bluuebunny/crossref_metadata_2025 huggingface dataset:
The Dingo Barrier Fence: Presenting the case to decommission the world’s longest environmental barrier in the United Nations Decade on Ecosystem Restoration 2021–2030
Authors: Philip Justine
Published: November 2021

The longest environmental barrier in the world is Australia's 5614 km Dingo Barrier Fence. The structure was completed in the 1950s, designed to facilitate the eradication of the country's apex predator and cultural keystone species the dingo (Canis dingo) from sheep (Ovis aries) grazing areas to the south-east of the continent. The fence and its support systems now present an immense obstacle to ecological restoration in Australia's arid zone, preventing traditional management practices, and are hazardous to all terrestrial wildlife in the immediate vicinity. The barrier presents a worst-case scenario for animal-generated seed dispersal patterns over the wider region and limits genetic transfer. Plummeting biodiversity inside the fence line and increasing pressures of climate change have left this region highly vulnerable to ecological collapse. Concurrently, sheep numbers have contracted over 75% in the arid zone since 1991, due to market forces and climate change, while demand for ethically produced goods such as predator-friendly meat production and organic produce is increasing. Decommissioning the Dingo Barrier Fence, moving the stock protection zone south and diversifying land use would not impact significantly on the current livestock production. It offers a sound economic alternative for the region, with the potential for regeneration of 82 million hectares of land, a scale encouraged for inclusion in the global initiative the United Nations Decade for Ecosystem Restoration (2021–2030). This would restore connectivity across the region, including vital access to the waters of the Murray Darling Basin. This would provide mitigation for the effects of climate change, new markets in organic and sustainable industries, and support ecological and cultural renewal.
Dauerhaftes Sporttreiben im Sportverein und motorische Entwicklung: Ergebnisse der MoMo-Längsschnittstudie (2003–2017)
Authors: Hanssen-Doose Anke , Oriwol Doris , Niessner Claudia , Schmidt Steffen Christian Eckehard , Klemm Katja , Woll Alexander , Worth Annette
Published: November 2021

Bereits im Kindes- und Jugendalter gilt die motorische Leistungsfähigkeit als wichtiger Gesundheitsmarker. Auf Basis von Daten der Motorik Modul-Studie wird in diesem Artikel längsschnittlich über die Jahre 2003–2017 untersucht, inwieweit sich Sportvereinsmitglieder, die konstant im Sportverein aktiv waren, hinsichtlich ihrer motorischen Entwicklung von denjenigen unterscheiden, die nie im Sportverein aktiv waren. Es wurden Daten aus drei Messwellen untersucht: T1 (2003–2006), T2 (2009–2012) und T3 (2014–2017). Aus insgesamt N = 1092 Teilnehmenden, von denen über T1 bis T3 Daten zur Motorik vorlagen, wurden all diejenigen mit konstanter Mitgliedschaft und Nicht-Mitgliedschaft im Sportverein über drei Messwellen ausgewählt. Das sind 46 % der Gesamtstichprobe (N = 498). Von den N = 498 Teilnehmer*innen (Alter T1: 8,9 ± 3,8 Jahre, T2: 15,1 ± 3,9 Jahre, T3: 20,3 ± 4,0 Jahre) waren 15 % dauerhafte Sportvereinsmitglieder mit Wettkampfengagement, 53 % dauerhafte Sportvereinsmitglieder ohne Wettkampfengagement sowie 32 % dauerhaft Sportvereinsabstinente. Zur Ermittlung der motorischen Leistungsfähigkeit wurden konditionelle und koordinative Fähigkeiten anhand des MoMo-Testprofils erhoben (Kondition: Standweitsprung, Liegestütz, Fahrrad-Ausdauertest, Koordination: Seitliches Hin- und Herspringen, Einbeinstand, Balancieren rückwärts). Die Unterschiede in der Entwicklung wurden anhand von alters- und geschlechtsadjustierten Perzentilen mittels Varianzanalysen mit Messwiederholung berechnet, mit dem Sozialstatus als Kovariate. Innerhalb der Sportvereinsmitglieder waren Teilnehmende mit niedrigem Sozialstatus deutlich unterrepräsentiert. Insgesamt betrachtet, ist die Entwicklung der koordinativen und konditionellen Fähigkeiten bei Sportvereinsmitgliedern als signifikant besser zu beurteilen im Vergleich zu Sportvereinsabstinenten (Modell Koordination * Sportverein: df = 3,870 | F = 2,931 | p = 0,021 | ETA = 0,015 | f = 0,123; Modell Kondition * Sportverein: df = 4 | F = 3,794 | p = 0,005 | ETA = 0,048 | f = 0,225). Die Ergebnisse untermauern die Wichtigkeit der Sportvereine für die motorische Entwicklung von Kindern, Jugendlichen und jungen Erwachsenen in Deutschland.
Approximations of geometrically ergodic reversible markov chains
Authors: Negrea Jeffrey , Rosenthal Jeffrey S.
Published: November 2021

A common tool in the practice of Markov chain Monte Carlo (MCMC) is to use approximating transition kernels to speed up computation when the desired kernel is slow to evaluate or is intractable. A limited set of quantitative tools exists to assess the relative accuracy and efficiency of such approximations. We derive a set of tools for such analysis based on the Hilbert space generated by the stationary distribution we intend to sample,$L_2(\pi)$. Our results apply to approximations of reversible chains which are geometrically ergodic, as is typically the case for applications to MCMC. The focus of our work is on determining whether the approximating kernel will preserve the geometric ergodicity of the exact chain, and whether the approximating stationary distribution will be close to the original stationary distribution. For reversible chains, our results extend the results of Johndrowet al.(2015) from the uniformly ergodic case to the geometrically ergodic case, under some additional regularity conditions. We then apply our results to a number of approximate MCMC algorithms.
Exact simulation of coupled Wright–Fisher diffusions
Authors: García-Pareja Celia , Hult Henrik , Koski Timo
Published: November 2021

