these complexities. Modeled uncertain input variables include costs of advanced energy technologies, energy efficiency trends, fossil fuel resource availability, elasticities of substitution for labor, capital, and energy across economic sectors, population growth, and labor and capital productivity. The sampled values are simulated through a multi‐sector, multi‐region, recursively dynamic model of the world economy to explore a range of possible future outcomes. We find that many patterns of energy and technology development are possible for various long‐term environmental pathways and that sectoral output for most sectors is little affected through 2050 by the long‐term temperature target, but with tight constraints on emissions, emission intensities must fall much more rapidly. Scenario discovery techniques are applied to the large uncertainty ensembles to explore if there are prevailing storylines behind outcomes of interest. An illustrative investigation focused on different levels of economic growth shows many combinations of pathways and no single storyline emerging for a given economic outcome. This method can be extended to other outcomes of interest, exploring the nature of scenarios with both tail and median outcomes. Sampling from a Monte Carlo generated ensemble provides a rich set of scenarios to investigate, and potentially aids in avoiding heuristic biases in less structured scenario approaches.
Equatorward Medium to Large‐Scale Traveling Ionospheric Disturbances of High Latitude Origin During Quiet Conditions
Authors: Thaganyana Golekamang P. , Habarulema John Bosco , Ngwira Chigomezyo , Azeem Irfan
Published: March 2022

This article presents observations of medium to large‐scale traveling ionospheric disturbances (TIDs) originating from high latitudes, and propagating across the equator into the opposite hemisphere in the African‐European sector during geomagnetically quiet conditions between 2010 and 2018. During the study period, four geomagnetically quiet days were selected each month. The Global Navigation Satellite Systems (GNSS) total electron content (TEC) data were used to obtain the two dimensional (2‐D) TEC residuals. We have identified seven transhemispheric TIDs from the days that were analyzed with five originating in the southern and the rest in northern wintertime hemisphere. The TIDs meridional propagation velocities, periods and wavelengths are in the range of 270–322 m/s, 48–80 min and 802–1,296 km, respectively. The horizontal propagation velocities and horizontal wavelengths ranges are cH = 120–274 m/s and λH = 379–1,104 km, respectively. Analysis of the conditions of the space weather environment rules out space weather as a source of the TIDs. While observations of the 4.3 μm brightness temperature (BT) from the Atmospheric Infrared Sounder (AIRS) instrument on board the NASA Aqua satellite show the existence of atmospheric gravity waves (AGWs) in the troposphere‐stratosphere region, it is suggested that the tertiary GWs from orographic forcing may be the likely source of the TIDs observed in this study.
A Global Centroid Single Force Catalog of P‐Wave Microseisms
Authors: Nishida Kiwamu , Takagi Ryota
Published: March 2022

P‐wave microseisms are excited by ocean swell activities. The recent development of an ocean wave model allows us to compare them quantitatively. For the comparison, a single force at a centroid location can characterize the seismic excitation. A beamforming method is feasible for locating the centroids efficiently. However, the required plane wave assumption reduces the accuracy for a large aperture array. The lack of information on the wavefront curvature also makes P and PP phases indistinguishable. To utilize information on the curvature, we developed the auto‐focusing method as a natural extension of beamforming: (a) We estimated the slowness vector and the wavefront curvature by a grid‐search method, which maximizes the beam power. (b) We iteratively update the values based on the perturbation theory. (c) Based on the classified phase according to the wavefront curvature and the slowness, we locate the centroid from the slowness vector with corrections for a global 3‐D P‐wave velocity structure. We also infer the centroid‐single‐force (CSF) from the beam power. We applied this method to the vertical components of seismic records at approximately 780 Hi‐net stations in Japan from 2004 to 2020. We also compare the CSF catalog with a synthetic CSF catalog based on a numerical ocean wave model: WAVEWATCH III. Both catalogs generally show similar temporal‐spatial patterns of centroids. The amplitudes of CSF are consistent with each other, although the seismic signal‐to‐noise ratio limits the detected events. The ocean wave model cannot explain significant activities in the Gulf of Carpentaria.
Electron‐Only Magnetic Reconnection: Lessons Learned From Magnetic Island Coalescence
Authors: Yi Yongyuan , Zhou Meng , Song Liangjin , Pang Ye , Deng Xiaohua
Published: March 2022

Electron‐only magnetic reconnection, in which ions do not couple, has recently been observed in turbulent magnetosheath and magnetotail, and in association with magnetic flux rope coalescence. This study reproduces the electron‐only reconnection during magnetic island coalescence via 2.5‐D particle‐in‐cell simulations. We find that the degree of ion coupling is not sensitive to the spatial scale of the merging current sheet but is determined by the persistent time of the coalescence, which suggests that the electron‐only reconnection is the early stage of the coalescence. During the electron‐only reconnection, ions are affected by the reconnection electric field though the ion bulk outflow is absent. It is revealed that the pre‐existing inflows and Hall electric field Ez from the adjacent main reconnection impede the formation of ion outflow during coalescence. This study provides in‐depth knowledge of electron‐only reconnection through the perspective of ion kinetics.
Perceptions of pharmacists on the quality of automated blood pressure devices: a national survey
Authors: Picone Dean S. , Peterson Gregory M. , Jackson Shane L. , Campbell Norm R. C. , Delles Christian , Olsen Michael Hecht , Padwal Raj , Schutte Aletta E. , Sharman James E.
Published: March 2022

