Tweeting with Authority: Identifying Influential Participants in Agriculture-Related Water Quality Twitter Conversations

In August 2014, Toledo, Ohio, experienced a dangerous algae bloom that led to a citywide water ban. News media coverage of the incident was widespread, as was social media conversation. Opinion leadership has been linked to news media agenda setting, and social media users are capable of generating considerable social influence within the sphere of their social networks. To better understand the dynamics of the conversation—especially as it pertained to agriculture—both during and after the water ban, the researchers used a social media analysis platform to identify high-influence Twitter users who participated in water-quality discussions about the Toledo water ban. Narrowing the search to agriculture-related discussion, the researchers revealed a dearth of agriculture-related content and also identified three categories of Twitter users in the conversation, including news sources, activists, and agriculture advocates. The researchers also found that Ohio users in post-ban discussions tended to be more influential than those who participated during the water ban. Identifying these users allows practitioners to monitor influential accounts for emerging issues and to engage with authoritative users in their geographic regions. The researchers also recommend that agriculture advocates exercise restraint in publicly speaking out about the industry’s involvement in environmental issues

Bactericidal activity of extended 9-glycyl-amido-minocyclines

The need for self-protecting polymer or alloy implants resistant to a broad spectrum of bacterial challenges led us to investigate covalent bonding of minocycline (MIN), a tetracycline derivative, to polystyrene beads and to titanium alloy foils by oligoethylene glycol spacers. 9-Hydrazino-acetyl-amido-MIN, and simpler glycylcycline derivatives, retained minimum inhibitory concentration (MIC) against Staphylococcus aureus comparable to MIN. However, PEG-glycyl-amido-MIN showed very low activity. Hence, we coupled 9-hydrazino-acetyl-amido-MIN to the aldehyde termini of oligoethylene glycol spacers bonded to polystyrene and titanium alloy surfaces to form acid-releasable hydrazone linkages. 9-Hydrazino-acetyl-amido-MIN was released from the monolayers more rapidly at pH 5.0 than at pH 7.4

Where I Come From: Exploring Regional Differences in California Consumers’ Attitudes and Beliefs About Fluid Milk

Guided by the theory of reasoned action and social cognitive theory, this study was conducted to better understand how decisions to purchase organic or conventional milk are influenced by norms and attitudes established via human interactions and how those norms and attitudes vary by geographic region. An online Qualtrics survey was used to gain insight into behaviors, attitudes, and interactions of 308 milk consumers in various geographical regions of [State]. The findings indicate that urban, suburban, and rural consumers differ in some ways in their interactions related to milk information, as well as their perceptions of organic versus conventional milk. Based on the findings of the study, differences in personal networks and exposure to certain messaging in varying regions might perpetuate a more positive, confident, and informed view of organic or conventional milk products in some areas more so than others. The researchers recommend using the results of the study to tailor messages to the specific information needs of consumers in urban, suburban, and rural regions of [State]

Molecular rulers for measuring RNA structure: sites of crosslinking in chlorambucilyl-phenylalanyl-tRNA^(Phe) (yeast) and chlorambucilyl-pentadecaprolyl-phenylalanyl-tRNA^(Phe) (yeast) intramolecularly crosslinked in aqueous solution

Intramolecular crosslinking of yeast phenylalanine tRNA in aqueous solution with rigid, variable-length crosslinking reagents, which we call "molecular rulers," has given results in reasonable agreement with the crystal structure. Chlorambucilyl-[^(3)H]phenylalanyl-tRNA^(Phe) crosslinked intramolecularly at G-71 and A-73, whereas chlorambucilyl-pentadecaprolyl-[^(3)H]phenylalanyl-tRNA^(Phe) crosslinked at G-20 and Y-37. The pentadecaprolyl reagent was predicted to be 62 Å long, including chlorambucil and phenylalanine; the sites that it reached are 60 Å distant from the 3' OH (in the case of G-20) or 80 Å distant (in the case of Y-37) in the crystal structure of tRNA^(Phe). The close agreement between the length of the reagent and the distance of G-20 from the 3' OH in the crystal structure illustrates the rigidity of the tRNA^(Phe) molecule in the dihydrouridine loop region at the corner of the molecule. The apparent ability of the 62-Å-long reagent to crosslink to a site, Y-37, that is 80 Å distant from the 3' OH in the crystal structure appears to illustrate the flexibility of both the 3' A-C-C-A terminus and the anticodon stem and loop, with respect to the tRNA molecule. These observations demonstrate the utility of oligoproline-based crosslinking reagents as rigid, variable-length molecular rulers for biological macromolecules in solution

Characterising seizures in anti-NMDA-receptor encephalitis with dynamic causal modelling

