bluuebunny/crossref_metadata_2025 huggingface dataset:
Isolating a culture of son preference among Armenian, Georgian and Azeri Parents in Soviet-era Russia
Authors: Schief Matthias , Vogt Sonja , Churilova Elena , Efferson Charles
Published: March 2024

A basic hypothesis is that cultural evolutionary processes sustain differences between groups, these differences have evolutionary relevance and they would not otherwise occur in a system without cultural transmission. The empirical challenge is that groups vary for many reasons, and isolating the causal effects of culture often requires appropriate data and a quasi-experimental approach to analysis. We address this challenge with historical data from the final Soviet census of 1989, and our analysis is an example of the epidemiological approach to identifying cultural variation. We find that the fertility decisions of Armenian, Georgian and Azeri parents living in Soviet-era Russia were significantly more son-biased than those of other ethnic groups in Russia. This bias for sons took the form of differential stopping rules; families with sons stopped having children sooner than families without sons. This finding suggests that the increase in sex ratios at birth in the Caucasus, which began in the 1990s, reflects a cultural preference for sons that predates the end of the Soviet Union. This result also supports one of the key hypotheses of gene–culture coevolution, namely that cultural evolutionary processes can support group-level differences in selection pressures that would not otherwise occur in a system without culture.
Saving sheep – On extinction narratives in Namibian Swakara farming
Authors: Schaumann Eleanor
Published: March 2024

The Namibian Swakara industry, a type of sheep farming focused on the production of lamb pelts for the fashion industry, currently faces a crisis situation. Formerly one of the most important export products from Namibia, a combination of drought, falling pelt prices and the effects of the COVID-19 pandemic now threaten the survival of Swakara, the Namibian Karakul. The current crisis is articulated in extinction narratives. The potential end of Swakara farming as a way of life and a set of knowledge practices is narratively interwoven with the potential disappearance of Swakara from the Namibian landscape. Extinction narratives in the context of Swakara farming in Namibia blur the lines of human and nonhuman ways of life and their disappearance.
“Like Seeking out a Lost Friend”: Reconsidering “Pioneer” Arab Feminists and Their Networks as Part of a/the First Wave
Authors: Douglas Roxanne
Published: March 2024

Contemporary Arab feminist writers such as Margot Badran and Mona Eltahawy describe their personal discovery of Arab “pioneers.” This label positions “pioneers” as exceptional figures, which untethers their legacy from contemporary Arab feminists, and from one another. Drawing on the Warwick Research Collective's concept of “combined and uneven development,” this essay rethinks how we understand the first wave to account for the feminist histories in al-mashreq, and therefore reimagines the feminist wave model to account for waves of transmission, of emotion such as inspiration drawn from solidarity with other women. Through analysis of Anglophone scholarship and biographies, translated autobiographical writings of “pioneers,” and analysis of L'Egyptienne magazine, this article offers a new way of framing the work of “pioneer” feminists as part of a wide network of collaborators, and a wave of feminist activism that is locally and globally imbricated. This paper examines women's journals and salons which contribute to a period of “invisible feminism” from 1860 to the early 1920s. The endeavors of three “pioneer” figures, Huda Sha'rawi (Egypt, 1879–1947), Anbara Salam Khalidi (Lebanon, 1897–1986), and May Ziadeh (Palestine/Lebanon, 1886–1941) are then discussed through the lens of their influential friendships with other women.
Influence of immersed particles on the stability of the liquid–liquid interface in a two-layer channel flow
Authors: Ruiz-Martín Désirée , Rivero-Rodríguez Javier , Sánchez-Sanz Mario
Published: March 2024

The current study investigates the global linear stability of a two-layer channel flow with a train of solid particles flowing near the liquid–liquid interface. Three different mechanisms of instability (shear, interfacial and migration modes) are identified, and their interactions are examined. The interfacial instability, associated with the viscosity jump at the liquid–liquid interface, is found to be coupled to the migration of the particle. The stability of the flow configuration is evaluated for various governing parameters, including fluid viscosities and flow rate ratios, particle position, inter-particle distance, and Reynolds and capillary numbers. Our numerical results are compared with the particle-free flow configuration, indicating that the presence of the particle in the more viscous fluid promotes the destabilization of the interface. Remarkably, under certain flow parameters, the presence of the particle stabilizes the interface when flowing in the less viscous liquid. The impact of particles is more significant as the capillary number increases or the Reynolds number decreases.
Explorando la desigualdad social y sexual en contextos urbanos coloniales a través de la enfermedad degenerativa articular: El caso de Mendoza (Argentina)
Authors: Giannotti P. Sebastián , Chiavazza Horacio D. , Luna Leandro H.
Published: March 2024

