bluuebunny/crossref_metadata_2025 huggingface dataset:
Fragmented Transparency: The Visibility of Agency Science in European Union Risk Regulation
Authors: de Boer Alie , Morvillo Marta , Röttger-Wirtz Sabrina
Published: January 2023

Responding to mistrust in the European agencies’ risk assessments in politically salient cases, the European Union (EU) legislator, the European Food Safety Authority and the European Medicines Agency alike have accelerated their efforts to foster EU regulatory science transparency. These simultaneous endeavours have, however, taken place in a fragmented legislative and administrative context, with each agency operating under a different legal framework. By focusing on authorisation procedures, from registration of studies to authorisation of novel foods, pesticides and human medicines, this article examines the resulting regimes governing the disclosure of scientific data by EU agencies to identify common trends and sectoral specificities. Against the background of an overall shift towards enhanced transparency, we shed light on, first, the circulation of institutional arrangements and practices among agencies and, second, the new dimensions of transparency emerging from these developments. We also highlight the remaining sectoral differences and argue that they could have potentially large impacts on the amount and type of information disclosed and on the level of transparency perceived by stakeholders and citizens. We argue that more coherence across the sectoral transparency regimes is needed, in particular in light of the agencies’ contested legitimacy and of their increasing cooperation on cross-cutting issues like antimicrobial resistance and medicine and pesticide residues in food.
High temporal contrast 1053 nm laser source based on optical parametric amplification and second-harmonic generation
Authors: Shen Liya , Li Yanyan , Li Wenkai , Song Jiajun , Qian Junyu , Sun Jianyu , Feng Renyu , Peng Yujie , Leng Yuxin
Published: January 2023

Temporal contrast directly affects the interaction between ultraintense and ultrashort pulse lasers with matter. Seed laser sources with broad bandwidth and high temporal contrast are significant for overall temporal contrast enhancement. The technique of cascaded nonlinear processes with optical parametric amplification and second-harmonic generation is demonstrated for high temporal contrast seed source generation. Within 40 ps before the main pulse, the temporal contrast reaches over 1011. The pulse energy and duration of the high-contrast pulse are 112 μJ and 70 fs, respectively. Considering its high beam quality and stability, this laser source can serve as a high-quality seed for Nd:glass-based ultraintense and ultrashort pulse laser facilities.
As Seen from Bombay: An Iranian Zoroastrian Photo Album from the 1930s
Authors: Marashi Afshin , Patel Dinyar
Published: January 2023

This photo essay provides a visual archive of Parsi philanthropic efforts toward the Iranian Zoroastrian communities of Yazd, Kerman, and Tehran during the 1930s. The essay reproduces a collection of photographs from a photo album produced by the Iranian Zoroastrian Anjoman (est. 1918) for the benefit of Parsi audiences in Bombay. These photographs were taken and compiled by administrators of the Parsi-funded charities in order to demonstrate to Bombay-based Parsi benefactors how their charity efforts were being used inside Iran. The essay also discusses the importance of including visual archival material as part of the social and cultural history of modern Iran, as well as the unique sets of challenges that such archival preservation represents.
Special Issue: Parsis and Iranians in the Modern Period
Authors: Marashi Afshin , Patel Dinyar
Published: January 2023

A hundred years ago in colonial Bombay, on September 10, 1922, a group of Parsis established an organization called the Iran League. Meant to strengthen ties with their Iranian Zoroastrian coreligionists inside Iran, the Iran League also endeavored to recast wider economic and cultural relations between India and the country which Parsis regarded as their ancient homeland. That ancient homeland, after all, was undergoing seismic change. In the years following Reza Khan's 1921 coup and the establishment of the Pahlavi dynasty in 1925, Parsis watched with growing anticipation and excitement as Iran's new leader increasingly promoted a new national culture rooted in Iran's ancient past. Prominent Parsis, many of them leaders in the Iran League, fervently believed that Pahlavi Iran would herald all sorts of progressive change: improved conditions for the Iranian Zoroastrians, deeper appreciation of Zoroastrianism among Iran's Muslim majority, conditions for significant Parsi investment in Iran, and even the possibility of a mass Parsi “return” to the shah's domain, reversing the direction of centuries of Zoroastrian migration.1
Flow-induced surface instabilities in a flexible-walled channel with a heavy wall
Authors: Wang Danyang , Luo Xiaoyu , Liu Zishun , Stewart Peter S.
Published: January 2023

We consider the stability of laminar high-Reynolds-number flow through a planar channel formed by a rigid wall and a heavy compliant wall under longitudinal tension with motion resisted by structural damping. Numerical simulations indicate that the baseline state (with Poiseuille flow and a flat wall) exhibits two unstable normal modes: the Tollmien–Schlichting (TS) mode and a surface-based mode which manifests as one of two flow-induced surface instabilities (FISI), known as travelling wave flutter (TWF) and static divergence (SD), respectively. In the absence of wall damping the system is unstable to TWF, where the neutrally stable wavelength becomes shorter as the wall mass increases. With wall damping, TWF is restricted to long wavelengths through interaction with the most unstable centre mode, while for wall damping greater than a critical value the system exhibits an SD mode with a two branch neutral stability curve; the critical conditions along the upper and lower branches are constructed in the limit of large wall damping. We compute the Reynolds–Orr and activation energy descriptions of these neutrally stable FISI by continuing the linear stability analysis to the following order in perturbation amplitude. We find that both FISI are primarily driven by the working of normal stress on the flexible wall, lower-branch SD has negative activation energy, while upper-branch SD approaches zero activation energy in the limit of large wall damping. Finally, we elucidate interaction between TS and TWF modes for large wall mass, resulting in stable islands within unstable regions of parameter space.
High-resolution magnetochronology detects multiple stages of Pleistocene tectonic uplift and deformation in the Po Plain of northern Italy
Authors: Perini Serena , Muttoni Giovanni , Livio Franz , Zucali Michele , Michetti Alessandro M. , Zerboni Andrea
Published: January 2023

