bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of creatine supplementation on the myofibre characteristics and muscle protein synthesis of grass carp (Ctenopharyngodon idellus)
Authors: Tian Juan , Cheng Xiaoli , Yu Lijuan , Jiang Ming , Gao Weihua , Lu Xing , Zhang Wenbing , Wen Hua
Published: May 2022

To assess the role of dietary creatine on myofibre characteristics and protein synthesis in muscle, we fed grass carp (Ctenopharyngodon idellus, initial body weight: 88·47 ± 1·44 g) creatine-supplemented diets (1·84, 5·91, 8·48 and 15·44 g/kg diet) for 8 weeks. Creatine supplementation did not affect growth performance, but significantly increased creatine contents in muscle and liver. At 8·48 g/kg, creatine decreased the activities of alanine transaminase and aspartate aminotransferase in serum and improved hardness and chewiness of muscle due to shorter myofibre mean diameter, higher myofibre density and the frequencies of the diameters of classes I and III and collagen content, longer sarcomere length and upregulated mRNA levels of slow myosin heavy chains. Creatine supplementation upregulated the mRNA expressions of myogenic regulatory factors. The 8·48 g/kg creatine-supplemented diet significantly increased the contents of protein, total amino acids (AA), essential AA and free flavour AAs in muscle, the protein levels of insulin-like growth factor I, myogenic differentiation antigen and PPAR-γ coactlvator-1α in muscle and stimulated the phosphorylation of target of rapamycin (TOR) pathway in muscle. In summary, 8·48 mg/kg creatine improved fish health and skeletal muscle growth and increased hardness and protein synthesis in muscle of grass carp by affecting myofibre characteristics and the TOR signalling pathway. A second-order regression model revealed that the optimal dietary creatine supplementation of grass carp ranges between 8·48 and 12·04 g/kg.
Communication between the Militants of the ‘8 October’ Revolutionary Movement and the Peasants of Brotas de Macaúbas, Bahia, Brazil (1969–71)
Authors: Teló Fabricio
Published: May 2022

During the Brazilian military dictatorship (1964–85), the Movimento Revolucionário 8 de Outubro (‘8 October’ Revolutionary Movement, MR-8) attempted to mobilise peasants for its revolutionary project. This article analyses communication between MR-8 militants and peasants in Brotas de Macaúbas, Bahia. Based on interviews and document analysis, it documents the central role of José Campos Barreto (Zequinha) as a leader in this political process. The son of a local family, Zequinha enjoyed the respect of peasants and relied on his knowledge of their lives to better communicate with them. While the MR-8 made some inroads with peasants, its work in the region was prematurely ended when agents of the state descended on Brotas to arrest Carlos Lamarca, one of the dictatorship's most wanted militants.
Alternate Attendance Parades in the Japanese Domain of Satsuma, Seventeenth to Eighteenth Centuries: Pottery, Power and Foreign Spectacle
Authors: Clements Rebekah
Published: May 2022

This study examines the practice of ‘alternate attendance’ (sankin kōtai), in which the daimyo lords of Tokugawa Japan (1600–1868) marched with their retainers between their home territories and the shogunal capital of Edo, roughly once a year. Research on alternate attendance has focused on the meaning of daimyo processions outside their domains (han), along Japan's highways and in the city of Edo. Here I argue that, even as daimyo embarked upon a journey to pay obeisance to the shogun, the ambiguous nature of sovereignty in early modern Japan meant that alternate attendance could also be used for a local agenda, ritually stamping the daimyo's territory with signs of his dominance, much like what has been highlighted in the study of royal processions in world history. I focus on the seventeenth to eighteenth centuries, providing a case study of visits made by the Shimazu family, lords of Satsuma domain, to a village of Korean potters within their territory, whose antecedents had been brought as captives during the Imjin War of 1592–8. During daimyo visits, a relationship of mutual benefit and fealty between the Shimazu and the villagers was articulated through gift-giving, banqueting, dance and displays of local wares. This in turn was used to consolidate Shimazu power in their region.
The atypical pattern of irony comprehension in autistic children
Authors: Panzeri Francesca , Mazzaggio Greta , Giustolisi Beatrice , Silleresi Silvia , Surian Luca
Published: May 2022

Nonliteral language understanding has always been recognized as problematic in autistic individuals. We ran a study on 26 autistic children (mean age = 7.3 years) and 2 comparison groups of typically developing children, 1 matched for chronological age, and 1 of younger peers (mean age = 6.11 years) matched for linguistic abilities, aiming at assessing their understanding of ironic criticisms and compliments, and identifying the cognitive and linguistic factors that may underpin this ability. Autistic participants lagged behind the comparison groups in the comprehension of both types of irony, and their performance was related to mindreading and linguistic abilities. Significant correlations were found between first-order Theory of Mind (ToM) and both types of irony, between second-order ToM and ironic compliments, and between linguistic abilities and ironic criticisms. The autistic group displayed an interesting, and previously unattested in the literature, bimodal distribution: the great majority of them (n = 18) displayed a very poor performance in irony understanding, whereas some (n = 6) were at ceiling. We discuss these results in terms of two different profiles of autistic children.
Boundary making in the formative years of Tel Aviv Township, 1920–1923
Authors: Golan Arnon
Published: May 2022

