bluuebunny/crossref_metadata_2025 huggingface dataset:
Maternal fish consumption and child neurodevelopment in Nutrition 1 Cohort: Seychelles Child Development Study
Authors: Conway Marie C. , Yeates Alison J. , Love Tanzy M. , Weller Daniel , McSorley Emeir M. , Mulhern Maria S. , Wesolowska Maria , Watson Gene E. , Myers Gary J. , Shamlaye Conrad F. , Henderson Juliette , Davidson Philip W. , van Wijngaarden Edwin , Strain J. J.
Published: February 2023

Maternal fish consumption exposes the fetus to beneficial nutrients and potentially adverse neurotoxicants. The current study investigated associations between maternal fish consumption and child neurodevelopmental outcomes. Maternal fish consumption was assessed in the Seychelles Child Development Study Nutrition Cohort 1 (n 229) using 4-day food diaries. Neurodevelopment was evaluated at 9 and 30 months, and 5 and 9 years with test batteries assessing twenty-six endpoints and covering multiple neurodevelopmental domains. Analyses used multiple linear regression with adjustment for covariates known to influence child neurodevelopment. This cohort consumed an average of 8 fish meals/week and the total fish intake during pregnancy was 106·8 (sd 61·9) g/d. Among the twenty-six endpoints evaluated in the primary analysis there was one beneficial association. Children whose mothers consumed larger quantities of fish performed marginally better on the Kaufman Brief Intelligence Test (a test of nonverbal intelligence) at age 5 years (β 0·003, 95 % CI (0, 0·005)). A secondary analysis dividing fish consumption into tertiles found no significant associations when comparing the highest and lowest consumption groups. In this cohort, where fish consumption is substantially higher than current global recommendations, maternal fish consumption during pregnancy was not beneficially or adversely associated with children’s neurodevelopmental outcomes.
Business Accounting at Fengshengtai in Late Imperial China: Is There New Evidence of Double-Entry Bookkeeping?
Authors: Lowenstein Matthew , Cao Shuji
Published: February 2023

This article analyzes the accounting treatment of sales and purchasing at the Fengshengtai Company (丰盛泰号), a salt trader from Shanxi Province. We find evidence of “dualled entry” bookkeeping in that all transactions were recorded twice. Crucially, each set of dualled entries was recorded in two distinct accounts. For example, cash transactions were recorded in a “cash flowing account” as well as a specialized flowing account. We thus argue that, in light of clues from other records, a system of indigenous Chinese double-entry bookkeeping may well have been developed at Fengshengtai and other Shanxi merchants. Our study is based on Fengshengtai's surviving account books, a collection of primary sources spanning 1854 to 1881, that have recently become available to scholars.
Hydroclimatic conditions and sediment provenance in the northeastern Arabian Sea since the late Miocene: insights from geochemical and environmental magnetic records at IODP Site U1457 of the Laxmi Basin
Authors: Alam Mahboob , Muguli Tripti , Gurumurthy G.P. , Arif Mohammad , Sohrin Yoshiki , Singh Arun Deo , Radhakrishna T. , Pandey Dhananjai Kumar , Verma Komal
Published: February 2023

Palaeo-monsoon and palaeoclimate conditions over Southeast Asia are a matter of debate despite notable studies on the continental and oceanic sedimentary record. The present study investigates the environmental magnetic and geochemical records preserved in the deep marine sediments of the northeastern (NE) Arabian Sea to elucidate the erosion history of the western Himalayas and its link with the prevailing hydroclimatic conditions since the late Miocene. For this, the sediment core retrieved during International Ocean Discovery Program (IODP) Expedition 355 at Site U1457 in the NE Arabian Sea has been explored. The results reveal that the hydroclimatic conditions were predominantly arid during the late Miocene, except for humid intervals from 6.1 Ma to 5.6 Ma. Humid climate conditions in the Indus River Basin returned during the mid-Pliocene and continued to the Pleistocene with an intense chemical weathering regime from 1.9 Ma to 1.2 Ma. The dominant sediment source to the NE Arabian Sea at Site U1457 during the late Miocene and the Pliocene was the Indus River, while during the Pleistocene, mixed sediments brought by the Indus River and the Peninsular Indian rivers were observed. The sediment contribution from a chemically less altered mafic source (the Deccan basalts) increased between 1.2 Ma and 0.2 Ma, possibly linked to a weak Indian Summer Monsoon. The summer monsoon wind strength and associated shift in the Inter-Tropical Convergence Zone (ITCZ) influenced the dominant sediment provenance at Site U1457 of the Laxmi Basin.
A problematic taxonomy ofBathophilus(Stomiidae) collected from the Arabian Sea
Authors: Rajakrishnan Rajeev , Rajeeshkumar Meleppura , Saravanane Narayanane
Published: February 2023

The number of rays in pectoral and pelvic fins are the major diagnostic character for species discrimination in the genusBathophilus. However, all of the five species ofBathophiluswe studied showed considerable differences from the existing counts in the number of rays in pectoral and pelvic fins, which has made species identification and interrelations doubtful. We believe taxonomy focusing on the number of rays in the pelvic and pectoral fin alone does not fully discriminate species. At present, the importance of other characters has to be validated for correct species identification. We also report the first record ofBathophilus proximusfrom the Indian Ocean and additional new records ofBathophilus cwyanorum,Bathophilus altipinnisandBathophilus digitatusfrom the Arabian Sea.
Protected areas, Indigenous rights and land restitution: the Ogiek judgment of the African Court of Human and Peoples’ Rights and community land protection in Kenya
Authors: Claridge Lucy , Kobei Daniel
Published: February 2023

