Increasing phosphorus supply is not the mechanism by which arbuscular mycorrhiza increase attractiveness of bean (Vicia faba) to aphids

Peer reviewedPublisher PD

Cryptocephal, the Drosophila melanogaster ATF4, Is a Specific Coactivator for Ecdysone Receptor Isoform B2

We thank Yoonseung Park (Kansas State University) and Michael Adams (UC Riverside) for the ETH-GeneSwitch line, and David Durica, Lauren Evans, and Dahong Chen (University of Oklahoma) and Nancy Thompson (Indiana University) for technical assistance.Author Summary Nuclear receptors are proteins that regulate gene expression in response to steroid and thyroid hormones and other small lipid-soluble signaling molecules. In many cases, nuclear receptor genes encode multiple variants (isoforms) that direct tissue- and stage-specific hormonal responses. The sequence differences among isoforms are often found at the protein N-terminus, which mediates hormone-independent interactions with unknown regulatory partners to control target gene expression. Here, we show that the fruit fly Cryptocephal (CRC) protein is a specific coactivator for one of three isoforms of the receptor for the insect molting steroid, ecdysone. Our findings reveal a mechanism for differential activation of gene expression in response to ecdysone during insect molting and metamorphosis, and contribute to our understanding of isoform-specific functions of nuclear hormone receptors.Yeshttp://www.plosgenetics.org/static/editorial#pee

Modeling the System Parameters of 2M1533+3759: A New Longer-Period Low-Mass Eclipsing sdB+dM Binary

We present new photometric and spectroscopic observations for 2M 1533+3759 (= NSVS 07826147). It has an orbital period of 0.16177042 day, significantly longer than the 2.3--3.0 hour periods of the other known eclipsing sdB+dM systems. Spectroscopic analysis of the hot primary yields Teff = 29230 +/- 125 K, log g = 5.58 +/- 0.03 and log N(He)/N(H) = -2.37 +/- 0.05. The sdB velocity amplitude is K1 = 71.1 +/- 1.0 km/s. The only detectable light contribution from the secondary is due to the surprisingly strong reflection effect. Light curve modeling produced several solutions corresponding to different values of the system mass ratio, q(M2/M1), but only one is consistent with a core helium burning star, q=0.301. The orbital inclination is 86.6 degree. The sdB primary mass is M1 = 0.376 +/- 0.055 Msun and its radius is R1 = 0.166 +/- 0.007 Rsun. 2M1533+3759 joins PG0911+456 (and possibly also HS2333+3927) in having an unusually low mass for an sdB star. SdB stars with masses significantly lower than the canonical value of 0.48 Msun, down to as low as 0.30 Msun, were theoretically predicted by Han et al. (2002, 2003), but observational evidence has only recently begun to confirm the existence of such stars. The existence of core helium burning stars with masses lower than 0.40--0.43 Msun implies that at least some sdB progenitors have initial main sequence masses of 1.8--2.0 Msun or more, i.e. they are at least main sequence A stars. The secondary is a main sequence M5 star.Comment: 47 pages, 7 figure

A Crucial Role for Kupffer Cell-Derived Galectin-9 in Regulation of T Cell Immunity in Hepatitis C Infection

Approximately 200 million people throughout the world are infected with hepatitis C virus (HCV). One of the most striking features of HCV infection is its high propensity to establish persistence (∼70–80%) and progressive liver injury. Galectins are evolutionarily conserved glycan-binding proteins with diverse roles in innate and adaptive immune responses. Here, we demonstrate that galectin-9, the natural ligand for the T cell immunoglobulin domain and mucin domain protein 3 (Tim-3), circulates at very high levels in the serum and its hepatic expression (particularly on Kupffer cells) is significantly increased in patients with chronic HCV as compared to normal controls. Galectin-9 production from monocytes and macrophages is induced by IFN-γ, which has been shown to be elevated in chronic HCV infection. In turn, galectin-9 induces pro-inflammatory cytokines in liver-derived and peripheral mononuclear cells; galectin-9 also induces anti-inflammatory cytokines from peripheral but not hepatic mononuclear cells. Galectin-9 results in expansion of CD4+CD25+FoxP3+CD127low regulatory T cells, contraction of CD4+ effector T cells, and apoptosis of HCV-specific CTLs. In conclusion, galectin-9 production by Kupffer cells links the innate and adaptive immune response, providing a potential novel immunotherapeutic target in this common viral infection