La organización social de las colonias españolas en América se caracterizó por la desigualdad, configurando estilos de vida disímiles dependiendo de la casta y estamento de pertenencia. Las investigaciones desarrolladas desde una perspectiva paleopatológica en la ciudad colonial de Mendoza (siglos dieciséis al diecinueve), ubicada en el centro-oeste del actual territorio argentino, permitió identificar estados de salud diferenciados en individuos inhumados en cementerios según su procedencia espacial (interior/exterior de los templos). El objetivo de este trabajo es evaluar la distribución de la enfermedad degenerativa articular (EDA) entre grupos de distinta procedencia socioeconómica, inhumados en cinco cementerios católicos coloniales del sitio Área Fundacional de Mendoza. Se relevaron superficies articulares apendiculares de 66 adultos de ambos sexos. No se registraron diferencias estadísticamente significativas entre individuos de diferentes sectores de inhumación, pero sí niveles de estrés mecánico-funcional diferenciados entre sexos según su procedencia social. Se discute la influencia del sexo, la edad y el tamaño corporal en las tendencias identificadas, siendo este último la variable que mayor influencia presentó. Los patrones de uso del cuerpo son interpretados en función del contexto histórico, el sexo y el estatus social del difunto y su familia.
Index estimates of compact hypersurfaces in smooth metric measure spaces
Authors: Batista Márcio , Martins Matheus B.
Published: March 2024

In this article, we investigate the spectra of the stability and Hodge–Laplacian operators on a compact manifold immersed as a hypersurface in a smooth metric measure space, possibly with singularities. Using ideas developed by A. Ros and A. Savo, along with an ingenious computation, we have obtained a comparison between the spectra of these operators. As a byproduct of this technique, we have deduced an estimate of the Morse index of such hypersurfaces.
The political consequences of technological change that benefits low-skilled workers
Authors: Finseraas Henning , Nyhus Ole Henning
Published: March 2024

Technological change often increases demand for high-skilled jobs, with low-skilled losers turning to the populist right in response. The political effects of technological change that increases demand for low-skilled workers are largely unknown. The growth of the salmon fish-farming industry in rural Norway improved the labor-market situation for low-skilled workers, and we find that support for the populist right-wing party increased in municipalities that benefitted from the industry growth. The electoral change is due to a right-wing shift on the economic, but not the cultural dimension. Our results support political economy frameworks that point to lower demand for state interventions after positive labor market shocks, but raise the question of in what contexts support for populism will decline.
Associations between disturbed sleep and attenuated psychotic experiences in people at clinical high risk for psychosis
Authors: Formica M. J. C. , Fuller-Tyszkiewicz M. , Reininghaus U. , Kempton M. , Delespaul P. , de Haan L. , Nelson B. , Mikocka-Walus A. , Olive L. , Ruhrmann S. , Rutten B. , Riecher-Rössler A. , Sachs G. , Valmaggia L. , van der Gaag M. , McGuire P. , van Os J. ,   EU-GEI High-Risk Study, Hartmann J. A.
Published: March 2024

Background

Pre-diagnostic stages of psychotic illnesses, including ‘clinical high risk’ (CHR), are marked by sleep disturbances. These sleep disturbances appear to represent a key aspect in the etiology and maintenance of psychotic disorders. We aimed to examine the relationship between self-reported sleep dysfunction and attenuated psychotic symptoms (APS) on a day-to-day basis.

Methods

Seventy-six CHR young people completed the Experience Sampling Methodology (ESM) component of the European Union Gene-Environment Interaction Study, collected through PsyMate® devices, prompting sleep and symptom questionnaires 10 times daily for 6 days. Bayesian multilevel mixed linear regression analyses were performed on time-variant ESM data using the brms package in R. We investigated the day-to-day associations between sleep and psychotic experiences bidirectionally on an item level. Sleep items included sleep onset latency, fragmentation, and quality. Psychosis items assessed a range of perceptual, cognitive, and bizarre thought content common in the CHR population.

Results

Two of the seven psychosis variables were unidirectionally predicted by previous night's number of awakenings: every unit increase in number of nightly awakenings predicted a 0.27 and 0.28 unit increase in feeling unreal or paranoid the next day, respectively. No other sleep variables credibly predicted next-day psychotic symptoms or vice-versa.

Conclusion

In this study, the relationship between sleep disturbance and APS appears specific to the item in question. However, some APS, including perceptual disturbances, had low levels of endorsement amongst this sample. Nonetheless, these results provide evidence for a unidirectional relationship between sleep and some APS in this population.
A non-anthropocentric solution to the Fermi paradox
Authors: Rakić Vojin
Published: March 2024

A few dozens of solutions to the Fermi paradox have been proposed in the past. The most relevant ones will be concisely discussed in this paper. They will be classified as follows: exceptionality solutions, annihilation solutions and communication barrier solutions. The argument will be advanced that all existing resolutions to the Fermi paradox are in their essence anthropocentric. The epistemological groundwork of anthropocentrism will be discussed. Conversely, in this paper, a non-anthropocentric solution to the Fermi paradox will be proposed: the ‘lasting human epistemological limitations solution’. This resolution to the Fermi paradox acknowledges that human epistemological capacities are limited to the degree that not only extraterrestrial forms of life may be unobservable to the human perceptive apparatus, but that universes may exist around humans with forms of life, inorganic matter or entities of any other type that humans are incapable of perceiving. In light of the revolutionary developments in theoretical physics, it is likely that in the future these developments will be reflected in increasingly non-anthropocentric solutions to the Fermi paradox.
Consolidating political leadership in healthcare: a mediating institution for priority-setting as a political strategy in a local health system
Authors: Bergstedt Emma , Sandman Lars , Nedlund Ann-Charlotte
Published: March 2024