A recent study found that only 23.8% of blood pressure (BP) devices available for purchase from Australian pharmacies were validated for accuracy. The extent to which pharmacists are aware of this, and other issues related to the accuracy of BP devices, is not known and gathering this information was the aim of this study. An online survey of Australian pharmacists was distributed via the Pharmaceutical Society of Australia between 1 October and 25 November 2020. Questions were focused on the views of pharmacists related to the accuracy of BP devices. Two hundred and ten pharmacists completed the survey. The accuracy of BP devices sold by pharmacists was considered ‘quite’ or ‘extremely important’ to most respondents (94%). However, most respondents (90%) were unaware that less than one-quarter of BP devices sold by Australian pharmacies were validated, and this was ‘quite’ or ‘extremely surprising’ to many (69%). Many respondents (64%) associated a particular brand of BP device with greater accuracy. There was low awareness on proper ways to identify accurate BP devices, such as checking reputable online databases (43%). BP devices were stocked in respondents’ pharmacies based on perceived quality (50%), accuracy (40%), or as determined by the pharmacy chain (36%). In conclusion, providing accurate BP devices to consumers is important to pharmacists, but they were generally unaware that most devices available from pharmacies were not validated for accuracy. Pharmacist education, alongside advocacy for policies including regulations and strategic action, is required to ensure only validated BP devices are sold in Australia.
New opportunities for light-based tumor treatment with an “iron fist”
Authors: Marin Riccardo , Ximendes Erving , Jaque Daniel
Published: March 2022

The efficacy of photodynamic treatments of tumors can be significantly improved by using a new generation of nanoparticles that take advantage of the unique properties of the tumor microenvironment.
The proteomic characterization of the peritumor microenvironment in human hepatocellular carcinoma
Authors: Gu Yuhan , Guo Yuanyuan , Gao Na , Fang Yan , Xu Chen , Hu Guiming , Guo Mengxue , Ma Yaxing , Zhang Yunfei , Zhou Jun , Luo Yanlin , Zhang Haifeng , Wen Qiang , Qiao Hailing
Published: March 2022

The tumor microenvironment (TME) was usually studied in tumor tissue and in relation to only tumor progression, with little involved in occurrence, recurrence and metastasis of tumor. Thus, a new concept “peritumor microenvironment (PME)” was proposed in the proteomic characterization of peritumor liver tissues in human hepatocellular carcinoma (HCC). The PME for occurrence (PME-O) and progression (PME-P) were almost totally different at proteome composition and function. Proteins for occurrence and progression rarely overlapped and crossed. Immunity played a central role in PME-O, whereas inflammation, angiogenesis and metabolism were critical in PME-P. Proteome profiling identified three PME subtypes with different features of HCC. Thymidine phosphorylase (TYMP) was validated as an antiangiogenic target in an orthotopic HCC mouse model. Overall, the proteomic characterization of the PME revealed that the entire processes of HCC occurrence and progression differ substantially. These findings could enable advances in cancer biology, diagnostics and therapeutics.
CXCL9 inhibits tumour growth and drives anti-PD-L1 therapy in ovarian cancer
Authors: Seitz Stefanie , Dreyer Tobias F. , Stange Christoph , Steiger Katja , Bräuer Rosalinde , Scheutz Leandra , Multhoff Gabriele , Weichert Wilko , Kiechle Marion , Magdolen Viktor , Bronger Holger
Published: March 2022

Background

Response to immune checkpoint blockade (ICB) in ovarian cancer remains disappointing. Several studies have identified the chemokine CXCL9 as a robust prognosticator of improved survival in ovarian cancer and a characteristic of the immunoreactive subtype, which predicts ICB response. However, the function of CXCL9 in ovarian cancer has been poorly studied.

Methods

Impact of Cxcl9 overexpression in the murine ID8-Trp53−/− and ID8-Trp53−/–Brca2−/− ovarian cancer models on survival, cellular immune composition, PD-L1 expression and anti-PD-L1 therapy. CXCL9 expression analysis in ovarian cancer subtypes and correlation to reported ICB response.

Results

CXCL9 overexpression resulted in T-cell accumulation, delayed ascites formation and improved survival, which was dependent on adaptive immune function. In the ICB-resistant mouse model, the chemokine was sufficient to enable a successful anti-PD-L1 therapy. In contrast, these effects were abrogated in Brca2-deficient tumours, most likely due to an already high intrinsic chemokine expression. Finally, in ovarian cancer patients, the clear-cell subtype, known to respond best to ICB, displayed a significantly higher proportion of CXCL9high tumours than the other subtypes.

