Elucidating the regulation of complex signalling systems in plant cells

The pollen tube represents a model system for the study of tip growth, and the root provides a valuable system to study gene and signalling networks in plants. In the present article, using the two systems as examples, we discuss how to elucidate the regulation of complex signalling systems in plant cells. First, we discuss how hormones and related genes in plant root development form a complex interacting network, and their activities are interdependent. Therefore their roles in root development must be analysed as an integrated system, and elucidation of the regulation of each component requires the adaptation of a novel modelling methodology: regulation analysis. Secondly, hydrodynamics, cell wall and ion dynamics are all important properties that regulate plant cell growth. We discuss how regulation analysis can be applied to study the regulation of hydrodynamics, cell wall and ion dynamics, using pollen tube growth as a model system. Finally, we discuss future prospects for elucidating the regulation of complex signalling systems in plant cells

The Effects of Regulations on Private School Choice Program Participation: Experimental Evidence from California and New York

Although private school voucher programs provide subsidies to students for tuition and other education-related costs, private school leaders weigh program participation against any associated regulatory costs. The higher the regulatory costs of participation, the less likely a private school is to participate in a school voucher program. Since we do not know with certainty which regulations will be viewed by school leaders as more or less costly, we explore whether specific regulations that are common to private school choice programs do or do not deter likely voucher program participation.We use surveys to randomly assign different regulations to 4,825 private school leaders in the states of California and New York and ask them whether or not they would participate in a new private school choice program during the following school year. Relative to no regulations, our most conservative models find that open-enrollment mandates reduce the likelihood that private school leaders are certain to participate in a hypothetical choice program by about 19 percentage points, or 60 percent. State standardized testing requirements reduce the likelihood that private school leaders are certain to participate by 9 percentage points, or 29 percent. We find no evidence to suggest that the prohibition of copayment or nationally norm-referenced testing requirements affect the overall willingness to participate in a school choice program

Troup Factory: Archaeological Investigations of a Nineteenth Century Mill Site in LaGrange, Georgia.

Troup Factory, the first cotton mill in Troup County, and the second such plant in Georgia, was established in 1846 on Flat Shoal\u27s Creek. The mill was in operation throughout the latter half of the 19th century before being relocated to the city of LaGrange. Troup Factory sheetings and homespun were standards of excellence across a widespread area of Georgia. The purpose of this paper is to document the history of the mill site through archival research and archaeological survey. Through these means a better understanding of a once prestigious mill site was obtained in order to illuminate an important period of Georgia history

Physiological and Perceived Effects of Forearm or Head Cooling During Simulated Firefighting Activity and Rehabilitation.

CONTEXT:  Cooling devices aim to protect firefighters by attenuating a rise in body temperature. Devices for head cooling (HC) while firefighting and forearm cooling (FC) during rehabilitation (RHB) intervals are commonly marketed, but research regarding their efficacy is limited. OBJECTIVE:  To investigate the physiological and perceived effects of HC and FC during firefighting drills and RHB. DESIGN:  Randomized controlled clinical trial. SETTING:  Firefighter training center. PATIENTS OR OTHER PARTICIPANTS:  Twenty-seven male career firefighters (age = 39 ± 7 years; height = 169 ± 7 cm; weight = 95.4 ± 16.8 kg). INTERVENTION(S):  Firefighters were randomly assigned to 1 condition: HC (n = 9), in which participants completed drills wearing a cold gel pack inside their helmet; FC (n = 8), in which participants sat on a collapsible chair with water-immersion arm troughs during RHB; or control (n = 10), in which participants used no cooling devices. Firefighters completed four 15-minute drills (D1-D4) wearing full bunker gear and breathing apparatus. Participants had a 15-min RHB after D2 (RHB1) and D4 (RHB2). MAIN OUTCOME MEASURE(S):  Change (Δ) in gastrointestinal temperature (T RESULTS:  The T CONCLUSIONS:  The HC did not attenuate rises in physiological or perceptual variables during firefighting drills. The FC effectively reduced

Multiannual observations and modelling of seasonal thermal profiles through supraglacial debris in the Central Himalaya

Many glaciers in the Central Himalaya are covered with rock debris that modifies the transfer of heat from the atmosphere to the underlying ice. These debris-covered glaciers are experiencing rapid mass loss at rates that have accelerated during the last two decades. Quantifying recent and future glacier mass change requires understanding the relationship between debris thickness and ablation particularly through the summer monsoon season. We present air, near-surface and debris temperatures measured during three monsoon seasons at five sites on Khumbu Glacier in Nepal, and compare these results to similar measurements from two other debris-covered glaciers in this region. Seasonal debris temperature profiles are approximately linear and consistent between sites for thick (>?0.5?m) and thin (<?0.5?m) debris across thicknesses ranging from 0.26 to 2.0?m. The similarities between these multiannual data imply that they are representative of supraglacial debris layers in the monsoon-influenced Himalaya more generally. We compare three methods to calculate sub-debris ablation, including using our temperature measurements with a thermal diffusion model that incorporates a simplified treatment of debris moisture. Estimated ablation between 3 June and 11 October at around 5000?m above sea level ranged from 0.10?m water equivalent beneath 1.5?m of debris to 0.47?m water equivalent beneath 0.3?m debris. However, these values are small when compared to remotely observed rates of surface lowering, suggesting that mass loss from these debris-covered glaciers is greatly enhanced by supraglacial and englacial processes that locally amplify ablationauthorsversionPeer reviewe