In May 2017, the relationship between conservation and human and Indigenous peoples' rights was considered for the first time by the African Court of Human and Peoples' Rights. In a case brought by the Indigenous Ogiek of Kenya, the Court stated that the preservation of the Mau Forest could not justify the lack of recognition of the Indigenous status of the Ogiek, nor the denial of the rights associated with that status. It also confirmed that the Ogiek could not be held responsible for the depletion of the Mau Forest, and that preservation of the ecosystem could not justify their eviction from or the denial of access to their land. Although Kenyan institutions have still failed to remedy Ogiek rights, the Ogiek have identified a pathway for the Kenyan Government to follow to restitute Ogiek land, following principles of conservation and symbolizing the central role that Indigenous forest dwellers can and should play in forest management. They sought a further ruling from the Court to clarify the steps the Government should take. In June 2022, the Court issued a judgment ordering the Government to grant the Ogiek collective title of their lands through a process of delimitation and demarcation. In the meantime, the Ogiek have established community forest scouts in East Mau to replant native trees and protect the forest from illegal logging. In addition, they have developed an Ogiek community Bio-Cultural Protocol. Here we examine the feasibility of restituting Ogiek land both legally and practically. We conclude with some general comments related to global conservation policy and practice on the restitution of lands and support for Indigenous conservation practices, where protected areas have caused displacement and rights abuses of Indigenous peoples.
Current status of cystic echinococcosis control in the Falkland Islands: has elimination been achieved?
Authors: West D. , Pointing S. , Randhawa H. S. , Mastin A. , Rogan M. T.
Published: February 2023

Attempts to control cystic echinococcosis (CE) caused by Echinococcus granulosus in the Falkland Islands have been ongoing for over 50 years. No human cases have been recorded since the 1980s but there is a need to establish if the parasite has been completely eliminated from domestic animals. A study was carried out in 2018/2019 to identify dogs infected with E. granulosus using copro-antigen and copro-polymerase chain reaction (PCR) analysis. In addition, annual slaughter data were analysed to establish infection levels of E. granulosus and 2 other taeniid parasites. Results showed that 4 out of 589 dogs (0.7%) tested positive by copro-antigen analysis. Results from similar surveys carried out in 2010, 2012 and 2014 showed 17 (3%), 0 and 6 (1%) copro-antigen-positive dogs, respectively, with 8 dogs being confirmed by PCR in 2010. Annual abattoir data showed that from 2006 to 2020, 36 sheep were identified with E. granulosus (mean 0.0055%), 14 186 sheep with Taenia hydatigena (mean 2.2%) and 465 with Taenia ovis (mean 0.072%). Prevalences of T. hydatigena and T. ovis showed spontaneous rises in certain years where the infections could also be detected in lambs indicating that viable taeniid eggs were present. Observations of farm management procedures indicated that there were occasions when dogs could get access to infective taeniid material. In conclusion, E. granulosus is still present in sheep and dogs but at low prevalences. The increasing presence of T. hydatigena however, indicates that control measures are defective in some areas and there is potential for a re-emergence of CE.
A metaphysics of spiritual experience
Authors: Ellis Fiona
Published: February 2023

A discussion of the metaphysics of spiritual experience requires that we are clear about the nature of metaphysics, and I take as my starting point the ‘transcendent metaphysics’ described and supposedly eliminated by A. J. Ayer. Most analytic philosophers agree with Ayer (and Kant) that transcendent metaphysics in the relevant sense is deeply problematic, and they associate it with platonism, theism, and religious thinking more generally. Assuming then that spiritual experience takes us into religious territory, and this territory is forbidden, a metaphysics of spiritual experience is going to involve transcendent metaphysics, and it will be similarly problematic. Ayer's conception of transcendent reality is itself deeply problematic, and I shall argue that his metaphysical framework helps to motivate atheistic spirituality by ruling out the possibility of an empirically grounded and hence defensible religious alternative. I shall challenge this framework, set out an alternative with the help of Arthur Schopenhauer, and spell out the implications for a metaphysics of spiritual experience.
The Comedy of Crowds: Aristophanes and the Voice of the People—or the Poet
Authors: Saxonhouse Arlene W.
Published: February 2023

Aristophanes in his comedy theAcharnianseducates the crowd that he creates as a character on stage, as well as the crowd gathered to watch his comedy, about what is truly in their interest: the peace that allows them to be happy by satisfying their longings for good food and frequent sex. I suggest, invoking the medieval language ofvox populi vox dei, that Aristophanes (like the politicians and demagogues of today) competes to become the one who gives the people their voice. His comedy imagines that both the crowd in the play and the audience in the theater learn through the action of the comedy the value of peace for private happiness. The crowd so educated will give voice to Aristophanes's wisdom when they vote in their democratic assemblies about what seems best to the people.
Design of motor cable artificial muscle (MC-AM) with tendon sheath–pulley system (TSPS) for musculoskeletal robot
Authors: Yuan Jianbo , Fan Yerui , Wu Yaxiong
Published: February 2023