Boundaries are defined and maintained to establish and preserve cultural, societal and political integrity. Boundaries change as territorial structures and their related meanings change over time, reflecting the transformation of economic, political, administrative and cultural practices and discourses, and inherent relations of power. The Israeli metropolis of Tel Aviv is no different in this context. The end of World War I and establishment of a British Mandate regime in Palestine resulted in the transformation of political, economic, social and cultural structures. The British Mandate afforded the rise of and development of Tel Aviv from Jaffa's Jewish garden suburb into a separate urban entity. Different internal and external factors affected the delineation of the urban bounds of Tel Aviv following its declaration by the British Mandate government as an autonomous township.
Timing of surgical repair of the stented aortic arch and coarctation in neonates
Authors: González-Calle Antonio , Guillén-Rodríguez Inmaculada , Coserria-Sánchez Felix
Published: May 2022

We report a neonate with aortic arch hypoplasia and coarctation, in whom patency of the arterial duct could not be re-established and who was too ill to undergo primary surgical correction safely. This patient was treated in two stages: 1) angioplasty and stenting, 2) surgical correction. The safe period for surgical correction may be 2–3 weeks after angioplasty and stenting.
Leaving a lasting legacy: A scoping review of ethical wills
Authors: Neller Sarah A. , McFarland Mary M. , Edelman Linda S. , Towsley Gail L.
Published: May 2022

Objectives

Palliative care guidelines recommend an interdisciplinary approach to address patients’ awareness of mortality and need for end-of-life preparation. An ethical will is a nonlegal way to address mortality by communicating a lasting and intangible legacy of values to others. The aim of this scoping review is to clarify the operationalization of ethical wills across disciplines and map the purposes and outcomes of creating an ethical will.

Methods

We followed the Joanna Briggs Institute methodology for scoping reviews. We searched 14 databases in November 2019 and January 2021 without filtering publication date or type. Two reviewers independently screened 1,948 publications. We extracted frequently used terms describing content, audience, format, purpose, and outcomes identified in ethical will creation.

Results

Fifty-one publications met inclusion criteria. Six (11.7%) were research articles. Twenty-four (47.1%) were lay literature published within law, estate, and financial planning. Collectively, our included studies defined an ethical will as a nonlegal way to express values, beliefs, life lessons and experiences, wisdom, love, history, hope for the future, blessings, apology, or forgiveness using any format (e.g., text, audio, video) that is meant to be shared with family, friends, or community. The most common purposes were to be remembered, address mortality, clarify life's meaning, and communicate what matters most. Creation provided opportunity to learn about self, served as a gift to both writer and recipient, and fostered generativity and sense of symbolic immortality.

Significance of results

Our findings highlight interdisciplinary utilization and a lack of research of ethical wills. This review provides supportive evidence for ethical wills as a way for patients to address mortality, renew intergenerational connections, solidify self, and promote transcendence before their final days. Ethical wills have potential to be incorporated into interdisciplinary palliative care in the future to address psychological symptoms for patients anticipating the end of life.
LEARNING TO SPELL IN LINEAR B: ORTHOGRAPHY AND SCRIBAL TRAINING IN MYCENAEAN PYLOS
Authors: Judson Anna P.
Published: May 2022

This article analyses orthographic variation in the Linear B tablets from the Mycenaean palace of Pylos. Despite the general consistency in spelling found in Linear B texts from all sites, variation was in certain cases both permissible and entirely normal, even within the work of a single writer. Examining the patterns of orthographic variation found in the texts from Pylos, along with the factors which may have influenced this variation, sheds light on how the Mycenaean scribes were taught to write and how they applied this training in the process of creating their documents.
Determinants of Nutritional Differences in Mediterranean Rural Spain, 1840–1965 Birth Cohorts: A Comparison between Irrigated and Dry Farming Agriculture
Authors: Ayuda María-Isabel , Puche Javier , Martínez-Carrión José Miguel
Published: May 2022

Anthropometric studies have given much attention to the impact of industrialization and urbanization on the biological standards of living of urban populations. Instead, we know less about the evolution of height and the disparities within the rural world and how they have changed during the modern economic growth process. This article analyzes the evolution and the determining factors that would explain the inequality of the biological welfare of a group of rural populations in Mediterranean Spain. Using a database of the heights of military conscripts (N = 146,041) of the study area, a comparison is made of the biological well-being of the cohorts born between 1840 and 1965 in different rural environments (irrigated vs. dry farming). The results show that the recruits residing in irrigated areas were taller than those in dry farming areas and that the nutritional differences were greater among the latter. The advantage of the heights in irrigated areas widened with the development of commercial agriculture at the end of the nineteenth century and, although it began to reduce from the early decades of the twentieth century, the anthropometric gap persisted throughout the period analyzed. The data also suggest that the distribution of income was also more unequal in the dry farming areas, where the diet was less varied and rich than in the irrigated areas. This situation could be largely explained by the existence of low productivity agriculture in these dry farming areas, among other possible factors.
Athletic Performance in Immersive Virtual Reality
Authors: Shimi Andria , Papantoniou Antonis , Neokleous Kleanthis , Avraamides Marios N.
Published: May 2022

