bluuebunny/crossref_metadata_2025 huggingface dataset:
External cues improve visual working memory encoding in the presence of salient distractors in schizophrenia
Authors: Barnes-Scheufler Catherine V. , Rösler Lara , Schaum Michael , Schiweck Carmen , Peters Benjamin , Mayer Jutta S. , Reif Andreas , Wibral Michael , Bittner Robert A.
Published: March 2024

Background

People with schizophrenia (PSZ) are impaired in attentional prioritization of non-salient but relevant stimuli over salient distractors during visual working memory (VWM) encoding. Conversely, guidance of top–down attention by external predictive cues is intact. Yet, it is unknown whether this preserved ability can help PSZ encode more information in the presence of salient distractors.

Methods

We employed a visuospatial change-detection task using four Gabor patches with differing orientations in 66 PSZ and 74 healthy controls (HCS). Two Gabor patches flickered which were designated either as targets or distractors and either a predictive or a non-predictive cue was displayed to manipulate top–down attention, resulting in four conditions.

Results

We observed significant effects of group, salience and cue as well as significant interactions of salience by cue, group by salience and group by cue. Across all conditions, PSZ stored significantly less information in VWM than HCS. PSZ stored significantly less non-flickering than flickering information with a non-predictive cue. However, PSZ stored significantly more flickering and non-flickering information with a predictive cue.

Conclusions

Our findings indicate that control of attentional selection is impaired in schizophrenia. We demonstrate that additional top–down information significantly improves performance in PSZ. The observed deficit in attentional control suggests a disturbance of GABAergic inhibition in early visual areas. Moreover, our findings are indicative of a mechanism for enhancing attentional control in PSZ, which could be utilized by pro-cognitive interventions. Thus, the current paradigm is suitable to reveal both preserved and compromised cognitive component processes in schizophrenia.
Waka’ Stela 44 and the Early Classic Kaan hegemony
Authors: Kelly Mary Kate , Navarro-Farr Olivia , Freidel David A. , Pérez Calderón Juan Carlos , Pérez Robles Griselda
Published: March 2024

The Kaan (“Snake”) kings, a powerful political entity in the Classic Maya Lowlands, were housed in the Early Classic period at Dzibanche, and they moved their capital to Calakmul by the year a.d. 642 (Helmke and Awe 2016; Martin 2020:138–139). Their network of alliance and intermarriage radiated southward, and Waka's early eighth-century queen, Lady K'abel, was from the Kaan bloodline and married in to the Wak lineage, exemplifying the close connection between the two political entities. The discovery of Stela 44 in tunneling efforts in M13-1, the city's important ritual center, allows us to trace political ties between the Kaan and Wak kings to significantly earlier than previously known, which seem to begin around the mid-sixth century. This monument provides insight into three converging lines of evidence supporting the profound alliance these elites had built: first, the accession of a Wak king, Wa'oom Uch'ab Ahk, under the supervision of the Kaan king K'ahk’ Ti’ Ch'ich’; second, the father of the new king, Chak Tok Ich'aak, seems to be connected to La Corona, another early Kaan ally; and third, the mother of Wa'oom Uch'ab Ahk, Ix Ikoom, is also connected to La Corona and the broader Kaan hegemony through her title ix sak wahyis.
The duplication diacritic: A case study of variation and change in Mayan writing
Authors: Mora-Marín David F.
Published: March 2024

This article studies the duplication diacritic of Epigraphic Mayan (ISO 639-3 emy) during the Classic period (a.d. 200–900). Cataloged as grapheme 22A, it consists of two dots optionally and rarely affixed to another grapheme to command the reader, in the majority of cases, to read a syllabogram twice in sequence. This article reviews prior literature on the diacritic, elaborates a typology of four distinct but ultimately related functions, and employs a data set compiled by means of the Maya Hieroglyphic Database to determine via statistical tests whether scriptal, linguistic, media, geographic, and temporal factors were influential in its distribution, and more narrowly, its various functions. The results indicate that two lexemes, käkäw ‘cacao’ and k'ahk’ ‘fire,’ account for several of the scriptal and linguistic traits that show significant relationships with 22A, with the former, käkäw, likely serving as a major prototype in the evolution of 22A. It is also pointed out that 22A is absent from the Postclassic (a.d. 900–1521) codices, suggesting that one of the Classic regional subtraditions with lowest frequency of use of 22A may have been a direct ancestor of the subtraditions responsible for the codices.
Promoting standardisation in modern China: British and American engineers’ organisations, local Chinese engineers, and their transnational networks, 1901–41
Authors: Wu Lin-Chun
Published: March 2024

Standardisation is a product of the second wave of the Industrial Revolution in Europe and North America. This article examines how Western standardisation practices were introduced, transmitted, and promoted in China during the first half of the twentieth century. In particular, it looks at the critical role played by British, American, and local Chinese engineers in the transmission process. The topics covered in the present article have seldom been considered, and this article tries to fill the gap in scholarship. It analyses the shifting patterns of various standardisation efforts that are closely related to the governance of both cities and the wider nation. Work examined includes that of the Engineering Society of China, led by British engineers, which initiated standardisation in the Shanghai International Settlement in the early twentieth century; that of the Association of Chinese and American Engineers, founded by engineers of China and the USA, which, after World War I, began to implement the standardisation of railway infrastructure, with the cooperation of the Ministry of Transportation of the Beijing government; and efforts in the 1930s under the Nanjing government to establish an ‘engineering’ or ‘technocratic’ state, which included the execution of national schemes for the development of industrial standardisation. From the period of World War I until the 1930s, the orientation and practices of American standardisation strategies dominated China; then, due to the worsening situation of the Chinese–Japanese War, ideological tendencies and national strategies for standardisation began to diverge.
Foreign aromatics, olfactory culture, and scent connoisseurship in late medieval China
Authors: Feng Linda Rui
Published: March 2024