The allocation of resources is a crucial part of political decision-making in healthcare, but explicit priorities are rarely set when resources are distributed. Two areas that have received some attention in research about legitimacy and priority-setting decisions in healthcare are the role of technical expert agencies as mediating institutions and the role of elected politicians. This paper investigates a political priority-setting advisory committee within a regional authority in Sweden. The aim is to explore how a political body can serve as a mediating institution for priority-setting in healthcare by disentangling the arrangements of its work in terms of what role it performs in the organisation and what it should do. The findings illustrate that promoting the notion of explicit priority-setting and the political aspects inherent in priority-setting in political healthcare management can contribute to consolidating political governance and leadership. There is, however, a complex tension between stability and conflicting values which has implications for the role of politicians as citizens' democratic representatives. This paper enhances our understanding of the role of mediating institutions and political properties of healthcare priority-setting, as well as our understanding of political and democratic healthcare governance in local self-government.
The Role of Subjective Socioeconomic Status in Predicting Academic Performance: Exploring the Mediating Influence of Sense of Belonging among Students in a Distance Learning University
Authors: Vázquez Alexandra , Alba Beatriz , Lois David , García-Ael Cristina , Bustillos Antonio
Published: March 2024

Building upon existing research conducted in face-to-face universities, our research explored whether, in the context of a distance learning institution, the positive association between subjective socioeconomic status and academic performance can be explained by students’ sense of belonging. To that end, we conducted a three-wave correlational study with 2,261 students enrolled in Social Psychology in a distance learning university. At the start of the academic year, we measured participants’ subjective socioeconomic status relative to other students alongside their initial expectations in terms of time investment and grades and other relevant covariates. Midway through the course, we assessed their sense of belonging to the university and, at the end, we recorded their grades. Results suggested that sense of belonging potentially serves as a mediating factor in the positive relationship between subjective socioeconomic status and grades even after accounting for variables like initial grade expectations, time commitment, gender, age, and employment situation. These findings emphasize the pivotal role of students’ psychological connection to the university in shaping their academic achievement, even within the expanding landscape of distance education.
Chat-basierte Krebsberatung in der Schweiz
Authors: Haslbeck Jörg , Casanova Flurina , Cascais Diana , Staudacher Sandra
Published: March 2024

Zusammenfassung: Hintergrund: Die Zahl der Menschen nimmt zu, die an Krebs erkranken, als Cancer Survivors weiterleben und zusammen mit ihren Angehörigen im Krankheitsverlauf Informations- und Beratungsbedürfnisse haben. Die Krebsliga Schweiz bietet mit der Cancerline eine Chat-basierte Beratung für Cancer Survivors an. Fragestellung/Ziel: Welche Bedürfnisse äußern Cancer Survivors in der Chat-Beratung Cancerline und was bedeutet dies für die Weiterentwicklung sowie Qualitätssicherung von Chat-basierter Beratung bei Krebs? Methode: Basierend auf den Prinzipien der Interpretive Description ( Thorne, 2016 ) wurden in sechs Analyseschritten 669 Chat-Beratungsprotokolle mit reflexiver thematischer Analyse nach Braun et al. (2018) in einem iterativen Prozess ausgewertet. Ergebnisse: Die Bedürfnisse zu Cancer Survivorship in der Cancerline sind vielschichtig. Neun Themen wurden identifiziert: Anonymen Chat zur Kommunikation brauchen, sich informieren, ethische Dilemmata abwägen und Entscheidungen treffen, Sinn und Hoffnung suchen, Wege zum Umgang mit belastenden Emotionen finden, soziale Konflikte lösen und andere nicht belasten, sich verstanden fühlen und eigenen Bedürfnissen Raum geben, Angehörigen-Rolle klären und sich korrekt verhalten, sowie nach Sicherheit streben. Schlussfolgerungen: Chat-basierte Beratung kann möglicherweise dazu beitragen, Cancer Survivors alltagsnah und flexibel bei Informationsbedürfnissen zu Krebs zu unterstützen. Fachpersonen können Betroffene auf Chat-basierte Beratung aufmerksam und so niederschwellige Beratung zugänglich machen.
The Middle Niger Basin in Nigeria Has a Rift Origin, as Revealed by the Inversion and Modeling of Gravity and Magnetic Data
Authors: Salawu Naheem Banji , Omosanya Kamaldeen Olakunle L. , Fournier Dominique
Published: March 2024

The NW‐SE oriented Middle Niger Basin, which is a Campano‐Maastrichtian inland basin has been the subject of debate among geoscientists regarding its origin and development. This paper aims to unravel the basin's origin and evolution by using high‐resolution magnetic, gravity, and topographical data. The integration of aeromagnetic and gravity data provides a means to assess the influence of igneous intrusions during the basin's evolution. The study presents a new perspective on the origin of the basin, suggesting a rift origin where orthogonal extension played a crucial role in its evolution. The research also investigates the relationship between intrusive rocks and the formation of the basin, finding these rocks are solely located within the basement. The magnetic and gravity maps reveal anomalies associated with intrusive structures within the Precambrian crystalline basement. This is a common feature shared with rifted basins on a global scale.
3D Stresses and Velocities Caused by Continental Plateaus: Scaling Analysis and Numerical Calculations With Application to the Tibetan Plateau
Authors: Macherel Emilie , Räss Ludovic , Schmalholz Stefan M.
Published: March 2024

