bluuebunny/crossref_metadata_2025 huggingface dataset:
Translational value of choroid plexus imaging for tracking neuroinflammation in mice and humans
Authors: Fleischer Vinzenz , Gonzalez-Escamilla Gabriel , Ciolac Dumitru , Albrecht Philipp , Küry Patrick , Gruchot Joel , Dietrich Michael , Hecker Christina , Müntefering Thomas , Bock Stefanie , Oshaghi Mohammadsaleh , Radetz Angela , Cerina Manuela , Krämer Julia , Wachsmuth Lydia , Faber Cornelius , Lassmann Hans , Ruck Tobias , Meuth Sven G. , Muthuraman Muthuraman , Groppa Sergiu
Published: September 2021

Significance

Neuroinflammation is a hallmark of multiple sclerosis and is linked to neurodegeneration. This study provides pathophysiological insights into the cross-dependency between neuroinflammation and choroid plexus characteristics in both mice and humans. Our work relates an enlargement of choroid plexus volume to ongoing neuroinflammation and emerging clinical disability in two large cohorts of multiple sclerosis patients as well as in two mouse models, the cuprizone diet-related demyelination and the experimental autoimmune encephalomyelitis. Choroid plexus characterization as measured by high-resolution MRI thus represents a reliable and translatable interspecies marker for the quantification of neuroinflammation and disease trajectories that is strongly associated with functional outcomes.
Hairless regulates heterochromatin maintenance and muscle stem cell function as a histone demethylase antagonist
Authors: Liu Ling , Rodriguez-Mateo Cristina , Huang Polly , Huang Albin , Lieu Alexander , Mao Michelle , Chung Mingyu , Yang Sharon , Yu Kevin , Charville Gregory W. , Gan Qiang , Rando Thomas A.
Published: September 2021

Significance

Skeletal muscle stem cells (MuSCs) exhibit a high content of heterochromatin. However, little is known about the functional importance of heterochromatin maintenance in MuSC homeostasis. Our study uncovered the role of the Hairless (Hr) gene in protecting the integrity of heterochromatin in MuSCs. We characterized the molecular function of Hr and demonstrated its role as an antagonist to Histone 3 Lysine 9 demethylases. Our work has implications for the importance of heterochromatin maintenance in stem cell function during aging.
Mitochondria-localized AMPK responds to local energetics and contributes to exercise and energetic stress-induced mitophagy
Authors: Drake Joshua C. , Wilson Rebecca J. , Laker Rhianna C. , Guan Yuntian , Spaulding Hannah R. , Nichenko Anna S. , Shen Wenqing , Shang Huayu , Dorn Maya V. , Huang Kian , Zhang Mei , Bandara Aloka B. , Brisendine Matthew H. , Kashatus Jennifer A. , Sharma Poonam R. , Young Alexander , Gautam Jitendra , Cao Ruofan , Wallrabe Horst , Chang Paul A. , Wong Michael , Desjardins Eric M. , Hawley Simon A. , Christ George J. , Kashatus David F. , Miller Clint L. , Wolf Matthew J. , Periasamy Ammasi , Steinberg Gregory R. , Hardie D. Grahame , Yan Zhen
Published: September 2021

Significance

Here, we present unequivocal evidence of physical association of AMPK holoenzymes with mitochondrial reticulum (mitoAMPK) across multiple mouse tissues with evidence of conservation in human skeletal muscle and heart. We demonstrate that mitoAMPK is activated heterogeneously across the mitochondrial reticulum by mitochondrial energetic stress. Finally, we present evidence that suggests activation of mitoAMPK in skeletal muscle is required for mitophagy. We propose that mitoAMPK responds to mitochondrial microenvironment cues to maintain energetic homeostasis through mitochondrial quality control.
Ethnic studies increases longer-run academic engagement and attainment
Authors: Bonilla Sade , Dee Thomas S. , Penner Emily K.
Published: September 2021

Significance

Anti-racist curricula and teaching methods are a potentially potent way for schools to better promote a just society and improve educational outcomes for low-income students and students of color. Ethnic studies (ES) courses in K–12 schools are an increasingly common and prominent example of such culturally relevant and critically engaged practice. Proponents tout the benefits of ES for increasing student engagement and academic outcomes, yet there is little causal evidence supporting these claims. In this study, we use a preregistered regression-discontinuity research design to identify the longer-term impacts on educational attainment and engagement of being assigned to an ES course in grade 9. We find that assignment to ES substantially increased high school graduation, attendance, and the probability of enrolling in college.
Increasing and decreasing interregional brain coupling increases and decreases oscillatory activity in the human brain
Authors: Sel Alejandra , Verhagen Lennart , Angerer Katharina , David Raluca , Klein-Flügge Miriam C. , Rushworth Matthew F.S.
Published: September 2021

Significance

Oscillatory activity is prominent in the brain, and one hypothesis is that it is, in part, due to the nature of coupling or interaction patterns between brain areas. We tested this hypothesis by manipulating the strength of coupling between two brain regions (ventral premotor cortex, PMv, and motor cortex, M1) in two directions (increase or decrease) while carefully controlling for the impact each manipulation had on activity in each area. We looked at the PMv–M1 connection because it is the major cortical route by which prefrontal cortex might influence, inhibit, and curtail action-related activity in M1. Manipulating PMv–M1 coupling in accordance with Hebbian-like spike-timing–dependent plasticity resulted in changes in beta and theta frequencies linked to action control.
Actin filament debranching regulates cell polarity during cell migration and asymmetric cell division
Authors: Xie Chao , Jiang Yuxiang , Zhu Zhiwen , Huang Shanjin , Li Wei , Ou Guangshuo
Published: September 2021

