From the Cover: The skeleton of tropical intraseasonal oscillations

The Madden–Julian oscillation (MJO) is the dominant mode of variability in the tropical atmosphere on intraseasonal timescales and planetary spatial scales. Despite the primary importance of the MJO and the decades of research progress since its original discovery, a generally accepted theory for its essential mechanisms has remained elusive. Here, we present a minimal dynamical model for the MJO that recovers robustly its fundamental features (i.e., its “skeleton”) on intraseasonal/planetary scales: (i) the peculiar dispersion relation of dω/dk ≈ 0, (ii) the slow phase speed of ≈5 m/s, and (iii) the horizontal quadrupole vortex structure. This is accomplished here in a model that is neutrally stable on planetary scales; i.e., it is tacitly assumed that the primary instabilities occur on synoptic scales. The key premise of the model is that modulations of synoptic scale wave activity are induced by low-level moisture preconditioning on planetary scales, and they drive the “skeleton” of the MJO through modulated heating. The “muscle” of the MJO—including tilts, vertical structure, etc.—is contributed by other potential upscale transport effects from the synoptic scales.     

The role of terrestrially derived organic carbon in the coastal ocean: a changing paradigm and the priming effect

One of the major conundrums in oceanography for the past 20 y has been that, although the total flux of dissolved organic carbon (OC; DOC) discharged annually to the global ocean can account for the turnover time of all oceanic DOC (ca. 4,000–6,000 y), chemical biomarker and stable isotopic data indicate that there is very little terrestrially derived OC (TerrOC) in the global ocean. Similarly, it has been estimated that only 30% of the TerrOC buried in marine sediments is of terrestrial origin in muddy deltaic regions with high sedimentation rates. If vascular plant material—assumed to be highly resistant to decay—makes up much of the DOC and particulate OC of riverine OC (along with soil OC), why do we not see more TerrOC in coastal and oceanic waters and sediments? An explanation for this “missing” TerrOC in the ocean is critical in our understanding of the global carbon cycle. Here, I consider the origin of vascular plants, the major component of TerrOC, and how their appearance affected the overall cycling of OC on land. I also examine the role vascular plant material plays in soil OC, inland aquatic ecosystems, and the ocean, and how our understanding of TerrOC and “priming” processes in these natural systems has gained considerable interests in the terrestrial literature, but has largely been ignored in the aquatic sciences. Finally, I close by postulating that priming is in fact an important process that needs to be incorporated into global carbon models in the context of climate change.     

Comparison of lunar with terrestrial and meteoritic rocks

This note examines critically recent attempts to identify or closely correlate lunar surface samples—on the basis of alpha-scattering analysis—with terrestrial igneous rocks (basalts) or with eucrite meteorites. Basalts show considerable variety; but all have chemical characteristics inherited from terrestrial mantle rock melted under a limited range of terrestrial pressure-temperature conditions. What is characteristic is not so much the content of any particular element or oxide—e.g., SiO₂ 47-52 per cent—but rather a complete chemical pattern in which such ratios as Fe/Mg and Ca/(Na + K) show consistent relationships to Si content. These are the chemical criteria that might be useful in comparing terrestrial basalt with extraterrestrial rocks. Basalts also have distinctive mineralogical and textural characteristics; and if a lunar or meteoritic rock is to be identified as basalt it must possess these, too.

Turkevich's analysis of alpha-scattering data for lunar samples (Surveyor V) show significant departure from basaltic composition: Very high (Ca + K)/Na associated with distinctly high Fe/Mg. In basalts relatively high (Ca + K)/Na—in no case approaching the reported lunar values—tends to be associated with Fe/Mg values lower than average. The same “lunar” pattern of high (Ca + K)/Na and Fe/Mg appears in recorded analyses of eucrite meteorites. In the lunar samples, Ti is notably higher than in basalts, and even more so than in eucrites. If eucrites are of lunar origin their Ti values are, so far, a real anomaly.

     

Loneliness before and during the COVID-19 pandemic—are unpartnered and childless older adults at higher risk?