By the end of the Tang Dynasty (618–907 CE), olfactory culture in China had evolved significantly as coveted aromatics continued to be imported and in increasing quantities from Southeast Asia. Although there is no surviving treatise dedicated to aromatics from this period, anecdotes in prose literature describing the uses and curation of scents reveal a process in which imported aromatics were being actively incorporated into existing olfactory culture and accrued new social, aesthetic, and ritual significance. This process is discernible in two major respects. First, a discourse of connoisseurship for aromatics arose in contrast to the conspicuous consumption of imported aromatics that flaunted wealth and status. Secondly, aromatics that were once the privilege of the very few began to be circulated among a wider (admittedly still elite) population, as seen in the case of the dragon brain aromatic in late-Tang and Five Dynasties accounts. By delving into these and related prose narratives and by cross-examining these accounts against other types of records, this article examines how imported aromatic goods shaped the Tang elite's perception of how scent was—and could be—used as part of a socially rooted sensory experience.
How energy balance-related behaviours, temperament, stress and overweight associate: a cross-sectional study of Finnish preschoolers
Authors: Vepsäläinen Henna , Korkalo Liisa , Skaffari Essi , Abdollahi Anna M , Pajulahti Riikka , Lehto Reetta , Engberg Elina , Leppänen Marja H , Lehto Elviira , Ray Carola , Roos Eva , Erkkola Maijaliisa
Published: March 2024

Objective:

This study aimed to (1) examine the clustering of energy balance-related behaviours (EBRB) and (2) investigate whether EBRB clusters, temperament and hair cortisol concentration (HCC) associate with overweight.

Design:

We assessed food consumption using food records, screen time (ST) using sedentary behaviour diaries, sleep consistency and temperament (negative affectivity, surgency, effortful control) using questionnaires and HCC using hair samples. Accelerometers were used to assess physical activity (PA) intensities, sleep duration and sleep efficiency. Researchers measured each child’s weight and height. We used finite mixture models to identify EBRB clusters and multilevel logistic regression models to examine the associations between EBRB clusters, temperament, HCC and overweight.

Setting:

The cross-sectional DAGIS survey, data collected in 2015–2016.

Participants:

Finnish 3–6-year-olds (n 864) recruited through preschools.

Results:

One-third of the participants were categorised into the cluster labelled ‘Unhealthy diet, excessive screen time’, characterised by unhealthy dietary choices (e.g. greater consumption of high-fat, high-sugar dairy products) and longer ST. Two-thirds were categorised into the second cluster, labelled ‘Healthy diet, moderate screen time’. PA and sleep were irrelevant for clustering. Higher negative affectivity and lower effortful control associated with the ‘Unhealthy diet, excessive screen time’ cluster. EBRB clusters and HCC did not associate with overweight, but surgency was positively associated with overweight (OR = 1·63, 95 % CI 1·17, 2·25).

Conclusions:

Of the EBRB, food consumption and ST seem to associate. As temperament associates with EBRB clusters and overweight, tailored support acknowledging the child’s temperament could be profitable in maintaining a healthy weight.
Utilization of spatially fractionated radiotherapy in the management of a patient with inoperable uterine leiomyosarcoma
Authors: Sillanpaa Jussi , Donnelly Eric D.
Published: March 2024

Introduction:

A 53-year-old female presented with a large (945 cc) unresectable leiomyosarcoma of the uterus, with metastasis in the lungs, significant abdominal/pelvic pain and evidence of hydronephrosis secondary to obstruction caused by the mass. In an effort to palliate symptoms, radiation was recommended.

Methods:

Given the size of the lesion, the patient was treated with crossfire GRID, a type of spatially fractionated radiotherapy (18 Gy × 1), followed four weeks later by a short course of external beam radiation (4 Gy × 5).

Results:

The patient experienced significant symptom relief. Her abdominal/pelvic pain resolved, and a stent was placed to relieve her hydronephrosis. The tumour volume had decreased significantly (5·5 months post-treatment 276 cc, 8·5 months post-treatment 17 cc). Unfortunately, at 9 months post-treatment, the patient died from progression of her metastatic disease in the lungs.

Conclusions:

The use of GRID radiotherapy resulted in effective and sustained palliation of a large uterine leiomyosarcoma in this patient’s case.
Strong lensing by edge-on galaxies in UNIONS
Authors: Acevedo Barroso J. A. , Clément B. , Courbin F. , Gavazzi R. , Lemon C. , Rojas K. , Savary E.
Published: March 2024

Current searches for galaxy-scale strong lenses focus on massive Luminous Red Galaxies but tend to overlook late-type lenses, in part because of their smaller Einstein radii. We take advantage of the superb seeing of the UNIONS survey in the r-band to perform an imaging search for edge-on late-type lenses. We use Convolutional Neural Networks trained with simulated observations composed of images of real galaxies from UNIONS and real sources from HST. Using 3600 square degrees of the survey we test ∼7 million galaxies and find 56 systems with obvious signs of lensing. In addition, we empirically estimate the true prevalence of lenses in UNIONS by visually inspecting 120,000 randomly chosen images in the survey. We find that the number of edge-on lenses we discover with CNNs is compatible with these estimates.
Accounting for population-level systematic effects using a hierarchical strategy
Authors: Gomer Matthew R.
Published: March 2024

