Phosphate (P) is an essential macronutrient for plant growth. Roots employ adaptive mechanisms to forage for P in soil. Root hair elongation is particularly important since P is immobile. Here we ...report that auxin plays a critical role promoting root hair growth in Arabidopsis in response to low external P. Mutants disrupting auxin synthesis (taa1) and transport (aux1) attenuate the low P root hair response. Conversely, targeting AUX1 expression in lateral root cap and epidermal cells rescues this low P response in aux1. Hence auxin transport from the root apex to differentiation zone promotes auxin-dependent hair response to low P. Low external P results in induction of root hair expressed auxin-inducible transcription factors ARF19, RSL2, and RSL4. Mutants lacking these genes disrupt the low P root hair response. We conclude auxin synthesis, transport and response pathway components play critical roles regulating this low P root adaptive response.
West Nile Virus (WNV), an emerging and re-emerging RNA virus, is the leading source of arboviral encephalitic morbidity and mortality in the United States. WNV infections are acutely controlled by ...innate immunity in peripheral tissues outside of the central nervous system (CNS) but WNV can evade the actions of interferon (IFN) to facilitate CNS invasion, causing encephalitis, encephalomyelitis, and death. Recent studies indicate that STimulator of INterferon Gene (STING), canonically known for initiating a type I IFN production and innate immune response to cytosolic DNA, is required for host defense against neurotropic RNA viruses. We evaluated the role of STING in host defense to control WNV infection and pathology in a murine model of infection. When challenged with WNV, STING knock out (-/-) mice displayed increased morbidity and mortality compared to wild type (WT) mice. Virologic analysis and assessment of STING activation revealed that STING signaling was not required for control of WNV in the spleen nor was WNV sufficient to mediate canonical STING activation in vitro. However, STING-/- mice exhibited a clear trend of increased viral load and virus dissemination in the CNS. We found that STING-/- mice exhibited increased and prolonged neurological signs compared to WT mice. Pathological examination revealed increased lesions, mononuclear cellular infiltration and neuronal death in the CNS of STING-/- mice, with sustained pathology after viral clearance. We found that STING was required in bone marrow derived macrophages for early control of WNV replication and innate immune activation. In vivo, STING-/- mice developed an aberrant T cell response in both the spleen and brain during WNV infection that linked with increased and sustained CNS pathology compared to WT mice. Our findings demonstrate that STING plays a critical role in immune programming for the control of neurotropic WNV infection and CNS disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Infection with West Nile virus (WNV) leads to a range of disease outcomes, including chronic infection, though lack of a robust mouse model of chronic WNV infection has precluded identification of ...the immune events contributing to persistent infection. Using the Collaborative Cross, a population of recombinant inbred mouse strains with high levels of standing genetic variation, we have identified a mouse model of persistent WNV disease, with persistence of viral loads within the brain. Compared to lines exhibiting no disease or marked disease, the F1 cross CC(032x013)F1 displays a strong immunoregulatory signature upon infection that correlates with restraint of the WNV-directed cytolytic response. We hypothesize that this regulatory T cell response sufficiently restrains the immune response such that a chronic infection can be maintained in the CNS. Use of this new mouse model of chronic neuroinvasive virus will be critical in developing improved strategies to prevent prolonged disease in humans.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Conventional directional hearing aid microphone technology may obstruct listening intentions when the talker and listener walk side by side. The purpose of the current study was to evaluate hearing ...aids that use a motion sensor to address listening needs during walking.
Each participant completed two walks in randomised order, one walk with each of two hearing aid programs: (1) conventional beamformer adaptation that activated an adaptive, multiband beamformer in loud environments and (2) motion-based beamformer adaptation that activated a pinna-mimicking microphone setting when walking was detected. Participants walked along a pre-defined track and completed tasks assessing speech understanding and environmental awareness.
Participants were 22 older adults with moderate-to-severe hearing loss and experience using hearing aids.
More participants preferred the motion-based than conventional beamformer adaptation for speech understanding, environmental awareness, overall listening, and sound quality (p < 0.05). Measures of speech understanding (p < 0.01) and localisation of sound stimuli (p < 0.05) were significantly better with motion-based than conventional beamformer adaptation.
The results suggest that hearing aid users can benefit from beamforming that uses motion sensor input to adapt the signal processing according to the user's activity. The real-world setup of this study had limitations.
A challenge to the design of improved therapeutic agents and prevention strategies for neuroinvasive infection and associated disease is the lack of known natural immune correlates of protection. A ...relevant model to study such correlates is offered by the Collaborative Cross (CC), a panel of recombinant inbred mouse strains that exhibit a range of disease manifestations upon infection.
We performed an extensive screen of CC-F1 lines infected with West Nile virus (WNV), including comprehensive immunophenotyping, to identify groups of lines that exhibited viral neuroinvasion or neuroinvasion with disease and lines that remained free of WNV neuroinvasion and disease.
Our data reveal that protection from neuroinvasion and disease is multifactorial and that several immune outcomes can contribute. Immune correlates identified include decreased suppressive activity of regulatory T cells at steady state, which correlates with peripheral restriction of the virus. Further, a rapid contraction of WNV-specific CD8+ T cells in the brain correlated with protection from disease.
These immune correlates of protection illustrate additional networks and pathways of the WNV immune response that cannot be observed in the C57BL/6 mouse model. Additionally, correlates of protection exhibited before infection, at baseline, provide insight into phenotypic differences in the human population that may predict clinical outcomes upon infection.