COVID-19 mitigation efforts had the potential to exacerbate loneliness among older adults, particularly for the unpartnered or childless, yet specific studies on loneliness among these groups during the COVID-19 pandemic are lacking. Using data from the Survey of Health, Ageing and Retirement in Europe (SHARE) collected before (October 2019–March 2020) and during the pandemic (June–August 2020), we examine two loneliness outcomes: (1) “have you felt lonely recently?” (both datasets) and (2) “have you felt lonelier than before the pandemic?” (2020), and examine differences by partnership and parenthood status. Before COVID-19, those who lacked one tie but had the other (unpartnered parents or partnered childless) were at highest loneliness risk. During COVID-19, unpartnered and childless—especially unpartnered—remain at higher risk for loneliness, entering loneliness, and not “exiting” loneliness. We discuss these findings in light of family norms and needs in pandemic and non-pandemic times and provide recommendations for future research.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10433-022-00718-x.     

Large-river delta-front estuaries as natural “recorders” of global environmental change

Large-river delta-front estuaries (LDE) are important interfaces between continents and the oceans for material fluxes that have a global impact on marine biogeochemistry. In this article, we propose that more emphasis should be placed on LDE in future global climate change research. We will use some of the most anthropogenically altered LDE systems in the world, the Mississippi/Atchafalaya River and the Chinese rivers that enter the Yellow Sea (e.g., Huanghe and Changjiang) as case-studies, to posit that these systems are both “drivers” and “recorders” of natural and anthropogenic environmental change. Specifically, the processes in the LDE can influence (“drive”) the flux of particulate and dissolved materials from the continents to the global ocean that can have profound impact on issues such as coastal eutrophication and the development of hypoxic zones. LDE also record in their rapidly accumulating subaerial and subaqueous deltaic sediment deposits environmental changes such as continental-scale trends in climate and land-use in watersheds, frequency and magnitude of cyclonic storms, and sea-level change. The processes that control the transport and transformation of carbon in the active LDE and in the deltaic sediment deposit are also essential to our understanding of carbon sequestration and exchange with the world ocean—an important objective in global change research. U.S. efforts in global change science including the vital role of deltaic systems are emphasized in the North American Carbon Plan (www.carboncyclescience.gov).     

Mitochondrial genomes and exceptional longevity in a Chinese population: the Rugao longevity study

Genetic variants of whole mitochondrial DNA (mtDNA) that predispose to exceptional longevity need to be systematically identified and appraised. Here, we conducted a case-control study with 237 exceptional longevity subjects (aged 95–107) and 444 control subjects (aged 40–69) randomly recruited from a “longevity town”—the city of Rugao in China—to investigate the effects of mtDNA variants on exceptional longevity. We sequenced the entire mtDNA genomes of the 681 subjects using a next-generation platform and employed a complete mtDNA phylogenetic analytical strategy. We identified T3394C as a candidate that counteracts longevity, and we observed a higher load of private nonsynonymous mutations in the COX1 gene predisposing to female longevity. Additionally, for the first time, we identified several variants and new subhaplogroups related to exceptional longevity. Our results provide new clues for genetic mechanisms of longevity and shed light on strategies for evaluating rare mitochondrial variants that underlie complex traits.

Electronic supplementary material

The online version of this article (doi:10.1007/s11357-015-9750-8) contains supplementary material, which is available to authorized users.     

From the Cover: Infochemistry and infofuses for the chemical storage and transmission of coded information

This article describes a self-powered system that uses chemical reactions—the thermal excitation of alkali metals—to transmit coded alphanumeric information. The transmitter (an “infofuse”) is a strip of the flammable polymer nitrocellulose patterned with alkali metal ions; this pattern encodes the information. The wavelengths of 2 consecutive pulses of light represent each alphanumeric character. While burning, infofuses transmit a sequence of pulses (at 5–20 Hz) of atomic emission that correspond to the sequence of metallic salts (and therefore to the encoded information). This system combines information technology and chemical reactions into a new area—“infochemistry”—that is the first step toward systems that combine sensing and transduction of chemical signals with multicolor transmission of alphanumeric information.     