In an unstructured environment, the arm can perform complicated tasks with rapidity, flexibility, and robustness. It is difficult to configure multiple artificial muscles similar to an arm in the compact space of a robotic arm. When muscle tension is transferred, mechanisms like tendon-sheath/tendon-pulley may be installed in a compact space to develop musculoskeletal robots that are closer to the arm. However, handling variable frictional nonlinearity and elastic cable deformation is necessary for transmission stability. In this study, the modular artificial muscle system (MAMS), including motor cable artificial muscle and tendon sheath–pulley system (TSPS), that can be installed remotely and transmit muscle tension in narrow paths, is designed. The feed-forward multi-layer neural network (FF-MNN) approach is utilized to discuss the relationship between the measurable input tension of TSPS and the unmeasurable output tension and cable elongation. Subsequently, the lightweight musculoskeletal arm (LM-Arm) is built to verify the validity of MAMS. Through trials, the experiments of MAMS after friction compensating and the LM-Arm’s end-point 3D trajectory tracking are investigated. The results show that average errors of the active and passive muscles tension are 3.87 N and 3.51 N, respectively, under conditions of larger load and higher contraction velocity. The average muscle length error of trajectory tracking is 0.00078 m (0.72%). The suggested MAMS may successfully build a musculoskeletal robot that has similar flexibility and morphology to the arm. It can also be utilized to power various pieces of machinery, such as rescue robot, invasive surgical robots, dexterous hands, and wearable exoskeletons.
Feasibility, reliability, and validity of ambulatory cognitive tests in fibromyalgia and matched controls
Authors: Valentine Thomas R. , Kratz Anna L.
Published: February 2023

Objective:

This observational study examined the feasibility, reliability, and validity of repeated ambulatory cognitive tests in fibromyalgia (FM).

Method:

Adults with FM (n = 50) and matched controls (n = 50) completed lab-based neuropsychological tests (NIH Toolbox) followed by eight days of smartphone-based ambulatory testing of processing speed (symbol search) and working memory (dot memory) five times daily. Feasibility was assessed based on response rates. Reliability was evaluated using overall average between-person reliabilities for the full assessment period and by determining the number of assessment days necessary to attain reliabilities of >.80 and >.90. To assess convergent validity, correlations were calculated between ambulatory test scores and NIH Toolbox scores. Test performance was contrasted between the FM and non-FM groups to examine known-groups validity.

Results:

Average rates of response to the ambulatory cognitive tests were 89.5% in FM and 90.0% in non-FM. Overall average between-person reliabilities were ≥.96. In FM, between-person reliability exceeded .90 after two days for symbol search and three days for dot memory. Symbol search scores correlated with NIH Toolbox processing speed scores in both groups, though there were no significant group differences in symbol search performance. Dot memory scores correlated with NIH Toolbox working memory scores in both groups. FM participants exhibited worse dot memory performance than did non-FM participants.

Conclusions:

Repeated ambulatory tests of processing speed and working memory demonstrate feasibility and reliability in FM, though evidence for construct validity is mixed. The findings demonstrate promise for future research and clinical applications of this approach to assessing cognition in FM.
Historical trends in reporting effect sizes in clinical neuropsychology journals: A call to venture beyond the results section
Authors: Woods Steven Paul , Mustafa Andrea , Beltran-Najera Ilex , Matchanova Anastasia , Thompson Jennifer L. , Ridgely Natalie C.
Published: February 2023

Objective:

For decades, quantitative psychologists have recommended that authors report effect sizes to convey the magnitude and potential clinical relevance of statistical associations. However, fewer than one-third of neuropsychology articles published in the early 2000s reported effect sizes. This study re-examines the frequency and extent of effect size reporting in neuropsychology journal articles by manuscript section and over time.

Methods:

A sample of 326 empirical articles were drawn from 36 randomly selected issues of six neuropsychology journals at 5-year intervals between 1995 and 2020. Four raters used a novel, reliable coding system to quantify the extent to which effect sizes were included in the major sections of all 326 articles.

Results:

Findings showed medium-to-large increases in effect size reporting in the Methods and Results sections of neuropsychology journal articles that plateaued in recent years; however, there were only very small and nonsignificant changes in effect size reporting in the Abstract, Introduction, and Discussion sections.

Conclusions:

Authors in neuropsychology journals have markedly improved their effect size reporting in the core Methods and Results sections, but are still unlikely to consider these valuable metrics when motivating their study hypotheses and interpreting the conceptual and clinical implications of their findings. Recommendations are provided to encourage more widespread integration of effect sizes in neuropsychological research.
A detailed insight of 2 × 2 high isolation wideband dual notched band MIMO antenna with evolution initiated by theory of characteristics mode
Authors: Sharma Manish , Addepalli Tathababu , Manda Rajasekhar , Vidyavathi T. , Kapula Prabhakara Rao
Published: February 2023

This research investigates the MIMO antenna by using the Theory of Characteristics Mode (TCM) where 10 modes are subjected in designing. Also, 5 modes are the significant mode and 2 modes correspond to non-significant which defines the operating bandwidth and notched bands. The proposed 2 × 2 MIMO antenna configuration is designed for wideband applications with a size of 0.44 × 0.68 mm2. The two isolated 12-sided polygons radiating patches placed adjacent to each other share a common ground which is printed on an FR4 substrate. The measured impedance bandwidth covers bandwidth 3.11–11.98 GHz with two bands rejecting capability: Wireless Local Area Network (WLAN) and Downlink-Uplink Satellite (DUS) system. These two interfering bands are mitigated by etching a C-type slot on the radiating patch and an inverted U-type slot in the microstrip feed. The simulated and measured results are also compared in the far-field region (Normalized Radiation Efficiency (NRE), Peak Gain (PG), and 2-D/3-D radiation pattern). Proposed MIMO antenna also offers good diversity performance with ECC2×2 < 0.00001, DG2×2 > 9.999 dB, TARC2×2 < −15.0 dB, CCL2×2 < 0.001 b/s/Hz and MEG2×2 ≅ −3.0 dB.
The regulation of crimes against water in armed conflicts and other situations of violence
Authors: Tignino Mara
Published: February 2023

