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In infantile abusive head injury (AHT), subdural haemorrhage (SDH) is commonly held to result from traumatic damage to bridging veins traversing from the surface of the brain to the dura and dural venous sinuses. However, there are limited published radiological or autopsy demonstrations of ruptured bridging veins and several authors also assert that bridging veins are too large to rupture due to the forces associated with AHT. There have been several studies on the size, locations and numbers of adult bridging veins and there is one small study of infant bridging veins. However, there are no microscopic studies of infant bridging veins and only a select few ultrastructural investigations of adult bridging veins. Hitherto, it has been assumed that bridging veins from infants and younger children will display the same anatomical characteristics as those in adulthood. At 19 neonatal, infant and young child post-mortem examinations, we macroscopically examined and sampled bridging veins for microscopy. We compared the histology of those samples with bridging veins from an older child and two adults. We demonstrate that adult bridging veins are usually surrounded by supportive meningeal tissue that appears to be lacking or minimally present around the bridging veins of younger children. Neonatal, infant and young children's veins had a free 'bridging' section. Neonatal and infant bridging veins had smaller diameter ranges and thinner walls (some only 5-7 µm) than those seen in older children and adults. Bridging vein walls contained both fine strands of elastic fibers and a more pronounced elastic lamina. The presence of an elastic lamina occurred more frequently in the older age groups These anatomical differences between the veins of adults and young children may help to explain apparent increased vulnerability of neonatal/infant bridging veins to the forces associated with a shaking-type traumatic event., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Understanding variation in food web structure over large spatial scales is an emerging research agenda in food web ecology. The density of predator-prey links in a food web (i.e., connectance) is a key measure of network complexity that describes the mean proportional dietary breadth of species within a food web. Connectance is a critical component of food web robustness to species loss: food webs with lower connectance have been shown to be more susceptible to secondary extinctions. Identifying geographic variation in food web connectance and its drivers may provide insight into community robustness to species loss. We investigated the food web connectance of ground-dwelling tropical forest mammal communities in multiple biogeographic regions to test for differences among regions in food web connectance and to test three potential drivers: primary productivity, contemporary anthropogenic pressure, and variation in mammal body mass distributions reflective of historical extinctions. Mammal communities from fifteen protected forests throughout the Neo-, Afro-, and Asian tropics were identified from systematic camera trap arrays. Predator-prey interaction data were collected from published literature, and we calculated connectance for each community as the number of observed predator-prey links relative to the number of possible predator-prey links. We used generalized linear models to test for differences among regions and to identify the site level characteristics that best predicted connectance. We found that mammal food web connectance varied significantly among continents and that body size range was the only significant predictor. More possible predator-prey links were observed in communities with smaller ranges in body size and therefore sites with smaller body size ranges had higher mean proportional dietary breadth. Specifically, mammal communities in the Neotropics and in Madagascar had significantly higher connectance than mammal communities in Africa. This geographic variation in contemporary mammalian food web structure may be the product of historical extinctions in the Late Quaternary, which led to greater losses of large-bodied species in the Neotropics and Madagascar thus contributing to higher average proportional dietary breadth among the remaining smaller bodied species in these regions., (© 2024. The Author(s).)

Protected areas largely now exist as coupled natural-human ecosystems where human activities are increasingly forcing wildlife to adjust behaviors. For many ungulate species that rely on protected areas for their persistence, they must balance these anthropogenic pressures amid natural regulators. Here, we investigated the pressures exerted from humans and livestock, apex predators, and within guild competitors on ungulate co-occurrence patterns in a fragile protected area complex in West Africa. Specifically, we used multi-species occupancy modeling to quantify co-occurrence among four ungulates (Tragelaphus scriptus, Redunca redunca, Kobus kob, Phacochoerus africanus) and applied structural equation models to discern the relative contributions of pressures on co-occurrence patterns. We observed a strong spatial gradient across with higher co-occurrence in the wetter western portion of our ~13,000 km 2 study area. Co-occurrence patterns among ungulate dyads ranged from 0.15 to 0.49 with the smallest body sized pair showing highest levels of sympatry, warthog and reedbuck. We found that anthropogenic pressures, namely cattle had the greatest effect in reducing sympatry among wild ungulates more strongly than the presence of African lions that also exhibited negative effects. Humans, hyenas, and competitors showed positive effects on ungulate co-occurrence. In a region of the world ongoing rapid socio-ecological change with increasing threats from climate and environmental instability, protected areas in West Africa represent a major safeguard for wildlife and human livelihoods alike. Our findings highlight the need for effective interventions that focus on large carnivore conservation, habitat restoration, and containment of livestock grazing to promote the coexistence of biodiversity and socio-economic goals within the region., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Ongoing anthropogenic change is altering the planet at an unprecedented rate, threatening biodiversity, and ecosystem functioning. Species are responding to abiotic pressures at both individual and population levels, with changes affecting trophic interactions through consumptive pathways. Collectively, these impacts alter the goods and services that natural ecosystems will provide to society, as well as the persistence of all species. Here, we describe the physiological and behavioral responses of species to global changes on individual and population levels that result in detectable changes in diet across terrestrial and marine ecosystems. We illustrate shifts in the dynamics of food webs with implications for animal communities. Additionally, we highlight the myriad of tools available for researchers to investigate the dynamics of consumption patterns and trophic interactions, arguing that diet data are a crucial component of ecological studies on global change. We suggest that a holistic approach integrating the complexities of diet choice and trophic interactions with environmental drivers may be more robust at resolving trends in biodiversity, predicting food web responses, and potentially identifying early warning signs of diversity loss. Ultimately, despite the growing body of long-term ecological datasets, there remains a dearth of diet ecology studies across temporal scales, a shortcoming that must be resolved to elucidate vulnerabilities to changing biophysical conditions., (© 2023 The Authors. Global Change Biology published by John Wiley & Sons Ltd.)