Tropical nighttime warming as a dominant driver of variability in the terrestrial carbon sink

The terrestrial biosphere is currently a strong carbon (C) sink but may switch to a source in the 21st century as climate-driven losses exceed CO₂-driven C gains, thereby accelerating global warming. Although it has long been recognized that tropical climate plays a critical role in regulating interannual climate variability, the causal link between changes in temperature and precipitation and terrestrial processes remains uncertain. Here, we combine atmospheric mass balance, remote sensing-modeled datasets of vegetation C uptake, and climate datasets to characterize the temporal variability of the terrestrial C sink and determine the dominant climate drivers of this variability. We show that the interannual variability of global land C sink has grown by 50–100% over the past 50 y. We further find that interannual land C sink variability is most strongly linked to tropical nighttime warming, likely through respiration. This apparent sensitivity of respiration to nighttime temperatures, which are projected to increase faster than global average temperatures, suggests that C stored in tropical forests may be vulnerable to future warming.Terrestrial ecosystems have been a substantial net sink of anthropogenic carbon (C) emissions since the 1960s (1–4), but the terrestrial C sink could switch to a C source in the 21st century, resulting in a positive C cycle-climate feedback that would accelerate global surface warming with potentially major consequences for the biosphere (5–7). The interannual variability of the terrestrial C sink can help constrain our understanding of C/climate feedbacks and identify regions and mechanisms of the terrestrial C cycle that are most sensitive to climate parameters, shedding light on the future of the sink and its possible transition to a source (8). Currently, several major drivers have been shown to be correlated with the interannual variability of the terrestrial C sink, including (i) tropical temperature, which is tightly coupled to interannual variability in the atmospheric growth rate (AGR) of CO₂ (8, 9); (ii) tropical drought stress, including major droughts in the Amazon (10–12), which has been suggested to underlie increasing sensitivity of the AGR to tropical temperature over the period from 1959–2010 (13); (iii) temperature and precipitation variability in semiarid regions (14, 15); and (iv) average minimum daily (hereafter “nighttime”) temperatures, which studies of several local field sites in the tropics have found play a major role in interannual productivity (16–18).Determining the mechanism underlying the interannual variability of the terrestrial C sink, including the relative roles of precipitation vs. temperature stress and their effects on gross primary productivity (GPP) vs. total respiration (both autotrophic and heterotrophic; R), is critical to predict the sink’s future and to improve Earth system models. Here, we quantify changes in the interannual variability of the terrestrial C sink over the past half-century and then statistically evaluate four hypotheses that the variability of the terrestrial sink is most strongly influenced by (i) tropical mean temperature, (ii) tropical precipitation, (iii) precipitation and temperature in semiarid regions, and (iv) nighttime tropical temperatures. We combine multiple simulations from an atmospheric mass balance of the land C sink [net ecosystem exchange (NEE)] from 1959 to 2010, remote sensing-modeled datasets of vegetation greenness and GPP from 1982 to 2010, and global gridded climate datasets to constrain globally the fundamental equation NEE = GPP − R and the relative sensitivities of each component to temperature and precipitation. We draw on a combination of model selection and partial correlation analysis to provide relative likelihood estimates of each driver and to account for covariation between predictor variables (e.g., tropical mean temperature vs. nighttime temperature).     

From the Cover: Warming-induced reductions in body size are greater in aquatic than terrestrial species

Most ectothermic organisms mature at smaller body sizes when reared in warmer conditions. This phenotypically plastic response, known as the “temperature-size rule” (TSR), is one of the most taxonomically widespread patterns in biology. However, the TSR remains a longstanding life-history puzzle for which no dominant driver has been found. We propose that oxygen supply plays a central role in explaining the magnitude of ectothermic temperature-size responses. Given the much lower oxygen availability and greater effort required to increase uptake in water vs. air, we predict that the TSR in aquatic organisms, especially larger species with lower surface area–body mass ratios, will be stronger than in terrestrial organisms. We performed a meta-analysis of 1,890 body mass responses to temperature in controlled experiments on 169 terrestrial, freshwater, and marine species. This reveals that the strength of the temperature-size response is greater in aquatic than terrestrial species. In animal species of ∼100 mg dry mass, the temperature-size response of aquatic organisms is 10 times greater than in terrestrial organisms (−5.0% °C⁻¹ vs. −0.5% °C⁻¹). Moreover, although the size response of small (<0.1 mg dry mass) aquatic and terrestrial species is similar, increases in species size cause the response to become increasingly negative in aquatic species, as predicted, but on average less negative in terrestrial species. These results support oxygen as a major driver of temperature-size responses in aquatic organisms. Further, the environment-dependent differences parallel latitudinal body size clines, and will influence predicted impacts of climate warming on food production, community structure, and food-web dynamics.     

