The mammalian immune system is constantly challenged by signals from both pathogenic and non-pathogenic microbes. Many of these non-pathogenic microbes have pathogenic potential if the immune system ...is compromised. The importance of type I interferons (IFNs) in orchestrating innate immune responses to pathogenic microbes has become clear in recent years. However, the control of opportunistic pathogens-and especially intracellular bacteria-by type I IFNs remains less appreciated. In this study, we use the opportunistic, Gram-negative bacterial pathogen Burkholderia cenocepacia (Bc) to show that type I IFNs are capable of limiting bacterial replication in macrophages, preventing illness in immunocompetent mice. Sustained type I IFN signaling through cytosolic receptors allows for increased expression of autophagy and linear ubiquitination mediators, which slows bacterial replication. Transcriptomic analyses and in vivo studies also show that LPS stimulation does not replicate the conditions of intracellular Gram-negative bacterial infection as it pertains to type I IFN stimulation or signaling. This study highlights the importance of type I IFNs in protection against opportunistic pathogens through innate immunity, without the need for damaging inflammatory responses.
Specifying early developmental differences among neurodevelopmental disorders with distinct etiologies is critical to improving early identification and tailored intervention during the first years ...of life. Recent studies have uncovered important differences between infants with fragile X syndrome (FXS) and infants with familial history of autism spectrum disorder who go on to develop autism themselves (FH-ASD), including differences in brain development and behavior. Thus far, there have been no studies longitudinally investigating differential developmental skill profiles in FXS and FH-ASD infants.
The current study contrasted longitudinal trajectories of verbal (expressive and receptive language) and nonverbal (gross and fine motor, visual reception) skills in FXS and FH-ASD infants, compared to FH infants who did not develop ASD (FH-nonASD) and typically developing controls.
Infants with FXS showed delays on a nonverbal composite compared to FH-ASD (as well as FH-nonASD and control) infants as early as 6 months of age. By 12 months an ordinal pattern of scores was established between groups on all domains tested, such that controls > FH-nonASD > FH-ASD > FXS. This pattern persisted through 24 months. Cognitive level differentially influenced developmental trajectories for FXS and FH-ASD.
Our results demonstrate detectable group differences by 6 months between FXS and FH-ASD as well as differential trajectories on each domain throughout infancy. This work further highlights an earlier onset of global cognitive delays in FXS and, conversely, a protracted period of more slowly emerging delays in FH-ASD. Divergent neural and cognitive development in infancy between FXS and FH-ASD contributes to our understanding of important distinctions in the development and behavioral phenotype of these two groups.
Climate change poses significant challenges to protected area management globally. Anticipatory climate adaptation planning relies on vulnerability assessments that identify parks and resources at ...risk from climate change and associated vulnerability drivers. However, there is currently little understanding of where and how protected area assessments have been conducted and what assessment approaches best inform park management. To address this knowledge gap, we systematically evaluated climate‐change vulnerability assessments of natural resources in U.S. National Parks. We categorized the spatial scale, resources, methods, and handling of uncertainty for each assessment and mapped which parks have assessments and for what resources. We found that a few broad‐scale assessments provide baseline information—primarily regarding physical climate change exposure—for all parks and can support regional to national decisions. However, finer‐scale assessments are required to inform decisions for individual or small groups of parks. Only 10% of parks had park‐specific assessments describing key climate impacts and identifying priority resource vulnerabilities, and 37% lacked any regional or park‐specific assessments. We identify assessment approaches that match the scale and objectives of different protected area management decisions and recommend a multi‐scaled approach to implementing assessments to meet the information needs of a large, protected area network like the National Park system.
We reviewed climate‐change vulnerability assessments of natural resources in U.S. National Parks to identify common approaches and resources evaluated. Assessments varied widely in spatial scale, conceptual scope, and level of detail. We found that designing assessments to match the scale and objectives of protected‐area management decisions is essential and describe a multi‐scaled assessment approach to meet the information needs of a large protected‐area network like the National Park system.
Previous research has demonstrated that the amygdala is enlarged in children with autism spectrum disorder (ASD). However, the precise onset of this enlargement during infancy, how it relates to ...later diagnostic behaviors, whether the timing of enlargement in infancy is specific to the amygdala, and whether it is specific to ASD (or present in other neurodevelopmental disorders, such as fragile X syndrome) are all unknown.
Longitudinal MRIs were acquired at 6-24 months of age in 29 infants with fragile X syndrome, 58 infants at high likelihood for ASD who were later diagnosed with ASD, 212 high-likelihood infants not diagnosed with ASD, and 109 control infants (1,099 total scans).
