Differing susceptibility of C57BL/6J and DBA/2J mice—parents of the murine BXD family, to severe acute respiratory syndrome coronavirus infection

The ongoing coronavirus disease-2019 (COVID-19) pandemic, caused by a novel coronavirus termed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that is closely related to SARS-CoV, poses a grave threat to global health and has devastated societies worldwide. One puzzling aspect of COVID-19 is the impressive variation in disease manifestations among infected individuals, from a majority who are asymptomatic or exhibit mild symptoms to a smaller, largely age-dependent fraction who develop life-threatening conditions. Some of these differences are likely the consequence of host genetic factors. Systems genetics using diverse and replicable cohorts of isogenic mice represents a powerful way to dissect those host genetic differences that modulate microbial infections. Here we report that the two founders of the large BXD family of mice—C57BL/6J and DBA/2J, differ substantially in their susceptibility to a mouse-adapted SARS-CoV, MA15. Following intranasal viral challenge, DBA/2J develops a more severe disease than C57BL/6J as evidenced by more pronounced and sustained weight loss. Disease was accompanied by high levels of pulmonary viral replication in both strains early after infection but substantially delayed viral clearance in DBA/2J. Our data reveal that the parents of the BXD family are segregated by clear phenotypic differences during MA15 infection and support the feasibility of using this family to systemically dissect the complex virus-host interactions that modulate disease progression and outcome of infection with SARS-CoV, and provisionally also with SARS-CoV-2.

Unilateral body neglect: schemas versus images?

Unilateral spatial neglect has been extensively described for visual and representational manifestations but tactile and motor manifestations as well as body neglect point to bodily manifestations of this neurological condition. This chapter reviews the perceptual, motoric and high-level representational symptoms manifested in neglect patients and attempt to classify them according to the body image/schema framework. One puzzling aspect of the wide spectrum of body neglect symptoms is that physiological bottom-up maneuvers, such as prism adaptation, which act at the level of body schema, do also efficiently improve body image manifestations of neglect. This relationship allows us to elaborate on the dialectical relationships between body image and body schema. Thus, understanding body neglect in terms of diagnosis, evaluation, physiopathology and therapeutics through the dynamical interactions between body schema and body neglect, provide perspectives to manage other lateralized body troubles, neglect-like manifestations of bodily attention or distorted representations.

Recent African strains of Zika virus display higher transmissibility and fetal pathogenicity than Asian strains

The global emergence of Zika virus (ZIKV) revealed the unprecedented ability for a mosquito-borne virus to cause congenital birth defects. A puzzling aspect of ZIKV emergence is that all human outbreaks and birth defects to date have been exclusively associated with the Asian ZIKV lineage, despite a growing body of laboratory evidence pointing towards higher transmissibility and pathogenicity of the African ZIKV lineage. Whether this apparent paradox reflects the use of relatively old African ZIKV strains in most laboratory studies is unclear. Here, we experimentally compare seven low-passage ZIKV strains representing the recently circulating viral genetic diversity. We find that recent African ZIKV strains display higher transmissibility in mosquitoes and higher lethality in both adult and fetal mice than their Asian counterparts. We emphasize the high epidemic potential of African ZIKV strains and suggest that they could more easily go unnoticed by public health surveillance systems than Asian strains due to their propensity to cause fetal loss rather than birth defects.

High transmissibility and fetal pathogenicity of recent Zika virus strains from the African lineage

SummaryThe global emergence of Zika virus (ZIKV) in the last decade revealed the unprecedented ability for a mosquito-borne virus to cause congenital birth defects such as microcephaly. A puzzling aspect of ZIKV emergence is that all human outbreaks and birth defects to date have been exclusively associated with the Asian ZIKV lineage, despite a growing body of laboratory evidence pointing towards higher transmissibility and pathogenicity of the African ZIKV lineage. Whether this apparent paradox reflects the use of relatively old African ZIKV strains in most laboratory studies is unclear. Here, we experimentally compared the transmissibility and pathogenicity of seven low-passage ZIKV strains representing the recently circulating viral genetic diversity. We found that recent African ZIKV strains largely outperformed their Asian counterparts in mosquito transmission kinetics experiments, which translated into a markedly higher epidemic potential in outbreak computer simulations. In addition, African ZIKV strains were significantly more lethal than Asian ZIKV strains in immunocompromised adult mice. Finally, prenatal infection of immunocompetent mouse embryos with an African ZIKV strain resulted in embryonic death whereas it caused microcephaly with Asian ZIKV strains. Together, our results demonstrate the high epidemic potential and pathogenicity of recent ZIKV strains from Africa. Importantly, they also imply that the African ZIKV lineage could more easily go unnoticed by public health surveillance systems than the Asian ZIKV lineage due to its propensity to cause fetal loss rather than birth defects.

