The 17-subunit RNA polymerase III (RNAP III) synthesizes essential untranslated RNAs such as tRNAs and 5S rRNA. In yeast and vertebrates, subunit C82 forms a stable subcomplex with C34 and C31 that is necessary for promoter-specific transcription initiation. Little is known about RNAP III transcription in trypanosomatid parasites. To narrow this knowledge gap, we characterized the C82 subunit in Trypanosoma brucei and Leishmania major. Bioinformatic analyses showed that the 4 distinctive extended winged-helix (eWH) domains and the coiled-coil motif are present in C82 in these microorganisms. Nevertheless, C82 in trypanosomatids presents certain unique traits, including an exclusive loop within the eWH1 domain. We found that C82 localizes to the nucleus and binds to RNAP III-dependent genes in the insect stages of both parasites. Knock-down of C82 by RNA interference significantly reduced the levels of tRNAs and 5S rRNA and led to the death of procyclic forms of T. brucei. Tandem affinity purifications with both parasites allowed the identification of several C82-interacting partners, including C34 and some genus-specific putative regulators of transcription. However, the orthologue of C31 was not found in trypanosomatids. Interestingly, our data suggest a strong association of C82 with TFIIIC subunits in T. brucei, but not in L. major.

With the efflorescence of palaeoscientific approaches to the past, historians have been confronted with a wealth of new evidence on both human and natural phenomena, from human disease and migration to landscape change and climate. These new data require a rewriting of our narratives of the past, questioning what constitutes an authoritative historical source and who is entitled to recount history to contemporary societies. Humanities-based historical inquiry must embrace this new evidence, but to do so historians need to engage with it critically, just as they do with textual and material sources. This article highlights the most vital methodological issues, ranging from the spatiotemporal scales and heterogeneity of the new evidence to the new roles attributed to quantitative methods and the place of scientific data in narrative construction. It considers areas of study where the palaeosciences have “intruded” into fields and subjects previously reserved for historians, especially socioeconomic, climate, and environmental history. The authors argue that active engagement with new approaches is urgently needed if historians want to contribute to our evolving understanding of the challenges of the Anthropocene.

Avec l’efflorescence des approches paléoscientifiques du passé, les historiens ont été confrontés à une multitude de nouveaux indices sur des phénomènes tant humains que naturels, des maladies aux migrations en passant par les transformations du paysage et le climat. Ces données inédites exigent une réécriture des récits portant sur les périodes lointaines, remettant en cause à la fois les fondements de l’autorité des sources historiques traditionnelles et la légitimité des personnes habilitées à narrer le passé aux sociétés contemporaines. Les travaux d’histoire appuyés sur les sciences humaines doivent embrasser ces nouveaux types d’indices ; cependant, pour y parvenir, il est nécessaire pour les chercheurs de s’engager dans cette voie de manière critique, comme ils le font pour les sources textuelles et matérielles. Cet article souhaite mettre en lumière les questions méthodologiques les plus essentielles, qui vont des échelles spatio-temporelles et de l’hétérogénéité des nouvelles preuves au rôle à attribuer aux méthodes quantitatives et à la place des données scientifiques dans la construction narrative. Il examine les domaines d’étude où les paléosciences se sont « immiscées » dans des champs et des sujets auparavant réservés aux historiens, notamment l’histoire socio-économique, climatique et environnementale. Les auteurs soutiennent qu’il est urgent pour ces spécialistes d’explorer activement ces pistes novatrices, s’ils entendent contribuer à l’évolution de notre compréhension des défis de l’Anthropocène.

Condensation and faithful separation of the genome are crucial for the cellular life cycle. During chromosome segregation, mechanical forces generated by the mitotic spindle pull apart the sister chromatids. The mechanical nature of this process has motivated a lot of research interest into the mechanical properties of mitotic chromosomes. Although their fundamental mechanical characteristics are known, it still remains unclear how these characteristics emerge from the structure of the mitotic chromosome. Recent advances in genomics, computational and super-resolution microscopy techniques have greatly promoted our understanding of the chromosomal structure and have motivated us to review the mechanical characteristics of chromosomes in light of the current structural insights. In this review, we will first introduce the current understanding of the chromosomal structure, before reviewing characteristic mechanical properties such as the Young's modulus and the bending modulus of mitotic chromosomes. Then we will address the approaches used to relate mechanical properties to the structure of chromosomes and we will also discuss how mechanical characterization can aid in elucidating their structure. Finally, future challenges, recent developments and emergent questions in this research field will be discussed.