Historical perspectives (e.g., moments of social, political, and economic significance) are increasingly relevant for developing insights into landscape change and ecosystem degradation. However, the question of how to incorporate historical events into ecological inquiry is still under development, owing to the evolving paradigm of transdisciplinary thinking between natural science and the humanities. In the present article, we call for the inclusion of negative human histories (e.g., evictions of communities and environmental injustices) as important factors that drive landscape change and shape research questions relevant to environmental conservation. We outline the detrimental effects of conservationists not addressing negative human histories by likening this social phenomenon to the ecological concept of landscapes of fear, which describes how not acknowledging these histories produces a landscape that constrains where and how research is conducted by scientists. Finally, we provide three positive recommendations for scholars or practitioners to address the manifestation of historic place-based bias in ecological research. What we call the social-ecological landscapes of fear provides a conceptual framework for more inclusive practices in ecology to increase the success of environmental and conservation goals., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Institute of Biological Sciences.)

Research on the evolutionary ecology of urban areas reveals how human-induced evolutionary changes affect biodiversity and essential ecosystem services. In a rapidly urbanizing world imposing many selective pressures, a time-sensitive goal is to identify the emergent issues and research priorities that affect the ecology and evolution of species within cities. Here, we report the results of a horizon scan of research questions in urban evolutionary ecology submitted by 100 interdisciplinary scholars. We identified 30 top questions organized into six themes that highlight priorities for future research. These research questions will require methodological advances and interdisciplinary collaborations, with continued revision as the field of urban evolutionary ecology expands with the rapid growth of cities., Competing Interests: Declaration of interests No interests are declared., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Spatial partitioning in ecological communities has predominantly been described in two dimensions, yet habitat is complex and 3D. Complex space use mediates community structure and interaction strength by expanding spatial, temporal, and dietary dimensions. Vertical stratification of resources provides opportunities for novel specializations, creating a 3D niche. Competition and predation are mediated by 3D space use, as individuals use the vertical axis to access prey, flee predators, or avoid competitors. The 3D niche is important for long-term conservation strategies as species must navigate tradeoffs in habitat use between strata-specific threats and suboptimal habitat patches. Ultimately, elucidating the 3D niche has implications for protected area management and corridor design that directly influence species persistence and ecosystem function in a rapidly changing world., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Conservation requires both a needs assessment and prioritization scheme for planning and implementation. Range maps are critical for understanding and conserving biodiversity, but current range maps often omit content, negating important metrics of variation in populations and places. Here, we integrate a myriad of conditions that are spatially explicit across distributions of carnivores to identify gaps in capacity necessary for their conservation. Expanding on traditional gap analyses that focus almost exclusively on quantifying discordance in protected area coverage across a species' range, our work aggregates threat layers (e.g., drought, human pressures) with resources layers (e.g., protected areas, cultural diversity) to identify gaps in available conservation capacity (ACC) across ranges for 91 African carnivores. Our model indicated that all species have some portion of their range at risk of contraction, with an average of 15 percentage range loss. We found that the ACC differed based on body size and taxonomy. Results deviated from current perceptions of extinction risks for species with an International Union for Conservation of Nature (IUCN) threat status of Least Concern and yielded insights for species categorized as Data Deficient. Our socio-ecological gap analysis presents a geospatial approach to inform decision-making and resource allocation in conservation. Ultimately, our work advances forecasting dynamics of species' ranges that are increasingly vital in an era of great socio-ecological change to mitigate human-wildlife conflict and promote inclusive carnivore conservation across geographies.

Animals exhibit variation in their space and time use across an urban-rural gradient. As the top-down influences of apex predators wane due to human-driven declines, landscape-level anthropogenic pressures are rising. Human impacts can be analogous to apex predators in that humans can drive increased mortality in both prey species and carnivores, and impact communities through indirect fear effects and food subsidies. Here, we evaluate the time use of a common mesocarnivore across an urban-rural gradient and test whether it is influenced by the intensity of the use of a larger carnivore. Using multiple camera-trap surveys, we compared the temporal response of a small carnivore, the raccoon ( Procyon lotor ), to the larger coyote ( Canis latrans ) in four study areas across Michigan that represented a gradient of pressure from humans. We found that raccoon time use varied by study area and was most unique at the rural extreme. Raccoons consistently did not shift their activity pattern in response to coyotes in the study area with the highest anthropogenic pressures despite the considerable interannual variation, and instead showed stronger responses to coyotes in more rural study areas. Temporal shifts were characterized by raccoons being more diurnal in areas of high coyote activity. We conclude that raccoons may shift time use in the presence of coyotes, dependent on the level of anthropogenic pressure. Our results highlight that the variation in raccoon time use across the entirety of the urban-rural gradient needed to be considered, as anthropogenic pressures may dominate and obscure the dynamics of this interaction., Competing Interests: All authors declare that they have no conflict of interest., (© 2022 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Predation is a fundamental ecological process that shapes communities and drives evolutionary dynamics. As the world rapidly urbanizes, it is critical to understand how human perturbations alter predation and meat consumption across taxa. We conducted a meta-analysis to quantify the effects of urban environments on three components of trophic ecology in predators: dietary species richness, dietary evenness and stable isotopic ratios (IRs) ( δ 13 C and δ 15 N IR). We evaluated whether the intensity of anthropogenic pressure, using the human footprint index (HFI), explained variation in effect sizes of dietary attributes using a meta-regression. We calculated Hedges' g effect sizes from 44 studies including 11 986 samples across 40 predatory species in 39 cities globally. The direction and magnitude of effect sizes varied among predator taxa with reptilian diets exhibiting the most sensitivity to urbanization. Effect sizes revealed that predators in cities had comparable diet richness, evenness and nitrogen ratios, though carbon IRs were more enriched in cities. We found that neither the 1993 nor 2009 HFI editions explained effect size variation. Our study provides, to our knowledge, the first assessment of how urbanization has perturbed predator-prey interactions for multiple taxa at a global scale. We conclude that the functional role of predators is conserved in cities and urbanization does not inherently relax predation, despite diets broadening to include anthropogenic food sources such as sugar, wheat and corn.

People and wildlife are living in an increasingly urban world, replete with unprecedented human densities, sprawling built environments, and altered landscapes. Such anthropogenic pressures can affect multiple processes within an ecological community, from spatial patterns to interspecific interactions. We tested two competing hypotheses, human shields vs. human competitors, to characterize how humans affect the carnivore community using multispecies occupancy models. From 2017 to 2020, we conducted the first camera survey of city parks in Detroit, Michigan, and collected spatial occurrence data of the local native carnivore community. Our 12,106-trap night survey captured detection data for coyotes (Canis latrans), red foxes (Vulpes vulpes), raccoons (Procyon lotor), and striped skunks (Mephitis mephitis). Overall occupancy varied across species (Ψ coyote  = 0.40, Ψ raccoon  = 0.54, Ψ red fox  = 0.19, Ψ striped skunk  = 0.09). Contrary to expectations, humans did not significantly affect individual occupancy for these urban carnivores. However, co-occurrence between coyote and skunk increased with human activity. The observed positive spatial association between an apex and subordinate pair supports the human shield hypothesis. Our findings demonstrate how urban carnivores can exploit spatial refugia and coexist with humans in the cityscape., (© 2021 The Authors. Ecological Applications published by Wiley Periodicals LLC on behalf of Ecological Society of America.)

Human activity and land use change impact every landscape on Earth, driving declines in many animal species while benefiting others. Species ecological and life history traits may predict success in human-dominated landscapes such that only species with "winning" combinations of traits will persist in disturbed environments. However, this link between species traits and successful coexistence with humans remains obscured by the complexity of anthropogenic disturbances and variability among study systems. We compiled detection data for 24 mammal species from 61 populations across North America to quantify the effects of (1) the direct presence of people and (2) the human footprint (landscape modification) on mammal occurrence and activity levels. Thirty-three percent of mammal species exhibited a net negative response (i.e., reduced occurrence or activity) to increasing human presence and/or footprint across populations, whereas 58% of species were positively associated with increasing disturbance. However, apparent benefits of human presence and footprint tended to decrease or disappear at higher disturbance levels, indicative of thresholds in mammal species' capacity to tolerate disturbance or exploit human-dominated landscapes. Species ecological and life history traits were strong predictors of their responses to human footprint, with increasing footprint favoring smaller, less carnivorous, faster-reproducing species. The positive and negative effects of human presence were distributed more randomly with respect to species trait values, with apparent winners and losers across a range of body sizes and dietary guilds. Differential responses by some species to human presence and human footprint highlight the importance of considering these two forms of human disturbance separately when estimating anthropogenic impacts on wildlife. Our approach provides insights into the complex mechanisms through which human activities shape mammal communities globally, revealing the drivers of the loss of larger predators in human-modified landscapes., (© 2021 John Wiley & Sons Ltd.)

Photonic system component counts are increasing rapidly, particularly in CMOS-compatible silicon photonics processes. Large numbers of cascaded active photonic devices are difficult to implement when accounting for constraints on area, power dissipation, and response time. Plasma dispersion and the thermo-optic effect, both available in CMOS-compatible silicon processes, address a subset of these criteria. With the addition of a few back-end-of-line etch processing steps, silicon photonics platforms can support nano-opto-electro-mechanical (NOEM) phase shifters. Realizing NOEM phase shifters that operate at CMOS-compatible voltages (≤ 1.2 V) and with low insertion loss remains a challenge. Here, we introduce a novel NOEM phase shifter fabricated alongside 90 nanometer transistors that imparts 5.63 radians phase shift at 1.08 volts bias over an actuation length of 25μm with an insertion loss of less than 0.04 dB and 3 dB bandwidth of 0.26 MHz.

With the accelerating pace of global change, it is imperative that we obtain rapid inventories of the status and distribution of wildlife for ecological inferences and conservation planning. To address this challenge, we launched the SNAPSHOT USA project, a collaborative survey of terrestrial wildlife populations using camera traps across the United States. For our first annual survey, we compiled data across all 50 states during a 14-week period (17 August-24 November of 2019). We sampled wildlife at 1,509 camera trap sites from 110 camera trap arrays covering 12 different ecoregions across four development zones. This effort resulted in 166,036 unique detections of 83 species of mammals and 17 species of birds. All images were processed through the Smithsonian's eMammal camera trap data repository and included an expert review phase to ensure taxonomic accuracy of data, resulting in each picture being reviewed at least twice. The results represent a timely and standardized camera trap survey of the United States. All of the 2019 survey data are made available herein. We are currently repeating surveys in fall 2020, opening up the opportunity to other institutions and cooperators to expand coverage of all the urban-wild gradients and ecophysiographic regions of the country. Future data will be available as the database is updated at eMammal.si.edu/snapshot-usa, as will future data paper submissions. These data will be useful for local and macroecological research including the examination of community assembly, effects of environmental and anthropogenic landscape variables, effects of fragmentation and extinction debt dynamics, as well as species-specific population dynamics and conservation action plans. There are no copyright restrictions; please cite this paper when using the data for publication., (© 2021 The Authors. Ecology © 2021 The Ecological Society of America.)

Ecological research includes social-ecological-evolutionary processes, but the intersectionality and feedbacks between ecology and environmental justice (EJ) remain low. We here present opportunities for ecological research contributions to EJ. Ultimately, such work can reduce racial and social disparities in environmental provisioning and improve global environmental sustainability., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

As the field of artificial intelligence advances, the demand for algorithms that can learn quickly and efficiently increases. An important paradigm within artificial intelligence is reinforcement learning 1 , where decision-making entities called agents interact with environments and learn by updating their behaviour on the basis of the obtained feedback. The crucial question for practical applications is how fast agents learn 2 . Although various studies have made use of quantum mechanics to speed up the agent's decision-making process 3,4 , a reduction in learning time has not yet been demonstrated. Here we present a reinforcement learning experiment in which the learning process of an agent is sped up by using a quantum communication channel with the environment. We further show that combining this scenario with classical communication enables the evaluation of this improvement and allows optimal control of the learning progress. We implement this learning protocol on a compact and fully tunable integrated nanophotonic processor. The device interfaces with telecommunication-wavelength photons and features a fast active-feedback mechanism, demonstrating the agent's systematic quantum advantage in a setup that could readily be integrated within future large-scale quantum communication networks.