Abstract. Background: In a goalkeeping task that entailed intercepting fast-approaching balls, the present research examined whether training under conditions more intense than those of a subsequent test yields a performance improvement. Methods: Fifty participants (38 males) carried out the goalkeeping task in two conditions: In the progressive-intensity condition, participants carried out three training sessions with increasing intensity (i.e., balls shot at increasingly faster speeds) that exceeded that of a pretest and a posttest; in the fixed-intensity condition, participants also carried out three training conditions but at a fixed intensity equal to that of both the pretest and the posttest. Results: Performance in the goalkeeping task improved from pretest to posttest equally under the two intensity conditions. Similarly, performance on a different task that required fast responses to visual targets also increased from pretest to posttest, likewise equally for the two intensity conditions. Conclusions: Overall, these results challenge the common belief in sports that more intense training than a subsequent test is beneficial for performance.
Relationship of Interoceptive Accuracy With Risky Decision-Making and	Treatment Outcomes in Male Patients With Alcohol Use Disorder
Authors: Sönmez Mehmet Bülent , Meriç Işıl Avcu , Sübay Büşra , Görgülü Yasemin
Published: May 2022

Abstract. Lower levels of interoceptive awareness (IA) may be present in individuals with substance use disorder (SUD), and damage to related brain regions caused by substance use may disrupt IA. Disturbance in the bodily feedback system may fail to engage in effective decision-making. This study focused on the premise that interoceptive accuracy (IAc), as the primary construct of IA, is implicated in SUD and that poor IAc is linked to risky decision-making and adversely affects treatment outcomes. Eighty-five patients with alcohol use disorder (AUD) (current severity: moderate or severe) and 87 healthy control subjects were enrolled in the present study. All participants performed the heart rate tracking task and a computerized version of the Iowa gambling task (IGT). Characteristics of patients’ addiction profiles were assessed with the Addiction Profile Index (API) Clinical Form. IAc and IGT scores of patients with AUD were lower than healthy controls. IGT scores of patients with low IAc were lower than those of patients with high IAc and decreased IAc is predictive of decreased IGT scores. No significant differences were determined in treatment outcomes at 3, 6, and 12 months after hospitalization between the low-IAc and high-IAc patient groups. Our results suggest that IAc is implicated in AUD and that poor IAc is predictive of increased risky decision-making. Risky decision-making that results in substance use may be partly related to a deficit in the interoceptive ability to guide behavior. Focus on IAc without reference to complex clinical case presentations in AUD makes it difficult to draw any definitive conclusions about the role of IAc in clinical outcomes.
Thresholds in Road Network Functioning on US Atlantic and Gulf Barrier Islands
Authors: Aldabet Sofia , Goldstein Evan B. , Lazarus Eli D.
Published: May 2022

Barrier islands predominate the Atlantic and Gulf coastlines of the USA, where population and infrastructure growth exceed national trends. Forward‐looking models of barrier island dynamics often include feedbacks with real estate markets and management practices aimed at mitigating damage to buildings from natural hazards. However, such models thus far do not account for networks of infrastructure, such as roads, and how the functioning of infrastructure networks might influence management strategies. Understanding infrastructure networks on barrier islands is an essential step toward improved insight into the future dynamics of human‐altered barriers. Here, we examine thresholds in the functioning of 72 US Atlantic and Gulf Coast barrier islands. We use digital elevation models to assign an elevation to each intersection in each road network. From each road network we sequentially remove intersections, starting from the lowest elevation. We use the maxima of the second giant connected component to identify a specific intersection—and corresponding elevation—at which functioning of the network fails, and we match the elevation of each critical intersection to local annual exceedance probabilities for extreme high‐water levels. We find a range of failure thresholds for barrier island road network functioning, and also find that no single metric—absolute elevation, annual exceedance probability, or a quantitative metric of robustness—sufficiently ranks the susceptibility of barrier road networks to failure. Future work can incorporate thresholds for road network into forward‐looking models of barrier island dynamics that include hazard‐mitigation practices for protecting infrastructure.
Towards Retrieving Reliable Ocean Surface Currents in the Coastal Zone From the Sentinel‐1 Doppler Shift Observations
Authors: Moiseev A. , Johannessen J. A. , Johnsen H.
Published: May 2022

Recent developments on calibration and partitioning of the signal between the wave and current contributions significantly improve the accuracy of geophysical retrievals from Sentinel‐1 Synthetic Aperture Radar‐based Doppler shift measurements in the open ocean. In this study, we revise the Sentinel‐1B Interferometric Wide products acquired from December 2017 to January 2018 along the coastal zone of northern Norway. We find that the satellite attitude is responsible for 30% of the variation in the Doppler shift observations, while the antenna pattern can describe an additional 15%. The residual variation after recalibration is about 3.8 Hz, corresponding to 0.21–0.15 m/s radial velocity (RVL) depending on the incidence angle. Using recalibrated Sentinel‐1 observations, collocated with near‐surface wind from MetCoOp‐Ensemble Prediction System and sea state from MyWaveWAM, we develop an empirical function (CDOP3SiX) for estimating the sea‐state‐induced Doppler shift. CDOP3SiX improves the accuracy of sea state contribution estimates under mixed wind fetch conditions and demonstrates that the Norwegian Coastal Current can be detected in the Sentinel‐1 derived ocean surface current RVL maps. Moreover, two anticyclonic mesoscale eddies with radial velocities of about 0.5 m/s are detected. The surface current patterns are consistent with the collocated sea surface temperature observations. The Doppler shift observations from Sentinel‐1 can therefore be used to study ocean surface currents in the coastal zone with a 1.5 km spatial resolution.
An Analog Offline EnKF for Paleoclimate Data Assimilation
Authors: Sun Haohao , Lei Lili , Liu Zhengyu , Ning Liang , Tan Zhe‐Min
Published: May 2022

