Passive phloem loading and long-distance transport in a synthetic tree-on-a-chip

Vascular plants rely on differences of osmotic pressure to export sugars from regions of synthesis (mature leaves) to sugar sinks (roots, fruits). In this process, known as M\"unch pressure flow, the loading of sugars from photosynthetic cells to the export conduit (the phloem) is crucial, as it sets the pressure head necessary to power long-distance transport. Whereas most herbaceous plants use active mechanisms to increase phloem concentration above that of the photosynthetic cells, in most tree species, for which transport distances are largest, loading seems to occur via passive symplastic diffusion from the mesophyll to the phloem. Here, we use a synthetic microfluidic model of a passive loader to explore the nonlinear dynamics that arise during export and determine the ability of passive loading to drive long-distance transport. We first demonstrate that in our device, phloem concentration is set by the balance between the resistances to diffusive loading from the source and convective export through the phloem. Convection-limited export corresponds to classical models of M\"unch transport, where phloem concentration is close to that of the source; in contrast, diffusion-limited export leads to small phloem concentrations and weak scaling of flow rates with the hydraulic resistance. We then show that the effective regime of convection-limited export is predominant in plants with large transport resistances and low xylem pressures. Moreover, hydrostatic pressures developed in our synthetic passive loader can reach botanically relevant values as high as 10 bars. We conclude that passive loading is sufficient to drive long-distance transport in large plants, and that trees are well suited to take full advantage of passive phloem loading strategies

Limited effect of patient and disease characteristics on compliance with hospital antimicrobial guidelines

Objective: Physicians frequently deviate from guidelines that promote prudent use of antimicrobials. We explored to what extent patient and disease characteristics were associated with compliance with guideline recommendations for three common infections. Methods: In a 1-year prospective observational study, 1,125 antimicrobial prescriptions were analysed for compliance with university hospital guidelines. Results: Compliance varied significantly between and within the groups of infections studied. Compliance was much higher for lower respiratory tract infections (LRTIs; 79%) than for sepsis (53%) and urinary tract infections (UTIs; 40%). Only predisposing illnesses and active malignancies were associated with more compliant prescribing, whereas alcohol/ intravenous drug abuse and serum creatinine levels > 130 mu mol/l were associated with less compliant prescribing. Availability of culture results had no impact on compliance with guidelines for sepsis but was associated with more compliance in UTIs and less in LRTIs. Narrowing initial broad-spectrum antimicrobial therapy to cultured pathogens was seldom practised. Most noncompliant prescribing concerned a too broad spectrum of activity when compared with guideline-recommended therapy. Conclusion: Patient characteristics had only a limited impact on compliant prescribing for a variety of reasons. Physicians seemed to practise defensive prescribing behaviour, favouring treatment success in current patients over loss of effectiveness due to resistance in future patients

The circadian clock rephases during lateral root organ initiation in Arabidopsis thaliana

The endogenous circadian clock enables organisms to adapt their growth and development to environmental changes. Here we describe how the circadian clock is employed to coordinate responses to the key signal auxin during lateral root (LR) emergence. In the model plant, Arabidopsis thaliana, LRs originate from a group of stem cells deep within the root, necessitating that new organs emerge through overlying root tissues. We report that the circadian clock is rephased during LR development. Metabolite and transcript profiling revealed that the circadian clock controls the levels of auxin and auxin-related genes including the auxin response repressor IAA14 and auxin oxidase AtDAO2. Plants lacking or overexpressing core clock components exhibit LR emergence defects. We conclude that the circadian clock acts to gate auxin signalling during LR development to facilitate organ emergence

