bluuebunny/crossref_metadata_2025 huggingface dataset:
DATED HOLOCENE HUMAN REMAINS FROM SOUTH AFRICA: RECALIBRATION AND BROAD CONTEXTUALIZATION
Authors: Loftus Emma , Lombard Marlize , Steyn Maryna
Published: March 2024

The study of human remains can provide valuable information about aspects of past populations. Here we present an updated database consisting of 590 radiocarbon (14C) dates for human remains from Holocene South Africa before European contact. We calibrated or recalibrated all the previously published dates using the most recent calibration curve for the southern hemisphere. Each date is roughly georeferenced and plotted according to their Stone Age or Iron Age contexts, revealing the broad distribution pattern of dated Holocene human remains across South Africa—perhaps reflecting aspects of past population distribution and densities, but also underscoring historical collection practices, archaeological research focus, and preservation conditions. We use Kernel Density Estimation models to show peaks and troughs of dated remains through time, with Later Stone Age peaks at ∼5.5 ka cal BP, ∼2 ka cal BP and ∼0.5 ka cal BP, and Iron Age peaks ∼1.1 ka cal BP and ∼0.5 ka cal BP, some of which show broad correspondence to climatic data. Our data, based on dated remains only, do not provide a full reflection of past populations, and our large-scale, coarse-grained analysis cannot yet assess the reasons for the peaks in dated human remains in detail. Yet, the study provides a new resource, and a data-driven overview that highlights aspects to be explored with further contextual analyses against the available archaeological records, population histories and climatic indicators through time and across space.
WEIERSTRASS ZETA FUNCTIONS AND p-ADIC LINEAR RELATIONS
Authors: PHAM DUC HIEP
Published: March 2024

We discuss the p-adic Weierstrass zeta functions associated with elliptic curves defined over the field of algebraic numbers and linear relations for their values in the p-adic domain. These results are extensions of the p-adic analogues of results given by Wüstholz in the complex domain [see A. Baker and G. Wüstholz, Logarithmic Forms and Diophantine Geometry, New Mathematical Monographs, 9 (Cambridge University Press, Cambridge, 2007), Theorem 6.3] and also generalise a result of Bertrand to higher dimensions [‘Sous-groupes à un paramètre p-adique de variétés de groupe’, Invent. Math.40(2) (1977), 171–193].
Does coinoculation with bradyrhizobia and cyanobacteria improve groundnut growth and yield?
Authors: Andrade Diva Souza , Lovato Gisele Milani , Kaschuk Glaciela , Hungria Mariangela
Published: March 2024

Groundnut plants can obtain N from N2 fixation via symbiosis with rhizobia, and inoculation with selected strains can improve grain yields. We report the results of four field experiments carried out under subtropical conditions to confirm whether microbial inoculants can improve groundnut performance through the effects of single inoculation with Bradyrhizobium arachidis (SEMIA6144), coinoculation with Arthrospira platensis (IPR7059) or Synechocystis sp. (IPR7061), or N fertilization with 100 kg ha-1 N on plant growth, nodulation, N accumulation in tissues, grain protein concentration (GPC), and grain yield. There were no effects of inoculation treatment or N fertilizer on shoot or root dry weight. In clayey soil, coinoculation with B. arachidis and cyanobacteria increased grain productivity by an average of 19% compared to that in the noninoculated control. In this clayey soil with a higher P content, regardless of whether coinoculated with B. arachidis or cyanobacteria or single inoculated, grain productivity was 16% greater on average than that resulting from N fertilizer addition. In conclusion, the success of rhizobial inoculation in groundnuts is dependent on the soil, probably due to P limitation and weather conditions.
Does epidemiological evidence support the success story of Uganda’s response to COVID-19?
Authors: Laing Nicolas , Mylan Sophie , Parker Melissa
Published: March 2024

Uganda has received praise for its success in dealing with the COVID-19 pandemic. This opinion piece uses publically available data from Johns Hopkins University to suggest that it is far from clear whether the Public Health and Social Measures (PHSM) introduced in Uganda influenced the course of the first outbreak. In addition, the analysis of data from the second and third waves in Uganda suggest that government action had little or no effect on these outbreaks. The dominant narrative of successful PHSM, therefore, needs to be reconsidered, and alternative explanations for the low rates of COVID-19-related mortality in the country need to be further understood.
An integrative taxonomy study reveals a rare new species of the genus Creptotrema (Trematoda: Allocreadiidae) in an endangered frog in South America
Authors: Alcantara E.P. , Ebert M.B. , Ferreira-Silva C. , Forti L.R. , Morais D.H. , Pérez-Ponce de León G. , Silva R. J.
Published: March 2024