Conclusions

CXCL9 is a driver of successful ICB in preclinical ovarian cancer. Besides being a feasible predictive biomarker, CXCL9-inducing agents thus represent attractive combination partners to improve ICB in this cancer entity.
Deficiency of thyroid hormone receptor protects retinal pigment epithelium and photoreceptors from cell death in a mouse model of age-related macular degeneration
Authors: Ma Hongwei , Yang Fan , Ding Xi-Qin
Published: March 2022

Age-related macular degeneration (AMD) is the leading cause of vision loss in the elderly. Progressive dystrophy of the retinal pigment epithelium (RPE) and photoreceptors is the characteristic of dry AMD, and oxidative stress/damage plays a central role in the pathogenic lesion of the disease. Thyroid hormone (TH) regulates cell growth, differentiation, and metabolism, and regulates development/function of photoreceptors and RPE in the retina. Population-/patient-based studies suggest an association of high free-serum TH levels with increased risk of AMD. We recently showed that suppressing TH signaling by antithyroid treatment reduces cell damage/death of the RPE and photoreceptors in an oxidative-stress/sodium iodate (NaIO3)-induced mouse model of AMD. This work investigated the effects of TH receptor (THR) deficiency on cell damage/death of the RPE and photoreceptors and the contribution of the receptor subtypes. Treatment with NaIO3 induced RPE and photoreceptor cell death/necroptosis, destruction, and oxidative damage. The phenotypes were significantly diminished in Thrα1−/−, Thrb−/−, and Thrb2−/− mice, compared with that in the wild-type (C57BL/6 J) mice. The involvement of the receptor subtypes varies in the RPE and retina. Deletion of Thrα1 or Thrb protected RPE, rods, and cones, whereas deletion of Thrb2 protected RPE and cones but not rods. Gene-expression analysis showed that deletion of Thrα1 or Thrb abolished/suppressed the NaIO3-induced upregulation of the genes involved in cellular oxidative-stress responses, necroptosis/apoptosis signaling, and inflammatory responses. In addition, THR antagonist effectively protected ARPE-19 cells and hRPE cells from NaIO3-induced cell death. This work demonstrates the involvement of THR signaling in cell damage/death of the RPE and photoreceptors after oxidative-stress challenge and the receptor-subtype contribution. Findings from this work support a role of THR signaling in the pathogenesis of AMD and the strategy of suppressing THR signaling locally in the retina for protection of the RPE/retina in dry AMD.
Massively parallel reporter perturbation assays uncover temporal regulatory architecture during neural differentiation
Authors: Kreimer Anat , Ashuach Tal , Inoue Fumitaka , Khodaverdian Alex , Deng Chengyu , Yosef Nir , Ahituv Nadav
Published: March 2022

Gene regulatory elements play a key role in orchestrating gene expression during cellular differentiation, but what determines their function over time remains largely unknown. Here, we perform perturbation-based massively parallel reporter assays at seven early time points of neural differentiation to systematically characterize how regulatory elements and motifs within them guide cellular differentiation. By perturbing over 2,000 putative DNA binding motifs in active regulatory regions, we delineate four categories of functional elements, and observe that activity direction is mostly determined by the sequence itself, while the magnitude of effect depends on the cellular environment. We also find that fine-tuning transcription rates is often achieved by a combined activity of adjacent activating and repressing elements. Our work provides a blueprint for the sequence components needed to induce different transcriptional patterns in general and specifically during neural differentiation.
Atomic resolution dynamics of cohesive interactions in phase-separated Nup98 FG domains
Authors: Najbauer Eszter E. , Ng Sheung Chun , Griesinger Christian , Görlich Dirk , Andreas Loren B.
Published: March 2022

Cohesive FG domains assemble into a condensed phase forming the selective permeability barrier of nuclear pore complexes. Nanoscopic insight into fundamental cohesive interactions has long been hampered by the sequence heterogeneity of native FG domains. We overcome this challenge by utilizing an engineered perfectly repetitive sequence and a combination of solution and magic angle spinning NMR spectroscopy. We map the dynamics of cohesive interactions in both phase-separated and soluble states at atomic resolution using TROSY for rotational correlation time (TRACT) measurements. We find that FG repeats exhibit nanosecond-range rotational correlation times and remain disordered in both states, although FRAP measurements show slow translation of phase-separated FG domains. NOESY measurements enable the direct detection of contacts involved in cohesive interactions. Finally, increasing salt concentration and temperature enhance phase separation and decrease local mobility of FG repeats. This lower critical solution temperature (LCST) behaviour indicates that cohesive interactions are driven by entropy.
Progression of type 1 diabetes from latency to symptomatic disease is predicted by distinct autoimmune trajectories
Authors: Kwon Bum Chul , Anand Vibha , Achenbach Peter , Dunne Jessica L. , Hagopian William , Hu Jianying , Koski Eileen , Lernmark Åke , Lundgren Markus , Ng Kenney , Toppari Jorma , Veijola Riitta , Frohnert Brigitte I. ,   the T1DI Study Group
Published: March 2022