Understanding stresses is crucial for geodynamics since they govern rock deformation and metamorphic reactions. However, the magnitudes and distribution of crustal stresses are still uncertain. Here, we use a 3D numerical model in spherical coordinates to investigate stresses and velocities that result from lateral crustal thickness variations around continental plateaus like those observed for the Tibetan plateau. We do not consider any far‐field deformation so that the plateau deforms by horizontal dilatation and vertical thinning. We assume viscous creep, a simplified plateau geometry, and simplified viscosity and density distributions to couple the numerical results with a scaling analysis. Specifically, we study the impact of the viscosity ratio between crust and lithospheric mantle, a rectangular plateau corner, a stress‐dependent power‐law flow law and Earth's double curvature on the crustal stress field and horizontal velocities. Two orders of magnitude variation in crustal and lithospheric mantle viscosities change the maximum crustal differential stress only by a factor of ≈2. We derive simple analytical estimates for the crustal deviatoric stress and horizontal velocity which agree to first order with 3D numerical calculations. We apply these estimates to calculate the average crustal viscosity in the eastern Tibetan plateau as ≈1022 Pa · s. Furthermore, our results show that a corner strongly affects the stress distribution, particularly the shear stresses, while Earth's curvature has a minor impact on the stresses. We further discuss potential implications of our results to strike‐slip faulting and fast exhumation around the Tibetan plateau's syntaxes.
Perceived Challenges to Tribally Led Shellfish Toxin Testing in Southeast Alaska: Findings From Key Informant Interviews
Authors: Roland Hugh B. , Kohlhoff Jacob , Lanphier Kari , Hoysala Sneha , Kennedy Esther G. , Harley John , Whitehead Christopher , Gribble Matthew O.
Published: March 2024

Shellfish harvesting is central to coastal Alaska Native ways of life, and tribes in Southeast Alaska are committed to preserving sustainable and safe access to subsistence foods. However, consumption of non‐commercially harvested shellfish puts Alaska Native communities at elevated risk of exposure to shellfish toxins. To address a lack of state or federal toxin testing for subsistence and recreational harvesting, tribes across Southeast Alaska have formed their own toxin testing and ocean monitoring program. In this study, we interviewed environmental managers responsible for tribes' testing and others with shellfish toxin expertise to report on perceptions of barriers to tribally led testing in Southeast Alaska. Tribal staff identified 40 prospective key informants to interview, including all environmental managers responsible for shellfish toxin testing at subsistence sites in Southeast Alaska. All 40 individuals were invited to participate in an interview and 27 individuals were interviewed. The most frequently discussed barriers to shellfish toxin testing in Southeast Alaska relate to logistical and staffing difficulties associated with communities' remote locations, inconsistent and inadequate funding and funding structures that increase staff burdens, risk communication challenges related to conveying exposure risks while supporting subsistence harvesting, and implications of climate change‐related shifts in toxin exposures for risk perception and risk communication. Participants stressed the social origins of perceived barriers. Disinvestment may create and sustain barriers and be most severely felt in Native communities and remote places. Climate change impacts may interact with social and cultural factors to further complicate risk management.
Intermittent Criticality Multi‐Scale Processes Leading to Large Slip Events on Rough Laboratory Faults
Authors: Kwiatek Grzegorz , Martínez‐Garzón Patricia , Goebel Thomas , Bohnhoff Marco , Ben‐Zion Yehuda , Dresen Georg
Published: March 2024

We discuss data of three laboratory stick‐slip experiments on Westerly Granite samples performed at elevated confining pressure and constant displacement rate on rough fracture surfaces. The experiments produced complex slip patterns including fast and slow ruptures with large and small fault slips, as well as failure events on the fault surface producing acoustic emission bursts without externally‐detectable stress drop. Preparatory processes leading to large slips were tracked with an ensemble of ten seismo‐mechanical and statistical parameters characterizing local and global damage and stress evolution, localization and clustering processes, as well as event interactions. We decompose complex spatio‐temporal trends in the lab‐quake characteristics and identify persistent effects of evolving fault roughness and damage at different length scales, and local stress evolution approaching large events. The observed trends highlight labquake localization processes on different spatial and temporal scales. The preparatory process of large slip events includes smaller events marked by confined bursts of acoustic emission activity that collectively prepare the fault surface for a system‐wide failure by conditioning the large‐scale stress field. Our results are consistent overall with an evolving process of intermittent criticality leading to large failure events, and may contribute to improved forecasting of large natural earthquakes.
Enriched Regions of 228Ra Along the U.S. GEOTRACES Pacific Meridional Transect (GP15)
Authors: Moore Willard S. , Charette Matthew A. , Henderson Paul B. , Hammond Douglas E. , Kemnitz Nathaniel , Le Roy Emilie , Kwon Eun Young , Hult Mikael
Published: March 2024

The half‐life of 228Ra (5.7 years) aligns well with near‐surface and near‐bottom ocean mixing timescales. Because 228Ra is sourced from sediments, regions of enhanced activity represent water that has recently interacted with sediments on the continental margin or seabed. The GP15 meridional transect from Alaska to Tahiti along152°W encountered several regions in the upper ocean where 228Ra was enriched. These enrichments follow surface and subsurface ocean current patterns and pair with earlier measurements of 228Ra and transient radionuclides to reveal the origins of these enriched regions. An enriched region at Alaska margin stations 1–3 was sourced locally but did not extend to the Alaskan trench at station 4. A large shallow region between 47° and 32°N. was sourced from the west by the North Pacific Current; another shallow enriched region between 11° and 5° N was also sourced from the west by the North Equatorial Countercurrent. Subsurface enrichments (100–400 m) between 18 and 47°N were associated with Central Mode Water and North Pacific Intermediate Water. The 228Ra activities in the upper Pacific were six times lower than activities in the Atlantic. In deep waters the primary enrichment was 27°–47°N. Two stations (32° and 37°N) were especially enriched, having near‐bottom inventories several times greater than other stations. With these two exceptions the remaining Pacific stations exhibited averaged inventories lower than those in the Atlantic. There was one region of enriched 223Ra (half‐life = 11 days) above the Puna Ridge near Hawaii.
Design, simulation, and testing of a tunable MEMS multi-threshold inertial switch
Authors: Xu Qiu , Rocha Rodrigo T. , Algoos Yousef , Feron Eric , Younis Mohammad I.
Published: March 2024