An analog offline ensemble Kalman filter (AOEnKF) is proposed, which constructs ensemble priors from a control climate simulation for each assimilation time based on an analog criterion using proxy observations. Even though AOEnKF is an offline scheme and is therefore computationally economical, it has the ability to capture “flow‐dependent” background error covariances that help spread observation information through climate fields. Extensive tests in the Lorenz05 model demonstrate that, compared to the online cycling EnKF (CEnKF), AOEnKF generates smaller posterior errors and requires much less computational cost. Compared to the commonly applied offline EnKF (OEnKF), AOEnKF has the advantages of having a more accurate prior ensemble mean and “flow‐dependent” background error covariances, even though the assimilation time scale is beyond significant forecast skill of the climate model. With varying ensemble sizes, sample sizes, observation error covariances and observing networks, AOEnKFs generally produce statistically significant error reduction relative to OEnKF, especially for larger sample sizes, increased observation uncertainties and sparser observing networks. The AOEnKF can be applied based on either the error of state variables from observations (AOEnKF_E) or the spatial correlation of state variables with observations (AOEnKF_C), with generally comparable results.
Comparative characterization of 3D chromatin organization in triple-negative breast cancers
Authors: Kim Taemook , Han Sungwook , Chun Yujin , Yang Hyeokjun , Min Hyesung , Jeon Sook Young , Kim Jang-il , Moon Hyeong-Gon , Lee Daeyoup
Published: May 2022

Triple-negative breast cancer (TNBC) is a malignant cancer subtype with a high risk of recurrence and an aggressive phenotype compared to other breast cancer subtypes. Although many breast cancer studies conducted to date have investigated genetic variations and differential target gene expression, how 3D chromatin architectures are reorganized in TNBC has been poorly elucidated. Here, using in situ Hi-C technology, we characterized the 3D chromatin organization in cells representing five distinct subtypes of breast cancer (including TNBC) compared to that in normal cells. We found that the global and local 3D architectures were severely disrupted in breast cancer. TNBC cell lines (especially BT549 cells) showed the most dramatic changes relative to normal cells. Importantly, we detected CTCF-dependent TNBC-susceptible losses/gains of 3D chromatin organization and found that these changes were strongly associated with perturbed chromatin accessibility and transcriptional dysregulation. In TNBC tissue, 3D chromatin disorganization was also observed relative to the 3D chromatin organization in normal tissues. We observed that the perturbed local 3D architectures found in TNBC cells were partially conserved in TNBC tissues. Finally, we discovered distinct tissue-specific chromatin loops by comparing normal and TNBC tissues. In this study, we elucidated the characteristics of the 3D chromatin organization in breast cancer relative to normal cells/tissues at multiple scales and identified associations between disrupted structures and various epigenetic features and transcriptomes. Collectively, our findings reveal important 3D chromatin structural features for future diagnostic and therapeutic studies of TNBC.
Maternal prenatal depressive symptoms and toddler behavior: an umbilical cord blood epigenome-wide association study
Authors: Kallak Theodora Kunovac , Fransson Emma , Bränn Emma , Berglund Hanna , Lager Susanne , Comasco Erika , Lyle Robert , Skalkidou Alkistis
Published: May 2022

Children of mothers with prenatal depressive symptoms (PND) have a higher risk of behavioral problems; fetal programming through DNA methylation is a possible underlying mechanism. This study investigated DNA methylation in cord blood to identify possible “at birth” signatures that may indicate susceptibility to behavioral problems at 18 months of age. Cord blood was collected from 256 children of mothers who had self-reported on symptoms of depression during pregnancy and the behavior of their child at 18 months of age. Whole genome DNA methylation was assessed using Illumina MethylationEPIC assay. The mother and child pairs were categorized into four groups, based on both self-reported depressive symptoms, PND or Healthy control (HC), and scores from the Child Behavior checklist (high or low for internalizing, externalizing, and total scores). Adjustments were made for batch effects, cell-type, and clinical covariates. Differentially methylated sites were identified using Kruskal–Wallis test, and Benjamini–Hochberg adjustedpvalues < 0.05 were considered significant. The analysis was also stratified by sex of the child. Among boys, we observed higher and correlated DNA methylation of one CpG-site in the promoter region ofTPP1in the HC group, with high externalizing scores compared to HC with low externalizing scores. Boys in the PND group showed lower DNA methylation inNUDT15among those with high, compared to low, internalizing scores; the DNA methylation levels of CpGs in this gene were positively correlated with the CBCL scores. Hence, the differentially methylated CpG sites could be of interest for resilience, regardless of maternal mental health during pregnancy. The findings are in a relatively healthy study cohort, thus limiting the possibility of detecting strong effects associated with behavioral difficulties. This is the first investigation of cord blood DNA methylation signs of fetal programming of PND on child behavior at 18 months of age and thus calls for independent replications.
Small extracellular vesicle-mediated miR-320e transmission promotes osteogenesis in OPLL by targeting TAK1
Authors: Xu Chen , Zhang Zicheng , Liu Ning , Li Li , Zhong Huajian , Wang Ruizhe , Shi Qianghui , Zhang Zifan , Wei Leixin , Hu Bo , Zhang Hao , Shen Xiaolong , Wang Yue , Liu Yang , Yuan Wen
Published: May 2022