In this paper an exact rejection algorithm for simulating paths of the coupled Wright–Fisher diffusion is introduced. The coupled Wright–Fisher diffusion is a family of multivariate Wright–Fisher diffusions that have drifts depending on each other through a coupling term and that find applications in the study of networks of interacting genes. The proposed rejection algorithm uses independent neutral Wright–Fisher diffusions as candidate proposals, which are only needed at a finite number of points. Once a candidate is accepted, the remainder of the path can be recovered by sampling from neutral multivariate Wright–Fisher bridges, for which an exact sampling strategy is also provided. Finally, the algorithm’s complexity is derived and its performance demonstrated in a simulation study.
Clinical Utility of Dual Anterior Nares and Oropharynx MRSA Screening PCR for Patients with Suspected Pneumonia
Authors: Kessler Michael A. , Biswas Sandip , Choera Tsokyi , Chen Derrick J. , Lepak Alexander J.
Published: November 2021

We reviewed the electronic health records of 1,419 inpatients with anterior nares (AN) and oropharynx (OP) MRSA PCR tests. Concordance was 96.5%. In discordant cases, AN negative–OP positive results increased detection of probable MRSA pneumonia by only 0.3%. A dual testing approach has limited utility in detecting MRSA pneumonia and increases resource utilization.
Universal scaling of temperature variance in Rayleigh–Bénard convection near the transition to the ultimate state
Authors: He Xiaozhou , Bodenschatz Eberhard , Ahlers Guenter
Published: November 2021

We report measurements of the temperature frequency spectra

$P(\,f, z, r)$

, the variance

$\sigma ^2(z,r)$

and the Nusselt number

$Nu$

in turbulent Rayleigh–Bénard convection (RBC) over the Rayleigh number range

$4\times 10^{11} \underset{\smash{\scriptscriptstyle\thicksim}} { < } Ra \underset{\smash{\scriptscriptstyle\thicksim}} { < } 5\times 10^{15}$

and for a Prandtl number

$Pr \simeq ~0.8$

(

$z$

is the vertical distance from the bottom plate and

$r$

is the radial position). Three RBC samples with diameter

$D = 1.12$

m yet different aspect ratios

$\varGamma \equiv D/L = 1.00$

,

$0.50$

and

$0.33$

(

$L$

is the sample height) were used. In each sample, the results for

$\sigma ^2/\varDelta ^2$

(

$\varDelta$

is the applied temperature difference) in the classical state over the range

$0.018 \underset{\smash{\scriptscriptstyle\thicksim}} { < } z/L \underset{\smash{\scriptscriptstyle\thicksim}} { < } 0.5$

can be collapsed onto a single curve, independent of

$Ra$

, by normalizing the distance

$z$

by the thermal boundary layer thickness

$\lambda = L/(2 Nu)$

. One can derive the equation

$\sigma ^2/\varDelta ^2 = c_1\times \ln (z/\lambda )+c_2+c_3(z/\lambda )^{-0.5}$

from the observed

$f^{-1}$

scaling of the temperature frequency spectrum. It fits the collapsed

$\sigma ^2(z/\lambda )$

data in the classical state over the large range

$20 \underset{\smash{\scriptscriptstyle\thicksim}} { < } z/\lambda \underset{\smash{\scriptscriptstyle\thicksim}} { < } 10^4$

. In the ultimate state (

$Ra \underset{\smash{\scriptscriptstyle\thicksim}} { > } Ra^*_2$

) the data can be collapsed only when an adjustable parameter

$\tilde \lambda = L/(2 \widetilde {Nu})$

is used to replace

$\lambda$

. The values of

$\widetilde {Nu}$

are larger by about 10 % than the experimentally measured

$Nu$

but follow the predicted

$Ra$

dependence of

$Nu$

for the ultimate RBC regime. The data for both the global heat transport and the local temperature fluctuations reveal the ultimate-state transitions at

$Ra^*_2(\varGamma )$

. They yield

$Ra^*_2 \propto \varGamma ^{-3.0}$

in the studied

$\varGamma$

range.
The semiotics of the deictic field: Reckoning language and experience in East Los Angeles
Authors: Osborne Dana
Published: November 2021

This analysis examines the ways in which a single speaker, Ana, born in mid-century East Los Angeles, organizes and reflects upon her experiences of the city through language. Ana’s story is one that sheds light on the experiences of many Mexican Americans who came of age at a critical time in a transitioning L.A., and the slow move of people who had been up until mid-century relegated largely in and around racially and socioeconomically segregated parts of L.A. These formative experiences are demonstrated to have informed the ways that speakers parse the social and geographical landscape along several dimensions, and this analysis interrogates the symbolic value of a special category of everyday language, deixis, to reveal the intersection between language and social experience in the cityscape of L.A. In this way, it is analytically possible to not only approach the habituation and reproduction of specific deictic fields as indexical of the ways that speakers parse the city, but also to demonstrate the ways in which key moments in the history of the city have shaped the emergence and meaning of those fields.
Two poisson limit theorems for the coupon collector’s problem with group drawings
Authors: Schilling Judith , Henze Norbert
Published: November 2021