One of the largest sources of systematics in time-delay cosmography arises from Mass Sheet Transformation (MST). The degeneracy associated with this transformation is often broken by an assumed profile shape, such as a power-law. A hierarchical strategy has been developed which constrains the global profile shape on a population level, constrained collectively by the kinematics measurements of the lenses. This framework allows one to include non-time-delay lenses to provide constraints to the global profile, improving the H0 constraints. This work tests the hierarchical framework using analytical profiles, and additionally tests the capacity to combine two populations which come from the same profiles but probe different radii due to a change in source redshift. We find that the hierarchical framework is able to compensate for this effect, and the addition of non-time-delay lenses improves the H0 constraint, even though these lenses have different Einstein radii than their time-delay counterparts.
Incidence of mental health diagnoses during the COVID-19 pandemic: a multinational network study
Authors: Chai Yi , Man Kenneth K. C. , Luo Hao , Torre Carmen Olga , Wing Yun Kwok , Hayes Joseph F. , Osborn David P. J. , Chang Wing Chung , Lin Xiaoyu , Yin Can , Chan Esther W. , Lam Ivan C. H. , Fortin Stephen , Kern David M. , Lee Dong Yun , Park Rae Woong , Jang Jae-Won , Li Jing , Seager Sarah , Lau Wallis C. Y. , Wong Ian C. K.
Published: March 2024

Aims

Population-wide restrictions during the COVID-19 pandemic may create barriers to mental health diagnosis. This study aims to examine changes in the number of incident cases and the incidence rates of mental health diagnoses during the COVID-19 pandemic.

Methods

By using electronic health records from France, Germany, Italy, South Korea and the UK and claims data from the US, this study conducted interrupted time-series analyses to compare the monthly incident cases and the incidence of depressive disorders, anxiety disorders, alcohol misuse or dependence, substance misuse or dependence, bipolar disorders, personality disorders and psychoses diagnoses before (January 2017 to February 2020) and after (April 2020 to the latest available date of each database [up to November 2021]) the introduction of COVID-related restrictions.

Results

A total of 629,712,954 individuals were enrolled across nine databases. Following the introduction of restrictions, an immediate decline was observed in the number of incident cases of all mental health diagnoses in the US (rate ratios (RRs) ranged from 0.005 to 0.677) and in the incidence of all conditions in France, Germany, Italy and the US (RRs ranged from 0.002 to 0.422). In the UK, significant reductions were only observed in common mental illnesses. The number of incident cases and the incidence began to return to or exceed pre-pandemic levels in most countries from mid-2020 through 2021.

Conclusions

Healthcare providers should be prepared to deliver service adaptations to mitigate burdens directly or indirectly caused by delays in the diagnosis and treatment of mental health conditions.
Oriented Bedrock Samples Drilled by the Perseverance Rover on Mars
Authors: Weiss Benjamin P. , Mansbach Elias N. , Carsten Joseph L. , Kaplan Kyle W. , Maki Justin N. , Wiens Roger C. , Bosak Tanja , Collins Curtis L. , Fentress Jennifer , Feinberg Joshua M. , Goreva Yulia , Kennedy Wu Megan , Estlin Tara A. , Klein Douglas E. , Kronyak Rachel E. , Moeller Robert C. , Peper Nicholas , Reyes‐Newell Adriana , Sephton Mark A. , Shuster David L. , Simon Justin I. , Williford Kenneth H. , Stack Kathryn W. , Farley Kenneth A.
Published: March 2024

A key objective of the Perseverance rover mission is to acquire samples of Martian rocks for future return to Earth. Eventual laboratory analyses of these samples would address key questions about the evolution of the Martian climate, interior, and habitability. Many such investigations would benefit greatly from samples of Martian bedrock that are oriented in absolute Martian geographic coordinates. However, the Mars 2020 mission was designed without a requirement for orienting the samples. Here we describe a methodology that we developed for orienting rover drill cores in the Martian geographic frame and its application to Perseverance's first 20 rock samples. To orient the cores, three angles were measured: the azimuth and hade of the core pointing vector (i.e., vector oriented along the core axis) and the core roll (i.e., the solid body angle of rotation around the pointing vector). We estimated the core pointing vector from the attitude of the rover's Coring Drill during drilling. To orient the core roll, we used oriented images of asymmetric markings on the bedrock surface acquired with the rover's Wide Angle Topographic Sensor for Operations and eNgineering (WATSON) camera. For most samples, these markings were in the form of natural features on the outcrop, while for four samples they were artificial ablation pits produced by the rover's SuperCam laser. These cores are the first geographically‐oriented (<2.7° 3σtotal uncertainty) bedrock samples from another planetary body. This will enable a diversity of paleomagnetic, sedimentological, igneous, tectonic, and astrobiological studies on the returned samples.
Combined Genomic and Imaging Techniques Show Intense Arsenic Enrichment Caused by Detoxification in a Microbial Mat of the Dead Sea Shore
Authors: Thomas C. , Filella M. , Ionescu D. , Sorieul S. , Pollier C. G. L. , Oehlert A. M. , Zahajská P. , Gedulter N. , Agnon A. , Ferreira Sanchez D. , Ariztegui D.
Published: March 2024