Development of islet autoimmunity precedes the onset of type 1 diabetes in children, however, the presence of autoantibodies does not necessarily lead to manifest disease and the onset of clinical symptoms is hard to predict. Here we show, by longitudinal sampling of islet autoantibodies (IAb) to insulin, glutamic acid decarboxylase and islet antigen-2 that disease progression follows distinct trajectories. Of the combined Type 1 Data Intelligence cohort of 24662 participants, 2172 individuals fulfill the criteria of two or more follow-up visits and IAb positivity at least once, with 652 progressing to type 1 diabetes during the 15 years course of the study. Our Continuous-Time Hidden Markov Models, that are developed to discover and visualize latent states based on the collected data and clinical characteristics of the patients, show that the health state of participants progresses from 11 distinct latent states as per three trajectories (TR1, TR2 and TR3), with associated 5-year cumulative diabetes-free survival of 40% (95% confidence interval [CI], 35% to 47%), 62% (95% CI, 57% to 67%), and 88% (95% CI, 85% to 91%), respectively (p < 0.0001). Age, sex, and HLA-DR status further refine the progression rates within trajectories, enabling clinically useful prediction of disease onset.
Single amino acid bionanozyme for environmental remediation
Authors: Makam Pandeeswar , Yamijala Sharma S. R. K. C. , Bhadram Venkata S. , Shimon Linda J. W. , Wong Bryan M. , Gazit Ehud
Published: March 2022

Enzymes are extremely complex catalytic structures with immense biological and technological importance. Nevertheless, their widespread environmental implementation faces several challenges, including high production costs, low operational stability, and intricate recovery and reusability. Therefore, the de novo design of minimalistic biomolecular nanomaterials that can efficiently mimic the biocatalytic function (bionanozymes) and overcome the limitations of natural enzymes is a critical goal in biomolecular engineering. Here, we report an exceptionally simple yet highly active and robust single amino acid bionanozyme that can catalyze the rapid oxidation of environmentally toxic phenolic contaminates and serves as an ultrasensitive tool to detect biologically important neurotransmitters similar to the laccase enzyme. While inspired by the laccase catalytic site, the substantially simpler copper-coordinated bionanozyme is ∼5400 times more cost-effective, four orders more efficient, and 36 times more sensitive compared to the natural protein. Furthermore, the designed mimic is stable under extreme conditions (pH, ionic strength, temperature, storage time), markedly reusable for several cycles, and displays broad substrate specificity. These findings hold great promise in developing efficient bionanozymes for analytical chemistry, environmental protection, and biotechnology.
RUFY3 links Arl8b and JIP4-Dynein complex to regulate lysosome size and positioning
Authors: Kumar Gaurav , Chawla Prateek , Dhiman Neha , Chadha Sanya , Sharma Sheetal , Sethi Kanupriya , Sharma Mahak , Tuli Amit
Published: March 2022

The bidirectional movement of lysosomes on microtubule tracks regulates their whole-cell spatial arrangement. Arl8b, a small GTP-binding (G) protein, promotes lysosome anterograde trafficking mediated by kinesin-1. Herein, we report an Arl8b effector, RUFY3, which regulates the retrograde transport of lysosomes. We show that RUFY3 interacts with the JIP4-dynein-dynactin complex and facilitates Arl8b association with the retrograde motor complex. Accordingly, RUFY3 knockdown disrupts the positioning of Arl8b-positive endosomes and reduces Arl8b colocalization with Rab7-marked late endosomal compartments. Moreover, we find that RUFY3 regulates nutrient-dependent lysosome distribution, although autophagosome-lysosome fusion and autophagic cargo degradation are not impaired upon RUFY3 depletion. Interestingly, lysosome size is significantly reduced in RUFY3 depleted cells, which could be rescued by inhibition of the lysosome reformation regulatory factor PIKFYVE. These findings suggest a model in which the perinuclear cloud arrangement of lysosomes regulates both the positioning and size of these proteolytic compartments.
Inorganic phosphate in growing calcium carbonate abalone shell suggests a shared mineral ancestral precursor
Authors: Ajili Widad , Tovani Camila B. , Fouassier Justine , de Frutos Marta , Laurent Guillaume Pierre , Bertani Philippe , Djediat Chakib , Marin Frédéric , Auzoux-Bordenave Stéphanie , Azaïs Thierry , Nassif Nadine
Published: March 2022