In the collector’s problem with group drawings, s out of n different types of coupon are sampled with replacement. In the uniform case, each s-subset of the types has the same probability of being sampled. For this case, we derive a Poisson limit theorem for the number of types that are sampled at most
$c-1$
times, where
$c \ge 1$
is fixed. In a specified approximate nonuniform setting, we prove a Poisson limit theorem for the special case
$c=1$
. As corollaries, we obtain limit distributions for the waiting time for c complete series of types in the uniform case and a single complete series in the approximate nonuniform case.
The Democratic Conference and the Pre-Parliament in Russia, 1917: Class, Nationality, and the Building of a Postimperial Community
Authors: Sablin Ivan
Published: November 2021

The article offers a detailed analysis of the debates at the All-Russian Democratic Conference and in the Provisional Council of the Russian Republic (the Pre-Parliament), which followed the proclamation of the republic on September 1, 1917, and predated the Bolshevik-led insurgency on October 25. The two assemblies were supposed to help resolve the multilayered political, economic, and military crises of the First World War and the Revolution by consolidating a Russian postimperial political community and establishing a solid government. The debates demonstrated that grievances and antagonism, which were articulated in terms of class and nationality, made the idea of a broad nationalist coalition unpopular, since it would halt agrarian and other reforms and continue the negligence of non-Russian groups. Furthermore, those who still called for all-Russian national or civic unity split on the issue of community-building. The top-down, homogenizing and bottom-up, composite approaches proved irreconcilable and precluded a compromise between non-socialist and moderate socialist groups. The two assemblies hence failed to ensure a peaceful continuation of the postimperial transformation and did not lead to a broad coalition against right and left radicalism. The divisions, which were articulated in the two assemblies, translated into the main rifts of the Russian Civil War.
The effect of conventional preservatives on spicule length ofHeligmosomoides bakeri(Nematoda, Heligmosomidae)
Authors: Musah-Eroje M. , Burton L. , Behnke J.M.
Published: November 2021

Nematode spicules vary in shape and size even between closely related species and, therefore, constitute key characters in nematode taxonomy for distinguishing between species. Spicules are seldom measured on fresh specimens, but rather at some time after extraction from culled hosts and after a period of preservation of the worms in chemical fixatives or by freezing. We carried out two experiments to assess the effects of freezing in Hanks’ balanced salt solution, 70% or 80% ethanol and 10% formalin (both of the latter at room temperature and after storage at −80°C) on spicule length ofHeligmosomoides bakeriat two time intervals after extraction from mice (Experiment 1, one and four weeks; Experiment 2, one and four months). In Experiment 1, no significant differences were detected, although there was some variation between treatments and over time. In Experiment 2, spicule length varied significantly between treatments and over time, the greatest shrinkage being in 80% ethanol and the least in 10% formalin. However, overall variation in spicule length was very limited, accounting for no more than 5.03% change in length over time and 4.95% between treatments at any of the periods of assessment. Therefore, while whole nematodes can shrivel and shrink in preservatives, making many measurements unreliable, our data indicated that spicule lengths are very little changed by preservation techniques over time, and so spicule length remains as a reliable taxonomic character.
Impact of guidance on intervention adherence in computerised interventions for mental health problems: a meta-analysis
Authors: Musiat Peter , Johnson Catherine , Atkinson Melissa , Wilksch Simon , Wade Tracey
Published: November 2021

Web-based interventions are increasingly used for the prevention, treatment and aftercare of mental disorders. A crucial factor to the efficacy of such online programmes is adherence to the intervention content and procedure. It has been frequently suggested that adherence in web-based interventions is low and little is known about which factors influence adherence. To increase intervention uptake and completion, studies increasingly include interventions with some form of guidance. Guided interventions have been shown to have higher efficacy, however, evidence for the impact on adherence is limited and mixed. This meta-analysis explored the impact of human guidance on intervention completion in web-based mental health interventions. A total of 22 studies were included with interventions primarily targeting symptoms of depression and anxiety disorders. Results showed that guidance significantly increases the average amount of intervention completion [g = 0.29, 95% confidence interval (CI) 0.18–0.40] and the proportion of intervention completers [log odds ratio (OR) = 0.50, 95% CI 0.34–0.66] with small effects. On average, full completion rates were 12% higher in guided intervention groups. This meta-analysis demonstrated that guidance in web-based mental health interventions does increase adherence, but more research is required to better understand the specific mechanisms between guidance, adherence and outcomes.
Working Group 2: Atomic Transition Probabilities
Authors: Wiese W.L.
Published: November 2021

The Data Center on Atomic Transition Probabilities at the National Bureau of Standards, Washington, D.C., has continued its bibliographical and critical compilation work on transition probabilities. A new general bibliography has been published, covering the literature references through October 1977 (1).
Potential range shifts and climatic refugia of rupicolous reptiles in a biodiversity hotspot of South Africa
Authors: Petford Melissa Anne , Alexander Graham John
Published: November 2021

Climate change is causing the geographical ranges of some species to track suitable conditions. Habitat specialists, range-restricted species and species with limited dispersal abilities may be unable to track changing conditions, increasing their extinction risk. In response to changing conditions and species movement patterns, there is a need to account for the effects of climate change when designing protected areas and identifying potential climate refugia. We used ecological niche models projected into future climates to identify potential impacts of climate change on the distribution of 11 rupicolous reptile species in the Soutpansberg Mountains, South Africa.Lygodactylus incognitus, Lygodactylus soutpansbergensis, Platysaurus relictusandVhembelacerta rupicolawere identified as being vulnerable to climate change due to substantial reductions in suitable habitat and low spatial overlap between current and future niche envelopes. We identified areas of high conservation importance for the persistence of these species under present-day and projected future conditions. The western Soutpansberg was identified as an area of high conservation priority as it is a potential refuge under future projections. Projecting distributions of vulnerable species into future climate predictions can guide future research and identify potential refugia that will best conserve species with restricted ranges in a world with climate change.
Extraterritoriality and Legal Belonging in the Nineteenth-Century Mediterranean
Authors: Marglin Jessica M.
Published: November 2021