Rabies in Endangered Ethiopian Wolves

With rabies emerging as a particular threat to wild canids, we report on a rabies outbreak in a subpopulation of endangered Ethiopian wolves in the Bale Mountains, Ethiopia, in 2003 and 2004. Parenteral vaccination of wolves was used to manage the outbreak

Functional drug screening reveals anticonvulsants as enhancers of mTOR-independent autophagic killing of Mycobacterium tuberculosis through inositol depletion.

Mycobacterium tuberculosis (MTB) remains a major challenge to global health made worse by the spread of multidrug resistance. We therefore examined whether stimulating intracellular killing of mycobacteria through pharmacological enhancement of macroautophagy might provide a novel therapeutic strategy. Despite the resistance of MTB to killing by basal autophagy, cell-based screening of FDA-approved drugs revealed two anticonvulsants, carbamazepine and valproic acid, that were able to stimulate autophagic killing of intracellular M. tuberculosis within primary human macrophages at concentrations achievable in humans. Using a zebrafish model, we show that carbamazepine can stimulate autophagy in vivo and enhance clearance of M. marinum, while in mice infected with a highly virulent multidrug-resistant MTB strain, carbamazepine treatment reduced bacterial burden, improved lung pathology and stimulated adaptive immunity. We show that carbamazepine induces antimicrobial autophagy through a novel, evolutionarily conserved, mTOR-independent pathway controlled by cellular depletion of myo-inositol. While strain-specific differences in susceptibility to in vivo carbamazepine treatment may exist, autophagy enhancement by repurposed drugs provides an easily implementable potential therapy for the treatment of multidrug-resistant mycobacterial infection

Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer's disease

Neurofilament light chain (NfL) is a promising fluid biomarker of disease progression for various cerebral proteopathies. Here we leverage the unique characteristics of the Dominantly Inherited Alzheimer Network and ultrasensitive immunoassay technology to demonstrate that NfL levels in the cerebrospinal fluid (n = 187) and serum (n = 405) are correlated with one another and are elevated at the presymptomatic stages of familial Alzheimer's disease. Longitudinal, within-person analysis of serum NfL dynamics (n = 196) confirmed this elevation and further revealed that the rate of change of serum NfL could discriminate mutation carriers from non-mutation carriers almost a decade earlier than cross-sectional absolute NfL levels (that is, 16.2 versus 6.8 years before the estimated symptom onset). Serum NfL rate of change peaked in participants converting from the presymptomatic to the symptomatic stage and was associated with cortical thinning assessed by magnetic resonance imaging, but less so with amyloid-β deposition or glucose metabolism (assessed by positron emission tomography). Serum NfL was predictive for both the rate of cortical thinning and cognitive changes assessed by the Mini-Mental State Examination and Logical Memory test. Thus, NfL dynamics in serum predict disease progression and brain neurodegeneration at the early presymptomatic stages of familial Alzheimer's disease, which supports its potential utility as a clinically useful biomarker

Bureaucracy as a Lens for Analyzing and Designing Algorithmic Systems

Scholarship on algorithms has drawn on the analogy between algorithmic systems and bureaucracies to diagnose shortcomings in algorithmic decision-making. We extend the analogy further by drawing on Michel Crozier’s theory of bureaucratic organizations to analyze the relationship between algorithmic and human decision-making power. We present algorithms as analogous to impartial bureaucratic rules for controlling action, and argue that discretionary decision-making power in algorithmic systems accumulates at locations where uncertainty about the operation of algorithms persists. This key point of our essay connects with Alkhatib and Bernstein’s theory of ’street-level algorithms’, and highlights that the role of human discretion in algorithmic systems is to accommodate uncertain situations which inflexible algorithms cannot handle. We conclude by discussing how the analysis and design of algorithmic systems could seek to identify and cultivate important sources of uncertainty, to enable the human discretionary work that enhances systemic resilience in the face of algorithmic errors.Peer reviewe

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy