bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of anthelmintic effectiveness to control Fasciola hepatica and paramphistome mixed infection in cattle in the humid tropics of Mexico
Authors: Ico-Gómez Rodrigo , González-Garduño Roberto , Ortiz-Pérez Diego , Mosqueda-Gualito Juan J. , Flores-Santiago Ever del J. , Sosa-Pérez Gustavo , Salazar-Tapia Abel A.
Published: July 2021

The objective of this study was to evaluate the effectiveness of the main anthelmintics used for the control of trematodes in cattle in an endemic area in the humid Mexican tropics. A diagnostic study was carried out in nine cattle farms to determine the prevalence of flukes through faecal examination. Only three farms with more than 20 cows positive to trematodes were chosen to determine the effectiveness of commercial anthelmintics (triclabendazole, TCBZ; ivermectin + closantel, (IVM + CLOS); IVM + clorsulon, (CLORS); nitroxynil, NITROX). The prevalence of Fasciola hepatica was 27.1% and 29.6% of paramphistomes. The faecal egg count of trematodes ranged from 0.0 to 12.2 eggs per gram of faeces. The highest effectiveness against F. hepatica was 96.7%, and 92.7% against paramphistomes. NITROX was the most effective in the control of trematodes, while other products, such as IVM + CLORS and TCBZ obtained values lower than 90%, which puts sustainable trematode control at risk. The presence of trematodes was observed on most farms, although the prevalence per herd was highly variable, which indicates that the trematodes F. hepatica and paramphistomes are endemic to the region and a suitable management programme is suggested to control infections caused by these parasites.
Technological Change and the International System
Authors: Milner Helen V. , Solstad Sondre Ulvund
Published: July 2021

Do world politics affect the adoption of new technology? States overwhelmingly rely on technology invented abroad, and their differential intensity of technology use accounts for many of their differences in economic development. Much of the literature on technology adoption focuses on domestic conditions. The authors argue instead that the structure of the international system is critical because it affects the level of competition among states, which in turn affects leaders’ willingness to enact policies that speed technology adoption. Countries adopt new technology as they seek to avoid being vulnerable to attack or coercion by other countries. By systematically examining states’ adoption of technology over the past two hundred years, the authors find that countries adopt new technologies faster when the international system is less concentrated, that changes in systemic concentration have a temporally causal effect on technology adoption, and that government policies to promote technology adoption are related to concerns about rising international competition. A competitive international system is an important incentive for technological change and may underlie global technology waves.
What is Social Science History, Anyway?
Authors: Baker Paula
Published: July 2021

This group of essays came out of an attempt to address the “usually unasked,” “bound to embarrass” question that Eric Monkkonen raised in his 1994 presidential address to the Social Science History Association. As both the social sciences and history have been reshaped in recent years by intellectual tendencies variously labeled “postmodernism,” “poststructuralism,” or the “linguistic turn,” the never especially clear relationship between the social sciences and history has grown even more muddy. The essays that follow are drawn from two sessions of the 1998 annual program of the Social Science History Association. The sessions brought together scholars from a variety of disciplines and cohorts who held divergent ideas about the links between social science and history and different substantive agendas for explaining historical change. A mix of essays that highlight new methodologies for analyzing the past and pieces that offer explanations or remedies, the articles printed here point to some of the central issues in the debate about what social science history might mean today.
PHONOLOGICAL PROCESSING OF STRESS BY NATIVE ENGLISH SPEAKERS LEARNING SPANISH AS A SECOND LANGUAGE
Authors: Ortín Ramsés , Simonet Miquel
Published: July 2021

One feature of Spanish that presents some difficulties to second language (L2) learners whose first language (L1) is English concerns lexical stress. This study explores one aspect of the obstacle these learners face, weak phonological processing routines concerning stress inherited from their native language. Participants were L1 English L2 learners of Spanish. The experiment was a sequence-recall task with auditory stimuli minimally contrasting in stress (target) or segmental composition (baseline). The results suggest that learners are more likely to accurately recall sequences with stimuli contrasting in segmental composition than stress, suggesting reduced phonological processing of stress relative to a processing baseline. Furthermore, an increase in proficiency—assessed by means of grammatical and lexical tests—was found to be modestly associated with an increase in the accuracy of processing stress. We conclude that the processing routines of native English speakers lead to an acquisitional obstacle when learning Spanish as a L2.
The Starting Big approach to language learning
Authors: ARNON Inbal
Published: July 2021

The study of language acquisition has a long and contentious history: researchers disagree on what drives this process, the relevant data, and the interesting questions. Here, I outline the Starting Big approach to language learning, which emphasizes the role of multiword units in language, and of coarse-to-fine processes in learning. I outline core predictions and supporting evidence. In short, the approach argues that multiword units are integral building blocks in language; that such units can facilitate mastery of semantically opaque relations between words; and that adults rely on them less than children, which can explain (some of) their difficulty in learning a second language. The Starting Big approach is a theory of how children learn language, how language is represented, and how to explain differences between first and second language learning. I discuss the learning and processing models at the heart of the approach and their cross-linguistic implications.
Food insecurity and the double burden of malnutrition in Colombian rural households
Authors: Sansón-Rosas Ana María , Bernal-Rivas Jennifer , Kubow Stan , Suarez-Molina Andrés , Melgar-Quiñonez Hugo
Published: July 2021

Objective:

This study aimed to examine in Colombian rural households the association between different severity levels of household food insecurity and the presence of the double burden of malnutrition (SCOWT), defined as the coexistence of a stunted child under 5 years of age and an overweight or obese (OWOB) mother.

