Body size has been shown to decrease with increasing temperature in many species, prompting the suggestion that it is a universal ecological response. However, species with complex life cycles, such ...as holometabolous insects, may have correspondingly complicated temperature–size responses. Recent research suggests that life history and ecological traits may be important for determining the direction and strength of temperature–size responses. Yet, these factors are rarely included in analyses. Here, we aim to determine whether the size of the bivoltine butterfly, Polyommatus bellargus, and the univoltine butterflies, Plebejus argus and Polyommatus coridon, change in response to temperature and whether these responses differ between the sexes, and for P. bellargus, between generations. Forewing length was measured using digital specimens from the Natural History Museum, London (NHM), from one locality in the UK per species. The data were initially compared to annual and seasonal temperature values, without consideration of life history factors. Sex and generation of the individuals and mean monthly temperatures, which cover the growing period for each species, were then included in analyses. When compared to annual or seasonal temperatures only, size was not related to temperature for P. bellargus and P. argus, but there was a negative relationship between size and temperature for P. coridon. When sex, generation, and monthly temperatures were included, male adult size decreased as temperature increased in the early larval stages, and increased as temperature increased during the late larval stages. Results were similar but less consistent for females, while second generation P. bellargus showed no temperature–size response. In P. coridon, size decreased as temperature increased during the pupal stage. These results highlight the importance of including life history factors, sex, and monthly temperature data when studying temperature–size responses for species with complex life cycles.
Life history and ecological factors are important for determining temperature–size responses of a species, but they are very rarely included in analyses. We show that sex and generation, as well as the use of appropriate temperature records, are important for understanding the temperature–size responses of three butterfly species. Within a species, temperature–size responses can vary between the sexes, generations, and immature stages.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Uncertainty is a common and increasingly acknowledged problem in clinical practice. Current single best answer (SBA) style assessments test areas where there is one correct answer, and as the ...approach to assessment impacts on the approach to learning, these exams may poorly prepare our future doctors to handle uncertainty. We therefore, need to modify our approach to assessment to emphasize reasoning and introduce the possibility of more than one 'correct' answer. We have developed clinical prioritization questions (CPQs), a novel formative assessment tool in which students prioritize possible responses in order of likelihood. This assessment format was piloted with a group of medical students and evaluated in comparison with the more traditional SBA question format in a team-based learning setting. Students reported that they felt ongoing use would help improve their tolerance of uncertainty (p < 0.01). Furthermore, over 80% of students felt that CPQs were more reflective of real-life clinical practice. Group based discussions were significantly longer when answering CPQs (p < 0.01), suggesting they may promote richer discourse. CPQs may have a role in formative assessment to help equip students with the skills to cope with ambiguity and strengthen clinical reasoning and decision-making. Institutions may find them more practical to implement compared with other clinical reasoning assessment tools.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Unc51 like autophagy activating kinase 1 (Ulk1), the primary autophagy regulator, has been linked to metabolic adaptation in skeletal muscle to exercise training. Here we compared the roles of Ulk1 ...and homologous Ulk2 in skeletal muscle insulin action following exercise training to gain more mechanistic insights. Inducible, skeletal muscle-specific
knock-out (Ulk1-iMKO) mice and global
knock-out (Ulk2
) mice were subjected to voluntary wheel running for 6 weeks followed by assessment of exercise capacity, glucose tolerance, and insulin signaling in skeletal muscle after a bolus injection of insulin. Both Ulk1-iMKO and Ulk2
mice had improved endurance exercise capacity post-exercise. Ulk1-iMKO did not improve glucose clearance during glucose tolerance test, while Ulk2
had only marginal improvement. However, exercise training-induced improvement of insulin action in skeletal muscle, indicated by Akt-S473 phosphorylation, was only impaired in Ulk1-iMKO. These data suggest that Ulk1, but not Ulk2, is required for exercise training-induced improvement of insulin action in skeletal muscle, implicating crosstalk between catabolic and anabolic signaling as integral to metabolic adaptation to energetic stress.
Placental dysfunction is an underlying cause of many major obstetric diseases and treatment options for complications like fetal growth restriction (FGR) are limited .We previously demonstrated ...nanoparticle delivery of the human insulin-like growth factor 1 (hIGF1) transgene under control of the trophoblast-specific PLAC1 promoter maintains normal fetal growth in a surgically-induced FGR mouse model. However, uptake by human placental syncytiotrophoblast has yet to be determined.
An ex vivo human placenta perfusion model, term placenta villous fragments, and other in vitro syncytiotrophoblast models were used to determine nanoparticle uptake, transgene expression, and functional responses under oxidative stress conditions.
In the ex vivo perfusion, fluorescence from a Texas-Red conjugated nanoparticle increased in maternal perfusate upon nanoparticle addition and declined by the conclusion of the experiment (P < 0.001. Fluorescent histology confirmed localization in the syncytiotrophoblasts. No Texas-Red fluorescence was detected in the fetal perfusate. Transgene expression of hIGF1 in differentiated BeWo cells, isolated primary trophoblasts and fragments was increased compared to untreated (55,000-fold, P = 0.0003; 95-fold, P = 0.003; 400-fold, P < 0.001, respectively). Functionally, increased hIGF1 expression in villous fragments resulted in translocation of glucose transporter 1 to the syncytiotrophoblast cell membrane and under conditions of oxidative stress in BeWo cells, protected against increased cell death (P < 0.01) and decreased mitochondrial activity (P < 0.01).