Significance

We find that the coronin family protein POD-1 debranches the actin network in vitro. Our results reveal that POD-1 regulates actin organization and cell polarity in migrating neuroblasts and one-cell−stage embryos of
C. elegans
. We provide evidence that F-actin debranching is critical for establishing cell polarity during cell migration and asymmetric cell division.
Learning nonnative speech sounds changes local encoding in the adult human cortex
Authors: Yi Han G. , Chandrasekaran Bharath , Nourski Kirill V. , Rhone Ariane E. , Schuerman William L. , Howard Matthew A. , Chang Edward F. , Leonard Matthew K.
Published: September 2021

Significance

Speech sound learning in adulthood is a highly dynamic process. Here, we used direct neurophysiology of the human brain to examine learning-associated changes in neural activity with unprecedented spatiotemporal detail. While native English listeners were trained to identify unfamiliar pitch patterns in Mandarin, local neural populations throughout the cortex showed a diverse set of encoding properties for Mandarin sounds that tracked behavioral performance. While previous neuroimaging studies have focused on highlighting general differences across broad cortical regions, we demonstrate that these functionally heterogeneous populations are spatially interspersed with one another. These findings provide insight into how the human brain strikes a balance between stability and plasticity during learning in adulthood.
A second S4 movement opens hyperpolarization-activated HCN channels
Authors: Wu Xiaoan , Ramentol Rosamary , Perez Marta E. , Noskov Sergei Yu , Larsson H. Peter
Published: September 2021

Significance

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are essential for the rhythmic activity of pacemaker cells in the heart and brain. How the movement of the voltage sensor, which is triggered by hyperpolarization of the membrane voltage, causes HCN channels to open is not clear. Here, we found that in HCN channels, the voltage sensor moves in two steps in response to hyperpolarizations and that the second voltage sensor step correlates with gate opening. A better understanding of HCN channel gating will aid in the development of better antiarrhythmic drugs.
Optimal renormalization of multiscale systems
Authors: Price Jacob , Meuris Brek , Shapiro Madelyn , Stinis Panos
Published: September 2021

Significance

Many systems involve more variables than can be reasonably simulated. Even when only some of these variables are of interest, they usually depend strongly on the other variables. Reduced order models of the relevant variables, which behave as those variables would in a full simulation, are of great interest. Many such models involve a “memory” term that is difficult to compute and can lead to instability if not properly approximated. We have developed a time-dependent renormalization approach to stabilize such models. We validate the approach on the inviscid Burgers equation. We use it to obtain a perturbative renormalization of the three-dimensional Euler equations of incompressible fluid flow including all the complex effects present in the dynamics.
Local thermodynamics govern formation and dissolution ofCaenorhabditiselegans P granule condensates
Authors: Fritsch Anatol W. , Diaz-Delgadillo Andrés F. , Adame-Arana Omar , Hoege Carsten , Mittasch Matthäus , Kreysing Moritz , Leaver Mark , Hyman Anthony A. , Jülicher Frank , Weber Christoph A.
Published: September 2021

Significance

Living cells rely on a continuous flux of energy to spatially organize biochemical processes. It remains unclear whether cells can achieve this spatial organization via thermodynamic principles. Here, we report the striking behavior of a cold-blooded organism that reacts to environmental temperature changes similar to a thermodynamic system at local equilibrium. Our key finding is that protein-rich droplets form and dissolve reversibly with temperature due to changes in the organism’s entropy. We show that the organism uses a specific molecule to extend droplet stability to the natural temperature range of the organism’s habitat. Due to the relevance of such protein droplets for the organism’s fertility, our work sheds light on how molecular components could facilitate biological functions via thermodynamic principles.
Governing complexity: Integrating science, governance, and law to manage accelerating change in the globalized commons
Authors: Cosens Barbara , Ruhl J. B. , Soininen Niko , Gunderson Lance , Belinskij Antti , Blenckner Thorsten , Camacho Alejandro E. , Chaffin Brian C. , Craig Robin Kundis , Doremus Holly , Glicksman Robert , Heiskanen Anna-Stiina , Larson Rhett , Similä Jukka
Published: September 2021

The speed and uncertainty of environmental change in the Anthropocene challenge the capacity of coevolving social–ecological–technological systems (SETs) to adapt or transform to these changes. Formal government and legal structures further constrain the adaptive capacity of our SETs. However, new, self-organized forms of adaptive governance are emerging at multiple scales in natural resource-based SETs. Adaptive governance involves the private and public sectors as well as formal and informal institutions, self-organized to fill governance gaps in the traditional roles of states. While new governance forms are emerging, they are not yet doing so rapidly enough to match the pace of environmental change. Furthermore, they do not yet possess the legitimacy or capacity needed to address disparities between the winners and losers from change. These emergent forms of adaptive governance appear to be particularly effective in managing complexity. We explore governance and SETs as coevolving complex systems, focusing on legal systems to understand the potential pathways and obstacles to equitable adaptation. We explore how governments may facilitate the emergence of adaptive governance and promote legitimacy in both the process of governance despite the involvement of nonstate actors, and its adherence to democratic values of equity and justice. To manage the contextual nature of the results of change in complex systems, we propose the establishment of long-term study initiatives for the coproduction of knowledge, to accelerate learning and synergize interactions between science and governance and to foster public science and epistemic communities dedicated to navigating transitions to more just, sustainable, and resilient futures.
IL-6 enhances CD4 cell motility by sustaining mitochondrial Ca2+through the noncanonical STAT3 pathway
Authors: Valença-Pereira Felipe , Fang Qian , Marié Isabelle J. , Giddings Emily L. , Fortner Karen A. , Yang Rui , Villarino Alejandro V. , Huang Yina H. , Frank David A. , Wen Haitao , Levy David E. , Rincon Mercedes
Published: September 2021