Guest warriors: The phenomenon of post-soviet fighters in the Syrian conflict

A puzzling aspect of the Syrian war has been the seemingly endless infusion of foreign fighters who have fueled and sustained the conflict. Unique among these are the militants from former Soviet regions such as Northern Caucasus in Russia and republics of Central Asia. In the evolving complexity of a layered and multifaceted conflict, it is easy to overlook the incongruousness of their presence in the conflict. Unlike most other foreign fighters, including those joining from Western Europe and North America, the post-Soviet militants lack the ethno-linguistic ties to the region. Rather, they hail from areas steeped in comparatively secular traditions and largely detached from the central tenants of the Syrian war. This makes their presence among extremist groups, such as the Islamic State, somewhat intriguing and anomalous. A key question, therefore, is why would these individuals join what to them in many ways is an alien war with extremely prohibitive costs? This articles proposes, as complementary to the dominant religious-ideological accounts, an explanation rooted in the enabling effect of marginalization processes in militants’ domestic settings.

The classification of the Japonic languages

The chapter starts with an overview of the history of dialect classification in Japan. A puzzling aspect of the distribution pattern of the Japanese dialects is the fact that many features, which cannot all be explained as retentions or simplifications, recur in geographically distant areas. These similarities have been commonly but unsatisfyingly regarded as the result of parallel independent developments. Phonological (including tonal), morphological, and lexical features are selected to illustrate the splits that result in the different branches of Japonic. Based on shared innovations, the new classification at the end of the chapter proposes a Izumo-Tōhoku branch, as well as a Kyūshū-Ryūkyū branch.

The numerator bias exists in millions of real-world comparisons

Fractions are crucial, from math and science education to daily activities, but they are hard. A puzzling aspect of fractions is that people over-rely on the numerator when comparing a pair of fractions. Previous work has considered this numerator bias mostly as a reasoning mishap. Still, in a vast amount of pairwise comparisons, across many real-world domains, not just education textbooks, we report a high prior probability that the larger fraction has the larger numerator, and, for a relevant case, we provide formal arguments why. The existence of such a regularity suggests that the numerator bias may reflect a rational adaptation that detects and exploits likely events. In a pair of visual-proportion tasks (discrete and continuous fractions), we confirm that the numerator bias in participants adapts to experimented regularities. Even though weak education and math abilities play a role, adaptation to informative priors outside the classroom poses a challenge to educators, learners, and decision-makers.

Metabolic adaptations underlying genome flexibility in prokaryotes

Even across genomes of the same species, prokaryotes exhibit remarkable flexibility in gene content. We do not know whether this flexible or “accessory” content is mostly neutral or adaptive, largely due to the lack of explicit analyses of accessory gene function. Here, across 96 diverse prokaryotic species, I show that a considerable fraction (~40%) of accessory genomes harbours beneficial metabolic functions. These functions take two forms: (1) they significantly expand the biosynthetic potential of individual strains, and (2) they help reduce strain-specific metabolic auxotrophies via intra-species metabolic exchanges. I find that the potential of both these functions increases with increasing genome flexibility. Together, these results are consistent with a significant adaptive role for prokaryotic pangenomes.Author SummaryRecent and rapid advancements in genome sequencing technologies have revealed key insights into the world of bacteria and archaea. One puzzling aspect uncovered by these studies is the following: genomes of the same species can often look very different. Specifically, some “core” genes are maintained across all intraspecies genomes, but many “accessory” genes differ between strains. A major ongoing debate thus asks: do most of these accessory genes provide a benefit to different strains, and if so, in what form? In this study, I suggest that the answer is “yes, through metabolic interactions”. I show that many accessory genes provide significant metabolic advantages to different strains in different conditions. I achieve this by explicitly conducting a large-scale systematic analysis of 1,339 genomes across 96 diverse species of bacteria and archaea. A surprising prediction of this study that in many ecological niches, co-occurring strains of the same species may help each other survive by exchanging metabolites exclusively produced by these different accessory genes. More pronounced gene differences lead to more underlying metabolic advantages.

Politics does not stop at the ‘nuclear edge’: neoclassical realism and the making of China’s military doctrine

The article tries to explain why China, after having launched a crash programme in the mid-1950s to develop a nuclear deterrent, did not formulate a clear operational doctrine with respect to the targeting and employment of atomic weapons until the mid-1980s. Propositions derived from neoclassical realism are used to shed some light on this puzzling aspect of China’s nuclear doctrine. The general hypothesis of the study is that, international predicaments notwithstanding, China’s domestic politics prevented the possibility of articulating a clear and detailed nuclear doctrine during the period following the first nuclear test, when such a doctrine was more necessary.

The Outermost Solar System

This chapter illustrates how, until the mid-20th century, little was known about the true nature of asteroids and comets. Asteroids looked like single points of light through a telescope, and astronomers tended to think of them as miniature planets, albeit ones with somewhat more elliptical and inclined orbits. Comets seemed to constitute a separate family, distinct from asteroids. They grew much brighter as they approached the Sun, becoming enormously extended objects with a diffuse coma and one or more tails that could extend for millions of kilometers. The most puzzling aspect of comets was how they had managed to survive for the age of the solar system. Comets had such low masses that they could not be measured, yet they shed large amounts of material each time they passed close to the Sun to form their coma and tails.