Design:

A secondary data analysis was conducted using cross-sectional data from the Colombian National Nutritional Survey (ENSIN) 2015. Household food insecurity status was assessed by using the Latin-American and Caribbean Food Security Scale (ELCSA). The household SCOWT status (child stunting and OWOB mother) was determined using anthropometric data from a mother and her child.

Setting:

Rural Colombia.

Participants:

Totally, 2·350 mother–child pairs living in the same household.

Results:

Sixty-two per cent of the households were food-insecure and SCOWT was present in 7·8 % of the households. Moderate (OR: 2·39, 95 % CI (1·36, 4·21)) and severe (OR: 1·86, 95 % CI (1·10, 3·15)) food insecurity was associated with SCOWT in an unadjusted logistic regression. Only moderate food insecurity remained significantly associated with SCOWT in a multivariate logistic regression (adjusted OR: 2·41, 95 % CI (1·24, 4·68)).

Conclusions:

Colombian rural areas are not exempt from the worldwide concern of increasing OWOB rates while stunting is still persistent. These results highlight the need of implementing double-duty rural actions targeting the most vulnerable households to SCOWT, particularly in terms of overcoming food insecurity beyond hunger satisfaction to prevent all forms of malnutrition.
Design of a linear to circular polarization converter integrated into a concrete construction for radome applications
Authors: Öztürk Murat , Sevim Umur Korkut , Altıntaş Olcay , Ünal Emin , Akgöl Oğuzhan , Karaaslan Muharrem , Sabah Cumali
Published: July 2021

In this paper, we present a linear to circular polarization converter integrated in a concrete structure to eliminate signal transmission problem originated from the concrete buildings in microwave regime. Two polarization converter samples and a control specimen made by traditional concrete are designed and their signal transmission responses are compared experimentally. Axial ratio values which can be calculated by the ratio between the co-polar transmission and cross-polar transmission results of the proposed samples are below 3 dB and highly sufficient for linear to circular polarization conversion activity. The operating frequency for the proposed sample 1 is between 6 and 6.5 GHz with 500 MHz of bandwidth. The proposed sample 2 exhibits dual-band operation covering frequency bands, 4.58–5.13 and 6.0–6.4 GHz with bandwidths of 550 and 400 MHz, respectively. Operating frequencies of the samples are in the WIMAX frequency bands. In addition, the liner to circular polarization converter design integrated to concrete has a huge potential to improve reflection and directivity parameters of many antennas if it is considered as a radome.
Evaluating Precipitation Errors Using the Environmentally Conditioned Intensity‐Frequency Decomposition Method
Authors: Di Luca A. , Argüeso D. , Sherwood S. , Evans J. P.
Published: July 2021

A fundamental issue when evaluating the simulation of precipitation is the difficulty of quantifying specific sources of errors and recognizing compensation of errors. We assess how well a large ensemble of high‐resolution simulations represents the precipitation associated with strong cyclones. We propose a framework to breakdown precipitation errors according to different dynamical (vertical velocity) and thermodynamical (vertically integrated water vapor) regimes and the frequency and intensity of precipitation. This approach approximates the error in the total precipitation of each regime as the sum of three terms describing errors in the large‐scale environmental conditions, the frequency of precipitation and its intensity. We show that simulations produce precipitation too often, that its intensity is too weak, that errors are larger for weak than for strong dynamical forcing and that biases in the vertically integrated water vapor can be large. Using the error breakdown presented above, we define four new error metrics differing on the degree to which they include the compensation of errors. We show that convection‐permitting simulations consistently improve the simulation of precipitation compared to coarser‐resolution simulations using parameterized convection, and that these improvements are revealed by our new approach but not by traditional metrics which can be affected by compensating errors. These results suggest that convection‐permitting models are more likely to produce better results for the right reasons. We conclude that the novel decomposition and error metrics presented in this study give a useful framework that provides physical insights about the sources of errors and a reliable quantification of errors.
Dysregulation of complement and coagulation pathways: emerging mechanisms in the development of psychosis
Authors: Heurich Meike , Föcking Melanie , Mongan David , Cagney Gerard , Cotter David R.
Published: July 2021

Early identification and treatment significantly improve clinical outcomes of psychotic disorders. Recent studies identified protein components of the complement and coagulation systems as key pathways implicated in psychosis. These specific protein alterations are integral to the inflammatory response and can begin years before the onset of clinical symptoms of psychotic disorder. Critically, they have recently been shown to predict the transition from clinical high risk to first-episode psychosis, enabling stratification of individuals who are most likely to transition to psychotic disorder from those who are not. This reinforces the concept that the psychosis spectrum is likely a central nervous system manifestation of systemic changes and highlights the need to investigate plasma proteins as diagnostic or prognostic biomarkers and pathophysiological mediators. In this review, we integrate evidence of alterations in proteins belonging to the complement and coagulation protein systems, including the coagulation, anticoagulation, and fibrinolytic pathways and their dysregulation in psychosis, into a consolidated mechanism that could be integral to the progression and manifestation of psychosis. We consolidate the findings of altered blood proteins relevant for progression to psychotic disorders, using data from longitudinal studies of the general population in addition to clinical high-risk (CHR) individuals transitioning to psychotic disorder. These are compared to markers identified from first-episode psychosis and schizophrenia as well as other psychosis spectrum disorders. We propose the novel hypothesis that altered complement and coagulation plasma levels enhance their pathways’ activating capacities, while low levels observed in key regulatory components contribute to excessive activation observed in patients. This hypothesis will require future testing through a range of experimental paradigms, and if upheld, complement and coagulation pathways or specific proteins could be useful diagnostic or prognostic tools and targets for early intervention and preventive strategies.
Mental health and music engagement: review, framework, and guidelines for future studies
Authors: Gustavson Daniel E. , Coleman Peyton L. , Iversen John R. , Maes Hermine H. , Gordon Reyna L. , Lense Miriam D.
Published: July 2021