We developed a high-resolution magnetochronology of the Pleistocene stratigraphy of the Monte Netto hillock, a tectonically uplifted structure in the Po Plain of northern Italy. Our data allowed reconstructing the depositional age of the sequence and assessing rates of deformation and rock uplift of the neotectonic structure, thus providing constraints on the tectono-sedimentary evolution of this seismically active part of the buried Southern Alps. Using a combination of magnetostratigraphy and paleosecular variation analysis, we generated an age-depth model for the Monte Netto stratigraphy that encompasses, from the top, Upper Pleistocene (11–72 ka) loess-paleosols overlaying fluvial sediments spanning the Brunhes-Matuyama boundary (773 ka) and the top of the Jaramillo (990 ka). The identification of the same magneto-chronostratigraphic surfaces in nearby drill cores from regions of the Po Plain that have not been affected by neotectonic deformation allowed estimating a mean rate of tectonic uplift of the hillock relative to the neighboring plain of 11.3 ± 1.5 cm/ka, and an absolute uplift relative to sea level of ~19.3 cm/ka. Finally, our paleomagnetic analyses from the uppermost loess sequence disclosed the complexity of the tectonic evolution of the Monte Netto structure, which shows evidence of a two-phase rotational deformation linked to coseismic surface faulting due to recent seismic activity.
The transnational historiography of a dynastic transition: Writing the Ming-Qing transition in seventeenth-century China, Korea, and Japan
Authors: Tham Chui–Joe
Published: January 2023

The Ming-Qing transition (1618–1683), a dynastic upheaval that not only consumed much of China, but also saw the Qing invasion of Joseon Korea and an influx of refugees into Tokugawa Japan, was a source of inspiration for writers across East Asia. Unofficial, contemporary histories written by Ming and early Qing subjects made their way by land and sea to Korea and Japan, where they were either adapted for domestic audiences or used as the basis for new unofficial histories of the dynastic transition.

This article makes the argument that unofficial, contemporary history-writing about the Ming-Qing transition in China, Korea, and Japan was part of a regional trend towards an intellectual culture of contemporaneity. While scholars have focused on the transition and its impact upon notions of cultural centrality, it should be emphasized that these notions emerged alongside developments encouraging the production and circulation of contemporary, cross-cultural knowledge and information. In other words, the flourishing of print, diversification of reading audiences, and evolution of new modes of knowledge-production and transmission formed a background against which demand increased for updated information about a shared world. Participation as producers (writers and editors) and consumers (readers) in this seventeenth-century culture of contemporaneity was restricted by language, schooling, and economic standing. Nonetheless, a transnational history perspective will show that the unofficial, multi-vocal, and multilingual historiography of the Ming-Qing transition encourages a re-evaluation of not only the intellectual history of East Asia, but also the history of the transition.
An Eastern hero: Biographies of Muhammad in imperial Japan
Authors: Koyagi Mikiya
Published: January 2023

While participating in the discourse of world religions, Japanese biographers published accounts of Muhammad’s life in many genres of academic and popular books during the Meiji and Taisho eras (1868–1926). This article unravels how these biographical accounts played a crucial role in facilitating a geographical imaginary of Asia/the East which incorporated both Japan and West Asia. Situated in a radically different context from the Victorian biographers who inspired them, Japanese biographers constantly compared Muhammad to historical figures familiar to them, most notably Buddha and Nichiren, and reinterpreted the life of Muhammad, relying exclusively on European-language sources. In particular, in contrast to another strand of pan-Asianism that stressed peacefulness as an inherent quality of the East, the biographers identified Muhammad’s perceived militancy and the miracles he performed as signs of the values shared by Japan and Islamic civilization. Using the person of Muhammad as a concrete piece of evidence, Japanese biographers reimagined an Eastern civilizational space that could stretch from Tokyo to Mecca.
How does having a good ear promote successful second language speech acquisition in adulthood? Introducing Auditory Precision Hypothesis-L2
Authors: Saito Kazuya
Published: January 2023

In this paper, I first provide a brief review of how scholars have conceptualized, tested, and elaborated aptitude frameworks relevant to second language (L2) speech learning. Subsequently, I introduce an emerging paradigm that assigns a fundamental role to domain-general auditory processing (i.e., having a good ear) in L1 speech acquisition and proposes that the same faculty acts as a cornerstone of L2 speech learning (i.e., the Auditory Precision Hypothesis-L2). This hypothesis predicts that learners with more precise auditory processing ability will be able to make the most of every input opportunity, which will result in more advanced L2 speech proficiency. To close, I will provide suggestions on how scholars can assess L2 students’ auditory processing ability (e.g., our team's offline test deposited at L2 Speech Tools for Researchers & Teachers [http://sla-speech-tools.com/]) and discuss how the results can be used to maximize learners’ L2 speech learning opportunities via optimal, profile-matched training programs (e.g., explicit vs. incidental training; naturalistic vs. classroom learning; phonetic vs. auditory training).
Weighted synchronous automata
Authors: Gomes Leandro , Madeira Alexandre , Barbosa Luis Soares
Published: January 2023

