The 5'-3' exoribonuclease Pacman (Xrn1) regulates expression of the heat shock protein Hsp67Bc and the microRNA miR-277-3p in Drosophila wing imaginal discs

Pacman/Xrn1 is a highly conserved exoribonuclease known to play a critical role in gene regulatory events such as control of mRNA stability, RNA interference and regulation via miRNAs. Although Pacman has been well studied in Drosophila tissue culture cells, the biologically relevant cellular pathways controlled by Pacman in natural tissues are unknown. This study shows that a hypomorphic mutation in pacman (pcm5) results in smaller wing imaginal discs. These tissues, found in the larva, are known to grow and differentiate to form wing and thorax structures in the adult fly. Using microarray analysis, followed by quantitative RT-PCR, we show that eight mRNAs were increased in level by >2 fold in the pcm5 mutant wing discs compared to the control. The levels of pre mRNAs were tested for five of these mRNAs; four did not increase in the pcm5 mutant, showing that they are regulated at the post-transcriptional level and therefore could be directly affected by Pacman. These transcripts include one that encodes the heat-shock protein Hsp67Bc, which is upregulated 11.9-fold at the post-transcriptional level and 2.3-fold at the protein level. One miRNA, miR-277-3p, is 5.6-fold downregulated at the post-transcriptional level in mutant discs, suggesting that Pacman affects its processing in this tissue. Together, these data show that a relatively small number of mRNAs and miRNAs substantially change in abundance in pacman mutant wing imaginal discs. Since Hsp67Bc is known to regulate autophagy and protein synthesis, it is possible that Pacman may control the growth of wing imaginal discs by regulating these processes

The impact of visual impairment on nutritional status: A systematic review

The aim of this review was to evaluate the literature that has investigated the impact of visual impairment on nutritional status. We identified relevant articles through a multi-staged systematic approach. Fourteen articles were identified as meeting the inclusion criteria. The sample size of the studies ranged from 9 to 761 participants. It was found that visual impairment significantly affects nutritional status. The studies reported that visually impaired people have an abnormal body mass index (BMI); a higher prevalence of obesity and malnutrition was reported. Visually impaired people find it difficult to shop for, eat, and prepare meals. Most studies had a small sample size, and some studies did not include a study control group for comparison. The limitations of these studies suggest that the findings are not conclusive enough to hold true for only those who are visually impaired. Further studies with a larger sample size are required with the aim of developing interventions

Elevated temperature drives a shift from selfing to outcrossing in the insect pollinated legume, faba bean (Vicia faba)

Climate change can threaten the reproductive success of plants, both directly, through physiological damage during increasingly extreme weather events, and indirectly, through disruption of plant–pollinator interactions. To explore how plant–pollinator interactions are modified by extreme weather, we exposed faba bean (Vicia faba) plants to elevated temperature for 5 d during flowering, simulating a heatwave. We then moved the plants to flight cages with either bumblebees or no pollinators, or to two field sites, where plants were enclosed in mesh bags or pollinated by wild insect communities. We used a morphological marker to quantify pollen movement between experimental plants. There was a substantial increase in the level of outcrossing by insect pollinators following heat stress. Proportion outcrossed seed increased from 17 % at control temperature to 33 % following heat stress in the flight cages, and from 31 % to 80 % at one field site, but not at the other (33 % to 32 %). Abiotic stress can dramatically shift the relative contributions of cross- and self-pollination to reproduction in an insect pollinated plant. The resulting increases in gene flow have broad implications for genetic diversity and functioning of ecosystems, and may increase resilience by accelerating the selection of more stress-tolerant genotypes

Neural correlates of early deliberate emotion regulation: Young children\u27s responses to interpersonal scaffolding.

Deliberate emotion regulation, the ability to willfully modulate emotional experiences, is shaped through interpersonal scaffolding and forecasts later functioning in multiple domains. However, nascent deliberate emotion regulation in early childhood is poorly understood due to a paucity of studies that simulate interpersonal scaffolding of this skill and measure its occurrence in multiple modalities. Our goal was to identify neural and behavioral components of early deliberate emotion regulation to identify patterns of competent and deficient responses. A novel probe was developed to assess deliberate emotion regulation in young children. Sixty children (age 4-6 years) were randomly assigned to deliberate emotion regulation or control conditions. Children completed a frustration task while lateral prefrontal cortex (LPFC) activation was recorded via functional near-infrared spectroscopy (fNIRS). Facial expressions were video recorded and children self-rated their emotions. Parents rated their child\u27s temperamental emotion regulation. Deliberate emotion regulation interpersonal scaffolding predicted a significant increase in frustration-related LPFC activation not seen in controls. Better temperamental emotion regulation predicted larger LPFC activation increases post- scaffolding among children who engaged in deliberate emotion regulation interpersonal scaffolding. A capacity to increase LPFC activation in response to interpersonal scaffolding may be a crucial neural correlate of early deliberate emotion regulation

