Circadian signaling in Homarus americanus: Region-specific de novo assembled transcriptomes show that both the brain and eyestalk ganglia possess the molecular components of a putative clock system

Essentially all organisms exhibit recurring patterns of physiology/behavior that oscillate with a period of ~24-h and are synchronized to the solar day. Crustaceans are no exception, with robust circadian rhythms having been documented in many members of this arthropod subphylum. However, little is known about the molecular underpinnings of their circadian rhythmicity. Moreover, the location of the crustacean central clock has not been firmly established, although both the brain and eyestalk ganglia have been hypothesized as loci. The American lobster, Homarus americanus, is known to exhibit multiple circadian rhythms, and immunodetection data suggest that its central clock is located within the eyestalk ganglia rather than in the brain. Here, brain- and eyestalk ganglia-specific transcriptomes were generated and used to assess the presence/absence of transcripts encoding the commonly recognized protein components of arthropod circadian signaling systems in these two regions of the lobster central nervous system. Transcripts encoding putative homologs of the core clock proteins clock, cryptochrome 2, cycle, period and timeless were found in both the brain and eyestalk ganglia assemblies, as were transcripts encoding similar complements of putative clock-associated, clock input pathway and clock output pathway proteins. The presence and identity of transcripts encoding core clock proteins in both regions were confirmed using PCR. These findings suggest that both the brain and eyestalk ganglia possess all of the molecular components needed for the establishment of a circadian signaling system. Whether the brain and eyestalk clocks are independent of one another or represent a single timekeeping system remains to be determined. Interestingly, while most of the proteins deduced from the identified transcripts are shared by both the brain and eyestalk ganglia, assembly-specific isoforms were also identified, e.g., several period variants, suggesting the possibility of region-specific variation in clock function, especially if the brain and eyestalk clocks represent independent oscillators

Possible detection of two giant extrasolar planets orbiting the eclipsing polar UZ Fornacis

We present new high-speed, multi-observatory, multi-instrument photometry of the eclipsing polar UZ For in order to measure precise mid-eclipse times with the aim of detecting any orbital period variations. When combined with published eclipse times and archival data spanning ~27 years, we detect departures from a linear and quadratic trend of ~60 s. The departures are strongly suggestive of two cyclic variations of 16(3) and 5.25(25) years. The two favoured mechanisms to drive the periodicities are either two giant extrasolar planets as companions to the binary (with minimum masses of 6.3(1.5)M(Jupiter) and 7.7(1.2)M(Jupiter)) or a magnetic cycle mechanism (e.g. Applegate's mechanism) of the secondary star. Applegate's mechanism would require the entire radiant energy output of the secondary and would therefore seem to be the least likely of the two, barring any further refinements in the effect of magnetic fieilds (e.g. those of Lanza et al.). The two planet model can provide realistic solutions but it does not quite capture all of the eclipse times measurements. A highly eccentric orbit for the outer planet would fit the data nicely, but we find that such a solution would be unstable. It is also possible that the periodicities are driven by some combination of both mechanisms. Further observations of this system are encouraged.Comment: 10 pages, 4 figures, 2 table

Ecology and diversity of culturable fungal species associated with soybean seedling diseases in the Midwestern United States

Aims: To isolate and characterize fungi associated with diseased soybean seedlings in Midwestern soybean production fields and to determine the influence of environmental and edaphic factors on their incidence. Methods and Results: Seedlings were collected from fields with seedling disease history in 2012 and 2013 for fungal isolation. Environmental and edaphic data associated with each field was collected. 3036 fungal isolates were obtained and assigned to 76 species. The most abundant genera recovered were Fusarium (73%) and Trichoderma (11.2%). Other genera included Mortierella, Clonostachys, Rhizoctonia, Alternaria, Mucor, Phoma, Macrophomina and Phomopsis. Most recovered species are known soybean pathogens. However, non-pathogenic organisms were also isolated. Crop history, soil density, water source, precipitation and temperature were the main factors influencing the abundance of fungal species. Conclusion: Key fungal species associated with soybean seedling diseases occurring in several US production regions were characterized. This work also identified major environment and edaphic factors affecting the abundance and occurrence of these species. Significance and Impact of the Study: The identification and characterization of the main pathogens associated with seedling diseases across major soybean-producing areas could help manage those pathogens, and devise more effective and sustainable practices to reduce the damage they cause

