Regulation of spindle orientation and neural stem cell fate in the Drosophila optic lobe

BACKGROUND: The choice of a stem cell to divide symmetrically or asymmetrically has profound consequences for development and disease. Unregulated symmetric division promotes tumor formation, whereas inappropriate asymmetric division affects organ morphogenesis. Despite its importance, little is known about how spindle positioning is regulated. In some tissues cell fate appears to dictate the type of cell division, whereas in other tissues it is thought that stochastic variation in spindle position dictates subsequent sibling cell fate. RESULTS: Here we investigate the relationship between neural progenitor identity and spindle positioning in the Drosophila optic lobe. We use molecular markers and live imaging to show that there are two populations of progenitors in the optic lobe: symmetrically dividing neuroepithelial cells and asymmetrically dividing neuroblasts. We use genetically marked single cell clones to show that neuroepithelial cells give rise to neuroblasts. To determine if a change in spindle orientation can trigger a neuroepithelial to neuroblast transition, we force neuroepithelial cells to divide along their apical/basal axis by misexpressing Inscuteable. We find that this does not induce neuroblasts, nor does it promote premature neuronal differentiation. CONCLUSION: We show that symmetrically dividing neuroepithelial cells give rise to asymmetrically dividing neuroblasts in the optic lobe, and that regulation of spindle orientation and division symmetry is a consequence of cell type specification, rather than a mechanism for generating cell type diversity

Our Reflections on the Reactions to “Theories in the Field of Community Psychology”

We recognize that our article (Jason, Stevens, Ram, Miller, Beasley, & Gleason, 2016) will be controversial, and we are delighted that it has sparked some lively discussions. Our thesis is that research in our field could benefit from being evaluated on how it contributes to theory (including the development of one’s own). We believe that this recommendation represents a significant and constructive step forward. Our reflections on a number of the issues raised by those who wrote reactions to our article are below

Our Reflections on the Reactions to “Theories in the Field of Community Psychology”

We recognize that our article (Jason, Stevens, Ram, Miller, Beasley, & Gleason, 2016) will be controversial, and we are delighted that it has sparked some lively discussions. Our thesis is that research in our field could benefit from being evaluated on how it contributes to theory (including the development of one’s own). We believe that this recommendation represents a significant and constructive step forward. Our reflections on a number of the issues raised by those who wrote reactions to our article are below

An excess of star-forming galaxies in the fields of high-redshift QSOs

We present submillimetre (submm) and mid-infrared (MIR) imaging observations of five fields centred on quasi-stellar objects (QSOs) at 1.7 <z< 2.8. All five QSOs were detected previously at submm wavelengths. At 850 (450) μm, we detect 17 (11) submillimetre galaxies (SMGs) in addition to the QSOs. The total area mapped at 850 μm is ∼28 arcmin2 down to rms noise levels of 1–2 mJy beam−1, depending on the field. Integral number counts are computed from the 850-μm data using the same analytical techniques adopted by ‘blank-field’ submm surveys. We find that the ‘QSO-field’ counts show a clear excess over the blank-field counts at deboosted flux densities of ∼2–4 mJy; at higher flux densities, the counts are consistent with the blank-field counts. Robust MIR counterparts are identified for all four submm detected QSOs and ∼60 per cent of the SMGs. The MIR colours of the QSOs are similar to those of the local ultraluminous infrared galaxy (ULIRG)/active galactic nuclei (AGN) Mrk 231 if placed at 1 <z< 3 whilst most of the SMGs have colours very similar to those of the local ULIRG Arp 220 at 1 <z< 3. MIR diagnostics therefore find no strong evidence that the SMGs host buried AGN although we cannot rule out such a possibility. Taken together our results suggest that the QSOs sit in regions of the early universe which are undergoing an enhanced level of major star formation activity, and should evolve to become similarly dense regions containing massive galaxies at the present epoch. Finally, we find evidence that the level of star formation activity in individual galaxies appears to be lower around the QSOs than it is around more powerful radio-loud AGN at higher redshifts.We thank Ian Smail for extensive comments on the draft manuscript and Mark Thompson for useful discussions. The JCMT is operated by The Joint Astronomy Centre on behalf of the Science and Technology Facilities Council of the United Kingdom, the Netherlands Organisation for Scientific Research and the National Research Council of Canada. JCMT data were taken under project IDs M03AU46, M03BU32 and M04BU14. This work is based (in part) on observations made with the Spitzer Space Telescope, which is operated by the Jet Propulsion Laboratory, California Institute of Technology under a contract with NASA. Support for this work was provided by NASA through an award issued by JPL/Caltech. JAS, MJP and FJC acknowledge support from the Royal Society. FJC acknowledges further support from the Spanish Ministerio de Educación y Ciencia under project ESP2006-13608

