bluuebunny/crossref_metadata_2025 huggingface dataset:
West African Iron Production in Its Sub-Saharan Context
Authors: de Barros Philip L.
Published: May 2022

The study of ironworking in West Africa encompasses a fascinating set of research topics which inevitably draw upon theories, methods, and issues from the African continent as a whole. An underlying perspective is the notion that African iron production can best be understood within its various cultural contexts, rather than from strictly Western technological perspectives, theoretical models, and universalist generalizations that have often separated science from anthropology, and which often do not work well, especially in sub-Saharan Africa.

Among the many topics of interest, the most intellectually useful and rewarding for their insights include those that: (a) involve debates that have been of importance in the literature on African ironworking, such as the extent to which ironworking led to serious deforestation; (b) investigate important methodological, typological, theoretical, and ontological issues, such as understanding the role of ritual and ideology within ironworking processes; (c) involve important substantive issues, such as the rise and utility of archaeometallurgy in the study of ironworking; (d) are historically important in our changing concepts of sub-Saharan Africa, African peoples, and African societies, such as African invention and innovation within ironworking technology in the historical and racial context of the African’s supposed lack of technological inventiveness; and (e) taken together, and individually, emphasize a holistic approach to the field of African ironworking, especially the interrelationships between the technical and the social, such as the development of distinct technological styles and understanding the significant variability in African furnace designs and ironworking technologies. Indeed, the rise of ironworking in Africa had major effects upon the technical, social, cultural, political, symbolic, and ideological aspects of African societies over time. This is especially true for West Africa which became the center of several major iron-producing regions.
A Postcolonial Approach to the Right to the City
Authors: de Oliviera Lucas Amaral , Triana Bruna
Published: May 2022

A postcolonial approach to the right to the city involves the intersection of two multifaceted topics that has yielded an extensive body of scholarship. On the one hand, a postcolonial perspective conceives knowledge production as connected to the colonial matrix of power—a process that resulted in a narrow, Western-centered understanding of the world. On the other, the right to the city, a political motto associated with the French Marxist Henri Lefebvre, focuses on rebalancing the power over urbanization processes by embracing citizens’ prerogatives to co-participate in decision-making concerning the city.

Tackling the debate on the right to the city from the standpoint of postcolonial spaces includes exploring a range of social, political, economic, cultural, and spatial axes that offer renewed engagements with the “urban question” from across the social sciences and humanities. In this sense, it is essential to question the universal grammar of the “city,” considering urban changes and local variations, as well as the metrocentric tendencies in the dominant urban theory, such as the concentration on large cities based on a normative and Eurocentric conception of urbanity.

A postcolonial approach to the right to the city takes various processes, histories, experiences, projects, spatial perspectives, and agencies into account, considering epistemological and political proposals from the Global South. Critical Urban Theory, for instance, has analyzed varied contexts, times, and places to determine current patterns of urbanization under global capitalism and their far-reaching consequences for contemporary urban life, especially for groups at the margins. In the early 21st century, Postcolonial Urbanism, whether led by political and social movements or scholars, has drawn attention to how imperialism and colonialism have profoundly shaped city landscapes and positioned urbanism within a singular script centered on Western capitalism, modernization, and progress. Both perspectives outline a critical call to rethink and decenter the debate on the right to the city, confronting topics related to contemporary urban dynamics. These topics may include but are not limited to the new designs of citizenship and agency, center-periphery relations, city-making processes not restricted to the Western system of meaning, urban precarity, housing displacement, gentrification, environmental racism, and the costs of housing injustice in different geographical contexts.
Nāgārjuna
Authors: Siderits Mark
Published: May 2022

Nāgārjuna was the 2nd-century ce founder of the Madhyamaka school of Indian Buddhist philosophy. He is best known for his articulation and defense of the core Mahāyāna claim that all things are empty (śūnya) or devoid of intrinsic nature. When this claim is understood against the background of the metaphysical theories of the Abhidharma schools of Buddhism, it amounts to the denial that anything is ultimately, or strictly speaking, real. This appears tantamount to the (seemingly absurd) claim that nothing whatsoever really exists, and this interpretation has been common among Nāgārjuna’s opponents, both classical and modern. Defenders of Nāgārjuna and the Madhyamaka school have developed a variety of ways of understanding emptiness that seek to do justice to Nāgārjuna’s denial that he is a nihilist. An additional constraint on interpreting Nāgārjuna’s arguments has been arriving at a reading that also accommodates the soteriological significance claimed for the doctrine: How might the realization that nothing has its nature intrinsically prove crucial to attaining the Buddhist goal of the cessation of suffering? Given the many challenges inherent in developing a suitable hermeneutical strategy, Nāgārjuna’s work has garnered much attention both in the world of Asian Buddhism and among modern scholars.
“Estos gringos no entienden nada”: Anastasio Somoza and the Regional Dimension of the 1954 Coup d’etat in Guatemala
Authors: García Roberto
Published: May 2022