Significance

In this manuscript, we identify a pathway involving mitochondrial Ca2+and mitochondrial Stat3 that strengthens the motility fitness of activated CD4 T cells. Considering that motility is essential for CD4 T cells to find and reach their targets and mediate pathogenesis, these findings could lead to the development of therapeutic strategies to intervene in CD4 T cell–mediated inflammatory diseases.
Mechanism of
Staphylococcus aureus
peptidoglycan
O
-acetyltransferase A as an
O
-acyltransferase
Authors: Jones Carys S. , Anderson Alexander C. , Clarke Anthony J.
Published: September 2021

Significance

Enzymes comprised of membrane-spanning acyltransferase-3 (AT-3) domains catalyze the O-acetylation of diverse extracytoplasmic glycans in all forms of life. In many cases, such as peptidoglycan, these glycans represent important cell wall components, and their O-acetylation confers resistance to lytic enzymes. The enzyme responsible for peptidoglycan O-acetylation in gram-positive bacteria, OatA, is a single bimodal protein of an AT-3 domain fused to an SGNH domain. The AT-3 domain adopts a different topology to that predicted in silico. Moreover, its utilization of a unique mechanism for the translocation of acetyl groups across the cytoplasmic membrane for their transfer to peptidoglycan involving catalytic Tyr and Ser residues may be broadly applicable to homologs involved in the modification of other important cell wall glycans.
Biochemical reconstitution defines new functions for membrane-bound glycosidases in assembly of the bacterial cell wall
Authors: Taguchi Atsushi , Page Julia E. , Tsui Ho-Ching Tiffany , Winkler Malcolm E. , Walker Suzanne
Published: September 2021

Significance

Bacteria are protected from their surrounding environment by the peptidoglycan cell wall, which is a major target for antibiotics. Counterintuitively, cell wall assembly requires enzymes that cleave newly built peptidoglycan chains. Here, using nascent peptidoglycan we assembled in vitro, we characterized two membrane-bound glycosidases that are vital for proper cell division and elongation in
Streptococcus pneumoniae
. These enzymes were proposed to perform different chemical reactions. Instead, we show that they perform the same chemical reaction but cut the peptidoglycan backbone at different sites. We identify the mechanistic basis for cleavage site selection and also identify an amino acid switch that alters the cleavage chemistry. This work advances our understanding of how peptidoglycan glycosidases help build the cell wall.
Prediction of arrhythmia susceptibility through mathematical modeling and machine learning
Authors: Varshneya Meera , Mei Xueyan , Sobie Eric A.
Published: September 2021

Significance

Despite our understanding of the many factors that promote ventricular arrhythmias, it remains difficult to predict which specific individuals within a population will be especially susceptible to these events. We present a computational framework that combines supervised machine learning algorithms with population-based cellular mathematical modeling. Using this approach, we identify electrophysiological signatures that classify how myocytes respond to three arrhythmic triggers. Our predictors significantly outperform the standard myocyte-level metrics, and we show that the approach provides insight into the complex mechanisms that differentiate susceptible from resistant cells. Overall, our pipeline improves on current methods and suggests a proof of concept at the cellular level that can be translated to the clinical level.
Tril dampens Nodal signaling through Pellino2- and Traf6-mediated activation of Nedd4l
Authors: Kim Hyung-Seok , Green Yangsook Song , Xie Yuanyuan , Christian Jan L.
Published: September 2021

Significance

A proper balance of Bmp and Tgf-ß/Nodal signaling is critical to ensure normal development and to prevent disease. Our studies identify a signaling cascade that functions to coordinately enhance Bmp signaling and reduce Nodal output by activating the ubiquitin ligase Nedd4l. Mutations inNEDD4Lthat lead to gain or loss of activity underlie congenital disorders and disease in humans. Understanding how Nedd4l activity is regulated in different contexts may provide insight into how mutations inNEDD4Lresult in human pathology.
DeepLINK: Deep learning inference using knockoffs with applications to genomics
Authors: Zhu Zifan , Fan Yingying , Kong Yinfei , Lv Jinchi , Sun Fengzhu
Published: September 2021

Significance

Although practically attractive with high prediction and classification power, complicated learning methods often lack interpretability and reproducibility, limiting their scientific usage. A useful remedy is to select truly important variables contributing to the response of interest. We develop a method for deep learning inference using knockoffs, DeepLINK, to achieve the goal of variable selection with controlled error rate in deep learning models. We show that DeepLINK can also have high power in variable selection with a broad class of model designs. We then apply DeepLINK to three real datasets and produce statistical inference results with both reproducibility and biological meanings, demonstrating its promising usage to a broad range of scientific applications.
Cyclodextrins increase membrane tension and are universal activators of mechanosensitive channels
Authors: Cox Charles D. , Zhang Yixiao , Zhou Zijing , Walz Thomas , Martinac Boris
Published: September 2021