Water is the lifeblood of human beings and society, but threats to water, such as the pollution of rivers, cyber crimes, and attacks against water infrastructure, are increasing. In green criminology, scholars have relied on domestic criminal law to develop the concept of crimes against water. This paper argues that international law could provide several frameworks for addressing these crimes. A number of international treaties and customary rules deal directly or indirectly with crimes against water, and the United Nations Security Council has also dealt with crimes against water committed by terrorist groups and parties to armed conflict. Crimes against water may represent violations not only of domestic criminal laws but also of international humanitarian law and human rights law.
Tectonic Rotation Pattern at the Northern End of the Red River Fault System in SE Tibet: New Paleomagnetic Evidence From Cretaceous Red Beds
Authors: Wang Heng , Yang Zhen‐Yu , Liu‐Zeng Jing , Tong Ya‐Bo , Jing Xian‐Qing
Published: February 2023

In order to study the rotations of crustal material along the boundary faults in the southeastern Tibetan Plateau, and to better understand the tectonic evolution of this region, in this study we conducted a paleomagnetic study of Cretaceous red beds in the Binchuan and Xiangyun sections near the Chenghai‐Binchuan fault, a branch fault at the northern end of the Red River fault in China. Analyses of rock magnetic properties and magnetization components, combined with scanning electron microscopy, show that two types of hematite are present in the Lower Cretaceous rocks: pigmentary hematite and specularite. High‐temperature components (HTCs) were isolated by stepwise thermal demagnetization between 300 and 660°C carried by pigmentary hematite and all of the HTCs are of normal polarity. An additional magnetization component carried by specular hematite cannot be isolated efficiently. Progressive unfolding of both the Binchuan and Xiangyun sections shows that the best grouping of the precision parameter was obtained at 75%–80% untilting, indicating that the remanence of syn‐folding origin is carried by pigmentary hematite. These syn‐folding remanent magnetizations indicate the Binchuan and Xiangyun sections accumulated 20.5 ± 5.3° of clockwise rotation and 9.9 ± 4.6° of counterclockwise rotation, respectively, with respect to East Asia since the early Cretaceous, despite the two sections being only ∼45 km apart. The counterclockwise rotation of the Xiangyun section was likely caused by the left‐lateral shear motion of the Red River Fault; and since the Miocene, the Binchuan section experienced integral clockwise rotations, together with most parts of the Chuan‐Dian Block.
Characterizing Hydrogen Storage Potential in U.S. Underground Gas Storage Facilities
Authors: Lackey Greg , Freeman Gerad M. , Buscheck Thomas A. , Haeri Foad , White Joshua A. , Huerta Nicolas , Goodman Angela
Published: February 2023

Underground hydrogen storage is a long‐duration energy storage option for a low‐carbon economy. Although research into the technical feasibility of underground hydrogen storage is ongoing, existing underground gas storage (UGS) facilities are appealing candidates for the technology because of their ability to store and deliver natural gas. We estimate that UGS facilities in the United States (U.S.) can store 327 TWh (9.8 MMT) of pure hydrogen. A complete transition to hydrogen storage would reduce the collective working‐gas energy of UGS facilities by ∼75%; however, most (73.2%) UGS facilities could maintain current energy demand using a 20% hydrogen‐natural gas blend. U.S. UGS facilities can buffer 23.9%–44.6% of the high and low hydrogen demand projected for 2050, respectively, which exceeds the current percentage of natural gas demand buffered by storage. Thus, transitioning UGS infrastructure to hydrogen could substantially reduce the number of new hydrogen storage facilities needed to support a hydrogen economy.
TRAF4-mediated ubiquitination-dependent activation of JNK/Bcl-xL drives radioresistance
Authors: Dong Xin , Li Xiaoying , Gan Yu , Ding Jie , Wei Baojun , Zhou Li , Cui Wei , Li Wei
Published: February 2023

The E3 ligase TNF receptor-associated factor 4 (TRAF4) is upregulated and closely associated with tumorigenesis and the progression of multiple human malignancies. However, its effect on radiosensitivity in colorectal cancer (CRC) has not been elucidated. The present study found that TRAF4 was significantly increased in CRC clinical tumor samples. Depletion of TRAF4 impaired the malignant phenotype of CRC cells and sensitized irradiation-induced cell death. Irradiation activated the c-Jun N-terminal kinases (JNKs)/c-Jun signaling via increasing JNKs K63-linked ubiquitination and phosphorylation. Furthermore, c-Jun activation triggered the transcription of the antiapoptotic protein Bcl-xL, thus contributing to the radioresistance of CRC cells. TRAF4 was positively correlated with c-Jun and Bcl-xL, and blocking TRAF4 or inhibiting Bcl-xL with inhibitor markedly promoted ionizing radiation (IR)-induced intrinsic apoptosis and sensitized CRC cells to radiotherapy in vitro and in vivo. Our findings illustrate a potential mechanism of radioresistance, emphasizing the clinical value of targeting the TRAF4/Bcl-xL axis in CRC therapy.
Forecasting individual progression trajectories in Alzheimer’s disease
Authors: Maheux Etienne , Koval Igor , Ortholand Juliette , Birkenbihl Colin , Archetti Damiano , Bouteloup Vincent , Epelbaum Stéphane , Dufouil Carole , Hofmann-Apitius Martin , Durrleman Stanley
Published: February 2023