Infants who developed ASD had typically sized amygdala volumes at 6 months, but exhibited significantly faster amygdala growth between 6 and 24 months, such that by 12 months the ASD group had significantly larger amygdala volume (Cohen's d=0.56) compared with all other groups. Amygdala growth rate between 6 and 12 months was significantly associated with greater social deficits at 24 months when the infants were diagnosed with ASD. Infants with fragile X syndrome had a persistent and significantly enlarged caudate volume at all ages between 6 and 24 months (d=2.12), compared with all other groups, which was significantly associated with greater repetitive behaviors.
This is the first MRI study comparing fragile X syndrome and ASD in infancy, demonstrating strikingly different patterns of brain and behavior development. Fragile X syndrome-related changes were present from 6 months of age, whereas ASD-related changes unfolded over the first 2 years of life, starting with no detectable group differences at 6 months. Increased amygdala growth rate between 6 and 12 months occurs prior to social deficits and well before diagnosis. This gradual onset of brain and behavior changes in ASD, but not fragile X syndrome, suggests an age- and disorder-specific pattern of cascading brain changes preceding autism diagnosis.
Treatment of H2OsBr6 with C5Me5H in tert-butyl alcohol affords the dinuclear osmium(III) species (C5Me5)2Os2Br4, a mono(pentamethylcyclopentadienyl) complex that serves as the key synthetic entry ...into a wide array of “half-sandwich” complexes of osmium. The X-ray crystal structure shows it to contain two bridging and two terminal bromide ligands, with the Os−Br bond distances being shorter for the bridging bromide ligands than for the terminal bromide ligands. The Os−Os distance of 2.970(1) Å is indicative of a single osmium−osmium bond. The compound is weakly paramagnetic in solution and in the solid state, and the magnetic susceptibility determined over the range 4−300 K gives a singlet−triplet splitting of >800 cm-1. The reactions of (C5Me5)2Os2Br4 with oxygen, bromine, lithium anilide, acetonitrile, and norbornadiene (NBD) are described, affording the compounds (C5Me5)2Os2(μ-O)Br4, (C5Me5)OsBr4, (C5Me5)2Os2(μ-NPh)2Br2, (C5Me5)Os(MeCN)3BPh4, and (C5Me5)Os(NBD)Br; the crystal structures of the bridging oxo and bridging imido complexes are given.
The role of epidermal growth factor (EGF) in the maturation of mammalian oocytes is well known but not well characterized. It is known that EGF enhances oocyte maturation in vitro and that EGF ...stimulation of cumulus-oocyte complexes (COCs) induces pulsatile Ca(2+) efflux from the cell complex. By use of quantitative Fura-2 imaging, EGF-stimulated changes in intracellular Ca(2+) in germinal vesicle stage murine COCs are shown to occur in a subpopulation of cumulus cells that interact cooperatively within individual COCs. Oocytes fail to respond to EGF stimulus. In many of the cumulus cells responding with a rise in intracellular Ca(2+), a concomitant permeabilization of the plasma membrane is found. Neither cumulus cells of control COCs nor those that show a rise in intracellular Ca(2+) in response to calcium ionophore treatment display a similar membrane permeabilization, although those cells responding with a prolonged Ca(2+) increase in response to thimerosal or thapsigargin do display plasma membrane permeabilization. Thus, EGF stimulation of mammalian COCs activates release of Ca(2+) from intracellular stores of cumulus cells, the depletion of which activates permeabilization of the plasma membrane. This membrane permeabilization leads to loss of cell contents and presumptive cumulus cell death. This catastrophic EGF-induced plasma membrane permeabilization of individual cumulus cells within a COC leads to pulsatile Ca(2+) efflux as previously seen, and may lead to improved cumulus cell expansion during COC maturation.
Treatment of Cp*2Os2Br4 with 3-bromo-2-methylpropene or 1,3-cyclooctadiene affords the 2-methylpropenyl and cyclooctenyl products Cp*Os(η3-C4H7)Br2 and Cp*Os(η3-C8H13)Br2, respectively. The monoalkyl ...complexes Cp*Os(η3-C4H7)MeBr and Cp*Os(η3-C4H7)(CH2SiMe3)Br can be generated by treating Cp*Os(η3-C4H7)Br2 with MgMe2 or LiCH2SiMe3. The dimethyl complex Cp*Os(η3-C4H7)Me2 can be synthesized from Cp*Os(η3-C4H7)Br2 by addition of methyllithium. In contrast, addition of ethyllithium to Cp*Os(η3-C4H7)Br2 yields the ethylene complex Cp*Os(η3-C4H7)(η2-C2H4) and a small amount of Cp*Os(η3-C4H7)H2. The latter dihydride can be synthesized in better yield by treating Cp*Os(η3-C4H7)Br2 with LiAlH4. When the dimethyl complex Cp*Os(η3-C4H7)Me2 is protonated with HBF4 in the presence of H2O, the aqua complex Cp*Os(η3-C4H7)Me(H2O)BF4 is formed.
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