Significance

Mechanosensitive (MS) channels play a key role in the physiology of organisms from bacteria to man. Many prokaryotic and eukaryotic MS channels respond to membrane tension. Here, we show that cyclodextrin (CD)–mediated lipid removal induces membrane tension that activates not only the mechanosensitive channel of small conductance but the structurally unrelated mechanosensitive channel of large conductance, which gates at almost lytic membrane tensions. This finding suggests that for both functional and structural studies, provided that sufficient CD is added and enough lipids are removed, any tension-sensitive ion channel can be activated. Moreover, CDs may also prove useful for the in vitro study of other membrane proteins that are sensitive to mechanical forces.
MSX2 safeguards syncytiotrophoblast fate of human trophoblast stem cells
Authors: Hornbachner Ruth , Lackner Andreas , Papuchova Henrieta , Haider Sandra , Knöfler Martin , Mechtler Karl , Latos Paulina A.
Published: September 2021

Significance

The human placenta contains progenitors that give rise to highly specialized trophoblast cell types, and failures in their differentiation are associated with placental pathologies. Importantly, transcription factors controlling these cell fate decisions in humans are poorly understood. Here, we uncovered MSX2 as a human-specific regulator of trophoblast cell identity and implicate its role in placental development and disease. We found that MSX2 interacts and cobinds many target genes with components of the SWI/SNF chromatin remodeling complex, suggesting a mechanistic link. Given the critical function of SWI/SNF in gene expression, organogenesis, and disease, we provided characterization of its composition and possible role in the placental context.
Activation of Smad2/3 signaling by low fluid shear stress mediates artery inward remodeling
Authors: Deng Hanqiang , Min Elizabeth , Baeyens Nicolas , Coon Brian G. , Hu Rui , Zhuang Zhen W. , Chen Minghao , Huang Billy , Afolabi Titilayo , Zarkada Georgia , Acheampong Angela , McEntee Kathleen , Eichmann Anne , Liu Fang , Su Bing , Simons Michael , Schwartz Martin A.
Published: September 2021

Significance

This paper analyzes the signaling network that regulates the size of artery lumens and thus their ability to transport blood to tissues. Lumen diameter is under close homeostatic regulation to match artery flow to the needs of downstream tissues. However, in atherosclerosis, this regulation is compromised, resulting in restricted blood flow and tissue ischemia. The elucidation of a Smad2/3 pathway that is specifically activated at low flow to trigger inward remodeling and thus restore normal shear stress levels not only reveals a mechanism of physiological regulation but also explains how activation of the same pathway by inflammatory factors in diseased arteries can lead to artery restriction.
All-or-none disconnection of pyramidal inputs onto parvalbumin-positive interneurons gates ocular dominance plasticity
Authors: Severin Daniel , Hong Su Z. , Roh Seung-Eon , Huang Shiyong , Zhou Jiechao , Bridi Michelle C. D. , Hong Ingie , Murase Sachiko , Robertson Sarah , Haberman Rebecca P. , Huganir Richard L. , Gallagher Michela , Quinlan Elizabeth M. , Worley Paul , Kirkwood Alfredo
Published: September 2021

Significance

We report a unique form of neural plasticity in the visual cortex. Unlike well-known forms of neural plasticity, in which synaptic connections are slowly weakened or strengthened, we found that visual deprivation causes a rapid and transient “all-or-none” loss of local connections between pyramidal cells and parvalbumin-positive interneurons (Pyr→PV). After 1 d of visual deprivation, half of these connections are lost, whereas the spared ones remain unchanged; after 2 d of deprivation, the connectivity levels return to normal. Finally, we show that this early transient all-or-none loss of Pyr→PV connections is an obligatory step for subsequent changes in the cortical function induced by visual deprivation.
An Early Oligocene age for the oldest known monkeys and rodents of South America
Authors: Campbell Kenneth E. , O’Sullivan Paul B. , Fleagle John G. , de Vries Dorien , Seiffert Erik R.
Published: September 2021

Significance

The Paleogene dispersals of monkeys and rodents from Africa to South America permanently and profoundly altered the composition of mammalian communities in the Neotropics, but the timing of these colonization events remains uncertain. Through a combination of geochronological analyses (detrital zircon dating of the Santa Rosa fossil locality in eastern Perú) and phylogenetic biochronological analyses (tip-dating age estimation of caviomorph rodents), we demonstrate that the oldest known primates and rodents of South America are unlikely to be older than Early Oligocene in age and are not Eocene in age as previously postulated. There are no grounds for rejecting the possibility of an earlier arrival for either clade, but at present the fossil record provides no evidence for earlier dispersals.
Discovery of complex oxides via automated experiments and data science
Authors: Yang Lusann , Haber Joel A. , Armstrong Zan , Yang Samuel J. , Kan Kevin , Zhou Lan , Richter Matthias H. , Roat Christopher , Wagner Nicholas , Coram Marc , Berndl Marc , Riley Patrick , Gregoire John M.
Published: September 2021