Ossification of the posterior longitudinal ligament (OPLL) is an emerging spinal disease caused by heterotopic ossification of the posterior longitudinal ligament. The pathological mechanism is poorly understood, which hinders the development of nonsurgical treatments. Here, we set out to explore the function and mechanism of small extracellular vesicles (sEVs) in OPLL. Global miRNA sequencings are performed on sEVs derived from ligament cells of normal and OPLL patients, and we have showed that miR-320e is abundantly expressed in OPLL-derived sEVs compare to other sEVs. Treatment with either sEVs or miR-320e significantly promote the osteoblastic differentiation of normal longitudinal ligament cells and mesenchymal stem cells and inhibit the osteoclastic differentiation of monocytes. Through a mechanistic study, we find that TAK1 is a downstream target of miR-320e, and we further validate these findings in vivo using OPLL model mice. Together, our data demonstrate that OPLL ligament cells secrete ossification-promoting sEVs that contribute to the development of ossification through the miR-320e/TAK1 axis.
Recycling of memory B cells between germinal center and lymph node subcapsular sinus supports affinity maturation to antigenic drift
Authors: Zhang Yang , Garcia-Ibanez Laura , Ulbricht Carolin , Lok Laurence S. C. , Pike Jeremy A. , Mueller-Winkler Jennifer , Dennison Thomas W. , Ferdinand John R. , Burnett Cameron J. M. , Yam-Puc Juan C. , Zhang Lingling , Alfaro Raul Maqueda , Takahama Yousuke , Ohigashi Izumi , Brown Geoffrey , Kurosaki Tomohiro , Tybulewicz Victor L. J. , Rot Antal , Hauser Anja E. , Clatworthy Menna R. , Toellner Kai-Michael
Published: May 2022

Infection or vaccination leads to the development of germinal centers (GC) where B cells evolve high affinity antigen receptors, eventually producing antibody-forming plasma cells or memory B cells. Here we follow the migratory pathways of B cells emerging from germinal centers (BEM) and find that many BEM cells migrate into the lymph node subcapsular sinus (SCS) guided by sphingosine-1-phosphate (S1P). From the SCS, BEM cells may exit the lymph node to enter distant tissues, while some BEM cells interact with and take up antigen from SCS macrophages, followed by CCL21-guided return towards the GC. Disruption of local CCL21 gradients inhibits the recycling of BEM cells and results in less efficient adaption to antigenic variation. Our findings thus suggest that the recycling of antigen variant-specific BEM cells and transport of antigen back to GC may support affinity maturation to antigenic drift.
ON/OFF domains shape receptive field structure in mouse visual cortex
Authors: Tring Elaine , Duan Konnie K. , Ringach Dario L.
Published: May 2022

In higher mammals, thalamic afferents to primary visual cortex (area V1) segregate according to their responses to increases (ON) or decreases (OFF) in luminance. This organization induces columnar, ON/OFF domains postulated to provide a scaffold for the emergence of orientation tuning. To further test this idea, we asked whether ON/OFF domains exist in mouse V1. Here we show that mouse V1 is indeed parceled into ON/OFF domains. Interestingly, fluctuations in the relative density of ON/OFF neurons on the cortical surface mirror fluctuations in the relative density of ON/OFF receptive field centers on the visual field. Moreover, the local diversity of cortical receptive fields is explained by a model in which neurons linearly combine a small number of ON and OFF signals available in their cortical neighborhoods. These findings suggest that ON/OFF domains originate in fluctuations of the balance between ON/OFF responses across the visual field which, in turn, shapes the structure of cortical receptive fields.
Observing polarization patterns in the collective motion of nanomechanical arrays
Authors: Doster Juliane , Shah Tirth , Fösel Thomas , Paulitschke Philipp , Marquardt Florian , Weig Eva M.
Published: May 2022

In recent years, nanomechanics has evolved into a mature field, and it has now reached a stage which enables the fabrication and study of ever more elaborate devices. This has led to the emergence of arrays of coupled nanomechanical resonators as a promising field of research serving as model systems to study collective dynamical phenomena such as synchronization or topological transport. From a general point of view, the arrays investigated so far can be effectively treated as scalar fields on a lattice. Moving to a scenario where the vector character of the fields becomes important would unlock a whole host of conceptually interesting additional phenomena, including the physics of polarization patterns in wave fields and their associated topology. Here we introduce a new platform, a two-dimensional array of coupled nanomechanical pillar resonators, whose orthogonal vibration directions encode a mechanical polarization degree of freedom. We demonstrate direct optical imaging of the collective dynamics, enabling us to analyze the emerging polarization patterns, follow their evolution with drive frequency, and identify topological polarization singularities.
Atomistic mechanism of phase transformation between topologically close-packed complex intermetallics
Authors: Jin Huixin , Zhang Jianxin , Li Pan , Zhang Youjian , Zhang Wenyang , Qin Jingyu , Wang Lihua , Long Haibo , Li Wei , Shao Ruiwen , Ma En , Zhang Ze , Han Xiaodong
Published: May 2022