Potential Direct and Indirect Effects of Climate Change on a Shallow Natural Lake Fish Assemblage

Much uncertainty exists around how fish communities in shallow lakes will respond to climate change. In this study, we modelled the effects of increased water temperatures on consumption and growth rates of two piscivores (northern pike [Esox lucius] and largemouth bass [Micropterus salmoides]) and examined relative effects of consumption by these predators on two prey species (bluegill [Lepomis macrochirus] and yellow perch [Perca flavescens]). Bioenergetics models were used to simulate the effects of climate change on growth and food consumption using predicted 2040 and 2060 temperatures in a shallow Nebraska Sandhill lake, USA. The patterns and magnitude of daily and cumulative consumption during the growing season (April–October) were generally similar between the two predators. However, growth of northern pike was always reduced (–3 to –45% change) compared to largemouth bass that experienced subtle changes (4 to –6% change) in weight by the end of the growing season. Assuming similar population size structure and numbers of predators in 2040–2060, future consumption of bluegill and yellow perch by northern pike and largemouth bass will likely increase (range: 3–24%), necessitating greater prey biomass to meet future energy demands. The timing of increased predator consumption will likely shift towards spring and fall (compared to summer), when prey species may not be available in the quantities required. Our findings suggest that increased water temperatures may affect species at the edge of their native range (i.e. northern pike) and a potential mismatch between predator and prey could exist

Mitochondrial Overload and Incomplete Fatty Acid Oxidation Contribute to Skeletal Muscle Insulin Resistance

SummaryPrevious studies have suggested that insulin resistance develops secondary to diminished fat oxidation and resultant accumulation of cytosolic lipid molecules that impair insulin signaling. Contrary to this model, the present study used targeted metabolomics to find that obesity-related insulin resistance in skeletal muscle is characterized by excessive β-oxidation, impaired switching to carbohydrate substrate during the fasted-to-fed transition, and coincident depletion of organic acid intermediates of the tricarboxylic acid cycle. In cultured myotubes, lipid-induced insulin resistance was prevented by manipulations that restrict fatty acid uptake into mitochondria. These results were recapitulated in mice lacking malonyl-CoA decarboxylase (MCD), an enzyme that promotes mitochondrial β-oxidation by relieving malonyl-CoA-mediated inhibition of carnitine palmitoyltransferase 1. Thus, mcd−/− mice exhibit reduced rates of fat catabolism and resist diet-induced glucose intolerance despite high intramuscular levels of long-chain acyl-CoAs. These findings reveal a strong connection between skeletal muscle insulin resistance and lipid-induced mitochondrial stress

Trends in kidney function testing in UK primary care since the introduction of the Quality and Outcomes Framework:a retrospective cohort study using CPRD

Objectives: To characterise serum creatinine and urinary protein testing in UK general practices from 2005 to 2013 and to examine how the frequency of testing varies across demographic factors, with the presence of chronic conditions and with the prescribing of drugs for which kidney function monitoring is recommended. Design: Retrospective open cohort study. Setting: Routinely collected data from 630 UK general practices contributing to the Clinical Practice Research Datalink. Participants: 4 573 275 patients aged over 18 years registered at up-to-standard practices between 1 April 2005 and 31 March 2013. At study entry, no patients were kidney transplant donors or recipients, pregnant or on dialysis. Primary outcome measures: The rate of serum creatinine and urinary protein testing per year and the percentage of patients with isolated and repeated testing per year. Results: The rate of serum creatinine testing increased linearly across all age groups. The rate of proteinuria testing increased sharply in the 2009–2010 financial year but only for patients aged 60 years or over. For patients with established chronic kidney disease (CKD), creatinine testing increased rapidly in 2006–2007 and 2007–2008, and proteinuria testing in 2009–2010, reflecting the introduction of Quality and Outcomes Framework indicators. In adjusted analyses, CKD Read codes were associated with up to a twofold increase in the rate of serum creatinine testing, while other chronic conditions and potentially nephrotoxic drugs were associated with up to a sixfold increase. Regional variation in serum creatinine testing reflected country boundaries. Conclusions: Over a nine-year period, there have been increases in the numbers of patients having kidney function tests annually and in the frequency of testing. Changes in the recommended management of CKD in primary care were the primary determinant, and increases persist even after controlling for demographic and patient-level factors. Future studies should address whether increased testing has led to better outcomes.</p