Significance

Automation is accelerating the discovery of useful materials, yet testing even a small fraction of the billions of possible materials for a desired property is beyond the reach of workflows involving resource-intensive property measurements. Due to relationships among composition, structure, and properties, identifying a complex material with one interesting property makes it the proverbial needle in a haystack that merits testing for additional properties. We accelerate materials synthesis and optical characterization by employing physics-aware data science to identify materials for further investigation. With this approach, one does not need high-throughput methods for measuring every material property of interest since a single ultra-high–throughput workflow can guide material selection for other properties, which is a new paradigm for accelerated materials discovery.
Diffusion of a disordered protein on its folded ligand
Authors: Wiggers Felix , Wohl Samuel , Dubovetskyi Artem , Rosenblum Gabriel , Zheng Wenwei , Hofmann Hagen
Published: September 2021

Significance

Flexibility in complexes between intrinsically disordered proteins and folded ligands is widespread in nature. However, timescales and spatial amplitudes of such dynamics remained unexplored for most systems. Our results show that the disordered cytoplasmic tail of the cell adhesion protein E-cadherin diffuses across the entire surface of its folded binding partner β-catenin at fast submillisecond timescales. The nanometer amplitude of these motions could allow kinases to access their recognition motifs without requiring a dissociation of the complex. We expect that the rugged energy landscape found in the E-cadherin/β-catenin complex is a defining feature of dynamic and partially disordered protein complexes.
Structural basis of P[II] rotavirus evolution and host ranges under selection of histo-blood group antigens
Authors: Xu Shenyuan , McGinnis Kristen Rose , Liu Yang , Huang Pengwei , Tan Ming , Stuckert Michael Robert , Burnside Riley Erin , Jacob Elsa Grace , Ni Shuisong , Jiang Xi , Kennedy Michael A.
Published: September 2021

Significance

Group A rotaviruses cause severe gastroenteritis in infants and young children worldwide, with P[II] genogroup rotaviruses (RVs) responsible for >90% of global cases. Existing RV vaccines are successful in many developed countries, but their efficacy remains poor in developing countries, which could be due to lack of cross protection between RV genotypes more common in developed countries and other P-type RVs less common in developed countries but common in developing countries. In this study, crystal structures of major P[II] genogroup VP8* receptor domains in complex with Lewis epitope–containing histo-blood group antigen (HBGA) glycans were determined, revealing the structural basis for RV HBGA receptor specificities that determine RV host ranges. The data should enable rationale design of next-generation RV vaccines.
Regulation of P2X1 receptors by modulators of the cAMP effectors PKA and EPAC
Authors: Fong Zhihui , Griffin Caoimhín S. , Large Roddy J. , Hollywood Mark A. , Thornbury Keith D. , Sergeant Gerard P.
Published: September 2021

Significance

P2X1 receptors are important for neurogenic contraction of smooth muscle, thrombus formation, and regulation of neutrophil migration. Knockdown of P2X1 causes a 90% reduction in male fertility, and up-regulation of P2X1 receptors is associated with inflammatory bladder conditions, such as interstitial cystitis and idiopathic detrusor instability. This study identifies EPAC as a negative regulator of P2X1 receptors, but a positive regulator of P2X2 receptors. Substitution of residues 21 to 23 on P2X1 receptors, for the equivalent residues on P2X2, protected P2X1 receptors from the inhibitory effects of EPAC activation. An inhibitor of the Rho GTPase, Rac1, also prevented the inhibitory effects of EPAC activation on P2X1 currents. Our findings demonstrate regulation of P2X1 and P2X2 receptors by EPAC.
Cannabinoid and planar cell polarity signaling converges to direct placentation
Authors: Kim Yeon Sun , Li Yingju , Yuan Jia , Borg Jean-Paul , Sun Xiaofei , Dey Sudhansu K.
Published: September 2021

Significance

During placentation, some trophoblast cells, termed spiral artery trophoblast giant cells (SpA-TGCs), invade the maternal decidua and replace arterial endothelial cells to increase blood supply to the placenta; how this directional trophoblast migration occurs remains unknown. We show here that planar cell polarity (PCP) signaling mediated by
VANGL2
in SpA-TGCs plays a key role in trophoblast movement and successful placentation. Mice with SpA-TGC progenitors deficient in
Vangl2
had pregnancy termination in mid-gestation due to increased random cell protrusion and compromised cell migration. We also found endocannabinoid signaling intersects with PCP signaling in directing trophoblast migration by direct association of CB1 and
VANGL2
. These results demonstrated that trophoblast invasion in placentation requires organized PCP.
Rising nonmarital first childbearing among college-educated women: Evidence from three national studies
Authors: Cherlin Andrew J.
Published: September 2021

Significance

Until recently, one key way in which family formation in the United States was distinctive among college-educated young adults was their tendency to wait until after marriage to have a first birth. Even as nonmarital first childbearing became common among less-educated adults, levels among the college-educated remained very low. These levels now appear to be rising, according to data from three national surveys. The data suggest a change in the role of marriage in family formation among the college-educated population, although not necessarily a decline. Rather, the place of marriage in the sequence of life events that compose emerging adulthood may be shifting among college graduates: for a growing share, marriage may occur after a first birth rather than before.
Children’s text comprehension
Authors: Oakhill Jane
Published: September 2021