During an ecological study with a near-endangered anuran in Brazil, the Schmidt’s Spinythumb frog, Crossodactylus schmidti Gallardo, 1961, we were given a chance to analyze the gastrointestinal tract of a few individuals for parasites. In this paper, we describe a new species of an allocreadiid trematode of the genus Creptotrema Travassos, Artigas & Pereira, 1928, which possesses a unique trait among allocreadiids (i.e., a bivalve shell-like muscular structure at the opening of the ventral sucker); the new species represents the fourth species of allocreadiid trematode parasitizing amphibians. Besides, the new species is distinguished from other congeners by the combination of characters such as the body size, ventral sucker size, cirrus-sac size, and by having small eggs. DNA sequences through the 28S rDNA and COI mtDNA further corroborated the distinction of the new species. Phylogenetic analyses placed the newly generated sequences in a monophyletic clade together with all other sequenced species of Creptotrema. Genetic divergences between the new species and other Creptotrema spp. varied from 2.0 to 4.2% for 28S rDNA, and 15.1 to 16.8% for COI mtDNA, providing robust validation for the recognition of the new species. Even though allocreadiids are mainly parasites of freshwater fishes, our results confirm anurans as hosts of trematodes of this family. Additionally, we propose the reallocation of Auriculostoma ocloya Liquin, Gilardoni, Cremonte, Saravia, Cristóbal & Davies, 2022 to the genus Creptotrema. This study increases the known diversity of allocreadiids and contributes to our understanding of their evolutionary relationships, host–parasite relationships, and biogeographic history.
Large-scale spatial drivers of avian schistosomes in Northern Michigan inland lakes
Authors: Sckrabulis Jason P. , Messner Madelyn L. , Stanny Jenna , McWhinnie Ryan B. , Ansari Hamzah D. , Hajek Aleena M. , Bageris Alexander , Raffel Thomas R.
Published: March 2024

Avian schistosomes are snail-borne trematode parasites (Trichobilharzia spp.) that can cause a nasty skin rash in humans when their cercariae mistake us for their normal bird hosts. We sought to investigate drivers of the spatial distribution of Trichobilharzia cercaria abundance throughout Northern Michigan lakes. For 38 sites on 16 lakes, we assessed several dozen potential environmental predictors that we hypothesized might have direct or indirect effects on overall cercaria abundance, based on known relationships between abiotic and biotic factors in wetland ecosystems. We included variables quantifying local densities of intermediate hosts, temperature, periphyton growth rates, human land use and hydrology. We also measured daily abundance of schistosome cercariae in the water over a 5-week period, supported by community scientists who collected and preserved filtered water samples for qPCR. The strongest predictor of cercaria abundance was Lymnaea host snail density. Lymnaea density was higher in deeper lakes and at sites with more deciduous tree cover, consistent with their association with cool temperature habitats. Contrary to past studies of human schistosomes, we also found a significant negative relationship between cercaria abundance and submerged aquatic vegetation, possibly due to vegetation blocking cercaria movement from offshore snail beds. If future work shows that these effects are indeed causal, then these results suggest possible new approaches to managing swimmer's itch risk in northern MI lakes, such as modifying tree cover and shallow-water vegetation at local sites.
Who's being elitist? A debate about the enregisterment of Singlish
Authors: Lu Luke
Published: March 2024

This article is a rejoinder to Lee (2023) who makes certain claims about the enregisterment of Singlish via a case study of Spiaking Singlish. In challenging Lee's key claim that Spiaking Singlish deploys a form of elitist language, I argue that the Singlish features in the book need not demand a solely ludic reading and actually draw from everyday practices. Accordingly, enregisterment ought to be understood as a diachronic and evolving process in the vein of Butler's (1999) notion of sedimentation. Moreover, Lee's characterization of the ‘monolectal Singlish user’ is classist and reductionist, unsupported by recent research and census data. Consequently, Spiaking Singlish need not be seen as an elitist work, but as contributing to ever-changing attitudes towards Singlish in the public sphere. This article is an alternative iteration to Lee's (2023) that has implications for the way we understand enregisterment in Singapore and choose to represent it as a process. (Enregisterment, Singlish, Singapore, sociolinguistics, language ideological debates)*
Not your ordinary drone: odes to the Bayraktar in the Russia–Ukraine war
Authors: Andrianova Anastassiya
Published: March 2024

‘Bayraktar’, a pop/rap song written by a Ukrainian soldier following Russia's invasion of Ukraine on 24 February 2022, went viral, spawning various covers, from electronic dance music to hardcore punk. I analyse this digital archive of 19 ‘Bayraktar’ songs, including five that share only the title with Taras Borovok's paradigmatic song, and contextualise it within the broader historical and decolonial frameworks of Ukrainian resistance music, including the protest music of the Orange Revolution and the Euromaidan demonstrations, and the anti-war music produced during the Donbas war and in the first six months of the ongoing Russia–Ukraine war. I apply the method of multimodal critical discourse analysis to highlight the ways that sound, image (videos and stills) and text (lyrics and verbal descriptions on YouTube) forge nationalist and global protest rhetorics, and also function pragmatically to raise awareness, fundraise for the armed forces and humanitarian efforts, and boost morale in Ukraine and abroad.
Frugivory and seed predation of fishtail palm (Caryota mitis Lour.) on the remote oceanic island of Narcondam, India
Authors: Gopal Abhishek , Ghuman Sartaj , Ramachandran Vivek , Page Navendu , Naniwadekar Rohit
Published: March 2024

Oceanic islands, due to their evolutionary history and isolation, play a dual role of having high endemicity and being vulnerable to extinctions, with most known extinctions occurring on islands. Plant–animal interactions are particularly important on islands, as island systems generally have low redundancy and are more vulnerable to disruption either via extinction or by invasive species. Here, we examined the fruit removal and seed predation of a keystone palm, Caryota mitis, on Narcondam, a remote oceanic island. The island endemic Narcondam Hornbill (Rhyticeros narcondami) was the sole seed disperser of the palm (90 hours; N = 15 trees), with mean (± SE) visitation rate being 0.23 (± 0.06) individuals per hour and fruit removal rates of 3.5 (± 1.5; range: 0–16) fruits per visit, indicating a lack of redundancy in seed dispersal of the palm on this island. Whereas the invasive rodent, Rattus cf. tiomanicus, was the sole predator of palm seeds (N = 15 individual fruiting palms, 416 trap nights). Overall, 17.1% of the seeds placed (N = 375 seeds) were removed. Seeds placed under and away from the canopy, and at different densities (2 plots with 10 seeds each; 1 plot with 5 seeds, respectively), showed similar removal rates. This indicates density-independent seed predation and the lack of safe regeneration sites for Caryota mitis, with potential deleterious effects on subsequent stages of the ‘seed dispersal cycle’. Here, from a data-deficient site, we provide baseline information on the plant–frugivore interaction of a keystone palm and the potential impacts of an invasive rodent.
Divergent tracks: Korean Government Railways’ employment and training systems under Japanese colonial rule, 1910–45
Authors: Lim Chaisung
Published: March 2024