Between 1944 and 1954, Guatemala had a radical democratic experience that significantly impacted its closest neighbors. During that time, two revolutionary governments, one led by Juan José Arévalo and the other by Jacobo Árbenz, promoted a set of political, economic, and social reforms unprecedented in Central America. These reforms did not follow a linear process but were made possible within a framework of broad freedoms. Surrounded by dictatorships and authoritarian rulers, Guatemala was gradually becoming a kind of democratic refuge for many exiled and persecuted people from different locations, though most came from Central American and Caribbean countries. The reform cycle accelerated remarkably after the approval of agrarian reforms in mid-1952, which radicalized the conservative stance of Guatemala’s neighbors and angered the United Fruit Company, the country’s major agriculture company. After numerous attempts to overthrow both leaders, local forces, in convergence with their regional counterparts, managed to convince the new US administration, headed by Dwight Eisenhower, of the danger of Guatemala’s role. The success of the covert coup in Iran (1953) also acted as a catalyst and facilitated the execution of a similar, secret plan to finally cause the collapse of the Árbenz government. The coup, which ultimately achieved its objective in June 1954, constitutes one of the most explored and emblematic themes of international relations in Latin America during the Cold War. Its consequences have endured into the 21st century.
Woodrow Wilson in the Caribbean
Authors: Tillman Ellen D.
Published: May 2022

Woodrow Wilson entered the presidency in 1913, when the United States was already deeply involved in Caribbean interests and European nations were moving almost irrevocably toward war. Wilson’s 1912 election shifted domestic and international policy, though not always in the ways that people expected. Mired in his own ideas about constitutionalism and the progressive course of history toward some ultimate end goal, Wilson inherited an empire that complicated US strategic goals. Caribbean countries and territories, meanwhile, were undergoing massive changes in internal markets and shifts toward the global economy. As industrialization and rapid improvements in communications technology picked up pace, foreign investment reoriented Caribbean economies; the 1914 opening of the Panama Canal deepened US strategic interest in the region. During the years of World War I, from August 1914, Wilson’s administration proclaimed neutrality but increasingly became more interventionist in the Caribbean to protect the canal and to allow the United States to dominate trade in the absence of European powers. From the Mexican Revolution to World War I and the postwar peace process, Wilson’s presidency was largely dominated by the exigencies of foreign affairs—exactly what he had feared at his election. When Wilson became president, he and his secretary of state decried the willingness of the previous presidential administrations of Theodore Roosevelt and William H. Taft to use military force in policing the Western Hemisphere, and yet within a short time Wilson’s administration became the most likely to use force and even military occupation. He decried unequal financial relationships and tax burdens as detrimental to hemispheric solidarity and national sovereignty but expected Latin American nations to follow a particular “Anglo-Saxon” path under US tutelage. When the realities of Caribbean nations did not match his expectations, or when he and his appointees found certain populations unready for democratic government, he was willing in an unprecedented way to use military force to impose the US standard as he saw it. The Wilson presidency (1913–1920) tightened US control over the Caribbean, with the administration intervening intrusively and placing heavy foreign burdens upon Caribbean countries. The occupations in countries such as Haiti and the Dominican Republic worsened US–Latin America relations. Occupations failed in their stated goals as popular opposition forced withdrawals, although they left US-friendly militaries that guaranteed long-term support for US interests, often under militarily backed dictatorships.
Whaling in the South Atlantic: Hunting Whales along the Brazilian Coast (1760–1850)
Authors: Castelucci Junior Wellington
Published: May 2022

From the first half of the 18th century to 1850, whaling ships, coming from different New England ports, hunted whales in the South Atlantic, focusing their attentions on certain areas along the Brazilian coast, the loci of constant seasonal migration by these mammals for procreation. According to data about whaling voyages obtained from the Mystic Sea Port Museum, between 1700 and 1920, 16,379 expeditions left the Northeast of New England. At the heart of this temporal demarcation, between 1761 and 1844, around 650 whaling expeditions were carried out along the Brazilian coast, representing approximately 3.97% of the total excursions of the period. In other words, in 83 years an average of 7.83 expeditions were made each year to various regions of the Brazilian coast, specifically Bahia, Pernambuco, Rio de Janeiro, São Paulo, and Santa Catarina. From these areas, a huge amount of two whale species were caught: humpback whales and the southern right whale. In this period, the most desired prey was the sperm whale. However, these did not come close to the coast, so they were rarely killed in Brazilian waters. Whalers thus balanced hunting sperm whales in deep waters with the catching of the other types in Brazilian coastal waters. The results of these incursions were measured by the quantity of oil, extracted from animal fat, bones deposited on the decks of boats, and spermaceti, taken from the cranium of the sperm whale, brought to New England ports. The aim of this article is to trace the trajectory of the North American whaling incursions, from their port of origin to the places of whale hunting on the Brazilian coast. In addition, the text focuses on the typology of vessels, the duration of expeditions, experiences of crews, and the results of voyages, materialized in the production unloaded in U.S. ports.
Computational Models of Morphological Learning
Authors: Kodner Jordan
Published: May 2022

A computational learner needs three things: Data to learn from, a class of representations to acquire, and a way to get from one to the other. Language acquisition is a very particular learning setting that can be defined in terms of the input (the child’s early linguistic experience) and the output (a grammar capable of generating a language very similar to the input). The input is infamously impoverished. As it relates to morphology, the vast majority of potential forms are never attested in the input, and those that are attested follow an extremely skewed frequency distribution. Learners nevertheless manage to acquire most details of their native morphologies after only a few years of input. That said, acquisition is not instantaneous nor is it error-free. Children do make mistakes, and they do so in predictable ways which provide insights into their grammars and learning processes.