Sub-Threshold Fabrication of Laser-Induced Periodic Surface Structures on Diamond-like Nanocomposite Films with IR Femtosecond Pulses

In the paper, we study the formation of laser-induced periodic surface structures (LIPSS) on diamond-like nanocomposite (DLN) a-C:H:Si:O films during nanoscale ablation processing at low fluences—below the single-pulse graphitization and spallation thresholds—using an IR fs-laser (wavelength 1030 nm, pulse duration 320 fs, pulse repetition rate 100 kHz, scanning beam velocity 0.04–0.08 m/s). The studies are focused on microscopic analysis of the nanostructured DLN film surface at different stages of LIPSS formation and numerical modeling of surface plasmon polaritons in a thin graphitized surface layer. Important findings are concerned with (i) sub-threshold fabrication of high spatial frequency LIPSS (HSFL) and low spatial frequency LIPSS (LSFL) under negligible surface graphitization of hard DLN films, (ii) transition from the HSFL (periods of 140 ± 30 and 230 ± 40 nm) to LSFL (period of 830–900 nm) within a narrow fluence range of 0.21–0.32 J/cm², (iii) visualization of equi-field lines by ablated nanoparticles at an initial stage of the LIPSS formation, providing proof of larger electric fields in the valleys and weaker fields at the ridges of a growing surface grating, (iv) influence of the thickness of a laser-excited glassy carbon (GC) layer on the period of surface plasmon polaritons excited in a three-layer system “air/GC layer/DLN film”.     

Reducing abrupt climate change risk using the Montreal Protocol and other regulatory actions to complement cuts in CO2 emissions

Current emissions of anthropogenic greenhouse gases (GHGs) have already committed the planet to an increase in average surface temperature by the end of the century that may be above the critical threshold for tipping elements of the climate system into abrupt change with potentially irreversible and unmanageable consequences. This would mean that the climate system is close to entering if not already within the zone of “dangerous anthropogenic interference” (DAI). Scientific and policy literature refers to the need for “early,” “urgent,” “rapid,” and “fast-action” mitigation to help avoid DAI and abrupt climate changes. We define “fast-action” to include regulatory measures that can begin within 2–3 years, be substantially implemented in 5–10 years, and produce a climate response within decades. We discuss strategies for short-lived non-CO₂ GHGs and particles, where existing agreements can be used to accomplish mitigation objectives. Policy makers can amend the Montreal Protocol to phase down the production and consumption of hydrofluorocarbons (HFCs) with high global warming potential. Other fast-action strategies can reduce emissions of black carbon particles and precursor gases that lead to ozone formation in the lower atmosphere, and increase biosequestration, including through biochar. These and other fast-action strategies may reduce the risk of abrupt climate change in the next few decades by complementing cuts in CO₂ emissions.     

From the Cover: Stabilizing selection on Atlantic cod supergenes through a millennium of extensive exploitation

Life on Earth has been characterized by recurring cycles of ecological stasis and disruption, relating biological eras to geological and climatic transitions through the history of our planet. Due to the increasing degree of ecological abruption caused by human influences many advocate that we now have entered the geological era of the Anthropocene, or “the age of man.” Considering the ongoing mass extinction and ecosystem reshuffling observed worldwide, a better understanding of the drivers of ecological stasis will be a requisite for identifying routes of intervention and mitigation. Ecosystem stability may rely on one or a few keystone species, and the loss of such species could potentially have detrimental effects. The Atlantic cod (Gadus morhua) has historically been highly abundant and is considered a keystone species in ecosystems of the northern Atlantic Ocean. Collapses of cod stocks have been observed on both sides of the Atlantic and reported to have detrimental effects that include vast ecosystem reshuffling. By whole-genome resequencing we demonstrate that stabilizing selection maintains three extensive “supergenes” in Atlantic cod, linking these genes to species persistence and ecological stasis. Genomic inference of historic effective population sizes shows continued declines for cod in the North Sea–Skagerrak–Kattegat system through the past millennia, consistent with an early onset of the marine Anthropocene through industrialization and commercialization of fisheries throughout the medieval period.