This paper introduces a class of automata and associated languages, suitable to model a computational paradigm of fuzzy systems, in which both vagueness and simultaneity are taken as first-class citizens. This requires a weighted semantics for transitions and a precise notion of a synchronous product to enforce the simultaneous occurrence of actions. The usual relationships between automata and languages are revisited in this setting, including a specific Kleene theorem.
Euthanasia and Assisted Suicide Are Compatible with Palliative Care and Are Not Rendered Redundant by It
Authors: Riisfeldt Thomas D.
Published: January 2023

It is often argued by health professionals working within the field of palliative care that palliative care and euthanasia/assisted suicide are incompatible. Across the literature, this claim is grounded on the three claims that (1) palliative care and euthanasia/assisted suicide have different aims, (2) euthanasia/assisted suicide is at odds with the doctor’s fundamental role as a healer, and (3) euthanasia/assisted suicide constitutes patient abandonment. Furthermore, even if palliative care and euthanasia/assisted suicide are compatible, it is often argued that the availability of palliative care renders euthanasia/assisted suicide redundant. This depends on two claims that (1) palliative care is always available and effective, and (2) palliative care is always preferable to euthanasia/assisted suicide. This article argues that all of these claims are false, ultimately aiming to establish that palliative care and euthanasia/assisted suicide are complementary rather than mutually exclusive.
Slope‐Break Collisions: Comment on “Insight Into Granular Flow Dynamics Relying on Basal Stress Measurements: From Experimental Flume Tests” by K. Li et al.
Authors: Cagnoli B.
Published: January 2023

Numerical simulations show that the positive correlation observed in laboratory experiments by Li et al. (2022, https://doi.org/10.1029/2021jb022905) between an increase of grain size and particle agitation, on the one hand, and an increase of granular flow mobility, on the other hand, is not a valid cause‐and‐effect relationship. In other words, their mobility differential is not caused by a different energy dissipation rate that results from a different grain size content. Instead, the flows stop because of a head‐on collision with the horizontal flume at the bottom of a steep 40° incline. Essentially, the slope‐break jams the granular movement. Indeed, a combination of laboratory experiments and numerical simulations demonstrated that the mobility of unhindered dense granular flows increases as grain size and clast agitation decrease. Consequently, there is no evidence that the high mobility of large natural rock avalanches is due to an increase of particle agitation.
Quantifying the Aerodynamic Roughness Length of Snow Surfaces With Time‐Lapse Structure‐From‐Motion
Authors: Liu Junfeng , Chen Rensheng , Ma Shaoxiu , Guo Shuhai , Han Chuntan , Ding Yongjian
Published: January 2023

The aerodynamic roughness length (z0m) of snow surfaces plays an essential role in estimating turbulent fluxes of latent and sensible heat (LE and H). Constant z0m has been widely used in previous studies due to the difficulty in monitoring dynamic z0m. This leads to large uncertainties in simulating LE and H fluxes. In the current study we used a time‐lapse structure‐from‐motion (SfM) photogrammetric method to study temporal variation in z0m of snow surfaces. The study site was located at the edge of the August‐one ice cap in the Qilian Mountains of China. The study ran from August 2019 to September 2020. We measured aerodynamic roughness length over time (z0m_t) using SfM‐based micro‐topographic methods and validated our results by comparing z0m_t with z0m_prof (profile‐based) and z0m_EC (EC‐based) data. The validated dynamic z0m_t was then used to estimate LE and H fluxes using a bulk aerodynamic method. These results were then compared with LE and H measured by eddy covariance (EC) and with manual sublimation/condensation measurements to indirectly validate z0m_t. We found that z0m_t overall agreed with profile‐based z0m_prof and EC‐based z0m_EC. Indeed, our estimates of bulk LE and H fluxes using dynamic z0m_t agreed slightly better with EC and manual sublimation/condensation measurements than did static EC‐based z0m_EC. Micro‐topographic z0m_t can be helpful in precisely estimating varying LE and H fluxes over the course of a year.
What Happens to Drugs After They Leave Your Body?
Authors: Sidik Saima
Published: January 2023

It’s hard to predict with certainty how drugs break down once they enter waterways. In a new study, scientists devised a way to do just that.
The practices and beliefs of dental professionals regarding the management of patients taking anticoagulant and antiplatelet drugs
Authors: Kelly Niamh , Beaton Laura , Knights Jennifer , Stirling Douglas , West Michele , Young Linda
Published: January 2023

Aim

This study aimed to inform the implementation of the updated Scottish Dental Clinical Effectiveness Programme (SDCEP) guidance, ‘Management of Dental Patients taking Anticoagulant or Antiplatelet Drugs’, and to determine training needs by investigating dental professionals’ current practice and beliefs regarding management of patients taking these medications.

Methods

Dental professionals were recruited via the NHS Education for Scotland Portal. The online questionnaire collected demographic information, data on current practice and information about beliefs regarding behaviours related to the management of patients on anticoagulant or antiplatelet medication. Quantitative data were analysed using SPSS and subjected to frequency calculations, t-tests, one-way ANOVA and linear regression. Qualitative data were collected via free text boxes and analysed using thematic analysis.

Results

One hundred and fifty-seven participants responded to the questionnaire. The majority of respondents stated they were aware of the guidance and always based their practice on it. The majority of respondents always assessed the patient’s individual bleeding risk prior to dental procedures. Most respondents felt that they did not know how to appropriately manage patients taking low doses of low molecular weight heparins (LMWH), and only 38% of respondents always followed SDCEP guidance about direct oral anticoagulants (DOAC) medication and procedures with a low associated risk of bleeding.