Wildlife respond to human presence by adjusting their temporal niche, possibly modifying encounter rates among species and trophic dynamics that structure communities. We assessed wildlife diel activity responses to human presence and consequential changes in predator-prey overlap using 11,111 detections of 3 large carnivores and 11 ungulates across 21,430 camera trap-nights in West Africa. Over two-thirds of species exhibited diel responses to mainly diurnal human presence, with ungulate nocturnal activity increasing by 7.1%. Rather than traditional pairwise predator-prey diel comparisons, we considered spatiotemporally explicit predator access to several prey resources to evaluate community-level trophic responses to human presence. Although leopard prey access was not affected by humans, lion and spotted hyena access to three prey species significantly increased when prey increased their nocturnal activity to avoid humans. Human presence considerably influenced the composition of available prey, with implications for prey selection, demonstrating how humans perturb ecological processes via behavioral modifications., Competing Interests: KM, NH No competing interests declared, (© 2020, Mills and Harris.)

Urban areas are dynamic ecological systems defined by interdependent biological, physical, and social components. The emergent structure and heterogeneity of urban landscapes drives biotic outcomes in these areas, and such spatial patterns are often attributed to the unequal stratification of wealth and power in human societies. Despite these patterns, few studies have effectively considered structural inequalities as drivers of ecological and evolutionary outcomes and have instead focused on indicator variables such as neighborhood wealth. In this analysis, we explicitly integrate ecology, evolution, and social processes to emphasize the relationships that bind social inequities-specifically racism-and biological change in urbanized landscapes. We draw on existing research to link racist practices, including residential segregation, to the heterogeneous patterns of flora and fauna observed by urban ecologists. In the future, urban ecology and evolution researchers must consider how systems of racial oppression affect the environmental factors that drive biological change in cities. Conceptual integration of the social and ecological sciences has amassed considerable scholarship in urban ecology over the past few decades, providing a solid foundation for incorporating environmental justice scholarship into urban ecological and evolutionary research. Such an undertaking is necessary to deconstruct urbanization's biophysical patterns and processes, inform equitable and anti-racist initiatives promoting justice in urban conservation, and strengthen community resilience to global environmental change., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Cities are uniquely complex systems regulated by interactions and feedbacks between nature and human society. Characteristics of human society-including culture, economics, technology and politics-underlie social patterns and activity, creating a heterogeneous environment that can influence and be influenced by both ecological and evolutionary processes. Increasing research on urban ecology and evolutionary biology has coincided with growing interest in eco-evolutionary dynamics, which encompasses the interactions and reciprocal feedbacks between evolution and ecology. Research on both urban evolutionary biology and eco-evolutionary dynamics frequently focuses on contemporary evolution of species that have potentially substantial ecological-and even social-significance. Still, little work fully integrates urban evolutionary biology and eco-evolutionary dynamics, and rarely do researchers in either of these fields fully consider the role of human social patterns and processes. Because cities are fundamentally regulated by human activities, are inherently interconnected and are frequently undergoing social and economic transformation, they represent an opportunity for ecologists and evolutionary biologists to study urban "socio-eco-evolutionary dynamics." Through this new framework, we encourage researchers of urban ecology and evolution to fully integrate human social drivers and feedbacks to increase understanding and conservation of ecosystems, their functions and their contributions to people within and outside cities., Competing Interests: None declared., (© 2020 The Authors. Evolutionary Applications published by John Wiley & Sons Ltd.)

Generalist species, by definition, exhibit variation in niche attributes that promote survival in changing environments. Increasingly, phenotypes previously associated with a species, particularly those with wide or expanding ranges, are dissolving and compelling greater emphasis on population-level characteristics. In the present study, we assessed spatial variation in diet characteristics, gut microbiome and associations between these two ecological traits across populations of coyotes Canis latrans. We highlight the influence of the carnivore community in shaping these relationships, as the coyote varied from being an apex predator to a subordinate, mesopredator across sampled populations. We implemented a scat survey across three distinct coyote populations in Michigan, USA. We used carbon (δ 13 C) and nitrogen (δ 15 N) isotopic values to reflect consumption patterns and trophic level, respectively. Corresponding samples were also paired with 16S rRNA sequencing to describe the microbial community and correlate with isotopic values. Although consumption patterns were comparable, we found spatial variation in trophic level among coyote populations. Specifically, δ 15 N was highest where coyotes were the apex predator and lowest where coyotes co-occurred with grey wolves Canis lupus. The gut microbial community exhibited marked spatial variation across populations with the lowest operational taxonomic units diversity found where coyotes occurred at their lowest trophic level. Bacteriodes and Fusobacterium dominated the microbiome and were positively correlated across all populations. We found no correlation between δ 13 C and microbial community attributes. However, positive associations between δ 15 N and specific microbial genera increased as coyotes ascended trophic levels. Coyotes provide a model for exploring implications of niche plasticity because they are a highly adaptable, wide-ranging omnivore. As coyotes continue to vary in trophic position and expand their geographic range, we might expect increased divergence within their microbial community, changes in physiology and alterations in behaviour., (© 2020 British Ecological Society.)

Despite intensive study for 50 years, the biochemical and genetic links between lysine metabolism and central metabolism in Pseudomonas putida remain unresolved. To establish these biochemical links, we leveraged r andom b arcode t ra n sposon seq uencing (RB-TnSeq), a genome-wide assay measuring the fitness of thousands of genes in parallel, to identify multiple novel enzymes in both l- and d-lysine metabolism. We first describe three pathway enzymes that catabolize l-2-aminoadipate (l-2AA) to 2-ketoglutarate (2KG), connecting d-lysine to the TCA cycle. One of these enzymes, P. putida 5260 (PP_5260), contains a DUF1338 domain, representing a family with no previously described biological function. Our work also identified the recently described coenzyme A (CoA)-independent route of l-lysine degradation that results in metabolization to succinate. We expanded on previous findings by demonstrating that glutarate hydroxylase CsiD is promiscuous in its 2-oxoacid selectivity. Proteomics of selected pathway enzymes revealed that expression of catabolic genes is highly sensitive to the presence of particular pathway metabolites, implying intensive local and global regulation. This work demonstrated the utility of RB-TnSeq for discovering novel metabolic pathways in even well-studied bacteria, as well as its utility a powerful tool for validating previous research. IMPORTANCE P. putida lysine metabolism can produce multiple commodity chemicals, conferring great biotechnological value. Despite much research, the connection of lysine catabolism to central metabolism in P. putida remained undefined. Here, we used random barcode transposon sequencing to fill the gaps of lysine metabolism in P. putida We describe a route of 2-oxoadipate (2OA) catabolism, which utilizes DUF1338-containing protein P. putida 5260 (PP_5260) in bacteria. Despite its prevalence in many domains of life, DUF1338-containing proteins have had no known biochemical function. We demonstrate that PP_5260 is a metalloenzyme which catalyzes an unusual route of decarboxylation of 2OA to d-2-hydroxyglutarate (d-2HG). Our screen also identified a recently described novel glutarate metabolic pathway. We validate previous results and expand the understanding of glutarate hydroxylase CsiD by showing that can it use either 2OA or 2KG as a cosubstrate. Our work demonstrated that biological novelty can be rapidly identified using unbiased experimental genetics and that RB-TnSeq can be used to rapidly validate previous results.