Understanding how topologically close-packed phases (TCPs) transform between one another is one of the challenging puzzles in solid-state transformations. Here we use atomic-resolved tools to dissect the transition among TCPs, specifically the μ and P (or σ) phases in nickel-based superalloys. We discover that the P phase originates from intrinsic (110) faulted twin boundaries (FTB), which according to first-principles calculations is of extraordinarily low energy. The FTB sets up a pathway for the diffusional in-flux of the smaller 3d transition metal species, creating a Frank interstitial dislocation loop. The climb of this dislocation, with an unusual Burgers vector that displaces neighboring atoms into the lattice positions of the product phase, accomplishes the structural transformation. Our findings reveal an intrinsic link among these seemingly unrelated TCP configurations, explain the role of internal lattice defects in facilitating the phase transition, and offer useful insight for alloy design that involves different complex phases.
Estimating global economic well-being with unlit settlements
Authors: McCallum Ian , Kyba Christopher Conrad Maximillian , Bayas Juan Carlos Laso , Moltchanova Elena , Cooper Matt , Cuaresma Jesus Crespo , Pachauri Shonali , See Linda , Danylo Olga , Moorthy Inian , Lesiv Myroslava , Baugh Kimberly , Elvidge Christopher D. , Hofer Martin , Fritz Steffen
Published: May 2022

It is well established that nighttime radiance, measured from satellites, correlates with economic prosperity across the globe. In developing countries, areas with low levels of detected radiance generally indicate limited development – with unlit areas typically being disregarded. Here we combine satellite nighttime lights and the world settlement footprint for the year 2015 to show that 19% of the total settlement footprint of the planet had no detectable artificial radiance associated with it. The majority of unlit settlement footprints are found in Africa (39%), rising to 65% if we consider only rural settlement areas, along with numerous countries in the Middle East and Asia. Significant areas of unlit settlements are also located in some developed countries. For 49 countries spread across Africa, Asia and the Americas we are able to predict and map the wealth class obtained from ~2,400,000 geo-located households based upon the percent of unlit settlements, with an overall accuracy of 87%.
Combinatorial GxGxE CRISPR screen identifies SLC25A39 in mitochondrial glutathione transport linking iron homeostasis to OXPHOS
Authors: Shi Xiaojian , Reinstadler Bryn , Shah Hardik , To Tsz-Leung , Byrne Katie , Summer Luanna , Calvo Sarah E. , Goldberger Olga , Doench John G. , Mootha Vamsi K. , Shen Hongying
Published: May 2022

The SLC25 carrier family consists of 53 transporters that shuttle nutrients and co-factors across mitochondrial membranes. The family is highly redundant and their transport activities coupled to metabolic state. Here, we use a pooled, dual CRISPR screening strategy that knocks out pairs of transporters in four metabolic states — glucose, galactose, OXPHOS inhibition, and absence of pyruvate — designed to unmask the inter-dependence of these genes. In total, we screen 63 genes in four metabolic states, corresponding to 2016 single and pair-wise genetic perturbations. We recover 19 gene-by-environment (GxE) interactions and 9 gene-by-gene (GxG) interactions. One GxE interaction hit illustrates that the fitness defect in the mitochondrial folate carrier (SLC25A32) KO cells is genetically buffered in galactose due to a lack of substrate in de novo purine biosynthesis. GxG analysis highlights a buffering interaction between the iron transporter SLC25A37 (A37) and the poorly characterized SLC25A39 (A39). Mitochondrial metabolite profiling, organelle transport assays, and structure-guided mutagenesis identify A39 as critical for mitochondrial glutathione (GSH) import. Functional studies reveal that A39-mediated glutathione homeostasis and A37-mediated mitochondrial iron uptake operate jointly to support mitochondrial OXPHOS. Our work underscores the value of studying family-wide genetic interactions across different metabolic environments.
A multiplex platform for small RNA sequencing elucidates multifaceted tRNA stress response and translational regulation
Authors: Watkins Christopher P. , Zhang Wen , Wylder Adam C. , Katanski Christopher D. , Pan Tao
Published: May 2022

Small RNAs include tRNA, snRNA, micro-RNA, tRNA fragments and others that constitute > 90% of RNA copy numbers in a human cell and perform many essential functions. Popular small RNA-seq strategies limit the insights into coordinated small RNA response to cellular stress. Small RNA-seq also lacks multiplexing capabilities. Here, we report a multiplex small RNA-seq library preparation method (MSR-seq) to investigate cellular small RNA and mRNA response to heat shock, hydrogen peroxide, and arsenite stress. Comparing stress-induced changes of total cellular RNA and polysome-associated RNA, we identify a coordinated tRNA response that involves polysome-specific tRNA abundance and synergistic N3-methylcytosine (m3C) tRNA modification. Combining tRNA and mRNA response to stress we reveal a mechanism of stress-induced down-regulation in translational elongation. We also find that native tRNA molecules lacking several modifications are biased reservoirs for the biogenesis of tRNA fragments. Our results demonstrate the importance of simultaneous investigation of small RNAs and their modifications in response to varying biological conditions.
Detecting positive quantum capacities of quantum channels
Authors: Singh Satvik , Datta Nilanjana
Published: May 2022