The most elucidating computational model of morphology learning from the perspective of a linguist is one that learns morphology like a child does, that is, on child-like input and along a child-like developmental path. This article focuses on clarifying those aspects of morphology acquisition that should go into such an elucidating a computational model. Section 1 describes the input with a focus on child-directed speech corpora and input sparsity. Section 2 discusses representations with focuses on productivity, developmental paths, and formal learnability. Section 3 surveys the range of learning tasks that guide research in computational linguistics and NLP with special focus on how they relate to the acquisition setting. The conclusion in Section 4 presents a summary of morphology acquisition as a learning problem with Table 4 highlighting the key takeaways of this article.
Major Isoglosses in Romània
Authors: Barbato Marcello
Published: May 2022

An isogloss is defined as a line that divides two areas in which a single feature has distinct values. The features apply to all linguistic levels and can be synchronic or diachronic. In Romance studies, isoglosses are generally traced on the basis of phonological and diachronic features. Very early on it was observed that, depending on the feature selected, different zones were outlined (noncoincidence of isoglosses). From this arose skepticism with respect to the possibility of delineating dialect groups. It was noted, however, that isoglosses often follow a trend that is at least parallel, if not coinciding (isogloss bundles). Research has therefore recognized the existence of dialect boundaries and has continued to investigate the correlation between these boundaries and physical or cultural ones.

The isogloss is a problematic instrument for several aspects: It imposes a two-dimensional representation of linguistic reality that leaves no space for vertical variation (diastratic, diaphasic). Moreover, varieties do not always demonstrate a juxtaposition that can be represented by an isogloss (e.g., linguistic enclaves or bilingual areas). A further question is whether it is necessary to establish a hierarchy of isoglosses (phonological, morphological, lexical, etc.). Despite these issues, the isogloss remains a fundamental instrument for linguistic geography.

The major isogloss bundles distinguish dialect groups: Sardinian, Romanian, Galician-Portuguese, Astur-Leonese, Castilian, Navarro-Aragonese, Catalan, Gascon, Occitanic, French, Alpine Romance, Cisalpine Romance, and Italian. For each bundle, the article attempts to determine whether and how it has changed over time, and what the possible cultural correlations of this might be.
Zucconi, Angela
Authors: Dellavalle Marilena , Mozzone Carlotta
Published: May 2022

Angela Zucconi (1914–2000) was an expert in community social work and social work training. For many years, she directed the Centro di Educazione Professionale per Assistenti Sociali, a social work education center in Rome. After an early life devoted to literature, she embraced social and political commitment after World War Two.
Total Syntheses of Dihydro-β-agarofuran Natural Products
Authors: Ogura Yusuke
Published: May 2022

Dihydro-β-agarofuran sesquiterpenoids constitute a large family of natural products characterized by a tricyclic architecture comprising trans-decalin and tetrahydrofuran rings, and oxygen functionalities on them. Their pharmacologically and agriculturally important biological properties and intriguing molecular architectures have attracted considerable attention from synthetic organic and medicinal chemists. In 2020, our group achieved a scalable total synthesis of this type of natural product, (–)-isocelorbicol, by developing a highly stereocontrolled protocol, which enabled elaboration to naturally occurring ester derivatives, celafolins B-1, B-2, and B-3. Afterward, the total syntheses of more complex dihydro-β-agarofuran sesquiterpenoids, (–)-euonyminol and (–)-euonymine, were reported by two research groups via current state-of-the-art methods. This review summarizes the total syntheses of dihydro-β-agarofuran natural products from 1979 to 2021.
Establishing an effective gene knockdown system using cultured cells of the model fish medaka (Oryzias latipes)
Authors: Zenke Kosuke , Okinaka Yasushi
Published: May 2022

In spite of the growing attention given to medaka (Oryzias latipes) as an excellent vertebrate model, an effective gene knockdown system has not yet been established using cultured cells of this fish species. In this study, a gene knockdown system using short interfering RNA (siRNA) in medaka cell lines was established through the optimization of transfection conditions. By extensive screening of several medaka cell lines and transfection reagents, OLHNI-2 cells and X-tremeGENE siRNA Transfection Reagent were selected as the best combination to achieve high transfection efficiency of siRNA without cytotoxic effect. Knockdown conditions were then refined using the endogenous heat shock protein 90 (Hsp90) genes as the siRNA targets. Among the parameters tested, cell density, serum concentration in the culture medium, and duration of transfection improved knockdown efficiency, where the target mRNA in cells transfected with each of the siRNAs was reduced from 12.0% to 26.7% of the control level. Our results indicate that the established knockdown system using siRNA is a promising tool for functional analysis of medaka genes in vitro.
Unravelling the impact of frontal lobe impairment for social dysfunction in myotonic dystrophy type 1
Authors: Morin Alexandre , Funkiewiez Aurelie , Routier Alexandre , Le Bouc Raphael , Borderies Nicolas , Galanaud Damien , Levy Richard , Pessiglione Mathias , Dubois Bruno , Eymard Bruno , Michon Claire-Cecile , Angeard Nathalie , Behin Anthony , Laforet Pascal , Stojkovic Tanya , Azuar Carole
Published: May 2022