Metastasis via the lymphatic vasculature is an important step in cancer progression. The formation of new lymphatic vessels (lymphangiogenesis), or remodeling of existing lymphatics, is thought to facilitate the entry and transport of tumor cells into lymphatic vessels and on to distant organs. The migration of lymphatic endothelial cells (LEC) toward guidance cues is critical for lymphangiogenesis. While chemokines are known to provide directional navigation for migrating immune cells, their role in mediating LEC migration during tumor-associated lymphangiogenesis is not well defined. Here, we undertook gene profiling studies to identify chemokine-chemokine receptor pairs that are involved in tumor lymphangiogenesis associated with lymph node metastasis. CCL27 and CCL28 were expressed in tumor cells with metastatic potential, while their cognate receptor, CCR10, was expressed by LECs and upregulated by the lymphangiogenic growth factor VEGFD and the proinflammatory cytokine TNFα. Migration assays demonstrated that LECs are attracted to both CCL27 and CCL28 in a CCR10-dependent manner, while abnormal lymphatic vessel patterning in CCR10-deficient mice confirmed the significant role of CCR10 in lymphatic patterning. In vivo analyses showed that LECs are recruited to a CCL27 or CCL28 source, while VEGFD was required in combination with these chemokines to enable formation of coherent lymphatic vessels. Moreover, tumor xenograft experiments demonstrated that even though CCL27 expression by tumors enhanced LEC recruitment, the ability to metastasize was dependent on the expression of VEGFD. These studies demonstrate that CCL27 and CCL28 signaling through CCR10 may cooperate with inflammatory mediators and VEGFD during tumor lymphangiogenesis. SIGNIFICANCE: The study shows that the remodeling of lymphatic vessels in cancer is influenced by CCL27 and CCL28 chemokines, which may provide a future target to modulate metastatic spread., (©2019 American Association for Cancer Research.)

The electron-rich isonitrile is an important functionality in bioactive natural products, but its biosynthesis has been restricted to the IsnA family of isonitrile synthases. We herein provide the first structural and biochemical evidence of an alternative mechanism for isonitrile formation. ScoE, a putative non-heme iron(II)-dependent enzyme from Streptomyces coeruleorubidus, was shown to catalyze the conversion of (R)-3-((carboxymethyl)amino)butanoic acid to (R)-3-isocyanobutanoic acid through an oxidative decarboxylation mechanism. This work further provides a revised scheme for the biosynthesis of a unique class of isonitrile lipopeptides, of which several members are critical for the virulence of pathogenic mycobacteria., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Bragg waveguides are promising optical filters for pump suppression in spontaneous four-wave mixing (FWM) photon sources. In this work, we investigate the generation of unwanted photon pairs in the filter itself. We do this by taking advantage of the relation between spontaneous and classical FWM, which allows for the precise characterization of the nonlinear response of the device. The pair generation rate estimated from the classical measurement is compared with the theoretical value calculated by means of a full quantum model of the filter, which also allows investigation of the spectral properties of the generated pairs. We find a good agreement between theory and experiment, confirming that stimulated FWM is a valuable approach to characterize the nonlinear response of an integrated filter, and that the pairs generated in a Bragg waveguide are not a serious issue for the operation of a fully integrated nonclassical source.

Species reside in dynamic environments, simultaneously experiencing variations in climatic conditions, habitat availability and quality, interspecific interactions, and anthropogenic pressures. We investigated variation in foraging ecology of the small mammal community between land-use classifications (i.e., protected national parks and unprotected lands abutting them) in Mole National Park (MNP) and Digya National Park (DNP), representing distinct ecoregions of Ghana. In 5,064 trap nights, we sampled 153 individuals of 23 species within the 2 national parks and adjacent lands outside protected boundaries to describe variation in community composition. We also used δ 13 C and δ 15 N isotopic ratios from fresh feces to determine main effects and interactions between land use and ecoregion on trophic structure in species and communities of small mammals. Small mammals exhibited distinct community assemblages between ecoregions (i.e., national parks): Gerbilliscus guineae , Hybomys trivirgatus , Malacomys edwardsi , Lemniscomys bellieri , L. zebra , and Taterillus gracilis were only captured in the dry savanna ecoregion of MNP. Additionally, isotopic signatures for nitrogen were significantly lower in MNP (2.83 ± 0.17‰) compared to DNP (4.97 ± 0.33‰), indicating that small mammals occupied different trophic levels between ecoregions. The most common species, Praomys daltoni exhibited variation in isotopic signatures between ecoregions and land use, with higher δ 15 N found within MNP boundaries. We found no distinction in δ 13 C at the community or species level within or across protected areas. Ultimately, understanding shifts in the ecology of species can inform predictions about community structure and ecosystem function under future environmental and anthropogenic scenarios.