The presence of phosphate from different origins (inorganic, bioorganic) is found more and more in calcium carbonate-based biominerals. Phosphate is often described as being responsible for the stabilization of the transient amorphous calcium carbonate phase. In order to specify the composition of the mineral phase deposited at the onset of carbonated shell formation, the present study investigates, down to the nanoscale, the growing shell from the European abalone Haliotis tuberculata, using a combination of solid state nuclear magnetic resonance, scanning transmission electron microscope and spatially-resolved electron energy loss spectroscopy techniques. We show the co-occurrence of inorganic phosphate with calcium and carbonate throughout the early stages of abalone shell formation. One possible hypothesis is that this first-formed mixed mineral phase represents the vestige of a shared ancestral mineral precursor that appeared early during Evolution. In addition, our findings strengthen the idea that the final crystalline phase (calcium carbonate or phosphate) depends strongly on the nature of the mineral-associated proteins in vivo.
Rational design of hairpin RNA excited states reveals multi-step transitions
Authors: Han Ge , Xue Yi
Published: March 2022

RNA excited states represent a class of high-energy-level and thus low-populated conformational states of RNAs that are sequestered within the free energy landscape until being activated by cellular cues. In recent years, there has been growing interest in structural and functional studies of these transient states, but the rational design of excited states remains unexplored. Here we developed a method to design small hairpin RNAs with predefined excited states that exchange with ground states through base pair reshuffling, and verified these transient states by combining NMR relaxation dispersion technique and imino chemical shift prediction. Using van’t Hoff analysis and accelerated molecular dynamics simulations, a mechanism of multi-step sequential transition has been revealed. The efforts made in this study will expand the scope of RNA rational design, and also contribute towards improved predictions of RNA secondary structure.
New recognition specificity in a plant immune receptor by molecular engineering of its integrated domain
Authors: Cesari Stella , Xi Yuxuan , Declerck Nathalie , Chalvon Véronique , Mammri Léa , Pugnière Martine , Henriquet Corinne , de Guillen Karine , Chochois Vincent , Padilla André , Kroj Thomas
Published: March 2022

Plant nucleotide-binding and leucine-rich repeat domain proteins (NLRs) are immune sensors that recognize pathogen effectors. Here, we show that molecular engineering of the integrated decoy domain (ID) of an NLR can extend its recognition spectrum to a new effector. We relied for this on detailed knowledge on the recognition of the Magnaporthe oryzae effectors AVR-PikD, AVR-Pia, and AVR1-CO39 by, respectively, the rice NLRs Pikp-1 and RGA5. Both receptors detect their effectors through physical binding to their HMA (Heavy Metal-Associated) IDs. By introducing into RGA5_HMA the AVR-PikD binding residues of Pikp-1_HMA, we create a high-affinity binding surface for this effector. RGA5 variants carrying this engineered binding surface perceive the new ligand, AVR-PikD, and still recognize AVR-Pia and AVR1-CO39 in the model plant N. benthamiana. However, they do not confer extended disease resistance specificity against M. oryzae in transgenic rice plants. Altogether, our study provides a proof of concept for the design of new effector recognition specificities in NLRs through molecular engineering of IDs.
Breakdown of semiclassical description of thermoelectricity in near-magic angle twisted bilayer graphene
Authors: Ghawri Bhaskar , Mahapatra Phanibhusan S. , Garg Manjari , Mandal Shinjan , Bhowmik Saisab , Jayaraman Aditya , Soni Radhika , Watanabe Kenji , Taniguchi Takashi , Krishnamurthy H. R. , Jain Manish , Banerjee Sumilan , Chandni U. , Ghosh Arindam
Published: March 2022

The planar assembly of twisted bilayer graphene (tBLG) hosts multitude of interaction-driven phases when the relative rotation is close to the magic angle (θm = 1.1∘). This includes correlation-induced ground states that reveal spontaneous symmetry breaking at low temperature, as well as possibility of non-Fermi liquid (NFL) excitations. However, experimentally, manifestation of NFL effects in transport properties of twisted bilayer graphene remains ambiguous. Here we report simultaneous measurements of electrical resistivity (ρ) and thermoelectric power (S) in tBLG for several twist angles between θ ~ 1.0 − 1.7∘. We observe an emergent violation of the semiclassical Mott relation in the form of excess S close to half-filling for θ ~ 1.6∘ that vanishes for θ ≳ 2∘. The excess S (≈2 μV/K at low temperatures T ~ 10 K at θ ≈ 1.6∘) persists upto ≈40 K, and is accompanied by metallic T-linear ρ with transport scattering rate (τ−1) of near-Planckian magnitude τ−1 ~ kBT/ℏ. Closer to θm, the excess S was also observed for fractional band filling (ν ≈ 0.5). The combination of non-trivial electrical transport and violation of Mott relation provides compelling evidence of NFL physics intrinsic to tBLG.
Transposon insertional mutagenesis of diverse yeast strains suggests coordinated gene essentiality polymorphisms
Authors: Chen Piaopiao , Michel Agnès H. , Zhang Jianzhi
Published: March 2022

Due to epistasis, the same mutation can have drastically different phenotypic consequences in different individuals. This phenomenon is pertinent to precision medicine as well as antimicrobial drug development, but its general characteristics are largely unknown. We approach this question by genome-wide assessment of gene essentiality polymorphism in 16 Saccharomyces cerevisiaestrains using transposon insertional mutagenesis. Essentiality polymorphism is observed for 9.8% of genes, most of which have had repeated essentiality switches in evolution. Genes exhibiting essentiality polymorphism lean toward having intermediate numbers of genetic and protein interactions. Gene essentiality changes tend to occur concordantly among components of the same protein complex or metabolic pathway and among a group of over 100 mitochondrial proteins, revealing molecular machines or functional modules as units of gene essentiality variation. Most essential genes tolerate transposon insertions consistently among strains in one or more coding segments, delineating nonessential regions within essential genes.
Endothelial pannexin-1 channels modulate macrophage and smooth muscle cell activation in abdominal aortic aneurysm formation
Authors: Filiberto Amanda C. , Spinosa Michael D. , Elder Craig T. , Su Gang , Leroy Victoria , Ladd Zachary , Lu Guanyi , Mehaffey J. Hunter , Salmon Morgan D. , Hawkins Robert B. , Ravichandran Kodi S. , Isakson Brant E. , Upchurch Gilbert R. , Sharma Ashish K.
Published: March 2022

Pannexin-1 (Panx1) channels have been shown to regulate leukocyte trafficking and tissue inflammation but the mechanism of Panx1 in chronic vascular diseases like abdominal aortic aneurysms (AAA) is unknown. Here we demonstrate that Panx1 on endothelial cells, but not smooth muscle cells, orchestrate a cascade of signaling events to mediate vascular inflammation and remodeling. Mechanistically, Panx1 on endothelial cells acts as a conduit for ATP release that stimulates macrophage activation via P2X7 receptors and mitochondrial DNA release to increase IL-1β and HMGB1 secretion. Secondly, Panx1 signaling regulates smooth muscle cell-dependent intracellular Ca2+ release and vascular remodeling via P2Y2 receptors. Panx1 blockade using probenecid markedly inhibits leukocyte transmigration, aortic inflammation and remodeling to mitigate AAA formation. Panx1 expression is upregulated in human AAAs and retrospective clinical data demonstrated reduced mortality in aortic aneurysm patients treated with Panx1 inhibitors. Collectively, these data identify Panx1 signaling as a contributory mechanism of AAA formation.
cAMP and c-di-GMP synergistically support biofilm maintenance through the direct interaction of their effectors
Authors: Liu Cong , Sun Di , Liu Jiawen , Chen Ying , Zhou Xuge , Ru Yunrui , Zhu Jingrong , Liu Weijie
Published: March 2022

Nucleotide second messengers, such as cAMP and c-di-GMP, regulate many physiological processes in bacteria, including biofilm formation. There is evidence of cross-talk between pathways mediated by c-di-GMP and those mediated by the cAMP receptor protein (CRP), but the mechanisms are often unclear. Here, we show that cAMP-CRP modulates biofilm maintenance in Shewanella putrefaciens not only via its known effects on gene transcription, but also through direct interaction with a putative c-di-GMP effector on the inner membrane, BpfD. Binding of cAMP-CRP to BpfD enhances the known interaction of BpfD with protease BpfG, which prevents proteolytic processing and release of a cell surface-associated adhesin, BpfA, thus contributing to biofilm maintenance. Our results provide evidence of cross-talk between cAMP and c-di-GMP pathways through direct interaction of their effectors, and indicate that cAMP-CRP can play regulatory roles at the post-translational level.
Sociality predicts orangutan vocal phenotype
Authors: Lameira Adriano R. , Santamaría-Bonfil Guillermo , Galeone Deborah , Gamba Marco , Hardus Madeleine E. , Knott Cheryl D. , Morrogh-Bernard Helen , Nowak Matthew G. , Campbell-Smith Gail , Wich Serge A.
Published: March 2022

In humans, individuals’ social setting determines which and how language is acquired. Social seclusion experiments show that sociality also guides vocal development in songbirds and marmoset monkeys, but absence of similar great ape data has been interpreted as support to saltational notions for language origin, even if such laboratorial protocols are unethical with great apes. Here we characterize the repertoire entropy of orangutan individuals and show that in the wild, different degrees of sociality across populations are associated with different ‘vocal personalities’ in the form of distinct regimes of alarm call variants. In high-density populations, individuals are vocally more original and acoustically unpredictable but new call variants are short lived, whereas individuals in low-density populations are more conformative and acoustically consistent but also exhibit more complex call repertoires. Findings provide non-invasive evidence that sociality predicts vocal phenotype in a wild great ape. They prove false hypotheses that discredit great apes as having hardwired vocal development programmes and non-plastic vocal behaviour. Social settings mould vocal output in hominids besides humans.
DNA is loaded through the 9-1-1 DNA checkpoint clamp in the opposite direction of the PCNA clamp
Authors: Zheng Fengwei , Georgescu Roxana E. , Yao Nina Y. , O’Donnell Michael E. , Li Huilin
Published: March 2022