Myotonic dystrophy type 1 is an autosomal dominant multisystemic disorder affecting muscular and extra muscular systems, including the central nervous system. Cerebral involvement in myotonic dystrophy type 1 is associated with subtle cognitive and behavioural disorders, of major impact on socio-professional adaptation. The social dysfunction and its potential relation to frontal lobe neuropsychology remain under-evaluated in this pathology. The neuroanatomical network underpinning that disorder is yet to disentangle. Twenty-eight myotonic dystrophy type 1 adult patients (mean age: 46 years old) and 18 age and sex-matched healthy controls were included in the study. All patients performed an exhaustive neuropsychological assessment with a specific focus on frontal lobe neuropsychology (motivation, social cognition and executive functions). Among them, 18 myotonic dystrophy type 1 patients and 18 healthy controls had a brain MRI with T1 and T2 Flair sequences. Grey matter segmentation, Voxel-based morphometry and cortical thickness estimation were performed with Statistical Parametric Mapping Software SPM12 and Freesurfer software. Furthermore, T2 white matter lesions and subcortical structures were segmented with Automated Volumetry Software. Most patients showed significant impairment in executive frontal functions (auditory working memory, inhibition, contextualization and mental flexibility). Patients showed only minor difficulties in social cognition tests mostly in cognitive Theory of Mind, but with relative sparing of affective Theory of Mind and emotion recognition. Neuroimaging analysis revealed atrophy mostly in the parahippocampal and hippocampal regions and to a lesser extent in basal ganglia, regions involved in social navigation and mental flexibility, respectively. Social cognition scores were correlated with right parahippocampal gyrus atrophy. Social dysfunction in myotonic dystrophy type 1 might be a consequence of cognitive impairment regarding mental flexibility and social contextualization rather than a specific social cognition deficit such as emotion recognition. We suggest that both white matter lesions and grey matter disease could account for this social dysfunction, involving, in particular, the frontal-subcortical network and the hippocampal/arahippocampal regions, brain regions known, respectively, to integrate contextualization and social navigation.
Congenital anomaly epidemiological correlates of Δ8THC across USA 2003–16: panel regression and causal inferential study
Authors: Reece Albert Stuart , Hulse Gary Kenneth
Published: May 2022

Δ8-Tetrahydrocannabinol (Δ8THC) is marketed in many US states as ‘legal weed’. Concerns exist relating to class-wide genotoxic cannabinoid effects. We conducted an epidemiological investigation of Δ8THC-related genotoxicity expressed as 57 congenital anomaly (CA) rates (CARs) in the USA. CARs were taken from the Centers for Disease Control, Atlanta, Georgia. Drug exposure data were taken from the National Survey of Drug Use and Health, with a response rate of 74.1%. Ethnicity and income data were taken from the US Census Bureau. National cannabinoid exposure was taken from Drug Enforcement Agency publications and multiplied by state cannabis use data to derive state-based estimates of Δ8THC exposure. At bivariate continuous analysis, Δ8THC was associated with 23 CAs on raw CA rates, 33 CARs after correction for early termination for anomaly estimates and 41 on a categorical analysis comparing the highest and lowest exposure quintiles. At inverse probability weighted multivariable additive and interactive models lagged to 0, 2 and 4 years, Δ8THC was linked with 39, 8, 4 and 9 CAs. Chromosomal, cardiovascular, gastrointestinal, genitourinary, limb, central nervous system (CNS) and face systems were particularly affected. The minimum E-values ranged to infinity. Both the number of anomalies implicated and the effect sizes demonstrated were much greater for Δ8THC than for tobacco and alcohol combined. Δ8THC appears epidemiologically to be more strongly associated with many CAs than for tobacco and alcohol and is consistent with a cannabinoid class genotoxic/epigenotoxic effect. Quantitative causality criteria were fulfilled, and causal relationships either for Δ8THC or for cannabinoid/s, for which it is a surrogate marker, may be in operation.
Incidence of myocardial infarction, heart failure, and cardiovascular mortality in patients with peripheral artery disease: trends between 1997 and 2016
Authors: Kamil Sadaf , Sehested Thomas S G , Houlind Kim , Lassen Jens F , Gislason Gunnar H , Dominguez Helena
Published: May 2022

Aims

Over the past decades, there have been improvements in the management of cardiovascular (CV) disease and risk factors. Long-term contemporary data on the population-level incidence of myocardial infarction (MI), heart failure (HF), and CV mortality in patients with peripheral artery disease (PAD) are sparse, which we aim to investigate in this study.