This paper presents a tunable multi-threshold micro-electromechanical inertial switch with adjustable threshold capability. The demonstrated device combines the advantages of accelerometers in providing quantitative acceleration measurements and g-threshold switches in saving power when in the inactive state upon experiencing acceleration below the thresholds. The designed proof-of-concept device with two thresholds consists of a cantilever microbeam and two stationary electrodes placed at different positions in the sensing direction. The adjustable threshold capability and the effect of the shock duration on the threshold acceleration are analytically investigated using a nonlinear beam model. Results are shown for the relationships among the applied bias voltage, the duration of shock impact, and the tunable threshold. The fabricated prototypes are tested using a shock-table system. The analytical results agree with the experimental results. The designed device concept is very promising for the classification of the shock and impact loads in transportation and healthcare applications.
Phenotypes for general behavior, activity, and body temperature in 3q29 deletion model mice
Authors: Mori Daisuke , Ikeda Ryosuke , Sawahata Masahito , Yamaguchi Sho , Kodama Akiko , Hirao Takashi , Arioka Yuko , Okumura Hiroki , Inami Chihiro , Suzuki Toshiaki , Hayashi Yu , Kato Hidekazu , Nawa Yoshihiro , Miyata Seiko , Kimura Hiroki , Kushima Itaru , Aleksic Branko , Mizoguchi Hiroyuki , Nagai Taku , Nakazawa Takanobu , Hashimoto Ryota , Kaibuchi Kozo , Kume Kazuhiko , Yamada Kiyofumi , Ozaki Norio
Published: March 2024

Whole genome analysis has identified rare copy number variations (CNV) that are strongly involved in the pathogenesis of psychiatric disorders, and 3q29 deletion has been found to have the largest effect size. The 3q29 deletion mice model (3q29-del mice) has been established as a good pathological model for schizophrenia based on phenotypic analysis; however, circadian rhythm and sleep, which are also closely related to neuropsychiatric disorders, have not been investigated. In this study, our aims were to reevaluate the pathogenesis of 3q29-del by recreating model mice and analyzing their behavior and to identify novel new insights into the temporal activity and temperature fluctuations of the mouse model using a recently developed small implantable accelerometer chip, Nano-tag. We generated 3q29-del mice using genome editing technology and reevaluated common behavioral phenotypes. We next implanted Nano-tag in the abdominal cavity of mice for continuous measurements of long-time activity and body temperature. Our model mice exhibited weight loss similar to that of other mice reported previously. A general behavioral battery test in the model mice revealed phenotypes similar to those observed in mouse models of schizophrenia, including increased rearing frequency. Intraperitoneal implantation of Nano-tag, a miniature acceleration sensor, resulted in hypersensitive and rapid increases in the activity and body temperature of 3q29-del mice upon switching to lights-off condition. Similar to the 3q29-del mice reported previously, these mice are a promising model animals for schizophrenia. Successive quantitative analysis may provide results that could help in treating sleep disorders closely associated with neuropsychiatric disorders.
Enhancing prime editor activity by directed protein evolution in yeast
Authors: Weber Yanik , Böck Desirée , Ivașcu Anastasia , Mathis Nicolas , Rothgangl Tanja , Ioannidi Eleonora I. , Blaudt Alex C. , Tidecks Lisa , Vadovics Máté , Muramatsu Hiromi , Reichmuth Andreas , Marquart Kim F. , Kissling Lucas , Pardi Norbert , Jinek Martin , Schwank Gerald
Published: March 2024

Prime editing is a highly versatile genome editing technology that enables the introduction of base substitutions, insertions, and deletions. However, compared to traditional Cas9 nucleases prime editors (PEs) are less active. In this study we use OrthoRep, a yeast-based platform for directed protein evolution, to enhance the editing efficiency of PEs. After several rounds of evolution with increased selection pressure, we identify multiple mutations that have a positive effect on PE activity in yeast cells and in biochemical assays. Combining the two most effective mutations – the A259D amino acid substitution in nCas9 and the K445T substitution in M-MLV RT – results in the variant PE_Y18. Delivery of PE_Y18, encoded on DNA, mRNA or as a ribonucleoprotein complex into mammalian cell lines increases editing rates up to 3.5-fold compared to PEmax. In addition, PE_Y18 supports higher prime editing rates when delivered in vivo into the liver or brain. Our study demonstrates proof-of-concept for the application of OrthoRep to optimize genome editing tools in eukaryotic cells.
ProTInSeq: transposon insertion tracking by ultra-deep DNA sequencing to identify translated large and small ORFs
Authors: Miravet-Verde Samuel , Mazzolini Rocco , Segura-Morales Carolina , Broto Alicia , Lluch-Senar Maria , Serrano Luis
Published: March 2024