Microbial mats and microbialites are essential tools for reconstructing early life and its environments. To better understand microbial trace element cycling, a microbial mat was collected from the sinkhole systems of the western shores of the Dead Sea, a dynamic environment exhibiting diverse extreme environments. Intense arsenic enrichment was measured (up to 6.5 million times higher than current concentrations in water, and 400 times the bulk concentration in the mat). Arsenic was found predominantly as As(V) in organic molecules, as shown by XANES spectra and high‐resolution elemental mapping. Arsenic cycling genes obtained from metagenomic analysis were associated with arsenic detoxification, supporting an active mechanism of As(V) uptake, As(III) efflux and organoarsenic accumulation in the extracellular polymeric substances (EPS) of the mat. Thus, we propose that such localized As enrichment can be attributed to a transient increase in As(V) concentrations in the circulating subsurface water of the Dead Sea shore and its subsequent incorporation into organoarsenic molecules through microbial detoxification processes. Our data set supports the possibility of metalloid enrichment recorded in very localized facies due to rapid geogenic fluctuations in the chemistry of the water flowing over a biofilm. In this context, this example calls for caution in interpreting metal(loid) enrichment in organic matter‐rich layers and microbialites of Paleoproterozoic origin. Arsenic signatures in Precambrian organic matter and carbonate rocks may host biosignatures, including evidence for extracellular polymeric substances, As‐binding and detoxification processes, without supporting arsenotrophy. However, they provide clues to better assess the paleoenvironmental conditions at the time of microbial mat formation.
A Machine Learning Parameterization of Clouds in a Coarse‐Resolution Climate Model for Unbiased Radiation
Authors: Henn Brian , Jauregui Yakelyn R. , Clark Spencer K. , Brenowitz Noah D. , McGibbon Jeremy , Watt‐Meyer Oliver , Pauling Andrew G. , Bretherton Christopher S.
Published: March 2024

Coarse‐grid weather and climate models rely particularly on parameterizations of cloud fields, and coarse‐grained cloud fields from a fine‐grid reference model are a natural target for a machine‐learned parameterization. We machine‐learn the coarsened‐fine cloud properties as a function of coarse‐grid model state in each grid cell of NOAA's FV3GFS global atmosphere model with 200 km grid spacing, trained using a 3 km fine‐grid reference simulation with a modified version of FV3GFS. The ML outputs are coarsened‐fine fractional cloud cover and liquid and ice cloud condensate mixing ratios, and the inputs are coarse model temperature, pressure, relative humidity, and ice cloud condensate. The predicted fields are skillful and unbiased, but somewhat under‐dispersed, resulting in too many partially cloudy model columns. When the predicted fields are applied diagnostically (offline) in FV3GFS's radiation scheme, they lead to small biases in global‐mean top‐of‐atmosphere (TOA) and surface radiative fluxes. An unbiased global‐mean TOA net radiative flux is obtained by setting to zero any predicted cloud with grid‐cell mean cloud fraction less than a threshold of 6.5%; this does not significantly degrade the ML prediction of cloud properties. The diagnostic, ML‐derived radiative fluxes are far more accurate than those obtained with the existing cloud parameterization in the nudged coarse‐grid model, as they leverage the accuracy of the fine‐grid reference simulation's cloud properties.
Simulating the Role of Biogeochemical Hotspots in Driving Nitrogen Export From Dryland Watersheds
Authors: Ren Jianning , Hanan Erin J. , Greene Aral , Tague Christina , Krichels Alexander H. , Burke William D. , Schimel Joshua P. , Homyak Peter M.
Published: March 2024

Climate change and nitrogen (N) pollution are altering biogeochemical and ecohydrological processes in dryland watersheds, increasing N export, and threatening water quality. While simulation models are useful for projecting how N export will change in the future, most models ignore biogeochemical “hotspots” that develop in drylands as moist microsites in the soil become hydrologically disconnected from plant roots when soils dry out. These hotspots enable N to accumulate over dry periods and rapidly flush to streams when soils wet up. To better project future N export, we developed a framework for representing hotspots using the ecohydrological model RHESSys. We then conducted a series of virtual experiments to understand how uncertainties in model structure and parameters influence N export to streams. Modeled N export was sensitive to three major factors (a) the abundance of hotspots in a watershed: N export increased linearly and then reached an asymptote with increasing hotspot abundance; this occurred because carbon and N inputs eventually became limiting as hotspots displaced vegetation cover, (b) the soil moisture threshold required for subsurface flow from hotspots to reestablish: peak streamflow N export increased and then decreased with an increasing threshold due to tradeoffs between N accumulation and export that occur with increasingly disconnected hotspots, and (c) the rate at which water diffused out of hotspots as soils dried down: N export was generally higher when the rate was slow because more N could accumulate in hotspots over dry periods, and then be flushed more rapidly to streams at the onset of rain. In a case study, we found that when hotspots were modeled explicitly, peak streamflow nitrate export increased by 29%, enabling us to better capture the timing and magnitude of N losses observed in the field. N export further increased in response to interannual precipitation variability, particularly when multiple dry years were followed by a wet year. This modeling framework can improve projections of N export in watersheds where hotspots play an increasingly important role in water quality.
Targeting Galectin 3 illuminates its contributions to the pathology of uterine serous carcinoma
Authors: Matoba Yusuke , Zarrella Dominique T. , Pooladanda Venkatesh , Azimi Mohammadabadi Maryam , Kim Eugene , Kumar Shaan , Xu Mengyao , Qin Xingping , Ray Lauren J , Devins Kyle M. , Kumar Raj , Kononenko Artem , Eisenhauer Eric , Veillard Irva E. , Yamagami Wataru , Hill Sarah J. , Sarosiek Kristopher A. , Yeku Oladapo O. , Spriggs David R. , Rueda Bo R.
Published: March 2024

Background

Uterine serous cancer (USC) comprises around 10% of all uterine cancers. However, USC accounts for approximately 40% of uterine cancer deaths, which is attributed to tumor aggressiveness and limited effective treatment. Galectin 3 (Gal3) has been implicated in promoting aggressive features in some malignancies. However, Gal3’s role in promoting USC pathology is lacking.