Cell-Penetrating Peptides as a Tool for the Cellular Uptake of a Genetically Modified Nitroreductase for use in Directed Enzyme Prodrug Therapy

Directed enzyme prodrug therapy (DEPT) involves the delivery of a prodrug-activating enzyme to a solid tumour site, followed by the subsequent activation of an administered prodrug. One of the most studied enzyme–prodrug combinations is the nitroreductase from Escherichia coli (NfnB) with the prodrug CB1954 [5-(aziridin-1-yl)-2,4-dinitro-benzamide]. One of the major issues faced by DEPT is the ability to successfully internalize the enzyme into the target cells. NfnB has previously been genetically modified to contain cysteine residues (NfnB-Cys) which bind to gold nanoparticles for a novel DEPT therapy called magnetic nanoparticle directed enzyme prodrug therapy (MNDEPT). One cellular internalisation method is the use of cell-penetrating peptides (CPPs), which aid cellular internalization of cargo. Here the cell-penetrating peptides: HR9 and Pep-1 were tested for their ability to conjugate with NfnB-Cys. The conjugates were further tested for their potential use in MNDEPT, as well as conjugating with the delivery vector intended for use in MNDEPT and tested for the vectors capability to penetrate into cells

Identification of the transcriptional response of human intestinal mucosa to Lactobacillus plantarum WCFS1 in vivo

Contains fulltext : 69887.pdf ( ) (Open Access)BACKGROUND: There is limited knowledge on the extent and dynamics of the mucosal response to commensal and probiotic species in the human intestinal lumen. This study aimed to identify the acute, time-dependent responses of intestinal mucosa to commensal Lactobacillus plantarum WCFS1 in vivo in two placebo-controlled human intervention studies in healthy volunteers. Transcriptional changes in duodenal mucosa upon continuous intraduodenal infusion of L. plantarum WCFS1 for one- and six h, respectively, were studied using oro- and nasogastric intubations with dedicated orogastric catheters and tissue sampling by standard flexible gastroduodenoscopy. RESULTS: One- and six-h exposure of small intestinal mucosa to L. plantarum WCFS1 induced differential expression of 669 and 424 gene reporters, respectively. While short-term exposure to L. plantarum WCFS1 inhibited fatty acid metabolism and cell cycle progression, cells switched to a more proliferative phase after prolonged exposure with an overall expression profile characterized by upregulation of genes involved in lipid metabolism, cellular growth and development. Cell death and immune responses were triggered, but cell death-executing genes or inflammatory signals were not expressed. Proteome analysis showed differential expression of several proteins. Only the microsomal protein 'microsomal triglyceride transfer protein' was regulated on both the transcriptional and the protein level in all subjects. CONCLUSION: Overall, this study showed that intestinal exposure to L. plantarum WCFS1 induced consistent, time-dependent transcriptional responses in healthy intestinal mucosa. This extensive exploration of the human response to L. plantarum WCFS1 could eventually provide molecular support for specific or probiotic activity of this strain or species, and exemplifies the strength of the applied technology to identify the potential bio-activity of microbes in the human intestine

Structure-guided evolution of antigenically distinct adeno-associated virus variants for immune evasion

Preexisting neutralizing antibodies (NAbs) against adeno-associated viruses (AAVs) pose a major, unresolved challenge that restricts patient enrollment in gene therapy clinical trials using recombinant AAV vectors. To tackle this problem, we developed a structure-guided approach to evolve AAV variants with altered antigenic footprints that cannot be recognized by preexisting antibodies. These proof-of-principle studies demonstrate that synthetic AAV variants can be evolved to evade neutralizing sera from different species—mice, nonhuman primates, and humans—without compromising yield and transduction efficiency or altering tropism. Our approach provides a roadmap for engineering any AAV strain to evade NAbs in prospective patients for human gene therapy

Seasonally stable temperature gradients through supraglacial debris in the Everest region of Nepal, Central Himalaya

Rock debris covers about 30% of glacier ablation areas in the Central Himalaya and modifies the impact of atmospheric conditions on mass balance. The thermal properties of supraglacial debris are diurnally variable but remain poorly constrained for monsoon-influenced glaciers over the timescale of the ablation season. We measured vertical debris profile temperatures at 12 sites on four glaciers in the Everest region with debris thickness ranging from 0.08–2.8 m. Typically, the length of the ice ablation season beneath supraglacial debris was 160 days (15 May to 22 October)—a month longer than the monsoon season. Debris temperature gradients were approximately linear (r2 > 0.83), measured as –40°C m–1 where debris was up to 0.1 m thick, –20°C m–1 for debris 0.1–0.5 m thick, and –4°C m–1 for debris greater than 0.5 m thick. Our results demonstrate that the influence of supraglacial debris on the temperature of the underlying ice surface, and therefore melt, is stable at a seasonal timescale and can be estimated from near-surface temperature. These results have the potential to greatly improve the representation of ablation in calculations of debris-covered glacier mass balance and projections of their response to climate change.Peer reviewe