Identifying open reading frames (ORFs) being translated is not a trivial task. ProTInSeq is a technique designed to characterize proteomes by sequencing transposon insertions engineered to express a selection marker when they occur in-frame within a protein-coding gene. In the bacterium Mycoplasma pneumoniae, ProTInSeq identifies 83% of its annotated proteins, along with 5 proteins and 153 small ORF-encoded proteins (SEPs; ≤100 aa) that were not previously annotated. Moreover, ProTInSeq can be utilized for detecting translational noise, as well as for relative quantification and transmembrane topology estimation of fitness and non-essential proteins. By integrating various identification approaches, the number of initially annotated SEPs in this bacterium increases from 27 to 329, with a quarter of them predicted to possess antimicrobial potential. Herein, we describe a methodology complementary to Ribo-Seq and mass spectroscopy that can identify SEPs while providing other insights in a proteome with a flexible and cost-effective DNA ultra-deep sequencing approach.
Disentangling top-down drivers of mortality underlying diel population dynamics of Prochlorococcus in the North Pacific Subtropical Gyre
Authors: Beckett Stephen J. , Demory David , Coenen Ashley R. , Casey John R. , Dugenne Mathilde , Follett Christopher L. , Connell Paige , Carlson Michael C. G. , Hu Sarah K. , Wilson Samuel T. , Muratore Daniel , Rodriguez-Gonzalez Rogelio A. , Peng Shengyun , Becker Kevin W. , Mende Daniel R. , Armbrust E. Virginia , Caron David A. , Lindell Debbie , White Angelicque E. , Ribalet François , Weitz Joshua S.
Published: March 2024

Photosynthesis fuels primary production at the base of marine food webs. Yet, in many surface ocean ecosystems, diel-driven primary production is tightly coupled to daily loss. This tight coupling raises the question: which top-down drivers predominate in maintaining persistently stable picocyanobacterial populations over longer time scales? Motivated by high-frequency surface water measurements taken in the North Pacific Subtropical Gyre (NPSG), we developed multitrophic models to investigate bottom-up and top-down mechanisms underlying the balanced control of Prochlorococcus populations. We find that incorporating photosynthetic growth with viral- and predator-induced mortality is sufficient to recapitulate daily oscillations of Prochlorococcus abundances with baseline community abundances. In doing so, we infer that grazers in this environment function as the predominant top-down factor despite high standing viral particle densities. The model-data fits also reveal the ecological relevance of light-dependent viral traits and non-canonical factors to cellular loss. Finally, we leverage sensitivity analyses to demonstrate how variation in life history traits across distinct oceanic contexts, including variation in viral adsorption and grazer clearance rates, can transform the quantitative and even qualitative importance of top-down controls in shaping Prochlorococcus population dynamics.
Natural variation in BnaA9.NF-YA7 contributes to drought tolerance in Brassica napus L
Authors: Wang Jia , Mao Lin , Li Yangyang , Lu Kun , Qu Cunmin , Tang Zhanglin , Li Jiana , Liu Liezhao
Published: March 2024

Rapeseed (Brassica napus) is one of the important oil crops worldwide. Its production is often threatened by drought stress. Here, we identify a transcription factor (BnaA9.NF-YA7) that negatively regulates drought tolerance through genome-wide association study in B. napus. The presence of two SNPs within a CCAAT cis element leads to downregulation of BnaA9.NF-YA7 expression. In addition, the M63I (G-to-C) substitution in the transactivation domain can activate low level expression of BnaA4.DOR, which is an inhibitory factor of ABA-induced stomatal closure. Furthermore, we determine that Bna.ABF3/4s directly regulate the expression of BnaA9.NF-YA7, and BnaA9.NF-YA7 indirectly suppresses the expression of Bna.ABF3/4s by regulation of Bna.ASHH4s. Our findings uncover that BnaA9.NF-YA7 serves as a supplementary role for ABA signal balance under drought stress conditions, and provide a potential molecular target to breed drought-tolerant B. napus cultivars.
Chloride intracellular channel (CLIC) proteins function as fusogens
Authors: Manori Bar , Vaknin Alisa , Vaňková Pavla , Nitzan Anat , Zaidel-Bar Ronen , Man Petr , Giladi Moshe , Haitin Yoni
Published: March 2024

Chloride Intracellular Channel (CLIC) family members uniquely transition between soluble and membrane-associated conformations. Despite decades of extensive functional and structural studies, CLICs’ function as ion channels remains debated, rendering our understanding of their physiological role incomplete. Here, we expose the function of CLIC5 as a fusogen. We demonstrate that purified CLIC5 directly interacts with the membrane and induces fusion, as reflected by increased liposomal diameter and lipid and content mixing between liposomes. Moreover, we show that this activity is facilitated by acidic pH, a known trigger for CLICs’ transition to a membrane-associated conformation, and that increased exposure of the hydrophobic inter-domain interface is crucial for this process. Finally, mutation of a conserved hydrophobic interfacial residue diminishes the fusogenic activity of CLIC5 in vitro and impairs excretory canal extension inC. elegansin vivo. Together, our results unravel the long-sought physiological role of these enigmatic proteins.
Human IgG Fc-engineering for enhanced plasma half-life, mucosal distribution and killing of cancer cells and bacteria
Authors: Foss Stian , Sakya Siri A. , Aguinagalde Leire , Lustig Marta , Shaughnessy Jutamas , Cruz Ana Rita , Scheepmaker Lisette , Mathiesen Line , Ruso-Julve Fulgencio , Anthi Aina Karen , Gjølberg Torleif Tollefsrud , Mester Simone , Bern Malin , Evers Mitchell , Bratlie Diane B. , Michaelsen Terje E. , Schlothauer Tilman , Sok Devin , Bhattacharya Jayanta , Leusen Jeanette , Valerius Thomas , Ram Sanjay , Rooijakkers Suzan H. M. , Sandlie Inger , Andersen Jan Terje
Published: March 2024