This study employs annual reports, time-series statistics, and internal training records of the colonial-era Korean Government Railways (KGR) to conduct a quantitative analysis of its labour management practices. It addresses the colonial characteristics associated with Japanese techno-imperialism beyond ethnic discrimination, revealing a dual-pronged labour strategy that adopted a Japanese government employee system to manage middle- and upper-level personnel and directly recruited on-site workers for the lower echelons. This deviates from the low rates of local employment in Western colonies, particularly self-governing British territories or integrated French territories. In contrast, KGR's employment practices demonstrated economic and ethnic inequalities. It predominantly made Koreans on-site labourers, whereas Japanese not only held similar roles, but also occupied upper- and middle-management positions. Worker mobility, particularly among Japanese employees, grew following the outbreak of war between Japan and the USA, leading to the mass external recruitment of Koreans and the expansion of internal education to alleviate labour shortages. Nevertheless, preferential treatment toward Japanese individuals, which had been in relative decline for promotion, wages, and admission rates to training schools, ultimately persisted. Understanding KGR's employment structure shows how colonisation mediated Korea's modernisation and imposed technical limitations on the management of local labour. National technological decolonisation thus required Koreans to further introduce external technologies after the end of Japan's imperial reign.
Seeking employment during Japan's early industrialisation: new engineering graduates and their struggles before 1900
Authors: Wada Masanori
Published: March 2024

This article examines the social background of engineers in Meiji Japan by analysing their employment-seeking activities and their role in fostering industrial development. In particular, it focuses on the graduates from the Imperial College of Engineering (ICE) in Tokyo. One of the most prestigious schools for technical education, the ICE was established by the Meiji government in 1871 and opened in 1873. In traditional Japanese society, the handicraft manufacturing sector was held in low regard. The difficulties that graduates faced while the industry was still developing serve as a stark reminder of the widespread contempt and disdain for manufacturing that existed in Japan before the new profession of engineer gained traction. By scrutinising the memoirs of these engineers, this study shows that new engineering graduates faced barriers to employment in industry due to the low social prestige of those working in manufacturing in the private sector and the conflict with traditional workers, as well as the fact that private companies could not afford to employ engineers in the early years of industrialisation.
FINITENESS OF CANONICAL QUOTIENTS OF DEHN QUANDLES OF SURFACES
Authors: DHANWANI NEERAJ K. , SINGH MAHENDER
Published: March 2024

The Dehn quandle of a closed orientable surface is the set of isotopy classes of nonseparating simple closed curves with a natural quandle structure arising from Dehn twists. In this paper, we consider the finiteness of some canonical quotients of these quandles. For a surface of positive genus, we give a precise description of the 2-quandle of its Dehn quandle. Further, with some exceptions for genus more than 2, we determine all values of n for which the n-quandle of its Dehn quandle is finite. The result can be thought of as the Dehn quandle analogue of a similar result of Hoste and Shanahan for link quandles [‘Links with finite n-quandles’, Algebr. Geom. Topol.17(5) (2017), 2807–2823]. We also compute the size of the smallest nontrivial quandle quotient of the Dehn quandle of a surface. Along the way, we prove that the involutory quotient of an Artin quandle is precisely the corresponding Coxeter quandle, and also determine the smallest nontrivial quotient of a braid quandle.
A Deep Learning Method for Dynamic Process Modeling of Real Landslides Based on Fourier Neural Operator
Authors: Chen Yanglong , Ouyang Chaojun , Xu Qingsong , Yang Weibin
Published: March 2024

The conventional numerical solvers for partial differential equations encounter a formidable challenge, as their computational efficiency and accuracy are heavily contingent on grid size. Recently, machine learning (ML) has exhibited substantial promise in addressing partial differential equations. Nevertheless, substantial hurdles persist in practical applications. In this work, we endeavor to establish a deep learning framework founded on the Fourier neural operator (FNO) for resolving the intricacies of simulating real landslide dynamic processes. Our findings demonstrate that the current FNO approach adeptly replicates landslide dynamic processes and boasts exceptional computational efficiency. Additionally, it is noteworthy that this data‐driven ML methodology can seamlessly incorporate data from other experimental sources or numerical simulation techniques. Consequently, this work underscores the significant potential of utilizing ML methodologies to supplant conventional numerical simulation methods.
Variations of Inter‐Hemispheric Field‐Aligned Currents: Observations From Ground Geomagnetic Measurements
Authors: Archana R. K. , Arora Kusumita
Published: March 2024