We characterised the pathophysiology of seizure onset in terms of slow fluctuations in synaptic efficacy using EEG in patients with anti-N-methyl-d-aspartate receptor (NMDA-R) encephalitis. EEG recordings were obtained from two female patients with anti-NMDA-R encephalitis with recurrent partial seizures (ages 19 and 31). Focal electrographic seizure activity was localised using an empirical Bayes beamformer. The spectral density of reconstructed source activity was then characterised with dynamic causal modelling (DCM). Eight models were compared for each patient, to evaluate the relative contribution of changes in intrinsic (excitatory and inhibitory) connectivity and endogenous afferent input. Bayesian model comparison established a role for changes in both excitatory and inhibitory connectivity during seizure activity (in addition to changes in the exogenous input). Seizures in both patients were associated with a sequence of changes in inhibitory and excitatory connectivity; a transient increase in inhibitory connectivity followed by a transient increase in excitatory connectivity and a final peak of excitatory-inhibitory balance at seizure offset. These systematic fluctuations in excitatory and inhibitory gain may be characteristic of (anti NMDA-R encephalitis) seizures. We present these results as a case study and replication to motivate analyses of larger patient cohorts, to see whether our findings generalise and further characterise the mechanisms of seizure activity in anti-NMDA-R encephalitis

Antisense inhibition of cyclin D1 expression is equivalent to flavopiridol for radiosensitization of zebrafish embryos

Purpose: Flavopiridol, a small molecule pan-cyclin inhibitor, has been shown to enhance the radiation response of tumor cells both in vitro and in vivo. The clinical utility of flavopiridol, however, is limited by toxicity, previously attributed to pleiotropic inhibitory effects on several targets affecting multiple signal transduction pathways. Here we utilized zebrafish embryos to investigate radiosensitizing effects of flavopiridol in normal tissues. Methods and Materials: Zebrafish embryos at the 1-4 cell stage were treated with 500 nM flavopiridol or injected with 0.5 pmol antisense hydroxylprolyl-phosphono nucleic acid oligomers to reduce cyclin D1 expression, then subjected to ionizing radiation (IR) or no radiation. Results: Flavopiridol-treated embryos demonstrated a 2-fold increase in mortality following exposure to 40 Gy by 96 hours post fertilization (hpf) and developed distinct radiation-induced defects in midline development (curly-up phenotype) at higher rates when compared to embryos receiving IR only. Cyclin D1-deficient embryos had virtually identical IR sensitivity profiles when compared to embryos treated with flavopiridol. This was particularly evident for the IR-induced curly-up phenotype, which was greatly exacerbated by both flavopriridol and cyclin D1 downregulation. Conclusions: Treatment of zebrafish embryos with flavopiridol enhanced radiation sensitivity of zebrafish embryos to a degree that was very similar to that associated with downregulation of cyclin D1 expression. These results are consistent with the hypothesis that inhibition of cyclin D1 is sufficient to account for the radiosensitizing action of flavopiridol in the zebrafish embryo vertebrate model

Toe Pressure and Toe Brachial Index are Predictive of Cardiovascular Mortality, Overall Mortality, and Amputation Free Survival in Patients with Peripheral Artery Disease

Objective/Background: Peripheral haemodynamic parameters are used to assess the presence and severity of peripheral artery disease (PAD). The prognostic value of ankle brachial index (ABI) has been thoroughly delineated. Nonetheless, the relative usefulness of ankle pressure (AP), ABI, toe pressure (TP), and toe brachial index (TBI) in assessing patient outcome has not been investigated in a concurrent study setting. This study aimed to resolve the association of all four non-invasive haemodynamic parameters in clinically symptomatic patients with PAD with cardiovascular mortality, overall mortality, and amputation free survival (AFS). Methods: In total, 732 symptomatic patients with PAD admitted to the Department of Vascular Surgery for conventional angiography at Turku University Hospital, Turku, Finland, between January 2009 and August 2011 were reviewed retrospectively. Demographic factors, cardiovascular mortality, all-cause mortality, and above foot level amputations were obtained and assessed in relation to AP, ABI, TP, and TBI by means of Kaplan-Meier life tables and a multivariate Cox regression model. Results: The haemodynamic parameter that was associated with poor 36 month general outcome was TP <30 mmHg. Univariate Cox regression analysis of stratified values showed that TP and TBI associated significantly with mortality. In multivariate analysis both TP and TBI were associated with a significant risk of death. For TP <30 mmHg and TBI <0.25 the risk of cardiovascular mortality was hazard ratio [HR] 2.84, 95% confidence interval [CI] 1.75-4.61 [p Conclusion: Among non-invasive haemodynamic measurements and pressure indices both TP and TBI appear to be associated with cardiovascular and overall mortality and AFS for patients with PAD presenting symptoms of the disease. (C) 2017 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.Peer reviewe