Methods and results

Danish nationwide registers were used to identify all patients aged ≥18 years, with first diagnosis of PAD between 1997 and 2016. Age-standardized incidence rates (IRs) per 1000 person-years were calculated to estimate trends of MI, HF, and CV mortality. The risk of MI, HF, and CV mortality was estimated by 1-year cumulative incidence with death as the competing risk. A total of 131 568 patients with PAD were identified [median age 70.67 (interquartile range, IQR, 61–78) years and 53.05% males]. The IRs showed increasing trends of MI until 2002, with an estimated annual percentage change (APC) of + 0.6 [95% confidence interval (CI) 3.3–16.1, P-value 0.2]. After the year 2002, MI incidence persistently decreased until the study end with an estimated APC of −5.0 (95% CI 3.7–6.3, P < 0.0001), HF declined with an estimated APC of −3.3 (95% CI 2.0–4.6, P < 0.0001); and CV mortality declined, with an APC of −3.5 (95% CI 3.0–4.0, P < 0.0001).

Conclusion

The incidence of MI (since 2002) and HF in patients with PAD has significantly decreased over time, together with a decline in CV mortality. Our results suggest that preventive strategies have overall improved, most likely due to improvements in the application of guidelines in clinical care.
Age-dependent associations of body mass index with myocardial infarction, heart failure, and mortality in over 9 million Koreans
Authors: Lee Hyun Jung , Kim Hyung Kwan , Han Kyung Do , Lee Kyu na , Park Jun Bean , Lee Heesun , Lee Seung Pyo , Kim Yong Jin
Published: May 2022

Aims

While obesity is a well-known cardiovascular risk factor, little is known whether age has a modifying effect. The aim of this study is to determine the age-dependent associations of body mass index (BMI) with cardiovascular outcomes.

Methods and results

A population-based cohort of 9 278 433 Koreans without prior cardiovascular disease were followed up for the incidence of myocardial infarction (MI), heart failure (HF), and all-cause death. The effect of BMI with optimal normal weight (18.5–22.9 kg/m2) as reference was analysed according to age groups [young (20–39 years), middle-aged (40–64 years), and elderly (≥65 years)] and age decades. During 8.2 years, MI, HF, and all-cause death occurred in 65 607 (0.71%), 131 903 (1.42%), and 306 065 (3.30%), respectively. Associations between BMI and all outcomes were significantly modified by age (P-for-interaction < 0.001). There was a proportional increase in incident MI according to BMI in young subjects; this relationship became U-shaped in middle-aged subjects and inversely proportional/plateauing in elderly subjects. A U-shaped relationship between BMI and incident HF was observed, but the impact of obesity was stronger in young subjects while the impact of underweight was stronger in middle-aged and elderly subjects. Meanwhile, lower BMI was associated with higher all-cause mortality in all ages, although this association was attenuated at the young age, and pre-obesity was associated with the greatest survival benefit. These associations were independent of sex, smoking, physical activity, and comorbidities.

Conclusion

The impact of BMI on cardiovascular risk differs according to age. Weight loss may be recommended for younger overweight subjects, while being mildly overweight may be beneficial at old age.
Carotid ultrasonography improves residual risk stratification in guidelines-defined high cardiovascular risk patients
Authors: Georgiopoulos Georgios , Mavraganis Georgios , Delialis Dimitrios , Georgiou Stelios , Aivalioti Evmorfia , Patras Raphael , Petropoulos Ioannis , Dimopoulou Maria-Angeliki , Angelidakis Lasthenis , Sianis Alexandros , Bampatsias Dimitrios , Dimoula Anna , Maneta Eleni , Kosmopoulos Marinos , Vardavas Constantine , Stellos Konstantinos , Stamatelopoulos Kimon
Published: May 2022

Aims

The clinical value of carotid atherosclerosis markers for residual risk stratification in high atherosclerotic cardiovascular disease (ASCVD) risk patients is not established. We aimed to derive and validate optimal values of markers of carotid subclinical atherosclerosis improving risk stratification in guidelines-defined high ASCVD risk patients.

Methods and results

We consecutively analysed high or very high ASCVD risk patients from a cardiovascular (CV) prevention registry (n = 751, derivation cohort) and from the Atherosclerosis Risk in Communities (ARIC) study (n = 2,897, validation cohort). Baseline ASCVD risk was defined using the 2021 European Society of Cardiology guidelines (clinical ESCrisk). Intima-media thickness excluding plaque, average maximal (avg.maxWT), maximal wall thickness (maxWT) and number of sites with carotid plaque were assessed. As primary endpoint of the study was defined the composite of cardiac death, acute myocardial infarction and revascularization after a median of 3.4 years in both cohorts and additionally for 16.7 years in the ARIC cohort.

Results

MaxWT > 2.00 mm and avg.maxWT > 1.39 mm provided incremental prognostic value, improved discrimination and correctly reclassified risk over the clinical ESCrisk both in the derivation and the validation cohort (P < 0.05 for net reclassification index, integrated discrimination index and Delta Harrell’s C index). MaxWT < 0.9 mm predicted very low probability of CV events (negative predictive value = 97% and 92% in the derivation and validation cohort, respectively). These findings were additionally confirmed for very long-term events in the validation cohort.

Conclusion

Integration of carotid ultrasonography in guidelines-defined risk stratification may identify patients at very high-risk in need for further residual risk reduction or at very low probability for events.
Serum urate and heart failure: a bidirectional Mendelian randomization study
Authors: Yang Fangkun , Hu Teng , Cui Hanbin
Published: May 2022

Aims

Observational studies indicate that serum urate level is associated with heart failure (HF). However, whether this association is causal remains controversial, due to confounding factors and reverse causality. We aim to evaluate the causal relationship of genetically predicted serum urate level with HF.