Methods

We explored the relationship between LGALS3 levels and prognosis in USC patients using TCGA database, and examined the association between Gal3 levels in primary USC tumors and clinical-pathological features. CRISPR/Cas9-mediated Gal3-knockout (KO) and GB1107, inhibitor of Gal3, were employed to evaluate Gal3’s impact on cell function.

Results

TCGA analysis revealed a worse prognosis for USC patients with high LGALS3. Patients with no-to-low Gal3 expression in primary tumors exhibited reduced clinical-pathological tumor progression. Gal3-KO and GB1107 reduced cell proliferation, stemness, adhesion, migration, and or invasion properties of USC lines. Furthermore, Gal3-positive conditioned media (CM) stimulated vascular tubal formation and branching and transition of fibroblast to cancer-associated fibroblast compared to Gal3-negative CM. Xenograft models emphasized the significance of Gal3 loss with fewer and smaller tumors compared to controls. Moreover, GB1107 impeded the growth of USC patient-derived organoids.

Conclusion

These findings suggest inhibiting Gal3 may benefit USC patients.
Endothelial cells regulate alveolar morphogenesis by constructing basement membranes acting as a scaffold for myofibroblasts
Authors: Watanabe-Takano Haruko , Kato Katsuhiro , Oguri-Nakamura Eri , Ishii Tomohiro , Kobayashi Koji , Murata Takahisa , Tsujikawa Koichiro , Miyata Takaki , Kubota Yoshiaki , Hanada Yasuyuki , Nishiyama Koichi , Watabe Tetsuro , Fässler Reinhard , Ishii Hirotaka , Mochizuki Naoki , Fukuhara Shigetomo
Published: March 2024

Alveologenesis is a spatially coordinated morphogenetic event, during which alveolar myofibroblasts surround the terminal sacs constructed by epithelial cells and endothelial cells (ECs), then contract to form secondary septa to generate alveoli in the lungs. Recent studies have demonstrated the important role of alveolar ECs in this morphogenetic event. However, the mechanisms underlying EC-mediated alveologenesis remain unknown. Herein, we show that ECs regulate alveologenesis by constructing basement membranes (BMs) acting as a scaffold for myofibroblasts to induce septa formation through activating mechanical signaling. Rap1, a small GTPase of the Ras superfamily, is known to stimulate integrin-mediated cell adhesions. EC-specific Rap1-deficient (Rap1iECKO) mice exhibit impaired septa formation and hypo-alveolarization due to the decreased mechanical signaling in myofibroblasts. In Rap1iECKO mice, ECs fail to stimulate integrin β1 to recruit Collagen type IV (Col-4) into BMs required for myofibroblast-mediated septa formation. Consistently, EC-specific integrin β1-deficient mice show hypo-alveolarization, defective mechanical signaling in myofibroblasts, and disorganized BMs. These data demonstrate that alveolar ECs promote integrin β1-mediated Col-4 recruitment in a Rap1-dependent manner, thereby constructing BMs acting as a scaffold for myofibroblasts to induce mechanical signal-mediated alveologenesis. Thus, this study unveils a mechanism of organ morphogenesis mediated by ECs through intrinsic functions.
Genetic architecture of the structural connectome
Authors: Wainberg Michael , Forde Natalie J. , Mansour Salim , Kerrebijn Isabel , Medland Sarah E. , Hawco Colin , Tripathy Shreejoy J.
Published: March 2024

Myelinated axons form long-range connections that enable rapid communication between distant brain regions, but how genetics governs the strength and organization of these connections remains unclear. We perform genome-wide association studies of 206 structural connectivity measures derived from diffusion magnetic resonance imaging tractography of 26,333 UK Biobank participants, each representing the density of myelinated connections within or between a pair of cortical networks, subcortical structures or cortical hemispheres. We identify 30 independent genome-wide significant variants after Bonferroni correction for the number of measures studied (126 variants at nominal genome-wide significance) implicating genes involved in myelination (SEMA3A), neurite elongation and guidance (NUAK1, STRN, DPYSL2, EPHA3, SEMA3A, HGF, SHTN1), neural cell proliferation and differentiation (GMNC, CELF4, HGF), neuronal migration (CCDC88C), cytoskeletal organization (CTTNBP2, MAPT, DAAM1, MYO16, PLEC), and brain metal transport (SLC39A8). These variants have four broad patterns of spatial association with structural connectivity: some have disproportionately strong associations with corticothalamic connectivity, interhemispheric connectivity, or both, while others are more spatially diffuse. Structural connectivity measures are highly polygenic, with a median of 9.1 percent of common variants estimated to have non-zero effects on each measure, and exhibited signatures of negative selection. Structural connectivity measures have significant genetic correlations with a variety of neuropsychiatric and cognitive traits, indicating that connectivity-altering variants tend to influence brain health and cognitive function. Heritability is enriched in regions with increased chromatin accessibility in adult oligodendrocytes (as well as microglia, inhibitory neurons and astrocytes) and multiple fetal cell types, suggesting that genetic control of structural connectivity is partially mediated by effects on myelination and early brain development. Our results indicate pervasive, pleiotropic, and spatially structured genetic control of white-matter structural connectivity via diverse neurodevelopmental pathways, and support the relevance of this genetic control to healthy brain function.
Notch2 controls developmental fate choices between germinal center and marginal zone B cells upon immunization
Authors: Babushku Tea , Lechner Markus , Ehrenberg Stefanie , Rambold Ursula , Schmidt-Supprian Marc , Yates Andrew J. , Rane Sanket , Zimber-Strobl Ursula , Strobl Lothar J.
Published: March 2024