The anticipation of progression of Alzheimer’s disease (AD) is crucial for evaluations of secondary prevention measures thought to modify the disease trajectory. However, it is difficult to forecast the natural progression of AD, notably because several functions decline at different ages and different rates in different patients. We evaluate here AD Course Map, a statistical model predicting the progression of neuropsychological assessments and imaging biomarkers for a patient from current medical and radiological data at early disease stages. We tested the method on more than 96,000 cases, with a pool of more than 4,600 patients from four continents. We measured the accuracy of the method for selecting participants displaying a progression of clinical endpoints during a hypothetical trial. We show that enriching the population with the predicted progressors decreases the required sample size by 38% to 50%, depending on trial duration, outcome, and targeted disease stage, from asymptomatic individuals at risk of AD to subjects with early and mild AD. We show that the method introduces no biases regarding sex or geographic locations and is robust to missing data. It performs best at the earliest stages of disease and is therefore highly suitable for use in prevention trials.
Ferroelectric nematic liquids with conics
Authors: Kumari Priyanka , Basnet Bijaya , Wang Hao , Lavrentovich Oleg D.
Published: February 2023

Spontaneous electric polarization of solid ferroelectrics follows aligning directions of crystallographic axes. Domains of differently oriented polarization are separated by domain walls (DWs), which are predominantly flat and run along directions dictated by the bulk translational order and the sample surfaces. Here we explore DWs in a ferroelectric nematic (NF) liquid crystal, which is a fluid with polar long-range orientational order but no crystallographic axes nor facets. We demonstrate that DWs in the absence of bulk and surface aligning axes are shaped as conic sections. The conics bisect the angle between two neighboring polarization fields to avoid electric charges. The remarkable bisecting properties of conic sections, known for millennia, play a central role as intrinsic features of liquid ferroelectrics. The findings could be helpful in designing patterns of electric polarization and space charge.
Light-driven biological actuators to probe the rheology of 3D microtissues
Authors: Méry Adrien , Ruppel Artur , Revilloud Jean , Balland Martial , Cappello Giovanni , Boudou Thomas
Published: February 2023

The mechanical properties of biological tissues are key to their physical integrity and function. Although external loading or biochemical treatments allow the estimation of these properties globally, it remains difficult to assess how such external stimuli compare with cell-generated contractions. Here we engineer microtissues composed of optogenetically-modified fibroblasts encapsulated within collagen. Using light to control the activity of RhoA, a major regulator of cellular contractility, we induce local contractions within microtissues, while monitoring microtissue stress and strain. We investigate the regulation of these local contractions and their spatio-temporal distribution. We demonstrate the potential of our technique for quantifying tissue elasticity and strain propagation, before examining the possibility of using light to create and map local anisotropies in mechanically heterogeneous microtissues. Altogether, our results open an avenue to guide the formation of tissues while non-destructively charting their rheology in real time, using their own constituting cells as internal actuators.
Loss of phosphatase CTDNEP1 potentiates aggressive medulloblastoma by triggering MYC amplification and genomic instability
Authors: Luo Zaili , Xin Dazhuan , Liao Yunfei , Berry Kalen , Ogurek Sean , Zhang Feng , Zhang Liguo , Zhao Chuntao , Rao Rohit , Dong Xinran , Li Hao , Yu Jianzhong , Lin Yifeng , Huang Guoying , Xu Lingli , Xin Mei , Nishinakamura Ryuichi , Yu Jiyang , Kool Marcel , Pfister Stefan M. , Roussel Martine F. , Zhou Wenhao , Weiss William A. , Andreassen Paul , Lu Q. Richard
Published: February 2023

MYC-driven medulloblastomas are highly aggressive childhood brain tumors, however, the molecular and genetic events triggering MYC amplification and malignant transformation remain elusive. Here we report that mutations in CTDNEP1, a CTD nuclear-envelope-phosphatase, are the most significantly enriched recurrent alterations in MYC-driven medulloblastomas, and define high-risk subsets with poorer prognosis. Ctdnep1 ablation promotes the transformation of murine cerebellar progenitors into Myc-amplified medulloblastomas, resembling their human counterparts. CTDNEP1 deficiency stabilizes and activates MYC activity by elevating MYC serine-62 phosphorylation, and triggers chromosomal instability to induce p53 loss and Myc amplifications. Further, phosphoproteomics reveals that CTDNEP1 post-translationally modulates the activities of key regulators for chromosome segregation and mitotic checkpoint regulators including topoisomerase TOP2A and checkpoint kinase CHEK1. Co-targeting MYC and CHEK1 activities synergistically inhibits CTDNEP1-deficient MYC-amplified tumor growth and prolongs animal survival. Together, our studies demonstrate that CTDNEP1 is a tumor suppressor in highly aggressive MYC-driven medulloblastomas by controlling MYC activity and mitotic fidelity, pointing to a CTDNEP1-dependent targetable therapeutic vulnerability.
Strong charge carrier scattering at grain boundaries of PbTe caused by the collapse of metavalent bonding
Authors: Wu Riga , Yu Yuan , Jia Shuo , Zhou Chongjian , Cojocaru-Mirédin Oana , Wuttig Matthias
Published: February 2023