Methods and results

A bidirectional Mendelian randomization (MR) study was performed. Instrumental variables were obtained from the largest genome-wide association studies of serum urate (457 690 individuals) to date. We obtained summary statistics of HF from HERMES consortium (47 309 cases; 930 014 controls), the FinnGen study (13 087 cases; 195 091 controls), and the UK Biobank study (1088 cases; 360 106 controls). Inverse-variance-weighted method was applied to obtain MR estimates and other statistical methods were conducted in the sensitivity analyses. The reverse MR analysis was performed to evaluate the effect of HF on serum urate levels. Genetically determined serum urate level was associated with HF [odds ratio (OR), 1.07; 95% confidence interval (CI), 1.03–1.10; P = 8.6×10−5]. The main results kept robust in the most sensitivity analyses. The association pattern remained for the HF in FinnGen (OR, 1.10; 95% CI, 1.03–1.19; P = 0.008) and the combined results of three data sources (OR, 1.08; 95% CI, 1.04–1.13; P < 0.001). No consistent evidence was found for the causal effect of HF on serum urate levels.

Conclusion

We provide consistent evidence for the causal effect of genetically predicted serum urate level on HF, but not the reverse effect of HF. Urate-lowering therapy may be of cardiovascular benefit in the prevention of HF.
LKB1 is physiologically required for sleep from Drosophila melanogaster to the Mus musculus
Authors: Liu Ziyi , Jiang Lifen , Li Chaoyi , Li Chengang , Yang Jingqun , Yu Jianjun , Mao Renbo , Rao Yi
Published: May 2022

LKB1 is known as a master kinase for 14 kinases related to the adenosine monophosphate (AMP)-activated protein kinase (AMPK). Two of them (SIK3 and AMPKa) have previously been implicated in sleep regulation. We generated loss-of-function (LOF) mutants for Lkb1 in both Drosophila and mice. Sleep, but not circadian rhythms, was reduced in Lkb1-mutant flies and in flies with neuronal deletion of Lkb1. Genetic interactions between Lkb1 and AMPK T184A mutants in Drosophila sleep or those between Lkb1 and SIK3 T196A mutants in Drosophila viability have been observed. Sleep was reduced in mice after virally mediated reduction of Lkb1 in the brain. Electroencephalography (EEG) analysis showed that non-rapid eye movement (NREM) sleep and sleep need were both reduced in Lkb1-mutant mice. These results indicate that LKB1 plays a physiological role in sleep regulation conserved from flies to mice.
The state of Medusozoa genomics: current evidence and future challenges
Authors: Santander Mylena D , Maronna Maximiliano M , Ryan Joseph F , Andrade Sónia C S
Published: May 2022

Medusozoa is a widely distributed ancient lineage that harbors one-third of Cnidaria diversity divided into 4 classes. This clade is characterized by the succession of stages and modes of reproduction during metagenic lifecycles, and includes some of the most plastic body plans and life cycles among animals. The characterization of traditional genomic features, such as chromosome numbers and genome sizes, was rather overlooked in Medusozoa and many evolutionary questions still remain unanswered. Modern genomic DNA sequencing in this group started in 2010 with the publication of the Hydra vulgaris genome and has experienced an exponential increase in the past 3 years. Therefore, an update of the state of Medusozoa genomics is warranted. We reviewed different sources of evidence, including cytogenetic records and high-throughput sequencing projects. We focused on 4 main topics that would be relevant for the broad Cnidaria research community: (i) taxonomic coverage of genomic information; (ii) continuity, quality, and completeness of high-throughput sequencing datasets; (iii) overview of the Medusozoa specific research questions approached with genomics; and (iv) the accessibility of data and metadata. We highlight a lack of standardization in genomic projects and their reports, and reinforce a series of recommendations to enhance future collaborative research.
Generation and application of pseudo–long reads for metagenome assembly
Authors: Sim Mikang , Lee Jongin , Wy Suyeon , Park Nayoung , Lee Daehwan , Kwon Daehong , Kim Jaebum
Published: May 2022

Background

Metagenomic assembly using high-throughput sequencing data is a powerful method to construct microbial genomes in environmental samples without cultivation. However, metagenomic assembly, especially when only short reads are available, is a complex and challenging task because mixed genomes of multiple microorganisms constitute the metagenome. Although long read sequencing technologies have been developed and have begun to be used for metagenomic assembly, many metagenomic studies have been performed based on short reads because the generation of long reads requires higher sequencing cost than short reads.

Results

In this study, we present a new method called PLR-GEN. It creates pseudo–long reads from metagenomic short reads based on given reference genome sequences by considering small sequence variations existing in individual genomes of the same or different species. When applied to a mock community data set in the Human Microbiome Project, PLR-GEN dramatically extended short reads in length of 101 bp to pseudo–long reads with N50 of 33 Kbp and 0.4% error rate. The use of these pseudo–long reads generated by PLR-GEN resulted in an obvious improvement of metagenomic assembly in terms of the number of sequences, assembly contiguity, and prediction of species and genes.