Development of a Protocol for Obtaining Biological Samples for Genetic Testing from Remote Individuals

Pharmacogenomic sequencing allows individuals to learn more about how they will respond to certain medications but requires shipping of a biological sample. One complication of sending biological samples to remote laboratories is stability. Blood generally yields sufficient quantities of high-quality DNA but requires a clinic visit. Saliva and buccal swabs are routinely used for DNA extractions, but the DNA quality is notoriously low due to the presence of bacteria in the mouth. Additionally, elderly individuals have difficulty producing enough saliva for testing, and the tubes contain several milliliters of liquid and shipping requires special considerations. Dried blood spot cards, which serve as an alternative to saliva and buccal swabs, yield high-quality DNA and ship easily, but may produce a lower yield. This project aims to determine which biological sample methods can reasonably be obtained from remote individuals

The Structure of the Accretion Disk in the ADC X-Ray Binary 4U 1822-371 at Optical and Ultraviolet Wavelengths

The eclipsing low-mass X-ray binary 4U 1822-371 is the prototypical accretion disk corona (ADC) system. We have obtained new time-resolved UV spectroscopy of 4U 1822-371 with the Advanced Camera for Surveys/Solar Blind Channel (ACS/SBC) on the Hubble Space Telescope (HST) and new V- and J-band photometry with the 1.3-m SMARTS telescope at CTIO. We use the new data to construct its UV/optical spectral energy distribution and its orbital light curve in the UV, V, and J bands. We derive an improved ephemeris for the optical eclipses and confirm that the orbital period is changing rapidly, indicating extremely high rates of mass flow in the system; and we show that the accretion disk in the system has a strong wind with projected velocities up to 4000 km/s. We show that the disk has a vertically-extended, optically-thick component at optical wavelengths.This component extends almost to the edge of the disk and has a height equal to ~0.5 of the disk radius. As it has a low brightness temperature, we identify it as the optically-thick base of a disk wind, not as the optical counterpart of the ADC. Like previous models of 4U 1822-371, ours needs a tall obscuring wall near the edge of the accretion disk, but we interpret the wall as a layer of cooler material at the base of the disk wind, not as a tall, luminous disk rim.Comment: 37 pages, 12 figures, submitted to Ap

Farnesoid X receptor and liver X receptor ligands initiate formation of coated platelets

The liver X receptors (LXRs) and farnesoid X receptor (FXR) have been identified in human platelets. Ligands of these receptors have been shown to have nongenomic inhibitory effects on platelet activation by platelet agonists. This, however, seems contradictory with the platelet hyper-reactivity that is associated with several pathological conditions that are associated with increased circulating levels of molecules that are LXR and FXR ligands, such as hyperlipidemia, type 2 diabetes mellitus, and obesity. We, therefore, investigated whether ligands for the LXR and FXR receptors were capable of priming platelets to the activated state without stimulation by platelet agonists. Treatment of platelets with ligands for LXR and FXR converted platelets to the procoagulant state, with increases in phosphatidylserine exposure, platelet swelling, reduced membrane integrity, depolarization of the mitochondrial membrane, and microparticle release observed. Additionally, platelets also displayed features associated with coated platelets such as P-selectin exposure, fibrinogen binding, fibrin generation that is supported by increased serine protease activity, and inhibition of integrin αIIbβ3. LXR and FXR ligand-induced formation of coated platelets was found to be dependent on both reactive oxygen species and intracellular calcium mobilization, and for FXR ligands, this process was found to be dependent on cyclophilin D. We conclude that treatment with LXR and FXR ligands initiates coated platelet formation, which is thought to support coagulation but results in desensitization to platelet stimuli through inhibition of αIIbβ3 consistent with their ability to inhibit platelet function and stable thrombus formation in vivo

Progression of atypical parkinsonian syndromes: PROSPECT-M-UK study implications for clinical trials