The 9-1-1 DNA checkpoint clamp is loaded onto 5′-recessed DNA to activate the DNA damage checkpoint that arrests the cell cycle. The 9-1-1 clamp is a heterotrimeric ring that is loaded in Saccharomyces cerevisiae by Rad24-RFC (hRAD17-RFC), an alternate clamp loader in which Rad24 replaces Rfc1 in the RFC1-5 clamp loader of proliferating cell nuclear antigen (PCNA). The 9-1-1 clamp loading mechanism has been a mystery, because, unlike RFC, which loads PCNA onto a 3′-recessed junction, Rad24-RFC loads the 9-1-1 ring onto a 5′-recessed DNA junction. Here we report two cryo-EM structures of Rad24-RFC–DNA with a closed or 27-Å open 9-1-1 clamp. The structures reveal a completely unexpected mechanism by which a clamp can be loaded onto DNA. Unlike RFC, which encircles DNA, Rad24 binds 5′-DNA on its surface, not inside the loader, and threads the 3′ ssDNA overhang into the 9-1-1 clamp from above the ring.
Development and validation of a risk prediction model for chronic kidney disease among individuals with type 2 diabetes
Authors: Lin Cheng-Chieh , Niu May Jingchee , Li Chia-Ing , Liu Chiu-Shong , Lin Chih-Hsueh , Yang Shing-Yu , Li Tsai-Chung
Published: March 2022

Many studies had established the chronic kidney disease (CKD) prediction models, but most of them were conducted on the general population and not on patients with type 2 diabetes, especially in Asian populations. This study aimed to develop a risk prediction model for CKD in patients with type 2 diabetes from the Diabetes Care Management Program (DCMP) in Taiwan. This research was a retrospective cohort study. We used the DCMP database to set up a cohort of 4,601 patients with type 2 diabetes without CKD aged 40–92 years enrolled in the DCMP program of a Taichung medical center in 2002–2016. All patients were followed up until incidences of CKD, death, and loss to follow-up or 2016. The dataset for participants of national DCMP in 2002–2004 was used as external validation. The incident CKD cases were defined as having one of the following three conditions: ACR data greater than or equal to 300 (mg/g); both eGFR data less than 60 (ml/min/1.73 m2) and ACR data greater than or equal to 30 (mg/g); and eGFR data less than 45 (ml/min/1.73 m2). The study subjects were randomly allocated to derivation and validation sets at a 2:1 ratio. Cox proportional hazards regression model was used to identify the risk factors of CKD in the derivation set. Time-varying area under receiver operating characteristics curve (AUC) was used to evaluate the performance of the risk model. After an average of 3.8 years of follow-up period, 3,067 study subjects were included in the derivation set, and 786 (25.63%) were newly diagnosed CKD cases. A total of 1,534 participants were designated to the validation set, and 378 (24.64%) were newly diagnosed CKD cases. The final CKD risk factors consisted of age, duration of diabetes, insulin use, estimated glomerular filtration rate, albumin-to-creatinine ratio, high-density lipoprotein cholesterol, triglyceride, diabetes retinopathy, variation in HbA1c, variation in FPG, and hypertension drug use. The AUC values of 1-, 3-, and 5-year CKD risks were 0.74, 0.76, and 0.77 in the validation set, respectively, and were 0.76, 0.77, and 0.76 in the sample for external validation, respectively. The value of Harrell’s c-statistics was 0.76 (0.74, 0.78). The proposed model is the first CKD risk prediction model for type 2 diabetes patients in Taiwan. The 1-, 3-, and 5-year CKD risk prediction models showed good prediction accuracy. The model can be used as a guide for clinicians to develop medical plans for future CKD preventive intervention in Chinese patients with type 2 diabetes.
Combinatorial influence of environmental temperature, obesity and cholesterol on SARS-CoV-2 infectivity
Authors: Mandal Chandi C. , Panwar Mahaveer S. , Yadav Chandra P. , Tripathi Vaishnavi , Bandyopadhayaya Shreetama
Published: March 2022