The east–west component of the geomagnetic field (Y‐component) at the Trivandrum (TRD) station, an equatorial site, is used to investigate the characteristics of Inter‐Hemispheric Field‐Aligned Currents (IHFACs) in the Indian sector during solar cycles 21 and 22. The observations reveal an annual variation of IHFAC in the dawn/noon sector with positive/negative peaks around northern summer. Furthermore, it is noted that IHFAC amplitudes are modulated by solar activity, superimposed with seasonal effects, with consistently higher amplitudes during the northern summer months. The dusk‐time IHFAC also shows a pattern modulated by seasons and solar cycles, with negative peaks around northern summer only during the low solar active years. The seasonal pattern of IHFAC shows a similar trend from April to September, where dawn/noon IHFAC is south/north directed, and for the remaining months, both are northward directed. The dusk‐side IHFAC is mostly south‐directed irrespective of the season. Moreover, it is demonstrated that the seasonal pattern of dawn and noon‐time IHFAC amplitudes show a strong to moderate correlation with amplitudes of Sq asymmetries between two hemispheres, but dusk‐time IHFAC does not follow this trend. The IHFAC directions at TRD follow the Fukushima model for May to September during the dawn‐noon sector for 70%–95% of the days and less than 50% of the days for remaining months. The noon‐dusk sector shows Fukushima model‐type polarity for ∼60% of days in June–July and less than 50% for remaining months. The global analysis of IHFAC, using monthly averages of hourly values from eight observatories spanning Asia, Africa, and America, reveals spatial differences in amplitude and directions. The directions of noon‐time IHFAC in the Indian‐East Asian and East‐African sectors follow similar trends, and the amplitude variations of noon‐time IHFAC can be explained by DE‐3 tidal effects. The IHFAC from the South American and West African sectors show intense southward and northward currents compared to other sites, indicating the influence of the South Atlantic Anomaly (SAA).
Developing a General Daily Lake Evaporation Model and Demonstrating Its Application in the State of Texas
Authors: Zhao Bingjie , Huntington Justin , Pearson Christopher , Zhao Gang , Ott Thomas , Zhu John , Weinberg Andrew , Holman Kathleen D. , Zhang Shuai , Anderson Ron , Strickler Maxwell , Cotter Jerry , Fernando Nelun , Nowak Kenneth , Gao Huilin
Published: March 2024

Open water evaporation, which often consumes a large fraction of annual storage (especially in arid and semi‐arid regions), is a controlling variable for modern water resource management. Developing a daily reservoir evaporation data set is necessary for reservoir operations to consider the influence of evaporation in a timely manner. However, over the past few decades, the quantification of reservoir evaporation has primarily relied on monthly Class A pan evaporation observations, which might lead to largely biased estimations because they do not incorporate the effects of heat storage and fetch. In this study, we developed a general Daily Lake Evaporation Model (DLEM) based on Penman's equation combined with daily atmospheric reanalysis data sets, to improve the validity and frequency of reservoir evaporation monitoring. Compared with daily evaporation estimates from eddy covariance systems, the DLEM showed good quality and reliability, with R2 values ranging from 0.50 to 0.73 and RMSE values ranging from 1.13 to 1.97 mm day−1 in four different sites. By applying DLEM to all 188 major reservoirs in Texas, we generated a long‐term data set of (1 January 1981–31 December 2021) daily evaporation rates. The results reveal a clear geographic distribution and strong seasonality of evaporation throughout Texas, where the mean evaporation rate is highest during July, with 6.85 mm day−1. Trend analysis indicates that the annual average evaporation rate has significantly increased since 1981 at a rate of 0.076 mm day−1 decade−1. This study provides sufficient data support for water resource operations and management, and regional water planning.
Light People: Prof. Kei May Lau, newly elected US NAE member in Hong Kong, talks about future of photonics and women in science
Authors: Wan Yating , Guo Chenzi
Published: March 2024

Editorial

Photonics technology remains a driving force in today’s scientific landscape, marked by continuous innovation and cross-disciplinary relevance. In an enlighting conversation with Light: Science & Applications, Prof. Kei May Lau, a pioneer in photonics research, shares her deep insights on the evolution of technologies of LEDs, lasers, challenges of hetero-epitaxy, and the future of micro-LEDs and quantum dot lasers. Recently honored as a member of the US National Academy of Engineering (NAE) for her significant contributions to photonics and electronics using III-V semiconductors on silicon, Prof. Lau stands out as the sole Hong Kong scholar inducted into the NAE this year, joining 114 new and 21 international members. In this exclusive Light People interview, Prof. Lau shares her journey as a pioneering woman in engineering, her commitment to mentorship and academia, and her perspective on advancing female representation in science. The summary provided is distilled from Prof. Lau’s thoughtful responses during the interview. For a deeper exploration of Prof. Lau’s experiences and advice, the full interview is available in the Supplementary material.
Efficacy of BioMin F and NovaMin toothpastes against streptococcus mutans: an in vitro study
Authors: Doura Alomari Haya , Alsayed Tolibah Yasser , Kouchaji Chaza
Published: March 2024

Objective

This in vitro study was accomplished to demonstrate the antibacterial efficacy of BioMin F and NovaMin toothpastes against the recently-isolated Streptococcus Mutans in comparison with a commonly used fluoride toothpaste.

Materials and methods

Dental plaque collection method was adopted to isolate streptococcus mutans in children with dental caries. Then an ideal Streptococcus Mutans colony was incubated in 20 Petri dishes that contained Mueller-Hinton medium. Each dish had 3 wells; one well for each toothpaste (BioMin F, NovMin, and Signal) to perform the agar diffusion test. After incubating for 24 hours, the inhabitation zone around each well of each Petri dish was noticed and measured. Statistical Analysis was achieved using a statistical package, SPSS Windows version 17, by applying Kruskal-Wallis with Mann–Whitney U test (α = 0.05).

