Functional and Evolutionary Characterization of the CONSTANS Gene Family in Short-Day Photoperiodic Flowering in Soybean

CONSTANS (CO) plays a central role in photoperiodic flowering control of plants. However, much remains unknown about the function of the CO gene family in soybean and the molecular mechanisms underlying short-day photoperiodic flowering of soybean. We identified 26 CO homologs (GmCOLs) in the soybean genome, many of them previously unreported. Phylogenic analysis classified GmCOLs into three clades conserved among flowering plants. Two homeologous pairs in Clade I, GmCOL1a/GmCOL1b and GmCOL2a/GmCOL2b, showed the highest sequence similarity to Arabidopsis CO. The mRNA abundance of GmCOL1a and GmCOL1b exhibited a strong diurnal rhythm under flowering-inductive short days and peaked at dawn, which coincided with the rise of GmFT5a expression. In contrast, the mRNA abundance of GmCOL2a and GmCOL2b was extremely low. Our transgenic study demonstrated that GmCOL1a, GmCOL1b, GmCOL2a and GmCOL2b fully complemented the late flowering effect of the co-1 mutant in Arabidopsis. Together, these results indicate that GmCOL1a and GmCOL1b are potential inducers of flowering in soybean. Our data also indicate rapid regulatory divergence between GmCOL1a/GmCOL1b and GmCOL2a/GmCOL2b but conservation of their protein function. Dynamic evolution of GmCOL regulatory mechanisms may underlie the evolution of photoperiodic signaling in soybean.     

Finding Near-Optimal Groups of Epidemic Spreaders in a Complex Network

In this paper, we present algorithms to find near-optimal sets of epidemic spreaders in complex networks. We extend the notion of local-centrality, a centrality measure previously shown to correspond with a node''s ability to spread an epidemic, to sets of nodes by introducing combinatorial local centrality. Though we prove that finding a set of nodes that maximizes this new measure is NP-hard, good approximations are available. We show that a strictly greedy approach obtains the best approximation ratio unless P = NP and then formulate a modified version of this approach that leverages qualities of the network to achieve a faster runtime while maintaining this theoretical guarantee. We perform an experimental evaluation on samples from several different network structures which demonstrate that our algorithm maximizes combinatorial local centrality and consistently chooses the most effective set of nodes to spread infection under the SIR model, relative to selecting the top nodes using many common centrality measures. We also demonstrate that the optimized algorithm we develop scales effectively.     

Accuracy of StepWatch? and ActiGraph Accelerometers for Measuring Steps Taken among Persons with Multiple Sclerosis

Introduction

There has been increased interest in the objective monitoring of free-living walking behavior using accelerometers in clinical research involving persons with multiple sclerosis (MS). The current investigation examined and compared the accuracy of the StepWatch activity monitor and ActiGraph model GT3X+ accelerometer for capturing steps taken during various speeds of prolonged, over-ground ambulation in persons with MS who had mild, moderate, and severe disability.

Methods

Sixty-three persons with MS underwent a neurological examination for generation of an EDSS score and undertook two trials of walking on the GAITRite electronic walkway. Participants were fitted with accelerometers, and undertook three modified six-minute walk (6MW) tests that were interspersed with 10–15 minutes of rest. The first 6MW was undertaken at a comfortable walking speed (CWS), and the two remaining 6MW tests were undertaken above (faster walking speed; FWS) or below (slower walking speed; SWS) the participant''s CWS. The actual number of steps taken was counted through direct observation using hand-tally counters.

Results

The StepWatch activity monitor (99.8%–99.9%) and ActiGraph model GT3X+ accelerometer (95.6%–97.4%) both demonstrated highly accurate measurement of steps taken under CWS and FWS conditions. The StepWatch had better accuracy (99.0%) than the ActiGraph (95.5%) in the overall sample under the SWS condition, and this was particularly apparent in those with severe disability (StepWatch: 95.7%; ActiGraph: 87.3%). The inaccuracy in measurement for the ActiGraph was associated with alterations of gait (e.g., slower gait velocity, shorter step length, wider base of support).

Conclusions

This research will help inform the choice of accelerometer to be adopted in clinical trials of MS wherein the monitoring of free-living walking behavior is of particular value.     

Genetic Deletion of Mst1 Alters T Cell Function and Protects against Autoimmunity

Mammalian sterile 20-like kinase 1 (Mst1) is a MAPK kinase kinase kinase which is involved in a wide range of cellular responses, including apoptosis, lymphocyte adhesion and trafficking. The contribution of Mst1 to Ag-specific immune responses and autoimmunity has not been well defined. In this study, we provide evidence for the essential role of Mst1 in T cell differentiation and autoimmunity, using both genetic and pharmacologic approaches. Absence of Mst1 in mice reduced T cell proliferation and IL-2 production in vitro, blocked cell cycle progression, and elevated activation-induced cell death in Th1 cells. Mst1 deficiency led to a CD4⁺ T cell development path that was biased toward Th2 and immunoregulatory cytokine production with suppressed Th1 responses. In addition, Mst1^−/− B cells showed decreased stimulation to B cell mitogens in vitro and deficient Ag-specific Ig production in vivo. Consistent with altered lymphocyte function, deletion of Mst1 reduced the severity of experimental autoimmune encephalomyelitis (EAE) and protected against collagen-induced arthritis development. Mst1^−/− CD4⁺ T cells displayed an intrinsic defect in their ability to respond to encephalitogenic antigens and deletion of Mst1 in the CD4⁺ T cell compartment was sufficient to alleviate CNS inflammation during EAE. These findings have prompted the discovery of novel compounds that are potent inhibitors of Mst1 and exhibit desirable pharmacokinetic properties. In conclusion, this report implicates Mst1 as a critical regulator of adaptive immune responses, Th1/Th2-dependent cytokine production, and as a potential therapeutic target for immune disorders.     