Is engaging with music good for your mental health? This question has long been the topic of empirical clinical and nonclinical investigations, with studies indicating positive associations between music engagement and quality of life, reduced depression or anxiety symptoms, and less frequent substance use. However, many earlier investigations were limited by small populations and methodological limitations, and it has also been suggested that aspects of music engagement may even be associated with worse mental health outcomes. The purpose of this scoping review is first to summarize the existing state of music engagement and mental health studies, identifying their strengths and weaknesses. We focus on broad domains of mental health diagnoses including internalizing psychopathology (e.g., depression and anxiety symptoms and diagnoses), externalizing psychopathology (e.g., substance use), and thought disorders (e.g., schizophrenia). Second, we propose a theoretical model to inform future work that describes the importance of simultaneously considering music-mental health associations at the levels of (1) correlated genetic and/or environmental influences vs. (bi)directional associations, (2) interactions with genetic risk factors, (3) treatment efficacy, and (4) mediation through brain structure and function. Finally, we describe how recent advances in large-scale data collection, including genetic, neuroimaging, and electronic health record studies, allow for a more rigorous examination of these associations that can also elucidate their neurobiological substrates.
Operative ubiquitin-specific protease 22 deubiquitination confers a more invasive phenotype to cholangiocarcinoma
Authors: Tian Yu , Tang Bo , Wang Chengye , Wang Yan , Mao Jiakai , Yao Yifan , Gao Zhenming , Liang Rui , Ye Mingliang , Cai Shijie , Wang Liming
Published: July 2021

Oncogenic ubiquitin-specific protease 22 (USP22) is implicated in a variety of tumours; however, evidence of its role and underlying molecular mechanisms in cholangiocarcinoma (CCA) development remains unknown. We collected paired tumour and adjacent non-tumour tissues from 57 intrahepatic CCA (iCCA) patients and evaluated levels of the USP22 gene and protein by qPCR and immunohistochemistry. Both the mRNA and protein were significantly upregulated, correlated with the malignant invasion and worse OS of iCCA. In cell cultures, USP22 overexpression increased CCA cell proliferation and mobility, and induced epithelial-to-mesenchymal transition (EMT). Upon an interaction, USP22 deubiquitinated and stabilized sirtuin-1 (SIRT1), in conjunction with Akt/ERK activation. In implantation xenografts, USP22 overexpression stimulated tumour growth and metastasis to the lungs of mice. Conversely, the knockdown by USP22 shRNA attenuated the tumour growth and invasiveness in vitro and in vivo. Furthermore, SIRT1 overexpression reversed the USP22 functional deficiency, while the knockdown acetylated TGF-β-activated kinase 1 (TAK1) and Akt. Our present study defines USP22 as a poor prognostic predictor in iCCA that cooperates with SIRT1 and facilitates tumour development.
DNA demethylase Tet2 suppresses cisplatin-induced acute kidney injury
Authors: Bao Yinwu , Bai Mengqiu , Zhu Huanhuan , Yuan Yuan , Wang Ying , Zhang Yunjing , Wang Junni , Xie Xishao , Yao Xi , Mao Jianhua , Fu Xianghui , Chen Jianghua , Yang Yi , Lin Weiqiang
Published: July 2021

Demethylase Tet2 plays a vital role in the immune response. Acute kidney injury (AKI) initiation and maintenance phases are marked by inflammatory responses and leukocyte recruitment in endothelial and tubular cell injury processes. However, the role of Tet2 in AKI is poorly defined. Our study determined the degree of renal tissue damage associated with Tet2 gene expression levels in a cisplatin-induced AKI mice model. Tet2-knockout (KO) mice with cisplatin treatment experienced severe tubular necrosis and dilatation, inflammation, and AKI markers’ expression levels than the wild-type mice. In addition, the administration of Tet2 plasmid protected Tet2-KO mice from cisplatin-induced nephrotoxicity, but not Tet2-catalytic-dead mutant. Tet2 KO was associated with a change in metabolic pathways like retinol, arachidonic acid, linolenic acid metabolism, and PPAR signaling pathway in the cisplatin-induced mice model. Tet2 expression is also downregulated in other AKI mice models and clinical samples. Thus, our results indicate that Tet2 has a renal protective effect during AKI by regulating metabolic and inflammatory responses through the PPAR signaling pathway.
The emerging role of WWP1 in cancer development and progression
Authors: Hu Xiaoli , Yu Jiangtao , Lin Zixia , Feng Renqian , Wang Zhi-wei , Chen Gang
Published: July 2021