Discussion

This study demonstrates a need for further educational support surrounding LMWHs and management of patients on DOAC medication. Time and remuneration represent barriers to guidance implementation in primary care.

Conclusion

There is good awareness and adherence to the guidance in primary care settings, however training needs were identified to support implementation.
Verteporfin reverses progestin resistance through YAP/TAZ-PI3K-Akt pathway in endometrial carcinoma
Authors: Wei Lina , Ma Xiaohong , Hou Yixin , Zhao Tianyi , Sun Rui , Qiu Chunping , Liu Yao , Qiu Ziyi , Liu Zhiming , Jiang Jie
Published: January 2023

Progestin resistance is a problem for patients with endometrial carcinoma (EC) who require conservative treatment with progestin, and its underlying mechanisms remain unclear. YAP and TAZ (YAP/TAZ), downstream transcription coactivators of Hippo pathway, promote viability, metastasis and also drug resistance of malignant tumors. According to our microarray analysis, YAP/TAZ were upregulated in progestin resistant IshikawaPR cell versus progestin sensitive Ishikawa cell, which implied that YAP/TAZ may be a vital promotor of resistance to progestin. We found YAP/TAZ had higher expression levels among the resistant tissues than sensitive tissues. In addition, knocking down YAP/TAZ decreased cell viability, inhibited cell migration and invasion and increased the sensitivity of IshikawaPR cell to progestin. On the contrary, overexpression of YAP/TAZ increased cell proliferation, metastasis and promoted progestin resistance. We also confirmed YAP/TAZ were involved in progestin resistant process by regulating PI3K-Akt pathway. Furthermore, Verteporfin as an inhibitor of YAP/TAZ could increase sensitivity of IshikawaPR cells to progestin in vivo and in vitro. Our study for the first time indicated that YAP/TAZ play an important role in progestin resistance by regulating PI3K-Akt pathway in EC, which may provide ideas for clinical targeted therapy of progestin resistance.
Transcriptomic analyses of patient peripheral blood with hemoglobin depletion reveal glioblastoma biomarkers
Authors: Qi Dan , Geng Yiqun , Cardenas Jacob , Gu Jinghua , Yi S. Stephen , Huang Jason H. , Fonkem Ekokobe , Wu Erxi
Published: January 2023

Peripheral blood is gaining prominence as a noninvasive alternative to tissue biopsy to develop biomarkers for glioblastoma (GBM); however, widely utilized blood-based biomarkers in clinical settings have not yet been identified due to the lack of a robust detection approach. Here, we describe the application of globin reduction in RNA sequencing of whole blood (i.e., WBGR) and perform transcriptomic analysis to identify GBM-associated transcriptomic changes. By using WBGR, we improved the detection sensitivity of informatic reads and identified differential gene expression in GBM blood. By analyzing tumor tissues, we identified transcriptomic traits of GBM blood. Further functional enrichment analyses retained the most changed genes in GBM. Subsequent validation elicited a 10-gene panel covering mRNA, long noncoding RNA, and microRNA (i.e., GBM-Dx panel) that has translational potential to aid in the early detection or clinical management of GBM. Here, we report an integrated approach, WBGR, with comprehensive analytic capacity for blood-based marker identification.
Soft wearable flexible bioelectronics integrated with an ankle-foot exoskeleton for estimation of metabolic costs and physical effort
Authors: Kim Jihoon , Kantharaju Prakyath , Yi Hoon , Jacobson Michael , Jeong Hyungkeun , Kim Hojoong , Lee Jinwoo , Matthews Jared , Zavanelli Nathan , Kim Hyeonseok , Jeong Heejin , Kim Myunghee , Yeo Woon-Hong
Published: January 2023

Activities and physical effort have been commonly estimated using a metabolic rate through indirect calorimetry to capture breath information. The physical effort represents the work hardness used to optimize wearable robotic systems. Thus, personalization and rapid optimization of the effort are critical. Although respirometry is the gold standard for estimating metabolic costs, this method requires a heavy, bulky, and rigid system, limiting the system’s field deployability. Here, this paper reports a soft, flexible bioelectronic system that integrates a wearable ankle-foot exoskeleton, used to estimate metabolic costs and physical effort, demonstrating the potential for real-time wearable robot adjustments based on biofeedback. Data from a set of activities, including walking, running, and squatting with the biopatch and exoskeleton, determines the relationship between metabolic costs and heart rate variability root mean square of successive differences (HRV-RMSSD) (R = −0.758). Collectively, the exoskeleton-integrated wearable system shows potential to develop a field-deployable exoskeleton platform that can measure wireless real-time physiological signals.
Excessive daytime sleepiness in a model of Parkinson’s disease improved by low-frequency stimulation of the pedunculopontine nucleus
Authors: Davin Aurélie , Chabardès Stéphan , Devergnas Annaelle , Benstaali Caroline , Gutekunst Claire-Anne N. , David Olivier , Torres-Martinez Napoléon , Piallat Brigitte
Published: January 2023