Early In-Hospital Mortality following Trainee Doctors' First Day at Work

BACKGROUND:There is a commonly held assumption that early August is an unsafe period to be admitted to hospital in England, as newly qualified doctors start work in NHS hospitals on the first Wednesday of August. We investigate whether in-hospital mortality is higher in the week following the first Wednesday in August than in the previous week. METHODOLOGY:A retrospective study in England using administrative hospital admissions data. Two retrospective cohorts of all emergency patients admitted on the last Wednesday in July and the first Wednesday in August for 2000 to 2008, each followed up for one week. PRINCIPAL FINDINGS:The odds of death for patients admitted on the first Wednesday in August was 6% higher (OR 1.06, 95% CI 1.00 to 1.15, p=0.05) after controlling for year, gender, age, socio-economic deprivation and co-morbidity. When subdivided into medical, surgical and neoplasm admissions, medical admissions admitted on the first Wednesday in August had an 8% (OR 1.08, 95% CI 1.01 to 1.16, p=0.03) higher odds of death. In 2007 and 2008, when the system for junior doctors' job applications changed, patients admitted on Wednesday August 1(st) had 8% higher adjusted odds of death than those admitted the previous Wednesday, but this was not statistically significant (OR 1.08, 95% CI 0.95 to 1.23, p=0.24). CONCLUSIONS:We found evidence that patients admitted on the first Wednesday in August have a higher early death rate in English hospitals compared with patients admitted on the previous Wednesday. This was higher for patients admitted with a medical primary diagnosis

A novel technique for the production of electrospun scaffolds with tailored three-dimensional micro-patterns employing additive manufacturing

Electrospinning is a common technique used to fabricate fibrous scaffolds for tissue engineering applications. There is now growing interest in assessing the ability of collector plate design to influence the patterning of the fibres during the electrospinning process. In this study, we investigate a novel method to generate hybrid electrospun scaffolds consisting of both random fibres and a defined three-dimensional (3D) micro-topography at the surface, using patterned resin formers produced by rapid prototyping (RP). Poly(D,L-lactide-co-glycolide) was electrospun onto the engineered RP surfaces and the ability of these formers to influence microfibre patterning in the resulting scaffolds visualized by scanning electron microscopy. Electrospun scaffolds with patterns mirroring the microstructures of the formers were successfully fabricated. The effect of the resulting fibre patterns and 3D geometries on mammalian cell adhesion and proliferation was investigated by seeding enhanced green fluorescent protein labelled 3T3 fibroblasts onto the scaffolds. Following 24 h and four days of culture, the seeded scaffolds were visually assessed by confocal macro- and microscopy. The patterning of the fibres guided initial cell adhesion to the scaffold with subsequent proliferation over the geometry resulting in the cells being held in a 3D micro-topography. Such patterning could be designed to replicate a specific in vivo structure; we use the dermal papillae as an exemplar here. In conclusion, a novel, versatile and scalable method to produce hybrid electrospun scaffolds has been developed. The 3D directional cues of the patterned fibres have been shown to influence cell behaviour and could be used to culture cells within a similar 3D micro-topography as experienced in vivo

Hippocampal Neurogenesis and Dendritic Plasticity Support Running-Improved Spatial Learning and Depression-Like Behaviour in Stressed Rats

Exercise promotes hippocampal neurogenesis and dendritic plasticity while stress shows the opposite effects, suggesting a possible mechanism for exercise to counteract stress. Changes in hippocampal neurogenesis and dendritic modification occur simultaneously in rats with stress or exercise; however, it is unclear whether neurogenesis or dendritic remodeling has a greater impact on mediating the effect of exercise on stress since they have been separately examined. Here we examined hippocampal cell proliferation in runners treated with different doses (low: 30 mg/kg; moderate: 40 mg/kg; high: 50 mg/kg) of corticosterone (CORT) for 14 days. Water maze task and forced swim tests were applied to assess hippocampal-dependent learning and depression-like behaviour respectively the day after the treatment. Repeated CORT treatment resulted in a graded increase in depression-like behaviour and impaired spatial learning that is associated with decreased hippocampal cell proliferation and BDNF levels. Running reversed these effects in rats treated with low or moderate, but not high doses of CORT. Using 40 mg/kg CORT-treated rats, we further studied the role of neurogenesis and dendritic remodeling in mediating the effects of exercise on stress. Co-labelling with BrdU (thymidine analog) /doublecortin (immature neuronal marker) showed that running increased neuronal differentiation in vehicle- and CORT-treated rats. Running also increased dendritic length and spine density in CA3 pyramidal neurons in 40 mg/kg CORT-treated rats. Ablation of neurogenesis with Ara-c infusion diminished the effect of running on restoring spatial learning and decreasing depression-like behaviour in 40 mg/kg CORT-treated animals in spite of dendritic and spine enhancement. but not normal runners with enhanced dendritic length. The results indicate that both restored hippocampal neurogenesis and dendritic remodelling within the hippocampus are essential for running to counteract stress