Determining whether a noisy quantum channel can be used to reliably transmit quantum information is a challenging problem in quantum information theory. This is because it requires computation of the channel’s coherent information for an unbounded number of copies of the channel. In this paper, we devise an elementary perturbative technique to solve this problem in a wide variety of circumstances. Our analysis reveals that a channel’s ability to transmit information is intimately connected to the relative sizes of its input, output, and environment spaces. We exploit this link to develop easy tests which can be used to detect positivity of quantum channel capacities simply by comparing the channels’ input, output, and environment dimensions. Several noteworthy examples, such as the depolarizing and transpose-depolarizing channels (including the Werner-Holevo channel), dephasing channels, generalized Pauli channels, multi-level amplitude damping channels, and (conjugate) diagonal unitary covariant channels, serve to aptly exhibit the utility of our method. Notably, in all these examples, the coherent information of a single copy of the channel turns out to be positive.
Development of functionally relevant potency assays for monovalent and multivalent vaccines delivered by evolving technologies
Authors: Sanyal Gautam
Published: May 2022

A potency or potency-indicating assay is a regulatory requirement for the release of every lot of a vaccine. Potency is a critical quality attribute that is also monitored as a stability indicator of a vaccine product. In essence, a potency measurement is a test of the functional integrity of the antigen and is intended to ensure that the antigen retains immunocompetence, i.e., the ability to stimulate the desired immune response, in its final formulation. Despite its central importance, there is incomplete clarity about the definition and expectation of a potency assay. This article provides a perspective on the purpose, value, and challenges associated with potency testing for vaccines produced by new technologies. The focus is on messenger RNA vaccines in the light of experience gained with recombinant protein-based vaccines, which offer the opportunity to directly correlate in vitro antigenicity with in vivo immunogenicity. The challenges with developing immunologically relevant in vitro assays are discussed especially for multivalent vaccine products, the importance of which has been reinforced by the ongoing emergence of SARS-CoV-2 variants of concern. Immunoassay-based release of multivalent vaccine products, such as those containing multiple antigens from different variants or serotypes of the same virus, require antibodies that are selective for each antigen and do not significantly cross-react with the others. In the absence of such exclusively specific antibodies, alternative functional assays with demonstrable correlation to immunogenicity may be acceptable. Initiatives for geographically distributed vaccine technology facilities should include establishing these assay capabilities to enable rapid delivery of vaccines globally.
Fault-tolerant operation of a logical qubit in a diamond quantum processor
Authors: Abobeih M. H. , Wang Y. , Randall J. , Loenen S. J. H. , Bradley C. E. , Markham M. , Twitchen D. J. , Terhal B. M. , Taminiau T. H.
Published: May 2022

Solid-state spin qubits is a promising platform for quantum computation and quantum networks1,2. Recent experiments have demonstrated high-quality control over multi-qubit systems3–8, elementary quantum algorithms8–11 and non-fault-tolerant error correction12–14. Large-scale systems will require using error-corrected logical qubits that are operated fault tolerantly, so that reliable computation becomes possible despite noisy operations15–18. Overcoming imperfections in this way remains an important outstanding challenge for quantum science15,19–27. Here, we demonstrate fault-tolerant operations on a logical qubit using spin qubits in diamond. Our approach is based on the five-qubit code with a recently discovered flag protocol that enables fault tolerance using a total of seven qubits28–30. We encode the logical qubit using a new protocol based on repeated multi-qubit measurements and show that it outperforms non-fault-tolerant encoding schemes. We then fault-tolerantly manipulate the logical qubit through a complete set of single-qubit Clifford gates. Finally, we demonstrate flagged stabilizer measurements with real-time processing of the outcomes. Such measurements are a primitive for fault-tolerant quantum error correction. Although future improvements in fidelity and the number of qubits will be required to suppress logical error rates below the physical error rates, our realization of fault-tolerant protocols on the logical-qubit level is a key step towards quantum information processing based on solid-state spins.
Single-cell genomic profiling of human dopamine neurons identifies a population that selectively degenerates in Parkinson’s disease
Authors: Kamath Tushar , Abdulraouf Abdulraouf , Burris S. J. , Langlieb Jonah , Gazestani Vahid , Nadaf Naeem M. , Balderrama Karol , Vanderburg Charles , Macosko Evan Z.
Published: May 2022

The loss of dopamine (DA) neurons within the substantia nigra pars compacta (SNpc) is a defining pathological hallmark of Parkinson’s disease (PD). Nevertheless, the molecular features associated with DA neuron vulnerability have not yet been fully identified. Here, we developed a protocol to enrich and transcriptionally profile DA neurons from patients with PD and matched controls, sampling a total of 387,483 nuclei, including 22,048 DA neuron profiles. We identified ten populations and spatially localized each within the SNpc using Slide-seq. A single subtype, marked by the expression of the geneAGTR1and spatially confined to the ventral tier of SNpc, was highly susceptible to loss in PD and showed the strongest upregulation of targets ofTP53andNR2F2, nominating molecular processes associated with degeneration. This same vulnerable population was specifically enriched for the heritable risk associated with PD, highlighting the importance of cell-intrinsic processes in determining the differential vulnerability of DA neurons to PD-associated degeneration.
Hyperexcitability in young iPSC-derived C9ORF72 mutant motor neurons is associated with increased intracellular calcium release
Authors: Burley Sarah , Beccano-Kelly Dayne A. , Talbot Kevin , Llana Oscar Cordero , Wade-Martins Richard
Published: May 2022