Emerging evidence demonstrates that WW domain-containing E3 ubiquitin protein ligase 1 (WWP1) participates into carcinogenesis and tumor progression. In this review article, we will describe the association between dysregulated WWP1 expression and clinical features of cancer patients. Moreover, we summarize the both oncogenic and tumor suppressive functions of WWP1 in a variety of human cancers. Furthermore, we briefly describe the downstream substrates of WWP1 and its upstream factors to regulate the expression of WWP1. Notably, targeting WWP1 by its inhibitors or natural compounds is potentially useful for treating human malignancies. Finally, we provide the perspectives regarding WWP1 in cancer development and therapies. We hope this review can stimulate the research to improve our understanding of WWP1-mediated tumorigenesis and accelerate the discovery of novel therapeutic strategies via targeting WWP1 expression in cancers.
NF-κB is involved in the regulation of autophagy in mutant p53 cells in response to ionizing radiation
Authors: Zhu Ying , Zuo Wenqing , Shen Xiao , Liu Yali , Zhao Yifan , Xiong Yajie , Cao Huimin , Wang Yan , Liang Zhongqin
Published: July 2021

Chemotherapy and ionizing radiation (IR) can induce autophagy in tumor cells. Here, we report that the level of autophagy in tumor cells was related to the background of p53 gene that NF-κB acts as a negative regulator of autophagy in mutant p53 (p53-R273H) cells, and that acetylation was involved in the IR-induced nuclear translocation of NF-κB. We found that autophagy-related proteins were highly expressed in wild-type p53 (wt-p53) cells and that IR increased their levels further. p53-R273H cells exhibited low levels of autophagy; there was no change following IR treatment. The nuclear translocation of p65 was upregulated in p53-R273H cells following IR; when p65 was competitively inhibited from entering the nucleus with SN50, the level of autophagy increased. The nuclear translocation of p65 was mediated by p300; this factor also regulates the nuclear behavior of NF-κB. The knockdown of p300 in p53-R273H cells led to an inhibition of p65 expression and an increase in autophagy. In addition, the inhibition of p300 or p65 not only activated autophagy, it also induced radiosensitivity in p53-R273H cells. The relationship between the p53 gene, NF-κB, and autophagy was further analyzed in a mouse model of xenograft tumors and in clinical tumor pathological specimens; the results were consistent with the in vitro experiments. Our findings indicate that autophagy may be regulated by NF-κB in p53-R273H cells. These findings may help to improve the therapeutic strategy adopted for tumors related to the mutant p53-R273H gene; such therapy would aim to target NF-κB to induce autophagy.
PDS5B inhibits cell proliferation, migration, and invasion via upregulation of LATS1 in lung cancer cells
Authors: Xu Hui , Zhou Wenjing , Zhang Fan , Wu Linhui , Li Juan , Ma Tongtong , Cao Tong , Lian Chaoqun , Xia Jun , Wang Peter , Ma Jia , Li Yuyun
Published: July 2021

PDS5B (precocious dissociation of sisters 5B) plays a pivotal role in carcinogenesis and progression. However, the biological functions of PDS5B in lung cancer and its underlying mechanisms are not fully elucidated. In the present study, we used MTT assays, wound-healing assays, and transwell migration and invasion approach to examine the cell viability, migration, and invasion of non-small cell lung cancer (NSCLC) cells after PDS5B modulation. Moreover, we investigated the function of PDS5B overexpression in vivo. Furthermore, we detected the expression of PDS5B in tissue samples of lung cancer patients by immunohistochemical study. We found that upregulation of PDS5B repressed cell viability, migration, and invasion in NSCLC cells, whereas downregulation of PDS5B had the opposite effects. We also observed that PDS5B overexpression retarded tumor growth in nude mice. Notably, PDS5B positively regulated LATS1 expression in NSCLC cells. Strikingly, low expression of PDS5B was associated with lymph node metastasis in lung cancer patients. Our findings suggest that PDS5B might be a therapeutic target for lung cancer.
H-Ras gene takes part to the host immune response to COVID-19
Authors: Sciacchitano Salvatore , Sacconi Andrea , De Vitis Claudia , Blandino Giovanni , Piaggio Giulia , Salvati Valentina , Napoli Christian , Marchetti Paolo , Taurelli Beatrice Salimbeni , Coluzzi Flaminia , Rocco Monica , Vecchione Andrea , Anibaldi Paolo , Marcolongo Adriano , Ciliberto Gennaro , Mancini Rita , Capalbo Carlo
Published: July 2021

Ras gene family members play a relevant role in cancer, especially when they are mutated. However, they may play additional roles in other conditions beside cancer. We performed gene expression analysis using the NanoString PanCancer IO 360 panel in the peripheral blood mononuclear cell (PBMC) of six COVID-19 patients and we found that H-Ras gene was significantly upregulated, while both K-Ras and N-Ras genes were downregulated. In particular, H-Ras gene upregulation was more evident in COVID-19 patients with a more severe disease. We compared our results with those obtained by analyzing two different and independent datasets, including a total of 53 COVID-19 patients, in which the gene expression analysis was performed using the Immunology_V2 panel. Comparative analysis of the H-Ras gene expression in these patients confirmed our preliminary results. In both of them, in fact, we were able to confirm the upregulation of the expression of the H-Ras gene. The exact role of this specific upregulation of the H-Ras gene in response to SARS-CoV-2 infection and its possible role in cancer still remains to be elucidated. In conclusion, H-Ras gene participates to the host immune response to SARS-CoV-2 virus infection, especially in patients affected by the most severe form of the COVID-19.
Desmin aggrephagy in rat and human ischemic heart failure through PKCζ and GSK3β as upstream signaling pathways
Authors: Bouvet Marion , Dubois-Deruy Emilie , Turkieh Annie , Mulder Paul , Peugnet Victoriane , Chwastyniak Maggy , Beseme Olivia , Dechaumes Arthur , Amouyel Philippe , Richard Vincent , Lamblin Nicolas , Pinet Florence
Published: July 2021