Patients with Parkinson’s disease often complain of excessive daytime sleepiness which negatively impacts their quality of life. The pedunculopontine nucleus, proposed as a target for deep brain stimulation to improve freezing of gait in Parkinson’s disease, is also known to play a key role in the arousal system. Thus, the putative control of excessive daytime sleepiness by pedunculopontine nucleus area stimulation merits exploration for treating Parkinson’s disease patients. To this end, two adult nonhuman primates (macaca fascicularis) received a deep brain stimulation electrode implanted into the pedunculopontine nucleus area along with a polysomnographic equipment. Stimulation at low frequencies and high frequencies was studied, in healthy and then MPTP-treated nonhuman primates. Here, we observed that MPTP-treated nonhuman primates suffered from excessive daytime sleepiness and that low-frequency stimulation of the pedunculopontine nucleus area was effective in reducing daytime sleepiness. Indeed, low-frequency stimulation of the pedunculopontine nucleus area induced a significant increase in sleep onset latency, longer continuous periods of wakefulness and thus, a partially restored daytime wake architecture. These findings may contribute to the development of new therapeutic strategies in patients suffering from excessive daytime sleepiness.
Attosecond field emission
Authors: Kim H. Y. , Garg M. , Mandal S. , Seiffert L. , Fennel T. , Goulielmakis E.
Published: January 2023

Field emission of electrons underlies great advances in science and technology, ranging from signal processing at ever higher frequencies1 to imaging of the atomic-scale structure of matter2 with picometre resolution. The advancing of electron microscopy techniques to enable the complete visualization of matter on the native spatial (picometre) and temporal (attosecond) scales of electron dynamics calls for techniques that can confine and examine the field emission on sub-femtosecond time intervals. Intense laser pulses have paved the way to this end3,4 by demonstrating femtosecond confinement5,6 and sub-optical cycle control7,8 of the optical field emission9 from nanostructured metals. Yet the measurement of attosecond electron pulses has remained elusive. We used intense, sub-cycle light transients to induce optical field emission of electron pulses from tungsten nanotips and a weak replica of the same transient to directly investigate the emission dynamics in real time. Access to the temporal properties of the electron pulses rescattering off the tip surface, including the duration τ = (53 as ± 5 as) and chirp, and the direct exploration of nanoscale near fields open new prospects for research and applications at the interface of attosecond physics and nano-optics.
Annelid functional genomics reveal the origins of bilaterian life cycles
Authors: Martín-Zamora Francisco M. , Liang Yan , Guynes Kero , Carrillo-Baltodano Allan M. , Davies Billie E. , Donnellan Rory D. , Tan Yongkai , Moggioli Giacomo , Seudre Océane , Tran Martin , Mortimer Kate , Luscombe Nicholas M. , Hejnol Andreas , Marlétaz Ferdinand , Martín-Durán José M.
Published: January 2023

Indirect development with an intermediate larva exists in all major animal lineages1, which makes larvae central to most scenarios of animal evolution2–11. Yet how larvae evolved remains disputed. Here we show that temporal shifts (that is, heterochronies) in trunk formation underpin the diversification of larvae and bilaterian life cycles. We performed chromosome-scale genome sequencing in the annelid Owenia fusiformis with transcriptomic and epigenomic profiling during the life cycles of this and two other annelids. We found that trunk development is deferred to pre-metamorphic stages in the feeding larva of O. fusiformis but starts after gastrulation in the non-feeding larva with gradual metamorphosis of Capitella teleta and the direct developing embryo of Dimorphilus gyrociliatus. Accordingly, the embryos of O. fusiformis develop first into an enlarged anterior domain that forms larval tissues and the adult head12. Notably, this also occurs in the so-called ‘head larvae’ of other bilaterians13–17, with which the O. fusiformis larva shows extensive transcriptomic similarities. Together, our findings suggest that the temporal decoupling of head and trunk formation, as maximally observed in head larvae, facilitated larval evolution in Bilateria. This diverges from prevailing scenarios that propose either co-option9,10 or innovation11 of gene regulatory programmes to explain larva and adult origins.
Insulin-regulated serine and lipid metabolism drive peripheral neuropathy
Authors: Handzlik Michal K. , Gengatharan Jivani M. , Frizzi Katie E. , McGregor Grace H. , Martino Cameron , Rahman Gibraan , Gonzalez Antonio , Moreno Ana M. , Green Courtney R. , Guernsey Lucie S. , Lin Terry , Tseng Patrick , Ideguchi Yoichiro , Fallon Regis J. , Chaix Amandine , Panda Satchidananda , Mali Prashant , Wallace Martina , Knight Rob , Gantner Marin L. , Calcutt Nigel A. , Metallo Christian M.
Published: January 2023

Diabetes represents a spectrum of disease in which metabolic dysfunction damages multiple organ systems including liver, kidneys and peripheral nerves1,2. Although the onset and progression of these co-morbidities are linked with insulin resistance, hyperglycaemia and dyslipidaemia3–7, aberrant non-essential amino acid (NEAA) metabolism also contributes to the pathogenesis of diabetes8–10. Serine and glycine are closely related NEAAs whose levels are consistently reduced in patients with metabolic syndrome10–14, but the mechanistic drivers and downstream consequences of this metabotype remain unclear. Low systemic serine and glycine are also emerging as a hallmark of macular and peripheral nerve disorders, correlating with impaired visual acuity and peripheral neuropathy15,16. Here we demonstrate that aberrant serine homeostasis drives serine and glycine deficiencies in diabetic mice, which can be diagnosed with a serine tolerance test that quantifies serine uptake and disposal. Mimicking these metabolic alterations in young mice by dietary serine or glycine restriction together with high fat intake markedly accelerates the onset of small fibre neuropathy while reducing adiposity. Normalization of serine by dietary supplementation and mitigation of dyslipidaemia with myriocin both alleviate neuropathy in diabetic mice, linking serine-associated peripheral neuropathy to sphingolipid metabolism. These findings identify systemic serine deficiency and dyslipidaemia as novel risk factors for peripheral neuropathy that may be exploited therapeutically.
Triassic stem caecilian supports dissorophoid origin of living amphibians
Authors: Kligman Ben T. , Gee Bryan M. , Marsh Adam D. , Nesbitt Sterling J. , Smith Matthew E. , Parker William G. , Stocker Michelle R.
Published: January 2023