Results

BioMin F showed the highest mean of inhibition zone diameter ($$\bar{x}$$

x

¯

 = 2.67 mm) in compared with NovaMin and Signal ($$\bar{x}$$

x

¯

 = 0.39 mm and $$\bar{x}$$

x

¯

 = 2.19 mm; p < 0.001 in each pairwise comparison).

Conclusion

BioMin F toothpaste showed superior antibacterial effect against Streptococcus mutans to Signal and NovaMin toothpastes. Novamin showed the lowest antibacterial effect. This in vitro study suggests that BioMin F toothpaste shows encouraging potential to be recommended as a preventive measure to reduce the caries risk.
Cellular heterogeneity in TNF/TNFR1 signalling: live cell imaging of cell fate decisions in single cells
Authors: Preedy Marcus K. , White Michael R. H. , Tergaonkar Vinay
Published: March 2024

Cellular responses to TNF are inherently heterogeneous within an isogenic cell population and across different cell types. TNF promotes cell survival by activating pro-inflammatory NF-κB and MAPK signalling pathways but may also trigger apoptosis and necroptosis. Following TNF stimulation, the fate of individual cells is governed by the balance of pro-survival and pro-apoptotic signalling pathways. To elucidate the molecular mechanisms driving heterogenous responses to TNF, quantifying TNF/TNFR1 signalling at the single-cell level is crucial. Fluorescence live-cell imaging techniques offer real-time, dynamic insights into molecular processes in single cells, allowing for detection of rapid and transient changes, as well as identification of subpopulations, that are likely to be missed with traditional endpoint assays. Whilst fluorescence live-cell imaging has been employed extensively to investigate TNF-induced inflammation and TNF-induced cell death, it has been underutilised in studying the role of TNF/TNFR1 signalling pathway crosstalk in guiding cell-fate decisions in single cells. Here, we outline the various opportunities for pathway crosstalk during TNF/TNFR1 signalling and how these interactions may govern heterogenous responses to TNF. We also advocate for the use of live-cell imaging techniques to elucidate the molecular processes driving cell-to-cell variability in single cells. Understanding and overcoming cellular heterogeneity in response to TNF and modulators of the TNF/TNFR1 signalling pathway could lead to the development of targeted therapies for various diseases associated with aberrant TNF/TNFR1 signalling, such as rheumatoid arthritis, metabolic syndrome, and cancer.
GINS2 regulates temozolomide chemosensitivity via the EGR1/ECT2 axis in gliomas
Authors: He Hua , Liang Lu , Jiang Shiyao , Liu Yueying , Huang Jingjing , Sun Xiaoyan , Li Yi , Jiang Yiqun , Cong Li
Published: March 2024

Temozolomide (TMZ), a DNA alkylating agent, has become the primary treatment for glioma, the most common malignancy of the central nervous system. Although TMZ-containing regimens produce significant clinical response rates, some patients inevitably suffer from inferior treatment outcomes or disease relapse, likely because of poor chemosensitivity of glioma cells due to a robust DNA damage response (DDR). GINS2, a subunit of DNA helicase, contributes to maintaining genomic stability and is highly expressed in various cancers, promoting their development. Here, we report that GINS2 was upregulated in TMZ-treated glioma cells and co-localized with γH2AX, indicating its participation in TMZ-induced DDR. Furthermore, GINS2 regulated the malignant phenotype and TMZ sensitivity of glioma cells, mostly by promoting DNA damage repair by affecting the mRNA stability of early growth response factor 1 (EGR1), which in turn regulates the transcription of epithelial cell-transforming sequence 2 (ECT2). We constructed a GINS2–EGR1–ECT2 prognostic model, which accurately predicted patient survival. Further, we screened Palbociclib/BIX-02189 which dampens GINS2 expression and synergistically inhibits glioma cell proliferation with TMZ. These findings delineate a novel mechanism by which GINS2 regulates the TMZ sensitivity of glioma cells and propose a promising combination therapy to treat glioma.
Does renal denervation require cardiovascular outcome-driven data?
Authors: Haider Syedah Aleena , Wagener Max , Iqbal Talha , Shahzad Shirjeel , Del Sole Paolo Alberto , Leahy Niall , Murphy Darragh , Sharif Ruth , Ullah Ihsan , Sharif Faisal
Published: March 2024

Hypertension is a major driver of cardiovascular disease with a prevalence of 32–34% in adults worldwide. This poses a formidable unmet challenge for healthcare systems, highlighting the need for enhanced treatment strategies. Since 2017, eight major sham-controlled randomised controlled trials have examined the effectiveness and safety of renal denervation (RDN) as therapy for BP control. Although most trials demonstrated a reduction in systolic 24-hour/daytime ambulatory BP compared to control groups, open to discussion is whether major adverse cardiovascular events (MACE)-driven RDN trials are necessary or whether the proof of BP reduction as a surrogate for better cardiovascular outcomes is sufficient. We conducted an analysis of the statistical methods used in various trials to assess endpoint definitions and determine the necessity for MACE-driven outcome data. Such comprehensive analysis provides further evidence to confidently conclude that RDN significantly reduces blood pressure compared to sham controls. Importantly, this enables the interpolation of RDN trial endpoints with other studies that report on outcome data, such as pharmacological trials which demonstrate a significant reduction in MACE risk with a decrease in BP. Moreover, limitations associated with directly evaluating outcome data further support the use of BP as a surrogate endpoint. For example, conducting lengthier trials with larger numbers of participants to ensure robust statistical power presents a substantial challenge to evaluating outcome data. Thus, in light of the crucial need to tackle hypertension, there are notable advantages of considering BP as a surrogate for outcome data.
Ageing impairs the regenerative capacity of regulatory T cells in mouse central nervous system remyelination
Authors: de la Fuente Alerie Guzman , Dittmer Marie , Heesbeen Elise J. , de la Vega Gallardo Nira , White Jessica A. , Young Andrew , McColgan Tiree , Dashwood Amy , Mayne Katie , Cabeza-Fernández Sonia , Falconer John , Rodriguez-Baena Francisco Javier , McMurran Christopher E. , Inayatullah Mohammed , Rawji Khalil S. , Franklin Robin J. M. , Dooley James , Liston Adrian , Ingram Rebecca J. , Tiwari Vijay K. , Penalva Rosana , Dombrowski Yvonne , Fitzgerald Denise C.
Published: March 2024