Monoclonal IgG antibodies constitute the fastest growing class of therapeutics. Thus, there is an intense interest to design more potent antibody formats, where long plasma half-life is a commercially competitive differentiator affecting dosing, frequency of administration and thereby potentially patient compliance. Here, we report on an Fc-engineered variant with three amino acid substitutions Q311R/M428E/N434W (REW), that enhances plasma half-life and mucosal distribution, as well as allows for needle-free delivery across respiratory epithelial barriers in human FcRn transgenic mice. In addition, the Fc-engineered variant improves on-target complement-mediated killing of cancer cells as well as both gram-positive and gram-negative bacteria. Hence, this versatile Fc technology should be broadly applicable in antibody design aiming for long-acting prophylactic or therapeutic interventions.
Inter-site structural heterogeneity induction of single atom Fe catalysts for robust oxygen reduction
Authors: Zhang Peng , Chen Hsiao-Chien , Zhu Houyu , Chen Kuo , Li Tuya , Zhao Yilin , Li Jiaye , Hu Ruanbo , Huang Siying , Zhu Wei , Liu Yunqi , Pan Yuan
Published: March 2024

Metal-nitrogen-carbon catalysts with hierarchically dispersed porosity are deemed as efficient geometry for oxygen reduction reaction (ORR). However, catalytic performance determined by individual and interacting sites originating from structural heterogeneity is particularly elusive and yet remains to be understood. Here, an efficient hierarchically porous Fe single atom catalyst (Fe SAs-HP) is prepared with Fe atoms densely resided at micropores and mesopores. Fe SAs-HP exhibits robust ORR performance with half-wave potential of 0.94 V and turnover frequency of 5.99 e−1s−1site−1 at 0.80 V. Theoretical simulations unravel a structural heterogeneity induced optimization, where mesoporous Fe-N4 acts as real active centers as a result of long-range electron regulation by adjacent microporous sites, facilitating O2 activation and desorption of key intermediate *OH. Multilevel operando characterization results identify active Fe sites undergo a dynamic evolution from basic Fe-N4 to active Fe-N3 under working conditions. Our findings reveal the structural origin of enhanced intrinsic activity for hierarchically porous Fe-N4 sites.
Control of feeding by a bottom-up midbrain-subthalamic pathway
Authors: Reis Fernando M. C. V. , Maesta-Pereira Sandra , Ollivier Matthias , Schuette Peter J. , Sethi Ekayana , Miranda Blake A. , Iniguez Emily , Chakerian Meghmik , Vaughn Eric , Sehgal Megha , Nguyen Darren C. T. , Yuan Faith T. H. , Torossian Anita , Ikebara Juliane M. , Kihara Alexandre H. , Silva Alcino J. , Kao Jonathan C. , Khakh Baljit S. , Adhikari Avishek
Published: March 2024

Investigative exploration and foraging leading to food consumption have vital importance, but are not well-understood. Since GABAergic inputs to the lateral and ventrolateral periaqueductal gray (l/vlPAG) control such behaviors, we dissected the role of vgat-expressing GABAergic l/vlPAG cells in exploration, foraging and hunting. Here, we show that in mice vgat l/vlPAG cells encode approach to food and consumption of both live prey and non-prey foods. The activity of these cells is necessary and sufficient for inducing food-seeking leading to subsequent consumption. Activation of vgat l/vlPAG cells produces exploratory foraging and compulsive eating without altering defensive behaviors. Moreover, l/vlPAG vgat cells are bidirectionally interconnected to several feeding, exploration and investigation nodes, including the zona incerta. Remarkably, the vgat l/vlPAG projection to the zona incerta bidirectionally controls approach towards food leading to consumption. These data indicate the PAG is not only a final downstream target of top-down exploration and foraging-related inputs, but that it also influences these behaviors through a bottom-up pathway.
Safety assessment and gastrointestinal retention of orally administered cerium oxide nanoparticles in rats
Authors: Han Hyoung-Yun , Kim Bo-Kyung , Rho Jinhyung , Park Se-Myo , Choi Mi-Sun , Kim Soojin , Heo Min Beom , Yang Young-Su , Oh Jung-Hwa , Lee Tae Geol , Yoon Seokjoo
Published: March 2024