Sustained Notch2 signals induce trans-differentiation of Follicular B (FoB) cells into Marginal Zone B (MZB) cells in mice, but the physiology underlying this differentiation pathway is still elusive. Here, we demonstrate that most B cells receive a basal Notch signal, which is intensified in pre-MZB and MZB cells. Ablation or constitutive activation of Notch2 upon T-cell-dependent immunization reveals an interplay between antigen-induced activation and Notch2 signaling, in which FoB cells that turn off Notch2 signaling enter germinal centers (GC), while high Notch2 signaling leads to generation of MZB cells or to initiation of plasmablast differentiation. Notch2 signaling is dispensable for GC dynamics but appears to be re-induced in some centrocytes to govern expansion of IgG1+ GCB cells. Mathematical modelling suggests that antigen-activated FoB cells make a Notch2 dependent binary fate-decision to differentiate into either GCB or MZB cells. This bifurcation might serve as a mechanism to archive antigen-specific clones into functionally and spatially diverse B cell states to generate robust antibody and memory responses.
Non-Hermitian non-equipartition theory for trapped particles
Authors: Li Xiao , Cao Yongyin , Ng Jack
Published: March 2024

The equipartition theorem is an elegant cornerstone theory of thermal and statistical physics. However, it fails to address some contemporary problems, such as those associated with optical and acoustic trapping, due to the non-Hermitian nature of the external wave-induced force. We use stochastic calculus to solve the Langevin equation and thereby analytically generalize the equipartition theorem to a theory that we denote the non-Hermitian non-equipartition theory. We use the non-Hermitian non-equipartition theory to calculate the relevant statistics, which reveal that the averaged kinetic and potential energies are no longer equal to kBT/2 and are not equipartitioned. As examples, we apply non-Hermitian non-equipartition theory to derive the connection between the non-Hermitian trapping force and particle statistics, whereby measurement of the latter can determine the former. Furthermore, we apply a non-Hermitian force to convert a saddle potential into a stable potential, leading to a different type of stable state.
QTL mapping of human retina DNA methylation identifies 87 gene-epigenome interactions in age-related macular degeneration
Authors: Advani Jayshree , Mehta Puja A. , Hamel Andrew R. , Mehrotra Sudeep , Kiel Christina , Strunz Tobias , Corso-Díaz Ximena , Kwicklis Madeline , van Asten Freekje , Ratnapriya Rinki , Chew Emily Y. , Hernandez Dena G. , Montezuma Sandra R. , Ferrington Deborah A. , Weber Bernhard H. F. , Segrè Ayellet V. , Swaroop Anand
Published: March 2024

DNA methylation provides a crucial epigenetic mark linking genetic variations to environmental influence. We have analyzed array-based DNA methylation profiles of 160 human retinas with co-measured RNA-seq and >8 million genetic variants, uncovering sites of genetic regulation in cis (37,453 methylation quantitative trait loci and 12,505 expression quantitative trait loci) and 13,747 DNA methylation loci affecting gene expression, with over one-third specific to the retina. Methylation and expression quantitative trait loci show non-random distribution and enrichment of biological processes related to synapse, mitochondria, and catabolism. Summary data-based Mendelian randomization and colocalization analyses identify 87 target genes where methylation and gene-expression changes likely mediate the genotype effect on age-related macular degeneration. Integrated pathway analysis reveals epigenetic regulation of immune response and metabolism including the glutathione pathway and glycolysis. Our study thus defines key roles of genetic variations driving methylation changes, prioritizes epigenetic control of gene expression, and suggests frameworks for regulation of macular degeneration pathology by genotype–environment interaction in retina.
Limited impact of hydrogen co-firing on prolonging fossil-based power generation under low emissions scenarios
Authors: Oshiro Ken , Fujimori Shinichiro
Published: March 2024

Climate change mitigation generally require rapid decarbonization in the power sector, including phase-out of fossil fuel-fired generators. Given recent technological developments, co-firing of hydrogen or ammonia, could help decarbonize fossil-based generators, but little is known about how its effects would play out globally. Here, we explore this topic using an energy system model. The results indicate that hydrogen co-firing occurs solely in stringent mitigation like 1.5 °C scenarios, where around half of existing coal and gas power capacity can be retrofitted for hydrogen co-firing, reducing stranded capacity, mainly in the Organization for Economic Co-operation and Development (OECD) countries and Asia. However, electricity supply from co-firing generators is limited to about 1% of total electricity generation, because hydrogen co-firing is mainly used as a backup option to balance the variable renewable energies. The incremental fuel cost of hydrogen results in lower capacity factor of hydrogen co-fired generators, whereas low-carbon hydrogen contributes to reducing emission cost associated with carbon pricing. While hydrogen co-firing may play a role in balancing intermittency of variable renewable energies, it will not seriously delay the phase-out of fossil-based generators.
A non-canonical nucleophile unlocks a new mechanistic pathway in a designed enzyme
Authors: Hutton Amy E. , Foster Jake , Crawshaw Rebecca , Hardy Florence J. , Johannissen Linus O. , Lister Thomas M. , Gérard Emilie F. , Birch-Price Zachary , Obexer Richard , Hay Sam , Green Anthony P.
Published: March 2024