Grain boundaries (GBs) play a significant role in controlling the transport of mass, heat and charge. To unravel the mechanisms underpinning the charge carrier scattering at GBs, correlative microscopy combined with local transport measurements is realized. For the PbTe material, the strength of carrier scattering at GBs depends on its misorientation angle. A concomitant change in the barrier height is observed, significantly increasing from low- to high-angle GBs. Atom probe tomography measurements reveal a disruption of metavalent bonding (MVB) at the dislocation cores of low-angle GBs, as evidenced by the abrupt change in bond-rupture behavior. In contrast, MVB is completely destroyed at high-angle GBs, presumably due to the increased Peierls distortion. The collapse of MVB is accompanied by a breakdown of the dielectric screening, which explains the enlarged GB barrier height. These findings correlate charge carrier scattering with bonding locally, promising new avenues for the design of advanced functional materials.
Hedgehog is relayed through dynamic heparan sulfate interactions to shape its gradient
Authors: Gude Fabian , Froese Jurij , Manikowski Dominique , Di Iorio Daniele , Grad Jean-Noël , Wegner Seraphine , Hoffmann Daniel , Kennedy Melissa , Richter Ralf P. , Steffes Georg , Grobe Kay
Published: February 2023

Cellular differentiation is directly determined by concentration gradients of morphogens. As a central model for gradient formation during development, Hedgehog (Hh) morphogens spread away from their source to direct growth and pattern formation in Drosophila wing and eye discs. What is not known is how extracellular Hh spread is achieved and how it translates into precise gradients. Here we show that two separate binding areas located on opposite sides of the Hh molecule can interact directly and simultaneously with two heparan sulfate (HS) chains to temporarily cross-link the chains. Mutated Hh lacking one fully functional binding site still binds HS but shows reduced HS cross-linking. This, in turn, impairs Hhs ability to switch between both chains in vitro and results in striking Hh gradient hypomorphs in vivo. The speed and propensity of direct Hh switching between HS therefore shapes the Hh gradient, revealing a scalable design principle in morphogen-patterned tissues.
Wireless, multimodal sensors for continuous measurement of pressure, temperature, and hydration of patients in wheelchair
Authors: Cho Seokjoo , Han Hyeonseok , Park Hyunwoo , Lee Sung-Uk , Kim Jae-Hwan , Jeon Sung Woo , Wang Mengqiu , Avila Raudel , Xi Zhaoqian , Ko Kabseok , Park Minsu , Lee Jungyup , Choi Myungwoo , Lee Je-Sang , Min Weon Gi , Lee Byeong-Ju , Lee Soyeong , Choi Jungrak , Gu Jimin , Park Jaeho , Kim Min Seong , Ahn Junseong , Gul Osman , Han Chankyu , Lee Gihun , Kim Seunghwan , Kim Kyuyoung , Kim Jeonghyun , Kang Chang-Mo , Koo Jahyun , Kwak Sung Soo , Kim Sungbong , Choi Dong Yun , Jeon Seokwoo , Sung Hyung Jin , Park Yong Bae , Je Minkyu , Cho Young Tae , Oh Yong Suk , Park Inkyu
Published: February 2023

Individuals who are unable to walk independently spend most of the day in a wheelchair. This population is at high risk for developing pressure injuries caused by sitting. However, early diagnosis and prevention of these injuries still remain challenging. Herein, we introduce battery-free, wireless, multimodal sensors and a movable system for continuous measurement of pressure, temperature, and hydration at skin interfaces. The device design includes a crack-activated pressure sensor with nanoscale encapsulations for enhanced sensitivity, a temperature sensor for measuring skin temperature, and a galvanic skin response sensor for measuring skin hydration levels. The movable system enables power harvesting, and data communication to multiple wireless devices mounted at skin-cushion interfaces of wheelchair users over full body coverage. Experimental evaluations and numerical simulations of the devices, together with clinical trials for wheelchair patients, demonstrate the feasibility and stability of the sensor system for preventing pressure injuries caused by sitting.
Generation of a high yield vaccine backbone for influenza B virus in embryonated chicken eggs
Authors: Aslam Sadaf , Rajendran Madhusudan , Kriti Divya , Kurland Andrew , Johnson Jeffrey , van Bakel Harm , Krammer Florian , García-Sastre Adolfo , Ayllon Juan
Published: February 2023