Myelin regeneration (remyelination) is essential to prevent neurodegeneration in demyelinating diseases such as Multiple Sclerosis, however, its efficiency declines with age. Regulatory T cells (Treg) recently emerged as critical players in tissue regeneration, including remyelination. However, the effect of ageing on Treg-mediated regenerative processes is poorly understood. Here, we show that expansion of aged Treg does not rescue age-associated remyelination impairment due to an intrinsically diminished capacity of aged Treg to promote oligodendrocyte differentiation and myelination in male and female mice. This decline in regenerative Treg functions can be rescued by a young environment. We identified Melanoma Cell Adhesion Molecule 1 (MCAM1) and Integrin alpha 2 (ITGA2) as candidates of Treg-mediated oligodendrocyte differentiation that decrease with age. Our findings demonstrate that ageing limits the neuroregenerative capacity of Treg, likely limiting their remyelinating therapeutic potential in aged patients, and describe two mechanisms implicated in Treg-driven remyelination that may be targetable to overcome this limitation.
N6-methyladenosine modification is not a general trait of viral RNA genomes
Authors: Baquero-Pérez Belinda , Yonchev Ivaylo D. , Delgado-Tejedor Anna , Medina Rebeca , Puig-Torrents Mireia , Sudbery Ian , Begik Oguzhan , Wilson Stuart A. , Novoa Eva Maria , Díez Juana
Published: March 2024

Despite the nuclear localization of the m6A machinery, the genomes of multiple exclusively-cytoplasmic RNA viruses, such as chikungunya (CHIKV) and dengue (DENV), are reported to be extensively m6A-modified. However, these findings are mostly based on m6A-Seq, an antibody-dependent technique with a high rate of false positives. Here, we address the presence of m6A in CHIKV and DENV RNAs. For this, we combine m6A-Seq and the antibody-independent SELECT and nanopore direct RNA sequencing techniques with functional, molecular, and mutagenesis studies. Following this comprehensive analysis, we find no evidence of m6A modification in CHIKV or DENV transcripts. Furthermore, depletion of key components of the host m6A machinery does not affect CHIKV or DENV infection. Moreover, CHIKV or DENV infection has no effect on the m6A machinery’s localization. Our results challenge the prevailing notion that m6A modification is a general feature of cytoplasmic RNA viruses and underscore the importance of validating RNA modifications with orthogonal approaches.
PCDHA9 as a candidate gene for amyotrophic lateral sclerosis
Authors: Zhong Jie , Wang Chaodong , Zhang Dan , Yao Xiaoli , Zhao Quanzhen , Huang Xusheng , Lin Feng , Xue Chun , Wang Yaqing , He Ruojie , Li Xu-Ying , Li Qibin , Wang Mingbang , Zhao Shaoli , Afridi Shabbir Khan , Zhou Wenhao , Wang Zhanjun , Xu Yanming , Xu Zhiheng
Published: March 2024

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease. To identify additional genetic factors, we analyzed exome sequences in a large cohort of Chinese ALS patients and found a homozygous variant (p.L700P) in PCDHA9 in three unrelated patients. We generated Pcdhα9 mutant mice harboring either orthologous point mutation or deletion mutation. These mice develop progressive spinal motor loss, muscle atrophy, and structural/functional abnormalities of the neuromuscular junction, leading to paralysis and early lethality. TDP-43 pathology is detected in the spinal motor neurons of aged mutant mice. Mechanistically, we demonstrate that Pcdha9 mutation causes aberrant activation of FAK and PYK2 in aging spinal cord, and dramatically reduced NKA-α1 expression in motor neurons. Our single nucleus multi-omics analysis reveals disturbed signaling involved in cell adhesion, ion transport, synapse organization, and neuronal survival in aged mutant mice. Together, our results present PCDHA9 as a potential ALS gene and provide insights into its pathogenesis.
dCas13-mediated translational repression for accurate gene silencing in mammalian cells
Authors: Apostolopoulos Antonios , Kawamoto Naohiro , Chow Siu Yu A. , Tsuiji Hitomi , Ikeuchi Yoshiho , Shichino Yuichi , Iwasaki Shintaro
Published: March 2024