Conclusions

PLR-GEN can be used to generate artificial long read sequences without spending extra sequencing cost, thus aiding various studies using metagenomes.
Chemical induction of leaf senescence and powdery mildew resistance involves ethylene-mediated chlorophyll degradation and ROS metabolism in cucumber
Authors: Zhang Dingyu , Wu Shengdong , Li Ning , Gao Jiong , Liu Shihui , Zhu Shuai , Li Zilin , Ren Guodong , Kuai Benke
Published: May 2022

Timely initiation of leaf senescence is an integral part of plant development and, importantly, an adaptive strategy by which plants cope with various stresses, e.g. to limit the spread of pathogens. Powdery mildew is a major cucumber disease that promotes the initiation/progression of leaf senescence and reduces leaf photosynthesis, resulting in severe losses of yield and quality. However, how powdery mildew induces leaf senescence and how cucumber plants respond to enhance their resistance remain unclear. Here, with established agrochemical induction and pathogen inoculation systems, we demonstrate that both probenazole (PBZ) and powdery mildew activate ethylene (ET) biosynthesis and signal transduction, consequently promoting leaf senescence and enhancing plant resistance to powdery mildew through CsEIN3 to directly upregulate the expression of CsCCGs and CsRBOHs. Our analysis convincingly suggests that the regulation of leaf senescence and powdery mildew resistance is interconnected and mediated mainly by ET in cucumber.
Mechanism ofCsGPA1in regulating cold tolerance of cucumber
Authors: Yan Yan , Mintao Sun , Si Ma , Qian Feng , Yijia Wang , Qinghua Di , Mengdi Zhou , Chaoxing He , Yansu Li , Lihong Gao , Xianchang Yu
Published: May 2022

G proteins function directly in cold tolerance of plants. However, the framework of the Gα subunit in regulating cold tolerance remains to be explored. Here, we used protein interaction techniques to elucidate cold-related pathways regulated by CsGPA1. Suppression of CsGPA1 decreased the cold tolerance of cucumber. Further protein interaction experiments showed that CsGPA1 interacted with Csa_4G663630.1 located in the cell membrane and nucleus and with CsCOR413PM2 located in the cell membrane. Csa_4G663630.1 was named CsCDL1 due to its 71% protein sequence similarity to AtCDL1, a positive brassinolide signal gene. Suppression of CsGPA1 decreased the expression of most of brassinolide-related genes (including CsCDL1) under cold stress. Principal component and linear regression analyses showed that expressions of CsGPA1 and brassinolide-related genes were positively correlated. Suppression of CsCOR413PM2 also decreased cold tolerance of cucumber. The expression and protein content of CsCOR413PM2 and CsGPA1 in CsGPA1-RNAi and CsCOR413PM2-RNAi lines were determined under cold tolerance. Only CsGPA1 silencing affected the expression and protein content of CsCOR413PM2 during cold stress. Moreover, suppression of CsGPA1 or CsCOR413PM2 decreased Ca 2+ influx at low temperature and then decreased the expression of CsICE–CsCBF. These results indicated that the CsGPA1–CsCOR413PM2–Ca2+ axis regulated the expression of CsICE–CsCBF during cold stress. In conclusion, Our results provide the first framework of CsGPA1 in regulating cold tolerance of cucumber, laying the foundation for further mechanistic studies of cold tolerance for Gα in cucumber.
Tea GOLDEN2-LIKE genes enhance catechin biosynthesis through activating R2R3-MYB transcription factor
Authors: Wang Lihuan , Tang Xiaofeng , Zhang Shiqiang , Xie Xiang , Li Mengfei , Liu Yongsheng , Wang Songhu
Published: May 2022

The biosynthesis of catechins, a major type of flavonoids accumulated in tea, is mediated by developmental cues and environmental stimuli. Light enhances but shading treatment reduces catechin accumulation in tea leaves. However, the transcription factors involved in light-mediated catechin biosynthesis remain to be identified. Two GOLDEN2 LIKE genes from tea plant (CsGLK1 and CsGLK2) were isolated and characterized in both tomato and tea plants. Transcripts of both CsGLK1 and CsGLK2 were affected by light intensity in tea plants. Overexpression of CsGLK1 and CsGLK2 promoted chloroplast development and carotenoid accumulation in tomato fruits. An integrated metabolomic and transcriptomic approach revealed that both catechin content and related biosynthetic genes were upregulated in CsGLK-overexpressing tomato leaves. Our further studies in tea plants indicated that CsGLKs directly regulate the transcription of CsMYB5b, a transcription factor involved in catechin biosynthesis. Suppression of CsGLKs in tea leaves led to the reduction of both CsMYB5b expression and catechin accumulation. Taken together, the results show that CsGLKs are involved in light-regulated catechin accumulation in tea plants by regulating expression of CsMYB5b and have great potential for enhancing the accumulation of both carotenoids and flavonoids in fruits of horticultural crops.
A systematic review and meta-analysis of vineyard techniques used to delay ripening
Authors: Previtali Pietro , Giorgini Filippo , Mullen Randall S , Dookozlian Nick K , Wilkinson Kerry L , Ford Christopher M
Published: May 2022