Arctic mining has a bad reputation because the extractive industry is often responsible for a suite of environmental problems. Yet, few studies explore the gap between untouched tundra and messy megaproject from a historical perspective. Our paper focuses on Advent City as a case study of the emergence of coal mining in Svalbard (Norway) coupled with the onset of mining-related environmental change. After short but intensive human activity (1904–1908), the ecosystem had a century to respond, and we observe a lasting impact on the flora in particular. With interdisciplinary contributions from historical archaeology, archaeozoology, archaeobotany and botany, supplemented by stable isotope analysis, we examine 1) which human activities initially asserted pressure on the Arctic environment, 2) whether the miners at Advent City were “eco-conscious,” for example whether they showed concern for the environment and 3) how the local ecosystem reacted after mine closure and site abandonment. Among the remains of typical mining infrastructure, we prioritised localities that revealed the subtleties of long-term anthropogenic impact. Significant pressure resulted from landscape modifications, the import of non-native animals and plants, hunting and fowling, and the indiscriminate disposal of waste material. Where it was possible to identify individual inhabitants, these shared an economic attitude of waste not, want not, but they did not hold the environment in high regard. Ground clearances, animal dung and waste dumps continue to have an effect after a hundred years. The anthropogenic interference with the fell field led to habitat creation, especially for vascular plants. The vegetation cover and biodiversity were high, but we recorded no exotic or threatened plant species. Impacted localities generally showed a reduction of the natural patchiness of plant communities, and highly eutrophic conditions were unsuitable for liverworts and lichens. Supplementary isotopic analysis of animal bones added data to the marine reservoir offset in Svalbard underlining the far-reaching potential of our multi-proxy approach. We conclude that although damaging human–environment interactions formerly took place at Advent City, these were limited and primarily left the visual impact of the ruins. The fell field is such a dynamic area that the subtle anthropogenic effects on the local tundra may soon be lost. The fauna and flora may not recover to what they were before the miners arrived, but they will continue to respond to new post-industrial circumstances.

Understanding risk factors for death from Covid-19 is key to providing good quality clinical care. We assessed the presenting characteristics of the ‘first wave’ of patients with Covid-19 at Royal Oldham Hospital, UK and undertook logistic regression modelling to investigate factors associated with death. Of 470 patients admitted, 169 (36%) died. The median age was 71 years (interquartile range 57–82), and 255 (54.3%) were men. The most common comorbidities were hypertension (n = 218, 46.4%), diabetes (n = 143, 30.4%) and chronic neurological disease (n = 123, 26.1%). The most frequent complications were acute kidney injury (AKI) (n = 157, 33.4%) and myocardial injury (n = 21, 4.5%). Forty-three (9.1%) patients required intubation and ventilation, and 39 (8.3%) received non-invasive ventilation. Independent risk factors for death were increasing age (odds ratio (OR) per 10 year increase above 40 years 1.87, 95% confidence interval (CI) 1.57–2.27), hypertension (OR 1.72, 95% CI 1.10–2.70), cancer (OR 2.20, 95% CI 1.27–3.81), platelets <150 × 103/μl (OR 1.93, 95% CI 1.13–3.30), C-reactive protein ≥100 μg/ml (OR 1.68, 95% CI 1.05–2.68), >50% chest radiograph infiltrates (OR 2.09, 95% CI 1.16–3.77) and AKI (OR 2.60, 95% CI 1.64–4.13). There was no independent association between death and gender, ethnicity, deprivation level, fever, SpO2/FiO2, lymphopoenia or other comorbidities. These findings will inform clinical and shared decision making, including use of respiratory support and therapeutic agents.

Radiocarbon (14C) ages cannot provide absolutely dated chronologies for archaeological or paleoenvironmental studies directly but must be converted to calendar age equivalents using a calibration curve compensating for fluctuations in atmospheric 14C concentration. Although calibration curves are constructed from independently dated archives, they invariably require revision as new data become available and our understanding of the Earth system improves. In this volume the international 14C calibration curves for both the Northern and Southern Hemispheres, as well as for the ocean surface layer, have been updated to include a wealth of new data and extended to 55,000 cal BP. Based on tree rings, IntCal20 now extends as a fully atmospheric record to ca. 13,900 cal BP. For the older part of the timescale, IntCal20 comprises statistically integrated evidence from floating tree-ring chronologies, lacustrine and marine sediments, speleothems, and corals. We utilized improved evaluation of the timescales and location variable 14C offsets from the atmosphere (reservoir age, dead carbon fraction) for each dataset. New statistical methods have refined the structure of the calibration curves while maintaining a robust treatment of uncertainties in the 14C ages, the calendar ages and other corrections. The inclusion of modeled marine reservoir ages derived from a three-dimensional ocean circulation model has allowed us to apply more appropriate reservoir corrections to the marine 14C data rather than the previous use of constant regional offsets from the atmosphere. Here we provide an overview of the new and revised datasets and the associated methods used for the construction of the IntCal20 curve and explore potential regional offsets for tree-ring data. We discuss the main differences with respect to the previous calibration curve, IntCal13, and some of the implications for archaeology and geosciences ranging from the recent past to the time of the extinction of the Neanderthals.