Post-translational modifications of cardiac proteins could participate to left contractile dysfunction resulting in heart failure. Using a rat model of ischemic heart failure, we showed an accumulation of phosphorylated desmin leading to toxic aggregates in cardiomyocytes, but the cellular mechanisms are unknown. The same rat model was used to decipher the kinases involved in desmin phosphorylation and the proteolytic systems present in rat and human failing hearts. We used primary cultures of neonate rat cardiomyocytes for testing specific inhibitors of kinases and for characterizing the autophagic processes able to clear desmin aggregates. We found a significant increase of active PKCζ, no modulation of ubitiquitin-proteasome system, a defect in macroautophagy, and an activation of chaperone-mediated autophagy in heart failure rats. We validated in vitro that PKCζ inhibition induced a significant decrease of GSK3β and of soluble desmin. In vitro activation of ubiquitination of proteins and of chaperone-mediated autophagy is able to decrease soluble and insoluble forms of desmin in cardiomyocytes. These data demonstrate a novel signaling pathway implicating activation of PKCζ in desmin phosphorylation associated with a defect of proteolytic systems in ischemic heart failure, leading to desmin aggrephagy. Our in vitro data demonstrated that ubiquitination of proteins and chaperone-mediated autophagy are required for eliminating desmin aggregates with the contribution of its chaperone protein, α-crystallin Β-chain. Modulation of the kinases involved under pathological conditions may help preserving desmin intermediate filaments structure and thus protect the structural integrity of contractile apparatus of cardiomyocytes by limiting desmin aggregates formation.
Platinum drugs and taxanes: can we overcome resistance?
Authors: Sazonova Elena V. , Kopeina Gelina S. , Imyanitov Evgeny N. , Zhivotovsky Boris
Published: July 2021

Cancer therapy is aimed at the elimination of tumor cells and acts via the cessation of cell proliferation and induction of cell death. Many research publications discussing the mechanisms of anticancer drugs use the terms “cell death” and “apoptosis” interchangeably, given that apoptotic pathways are the most common components of the action of targeted and cytotoxic compounds. However, there is sound evidence suggesting that other mechanisms of drug-induced cell death, such as necroptosis, ferroptosis, autophagy, etc. may significantly contribute to the fate of cancer cells. Molecular cross-talks between apoptotic and nonapoptotic death pathways underlie the successes and the failures of therapeutic interventions. Here we discuss the nuances of the antitumor action of two groups of the widely used anticancer drugs, i.e., platinum salts and taxane derivatives. The available data suggest that intelligent interference with the choice of cell death pathways may open novel opportunities for cancer treatment.
A synthetic circuit for buffering gene dosage variation between individual mammalian cells
Authors: Yang Jin , Lee Jihwan , Land Michelle A. , Lai Shujuan , Igoshin Oleg A. , St-Pierre François
Published: July 2021

Precise control of gene expression is critical for biological research and biotechnology. However, transient plasmid transfections in mammalian cells produce a wide distribution of copy numbers per cell, and consequently, high expression heterogeneity. Here, we report plasmid-based synthetic circuits – Equalizers – that buffer copy-number variation at the single-cell level. Equalizers couple a transcriptional negative feedback loop with post-transcriptional incoherent feedforward control. Computational modeling suggests that the combination of these two topologies enables Equalizers to operate over a wide range of plasmid copy numbers. We demonstrate experimentally that Equalizers outperform other gene dosage compensation topologies and produce as low cell-to-cell variation as chromosomally integrated genes. We also show that episome-encoded Equalizers enable the rapid generation of extrachromosomal cell lines with stable and uniform expression. Overall, Equalizers are simple and versatile devices for homogeneous gene expression and can facilitate the engineering of synthetic circuits that function reliably in every cell.
High Mountain Asian glacier response to climate revealed by multi-temporal satellite observations since the 1960s
Authors: Bhattacharya Atanu , Bolch Tobias , Mukherjee Kriti , King Owen , Menounos Brian , Kapitsa Vassiliy , Neckel Niklas , Yang Wei , Yao Tandong
Published: July 2021

Knowledge about the long-term response of High Mountain Asian glaciers to climatic variations is paramount because of their important role in sustaining Asian river flow. Here, a satellite-based time series of glacier mass balance for seven climatically different regions across High Mountain Asia since the 1960s shows that glacier mass loss rates have persistently increased at most sites. Regional glacier mass budgets ranged from −0.40 ± 0.07 m w.e.a−1 in Central and Northern Tien Shan to −0.06 ± 0.07 m w.e.a−1 in Eastern Pamir, with considerable temporal and spatial variability. Highest rates of mass loss occurred in Central Himalaya and Northern Tien Shan after 2015 and even in regions where glaciers were previously in balance with climate, such as Eastern Pamir, mass losses prevailed in recent years. An increase in summer temperature explains the long-term trend in mass loss and now appears to drive mass loss even in regions formerly sensitive to both temperature and precipitation.
Particulate organic matter as a functional soil component for persistent soil organic carbon
Authors: Witzgall Kristina , Vidal Alix , Schubert David I. , Höschen Carmen , Schweizer Steffen A. , Buegger Franz , Pouteau Valérie , Chenu Claire , Mueller Carsten W.
Published: July 2021