Living amphibians (Lissamphibia) include frogs and salamanders (Batrachia) and the limbless worm-like caecilians (Gymnophiona). The estimated Palaeozoic era gymnophionan–batrachian molecular divergence1 suggests a major gap in the record of crown lissamphibians prior to their earliest fossil occurrences in the Triassic period2–6. Recent studies find a monophyletic Batrachia within dissorophoid temnospondyls7–10, but the absence of pre-Jurassic period caecilian fossils11,12 has made their relationships to batrachians and affinities to Palaeozoic tetrapods controversial1,8,13,14. Here we report the geologically oldest stem caecilian—a crown lissamphibian from the Late Triassic epoch of Arizona, USA—extending the caecilian record by around 35 million years. These fossils illuminate the tempo and mode of early caecilian morphological and functional evolution, demonstrating a delayed acquisition of musculoskeletal features associated with fossoriality in living caecilians, including the dual jaw closure mechanism15,16, reduced orbits17 and the tentacular organ18. The provenance of these fossils suggests a Pangaean equatorial origin for caecilians, implying that living caecilian biogeography reflects conserved aspects of caecilian function and physiology19, in combination with vicariance patterns driven by plate tectonics20. These fossils reveal a combination of features that is unique to caecilians alongside features that are shared with batrachian and dissorophoid temnospondyls, providing new and compelling evidence supporting a single origin of living amphibians within dissorophoid temnospondyls.
Structure of the lysosomal mTORC1–TFEB–Rag–Ragulator megacomplex
Authors: Cui Zhicheng , Napolitano Gennaro , de Araujo Mariana E. G. , Esposito Alessandra , Monfregola Jlenia , Huber Lukas A. , Ballabio Andrea , Hurley James H.
Published: January 2023

The transcription factor TFEB is a master regulator of lysosomal biogenesis and autophagy1. The phosphorylation of TFEB by the mechanistic target of rapamycin complex 1 (mTORC1)2–5is unique in its mTORC1 substrate recruitment mechanism, which is strictly dependent on the amino acid-mediated activation of the RagC GTPase activating protein FLCN6,7. TFEB lacks the TOR signalling motif responsible for the recruitment of other mTORC1 substrates. We used cryogenic-electron microscopy to determine the structure of TFEB as presented to mTORC1 for phosphorylation, which we refer to as the ‘megacomplex’. Two full Rag–Ragulator complexes present each molecule of TFEB to the mTOR active site. One Rag–Ragulator complex is bound to Raptor in the canonical mode seen previously in the absence of TFEB. A second Rag–Ragulator complex (non-canonical) docks onto the first through a RagC GDP-dependent contact with the second Ragulator complex. The non-canonical Rag dimer binds the first helix of TFEB with a RagCGDP-dependent aspartate clamp in the cleft between the Rag G domains. In cellulo mutation of the clamp drives TFEB constitutively into the nucleus while having no effect on mTORC1 localization. The remainder of the 108-amino acid TFEB docking domain winds around Raptor and then back to RagA. The double use of RagC GDP contacts in both Rag dimers explains the strong dependence of TFEB phosphorylation on FLCN and the RagC GDP state.
Fine-resolution global maps of root biomass carbon colonized by arbuscular and ectomycorrhizal fungi
Authors: Barceló Milagros , van Bodegom Peter M. , Soudzilovskaia Nadejda A.
Published: January 2023

Despite the recognized importance of mycorrhizal associations in ecosystem functioning, the actual abundance patterns of mycorrhizal fungi belowground are still unknown. This information is key for better quantification of mycorrhizal impacts on ecosystem processes and for incorporating mycorrhizal pathways into global biogeochemical models. Here we present the first high-resolution maps of fine root stocks colonized by arbuscular mycorrhizal (AM) and ectomycorrhizal (EcM) fungi (MgC ha−1). The maps were assembled by combining multiple open-source databases holding information on root biomass carbon, the proportion of AM and EcM tree biomass, plot-level relative abundance of plant species and intensity of AM and EcM root colonization. We calculated root-associated AM and EcM abundance in 881 spatial units, defined as the combination of ecoregions and land cover types across six continents. The highest AM abundances are observed in the (sub-)tropics, while the highest EcM abundances occur in the taiga regions. These maps serve as a basis for future research where continuous spatial estimates of root mycorrhizal stocks are needed.
Network pharmacology and experimental validation to identify the potential mechanism of Hedyotis diffusa Willd against rheumatoid arthritis
Authors: Deng Hui , Jiang Jing , Zhang Sisi , Wu Lijuan , Zhang Qinglian , Sun Wenkui
Published: January 2023