Current gene silencing tools based on RNA interference (RNAi) or, more recently, clustered regularly interspaced short palindromic repeats (CRISPR)‒Cas13 systems have critical drawbacks, such as off-target effects (RNAi) or collateral mRNA cleavage (CRISPR‒Cas13). Thus, a more specific method of gene knockdown is needed. Here, we develop CRISPRδ, an approach for translational silencing, harnessing catalytically inactive Cas13 proteins (dCas13). Owing to its tight association with mRNA, dCas13 serves as a physical roadblock for scanning ribosomes during translation initiation and does not affect mRNA stability. Guide RNAs covering the start codon lead to the highest efficacy regardless of the translation initiation mechanism: cap-dependent, internal ribosome entry site (IRES)-dependent, or repeat-associated non-AUG (RAN) translation. Strikingly, genome-wide ribosome profiling reveals the ultrahigh gene silencing specificity of CRISPRδ. Moreover, the fusion of a translational repressor to dCas13 further improves the performance. Our method provides a framework for translational repression-based gene silencing in eukaryotes.
Silencing CA1 pyramidal cells output reveals the role of feedback inhibition in hippocampal oscillations
Authors: Adaikkan Chinnakkaruppan , Joseph Justin , Foustoukos Georgios , Wang Jun , Polygalov Denis , Boehringer Roman , Middleton Steven J. , Huang Arthur J. Y. , Tsai Li-Huei , McHugh Thomas J.
Published: March 2024

The precise temporal coordination of neural activity is crucial for brain function. In the hippocampus, this precision is reflected in the oscillatory rhythms observed in CA1. While it is known that a balance between excitatory and inhibitory activity is necessary to generate and maintain these oscillations, the differential contribution of feedforward and feedback inhibition remains ambiguous. Here we use conditional genetics to chronically silence CA1 pyramidal cell transmission, ablating the ability of these neurons to recruit feedback inhibition in the local circuit, while recording physiological activity in mice. We find that this intervention leads to local pathophysiological events, with ripple amplitude and intrinsic frequency becoming significantly larger and spatially triggered local population spikes locked to the trough of the theta oscillation appearing during movement. These phenotypes demonstrate that feedback inhibition is crucial in maintaining local sparsity of activation and reveal the key role of lateral inhibition in CA1 in shaping circuit function.
A multi-demand operating system underlying diverse cognitive tasks
Authors: Cai Weidong , Taghia Jalil , Menon Vinod
Published: March 2024

The existence of a multiple-demand cortical system with an adaptive, domain-general, role in cognition has been proposed, but the underlying dynamic mechanisms and their links to cognitive control abilities are poorly understood. Here we use a probabilistic generative Bayesian model of brain circuit dynamics to determine dynamic brain states across multiple cognitive domains, independent datasets, and participant groups, including task fMRI data from Human Connectome Project, Dual Mechanisms of Cognitive Control study and a neurodevelopment study. We discover a shared brain state across seven distinct cognitive tasks and found that the dynamics of this shared brain state predicted cognitive control abilities in each task. Our findings reveal the flexible engagement of dynamic brain processes across multiple cognitive domains and participant groups, and uncover the generative mechanisms underlying the functioning of a domain-general cognitive operating system. Our computational framework opens promising avenues for probing neurocognitive function and dysfunction.
Tuning of the flat band and its impact on superconductivity in Mo5Si3−xPx
Authors: Khasanov Rustem , Ruan Bin-Bin , Shi Yun-Qing , Chen Gen-Fu , Luetkens Hubertus , Ren Zhi-An , Guguchia Zurab
Published: March 2024

The superconductivity in systems containing dispersionless (flat) bands is seemingly paradoxical, as traditional Bardeen-Cooper-Schrieffer theory requires an infinite enhancement of the carrier masses. However, the combination of flat and steep (dispersive) bands within the multiple band scenario might boost superconducting responses, potentially explaining high-temperature superconductivity in cuprates and metal hydrides. Here, we report on the magnetic penetration depths, the upper critical field, and the specific heat measurements, together with the first-principles calculations for the Mo5Si3−xPx superconducting family. The band structure features a flat band that gradually approaches the Fermi level as a function of phosphorus doping x, reaching the Fermi level at x ≃ 1.3. This leads to an abrupt change in nearly all superconducting quantities. The superfluid density data placed on the ’Uemura plot‘ results in two separated branches, thus indicating that the emergence of a flat band enhances correlations between conducting electrons.
Three-dimensional flat Landau levels in an inhomogeneous acoustic crystal
Authors: Cheng Zheyu , Guan Yi-Jun , Xue Haoran , Ge Yong , Jia Ding , Long Yang , Yuan Shou-Qi , Sun Hong-Xiang , Chong Yidong , Zhang Baile
Published: March 2024

When electrons moving in two dimensions (2D) are subjected to a strong uniform magnetic field, they form flat bands called Landau levels (LLs). LLs can also arise from pseudomagnetic fields (PMFs) induced by lattice distortions. In three-dimensional (3D) systems, there has been no experimental demonstration of LLs  as a type of flat band thus far. Here, we report the experimental realization of a flat 3D LL in an acoustic crystal. Starting from a lattice whose bandstructure exhibits a nodal ring, we design an inhomogeneous distortion corresponding to a specific pseudomagnetic vector potential (PVP). This distortion causes the nodal ring states to break up into LLs, including a zeroth LL that is flat along all three directions. These findings suggest the possibility of using nodal ring materials to generate 3D flat bands, allowing access to strong interactions and other attractive physical regimes in 3D.
Quantifying how single dose Ad26.COV2.S vaccine efficacy depends on Spike sequence features
Authors: Magaret Craig A. , Li Li , deCamp Allan C. , Rolland Morgane , Juraska Michal , Williamson Brian D. , Ludwig James , Molitor Cindy , Benkeser David , Luedtke Alex , Simpkins Brian , Heng Fei , Sun Yanqing , Carpp Lindsay N. , Bai Hongjun , Dearlove Bethany L. , Giorgi Elena E. , Jongeneelen Mandy , Brandenburg Boerries , McCallum Matthew , Bowen John E. , Veesler David , Sadoff Jerald , Gray Glenda E. , Roels Sanne , Vandebosch An , Stieh Daniel J. , Le Gars Mathieu , Vingerhoets Johan , Grinsztejn Beatriz , Goepfert Paul A. , de Sousa Leonardo Paiva , Silva Mayara Secco Torres , Casapia Martin , Losso Marcelo H. , Little Susan J. , Gaur Aditya , Bekker Linda-Gail , Garrett Nigel , Truyers Carla , Van Dromme Ilse , Swann Edith , Marovich Mary A. , Follmann Dean , Neuzil Kathleen M. , Corey Lawrence , Greninger Alexander L. , Roychoudhury Pavitra , Hyrien Ollivier , Gilbert Peter B.
Published: March 2024