This article examines the intersection between extraterritoriality--privileges afforded to European subjects in the Islamic Mediterranean--and various forms of state membership. To capture the multiplicity and instability of state membership, I introduce the phrase “legal belonging”--a neutral, umbrella term that encompasses a wide range of bonds between individuals and states (usually referred to as subjecthood, nationality, or citizenship). Adopting the methods of global legal history, I look at how laws regulating legal belonging responded to the extraterritorial context of the Mediterranean in both European and Middle Eastern states. In so doing, I offer an alternative to the centrifugal narrative of modernization, which presumes that modern citizenship was invented in Europe and then exported to the Islamic world. Instead, I contend that the evolution of legal belonging on both sides of the Mediterranean developed in response to the challenges and opportunities presented by extraterritoriality. The article consists of two cases studies: first, I look at the regulation of legal belonging in Tunisia, the Ottoman Empire, and Morocco, arguing that this legislation responded to the challenges posed by extraterritoriality. Second, I examine the influence of extraterritorial regimes on the nationality of Algerians under French colonial rule.
Negation as a predictor of clausal complement choice in World Englishes
Authors: ROMASANTA RAQUEL P.
Published: November 2021

Research on complementizer selection has shown that the presence of a negative particle in a subordinate complement clause influences complement choice, leading to a relatively higher proportion of finite complementation patterns by increasing the complexity of the syntactic environment. Studies have also shown that different types of negation, namelynot- andno-negation, increase the tendency towards more explicit complementation options (Rohdenburg 2015). The current study focuses on the effect ofnot- andno-negation on the complementation profile of the verbregret, which allows variation between finitethat/zero-complement clauses and nonfinite (S) -ingclauses. The GloWbE corpus was used to create a data set of more than 4,000 examples from 16 varieties of English. The results of the analysis support previous findings that the presence of a negative marker in the complement clause increases the preference for finite patterns, especially in L2 varieties of English. However, contrary to the expectations of this study,no-negation was found to have a stronger effect on complement choice thannot-negation.
Career Adaptability and Career Success
Authors: Krause Felix , Schmidt Sascha L. , Schreyer Dominik
Published: November 2021

Abstract. In this study, we contribute to the ongoing incremental validation efforts of the Career Adapt-Abilities Scale (CAAS). Using primary personality and cognition data from 164 German athletes in vocational careers, we intended to replicate Zacher’s (2014) seminal work in an alternative Western environment while also extending it in two significant ways: first, by adding two components of cognitive ability, and second, by introducing an alternative outcome variable – objective career success. In line with Zacher, we observe a significant role of career adaptability in predicting subjective career success. However, we also note that this initially robust relationship stems from a different psychosocial resource than expected. Interestingly, employing CAAS seems not to possess further incremental validity when predicting objective career success.
It's Only Abusive If I Care
Authors: Bormann Kai C. , Gellatly Ian R.
Published: November 2021

Abstract. Drawing on conservation of resources (COR) theory, we propose that abusive supervision increases stress responses in targets, which, in turn, diminishes their ability to perform extra- and in-role work behaviors. However, based on COR theory, we argue that followers who are driven by low rather than high organizational concern motives place less value on their work and the social context in which technical activities occur. As such, feeling low organizational concern should make people less susceptible to abusive supervision rather than more so. Thus, organizational concern was proposed to moderate the abuse–stress relationship. Across two multisource studies, we found support for most of our hypotheses. Abusive supervision negatively affected organizational citizenship behaviors via increased stress, and low organizational concern was found to attenuate the detrimental effects of abusive supervision. Implications for leadership literature and future research are discussed.
Trapping of Wind Momentum in a Salinity‐Stratified Ocean
Authors: Chaudhuri Dipanjan , Sengupta Debasis , D’Asaro Eric , Shivaprasad S.
Published: November 2021

We study the nature of ocean currents forced by summer monsoon winds in the Bay of Bengal using data from two cruises within a pool of low‐salinity (<32 psμ) river water, and one cruise outside the low‐salinity pool. Upper ocean (5–70 m) temperature, salinity, and velocity profiles were measured at sub‐kilometer horizontal resolution along the 800–1800‐km‐long cruise tracks. We find that beneath the river water, density stratification at 5–15 m depth can be 10 times stronger than typically seen in much of the subtropical or tropical ocean. The shallow salinity‐dominated stratification suppresses shear‐induced turbulence, thereby “trapping” momentum input from monsoon winds in the uppermost 20 m of the ocean. Estimates of directly wind‐forced ocean currents are consistent with Ekman depth scaling as , where N0 is stratification at the base of the mixed layer and f is Coriolis frequency. In the presence of river water, cruise‐mean wind‐forced currents resemble tightly surface trapped Ekman‐like spirals: The shallowest measured current at 5 m depth has a speed of nearly 0.2 m/s, directed 80° to the right of the wind. Outside the pool of river water, wind momentum penetrates to 40 m depth.
Impacts of Momentum Fluxes Modulated by Surface Waves on Near‐Inertial Motions in Tropical Cyclones
Authors: Zhang Lei , Liu Guoqiang , He Yijun , Perrie William
Published: November 2021