This paper first considers what is meant by good reading comprehension and makes a distinction between the product
of reading comprehension and the processes that are required to attain that product. It goes on to consider how less-skilled
comprehenders can be identified and provides a summary of the research into how less-skilled and skilled comprehenders differ in
terms of the skills and processes that they apply during text comprehension. Finally, the implications of these research findings
for instruction are considered, and generalizable research-based recommendations for teaching reading comprehension strategies are
considered.
Tunable enhanced Faraday rotation in a defected plasma photonic crystal under external magnetic field with different declinations
Authors: Pourali Nima , Alexander Kevon , Hessel Volker , Rebrov Evgeny V
Published: September 2021

Magneto-optical responses and the potential for tunability when changing the variables of a one-dimensional defected magnetized plasma photonic crystal have been studied using a transfer matrix method for operation in the mm-range wavelength region. The effect of the number and dielectric defect layer thickness as well as the intensity and declination angle of magnetic field on transmittance, Faraday rotation, and its ellipticity has been investigated. The results demonstrate the ability to alter the resonant modes frequency at multiple levels of precision. The structures with four, six, and eight defect layers have been investigated. The number of defect dielectric layers changes the number of resonance modes. A single defect mode appears within the photonic bandgap with four defect dielectric layers while two defect modes were observed with six layers, and three modes with eight layers. An increase in magnetic field declination decreased the Faraday rotation intensity and width of Faraday resonance mode.
Plasma-droplet interaction study to assess transport limitations and the role of ⋅OH, O⋅,H⋅,O2(a
1Δg),O3, He(23
S) and Ar(1s
5) in formate decomposition
Authors: Nayak Gaurav , Oinuma Gaku , Yue Yuanfu , Santos Sousa João , Bruggeman Peter J
Published: September 2021

Plasmas interacting with liquid microdroplets are gaining momentum due to their ability to significantly enhance the reactivity transfer from the gas phase plasma to the liquid. This is, for example, critically important for efficiently decomposing organic pollutants in water. In this contribution, the role of ⋅OH as well as non-⋅OH-driven chemistry initiated by the activation of small water microdroplets in a controlled environment by diffuse RF glow discharge in He with different gas admixtures (Ar, O2 and humidified He) at atmospheric pressure is quantified. The effect of short-lived radicals such as O⋅ and H⋅ atoms, singlet delta oxygen (O2(a
1Δg)), O3 and metastable atoms of He and Ar, besides ⋅OH radicals, on the decomposition of formate dissolved in droplets was analyzed using detailed plasma diagnostics, droplet characterization and ex situ chemical analysis of the treated droplets. The formate decomposition increased with increasing droplet residence time in the plasma, with ∼70% decomposition occurring within ∼15 ms of the plasma treatment time. The formate oxidation in the droplets is shown to be limited by the gas phase ⋅OH flux at lower H2O concentrations with a significant enhancement in the formate decomposition at the lowest water concentration, attributed to e−/ion-induced reactions. However, the oxidation is diffusion limited in the liquid phase at higher gaseous ⋅OH concentrations. The formate decomposition in He/O2 plasma was similar, although with an order of magnitude higher O⋅ radical density than the ⋅OH density in the corresponding He/H2O plasma. Using a one-dimensional reaction–diffusion model, we showed that O2(a
1Δg) and O3 did not play a significant role and the decomposition was due to O⋅, and possibly ⋅OH generated in the vapor containing droplet-plasma boundary layer.
Synthesis of yttrium aluminum garnet (Y3Al5O12, YAG) powder with nano and submicro size and high infrared transmittance using flame aerosol synthesis method
Authors: Tian Hui , Wang Lei , Yang Taisheng , Zhang Zili
Published: September 2021

In this study, the flame aerosol synthesis (FAS) method was used to synthesize a yttrium aluminum garnet (Y3Al5O12, YAG) nanopowder. The dominant reaction route in the FAS method is the liquid route; this shaped the primary morphology of the YAG nanopowder into hollow and solid spheres. The effects of precursor concentration and annealing parameters were systematically investigated. At a precursor concentration of 0.4 mol L−1 and an annealing temperature of 1400 °C, the YAG nanopowder exhibited excellent infrared transmittance. Compared to other conventional synthesis methods, the FAS method has the advantages of high yield, low cost, and ease of obtaining a nanosized powder. The FAS method is thought to be one of the best choices for the large-scale production of YAG powders.
Overgroups of regular unipotent elements in simple algebraic groups
Authors: Malle Gunter , Testerman Donna
Published: September 2021

We investigate positive-dimensional closed reductive subgroups of almost simple algebraic groups containing a regular unipotent element. Our main result states that such subgroups do not lie inside proper parabolic subgroups unless possibly when their connected component is a torus. This extends the earlier result of Testerman and Zalesski treating connected reductive subgroups.
Geriatric medicine in the era of climate change
Authors: Davies Bethan , Bhutta Mahmood F
Published: September 2021