Cerium oxide nanoparticles (CeO2 NPs, NM-212) are well-known for their catalytic properties and antioxidant potential, and have many applications in various industries, drug delivery, and cosmetic formulations. CeO2 NPs exhibit strong antimicrobial activity and can be used to efficiently remove pathogens from different environments. However, knowledge of the toxicological evaluation of CeO2 NPs is too limited to support their safe use. In this study, CeO2 NPs were orally administered to Sprague Dawley rats for 13 weeks at the doses of 0, 10, 100, and 1000 mg/kg bw/day, followed by a four week recovery period. The hematology values for the absolute and relative reticulocyte counts in male rats treated with 1000 mg/kg bw/day CeO2 NPs were lower than those in control rats. The clinical chemistry values for sodium and chloride in the treated male rat groups (100 and 1000 mg/kg/day) and total protein and calcium in the treated female rat groups (100 mg/kg/day) were higher than those in the control groups. However, these changes were not consistent in both sexes, and no abnormalities were found in the corresponding pathological findings. The results showed no adverse effects on any of the parameters assessed. CeO2 NPs accumulated in the jejunum, colon, and stomach wall of rats administered 1000 mg/kg CeO2 NPs for 90 days. However, these changes were not abnormal in the corresponding histopathological and immunohistochemical examinations. Therefore, 1000 mg/kg bw/day may be considered the “no observed adverse effect level” of CeO2 NPs (NM-212) in male and female SD rats under the present experimental conditions.
Direct TAMRA-dUTP labeling of M. tuberculosis genes using loop-mediated isothermal amplification (LAMP)
Authors: Altattan Basma , Ullrich Jasmin , Mattig Emily , Poppe Aline , Martins Renata , Bier Frank F.
Published: March 2024

Fluorescent molecule-based direct labeling of amplified DNA is a sensitive method employed across diverse DNA detection and diagnostics systems. However, using pre-labeled primers only allows for the attachment of a single fluorophore to each DNA strand and any modifications of the system are less flexible, requiring new sets of primers. As an alternative, direct labeling of amplified products with modified nucleotides is available, but still poorly characterized. To address these limitations, we sought a direct and adaptable approach to label amplicons produced through Loop-mediated isothermal amplification (LAMP), using labeled nucleotides (dUTPs) rather than primers. The focus of this study was the development and examination of a direct labeling technique of specific genes, including those associated with drug resistance in Mycobacterium tuberculosis. We used 5-(3-Aminoallyl)-2′-deoxyuridine-5′triphosphate, tagged with 5/6-TAMRA (TAMRA-dUTP) for labeling LAMP amplicons during the amplification process and characterized amplification and incorporation efficiency. The optimal TAMRA-dUTP concentration was first determined based on amplification efficiency (0.5% to total dNTPs). Higher concentrations of modified nucleotides reduced or completely inhibited the amplification yield. Target size also showed to be determinant to the success of amplification, as longer sequences showed lower amplification rates, thus less TAMRA incorporated amplicons. Finally, we were able to successfully amplify all four M. tuberculosis target genes using LAMP and TAMRA-modified dUTPs.
Exploring solar dynamo behavior using an annually resolved carbon-14 compilation during multiple grand solar minima
Authors: Inceoglu Fadil
Published: March 2024

In this study, we, for the first time, compiled all publicly available annually or biannually resolved $$^{14}$$

14

C records, which fully covers 7 grand solar minima at an annual and bi-annual resolution. Our results from 7 grand solar minima showed a clear relationship between the rate of decrease (increase) in solar activity levels and how long the onset (termination) of the grand solar minima will last. Additionally, we show a weaker relationship between the durations of onsets and terminations and between the rate of increase and decrease of solar activity levels. Our results also suggest there might be two or more types of grand solar minima.
A multimodal submillimeter MRI atlas of the human cerebellum
Authors: Lyu Wenjiao , Wu Ye , Huynh Khoi Minh , Ahmad Sahar , Yap Pew-Thian
Published: March 2024

The human cerebellum is engaged in a broad array of tasks related to motor coordination, cognition, language, attention, memory, and emotional regulation. A detailed cerebellar atlas can facilitate the investigation of the structural and functional organization of the cerebellum. However, existing cerebellar atlases are typically limited to a single imaging modality with insufficient characterization of tissue properties. Here, we introduce a multifaceted cerebellar atlas based on high-resolution multimodal MRI, facilitating the understanding of the neurodevelopment and neurodegeneration of the cerebellum based on cortical morphology, tissue microstructure, and intra-cerebellar and cerebello-cerebral connectivity.
Identification of microbial pathogens in Neolithic Scandinavian humans
Authors: Bergfeldt Nora , Kırdök Emrah , Oskolkov Nikolay , Mirabello Claudio , Unneberg Per , Malmström Helena , Fraser Magdalena , Sanchez-Quinto Federico , Jorgensen Roger , Skar Birgitte , Lidén Kerstin , Jakobsson Mattias , Storå Jan , Götherström Anders
Published: March 2024

With the Neolithic transition, human lifestyle shifted from hunting and gathering to farming. This change altered subsistence patterns, cultural expression, and population structures as shown by the archaeological/zooarchaeological record, as well as by stable isotope and ancient DNA data. Here, we used metagenomic data to analyse if the transitions also impacted the microbiome composition in 25 Mesolithic and Neolithic hunter-gatherers and 13 Neolithic farmers from several Scandinavian Stone Age cultural contexts. Salmonella enterica, a bacterium that may have been the cause of death for the infected individuals, was found in two Neolithic samples from Battle Axe culture contexts. Several species of the bacterial genus Yersinia were found in Neolithic individuals from Funnel Beaker culture contexts as well as from later Neolithic context. Transmission of e.g. Y. enterocolitica may have been facilitated by the denser populations in agricultural contexts.