Since the launch of the Materials Genome Initiative (MGI) the field of materials informatics (MI) emerged to remove the bottlenecks limiting the pathway towards rapid materials discovery. Although the machine learning (ML) and optimization techniques underlying MI were developed well over a decade ago, programs such as the MGI encouraged researchers to make the technical advancements that make these tools suitable for the unique challenges in materials science and engineering. Overall, MI has seen a remarkable rate in adoption over the past decade. However, for the continued growth of MI, the educational challenges associated with applying data science techniques to analyse materials science and engineering problems must be addressed. In this paper, we will discuss the growing use of materials informatics in academia and industry, highlight the need for educational advances in materials informatics, and discuss the implementation of a materials informatics course into the curriculum to jump-start interested students with the skills required to succeed in materials informatics projects.

Here we provide an update of the 2013 report on the Nigerian Twin and Sibling Registry (NTSR). The major aim of the NTSR is to understand genetic and environmental influences and their interplay in psychological and mental health development in Nigerian children and adolescents. Africans have the highest twin birth rates among all human populations, and Nigeria is the most populous country in Africa. Due to its combination of large population and high twin birth rates, Nigeria has one of the largest twin populations in the world. In this article, we provide current updates on the NTSR samples recruited, recruitment procedures, zygosity assessment and findings emerging from the NTSR.

An unexpected increase in gastroenteritis cases was reported by healthcare workers on the KwaZulu-Natal Coast, South Africa, January 2017 with >600 cases seen over a 3-week period. A case–control study was conducted to identify the source and risk factors associated with the outbreak so as to recommend control and prevention measures. Record review identified cases and controls and structured-telephonic interviews were conducted to obtain exposure history. Stool specimens were collected from 20 cases along with environmental samples and both screened for enteric pathogens. A total of 126 cases and 62 controls were included in the analysis. The odds of developing gastroenteritis were 6.0 times greater among holiday makers than residents (95% confidence interval (CI) 2.0–17.7). Swimming in the lagoon increased the odds of developing gastroenteritis by 3.3 times (95% CI 1.06–10.38). Lagoon water samples tested positive for norovirus (NoV) GI.6, GII.3 and GII.6, astrovirus and rotavirus. Eleven (55%) stool specimens were positive for NoV with eight genotyped as GI.1 (n = 2), GI.5 (n = 3), GI.6 (n = 2), and GI.7 (n = 1). A reported sewage contamination event impacting the lagoon was the likely source with person-to-person spread perpetuating the outbreak. Restriction to swimming in the lagoon was apparently ineffective at preventing the outbreak, possibly due to inadequate enforcement, communication and signage strategies.

Bacterial cultures exposed to iron-doped apatite nanoparticles (IDANPs) prior to the introduction of antagonistic viruses experience up to 2.3 times the bacterial destruction observed in control cultures. Maximum antibacterial activity of these bacteria-specific viruses, or phage, occurs after bacterial cultures have been exposed to IDANPs for 1 hr prior to phage introduction, demonstrating that IDANP-assisted phage therapy would not be straight forward, but would instead require controlled time release of IDANPs and phage. These findings motivated the design of an electrospun nanofiber mesh treatment delivery system that allows burst release of IDANPs, followed by slow, consistent release of phage for treatment of topical bacterial infections. IDANPs resemble hydroxyapatite, a biocompatible mineral analogous to the inorganic constituent of mammalian bone, which has been approved by the Food and Drug Administration for many biomedical purposes. The composite nanofiber mesh was designed for IDANP-assisted phage therapy treatment of topical wounds and consists of a superficial, rapid release layer of polyethylene oxide (PEO) fibers doped with IDANPs, followed by inner, coaxial polycaprolactone / polyethylene glycol (PCL/PEG) blended polymer fiber layer for slower phage delivery. Our investigations have established that IDANP-doped PEO fibers are effective vehicles for dissemination of IDANPs for bacterial exposure and resultant increased bacterial death by phage. In this work, slower delivery of the phage behind IDANPs was accomplished using coaxial, electrospun fibers composed of PCL/PEG polymer blend.

Lacustrine sediments from southeastern Arabia reveal variations in lake level corresponding to changes in the strength and duration of Indian Ocean Monsoon (IOM) summer rainfall and winter cyclonic rainfall. The late glacial/Holocene transition of the region was characterised by the development of mega-linear dunes. These dunes became stabilised and vegetated during the early Holocene and interdunal lakes formed in response to the incursion of the IOM at approximately 8500 cal yr BP with the development of C3 dominated savanna grasslands. The IOM weakened ca. 6000 cal yr BP with the onset of regional aridity, aeolian sedimentation and dune reactivation and accretion. Despite this reduction in precipitation, the lake was maintained by winter dominated rainfall. There was a shift to drier adapted C4 grasslands across the dune field. Lake sediment geochemical analyses record precipitation minima at 8200, 5000 and 4200 cal yr BP that coincide with Bond events in the North Atlantic. A number of these events correspond with changes in cultural periods, suggesting that climate was a key mechanism affecting human occupation and exploitation of this region.