Rheumatoid arthritis (RA) is a chronic, systemic, autoimmune disease that may lead to joint damage, deformity, and disability, if not treated effectively. Hedyotis diffusa Willd (HDW) and its main components have been widely used to treat a variety of tumors and inflammatory diseases. The present study utilized a network pharmacology approach, microarray data analysis and molecular docking to predict the key active ingredients and mechanisms of HDW against RA. Eleven active ingredients in HDW and 180 potential anti-RA targets were identified. The ingredients-targets-RA network showed that stigmasterol, beta-sitosterol, quercetin, kaempferol, and 2-methoxy-3-methyl-9,10-anthraquinone were key components for RA treatment. KEGG pathway results revealed that the 180 potential targets were inflammatory-related pathways with predominant enrichment of the AGE-RAGE, TNF, IL17, and PI3K-Akt signaling pathways. Screened through the PPI network and with Cytoscape software, RELA, TNF, IL6, TP53, MAPK1, AKT1, IL10, and ESR1 were identified as the hub targets in the HDW for RA treatment. Molecular docking was used to identify the binding of 5 key components and the 8 related-RA hub targets. Moreover, the results of network pharmacology were verified by vitro experiments. HDW inhibits cell proliferation in MH7A cells in a dose and time-dependent manner. RT-qPCR and WB results suggest that HDW may affect hub targets through PI3K/AKT signaling pathway, thereby exerting anti-RA effect. This study provides evidence for a clinical effect of HDW on RA and a research basis for further investigation into the active ingredients and mechanisms of HDW against RA.
Direct cell extraction of membrane proteins for structure–function analysis
Authors: Drulyte Ieva , Gutgsell Aspen Rene , Lloris-Garcerá Pilar , Liss Michael , Geschwindner Stefan , Radjainia Mazdak , Frauenfeld Jens , Löving Robin
Published: January 2023

Membrane proteins are the largest group of therapeutic targets in a variety of disease areas and yet, they remain particularly difficult to investigate. We have developed a novel one-step approach for the incorporation of membrane proteins directly from cells into lipid Salipro nanoparticles. Here, with the pannexin1 channel as a case study, we demonstrate the applicability of this method for structure–function analysis using SPR and cryo-EM.
Comparison of blood gas parameters, ions, and glucose concentration in polish Holstein-Friesian Dairy cows at different milk production levels
Authors: Pawliński Bartosz , Gołębiewski Marcin , Trela Michał , Witkowska-Piłaszewicz Olga
Published: January 2023

Genetic selection for increased milk yield has been a key driver of dairy intensification. The modern dairy cow produces much higher amounts of milk than the cattle of several years ago, and this may have an influence on hematologic values at different stages of lactation and on cows with different levels of milk production. The purpose of the study was to investigate the variations in blood parameters such as Ht, tHb, sO2, FO2Hb, FCOHb, FMetHb, FHHb, pH, pCO2, pO2, standard HCO3−, actual HCO3−, BE, BE ecf, ctCO2, BO2, p50, and ctO2in cows at different milk production levels. In addition, ions such as Na+, K+ , Ca++, Ca++ (7.4), and Cl−, and AnGap and glucose were examined. Our findings indicated that differences in the examined blood parameters between low and high-production dairy cattle do exist. The most apparent differences were connected with blood pH (p < 0.01), oxygen metabolism (Ht, tHb, sO2, FO2Hb;p < 0.01), and glucose utilization (p < 0.01) The results confirm that the parameters connected with blood oxygen metabolism and glucose metabolism increase significantly in high-production animals. In conclusion, reference values should be considered in light of the lactation stage and level of milk production, because these might influence how changes should be interpreted. The main limitation of the study is the delay to analysis. However, the blood was properly stored (4C), thus changes were delayed. Anyway, it is very hard in the field practice to perform it within 5 min after the blood collection and according to studies it has low impact on clinical outcomes.
Linear indium atom chains at graphene edges
Authors: Elibol Kenan , Susi Toma , Mangler Clemens , Eder Dominik , Meyer Jannik C. , Kotakoski Jani , Hobbs Richard G. , van Aken Peter A. , Bayer Bernhard C.
Published: January 2023

The presence of metal atoms at the edges of graphene nanoribbons (GNRs) opens new possibilities toward tailoring their physical properties. We present here formation and high-resolution characterization of indium (In) chains on the edges of graphene-supported GNRs. The GNRs are formed when adsorbed hydrocarbon contamination crystallizes via laser heating into small ribbon-like patches of a second graphitic layer on a continuous graphene monolayer and onto which In is subsequently physical vapor deposited. Using aberration-corrected scanning transmission electron microscopy (STEM), we find that this leads to the preferential decoration of the edges of the overlying GNRs with multiple In atoms along their graphitic edges. Electron-beam irradiation during STEM induces migration of In atoms along the edges of the GNRs and triggers the formation of longer In atom chains during imaging. Density functional theory (DFT) calculations of GNRs similar to our experimentally observed structures indicate that both bare zigzag (ZZ) GNRs as well as In-terminated ZZ-GNRs have metallic character, whereas in contrast, In termination induces metallicity for otherwise semiconducting armchair (AC) GNRs. Our findings provide insights into the creation and properties of long linear metal atom chains at graphitic edges.
Intersecting distributed networks support convergent linguistic functioning across different languages in bilinguals
Authors: Geng Shujie , Guo Wanwan , Rolls Edmund T. , Xu Kunyu , Jia Tianye , Zhou Wei , Blakemore Colin , Tan Li-Hai , Cao Miao , Feng Jianfeng
Published: January 2023