An Experimental Field Study of Delayed Density Dependence in Natural Populations of Aedes albopictus

Aedes albopictus, a species known to transmit dengue and chikungunya viruses, is primarily a container-inhabiting mosquito. The potential for pathogen transmission by Ae. albopictus has increased our need to understand its ecology and population dynamics. Two parameters that we know little about are the impact of direct density-dependence and delayed density-dependence in the larval stage. The present study uses a manipulative experimental design, under field conditions, to understand the impact of delayed density dependence in a natural population of Ae. albopictus in Raleigh, North Carolina. Twenty liter buckets, divided in half prior to experimentation, placed in the field accumulated rainwater and detritus, providing oviposition and larval production sites for natural populations of Ae. albopictus. Two treatments, a larvae present and larvae absent treatment, were produced in each bucket. After five weeks all larvae were removed from both treatments and the buckets were covered with fine mesh cloth. Equal numbers of first instars were added to both treatments in every bucket. Pupae were collected daily and adults were frozen as they emerged. We found a significant impact of delayed density-dependence on larval survival, development time and adult body size in containers with high larval densities. Our results indicate that delayed density-dependence will have negative impacts on the mosquito population when larval densities are high enough to deplete accessible nutrients faster than the rate of natural food accumulation

COL4A1 Mutations Cause Ocular Dysgenesis, Neuronal Localization Defects, and Myopathy in Mice and Walker-Warburg Syndrome in Humans

Muscle-eye-brain disease (MEB) and Walker Warburg Syndrome (WWS) belong to a spectrum of autosomal recessive diseases characterized by ocular dysgenesis, neuronal migration defects, and congenital muscular dystrophy. Until now, the pathophysiology of MEB/WWS has been attributed to alteration in dystroglycan post-translational modification. Here, we provide evidence that mutations in a gene coding for a major basement membrane protein, collagen IV alpha 1 (COL4A1), are a novel cause of MEB/WWS. Using a combination of histological, molecular, and biochemical approaches, we show that heterozygous Col4a1 mutant mice have ocular dysgenesis, neuronal localization defects, and myopathy characteristic of MEB/WWS. Importantly, we identified putative heterozygous mutations in COL4A1 in two MEB/WWS patients. Both mutations occur within conserved amino acids of the triple-helix-forming domain of the protein, and at least one mutation interferes with secretion of the mutant proteins, resulting instead in intracellular accumulation. Expression and posttranslational modification of dystroglycan is unaltered in Col4a1 mutant mice indicating that COL4A1 mutations represent a distinct pathogenic mechanism underlying MEB/WWS. These findings implicate a novel gene and a novel mechanism in the etiology of MEB/WWS and expand the clinical spectrum of COL4A1-associated disorders

Conditioning Individual Mosquitoes to an Odor: Sex, Source, and Time

Olfactory conditioning of mosquitoes may have important implications for vector-pathogen-host dynamics. If mosquitoes learn about specific host attributes associated with pathogen infection, it may help to explain the heterogeneity of biting and disease patterns observed in the field. Sugar-feeding is a requirement for survival in both male and female mosquitoes. It provides a starting point for learning research in mosquitoes that avoids the confounding factors associated with the observer being a potential blood-host and has the capability to address certain areas of close-range mosquito learning behavior that have not previously been described. This study was designed to investigate the ability of the southern house mosquito, Culex quinquefasciatus Say to associate odor with a sugar-meal with emphasis on important experimental considerations of mosquito age (1.2 d old and 3–5 d old), sex (male and female), source (laboratory and wild), and the time between conditioning and testing (<5 min, 1 hr, 2.5 hr, 5 hr, 10 hr, and 24 hr). Mosquitoes were individually conditioned to an odor across these different experimental conditions. Details of the conditioning protocol are presented as well as the use of binary logistic regression to analyze the complex dataset generated from this experimental design. The results suggest that each of the experimental factors may be important in different ways. Both the source of the mosquitoes and sex of the mosquitoes had significant effects on conditioned responses. The largest effect on conditioning was observed in the lack of positive response following conditioning for females aged 3–5 d derived from a long established colony. Overall, this study provides a method for conditioning experiments involving individual mosquitoes at close range and provides for future discussion of the relevance and broader questions that can be asked of olfactory conditioning in mosquitoes