A large hexanucleotide repeat expansion in the C9ORF72 gene is the most prevalent cause of amyotrophic lateral sclerosis (ALS). To better understand neuronal dysfunction during ALS progression, we studied motor neuron (MN) cultures derived from iPSC lines generated from C9ORF72 (C9) expansion carriers and unaffected controls. C9 and control MN cultures showed comparable mRNA levels for MN markers SMI-32, HB9 and ISL1 and similar MN yields (> 50% TUJ1/SMI-32 double-positive MNs). Using whole-cell patch clamp we showed that C9-MNs have normal membrane capacitance, resistance and resting potential. However, immature (day 40) C9-MNs exhibited a hyperexcitable phenotype concurrent with increased release of calcium (Ca2+) from internal stores, but with no changes to NaV and KV currents. Interestingly, this was a transient phenotype. By day 47, maturing C9-MNs demonstrated normal electrophysiological activity, displaying only subtle alterations on mitochondrial Ca2+ release. Together, these findings suggest the potential importance of a developmental component to C9ORF72-related ALS.
Cost-effectiveness of managing HBV reactivation in patients with resolved HBV infection treated with anti-CD20 antibody for B-cell non-Hodgkin lymphoma
Authors: Fujita Misuzu , Kusumoto Shigeru , Ishii Itsuko , Iwata Tadashi , Fujisawa Takehiko , Sugiyama Masaya , Hata Akira , Mizokami Masashi
Published: May 2022

There is no universal recommendation for managing the reactivation of HBV in patients with resolved HBV infection treated with anti-CD20 monoclonal antibodies for B-cell non-Hodgkin lymphoma. This study compared the cost-effectiveness of two commonly used strategies: prophylactic anti-HBV nucleos(t)ide analog therapy (Pro NAT), and HBV DNA monitoring followed by on-demand antiviral therapy (HBV DNA monitoring). Using a decision tree model, the incremental cost-effectiveness ratio (ICER) expressed as cost per quality-adjusted life-year (QALY) gained was calculated. The threshold for cost-effectiveness was set at 5,000,000 JPY, equivalent to 45,662 USD. In a base–case analysis, HBV DNA monitoring was found to be more cost-effective based on the calculation of ICER as 132,048 USD per QALY, a value that far exceeds 45,662 USD. The same results were consistently obtained by a one-way deterministic sensitivity analysis, even after changing each parameter value within the predetermined range. A probabilistic sensitivity analysis with 10,000 simulations also revealed that HBV DNA monitoring is more cost-effective than Pro NAT in 96.8% of cases. Therefore, this study suggests that HBV DNA monitoring is an appropriate managing measure in Japan from a cost-effectiveness perspective.
Admixture and breed traceability in European indigenous pig breeds and wild boar using genome-wide SNP data
Authors: Dadousis Christos , Muñoz Maria , Óvilo Cristina , Fabbri Maria Chiara , Araújo José Pedro , Bovo Samuele , Potokar Marjeta Čandek , Charneca Rui , Crovetti Alessandro , Gallo Maurizio , García-Casco Juan María , Karolyi Danijel , Kušec Goran , Martins José Manuel , Mercat Marie-José , Pugliese Carolina , Quintanilla Raquel , Radović Čedomir , Razmaite Violeta , Ribani Anisa , Riquet Juliet , Savić Radomir , Schiavo Giuseppina , Škrlep Martin , Tinarelli Silvia , Usai Graziano , Zimmer Christoph , Fontanesi Luca , Bozzi Riccardo
Published: May 2022

Preserving diversity of indigenous pig (Sus scrofa) breeds is a key factor to (i) sustain the pork chain (both at local and global scales) including the production of high-quality branded products, (ii) enrich the animal biobanking and (iii) progress conservation policies. Single nucleotide polymorphism (SNP) chips offer the opportunity for whole-genome comparisons among individuals and breeds. Animals from twenty European local pigs breeds, reared in nine countries (Croatia: Black Slavonian, Turopolje; France: Basque, Gascon; Germany: Schwabisch-Hällisches Schwein; Italy: Apulo Calabrese, Casertana, Cinta Senese, Mora Romagnola, Nero Siciliano, Sarda; Lithuania: Indigenous Wattle, White Old Type; Portugal: Alentejana, Bísara; Serbia: Moravka, Swallow-Bellied Mangalitsa; Slovenia: Krškopolje pig; Spain: Iberian, Majorcan Black), and three commercial breeds (Duroc, Landrace and Large White) were sampled and genotyped with the GeneSeek Genomic Profiler (GGP) 70 K HD porcine genotyping chip. A dataset of 51 Wild Boars from nine countries was also added, summing up to 1186 pigs (~ 49 pigs/breed). The aim was to: (i) investigate individual admixture ancestries and (ii) assess breed traceability via discriminant analysis on principal components (DAPC). Albeit the mosaic of shared ancestries found for Nero Siciliano, Sarda and Moravka, admixture analysis indicated independent evolvement for the rest of the breeds. High prediction accuracy of DAPC mark SNP data as a reliable solution for the traceability of breed-specific pig products.