Cost Effectiveness of Seasonal Intermittent Preventive Treatment Using Amodiaquine & Artesunate or Sulphadoxine-Pyrimethamine in Ghanaian Children

Background

Intermittent preventive treatment for malaria in children (IPTc) involves the administration of a full course of an anti-malarial treatment to children under 5 years old at specified time points regardless of whether or not they are known to be infected, in areas where malaria transmission is seasonal. It is important to determine the costs associated with IPTc delivery via community based volunteers and also the potential savings to health care providers and caretakers due to malaria episodes averted as a consequence of IPTc.

Methods

Two thousand four hundred and fifty-one children aged 3–59 months were randomly allocated to four groups to receive: three days of artesunate plus amodiaquine (AS+AQ) monthly, three days of AS+AQ bimonthly, one dose of sulphadoxine-pyrimethamine (SP) bi-monthly or placebo. This paper focuses on incremental cost effectiveness ratios (ICERs) of the three IPTc drug regimens as delivered by community based volunteers (CBV) in Hohoe, Ghana compared to current practice, i.e. case management in the absence of IPTc. Financial and economic costs from the publicly funded health system perspective are presented. Treatment costs borne by patients and their caretakers are also estimated to present societal costs. The costs and effects of IPTc during the intervention period were considered with and without a one year follow up. Probabilistic sensitivity analysis was undertaken to account for uncertainty.

Results

Economic costs per child receiving at least the first dose of each course of IPTc show SP bimonthly, at US$8.19, is the cheapest to deliver, followed by AS+AQ bimonthly at US$10.67 and then by AS+AQ monthly at US$14.79. Training, drug delivery and supervision accounted for approximately 20–30% each of total unit costs. During the intervention period AS & AQ monthly was the most cost effective IPTc drug regimen at US$67.77 (61.71–74.75, CI 95%) per malaria case averted based on intervention costs only, US$64.93 (58.92–71.92, CI 95%) per malaria case averted once the provider cost savings are included and US$61.00 (54.98, 67.99, CI 95%) when direct household cost savings are also taken into account. SP bimonthly was US$105.35 (75.01–157.31, CI 95%) and AS & AQ bimonthly US$211.80 (127.05–399.14, CI 95%) per malaria case averted based on intervention costs only. The incidence of malaria in the post intervention period was higher in children who were <1 year old when they received AS+AQ monthly compared to the placebo group leading to higher cost effectiveness ratios when one year follow up is included. The cost per child enrolled fell considerably when modelled to district level as compared to those encountered under trial conditions.

Conclusions

We demonstrate how cost-effective IPTc is using three different drug regimens and the possibilities for reducing costs further if the intervention was to be scaled up to the district level. The need for effective training, drug delivery channels and supervision to support a strong network of community based volunteers is emphasised.     

How Does the Crayfish Swimmeret System Work? Insights from Nearest-Neighbor Coupled Oscillator Models

Rhythmic movements of crayfish swimmerets are coordinated by a neural circuit that links their four abdominal ganglia. Each swimmeret is driven by its own small local circuit, or pattern-generating module. We modeled this networkas a chain of four oscillators, bidirectionally coupled to their nearest neighbors, and tested the models ability to reproduce experimentally observed changes in intersegmental phases and in period caused by differential excitation of selected abdominal ganglia. The choices needed to match the experimental data lead to the followingpredictions: coupling between ganglia is asymmetric; the ascending and descending coupling have approximately equal strengths; intersegmental coupling does not significantly affect the frequency of the system; and excitation affects the intrinsic frequencies of the oscillators and might also change properties ofintersegmental coupling.     

Genome of porcine transmissible gastroenteritis virus.

The Purdue strain of transmissible gastroenteritis virus, a porcine coronavirus, was grown to titers of greater than 10(8) PFU/ml in a swine testicle cell line, and the RNA was isotopically labeled with [3H]uridine. The RNA was extracted from purified virus and was found to have the following properties. (i) It consisted primarily of a homogeneous large-molecular-weight species which electrophoretically migrated with an apparent molecular weight of 6.8 X 10(6) under denaturing conditions. (ii) It migrated electrophoretically at the same rate on nondenaturing gels before and after heat denaturation, suggesting that it does not consist of subunits. (iii) It was susceptible to pancreatic RNase A digestion in high (0.3 M) NaCl. (iv) It was polyadenylated to the extent that greater than 60% of the native RNA bound to oligodeoxythymidilic acid-cellulose under conditions of high (0.5 M) NaCl. RNA extracted from virions was infectious. This coronavirus can therefore be characterized as a positive-strand RNA virus.     

Pyrenocine C,A phytotoxin-related metabolite produced by onion pink root fungus,Pyrenochaeta terrestris

The structure of pyrenocine C, a new metabolite isolated from onion pink root fungus, Pyrenochaeta terrestris (Hansen) has been elucidated as (±)-(2′E)-5-(1′-hydroxybut-2′-enyl)-4-methoxy-6-methyl-2-pyrone by spectroscopic methods and chemical correlation with pyrenocine A.     

Disruption of the mu-delta opioid receptor heteromer

The crystal structure of the mu and kappa opioid receptors has revealed dimeric structural arrangements. Mu-delta receptors heteromers also exist and we have identified discrete cytoplasmic regions in each receptor required for oligomer formation. In the carboxyl tail of the delta receptor we identified three glycine residues (-GGG), substitution of any of these residues prevented heteromer formation. In intracellular loop 3 of both mu and delta receptors we identified three residues (-SVR), substitution of any of these residues prevented heteromer formation.