The largest terrestrial organic carbon pool, carbon in soils, is regulated by an intricate connection between plant carbon inputs, microbial activity, and the soil matrix. This is manifested by how microorganisms, the key players in transforming plant-derived carbon into soil organic carbon, are controlled by the physical arrangement of organic and inorganic soil particles. Here we conduct an incubation of isotopically labelled litter to study effects of soil structure on the fate of litter-derived organic matter. While microbial activity and fungal growth is enhanced in the coarser-textured soil, we show that occlusion of organic matter into aggregates and formation of organo-mineral associations occur concurrently on fresh litter surfaces regardless of soil structure. These two mechanisms—the two most prominent processes contributing to the persistence of organic matter—occur directly at plant–soil interfaces, where surfaces of litter constitute a nucleus in the build-up of soil carbon persistence. We extend the notion of plant litter, i.e., particulate organic matter, from solely an easily available and labile carbon substrate, to a functional component at which persistence of soil carbon is directly determined.
Cell migration guided by long-lived spatial memory
Authors: d’Alessandro Joseph , Barbier--Chebbah Alex , Cellerin Victor , Benichou Olivier , Mège René Marc , Voituriez Raphaël , Ladoux Benoît
Published: July 2021

Living cells actively migrate in their environment to perform key biological functions—from unicellular organisms looking for food to single cells such as fibroblasts, leukocytes or cancer cells that can shape, patrol or invade tissues. Cell migration results from complex intracellular processes that enable cell self-propulsion, and has been shown to also integrate various chemical or physical extracellular signals. While it is established that cells can modify their environment by depositing biochemical signals or mechanically remodelling the extracellular matrix, the impact of such self-induced environmental perturbations on cell trajectories at various scales remains unexplored. Here, we show that cells can retrieve their path: by confining motile cells on 1D and 2D micropatterned surfaces, we demonstrate that they leave long-lived physicochemical footprints along their way, which determine their future path. On this basis, we argue that cell trajectories belong to the general class of self-interacting random walks, and show that self-interactions can rule large scale exploration by inducing long-lived ageing, subdiffusion and anomalous first-passage statistics. Altogether, our joint experimental and theoretical approach points to a generic coupling between motile cells and their environment, which endows cells with a spatial memory of their path and can dramatically change their space exploration.
Ultrasensitive nano-optomechanical force sensor operated at dilution temperatures
Authors: Fogliano Francesco , Besga Benjamin , Reigue Antoine , Mercier de Lépinay Laure , Heringlake Philip , Gouriou Clement , Eyraud Eric , Wernsdorfer Wolfgang , Pigeau Benjamin , Arcizet Olivier
Published: July 2021

Cooling down nanomechanical force probes is a generic strategy to enhance their sensitivities through the concomitant reduction of their thermal noise and mechanical damping rates. However, heat conduction becomes less efficient at low temperatures, which renders difficult to ensure and verify their proper thermalization. Here we implement optomechanical readout techniques operating in the photon counting regime to probe the dynamics of suspended silicon carbide nanowires in a dilution refrigerator. Readout of their vibrations is realized with sub-picowatt optical powers, in a situation where less than one photon is collected per oscillation period. We demonstrate their thermalization down to 32 ± 2 mK, reaching very large sensitivities for scanning probe force sensors, 40 zN Hz−1/2, with a sensitivity to lateral force field gradients in the fN m−1 range. This opens the road toward explorations of the mechanical and thermal conduction properties of nanoresonators at minimal excitation level, and to nanomechanical vectorial imaging of faint forces at dilution temperatures.
Four chromosome scale genomes and a pan-genome annotation to accelerate pecan tree breeding
Authors: Lovell John T. , Bentley Nolan B. , Bhattarai Gaurab , Jenkins Jerry W. , Sreedasyam Avinash , Alarcon Yanina , Bock Clive , Boston Lori Beth , Carlson Joseph , Cervantes Kimberly , Clermont Kristen , Duke Sara , Krom Nick , Kubenka Keith , Mamidi Sujan , Mattison Christopher P. , Monteros Maria J. , Pisani Cristina , Plott Christopher , Rajasekar Shanmugam , Rhein Hormat Shadgou , Rohla Charles , Song Mingzhou , Hilaire Rolston St. , Shu Shengqiang , Wells Lenny , Webber Jenell , Heerema Richard J. , Klein Patricia E. , Conner Patrick , Wang Xinwang , Grauke L. J. , Grimwood Jane , Schmutz Jeremy , Randall Jennifer J.
Published: July 2021