How bilingual brains accomplish the processing of more than one language has been widely investigated by neuroimaging studies. The assimilation-accommodation hypothesis holds that both the same brain neural networks supporting the native language and additional new neural networks are utilized to implement second language processing. However, whether and how this hypothesis applies at the finer-grained levels of both brain anatomical organization and linguistic functions remains unknown. To address this issue, we scanned Chinese-English bilinguals during an implicit reading task involving Chinese words, English words and Chinese pinyin. We observed broad brain cortical regions wherein interdigitated distributed neural populations supported the same cognitive components of different languages. Although spatially separate, regions including the opercular and triangular parts of the inferior frontal gyrus, temporal pole, superior and middle temporal gyrus, precentral gyrus and supplementary motor areas were found to perform the same linguistic functions across languages, indicating regional-level functional assimilation supported by voxel-wise anatomical accommodation. Taken together, the findings not only verify the functional independence of neural representations of different languages, but show co-representation organization of both languages in most language regions, revealing linguistic-feature specific accommodation and assimilation between first and second languages.
Rare earth upconversion luminescent composite based on energy transfer for specific and sensitive detection of cysteine
Authors: Zhu Yulian , Guo Xiaomei , Ma Xiao , Liu Kai , Han Yuting , Wu Yongquan , Li Xun
Published: January 2023

A rare-earth upconversion nanoprobe for highly sensitive detection of cysteine in vitro and in vivo.
A pyridine-based conjugated imprinted polymer as an adsorptive photocatalyst for efficient removal of aqueous Cr(vi)
Authors: Guo Zhipeng , Wei Wei , Li Yihang , Li Jin , Zhang Xiaoke , Hou Fengming , Wei Ang
Published: January 2023

A designed pyridine-based ion-imprinted polymer was constructed by introducing 4-vinylpyridine via an in situ copolymerization reaction, which exhibited impressive Cr(vi) adsorption performance and high efficiency for photocatalytic Cr(vi) reduction.
Wireless electrochemical actuation of soft materials towards chiral stimuli
Authors: Arnaboldi Serena
Published: January 2023

The synergy between wireless unconventional actuation and chiral stimuli can be used as a straightforward read out of chiral information.
Emergence of Linnett's “double quartets” from a model of “Lewis dots”
Authors: Herzfeld Judith
Published: January 2023

In a semiclassical model of electrons, attention to the physical origins of the spin dependence of electron–electron interactions illuminates limitations on electron pairing in diamagnetic molecules.
Phase transition-induced initial decomposition of nitrogen-rich binary CN compound 2,2′-azobis(5-azidotetrazole) and its precursor 2-amino-5-azidotetrazole via tetrazole ring opening under external electric fields: a comparative DFT-D study
Authors: Wu Xiaowei , Li Yunqiu , Xu Jianhua , Dong Wenshuai , Zhang Jian-Guo
Published: January 2023

External electric field induced phase transition of 2,2′-azobis(5-azidotetrazole) and its precursor 2-amino-5-azidotetrazole.
Switchable metallacycles and metallacages
Authors: Lin Hong-Yu , Wang Yu-Te , Shi Xueliang , Yang Hai-Bo , Xu Lin
Published: January 2023

This review mainly summarizes the recent development of switchable metallacycles and metallacages, their molecular design, switching behaviours and corresponding mechanisms are highlighted.
Highly efficient GeSe micro-air-brick-based thin film standalone solar water-splitting photoelectrode with solar-light-soaking accumulation process
Authors: Wang Kang , Ni Huanyang , Zhao Weidong , Wu Xiaomin , Hu Yucheng , Xiao Guohong , Jiang Feng
Published: January 2023

The GeSe-TEG integrated photoelectrode presented a remarkable and record STH efficiency of over 13.5% after a brief solar-light-soaking accumulation process for solar energy storage and conversion.
Particulate matter and ultrafine particles in urban air pollution and their effect on the nervous system
Authors: Flood-Garibay Jessica Andrea , Angulo-Molina Aracely , Méndez-Rojas Miguel Ángel
Published: January 2023

Pollutant particulate matter and ultrafine particles have been related to the rise of neurodegenerative diseases and other brain disorders. It is necessary to understand their potential health impacts in order to develop strategies to reduce risks.
Durability studies of underwater superoleophobic graphene oxide coated wire mesh
Authors: Saikiran Pichkari , Dhole Mayuri , Bhandaru Nandini
Published: January 2023

GO-coated brass mesh with good underwater superoleophobicity was fabricated with multiple dip coating and plasma treatment steps. A long-term immersion study in acidic, basic, and neutral media reveals the superior durability of the treated meshes.
Transverse magnetoconductance in two-terminal chiral spin-selective devices
Authors: Hossain Md Anik , Illescas-Lopez Sara , Nair Rahul , Cuerva Juan Manuel , Álvarez de Cienfuegos Luis , Pramanik Sandipan
Published: January 2023

In the transverse CISS measurement geometry, the magnetization is normal to the current. Transverse spin polarization has been found, even in the absence of electromagnetochiral effects. The CISS signal also satisfies Onsager's reciprocity.
Boosted photocatalytic performance on molecule/semiconductor hybrid materials: conversion of sunlight energy into hydrogen fuel
Authors: Xu Baotong , Li Xiangyang , Yang Ru , Yao Wei , Gao Enjun , Fedin Vladimir P.
Published: January 2023

Efficient charge transfer between a molecule and semiconductor based on grafting of a weak amide linkage facilitated the overall reaction kinetics.
Hierarchical self-assembly of a radical naphthalenediimide-based N-heterocyclic carbene-Au(i) macrocycle
Authors: Wang Chong , Zhu Qing-Wen , Yu Jian-Gang , Li Xin , Li Hao , Sun Li-Ying , Han Ying-Feng
Published: January 2023

A series of tertiary supramolecular architectures were constructed based on an NDI-derived NHC-Au(i) macrocycle that exhibited redox-switchable properties in a one-electron redox process.