Directed evolution of computationally designed enzymes has provided new insights into the emergence of sophisticated catalytic sites in proteins. In this regard, we have recently shown that a histidine nucleophile and a flexible arginine can work in synergy to accelerate the Morita-Baylis-Hillman (MBH) reaction with unrivalled efficiency. Here, we show that replacing the catalytic histidine with a non-canonical Nδ-methylhistidine (MeHis23) nucleophile leads to a substantially altered evolutionary outcome in which the catalytic Arg124 has been abandoned. Instead, Glu26 has emerged, which mediates a rate-limiting proton transfer step to deliver an enzyme (BHMeHis1.8) that is more than an order of magnitude more active than our earlier MBHase. Interestingly, although MeHis23 to His substitution in BHMeHis1.8 reduces activity by 4-fold, the resulting His containing variant is still a potent MBH biocatalyst. However, analysis of the BHMeHis1.8 evolutionary trajectory reveals that the MeHis nucleophile was crucial in the early stages of engineering to unlock the new mechanistic pathway. This study demonstrates how even subtle perturbations to key catalytic elements of designed enzymes can lead to vastly different evolutionary outcomes, resulting in new mechanistic solutions to complex chemical transformations.
Aqueous pyruvate partly dissociates under deep ultraviolet irradiation but is resilient to near ultraviolet excitation
Authors: Thøgersen Jan , Madzharova Fani , Weidner Tobias , Jensen Frank
Published: March 2024

The deep ultraviolet photochemistry of aqueous pyruvate is believed to have been essential to the origin of life, and near ultraviolet excitation of pyruvate in aqueous aerosols is assumed to contribute significantly to the photochemistry of the Earth’s atmosphere. However, the primary photochemistry of aqueous pyruvate is unknown. Here we study the susceptibility of aqueous pyruvate to photodissociation by deep ultraviolet and near ultraviolet irradiation with femtosecond spectroscopy supported by density functional theory calculations. The primary photo-dynamics of the aqueous pyruvate show that upon deep-UV excitation at 200 nm, about one in five excited pyruvate anions have dissociated by decarboxylation 100 ps after the excitation, while the rest of the pyruvate anions return to the ground state. Upon near-UV photoexcitation at a wavelength of 340 nm, the dissociation yield of aqueous pyruvate 200 ps after the excitation is insignificant and no products are observed. The experimental results are explained by our calculations, which show that aqueous pyruvate anions excited at 200 nm have sufficient excess energy for decarboxylation, whereas excitation at 340 nm provides the aqueous pyruvate anions with insufficient energy to overcome the decarboxylation barrier.
Filament formation drives catalysis by glutaminase enzymes important in cancer progression
Authors: Feng Shi , Aplin Cody , Nguyen Thuy-Tien T. , Milano Shawn K. , Cerione Richard A.
Published: March 2024

The glutaminase enzymes GAC and GLS2 catalyze the hydrolysis of glutamine to glutamate, satisfying the ‘glutamine addiction’ of cancer cells. They are the targets of anti-cancer drugs; however, their mechanisms of activation and catalytic activity have been unclear. Here we demonstrate that the ability of GAC and GLS2 to form filaments is directly coupled to their catalytic activity and present their cryo-EM structures which provide a view of the conformational states essential for catalysis. Filament formation guides an ‘activation loop’ to assume a specific conformation that works together with a ‘lid’ to close over the active site and position glutamine for nucleophilic attack by an essential serine. Our findings highlight how ankyrin repeats on GLS2 regulate enzymatic activity, while allosteric activators stabilize, and clinically relevant inhibitors block, filament formation that enables glutaminases to catalyze glutaminolysis and support cancer progression.
NDUFS4 regulates cristae remodeling in diabetic kidney disease
Authors: Mise Koki , Long Jianyin , Galvan Daniel L. , Ye Zengchun , Fan Guizhen , Sharma Rajesh , Serysheva Irina I. , Moore Travis I. , Jeter Collene R. , Anna Zal M. , Araki Motoo , Wada Jun , Schumacker Paul T. , Chang Benny H. , Danesh Farhad R.
Published: March 2024

The mitochondrial electron transport chain (ETC) is a highly adaptive process to meet metabolic demands of the cell, and its dysregulation has been associated with diverse clinical pathologies. However, the role and nature of impaired ETC in kidney diseases remains poorly understood. Here, we generate diabetic mice with podocyte-specific overexpression of Ndufs4, an accessory subunit of mitochondrial complex I, as a model investigate the role of ETC integrity in diabetic kidney disease (DKD). We find that conditional male mice with genetic overexpression of Ndufs4 exhibit significant improvements in cristae morphology, mitochondrial dynamics, and albuminuria. By coupling proximity labeling with super-resolution imaging, we also identify the role of cristae shaping protein STOML2 in linking NDUFS4 with improved cristae morphology. Together, we provide the evidence on the central role of NDUFS4 as a regulator of cristae remodeling and mitochondrial function in kidney podocytes. We propose that targeting NDUFS4 represents a promising approach to slow the progression of DKD.
Molecular basis of TMPRSS2 recognition by Paeniclostridium sordellii hemorrhagic toxin
Authors: Zhou Ruoyu , He Liuqing , Zhang Jiahao , Zhang Xiaofeng , Li Yanyan , Zhan Xiechao , Tao Liang
Published: March 2024