The continuing evolution of SARS-CoV-2 variants not only causes a long-term global health concerns but also encounters the vaccine/drug effectiveness. The degree of virus infectivity and its clinical outcomes often depend on various biological parameters (e.g., age, genetic factors, diabetes, obesity and other ailments) of an individual along with multiple environmental factors (e.g., air temperature, humidity, seasons). Thus, despite the extensive search for and use of several vaccine/drug candidates, the combinative influence of these various extrinsic and intrinsic risk factors involved in the SARS-CoV-2 virus infectivity has yet to be explored. Previous studies have reported that environment temperature is negatively associated with virus infectivity for SARS-CoV-2. This study elaborates on our previous findings, investigating the link between environmental temperature and other metabolic parameters, such as average total cholesterol and obesity, with the increase in COVID-19 cases. Statistical analysis conducted on a per country basis not only supports the existence of a significant negative correlation between environmental temperature and SARS-CoV-2 infections but also found a strong positive correlation between COVID-19 cases and these metabolic parameters. In addition, a multiphase growth curve model (GCM) was built to predict the contribution of these covariates in SARS-CoV-2 infectivity. These findings, for first time, support the idea that there might be a combinatorial impact of environmental temperature, average total cholesterol, and obesity in the inflation of the SARS-CoV-2 infectivity.
Charge-state resolved laser acceleration of gold ions to beyond 7 MeV/u
Authors: Lindner F. H. , Fitzpatrick E. G. , Haffa D. , Ponnath L. , Schmidt A.-K. , Speicher M. , Zielbauer B. , Schreiber J. , Thirolf P. G.
Published: March 2022

In the past years, the interest in the laser-driven acceleration of heavy ions in the mass range of $$\text {A}\approx 200$$

A
≈
200

has been increasing due to promising application ideas like the fission-fusion nuclear reaction mechanism, aiming at the production of neutron-rich isotopes relevant for the astrophysical r-process nucleosynthesis. In this paper, we report on the laser acceleration of gold ions to beyond 7 MeV/u, exceeding for the first time an important prerequisite for this nuclear reaction scheme. Moreover, the gold ion charge states have been detected with an unprecedented resolution, which enables the separation of individual charge states up to 4 MeV/u. The recorded charge-state distributions show a remarkable dependency on the target foil thickness and differ from simulations, lacking a straight-forward explanation by the established ionization models.
Maternal caretaking behavior towards a dead juvenile in a wild, multi-level primate society
Authors: Yang Bin , Anderson James R. , Mao Min , Wang Kaifeng , Li Baoguo
Published: March 2022

Maternal caretaking and transport of dead infants are widespread among nonhuman primates, having been reported in numerous species of monkeys and apes. By contrast, accounts of such behaviors toward dead juveniles are scarce. Here, we describe responses by the mother and other group members to the death of a juvenile in a wild, multi-level group of Sichuan snub-nosed monkeys (Rhinopithecus roxellana). Following the juvenile’s fatal accident, his mother transported and cared for the corpse for four days. Immature monkeys belonging to the same one-male unit, and some individuals from other social units also showed interest in and tended the corpse. Comparisons of this case with those involving the deaths of infants and an adult female in the same population highlight possible effects of physiological, psychological and emotional factors in primate thanatological responses, and provide an additional perspective on the origin and evolution of compassionate acts.
Dynamic modeling of female neutering interventions for free-roaming dog population management in an urban setting of southeastern Iran
Authors: Shamsaddini Saeedeh , Ahmadi Gohari Milad , Kamyabi Hossein , Nasibi Saeid , Derakhshani Ali , Mohammadi Mohammad Ali , Mousavi Seyed Mohammad , Baneshi Mohammad Reza , Hiby Elly , Harandi Majid Fasihi
Published: March 2022

Understanding dynamics of free-roaming dog (FRD) population is critical for planning and implementation of dog population management programs. FRD population size estimation as well as dynamic modeling of dog population under different female dog neutering interventions were investigated in order to determine the most appropriate animal birth control approach. We performed population size estimate of dogs using sight-resight surveys by photography in a randomly selected 25 blocks of the city and all the suburbs of greater Kerman area. Main demographic features were characterized and the dog density distribution was mapped. A dynamic model was developed to predict free-roaming dog population variations after 5 and 10 years. Different scenarios based on 10, 30, 50, 60 and 70% female dog sterilization were considered to predict the effects of animal birth control measures. Free roaming dog population was estimated at 6781 dogs (65.3% males) in Kerman and suburbs with several major population hotspots. Analysis of the dog locations within the city showed that the largest proportion of the dogs were observed in the vacant lots (46.2%). Modeling predictions indicated that, in the absence of management, the free-roaming dog population could increase from a baseline of 6781 to 13,665 dogs (2.02 fold increase) in 5 years and to 19,376 dogs in 10 years (2.86 fold increase). Using a population dynamics model, we simulated five neutering coverages to explore the impact of female neutering on free-roaming dog population size. The 5-year projections of the model have shown that 50% annual female dog sterilization significantly reduced free-roaming dog population by 0.44 comparing to the baseline population. Findings of the present study improve our knowledge on the nature and extent of dog population dynamics in Iran. Effective population control and selection of the most appropriate neutering interventions require a comprehensive knowledge of the characteristics and dynamics of FRD population.