As ecosystems worldwide are facing disturbance, overexploitation, and environmental shifts, evidence that we have entered the geological epoch of the Anthropocene (i.e., “the age of man”) is compelling (1, 2). In terrestrial ecosystems early human impacts in the form of foraging and land use is well documented, and human expansions are closely tied to species declines and extinctions (3–5). In marine environments recordable impacts of human expansions are often delayed relative to terrestrial environments, and extinctions have been less frequently recorded. These observations are attributed both to the reduced capacity of humans to access the marine environment and to the generally higher mobility of harvested marine species compared with their terrestrial counterparts (6).There are, however, pitfalls in assessing human impacts on biodiversity solely based on observed abundance or extinction rates. It has been postulated that the potential for stasis of species both spatially and temporally is determined by its standing portfolio of biological diversity (7–9), theoretically tying biodiversity, in terms of standing intraspecific variation, to stability (8, 9). In the face of current environmental challenges, species where intraspecific variation has been reduced due to human impacts may be particularly vulnerable. Additionally, the assessment of past ecological state, or baseline, is challenging in marine environments compared with terrestrial ones, as access to both faunal remains and ecological records is severely reduced. To assess the true extent of human impact on marine species and ecosystems, the use of proxies may thus be crucial. Genomic sciences now allow for the characterization of demographic history and molecular evolution at unprecedented time scales and resolutions, offering opportunities to improve our understanding of the trajectories of species and ecological assemblages.Through the fossil record, ecological assemblages are often observed to develop in a stepwise manner (10) despite the broadly acknowledged potential for continuous evolution. An advocated explanation for this paradoxical observation (i.e., “the paradox of stasis”) is the presence of stabilizing selective forces (8, 9) that maintain species, and thus ecological stasis, over long timescales (11). One of the strongest traditional arguments against such an explanatory model is that stabilizing selection is rarely observed in nature relative to directional selection (12). The reasoning for this argument is that a major fraction of species in an assemblage should be stabilized by selection for such a mechanism to be considered as a driver of stasis. However, theoretical and empirical work proposing that ecological assemblages may be destabilized by the removal of a single keystone species call this assumption into question (13–18).The Atlantic cod (Gadus morhua) is a marine fish that has been extensively exploited for centuries. It is a keystone predator in the ecosystems it occupies, and its persistence is closely tied to stability of marine ecosystems across the northern Atlantic Ocean (13–15). The Atlantic cod genome harbors a set of highly divergent haplotypes, caused by chromosomal inversions, that extend several megabases (19, 20). These polymorphisms act as biallelic “supergenes” that segregate across the species’ distributional range, on both sides of the Atlantic (21), adding an additional level of complexity to the overall genomic stratification of the species.Here we use whole-genome resequencing to show that stabilizing selection maintains the Atlantic cod supergenes, tying these extensive polymorphisms to species persistence, and potentially, to ecosystem stability. We further perform genomic inference to access historic effective population sizes, revealing continuing declines in the North Sea–Skagerrak–Kattegat system through the past millennium. These declines coincide with expansion and commercialization of North European fisheries through the past 1,000 y, starting at the intersect between the Viking period and the medieval period. Our results support an early onset of the marine Anthropocene in the North Sea system, with long-term human impacts shaping species and ecosystem trajectories.     

Finding of residues crucial for supersecondary structure formation

This work evaluates the hypothesis that proteins with an identical supersecondary structure (SSS) share a unique set of residues—SSS-determining residues—even though they may belong to different protein families and have very low sequence similarities. This hypothesis was tested on two groups of sandwich-like proteins (SPs). Proteins in each group have an identical SSS, but their sequence similarity is below the “twilight zone.” To find the SSS-determining residues specific to each group, a unique structure-based algorithm of multiple sequences alignment was developed. The units of alignment are individual strands and loops rather than whole sequences. The algorithm is based on the alignment of residues that form hydrogen bonds between corresponding strands. Structure-based alignment revealed that 30–35% of the positions in the sequences in each group of proteins are “conserved positions” occupied either by hydrophobic-only or hydrophilic-only residues. Moreover, each group of SPs is characterized by a unique set of SSS-determining residues found at the conserved positions. The set of SSS-determining residues has very high sensitivity and specificity for identifying proteins with a corresponding SSS: It is an “amino acid tag” that brands a sequence as having a particular SSS. Thus, the sets of SSS-determining residues can be used to classify proteins and to predict the SSS of a query amino acid sequence.     