Climate change has been termed the greatest threat to human health of the 21st century. Older people and those living with frailty are more vulnerable to the effects of climate change including heatwaves and extreme weather events, and therefore, we have a responsibility to advocate for action on the climate emergency and take steps to reduce the environmental impact of our care provision. The NHS contributes 5.7% to the carbon footprint of the UK, and by reviewing the financial costs associated with frailty, we estimate the carbon footprint of frailty to be 1.7 MtCO2e, or 7% of the total NHS carbon footprint. Resource use also increases with age with particular interventions and medical equipment such as hearing and mobility aids being predominantly associated with the care of older people. The NHS has committed to net zero carbon emissions by 2045 and in order to achieve this we all need to act—balancing the triple bottom line of environmental, social and financial impacts alongside outcomes for patients and populations when making decisions about care. The principles of sustainable healthcare are already embedded in the geriatrician’s holisitic approach to the care of older people and those living with frailty, and the imperative to reduce the carbon footprint of healthcare should add weight to the argument for extending the role of the geriatrician into other specialties. It is time to begin our journey to net-zero geriatric medicine.
Plasminogen Activator Inhibitor-1 and Adiponectin Are Associated With Metabolic Syndrome Components
Authors: Vecchiola Andrea , García Killén , González-Gómez Luis M , Tapia-Castillo Alejandra , Artigas Rocío , Baudrand René , Kalergis Alexis M , Carvajal Cristian A , Fardella Carlos E
Published: September 2021

BACKGROUND

We aimed to study the associations of adipocytokines, endothelial damage markers, and high-sensitivity C-reactive protein (hs-CRP) with metabolic syndrome (MetS) components.

METHODS

This cross-sectional study included 202 subjects categorized into MetS and No-MetS according to Harmonizing Adult Treatment Panel III.

RESULTS

Subjects with MetS showed higher levels of proinflammatory molecules but significantly lower adiponectin levels than subjects with No-MetS. Among the studied adipocytokines, plasminogen activator inhibitor-1 (PAI-1) and adiponectin showed the strongest associations with most MetS components. PAI-1 was associated with MetS (odds ratio (OR) 1.107 (1.065–1.151), P < 0.0001), whereas adiponectin was inversely associated with MetS (OR 0.710 (0.610–0.825), P < 0.0001). Following adjustment by sex, age, body mass index, and 24-hour urinary sodium excretion in a multivariate analysis, the association of PAI-1 (OR 1.090 (1.044–1.137), P < 0.0001) and adiponectin (OR 0.634 (0.519–0.775), P < 0.0001) with MetS remained significant. Multivariate analyses supported a model in which systolic blood pressure (BP) could be predicted by PAI-1, hs-CRP, and matrix metalloproteinase 2 (R2 = 0.125; P = 0.04); diastolic BP (R2 = 0.218; P = 0.0001) and glucose (R2 = 0.074; P = 0.0001) could be predicted by PAI-1; waist circumference could be predicted by PAI-1 and hs-CRP (R2 = 0.28; P = 0.016). Receiver operating characteristic curve analysis showed that a PAI-1 concentration had the best sensitivity and specificity for discriminating subjects with MetS.

CONCLUSION

PAI-1 and adiponectin rendered the most robust associations with MetS components in a general population, indicating that unfavorable adipose tissue performance is a key contributor to these metabolic anomalies. Further prospective analyses should allow establishing whether these adipocytokines can anticipate the progress of MetS and cardiovascular risk.
Sulfated polysaccharide ascophyllan prevents amyloid fibril formation of human insulin and inhibits amyloid-induced hemolysis and cytotoxicity in PC12 cells
Authors: Liang Yan , Ueno Mikinori , Zha Shijiao , Okimura Takasi , Jiang Zedong , Yamaguchi Kenichi , Hatakeyama Tomomitsu , Oda Tatsuya
Published: September 2021

We found that ascophyllan significantly inhibited the fibrillation of human insulin and was the most effective among the sulfated polysaccharides tested. Gel-filtration analysis suggested that ascophyllan was capable of forming a complex with insulin through a weak interaction. Secondary structure transition from native α-helix to β-sheet predominant structure of insulin under the fibrillation conditions was suppressed in the presence of ascophyllan. Interestingly, ascophyllan attenuated insulin fibril-induced hemolysis of human erythrocytes. Moreover, ascophyllan attenuated insulin amyloid-induced cytotoxicity on rat pheochromocytoma PC12 cells and reduced the level of intracellular reactive oxygen species. This is the first report indicating that a sulfated polysaccharide, ascophyllan, can suppress the insulin amyloid fibril formation and inhibit the fibril-induced detrimental bioactivities.
Validated prediction model for positive resection margins in breast-conserving surgery based exclusively on preoperative data
Authors: Ellbrant J , Gulis K , Plasgård E , Svensjö T , Bendahl P O , Rydén L
Published: September 2021

Background

Positive margins after breast-conserving surgery (BCS) and subsequent second surgery are associated with increased costs and patient discomfort. The aim of this study was to develop a prediction model for positive margins based on risk factors available before surgery.

Methods

Patients undergoing BCS for in situ or invasive cancer between 2015 and 2016 at site A formed a development cohort; those operated during 2017 in site A and B formed two validation cohorts. MRI was not used routinely. Preoperative radiographic and tumour characteristics and method of operation were collected from patient charts. Multivariable logistic regression was used to develop a prediction model for positive margins including variables with discriminatory capacity identified in a univariable model. The discrimination and calibration of the prediction model was assessed in the validation cohorts, and a nomogram developed.