The benefits of adult stem cells for repair of the heart have been attributed to the repertoire of salutary paracrine activities they appear to exert. We previously isolated human W8B2 + cardiac stem cells (CSCs) and found they powerfully influence cardiomyocytes and endothelial cells to collectively promote cardiac repair and regeneration. Here, the complexity of the W8B2 + CSC secretomes was characterised and examined in more detail. Using ion exchange chromatography to separate soluble proteins based on their net surface charge, the secreted factors responsible for the pro-survival activity of W8B2 + CSCs were found within the low and medium cation fractions. In addition to the soluble proteins, extracellular vesicles generated from W8B2 + CSCs not only exhibited pro-survival and pro-angiogenic activities, but also promoted proliferation of neonatal cardiomyocytes. These extracellular vesicles contain a cargo of proteins, mRNA and primary microRNA precursors that are enriched in exosomes and are capable of modulating collectively many of the cellular pathways involved in protein metabolism, cell growth, as well as cellular responses to stress and organisation of the extracellular matrix. Thus the W8B2 + CSC secretome contains a multitude of bioactive paracrine factors we have now characterised, that might well be harnessed for therapeutic application for cardiac repair and regeneration.

Betalains are a family of natural pigments found exclusively in the plant order Caryophyllales. All members of this chemical family are biosynthesized through the common intermediate betalamic acid, which is capable of spontaneously condensing with various primary and secondary amines to produce betalains. Of particular interest is the red-violet betanin, most commonly obtained from Beta vulgaris (beet) as a natural food dye. We demonstrate the first complete microbial production of betanin in Saccharomyces cerevisiae from glucose, an early step towards a fermentation process enabling rapid, on-demand production of this natural dye. A titer of 17mg/L was achieved, corresponding to a color intensity obtained from 10g/L of beetroot extract. Further, we expanded the spectrum of betalain colors by condensing betalamic acid with various amines fed to an engineered strain of S. cerevisiae. Our work establishes a platform for microbial production of betalains of various colors as a potential alternative to land- and resource-intensive agricultural production., (Copyright © 2017 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.)

Lymphatic vessels constitute a specialized vasculature that is involved in development, cancer, obesity, and immune regulation. The migration of lymphatic endothelial cells (LECs) is critical for vessel growth (lymphangiogenesis) and vessel remodeling, processes that modify the lymphatic network in response to developmental or pathological demands. Using the publicly accessible results of our genome-wide siRNA screen, we characterized the migratome of primary human LECs and identified individual genes and signaling pathways that regulate LEC migration. We compared our data set with mRNA differential expression data from endothelial and stromal cells derived from two in vivo models of lymphatic vessel remodeling, viral infection and contact hypersensitivity-induced inflammation, which identified genes selectively involved in regulating LEC migration and remodeling. We also characterized the top candidates in the LEC migratome in primary blood vascular endothelial cells to identify genes with functions common to lymphatic and blood vascular endothelium. On the basis of these analyses, we showed that LGALS1 , which encodes the glycan-binding protein Galectin-1, promoted lymphatic vascular growth in vitro and in vivo and contributed to maintenance of the lymphatic endothelial phenotype. Our results provide insight into the signaling networks that control lymphangiogenesis and lymphatic remodeling and potentially identify therapeutic targets and biomarkers in disease specific to lymphatic or blood vessels., (Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Climate change is a well-documented driver of both wildlife extinction and disease emergence, but the negative impacts of climate change on parasite diversity are undocumented. We compiled the most comprehensive spatially explicit data set available for parasites, projected range shifts in a changing climate, and estimated extinction rates for eight major parasite clades. On the basis of 53,133 occurrences capturing the geographic ranges of 457 parasite species, conservative model projections suggest that 5 to 10% of these species are committed to extinction by 2070 from climate-driven habitat loss alone. We find no evidence that parasites with zoonotic potential have a significantly higher potential to gain range in a changing climate, but we do find that ectoparasites (especially ticks) fare disproportionately worse than endoparasites. Accounting for host-driven coextinctions, models predict that up to 30% of parasitic worms are committed to extinction, driven by a combination of direct and indirect pressures. Despite high local extinction rates, parasite richness could still increase by an order of magnitude in some places, because species successfully tracking climate change invade temperate ecosystems and replace native species with unpredictable ecological consequences.

We demonstrate a large-scale tunable-coupling ring resonator array, suitable for high-dimensional classical and quantum transforms, in a CMOS-compatible silicon photonics platform. The device consists of a waveguide coupled to 15 ring-based dispersive elements with programmable linewidths and resonance frequencies. The ability to control both quality factor and frequency of each ring provides an unprecedented 30 degrees of freedom in dispersion control on a single spatial channel. This programmable dispersion control system has a range of applications, including mode-locked lasers, quantum key distribution, and photon-pair generation. We also propose a novel application enabled by this circuit - high-speed quantum communications using temporal-mode-based quantum data locking - and discuss the utility of the system for performing the high-dimensional unitary optical transformations necessary for a quantum data locking demonstration.

A putative lipopeptide biosynthetic gene cluster is conserved in many species of Actinobacteria, including Mycobacterium tuberculosis and M. marinum , but the specific function of the encoding proteins has been elusive. Using both in vivo heterologous reconstitution and in vitro biochemical analyses, we have revealed that the five encoding biosynthetic enzymes are capable of synthesizing a family of isonitrile lipopeptides (INLPs) through a thio-template mechanism. The biosynthesis features the generation of isonitrile from a single precursor Gly promoted by a thioesterase and a nonheme iron(II)-dependent oxidase homolog and the acylation of both amino groups of Lys by the same isonitrile acyl chain facilitated by a single condensation domain of a nonribosomal peptide synthetase. In addition, the deletion of INLP biosynthetic genes in M. marinum has decreased the intracellular metal concentration, suggesting the role of this biosynthetic gene cluster in metal transport., Competing Interests: The authors declare no conflict of interest.

Despite the number of virulent pathogens that are projected to benefit from global change and to spread in the next century, we suggest that a combination of coextinction risk and climate sensitivity could make parasites at least as extinction prone as any other trophic group. However, the existing interdisciplinary toolbox for identifying species threatened by climate change is inadequate or inappropriate when considering parasites as conservation targets. A functional trait approach can be used to connect parasites' ecological role to their risk of disappearance, but this is complicated by the taxonomic and functional diversity of many parasite clades. Here, we propose biological traits that may render parasite species particularly vulnerable to extinction (including high host specificity, complex life cycles and narrow climatic tolerance), and identify critical gaps in our knowledge of parasite biology and ecology. By doing so, we provide criteria to identify vulnerable parasite species and triage parasite conservation efforts.