Surface waves play an essential role in modifying the momentum fluxes across the air‐sea interface, especially under tropical cyclone (TC) conditions. A coupled wave‐ocean circulation model system, taking into consideration the surface wave effects on momentum fluxes, is applied to investigate the generation of near‐inertial motions (NIMs) under TC conditions. When surface waves are ignored, large overestimates in wind power input are obtained, about 10%–40%, occurring in the right and rear TC regions. Surprisingly, the modulation effects of surface waves on the momentum fluxes have impacts on NIMs that reach depths of ∼100 m; the resulting reduction in the near‐inertial velocity can exceed 0.1 m/s (up to 35%) and the reduction in the near‐inertial energy (NIE) is up to 20%. The largest modifications to NIMs are located at two times the radius of the maximum wind speed, relative to the TC center. In the upper ocean, the mixed‐layer NIE reductions due to surface waves are greater in medium‐speed TCs (3–6 m/s) than in rapidly moving TCs, by about ∼10%, because there are more young waves around the TC centers, and better overlapping between the regions with large wind stress changes and ocean current responses. Given that these effects are notable for surface waves impacts on NIMs, and thus on the currents and the resulting thermal redistribution under TCs, the feedbacks of these modified ocean properties must affect TC evolution and should be included in coupled atmosphere‐ocean studies.
Optical meta-waveguides for integrated photonics and beyond
Authors: Meng Yuan , Chen Yizhen , Lu Longhui , Ding Yimin , Cusano Andrea , Fan Jonathan A. , Hu Qiaomu , Wang Kaiyuan , Xie Zhenwei , Liu Zhoutian , Yang Yuanmu , Liu Qiang , Gong Mali , Xiao Qirong , Sun Shulin , Zhang Minming , Yuan Xiaocong , Ni Xingjie
Published: November 2021

The growing maturity of nanofabrication has ushered massive sophisticated optical structures available on a photonic chip. The integration of subwavelength-structured metasurfaces and metamaterials on the canonical building block of optical waveguides is gradually reshaping the landscape of photonic integrated circuits, giving rise to numerous meta-waveguides with unprecedented strength in controlling guided electromagnetic waves. Here, we review recent advances in meta-structured waveguides that synergize various functional subwavelength photonic architectures with diverse waveguide platforms, such as dielectric or plasmonic waveguides and optical fibers. Foundational results and representative applications are comprehensively summarized. Brief physical models with explicit design tutorials, either physical intuition-based design methods or computer algorithms-based inverse designs, are cataloged as well. We highlight how meta-optics can infuse new degrees of freedom to waveguide-based devices and systems, by enhancing light-matter interaction strength to drastically boost device performance, or offering a versatile designer media for manipulating light in nanoscale to enable novel functionalities. We further discuss current challenges and outline emerging opportunities of this vibrant field for various applications in photonic integrated circuits, biomedical sensing, artificial intelligence and beyond.
3D spheroids of human placenta-derived mesenchymal stem cells attenuate spinal cord injury in mice
Authors: Deng Junhao , Li Miao , Meng Fanqi , Liu Zhongyang , Wang Song , Zhang Yuan , Li Ming , Li Zhirui , Zhang Licheng , Tang Peifu
Published: November 2021

Mesenchymal stem cell (MSC) is an absorbing candidate for cell therapy in treating spinal cord injury (SCI) due to its great potential for multiple cell differentiation, mighty paracrine secretion as well as vigorous immunomodulatory effect, of which are beneficial to the improvement of functional recovery post SCI. However, the therapeutic effects of MSC on SCI have been limited because of the gradual loss of MSC stemness in the process of expanding culture. Therefore, in this study, we aimed to maintain those beneficial properties of MSC via three-dimensional spheroid cell culture and then compared them with conventionally-cultured MSCs in the treatment of SCI both in vitro and in vivo with the aid of two-photon microscope. We found that 3D human placenta-derived MSCs (3D-HPMSCs) demonstrated a significant increase in secretion of anti-inflammatory factors and trophic factors like VEGF, PDGF, FGF via QPCR and Bio-Plex assays, and showed great potentials on angiogenesis and neurite morphogenesis when co-cultured with HUVECs or DRGs in vitro. After transplantation into the injured spinal cord, 3D-HPMSCs managed to survive for the entire experiment and retained their advantageous properties in secretion, and exhibited remarkable effects on neuroprotection by minimizing the lesion cavity, inhibiting the inflammation and astrogliosis, and promoting angiogenesis. Further investigation of axonal dieback via two-photon microscope indicated that 3D-HPMSCs could effectively alleviate axonal dieback post injury. Further, mice only treated with 3D-HPMSCs obtained substantial improvement of functional recovery on electrophysiology, BMS score, and Catwalk analysis. RNA sequencing suggested that the 3D-HPMSCs structure organization-related gene was significantly changed, which was likely to potentiate the angiogenesis and inflammation regulation after SCI. These results suggest that 3D-HPMSCs may hold great potential for the treatment of SCI.
Particle-like topologies in light
Authors: Sugic Danica , Droop Ramon , Otte Eileen , Ehrmanntraut Daniel , Nori Franco , Ruostekoski Janne , Denz Cornelia , Dennis Mark R.
Published: November 2021

Three-dimensional (3D) topological states resemble truly localised, particle-like objects in physical space. Among the richest such structures are 3D skyrmions and hopfions, that realise integer topological numbers in their configuration via homotopic mappings from real space to the hypersphere (sphere in 4D space) or the 2D sphere. They have received tremendous attention as exotic textures in particle physics, cosmology, superfluids, and many other systems. Here we experimentally create and measure a topological 3D skyrmionic hopfion in fully structured light. By simultaneously tailoring the polarisation and phase profile, our beam establishes the skyrmionic mapping by realising every possible optical state in the propagation volume. The resulting light field’s Stokes parameters and phase are synthesised into a Hopf fibration texture. We perform volumetric full-field reconstruction of the $${{{\Pi }}}_{{{3}}}$$