Influenza B virus (IBV) strains are one of the components of seasonal influenza vaccines in both trivalent and quadrivalent formulations. The vast majority of these vaccines are produced in embryonated chickens’ eggs. While optimized backbones for vaccine production in eggs exist and are in use for influenza A viruses, no such backbones exist for IBVs, resulting in unpredictable production yields. To generate an optimal vaccine seed virus backbone, we have compiled a panel of 71 IBV strains from 1940 to present day, representing the known temporal and genetic variability of IBV circulating in humans. This panel contains strains from the B/Victoria/2/87-like lineage, B/Yamagata/16/88-like lineage and the ancestral lineage that preceded their split to provide a diverse set that would help to identify a suitable backbone which can be used in combination with hemagglutinin (HA) and neuraminidase (NA) glycoproteins from any IBV strain to be incorporated into the seasonal vaccine. We have characterized and ranked the growth profiles of the 71 IBV strains and the best performing strains were used for co-infection of eggs, followed by serial passaging to select for high-growth reassortant viruses. After serial passaging, we selected 10 clonal isolates based on their growth profiles assessed by hemagglutination and plaque-forming units. We then generated reverse genetics systems for the three clones that performed best in growth curves. The selected backbones were then used to generate different reassortant viruses with HA/NA combinations from high and low titer yielding wild type IBV. When the growth profiles of the recombinant reassortant viruses were tested, the low titer yielding HA/NA viruses with the selected backbones yielded higher titers similar to those from high titer yielding HA/NA combinations. The use of these IBV backbones with improved replication in eggs might increase yields for the influenza B virus components of seasonal influenza virus vaccines.
Characterization of antibiotic resistomes by reprogrammed bacteriophage-enabled functional metagenomics in clinical strains
Authors: Apjok Gábor , Számel Mónika , Christodoulou Chryso , Seregi Viktória , Vásárhelyi Bálint Márk , Stirling Tamás , Eszenyi Bálint , Sári Tóbiás , Vidovics Fanni , Nagrand Erika , Kovács Dorina , Szili Petra , Lantos Ildikó Ilona , Méhi Orsolya , Jangir Pramod K. , Herczeg Róbert , Gálik Bence , Urbán Péter , Gyenesei Attila , Draskovits Gábor , Nyerges Ákos , Fekete Gergely , Bodai László , Zsindely Nóra , Dénes Béla , Yosef Ido , Qimron Udi , Papp Balázs , Pál Csaba , Kintses Bálint
Published: February 2023

Functional metagenomics is a powerful experimental tool to identify antibiotic resistance genes (ARGs) in the environment, but the range of suitable host bacterial species is limited. This limitation affects both the scope of the identified ARGs and the interpretation of their clinical relevance. Here we present a functional metagenomics pipeline called Reprogrammed Bacteriophage Particle Assisted Multi-species Functional Metagenomics (DEEPMINE). This approach combines and improves the use of T7 bacteriophage with exchanged tail fibres and targeted mutagenesis to expand phage host-specificity and efficiency for functional metagenomics. These modified phage particles were used to introduce large metagenomic plasmid libraries into clinically relevant bacterial pathogens. By screening for ARGs in soil and gut microbiomes and clinical genomes against 13 antibiotics, we demonstrate that this approach substantially expands the list of identified ARGs. Many ARGs have species-specific effects on resistance; they provide a high level of resistance in one bacterial species but yield very limited resistance in a related species. Finally, we identified mobile ARGs against antibiotics that are currently under clinical development or have recently been approved. Overall, DEEPMINE expands the functional metagenomics toolbox for studying microbial communities.
Imaging ferroelectric domains with a single-spin scanning quantum sensor
Authors: Huxter William S. , Sarott Martin F. , Trassin Morgan , Degen Christian L.
Published: February 2023

The ability to sensitively image electric fields is important for understanding many nanoelectronic phenomena, including charge accumulation at surfaces1 and interfaces2 and field distributions in active electronic devices3. A particularly exciting application is the visualization of domain patterns in ferroelectric and nanoferroic materials4,5, owing to their potential in computing and data storage6–8. Here, we use a scanning nitrogen-vacancy (NV) microscope, well known for its use in magnetometry9, to image domain patterns in piezoelectric (Pb[Zr0.2Ti0.8]O3) and improper ferroelectric (YMnO3) materials through their electric fields. Electric field detection is enabled by measuring the Stark shift of the NV spin10,11 using a gradiometric detection scheme12. Analysis of the electric field maps allows us to discriminate between different types of surface charge distributions, as well as to reconstruct maps of the three-dimensional electric field vector and charge density. The ability to measure both stray electric and magnetic fields9,13 under ambient conditions opens opportunities for the study of multiferroic and multifunctional materials and devices8,14.
Freezing-induced wetting transitions on superhydrophobic surfaces
Authors: Lambley Henry , Graeber Gustav , Vogt Raphael , Gaugler Leon C. , Baumann Enea , Schutzius Thomas M. , Poulikakos Dimos
Published: February 2023

Supercooled droplet freezing on surfaces occurs frequently in nature and industry, often adversely affecting the efficiency and reliability of technological processes. The ability of superhydrophobic surfaces to rapidly shed water and reduce ice adhesion make them promising candidates for resistance to icing. However, the effect of supercooled droplet freezing—with its inherent rapid local heating and explosive vaporization—on the evolution of droplet–substrate interactions, and the resulting implications for the design of icephobic surfaces, are little explored. Here we investigate the freezing of supercooled droplets resting on engineered textured surfaces. On the basis of investigations in which freezing is induced by evacuation of the atmosphere, we determine the surface properties required to promote ice self-expulsion and, simultaneously, identify two mechanisms through which repellency falters. We elucidate these outcomes by balancing (anti-)wetting surface forces with those triggered by recalescent freezing phenomena and demonstrate rationally designed textures to promote ice expulsion. Finally, we consider the complementary case of freezing at atmospheric pressure and subzero temperature, where we observe bottom-up ice suffusion within the surface texture. We then assemble a rational framework for the phenomenology of ice adhesion of supercooled droplets throughout freezing, informing ice-repellent surface design across the phase diagram.
Physical properties of computationally informed phyto-engineered 2-D nanoscaled hydronium jarosite
Authors: Botha N. L. , Cloete K. J. , Welegergs G. G. , Akbari M. , Morad R. , Kotsedi L. , Matinise N. , Bucher R. , Azizi S. , Maaza M.
Published: February 2023