Genome-enabled biotechnologies have the potential to accelerate breeding efforts in long-lived perennial crop species. Despite the transformative potential of molecular tools in pecan and other outcrossing tree species, highly heterozygous genomes, significant presence–absence gene content variation, and histories of interspecific hybridization have constrained breeding efforts. To overcome these challenges, here, we present diploid genome assemblies and annotations of four outbred pecan genotypes, including a PacBio HiFi chromosome-scale assembly of both haplotypes of the ‘Pawnee’ cultivar. Comparative analysis and pan-genome integration reveal substantial and likely adaptive interspecific genomic introgressions, including an over-retained haplotype introgressed from bitternut hickory into pecan breeding pedigrees. Further, by leveraging our pan-genome presence–absence and functional annotation database among genomes and within the two outbred haplotypes of the ‘Lakota’ genome, we identify candidate genes for pest and pathogen resistance. Combined, these analyses and resources highlight significant progress towards functional and quantitative genomics in highly diverse and outbred crops.
α-TubK40me3 is required for neuronal polarization and migration by promoting microtubule formation
Authors: Xie Xuan , Wang Shaogang , Li Mingyi , Diao Lei , Pan Xingyu , Chen Jijun , Zou Weiguo , Zhang Xu , Feng Wenfeng , Bao Lan
Published: July 2021

Tri-methylation on lysine 40 of α-tubulin (α-TubK40me3) is a recently identified post-translational modification involved in mitosis and cytokinesis. However, knowledge about α-TubK40me3 in microtubule function and post-mitotic cells remains largely incomplete. Here, we report that α-TubK40me3 is required for neuronal polarization and migration by promoting microtubule formation. α-TubK40me3 is enriched in mouse cerebral cortex during embryonic day (E)14 to E16. Knockdown of α-tubulin methyltransferase SETD2 at E14 leads to the defects in neuronal migration, which could be restored by overexpressing either a cytoplasm-localized SETD2 truncation or α-TubK40me3-mimicking mutant. Furthermore, α-TubK40me3 is preferably distributed on polymerized microtubules and potently promotes tubulin nucleation. Downregulation of α-TubK40me3 results in reduced microtubule abundance in neurites and disrupts neuronal polarization, which could be rescued by Taxol. Additionally, α-TubK40me3 is increased after losing α-tubulin K40 acetylation (α-TubK40ac) and largely rescues α-TubK40ac function. This study reveals a critical role of α-TubK40me3 in microtubule formation and neuronal development.
The role of the PZP domain of AF10 in acute leukemia driven by AF10 translocations
Authors: Klein Brianna J. , Deshpande Anagha , Cox Khan L. , Xuan Fan , Zandian Mohamad , Barbosa Karina , Khanal Sujita , Tong Qiong , Zhang Yi , Zhang Pan , Sinha Amit , Bohlander Stefan K. , Shi Xiaobing , Wen Hong , Poirier Michael G. , Deshpande Aniruddha J. , Kutateladze Tatiana G.
Published: July 2021

Chromosomal translocations of the AF10 (or MLLT10) gene are frequently found in acute leukemias. Here, we show that the PZP domain of AF10 (AF10PZP), which is consistently impaired or deleted in leukemogenic AF10 translocations, plays a critical role in blocking malignant transformation. Incorporation of functional AF10PZP into the leukemogenic CALM-AF10 fusion prevents the transforming activity of the fusion in bone marrow-derived hematopoietic stem and progenitor cells in vitro and in vivo and abrogates CALM-AF10-mediated leukemogenesis in vivo. Crystallographic, biochemical and mutagenesis studies reveal that AF10PZP binds to the nucleosome core particle through multivalent contacts with the histone H3 tail and DNA and associates with chromatin in cells, colocalizing with active methylation marks and discriminating against the repressive H3K27me3 mark. AF10PZP promotes nuclear localization of CALM-AF10 and is required for association with chromatin. Our data indicate that the disruption of AF10PZP function in the CALM-AF10 fusion directly leads to transformation, whereas the inclusion of AF10PZP downregulates Hoxa genes and reverses cellular transformation. Our findings highlight the molecular mechanism by which AF10 targets chromatin and suggest a model for the AF10PZP-dependent CALM-AF10-mediated leukemogenesis.
A neuronal ensemble encoding adaptive choice during sensory conflict in Drosophila
Authors: Sareen Preeti F. , McCurdy Li Yan , Nitabach Michael N.
Published: July 2021

Feeding decisions are fundamental to survival, and decision making is often disrupted in disease. Here, we show that neural activity in a small population of neurons projecting to the fan-shaped body higher-order central brain region of Drosophila represents food choice during sensory conflict. We found that food deprived flies made tradeoffs between appetitive and aversive values of food. We identified an upstream neuropeptidergic and dopaminergic network that relays internal state and other decision-relevant information to a specific subset of fan-shaped body neurons. These neurons were strongly inhibited by the taste of the rejected food choice, suggesting that they encode behavioral food choice. Our findings reveal that fan-shaped body taste responses to food choices are determined not only by taste quality, but also by previous experience (including choice outcome) and hunger state, which are integrated in the fan-shaped body to encode the decision before relay to downstream motor circuits for behavioral implementation.
Enhanced regulation of prokaryotic gene expression by a eukaryotic transcriptional activator
Authors: MacDonald I. Cody , Seamons Travis R. , Emmons Jonathan C. , Javdan Shwan B. , Deans Tara L.
Published: July 2021