In the ENSEMBLE randomized, placebo-controlled phase 3 trial (NCT04505722), estimated single-dose Ad26.COV2.S vaccine efficacy (VE) was 56% against moderate to severe–critical COVID-19. SARS-CoV-2 Spike sequences were determined from 484 vaccine and 1,067 placebo recipients who acquired COVID-19. In this set of prespecified analyses, we show that in Latin America, VE was significantly lower against Lambda vs. Reference and against Lambda vs. non-Lambda [family-wise error rate (FWER) p < 0.05]. VE differed by residue match vs. mismatch to the vaccine-insert at 16 amino acid positions (4 FWER p < 0.05; 12 q-value ≤ 0.20); significantly decreased with physicochemical-weighted Hamming distance to the vaccine-strain sequence for Spike, receptor-binding domain, N-terminal domain, and S1 (FWER p < 0.001); differed (FWER ≤ 0.05) by distance to the vaccine strain measured by 9 antibody-epitope escape scores and 4 NTD neutralization-impacting features; and decreased (p = 0.011) with neutralization resistance level to vaccinee sera. VE against severe–critical COVID-19 was stable across most sequence features but lower against the most distant viruses.
YTHDF2 governs muscle size through a targeted modulation of proteostasis
Authors: Gilbert Christopher J. , Rabolli Charles P. , Golubeva Volha A. , Sattler Kristina M. , Wang Meifang , Ketabforoush Arsh , Arnold W. David , Lepper Christoph , Accornero Federica
Published: March 2024

The regulation of proteostasis is fundamental for maintenance of muscle mass and function. Activation of the TGF-β pathway drives wasting and premature aging by favoring the proteasomal degradation of structural muscle proteins. Yet, how this critical post-translational mechanism is kept in check to preserve muscle health remains unclear. Here, we reveal the molecular link between the post-transcriptional regulation of m6A-modified mRNA and the modulation of SMAD-dependent TGF-β signaling. We show that the m6A-binding protein YTHDF2 is essential to determining postnatal muscle size. Indeed, muscle-specific genetic deletion of YTHDF2 impairs skeletal muscle growth and abrogates the response to hypertrophic stimuli. We report that YTHDF2 controls the mRNA stability of the ubiquitin ligase ASB2 with consequences on anti-growth gene program activation through SMAD3. Our study identifies a post-transcriptional to post-translational mechanism for the coordination of gene expression in muscle.
Lipoarabinomannan mediates localized cell wall integrity during division in mycobacteria
Authors: Sparks Ian L. , Kado Takehiro , Prithviraj Malavika , Nijjer Japinder , Yan Jing , Morita Yasu S.
Published: March 2024

The growth and division of mycobacteria, which include clinically relevant pathogens, deviate from that of canonical bacterial models. Despite their Gram-positive ancestry, mycobacteria synthesize and elongate a diderm envelope asymmetrically from the poles, with the old pole elongating more robustly than the new pole. The phosphatidylinositol-anchored lipoglycans lipomannan (LM) and lipoarabinomannan (LAM) are cell envelope components critical for host-pathogen interactions, but their physiological functions in mycobacteria remained elusive. In this work, using biosynthetic mutants of these lipoglycans, we examine their roles in maintaining cell envelope integrity in Mycobacterium smegmatis and Mycobacterium tuberculosis. We find that mutants defective in producing mature LAM fail to maintain rod cell shape specifically at the new pole and para-septal regions whereas a mutant that produces a larger LAM becomes multi-septated. Therefore, LAM plays critical and distinct roles at subcellular locations associated with division in mycobacteria, including maintenance of local cell wall integrity and septal placement.
A framework for tracing timber following the Ukraine invasion
Authors: Mortier Thomas , Truszkowski Jakub , Norman Marigold , Boner Markus , Buliga Bogdan , Chater Caspar , Jennings Henry , Saunders Jade , Sibley Rosie , Antonelli Alexandre , Waegeman Willem , Deklerck Victor
Published: March 2024

Scientific testing including stable isotope ratio analysis (SIRA) and trace element analysis (TEA) is critical for establishing plant origin, tackling deforestation and enforcing economic sanctions. Yet methods combining SIRA and TEA into robust models for origin verification and determination are lacking. Here we report a (1) large Eastern European timber reference database (Betula, Fagus, Pinus, Quercus) tailored to sanctioned products following the Ukraine invasion; (2) statistical test to verify samples against a claimed origin; (3) probabilistic model of SIRA, TEA and genus distribution data, using Gaussian processes, to determine timber harvest location. Our verification method rejects 40–60% of simulated false claims, depending on the spatial scale of the claim, and maintains a low probability of rejecting correct origin claims. Our determination method predicts harvest location within 180 to 230 km of true location. Our results showcase the power of combining data types with probabilistic modelling to identify and scrutinize timber harvest location claims.