VEGF-C and VEGF-D are secreted glycoproteins that induce angiogenesis and lymphangiogenesis in cancer, thereby promoting tumor growth and spread. They exhibit structural homology and activate VEGFR-2 and VEGFR-3, receptors on endothelial cells that signal for growth of blood vessels and lymphatics. VEGF-C and VEGF-D were thought to exhibit similar bioactivities, yet recent studies indicated distinct signaling mechanisms (e.g. tumor-derived VEGF-C promoted expression of the prostaglandin biosynthetic enzyme COX-2 in lymphatics, a response thought to facilitate metastasis via the lymphatic vasculature, whereas VEGF-D did not). Here we explore the basis of the distinct bioactivities of VEGF-D using a neutralizing antibody, peptide mapping, and mutagenesis to demonstrate that the N-terminal α-helix of mature VEGF-D (Phe 93 -Arg 108 ) is critical for binding VEGFR-2 and VEGFR-3. Importantly, the N-terminal part of this α-helix, from Phe 93 to Thr 98 , is required for binding VEGFR-3 but not VEGFR-2. Surprisingly, the corresponding part of the α-helix in mature VEGF-C did not influence binding to either VEGFR-2 or VEGFR-3, indicating distinct determinants of receptor binding by these growth factors. A variant of mature VEGF-D harboring a mutation in the N-terminal α-helix, D103A, exhibited enhanced potency for activating VEGFR-3, was able to promote increased COX-2 mRNA levels in lymphatic endothelial cells, and had enhanced capacity to induce lymphatic sprouting in vivo This mutant may be useful for developing protein-based therapeutics to drive lymphangiogenesis in clinical settings, such as lymphedema. Our studies shed light on the VEGF-D structure/function relationship and provide a basis for understanding functional differences compared with VEGF-C., (© 2016 by The American Society for Biochemistry and Molecular Biology, Inc.)

Parasitic species, which depend directly on host species for their survival, represent a major regulatory force in ecosystems and a significant component of Earth's biodiversity. Yet the negative impacts of parasites observed at the host level have motivated a conservation paradigm of eradication, moving us farther from attainment of taxonomically unbiased conservation goals. Despite a growing body of literature highlighting the importance of parasite-inclusive conservation, most parasite species remain understudied, underfunded, and underappreciated. We argue the protection of parasitic biodiversity requires a paradigm shift in the perception and valuation of their role as consumer species, similar to that of apex predators in the mid-20th century. Beyond recognizing parasites as vital trophic regulators, existing tools available to conservation practitioners should explicitly account for the unique threats facing dependent species. We built upon concepts from epidemiology and economics (e.g., host-density threshold and cost-benefit analysis) to devise novel metrics of margin of error and minimum investment for parasite conservation. We define margin of error as the risk of accidental host extinction from misestimating equilibrium population sizes and predicted oscillations, while minimum investment represents the cost associated with conserving the additional hosts required to maintain viable parasite populations. This framework will aid in the identification of readily conserved parasites that present minimal health risks. To establish parasite conservation, we propose an extension of population viability analysis for host-parasite assemblages to assess extinction risk. In the direst cases, ex situ breeding programs for parasites should be evaluated to maximize success without undermining host protection. Though parasitic species pose a considerable conservation challenge, adaptations to conservation tools will help protect parasite biodiversity in the face of an uncertain environmental future., (© 2015 Society for Conservation Biology.)

Leakage of fluid from blood vessels, leading to oedema, is a key feature of many diseases including hyperoxic acute lung injury (HALI), which can occur when patients are ventilated with high concentrations of oxygen (hyperoxia). The molecular mechanisms driving vascular leak and oedema in HALI are poorly understood. VEGF-D is a protein that promotes blood vessel leak and oedema when overexpressed in tissues, but the role of endogenous VEGF-D in pathological oedema was unknown. To address these issues, we exposed Vegfd-deficient mice to hyperoxia. The resulting pulmonary oedema in Vegfd-deficient mice was substantially reduced compared to wild-type, as was the protein content of bronchoalveolar lavage fluid, consistent with reduced vascular leak. Vegf-d and its receptor Vegfr-3 were more highly expressed in lungs of hyperoxic, versus normoxic, wild-type mice, indicating that components of the Vegf-d signalling pathway are up-regulated in hyperoxia. Importantly, VEGF-D and its receptors were co-localized on blood vessels in clinical samples of human lungs exposed to hyperoxia; hence, VEGF-D may act directly on blood vessels to promote fluid leak. Our studies show that Vegf-d promotes oedema in response to hyperoxia in mice and support the hypothesis that VEGF-D signalling promotes vascular leak in human HALI. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland., (© 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.)

Glioblastoma multiforme is the most aggressive and lethal tumor of the central nervous system with limited treatment strategies on offer, and as such the identification of effective novel therapeutic agents is paramount. To examine the efficacy of proteasome inhibitors, we tested bortezomib, carfilzomib, nafamostat mesylate, gabexate mesylate and acetylsalicylic acid on glioblastoma cell viability, migration and invasion. Both bortezomib and carfilzomib produced significant reduction of cell viability, while nafamostat mesylate, gabexate mesylate and acetylsalicylic acid did not. Subsequent testing showed that carfilzomib significantly reduced cell viability at nM concentrations. Carfilzomib also reduced cell migration, secretion and activation of MMP2 and also cell invasion of all four glioblastoma cells tested. In summary, carfilzomib represents a novel, yet FDA-approved agent for the treatment of glioblastoma multiforme.

Compact silicon integrated devices, such as micro-ring resonators, have recently been demonstrated as efficient sources of quantum correlated photon pairs. The mass production of integrated devices demands the implementation of fast and reliable techniques to monitor the device performances. In the case of time-energy correlations, this is particularly challenging, as it requires high spectral resolution that is not currently achievable in coincidence measurements. Here we reconstruct the joint spectral density of photons pairs generated by spontaneous four-wave mixing in a silicon ring resonator by studying the corresponding stimulated process, namely stimulated four wave mixing. We show that this approach, featuring high spectral resolution and short measurement times, allows one to discriminate between nearly-uncorrelated and highly-correlated photon pairs.