Stencil Printing-A Novel Manufacturing Platform for Orodispersible Discs

Stencil printing is a commonly used printing method, but it has not previously been used for production of pharmaceuticals. The aim of this study was to explore whether stencil printing of drug containing polymer inks could be used to manufacture flexible dosage forms with acceptable mass and content uniformity. Formulation development was supported by physicochemical characterization of the inks and final dosage forms. The printing of haloperidol (HAL) discs was performed using a prototype stencil printer. Ink development comprised of investigations of ink rheology in combination with printability assessment. The results show that stencil printing can be used to manufacture HAL doses in the therapeutic treatment range for 6-17 year-old children. The therapeutic HAL dose was achieved for the discs consisting of 16% of hydroxypropyl methylcellulose (HPMC) and 1% of lactic acid (LA). The formulation pH remained above pH 4 and the results imply that the drug was amorphous. Linear dose escalation was achieved by an increase in aperture area of the print pattern, while keeping the stencil thickness fixed. Disintegration times of the orodispersible discs printed with 250 and 500 mu m thick stencils were below 30 s. In conclusion, stencil printing shows potential as a manufacturing method of pharmaceuticals

Coordinate control of cell cycle regulatory genes in zebrafish development tested by cyclin D1 knockdown with morpholino phosphorodiamidates and hydroxyprolyl-phosphono peptide nucleic acids

During early zebrafish (Danio rerio) development zygotic transcription does not begin until the mid-blastula transition (MBT) ∼3 h after fertilization. MBT demarcates transition from synchronous short cell cycles of S and M phases exclusively to full cycles encompassing G(1) and G(2) phases. Transcriptional profiling and RT–PCR analyses during these phases enabled us to determine that this shift corresponds to decreased transcript levels of S/M phase cell cycle control genes (e.g. ccna2, ccnb1, ccnb2 and ccne) and increased transcript levels of ccnd1, encoding cyclin D1, and orthologs of p21 (p21-like) and retinoblastoma (Rb-like 1). To investigate the regulation of this process further, the translation of ccnd1 mRNA, a G(1)/S checkpoint control element, was impaired by microinjection of ccnd1-specific morpholino phosphorodiamidate (MO) 20mer or hydroxyprolyl-phosphono peptide nucleic acid (HypNA-pPNA) 16mer antisense oligonucleotides. The resulting downregulation of cyclin D1 protein resulted in microophthalmia and microcephaly, but not lethality. The phenotypes were not seen with 3-mismatch MO 20mers or 1-mismatch HypNA-pPNA 16mers, and were rescued by an exogenous ccnd1 mRNA construct with five mismatches. Collectively, these results indicate that transcription of key molecular determinants of asynchronous cell cycle control in zebrafish embryos commences at MBT and that the reduction of cyclin D1 expression compromises zebrafish eye and head development

In vitro prediction of polycyclic aromatic hydrocarbon bioavailability of 14 different incidentally ingested soils in juvenile swine

Predicting mammalian bioavailability of PAH mixtures from in vitro bioaccessibility results has proven to be an elusive goal. In an attempt to improve in vitro predictions of PAH soil bioavailability we investigated how energetic input influences PAH bioaccessibility by using a high and low energetic shaking method. Co-inertia analysis (COIA), and Structural Equation Modeling (SEM) were also used to examine PAH-PAH interactions during ingestion. PAH bioaccessibility was determined from 14 historically contaminated soils using the fed organic estimation of the human simulation test (FOREhST) with inclusion of a silicone rod as a sorption sink and compared to bioavailability estimates from the juvenile swine model. Shaking method significantly affected PAH bioaccessibility in the FOREhST model, with PAH desorption from the high energy FOREhST almost an order of magnitude greater compared to the low energy FOREhST. PAH-PAH interactions significantly influenced PAH bioavailability and when these interactions were used in a linear model, the model predicted benzo(a)anthracene bioavailability with an slope of 1 and r2 of 0.66 and for benzo(a)pyrene bioavailability has a slope of 1 and r2 of 0.65. Lastly, to confirm the effects as determined by COIA and SEM, we spiked low levels of benzo(a)anthracene into historically contaminated soils, and observed a significant increase in benzo(a)pyrene bioaccessibility. By accounting for PAH interactions, and reducing the energetics of in vitro extractions, we were able to use bioaccessibility to predict bioavailability across 14 historically contaminated soils. Our work suggests that future work on PAH bioavailability and bioaccessibility should focus on the dynamics of how the matrix of PAHs present in the soil interact with mammalian systems. Such interactions should not only include the chemical interactions discussed here but also the interactions of PAH mixtures with mammalian uptake systems