A participatory approach to variety trials for organic systems

A participatory research methodology was used to compare the performance of UK wheat varieties under organic conditions. Plots of three breadmaking winter wheat varieties (Hereward, Solstice and Xi19) and a mixture (1:1:1) of the varieties were grown at 19 UK farms in two seasons (2003/04 and 2004/05). Meas-urements were taken of growth habit, yield and grain quality. Grain yields in both seasons showed significant site by variety interactions, although the variation among sites was greater than among varieties in both instances. Wheat grown at Western sites was significantly shorter and higher-yielding than that grown at Eastern sites in 2003/04 but significantly taller in 2004/05. As with grain yield, greater variation among site than variety was found in the Hagberg Falling Number and protein concentra-tion results in both seasons. The results from the two years of trials illustrate the variability of organic systems and the difficulty in selecting a single variety suitable for organic farms

Experiences of using mobile technologies and virtual field tours in Physical Geography: implications for hydrology education

Education in hydrology is changing rapidly due to diversification of students, emergent major scientific and practical challenges that our discipline must engage with, shifting pedagogic ideas and higher education environments, the need for students to develop new discipline specific and transferrable skills, and the advent of innovative technologies for learning and teaching. This paper focuses on new technologies in the context of learning and teaching in Physical Geography and reflects on the implications of our experiences for education in hydrology. We evaluate the experience of designing and trialling novel mobile technology-based field exercises and a virtual field tour for a Year 1 undergraduate Physical Geography module at a UK university. The new exercises are based on using and obtaining spatial data, operation of meteorological equipment (explained using an interactive DVD), and include introductions to global positioning systems (GPS) and geographical information systems (GIS). The technology and exercises were well received in a pilot study and subsequent rolling-out to the full student cohort (∼150 students). A statistically significant improvement in marks was observed following the redesign. Although the students enjoyed using mobile technology, the increased interactivity and opportunity for peer learning were considered to be the primary benefits by students. This is reinforced further by student preference for the new interactive virtual field tour over the previous "show-and-tell" field exercise. Despite the new exercises having many advantages, exercise development was not trivial due to the high start-up costs, the need for provision of sufficient technical support and the relative difficulty of making year-to-year changes (to the virtual field tour in particular). Our experiences are highly relevant to the implementation of novel learning and teaching technologies in hydrology education

Diffuse optical spectroscopic imaging reveals distinct early breast tumor hemodynamic responses to metronomic and maximum tolerated dose regimens.

BACKGROUND:Breast cancer patients with early-stage disease are increasingly administered neoadjuvant chemotherapy (NAC) to downstage their tumors prior to surgery. In this setting, approximately 31% of patients fail to respond to therapy. This demonstrates the need for techniques capable of providing personalized feedback about treatment response at the earliest stages of therapy to identify patients likely to benefit from changing treatment. Diffuse optical spectroscopic imaging (DOSI) has emerged as a promising functional imaging technique for NAC monitoring. DOSI uses non-ionizing near-infrared light to provide non-invasive measures of absolute concentrations of tissue chromophores such as oxyhemoglobin. In 2011, we reported a new DOSI prognostic marker, oxyhemoglobin flare: a transient increase in oxyhemoglobin capable of discriminating NAC responders within the first day of treatment. In this follow-up study, DOSI was used to confirm the presence of the flare as well as to investigate whether DOSI markers of NAC response are regimen dependent. METHODS:This dual-center study examined 54 breast tumors receiving NAC measured with DOSI before therapy and the first week following chemotherapy administration. Patients were treated with either a standard of care maximum tolerated dose (MTD) regimen or an investigational metronomic (MET) regimen. Changes in tumor chromophores were tracked throughout the first week and compared to pathologic response and treatment regimen at specific days utilizing generalized estimating equations (GEE). RESULTS:Within patients receiving MTD therapy, the oxyhemoglobin flare was confirmed as a prognostic DOSI marker for response appearing as soon as day 1 with post hoc GEE analysis demonstrating a difference of 48.77% between responders and non-responders (p < 0.0001). Flare was not observed in patients receiving MET therapy. Within all responding patients, the specific treatment was a significant predictor of day 1 changes in oxyhemoglobin, showing a difference of 39.45% (p = 0.0010) between patients receiving MTD and MET regimens. CONCLUSIONS:DOSI optical biomarkers are differentially sensitive to MTD and MET regimens at early timepoints suggesting the specific treatment regimen should be considered in future DOSI studies. Additionally, DOSI may help to identify regimen-specific responses in a more personalized manner, potentially providing critical feedback necessary to implement adaptive changes to the treatment strategy

Restoration of SMN in Schwann cells reverses myelination defects and improves neuromuscular function in spinal muscular atrophy

Spinal muscular atrophy (SMA) is a neuromuscular disease caused by low levels of SMN protein, primarily affecting lower motor neurons. Recent evidence from SMA and related conditions suggests that glial cells can influence disease severity. Here, we investigated the role of glial cells in the peripheral nervous system by creating SMA mice selectively overexpressing SMN in myelinating Schwann cells (Smn(−/−);SMN2(tg/0);SMN1(SC)). Restoration of SMN protein levels restricted solely to Schwann cells reversed myelination defects, significantly improved neuromuscular function and ameliorated neuromuscular junction pathology in SMA mice. However, restoration of SMN in Schwann cells had no impact on motor neuron soma loss from the spinal cord or ongoing systemic and peripheral pathology. This study provides evidence for a defined, intrinsic contribution of glial cells to SMA disease pathogenesis and suggests that therapies designed to include Schwann cells in their target tissues are likely to be required in order to rescue myelination defects and associated disease symptoms