Hemorrhagic toxin (TcsH) is a major virulence factor produced by Paeniclostridium sordellii, which is a non-negligible threat to women undergoing childbirth or abortions. Recently, Transmembrane Serine Protease 2 (TMPRSS2) was identified as a host receptor of TcsH. Here, we show the cryo-EM structures of the TcsH-TMPRSS2 complex and uncover that TcsH binds to the serine protease domain (SPD) of TMPRSS2 through the CROP unit-VI. This receptor binding mode is unique among LCTs. Five top surface loops of TMPRSS2SPD, which also determine the protease substrate specificity, constitute the structural determinants recognized by TcsH. The binding of TcsH inhibits the proteolytic activity of TMPRSS2, whereas its implication in disease manifestations remains unclear. We further show that mutations selectively disrupting TMPRSS2-binding reduce TcsH toxicity in the intestinal epithelium of the female mice. These findings together shed light on the distinct molecular basis of TcsH-TMPRSS2 interactions, which expands our knowledge of host recognition mechanisms employed by LCTs and provides novel targets for developing therapeutics against P. sordellii infections.
Adsorption of crystal violet dye from synthetic wastewater by ball-milled royal palm leaf sheath
Authors: Sen Neloy , Shefa Nawrin Rahman , Reza Kismot , Shawon Sk Md Ali Zaker , Rahman Md. Wasikur
Published: March 2024

The current study shows that using a batch approach to remove crystal violet dye from synthetic wastewater is feasible when using royal palm leaf sheath powder as an adsorbent. In order to investigate the effects of many parameters, including starting concentration, pH effect, dye concentration, adsorbent dose, contact time, and temperature, experiments were carried out under various operating conditions. Maximum removal was obtained at pH 6 and at a concentration of 100 ppm, which are considered as ideal values. The influence of pH and dye concentration was shown to be substantial. Langmuir, Freundlich, and Temkin isotherm models were fitted to equilibrium data. The Langmuir isotherm model, which showed a maximum monolayer adsorption capacity of 454.5455 mg/g, best described the equilibrium data. The Pseudo-second-order kinetic model was found to closely resemble rather than the first-order and intra-particle diffusion models. Standard enthalpy (∆H◦), entropy (∆S◦), and free energy (∆G◦) were evaluated as thermodynamic parameters. It was discovered that the adsorption contact was endothermic in nature. The outcomes highlight the applicability of the inexpensive, locally accessible adsorbent in the specialty area of wastewater treatment and can be used in commercial dye-enriched effluent.
Evidence for chronic headaches induced by pathological changes of myodural bridge complex
Authors: Song Xue , Yu Sheng-Bo , Yuan Xiao-Ying , Alam Shah M. Adeel , Li Chan , Chi Yan-Yan , Zheng Nan , Sui Hong-Jin
Published: March 2024

Clinical studies have shown that there may be a certain relationship between pathological changes of the myodural bridge complex (MDBC) and chronic headaches of unknown cause. But there is still a lack of experimental evidence to explain the possible mechanism. This study aims to further confirm this relationship between MDBC and chronic headaches and explore its potential occurrence mechanism in rats. Bleomycin (BLM) or phosphate-buffered saline (PBS) was injected into the myodural bridge fibers of rats to establish the hyperplastic model of MDBC. After 4 weeks, the occurrence of headaches in rats was evaluated through behavioral scores. The immunohistochemistry staining method was applied to observe the expression levels of headache-related neurotransmitters in the brain. Masson trichrome staining results showed that the number of collagen fibers of MDBC was increased in the BLM group compared to those of the other two groups. It revealed hyperplastic changes of MDBC. The behavioral scores of the BLM group were significantly higher than those of the PBS group and the blank control group. Meanwhile, expression levels of CGRP and 5-HT in the headache-related nuclei of the brain were increased in the BLM group. The current study further confirms the view that there is a relationship between pathological changes of MDBC and chronic headaches of unknown cause. This study may provide anatomical and physiological explanations for the pathogenesis of some chronic headaches of unknown cause.
A novel portable anechoic chamber using ultra-thin 2D microwave absorber for industrial 5.0
Authors: Baghel Amit Kumar , Bikrat Youssef , Tavares Joana , Chaves Henrique , Oliveira Vinicius Uchoa , Pinho Pedro , Carvalho Nuno Borges , Alves Helena
Published: March 2024

In this paper, the authors, for the first time, have shown the use of 2D conformal microwave absorbing material (MAM) in the design and fabrication of a portable Anechoic chamber (AC). The MAM is fabricated on the transparent and conductive metal oxide layer named indium-tin-oxide (ITO) with Polyethylene terephthalate as the substrate and the ground plane for zero transmission having overall thickness of 0.012$$\lambda$$
λ
where $$\lambda$$
λ
is calculated at 0.7 GHz. The MAM is characterized for 0.7 to 18 GHz for both TE- and TM-polarisation and oblique incidence. High sheet resistance, dipole-like resonance structure patterned on the ITO, and the air-spacing between the layers is optimized to achieve broadband absorption. The MAM is used to line the six sides of the rectangular anechoic chamber having inner dimensions of: (L × W × H: 850 × 650 × 720 mm3). The return loss (RL), gain, and radiation pattern of three antenna working at 1.56, 2.43, and 4.93 GHz are analyzed inside the AC. The measurement results for all frequencies very well match with the simulation studies, thus validating and opening the door for the future use of ultra-thin and planar MAM in the AC.