Background
Cadherin‐associated protein p120 catenin regulates cell adhesion and migration in cell cultures and is required for axial elongation in embryos. Its roles in adhesion and cell migration ...are regulated by phosphorylation. We determined the effects of phosphorylation of six serine and three threonine residues in p120 catenin during zebrafish (Danio rerio) embryogenesis.
Results
We knocked down endogenous p120 catenin‐δ1 with an antisense RNA‐splice‐site morpholino (Sp‐MO) causing defects in axis elongation. These defects were rescued by co‐injections of mRNAs for wildtype mouse p120 catenin‐δ1‐3A or various mutated forms. Several mRNAs containing serine or threonine codons singly or doubly mutated to phosphomimetic glutamic acid rescued, and some nonphosphorylatable mutants did not.
Conclusions
We discovered that phosphorylation of serine residue S252 or S879 is required for convergent extension of zebrafish embryos, since rescue occurred only when these residues were mutated to glutamic acid. In addition, the phosphorylation of either S268 or S269 is required, not both, consistent with the presence of only a single one of these residues in two isoforms of zebrafish and Xenopus laevis. In summary, phosphorylation of multiple serine and threonine residues of p120 catenin activates migration of presomitic mesoderm of zebrafish embryos facilitating elongation of the dorsal axis.
Key Findings
Knockdown of zebrafish p120 catenin‐δ1 with a morpholino blocks migration of presomitic mesoderm and extension of the dorsal axis.
We compared rescue of morphology by injecting mouse p120 catenin‐δ1‐3A (CTNND1‐3A) mRNAs mutated to phosphomimetic (E) and nonphosphorylatable (F) versions of serine and threonine residues.
Convergent extension of zebrafish embryos was partially rescued by phosphorylation of T310, S905, or T916. Importantly, it required phosphorylation of serine residues S252, S879, and either of S268 or S269.
We see normal morphogenesis as a dynamic interplay of motile filopodia and lamellipodia forming at the leading edge of the presomitic mesoderm cell as well as turnover of new cadherin‐mediated anchoring adherens junctions that facilitate a treadmilling action used by presomitic cells to migrate toward the dorsal aspect of the embryo.
A Comparison of 2 Intravenous Lipid Emulsions Nehra, Deepika; Fallon, Erica M.; Potemkin, Alexis K. ...
JPEN. Journal of parenteral and enteral nutrition,
08/2014, Letnik:
38, Številka:
6
Journal Article
Recenzirano
Objective. To assess the safety and efficacy of a fish oil–based intravenous fat emulsion (FIFE) in reducing the incidence of cholestasis in neonates compared with the traditional soybean oil–based ...intravenous fat emulsion (SIFE). Methods. A double-blind randomized controlled trial was conducted. Nineteen neonates were enrolled (10 SIFE; 9 FIFE). Nutrition assessments and laboratory studies were serially obtained for the duration of PN support or until 6 months’ corrected gestational age. Neurodevelopmental outcomes were assessed at 6 and 24 months’ corrected age. Results. There were no differences between groups in demographic characteristics, with an overall median age of 2 days, gestational age of 36 weeks, and birth weight of 2410 g. There were no differences between groups in baseline laboratory values other than alkaline phosphatase (lower in the FIFE group) or in the duration of parenteral nutrition (PN), amount of enteral intake, or the number of operative procedures. The incidence of cholestasis among enrolled patients was significantly lower than expected, resulting in early study termination and an inability to assess for differences in the incidence of cholestasis. The FIFE was associated with no increased risk of growth impairment, coagulopathy, infectious complications, hypertriglyceridemia, or adverse neurodevelopmental outcomes. No patient developed essential fatty acid deficiency. Conclusion. The FIFE at 1 g/kg/d was well tolerated in the neonates recruited for this study. Given the necessary early termination of this study, a follow-up trial with revised eligibility criteria is necessary to determine whether the provision of FIFE decreases the incidence of PN-cholestasis compared with the traditional SIFE.
Abstract
Background
Virus infections result in a range of clinical outcomes for the host, from asymptomatic to severe or even lethal disease. Despite global efforts to prevent and treat virus ...infections to limit morbidity and mortality, the continued emergence and re-emergence of new outbreaks as well as common infections such as influenza persist as a health threat. Challenges to the prevention of severe disease after virus infection include both a paucity of protective vaccines as well as the early identification of individuals with the highest risk that may require supportive treatment.
Methods
We completed a screen of mice from the Collaborative Cross (CC) that we infected with influenza, severe acute respiratory syndrome-coronavirus, and West Nile virus.
Results
The CC mice exhibited a range of disease manifestations upon infections, and we used this natural variation to identify strains with mortality after infection and strains exhibiting no mortality. We then used comprehensive preinfection immunophenotyping to identify global baseline immune correlates of protection from mortality to virus infection.
Conclusions
These data suggest that immune phenotypes might be leveraged to identify humans at highest risk of adverse clinical outcomes upon infection, who may most benefit from intensive clinical interventions, in addition to providing insight for rational vaccine design.
We used a screen of genetically diverse mice from the Collaborative Cross infected with RNA viruses in combination with comprehensive preinfection immunophenotyping to identify baseline immune correlates of protection from mortality to virus infection.
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