The advent of clinical trials of disease-modifying agents for neurodegenerative disease highlights the need for evidence-based endpoint selection. Here we report the longitudinal PROSPECT-M-UK study of progressive supranuclear palsy, corticobasal syndrome, multiple system atrophy and related disorders, to compare candidate clinical trial endpoints. In this multicentre United Kingdom study, participants were assessed with serial questionnaires, motor examination, neuropsychiatric and magnetic resonance imaging assessments at baseline, six and twelve-months. Participants were classified by diagnosis at baseline and study end, into Richardson syndrome, progressive supranuclear palsy-subcortical (progressive supranuclear palsy-parkinsonism and progressive gait freezing subtypes), progressive supranuclear palsy-cortical (progressive supranuclear palsy-frontal, progressive supranuclear palsy-speech-and-language, and progressive supranuclear palsy-corticobasal syndrome subtypes), multiple system atrophy-parkinsonism, multiple system atrophy-cerebellar, corticobasal syndrome with and without evidence of Alzheimer’s disease pathology and indeterminate syndromes. We calculated annual rate of change, with linear mixed modelling, and sample sizes for clinical trials of disease modifying agents, according to group and assessment type. Two hundred forty-three people were recruited (117 progressive supranuclear palsy, 68 corticobasal syndrome, 42 multiple system atrophy and 16 indeterminate; 138 [56.8%] male; age at recruitment 68.7 ± 8.61 years). One hundred fifty-nine completed six-month assessment (82 progressive supranuclear palsy, 27 corticobasal syndrome, 40 multiple system atrophy and 10 indeterminate) and 153 completed twelve-month assessment (80 progressive supranuclear palsy, 29 corticobasal syndrome, 35 multiple system atrophy and 9 indeterminate). Questionnaire, motor examination, neuropsychiatric and neuroimaging measures declined in all groups, with differences in longitudinal change between groups. Neuroimaging metrics would enable lower sample sizes to achieve equivalent power for clinical trials than cognitive and functional measures, often achieving N < 100 required for one-year two-arm trials (with 80% power to detect 50% slowing). However, optimal outcome measures were disease specific. In conclusion, phenotypic variance within progressive supranuclear palsy, corticobasal syndrome and multiple system atrophy is a major challenge to clinical trial design. Our findings provide an evidence base for selection of clinical trial endpoints, from potential functional, cognitive, clinical or neuroimaging measures of disease progression

Proceedings of the third international molecular pathological epidemiology (MPE) meeting

Molecular pathological epidemiology (MPE) is a transdisciplinary and relatively new scientific discipline that integrates theory, methods and resources from epidemiology, pathology, biostatistics, bioinformatics and computational biology. The underlying objective of MPE research is to better understand the etiology and progression of complex and heterogeneous human diseases with the goal of informing prevention and treatment efforts in population health and clinical medicine. Although MPE research has been commonly applied to investigating breast, lung, and colorectal cancers, its methodology can be used to study most diseases. Recent successes in MPE studies include: 1) the development of new statistical methods to address etiologic heterogeneity; 2) the enhancement of causal inference; 3) the identification of previously unknown exposure-subtype disease associations; and 4) better understanding of the role of lifestyle/behavioral factors on modifying prognosis according to disease subtype. Central challenges to MPE include the relative lack of transdisciplinary experts, educational programs, and forums to discuss issues related to the advancement of the field. To address these challenges, highlight recent successes in the field, and identify new opportunities, a series of MPE meetings have been held at the Dana-Farber Cancer Institute in Boston, MA. Herein, we share the proceedings of the Third International MPE Meeting, held in May 2016 and attended by 150 scientists from 17 countries. Special topics included integration of MPE with immunology and health disparity research. This meeting series will continue to provide an impetus to foster further transdisciplinary integration of divergent scientific fields

Characterization of biomolecular nanoconjugates by high-throughput delivery and spectroscopic difference

Nanoparticle conjugates have the potential for delivering siRNA, splice-shifting oligomers or nucleic acid vaccines, and can be applicable to anticancer therapeutics. This article compares tripartite conjugates with gold nanoparticles or synthetic methoxypoly(ethylene glycol)-block-polyamidoamine dendrimers