Bats host the most virulent—but not the most dangerous—zoonotic viruses

Identifying virus characteristics associated with the largest public health impacts on human populations is critical to informing “zoonotic risk” assessments and surveillance strategies. Efforts to assess zoonotic risk often use trait-based analyses to identify which viral and reservoir host groups are most likely to source zoonoses but have not fully addressed how and why the impacts of zoonotic viruses vary in terms of disease severity (“virulence”), capacity to spread within human populations (“transmissibility”), or total human mortality (“death burden”). We analyzed trends in human case fatality rates, transmission capacities, and total death burdens across a comprehensive dataset of mammalian and avian zoonotic viruses. Bats harbor the most virulent zoonotic viruses even when compared to birds, which alongside bats have been hypothesized to be special zoonotic reservoirs due to molecular adaptations that support the physiology of flight. Reservoir host groups more closely related to humans—in particular, primates—harbor less virulent but more highly transmissible viruses. Importantly, a disproportionately high human death burden, arguably the most important metric of zoonotic risk, is not associated with any animal reservoir, including bats. Our data demonstrate that mechanisms driving death burdens are diverse and often contradict trait-based predictions. Ultimately, total human mortality is dependent on context-specific epidemiological dynamics, which are shaped by a combination of viral traits and conditions in the animal host population and across and beyond the human–animal interface. Understanding the conditions that predict high zoonotic burden in humans will require longitudinal studies of epidemiological dynamics in wildlife and human populations.

The vast majority of human pathogens are derived from animal populations (1). In response to increasingly frequent zoonotic spillovers and their substantial public health risks (2), there has been a movement to identify the ecological systems and taxonomic groups of animals and pathogens that are most likely to source the next emerging zoonosis in the human population (3–9). However, most of this work has centered on a binary definition of zoonotic risk—whether particular pathogens are capable of infecting humans—without considering how pathogens vary with respect to their impacts on humans after spillover. The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has re-emphasized the reality that not all zoonoses pose risks of equal magnitude—some are exceptionally more “dangerous” than others due to the severity of disease they cause (“virulence”) or their capacity to spread within human populations (“transmissibility”), which combined influence the total number of human deaths (“death burden”) (10). Given the extraordinary diversity of both animal hosts and the viruses they harbor, understanding which animal and virus groups are more likely to source dangerous zoonoses is an important public health aim. Many high-profile zoonotic viruses—including Nipah and Hendra henipaviruses; Ebola filovirus; SARS, Middle East respiratory syndrome (MERS), and SARS-CoV-2 coronaviruses; pandemic avian influenzas; West Nile virus; and Eastern Equine encephalitis virus—have emerged from Chiropteran (bat) or avian reservoirs (11). The high number of zoonotic viruses found in bats and birds has been attributed to their large gregarious populations, mobility, ability to colonize anthropogenic environments, and sheer species diversity (7, 11). Nonetheless, the following question remains: are bat- and/or bird-borne viruses disproportionately dangerous?A recent analysis (10) found that mammalian reservoir hosts most closely related to humans harbor zoonoses of lower impact in terms of mortality relative to more phylogenetically distant hosts. These results were consistent with phylogenetic trends in virulence that have been reported in cross-species pathogen emergences in other systems (12, 13) and likely reflect mismatches in host biology, physiology, and ecology. Notably, order Chiroptera (bats)—one of the more distantly related host orders—had the highest positive effect size on case fatality rate (CFR) in humans. Nevertheless, this analysis considered only directly transmitted viruses and viruses derived from mammalian hosts, despite the existence of several high-profile vector-borne and avian zoonoses (11). In particular, birds occupy a separate taxonomic class from humans—a phylogenetic distance that might correlate with heightened virulence in humans.In vitro work has suggested that molecular adaptations that support the physiology of flight, a trait unique to bats among mammals, may allow bats to tolerate rapidly replicating viruses that express heightened virulence upon emergence in less tolerant hosts such as humans (14)—thus offering a possible explanation for bat virus virulence. Bats and birds share a suite of convergent flight adaptations—both taxa are remarkably long-lived for their body size and appear to circumvent metabolic constraints on longevity through cellular pathways evolved to mitigate oxidative stress induced by flight (11). These metabolic adaptations are hypothesized to be linked to the evolution of virulent viruses in bats, but they are only typically discussed with respect to their effect on lifespan in birds (15). A few papers have reviewed birds’ role as “special” zoonotic reservoirs (11, 16), but the virulence of avian zoonoses remains largely unexplored. Nonetheless, although the most virulent zoonotic viruses may garner the most publicity, these pathogens are not necessarily the most dangerous to human health. Rather, human health is most impacted by viruses that cause large volumes of cases and deaths (burden). Although some viruses such as Ebola and rabies are associated with both high CFRs and burden in the human population, pandemic viruses are often characterized by relatively low CFRs but high human transmissibility. The 2009 H1N1 influenza pandemic was estimated to have caused 60.8 million cases and more than 12,000 deaths in the United States alone with a CFR of less than 1% (17), and as of 9 July 2021, SARS-CoV-2 has caused over 185 million cases and 4 million deaths worldwide with a CFR of just 2.2% (18). To prevent the next zoonotic pandemic, it is important to think beyond the individual measures of zoonotic capacity, virulence, and transmissibility to consider collective burden on public health.We applied generalized additive models (GAMs) to a dataset of mammalian and avian zoonotic viruses to identify reservoir host and viral traits predictive of the 1) CFR, 2) capacity for forward transmission, and 3) death burden induced by infections in the human population—with the goal of characterizing sources of zoonotic viruses that pose the greatest “danger” to global health. Our work builds on a small body of analyses that have begun to explore variation in the virulence and between-human transmissibility of zoonotic viruses (4, 19–21). We provide an analysis of burden and the largest sample size—with trends examined across the majority of known zoonotic viruses. We hypothesized that birds—given their capacity for flight and phylogenetic distance from humans—might rival bats for the association with the most virulent zoonotic viruses. However, we did not expect bats or birds to be responsible for the greatest burden on global health, instead anticipating high burden to be largely a function of viral traits and association with reservoir orders that harbor less virulent, more transmissible viruses.     

False Appearance of Gene–Environment Interactions in Genetic Association Studies

Under the assumption of gene–environment independence, unknown/unmeasured environmental factors, irrespective of what they may be, cannot confound the genetic effects. This may lead many people to believe that genetic heterogeneity across different levels of the studied environmental exposure should only mean gene–environment interaction—even though other environmental factors are not adjusted for. However, this is not true if the odds ratio is the effect measure used for quantifying genetic effects. This is because the odds ratio is a “noncollapsible” measure—a marginal odds ratio is not a weighted average of the conditional odds ratios, but instead has a tendency toward the null. In this study, the authors derive formulae for gene–environment interaction bias due to noncollapsibility. They use computer simulation and real data example to show that the bias can be substantial for common diseases. For genetic association study of nonrare diseases, researchers are advised to use collapsible measures, such as risk ratio or peril ratio.     

Brief Report: Adaptive staffing can mitigate essential worker disease and absenteeism in an emerging epidemic

Essential worker absenteeism has been a pressing problem in the COVID-19 pandemic. Nearly 20% of US hospitals experienced staff shortages, exhausting replacement pools and at times requiring COVID-positive healthcare workers to remain at work. To our knowledge there are no data-informed models examining how different staffing strategies affect epidemic dynamics on a network in the context of rising worker absenteeism. Here we develop a susceptible–infected–quarantined-recovered adaptive network model using pair approximations to gauge the effects of worker replacement versus redistribution of work among remaining healthy workers in the early epidemic phase. Parameterized with hospital data, the model exhibits a time-varying trade-off: Worker replacement minimizes peak prevalence in the early phase, while redistribution minimizes final outbreak size. Any “ideal” strategy requires balancing the need to maintain a baseline number of workers against the desire to decrease total number infected. We show that one adaptive strategy—switching from replacement to redistribution at epidemic peak—decreases disease burden by 9.7% and nearly doubles the final fraction of healthy workers compared to pure replacement.     

The Potentials and Pitfalls of a Human Cervical Organoid Model Including Langerhans Cells

Three-dimensional cell culturing to capture a life-like experimental environment has become a versatile tool for basic and clinical research. Mucosal and skin tissues can be grown as “organoids” in a petri dish and serve a wide variety of research questions. Here, we report our experience with human cervical organoids which could also include an immune component, e.g., Langerhans cells. We employ commercially available human cervical keratinocytes and fibroblasts as well as a myeloid cell line matured and purified into langerin-positive Langerhans cells. These are then seeded on a layer of keratinocytes with underlying dermal equivalent. Using about 10-fold more than the reported number in healthy cervical tissue (1–3%), we obtain differentiated cervical epithelium after 14 days with ~1% being Langerhans cells. We provide a detailed protocol for interested researchers to apply the described “aseptic” organoid model for all sorts of investigations—with or without Langerhans cells.