Π

3

mapping, measuring a quantised topological charge, or Skyrme number, of 0.945. Such topological state control opens avenues for 3D optical data encoding and metrology. The Hopf characterisation of the optical hypersphere endows a fresh perspective to topological optics, offering experimentally-accessible photonic analogues to the gamut of particle-like 3D topological textures, from condensed matter to high-energy physics.
The main oxidative inactivation pathway of the plant hormone auxin
Authors: Hayashi Ken-ichiro , Arai Kazushi , Aoi Yuki , Tanaka Yuka , Hira Hayao , Guo Ruipan , Hu Yun , Ge Chennan , Zhao Yunde , Kasahara Hiroyuki , Fukui Kosuke
Published: November 2021

Inactivation of the phytohormone auxin plays important roles in plant development, and several enzymes have been implicated in auxin inactivation. In this study, we show that the predominant natural auxin, indole-3-acetic acid (IAA), is mainly inactivated via the GH3-ILR1-DAO pathway. IAA is first converted to IAA-amino acid conjugates by GH3 IAA-amidosynthetases. The IAA-amino acid conjugates IAA-aspartate (IAA-Asp) and IAA-glutamate (IAA-Glu) are storage forms of IAA and can be converted back to IAA by ILR1/ILL amidohydrolases. We further show that DAO1 dioxygenase irreversibly oxidizes IAA-Asp and IAA-Glu into 2-oxindole-3-acetic acid-aspartate (oxIAA-Asp) and oxIAA-Glu, which are subsequently hydrolyzed by ILR1 to release inactive oxIAA. This work established a complete pathway for the oxidative inactivation of auxin and defines the roles played by auxin homeostasis in plant development.
A Phase I/II randomized trial of H56:IC31 vaccination and adjunctive cyclooxygenase-2-inhibitor treatment in tuberculosis patients
Authors: Jenum Synne , Tonby Kristian , Rueegg Corina S. , Rühwald Morten , Kristiansen Max P. , Bang Peter , Olsen Inge Christoffer , Sellæg Kjersti , Røstad Kjerstin , Mustafa Tehmina , Taskén Kjetil , Kvale Dag , Mortensen Rasmus , Dyrhol-Riise Anne Ma
Published: November 2021

Host-directed-therapy strategies are warranted to fight tuberculosis. Here we assess the safety and immunogenicity of adjunctive vaccination with the H56:IC31 candidate and cyclooxygenase-2-inhibitor treatment (etoricoxib) in pulmonary and extra-pulmonary tuberculosis patients in a randomized open-label phase I/II clinical trial (TBCOX2, NCT02503839). A total of 222 patients were screened, 51 enrolled and randomized; 13 in the etoricoxib-group, 14 in the H56:IC31-group, 12 in the etoricoxib+H56:IC31-group and 12 controls. Three Serious Adverse Events were reported in the etoricoxib-groups; two urticarial rash and one possible disease progression, no Serious Adverse Events were vaccine related. H56:IC31 induces robust expansion of antigen-specific T-cells analyzed by fluorospot and flow cytometry, and higher proportion of seroconversions. Etoricoxib reduced H56:IC31-induced T-cell responses. Here, we show the first clinical data that H56:IC31 vaccination is safe and immunogenic in tuberculosis patients, supporting further studies of H56:IC31 as a host-directed-therapy strategy. Although etoricoxib appears safe, our data do not support therapy with adjunctive cyclooxygenase-2-inhibitors.
Hemisphere-asymmetric tropical cyclones response to anthropogenic aerosol forcing
Authors: Cao Jian , Zhao Haikun , Wang Bin , Wu Liguang
Published: November 2021

How anthropogenic forcing could change tropical cyclones (TCs) is a keen societal concern owing to its significant socio-economic impacts. However, a global picture of the anthropogenic aerosol effect on TCs has not yet emerged. Here we show that anthropogenic aerosol emission can reduce northern hemisphere (NH) TCs but increase southern hemisphere (SH) TCs primarily through altering vertical wind shear and mid-tropospheric upward motion in the TC formation zones. These circulation changes are driven by anthropogenic aerosol-induced NH-cooler-than-SH and NH-increased versus SH-decreased meridional (equator to mid-latitudes) temperature gradients. The cooler NH produces a low-level southward cross-equatorial transport of moist static energy, weakening the NH ascent in the TC formation zones; meanwhile, the increased meridional temperature gradients strengthen vertical wind shear, reducing NH TC genesis. The opposite is true for the SH. The results may help to constrain the models’ uncertainty in the future TC projection. Reduction of anthropogenic aerosol emission may increase the NH TCs threat.
Human RIPK3 maintains MLKL in an inactive conformation prior to cell death by necroptosis
Authors: Meng Yanxiang , Davies Katherine A. , Fitzgibbon Cheree , Young Samuel N. , Garnish Sarah E. , Horne Christopher R. , Luo Cindy , Garnier Jean-Marc , Liang Lung-Yu , Cowan Angus D. , Samson Andre L. , Lessene Guillaume , Sandow Jarrod J. , Czabotar Peter E. , Murphy James M.
Published: November 2021