Results

There were 432 patients in the development cohort, and 190 and 157 in site A and B validation cohorts respectively. Positive margins were identified in 77 patients (17.8 per cent) in the development cohort. A non-linear transformation of mammographic tumour size and six variables (visible on mammography, ductal carcinoma in situ, lobular invasive cancer, distance from nipple–areola complex, calcification, and type of surgery) were included in the final prediction model, which had an area under the curve of 0.80 (95 per cent c.i. 0.75 to 0.85). The discrimination and calibration of the prediction model was assessed in the validation cohorts, and a nomogram developed.

Conclusion

The prediction model showed good ability to predict positive margins after BCS and might, after further validation, be used before surgery in centres without the routine use of preoperative MRI.

Presented in part to the San Antonio Breast Cancer Symposium, San Antonio, Texas, USA, December 2018 and the Swedish Surgical Society Annual Meeting, Helsingborg, Sweden, August 2018.
Using Complex Adaptive Systems Theory to Understand the Complexities of Hospital Social Work Practice in Rural and Remote South Australia
Authors: Harvey Ellen , Jones Michelle
Published: September 2021

Working with complexity is a growing concern and challenge for social workers in contemporary practice. This study explored how rural social work practitioners experience complexity in their professional judgement and decision-making, giving voice to the unique understandings and perspectives of rural health social workers (RHSWs). Complex adaptive systems (CAS) theory is used to conceptualise participants’ experiences. An interpretive critical research paradigm valued the unique viewpoint of rural social workers whilst also disrupting the urban-centric focus of social work practice. The participants were recruited via their involvement in the Country Health South Australia social work leadership group. Data collected using a living lab approach, consisted of ten phone interviews sandwiched by two focus groups (n = 14). The data were analysed using both hand-coding and computer-assisted analysis (NVivo). The results demonstrated that RHSW encounter complexity within and across three main systems: client, organisational and rural systems. Importantly, the rural system plays an equally significant role in understanding complexity in this context, with each system overlapping and influencing one another. RHSW understanding of complexity was consistent with CAS, suggesting the advantage of using this theory to underpin understandings of complexity in social work practice and specifically in the rural practice domain.
Clinically relevant mitochondrial-targeted therapy improves chronic outcomes after traumatic brain injury
Authors: Hubbard W Brad , Spry Malinda L , Gooch Jennifer L , Cloud Amber L , Vekaria Hemendra J , Burden Shawn , Powell David K , Berkowitz Bruce A , Geldenhuys Werner J , Harris Neil G , Sullivan Patrick G
Published: September 2021

Pioglitazone, an FDA-approved compound, has been shown to target the novel mitochondrial protein mitoNEET and produce short-term neuroprotection and functional benefits following traumatic brain injury.

To expand on these findings, we now investigate the dose- and time-dependent effects of pioglitazone administration on mitochondrial function after experimental traumatic brain injury. We then hypothesize that optimal pioglitazone dosing will lead to ongoing neuroprotection and cognitive benefits that are dependent on pioglitazone-mitoNEET signalling pathways. We show that delayed intervention is significantly more effective than early intervention at improving acute mitochondrial bioenergetics in the brain after traumatic brain injury. In corroboration, we demonstrate that mitoNEET is more heavily expressed, especially near the cortical contusion, in the 18 h following traumatic brain injury. To explore whether these findings relate to ongoing pathological and behavioural outcomes, mice received controlled cortical impact followed by initiation of pioglitazone treatment at either 3 or 18 h post-injury. Mice with treatment initiation at 18 h post-injury exhibited significantly improved behaviour and tissue sparing compared to mice with pioglitazone initiated at 3 h post-injury. Further using mitoNEET knockout mice, we show that this therapeutic effect is dependent on mitoNEET. Finally, we demonstrate that delayed pioglitazone treatment improves serial motor and cognitive performance in conjunction with attenuated brain atrophy after traumatic brain injury.

This study illustrates that mitoNEET is the critical target for delayed pioglitazone intervention after traumatic brain injury, mitochondrial-targeting is highly time-dependent after injury and there is an extended therapeutic window to effectively treat mitochondrial dysfunction after brain injury.
Indirect inference of sensitive variables with peer network survey
Authors: Chen Saran , Lu Xin , Liljeros Fredrik , Jia Zhongwei , Rocha Luis E C
Published: September 2021

Misreporting is a common source of bias in population surveys involving sensitive topics such as sexual behaviours, abortion or criminal activity. To protect their privacy due to stigmatized or illegal behaviour, respondents tend to avoid fully disclosure of personal information deemed sensitive. This attitude however may compromise the results of survey studies. To circumvent this limitation, this article proposes a novel ego-centric sampling method (ECM) based on the respondent’s peer networks to make indirect inferences on sensitive traits anonymously. Other than asking the respondents to report directly on their own behaviour, ECM takes into account the knowledge the respondents have about their social contacts in the target population. By using various scenarios and sensitive analysis on model and real populations, we show the high performance, that is low biases, that can be achieved using our method and the novel estimator. The method is also applied on a real-world survey to study traits of college students. This real-world exercise illustrates that the method is easy-to-implement, requiring few amendments to standard sampling protocols, and provides a high level of confidence on privacy among respondents. The exercise revealed that students tend to under-report their own sensitive and stigmatized traits, such as their sexual orientation. Little or no difference was observed in reporting non-sensitive traits. Altogether, our results indicate that ECM is a promising method able to encourage survey participation and reduce bias due to misreporting of sensitive traits through indirect and anonymous data collection.