This study describes a molecular dynamics computational modelling informed bioengineering of nano-scaled 2-D hydronium jarosite. More specifically, a phyto-engineering approach using green nano-chemistry and agro-waste in the form of avocado seed natural extract was utilized as a green, economic, and eco-friendly approach to synthesize this unique mineral at the nanoscale via the reduction of iron (II) sulphate heptahydrate. The nanoproduct which was found to exhibit a quasi-2D structure was characterized using a multi-technique approach to describe its morphological, optical, electrochemical, and magnetic properties. Radial distribution function and electrostatic potential maps revealed that flavone, a phenolic compound within the avocado seed natural extract, has a higher affinity of interaction with the nanoparticle's surface, whilst vanillic acid has a higher wetting tendency and thus a lower affinity for interacting with the hydronium jarosite nanoparticle surface compared to other phytoactive compounds. XRD and HRTEM results indicated that the nanoscale product was representative of crystalline rhombohedral hydronium jarosite in the form of quasi-triangular nanosheets decorated on the edges with nanoparticles of approximately 5.4 nm diameter that exhibited significant electrochemical and electroconductive behaviours. Magnetic studies further showed a diamagnetic behaviour based on the relationship of the inverse susceptibility of the nanomaterial with temperature sweep.
Identifying links between monsoon variability and rice production in India through machine learning
Authors: Bowden Christopher , Foster Timothy , Parkes Ben
Published: February 2023

Climate change poses a major threat to global food security. Agricultural systems that rely on monsoon rainfall are especially vulnerable to changes in climate variability. This paper uses machine learning to deepen understanding of how monsoon variability impacts agricultural productivity. We demonstrate that random forest modelling is effective in representing rice production variability in response to monsoon weather variability. Our random forest modelling found monsoon weather predictors explain similar levels of detrended anomaly variation in both rice yield (33%) and area harvested (35%). The role of weather in explaining harvested rice area highlights that production area changes are an important pathway through which weather extremes impact agricultural productivity, which may exacerbate losses that occur through changes in per-area yields. We find that downwelling shortwave radiation flux is the most important weather variable in explaining variation in yield anomalies, with proportion of area under irrigation being the most important predictor overall. Machine learning modelling is capable of representing crop-climate variability in monsoonal agriculture and reveals additional information compared to traditional parametric models. For example, non-linear yield and area responses of irrigation, monsoon onset and season length all match biophysical expectations. Overall, we find that random forest modelling can reveal complex non-linearities and interactions between climate and rice production variability.
Comprehensive analysis of the correlation of the pan-cancer gene HAUS5 with prognosis and immune infiltration in liver cancer
Authors: Zhang Wenbing , Yang Chi , Hu Yan , Yi Ke , Xiao Wangwen , Xu Xiaohui , Chen Zhihua
Published: February 2023

Liver hepatocellular carcinoma (LIHC) is one of the most common malignancies and places a heavy burden on patients worldwide. HAUS augmin-like complex subunit 5 (HAUS5) is involved in the occurrence and development of various cancers. However, the functional role and significance of HAUS5 in LIHC remain unclear. The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Cancer Cell Line Encyclopedia (CCLE) and Gene Expression Omnibus (GEO) databases were used to analyze the mRNA expression of HAUS5. The value of HAUS5 in predicting LIHC prognosis and the relationship between HAUS5 and clinicopathological features were assessed by the Kaplan–Meier plotter and UALCAN databases. Functional enrichment analyses and nomogram prediction model construction were performed with the R packages. The LinkedOmics database was searched to reveal co-expressed genes associated with HAUS5. The relationship between HAUS5 expression and immune infiltration was explored by searching the TISIDB database and single-sample gene set enrichment analysis (ssGSEA). The Clinical Proteomic Tumor Analysis Consortium (CPTAC) and the Human Protein Atlas (HPA) databases were used to evaluate HAUS5 protein expression. Finally, the effect of HAUS5 on the proliferation of hepatoma cells was verified by CCK-8, colony formation and EdU assays. HAUS5 is aberrantly expressed and associated with a poor prognosis in most tumors, including LIHC. The expression of HAUS5 is significantly correlated with clinicopathological indicators in patients with LIHC. Functional enrichment analysis showed that HAUS5 was closely related to DNA replication, cell cycle and p53 signaling pathway. HAUS5 may serve as an independent risk factor for LIHC prognosis. The nomogram based on HAUS5 had area under the curve (AUC) values of 0.74 and 0.77 for predicting the 3-year and 5-year overall survival (OS) of LIHC patients. Immune correlation analysis showed that HAUS5 was significantly associated with immune infiltration. Finally, the results of in vitro experiments showed that when HAUS5 was knocked down, the proliferation of hepatoma cells was significantly decreased. The pan-oncogene HAUS5 is a positive regulator of LIHC progression and is closely associated with a poor prognosis in LIHC. Moreover, HAUS5 is involved in immune infiltration in LIHC. HAUS5 may be a new prognostic marker and therapeutic target for LIHC patients.