The ancestral origins of the lytic cell death mode, necroptosis, lie in host defense. However, the dysregulation of necroptosis in inflammatory diseases has led to widespread interest in targeting the pathway therapeutically. This mode of cell death is executed by the terminal effector, the MLKL pseudokinase, which is licensed to kill following phosphorylation by its upstream regulator, RIPK3 kinase. The precise molecular details underlying MLKL activation are still emerging and, intriguingly, appear to mechanistically-diverge between species. Here, we report the structure of the human RIPK3 kinase domain alone and in complex with the MLKL pseudokinase. These structures reveal how human RIPK3 structurally differs from its mouse counterpart, and how human RIPK3 maintains MLKL in an inactive conformation prior to induction of necroptosis. Residues within the RIPK3:MLKL C-lobe interface are crucial to complex assembly and necroptotic signaling in human cells, thereby rationalizing the strict species specificity governing RIPK3 activation of MLKL.
The diagnostic trajectory of infants and children with clinical features of genetic disease
Authors: Schroeder Brock E. , Gonzaludo Nina , Everson Katie , Than Kyi-Sin , Sullivan Jeff , Taft Ryan J. , Belmont John W.
Published: November 2021

We characterized US pediatric patients with clinical indicators of genetic diseases, focusing on the burden of disease, utilization of genetic testing, and cost of care. Curated lists of diagnosis, procedure, and billing codes were used to identify patients with clinical indicators of genetic disease in healthcare claims from Optum’s de-identified Clinformatics® Database (13,076,038 unique patients). Distinct cohorts were defined to represent permissive and conservative estimates of the number of patients. Clinical phenotypes suggestive of genetic diseases were observed in up to 9.4% of pediatric patients and up to 44.7% of critically-ill infants. Compared with controls, patients with indicators of genetic diseases had higher utilization of services (e.g., mean NICU length of stay of 31.6d in a cohort defined by multiple congenital anomalies or neurological presentations compared with 10.1d for patients in the control population (P < 0.001)) and higher overall costs. Very few patients received any genetic testing (4.2–8.4% depending on cohort criteria). These results highlight the substantial proportion of the population with clinical features associated with genetic disorders and underutilization of genetic testing in these populations.
XRCC1 protects transcription from toxic PARP1 activity during DNA base excision repair
Authors: Adamowicz Marek , Hailstone Richard , Demin Annie A. , Komulainen Emilia , Hanzlikova Hana , Brazina Jan , Gautam Amit , Wells Sophie E. , Caldecott Keith W.
Published: November 2021

Genetic defects in the repair of DNA single-strand breaks (SSBs) can result in neurological disease triggered by toxic activity of the single-strand-break sensor protein PARP1. However, the mechanism(s) by which this toxic PARP1 activity triggers cellular dysfunction are unclear. Here we show that human cells lacking XRCC1 fail to rapidly recover transcription following DNA base damage, a phenotype also observed in patient-derived fibroblasts with XRCC1 mutations and Xrcc1−/− mouse neurons. This defect is caused by excessive/aberrant PARP1 activity during DNA base excision repair, resulting from the loss of PARP1 regulation by XRCC1. We show that aberrant PARP1 activity suppresses transcriptional recovery during base excision repair by promoting excessive recruitment and activity of the ubiquitin protease USP3, which as a result reduces the level of monoubiquitinated histones important for normal transcriptional regulation. Importantly, inhibition and/or deletion of PARP1 or USP3 restores transcriptional recovery in XRCC1−/− cells, highlighting PARP1 and USP3 as possible therapeutic targets in neurological disease.
Robust IgM responses following intravenous vaccination with Bacille Calmette–Guérin associate with prevention of Mycobacterium tuberculosis infection in macaques
Authors: Irvine Edward B. , O’Neil Anthony , Darrah Patricia A. , Shin Sally , Choudhary Alok , Li Wenjun , Honnen William , Mehra Smriti , Kaushal Deepak , Gideon Hannah Priyadarshini , Flynn JoAnne L. , Roederer Mario , Seder Robert A. , Pinter Abraham , Fortune Sarah , Alter Galit
Published: November 2021

Development of an effective tuberculosis (TB) vaccine has suffered from an incomplete understanding of the correlates of protection againstMycobacterium tuberculosis(Mtb). Intravenous (i.v.) vaccination with Bacille Calmette–Guérin (BCG) provides nearly complete protection against TB in rhesus macaques, but the antibody response it elicits remains incompletely defined. Here we show that i.v. BCG drives superior antibody responses in the plasma and the lungs of rhesus macaques compared to traditional intradermal BCG administration. While i.v. BCG broadly expands antibody titers and functions, IgM titers in the plasma and lungs of immunized macaques are among the strongest markers of reduced bacterial burden. IgM was also enriched in macaques that received protective vaccination with an attenuated strain ofMtb. Finally, anMtb-specific IgM monoclonal antibody reducedMtbsurvival in vitro. Collectively, these data highlight the potential importance of IgM responses as a marker and mediator of protection against TB.
Structure of the human SAGA coactivator complex
Authors: Herbst Dominik A. , Esbin Meagan N. , Louder Robert K. , Dugast-Darzacq Claire , Dailey Gina M. , Fang Qianglin , Darzacq Xavier , Tjian Robert , Nogales Eva
Published: November 2021