A major challenge in nanofabrication is to pattern unconventional substrates that cannot be processed for a variety of reasons, such as incompatibility with spin coating, electron beam lithography, optical lithography, or wet chemical steps. Here, we present a versatile nanofabrication method based on re-usable silicon membrane hard masks, patterned using standard lithography and mature silicon processing technology. These masks, transferred precisely onto targeted regions, can be in the millimetre scale. They allow for fabrication on a wide range of substrates, including rough, soft, and non-conductive materials, enabling feature linewidths down to 10 nm. Plasma etching, lift-off, and ion implantation are realized without the need for scanning electron/ion beam processing, UV exposure, or wet etching on target substrates.

Photonic-integrated circuits have emerged as a scalable platform for complex quantum systems. A central goal is to integrate single-photon detectors to reduce optical losses, latency and wiring complexity associated with off-chip detectors. Superconducting nanowire single-photon detectors (SNSPDs) are particularly attractive because of high detection efficiency, sub-50-ps jitter and nanosecond-scale reset time. However, while single detectors have been incorporated into individual waveguides, the system detection efficiency of multiple SNSPDs in one photonic circuit-required for scalable quantum photonic circuits-has been limited to <0.2%. Here we introduce a micrometer-scale flip-chip process that enables scalable integration of SNSPDs on a range of photonic circuits. Ten low-jitter detectors are integrated on one circuit with 100% device yield. With an average system detection efficiency beyond 10%, and estimated on-chip detection efficiency of 14-52% for four detectors operated simultaneously, we demonstrate, to the best of our knowledge, the first on-chip photon correlation measurements of non-classical light.

We design a resistive heater optimized for efficient and low-loss optical phase modulation in a silicon-on-insulator (SOI) waveguide and characterize the fabricated devices. Modulation is achieved by flowing current perpendicular to a new ridge waveguide geometry. The resistance profile is engineered using different dopant concentrations to obtain localized heat generation and maximize the overlap between the optical mode and the high temperature regions of the structure, while simultaneously minimizing optical loss due to free-carrier absorption. A 61.6 μm long phase shifter was fabricated in a CMOS process with oxide cladding and two metal layers. The device features a phase-shifting efficiency of 24.77 ± 0.43 mW/π and a -3 dB modulation bandwidth of 130.0 ± 5.59 kHz; the insertion loss measured for 21 devices across an 8-inch wafer was only 0.23 ± 0.13 dB. Considering the prospect of densely integrated photonic circuits, we also quantify the separation necessary to isolate thermo-optic devices in the standard 220 nm SOI platform.

The black-footed ferret, Mustela nigripes, is an endangered carnivore endemic to the grasslands of North America. We present the first investigation of ectoparasites associated with black-footed ferrets since reintroduction. We sampled more than 200 individuals from one of the largest and most successful reintroduced populations located in the Conata Basin of South Dakota, USA. We compared our findings with ectoparasite assemblages of sympatric carnivores and historic ferret records. We collected more than 1,000 ectoparasites consisting mainly of three flea and tick species, two of which were known historically from South Dakota. Despite our extensive sampling efforts, we did not detect any lice. This is notable because a putative host-specific louse, Neotrichodectes sp., was presumed to have gone extinct when black-footed ferrets were extirpated from the wild. The ectoparasite assemblage on black-footed ferrets comprised only generalist parasites, particularly those found on their prey such as prairie dogs (Cynomys sp.). Oropsylla hirsuta was the most abundant ectoparasite, representing 57% of all ectoparasites detected; a flea vector important in the persistence and transmission of plague. Black-footed ferrets like other endangered species undergo repeated parasite removal and vaccination efforts to facilitate population recovery, which may have unintentionally contributed to their depauperate ectoparasite community.

The VEGFC/VEGFR3 signaling pathway is essential for lymphangiogenesis (the formation of lymphatic vessels from pre-existing vasculature) during embryonic development, tissue regeneration and tumor progression. The recently identified secreted protein CCBE1 is indispensible for lymphangiogenesis during development. The role of CCBE1 orthologs is highly conserved in zebrafish, mice and humans with mutations in CCBE1 causing generalized lymphatic dysplasia and lymphedema (Hennekam syndrome). To date, the mechanism by which CCBE1 acts remains unknown. Here, we find that ccbe1 genetically interacts with both vegfc and vegfr3 in zebrafish. In the embryo, phenotypes driven by increased Vegfc are suppressed in the absence of Ccbe1, and Vegfc-driven sprouting is enhanced by local Ccbe1 overexpression. Moreover, Vegfc- and Vegfr3-dependent Erk signaling is impaired in the absence of Ccbe1. Finally, CCBE1 is capable of upregulating the levels of fully processed, mature VEGFC in vitro and the overexpression of mature VEGFC rescues ccbe1 loss-of-function phenotypes in zebrafish. Taken together, these data identify Ccbe1 as a crucial component of the Vegfc/Vegfr3 pathway in the embryo.

The growth of blood vessels (angiogenesis) and lymphatic vessels (lymphangiogenesis) in and around solid tumors is central to the growth and metastatic spread of cancer. The therapeutic targeting of angiogenesis has become an established modality of cancer treatment, however, more comprehensive targeting of angiogenic signaling pathways may be required to enhance the clinical benefits of this approach. Angiogenesis and lymphangiogenesis are driven, or modulated, by a range of secreted glycoproteins including vascular endothelial growth factors, platelet-derived growth factors, and transforming growth factor-β. These key regulatory growth factors are subject to proteolytic activation, involving highly specific cleavage events, which can occur at the cell surface or in the extracellular milieu. These cleavage events are catalysed by a variety of enzymes including proprotein convertases. This proteolysis can regulate the activity of these growth factors by enhancing binding affinities for cell surface receptors and co-receptors, or by altering their interactions with heparan sulfate proteoglycans, thereby modulating bioavailability. The proteolytic processing of these growth factors complicates strategies for targeting them for diagnostic and/or therapeutic purposes in cancer, as processing can generate various forms with distinct biological properties. Hence it has been important to determine which forms are biologically active for promoting angiogenesis and lymphangiogenesis in cancer, so as to indicate clinical relevance. Here we review the regulation of tumor angiogenesis and lymphangiogenesis by proteolytic activation of growth factors, and the potential therapeutic and diagnostic strategies arising from our understanding of this process.