Expanding the genetic toolbox for prokaryotic synthetic biology is a promising strategy for enhancing the dynamic range of gene expression and enabling new engineered applications for research and biomedicine. Here, we reverse the current trend of moving genetic parts from prokaryotes to eukaryotes and demonstrate that the activating eukaryotic transcription factor QF and its corresponding DNA-binding sequence can be moved to E. coli to introduce transcriptional activation, in addition to tight off states. We further demonstrate that the QF transcription factor can be used in genetic devices that respond to low input levels with robust and sustained output signals. Collectively, we show that eukaryotic gene regulator elements are functional in prokaryotes and establish a versatile and broadly applicable approach for constructing genetic circuits with complex functions. These genetic tools hold the potential to improve biotechnology applications for medical science and research.
Probiotics impact the antibiotic resistance gene reservoir along the human GI tract in a person-specific and antibiotic-dependent manner
Authors: Montassier Emmanuel , Valdés-Mas Rafael , Batard Eric , Zmora Niv , Dori-Bachash Mally , Suez Jotham , Elinav Eran
Published: July 2021

Antimicrobial resistance poses a substantial threat to human health. The gut microbiome is considered a reservoir for potential spread of resistance genes from commensals to pathogens, termed the gut resistome. The impact of probiotics, commonly consumed by many in health or in conjunction with the administration of antibiotics, on the gut resistome is elusive. Reanalysis of gut metagenomes from healthy antibiotics-naïve humans supplemented with an 11-probiotic-strain preparation, allowing direct assessment of the gut resistome in situ along the gastrointestinal (GI) tract, demonstrated that probiotics reduce the number of antibiotic resistance genes exclusively in the gut of colonization-permissive individuals. In mice and in a separate cohort of humans, a course of antibiotics resulted in expansion of the lower GI tract resistome, which was mitigated by autologous faecal microbiome transplantation or during spontaneous recovery. In contrast, probiotics further exacerbated resistome expansion in the GI mucosa by supporting the bloom of strains carrying vancomycin resistance genes but not resistance genes encoded by the probiotic strains. Importantly, the aforementioned effects were not reflected in stool samples, highlighting the importance of direct sampling to analyse the effect of probiotics and antibiotics on the gut resistome. Analysing antibiotic resistance gene content in additional published clinical trials with probiotics further highlighted the importance of person-specific metagenomics-based profiling of the gut resistome using direct sampling. Collectively, these findings suggest opposing person-specific and antibiotic-dependent effects of probiotics on the resistome, whose contribution to the spread of antimicrobial resistance genes along the human GI tract merit further studies.
Epidemiology of hemorrhagic fever with renal syndrome in Tai’an area
Authors: Bi XiuJuan , Yi Shuying , Zhang Aihua , Zhao Zhenghua , Liu Yunqiang , Zhang Chao , Ye Zhen
Published: July 2021

Hemorrhagic fever with renal syndrome (HFRS), a serious threat to human health, is mainly transmitted by rodents in Eurasia. The risk of disease differs according to sex, age, and occupation. Further, temperature and rainfall have some lagging effects on the occurrence of the disease. The quantitative data for these factors in the Tai’an region of China are still unknown. We used a forest map to calculate the risk of HFRS in different populations and used four different mathematical models to explain the relationship between time factors, meteorological factors, and the disease. The results showed that compared with the whole population, the relative risk in rural medical staff and farmers was 5.05 and 2.00, respectively (p < 0.05). Joinpoint models showed that the number of cases decreased by 33.32% per year from 2005 to 2008 (p < 0.05). The generalized additive model showed that air temperature was positively correlated with disease risk from January to June, and that relative humidity was negatively correlated with risk from July to December. From January to June, with an increase in temperature, after 15 lags, the cumulative risk of disease increased at low temperatures. From July to December, the cumulative risk decreased with an increase in the relative humidity. Rural medical staff, farmers, men, and middle-aged individuals were at a high risk of HFRS. Moreover, air temperature and relative humidity are important factors that affect disease occurrence. These associations show lagged and differing effects according to the season.
Radionuclide, magnetic resonance and computed tomography imaging in European round back slugs (Arionidae) and leopard slugs (Limacidae)
Authors: Beindorff Nicola , Schmitz-Peiffer Fabian , Messroghli Daniel , Brenner Winfried , Eary Janet F.
Published: July 2021

Other than in animal models of human disease, little functional imaging has been performed in most of the animal world. The aim of this study was to explore the functional anatomy of the European round back slug (Arionidae) and leopard slug (Limacidae)and to establish an imaging protocol for comparative species study. Radionuclide images with single photon emission computed tomography (SPECT) and positron emission tomography (PET) were obtained after injections of standard clinical radiopharmaceuticals99mtechnetium dicarboxypropane diphosphonate (bone scintigraphy),99mtechnetium mercaptoacetyltriglycine (kidney function),99mtechnetium diethylenetriaminepentaacetic acid (kidney function),99mtechnetium pertechnetate (mediated by the sodium-iodide symporter),99mtechnetium sestamibi (cardiac scintigraphy) or18F-fluoro-deoxyglucose (glucose metabolism) in combination with magnetic resonance imaging (MRI) and computed tomography (CT) for uptake anatomic definition. Images were compared with anatomic drawings for theArionidaespecies. Additionally, organ uptake data was determined for a description of slug functional anatomy in comparison to human tracer biodistribution patterns identifying the heart, the open circulatory anatomy, calcified shell remnant, renal structure (nephridium), liver (digestive gland) and intestine. The results show the detailed functional anatomy ofArionidaeandLimacidae, and describe an in vivo whole-body imaging procedure for invertebrate species.