The SAGA complex is a regulatory hub involved in gene regulation, chromatin modification, DNA damage repair and signaling. While structures of yeast SAGA (ySAGA) have been reported, there are noteworthy functional and compositional differences for this complex in metazoans. Here we present the cryogenic-electron microscopy (cryo-EM) structure of human SAGA (hSAGA) and show how the arrangement of distinct structural elements results in a globally divergent organization from that of yeast, with a different interface tethering the core module to the TRRAP subunit, resulting in a dramatically altered geometry of functional elements and with the integration of a metazoan-specific splicing module. Our hSAGA structure reveals the presence of an inositol hexakisphosphate (InsP6) binding site in TRRAP and an unusual property of its pseudo-(Ψ)PIKK. Finally, we map human disease mutations, thus providing the needed framework for structure-guided drug design of this important therapeutic target for human developmental diseases and cancer.
Simple yet effective methods to probe hydrogel stiffness for mechanobiology
Authors: Gandin Alessandro , Murugesan Yaswanth , Torresan Veronica , Ulliana Lorenzo , Citron Anna , Contessotto Paolo , Battilana Giusy , Panciera Tito , Ventre Maurizio , Netti A. Paolo , Nicola Lucia , Piccolo Stefano , Brusatin Giovanna
Published: November 2021

In spite of tremendous advances made in the comprehension of mechanotransduction, implementation of mechanobiology assays remains challenging for the broad community of cell biologists. Hydrogel substrates with tunable stiffness are essential tool in mechanobiology, allowing to investigate the effects of mechanical signals on cell behavior. A bottleneck that slows down the popularization of hydrogel formulations for mechanobiology is the assessment of their stiffness, typically requiring expensive and sophisticated methodologies in the domain of material science. Here we overcome such barriers offering the reader protocols to set-up and interpret two straightforward, low cost and high-throughput tools to measure hydrogel stiffness: static macroindentation and micropipette aspiration. We advanced on how to build up these tools and on the underlying theoretical modeling. Specifically, we validated our tools by comparing them with leading techniques used for measuring hydrogel stiffness (atomic force microscopy, uniaxial compression and rheometric analysis) with consistent results on PAA hydrogels or their modification. In so doing, we also took advantage of YAP/TAZ nuclear localization as biologically validated and sensitive readers of mechanosensing, all in all presenting a suite of biologically and theoretically proven protocols to be implemented in most biological laboratories to approach mechanobiology.
Mutational status of plasma exosomal KRAS predicts outcome in patients with metastatic colorectal cancer
Authors: Lucchetti Donatella , Zurlo Ina Valeria , Colella Filomena , Ricciardi-Tenore Claudio , Di Salvatore Mariantonietta , Tortora Giampaolo , De Maria Ruggero , Giuliante Felice , Cassano Alessandra , Basso Michele , Crucitti Antonio , Laurenzana Ilaria , Artemi Giulia , Sgambato Alessandro
Published: November 2021

Liquid biopsy has become a useful alternative in metastatic colorectal cancer (mCRC) patients when tissue biopsy of metastatic sites is not feasible. In this study we aimed to investigate the clinical utility of circulating exosomes DNA in the management of mCRC patients. Exosomes level and KRAS mutational status in exosomal DNA was assesed in 70 mCRC patients and 29 CRC primary tumor and were analysed at different disease steps evaluating serial blood samples (240 blood samples). There was a significant correlation between the extension of disease and exosomes level and the resection of primary localized tumor was correlated with a decrease of KRAS G12V/ D copies and fractional abundance in metastatic disease. CEA expression and liver metastasis correlated with a higher number of KRAS G12V/D copies/ml and a higher fractional abundance; in the subgroup of mCRC patients eligible for surgery, the size of tumor and the radiological response were related to exosomes level but only the size was related to the number of KRAS WT copies; both KRAS wild-type and mutated levels were identified as a prognostic factor related to OS. Finally, we found that 91% of mutated mCRC patients became wild type after the first line chemotherapy but this status reverted in mutated one at progression in 80% of cases. In a prospective cohort of mCRC patients, we show how longitudinal monitoring using exosome-based liquid biopsy provides clinical information relevant to therapeutic stratification.
Insights into the nutritional properties and microbiome diversity in sweet and sour yogurt manufactured in Bangladesh
Authors: Islam S. M. Rafiqul , Tanzina Afsana Yeasmin , Foysal Md Javed , Hoque M. Nazmul , Rumi Meheadi Hasan , Siddiki A. M. A. M. Zonaed , Tay Alfred Chin-Yen , Hossain M. Jakir , Bakar Muhammad Abu , Mostafa Mohammad , Mannan Adnan
Published: November 2021

Yogurt is one of the most frequently consumed dairy products for nutritional benefits. Although yogurt is enriched with probiotics, it is susceptible to spoilage because of the presence of pathogenic microbes. Spoiled yogurt if consumed can cause food-borne diseases. This study aimed to assess the nutritional composition and microbiome diversity in yogurt manufactured in Bangladesh. Microbial diversity was analyzed through high-throughput sequencing of bacterial 16S rRNA gene and fungal internal transcribed spacer (ITS) region. From nutritional analysis, significantly (P < 0.05) higher pH, fat, moisture, total solid and solid-non-fat contents (%) were observed in sweet yogurt. Following the classification of Illumina sequences, 84.86% and 72.14% of reads were assigned to bacterial and fungal genera, respectively, with significantly higher taxonomic richness in sour yogurt prepared from buffalo. A significant difference in bacterial (Ppermanova = 0.001) and fungal (Ppermanova = 0.013) diversity between sweet and sour yogurt was recorded. A total of 76 bacterial and 70 fungal genera were detected across these samples which were mostly represented by Firmicutes (92.89%) and Ascomycota (98%) phyla, respectively. This is the first study that accentuates nutritional profiles and microbiome diversity of Bangladeshi yogurt which are crucial in determining both active and passive health effects of yogurt consumption in individuals.