Several vineyard techniques have been proposed to delay grape maturity in light of the advanced maturation driven by increasingly frequent water and heat stress events that are detrimental to grape quality. These studies differ in terms of their experimental conditions, and in the present work we have attempted to summarize previous observations in a quantitative, data-driven systematic review. A meta-analysis of quantitative data gathered across 43 relevant studies revealed the overall significance of the proposed treatments and evaluated the impact of different experimental conditions on the outcome of antitranspirants, delayed pruning and late source limitation. Antitranspirants were most effective when applied twice and closer to veraison, while di-1-p-menthene increased the ripening delay by about 1 °Brix compared to kaolin. Larger ripening delays were achieved with delayed pruning of low-yielding vines or by pruning at later stages of apical bud development. Late defoliation or shoot trimming delayed ripening in high-yielding vines and represent suitable solutions for late-harvested varieties, but became ineffective where the treatment decreased yield. This quantitative meta-analysis of 242 primary observations uncovers factors affecting the efficacy of vineyard practices to delay ripening, which should be carefully considered by grape growers attempting to achieve this outcome.
Growth and Mortality as Causes of Variation in Metabolic Scaling Among Taxa and Taxonomic Levels
Authors: Norin Tommy
Published: May 2022

Metabolic rate (MR) usually changes (scales) out of proportion to body mass (BM) as MR = aBMb, where a is a normalisation constant and b is the scaling exponent that reflects how steep this change is. This scaling relationship is fundamental to biology, but over a century of research has provided little consensus on the value of b, and why it appears to vary among taxa and taxonomic levels. By analysing published data on fish and taking an individual-based approach to metabolic scaling, I show that variation in growth of fish under naturally restricted food availability can explain variation in within-individual (ontogenetic) b for standard (maintenance) metabolic rate (SMR) of brown trout (Salmo trutta), with the fastest growers having the steepest metabolic scaling (b ≈ 1). Moreover, I show that within-individual b can vary much more widely than previously assumed from work on different individuals or different species, from –1 to 1 for SMR among individual brown trout. The negative scaling of SMR for some individuals was caused by reductions in metabolic rate in a food limited environment, likely to maintain positive growth. This resulted in a mean within-individual b for SMR that was significantly lower than the across-individual (“static”) b, a difference that also existed for another species, cunner (Tautogolabrus adspersus). Interestingly, the wide variation in ontogenetic b for SMR among individual brown trout did not exist for maximum (active) metabolic rate (MMR) of the same fish, showing that these two key metabolic traits (SMR and MMR) can scale independently of one another. I also show that across-species (“evolutionary”) b for SMR of 134 fishes is significantly steeper (b approaching 1) than the mean ontogenetic b for the brown trout and cunner. Based on these interesting findings, I hypothesise that evolutionary and static metabolic scaling can be systematically different from ontogenetic scaling, and that the steeper evolutionary than ontogenetic scaling for fishes arises as a by-product of natural selection for fast-growing individuals with steep metabolic scaling (b ≈ 1) early in life, where size-selective mortality is high for fishes. I support this by showing that b for SMR tends to increase with natural mortality rates of fish larvae within taxa.
How can the rate of nontherapeutic thymectomy be reduced?
Authors: Wang Shuai , Ao Yongqiang , Jiang Jiahao , Lin Miao , Chen Gang , Liu Junzhen , Zhao Shihai , Gao Jian , Zhang Yi , Ding Jianyong , Tan Lijie
Published: May 2022

OBJECTIVES

The aim of this study was to determine the prevalence of nontherapeutic thymectomy and define a clinical standard to reduce it.

METHODS

From 2016 to 2020, consecutive patients who underwent thymectomy were retrospectively reviewed. Univariable and multivariable analyses were used to identify the correlation factors of nontherapeutic thymectomy. A receiver operating characteristic curve was analysed to assess the cut-off threshold of factors correlated with nontherapeutic thymectomy.

RESULTS

A total of 1039 patients were included in this study. Overall, 78.4% (n = 814) of thymectomies were therapeutic and 21.6% (n = 225) were nontherapeutic. Thymoma (57.9%, n = 602) was the most common diagnosis in therapeutic thymectomy. Among those of nontherapeutic thymectomy, thymic cysts (11.9%, n = 124) were the most common lesion. Compared with therapeutic thymectomy, patients with nontherapeutic thymectomy were more likely to be younger (median age 50.1 vs 55.6 years, P < 0.001) with a smaller precontrast and postcontrast computed tomography (CT) value (P < 0.001, P < 0.001), as well as ΔCT value [10.7 vs 23.5 Hounsfield units (HU), P < 0.001]. Multivariable analysis indicated that only age and ΔCT value were significantly different between therapeutic and nontherapeutic thymectomy groups. Receiver operating characteristic curve analysis showed that cut-off values of age and ΔCT value were 44 years and 6 HU, respectively. Patients with age ≤44 years and a ΔCT value ≤6 HU had a 95% probability of nontherapeutic thymectomy.

CONCLUSIONS

Surgeons should be cautious to perform thymectomy for patients with age ≤44 years and ΔCT value ≤6 HU. This simple clinical standard is helpful to reduce the rate of nontherapeutic thymectomy.