The current study confirms that our nanoparticle is capable of uptake in human placental syncytium which results in enhanced transgene expression, functional changes to cellular activity and protection against increased oxidative stress.
•Nanoparticle uptake in human placenta syncytium was determined in an ex vivo and several in vitro models.•Nanoparticle treatment increased human insulin-like 1 growth factor (hIGF1) transgene expression.•Increased hIGF1 causes translocalisation of glucose transport 1 in syncytiotrophoblast cells.•Increased hIGF1 in trophoblast cels protects against increased cell death and decreased mitochondrial activity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Many multivariate time series observed in practice are second order nonstationary, i.e. their covariance properties vary over time. In addition, missing observations in such data are encountered in ...many applications of interest, due to recording failures or sensor dropout, hindering successful analysis. This article introduces a novel method for data imputation in multivariate nonstationary time series, based on the so-called locally stationary wavelet modelling paradigm. Our methodology is shown to perform well across a range of simulation scenarios, with a variety of missingness structures, as well as being competitive in the stationary time series setting. We also demonstrate our technique on data arising in a health monitoring application.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Natural history collections are invaluable resources for understanding biotic response to global change. Museums around the world are currently imaging specimens, capturing specimen data and making ...them freely available online. In parallel to the digitisation effort, there have been great advancements in computer vision: the computer trained automated recognition/detection, and measurement of features in digital images. Applying computer vision to digitised natural history collections has the potential to greatly accelerate the use of these collections for biotic response to global change research. In this paper, we apply computer vision to a very large, digitised collection to test hypotheses in an established area of biotic response to climate change research: temperature‐size responses.
We develop a computer vision pipeline (Mothra) and apply it to the NHM collection of British butterflies (>180,000 imaged specimens). Mothra automatically detects the specimen and other objects in the image, sets the scale, measures wing features (e.g. forewing length), determines the orientation of the specimen (pinned ventrally or dorsally) and identifies the sex. We pair these measurements and specimen collection data with temperature records for 17,726 specimens across a subset of 24 species to test how adult size varies with temperature during the immature stages of species. We also assess patterns of sexual size dimorphism across species and families for 32 species trained for automated sex ID.
Mothra accurately measures the forewing lengths of butterfly specimens compared to manual measurements and accurately determines the sex of specimens, with females as the larger sex in most species. An increase in adult body size with warmer monthly temperatures during the late larval stages is the most common temperature‐size response. These results confirm suspected patterns and support hypotheses based on recent studies using a smaller dataset of manually measured specimens.
We show that computer vision can be a powerful tool to efficiently and accurately extract phenotypic data from a very large collection of digital natural history collections. In the future, computer vision will become widely applied to digital collections to advance ecological and evolutionary research and to accelerate their use to investigate biotic response to global change.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
We describe herein our recent explorations in the field of isonitrile chemistry. An array of broadly useful coupling methodologies has been developed for the formation of peptidyl and glycopeptidyl ...amide bonds. We further describe the application of these methods to the syntheses of complex systems, including the cyclic peptide cyclosporine A, constrained peptide systems, and heterocycles.
New take on an old classic: Recent explorations in the field of isonitrile chemistry led to the development of an array of broadly useful coupling methods for the formation of peptidyl and glycopeptidyl amide bonds. The methods were applied to the syntheses of complex systems, including the cyclic peptide cyclosporine A, constrained peptide systems, and heterocycles (see scheme; FCMA=formimidate carboxylate mixed anhydride).
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Assessment of structural and functional changes of mitochondria is vital for biomedical research as mitochondria are the power plants essential for biological processes and tissue/organ functions. ...Others and we have developed a novel reporter gene, pMitoTimer, which codes for a redox sensitive mitochondrial targeted protein that switches from green fluorescence protein (GFP) to red fluorescent protein (DsRed) when oxidized. It has been shown in transfected cells, transgenic C. elegans and Drosophila m., as well as somatically transfected adult skeletal muscle that this reporter gene allows quantifiable assessment of mitochondrial structure, oxidative stress, and lysosomal targeting of mitochondria-containing autophagosomes. Here, we generated CAG-CAT-MitoTimer transgenic mice using a transgene containing MitoTimer downstream of LoxP-flanked bacterial chloramphenicol acetyltransferase (CAT) gene with stop codon under the control of the cytomegalovirus (CMV) enhancer fused to the chicken β-actin promoter (CAG). When CAG-CAT-MitoTimer mice were crossbred with various tissue-specific (muscle, adipose tissue, kidney, and pancreatic tumor) or global Cre transgenic mice, the double transgenic offspring showed MitoTimer expression in tissue-specific or global manner. Lastly, we show that hindlimb ischemia-reperfusion caused early, transient increases of mitochondrial oxidative stress, mitochondrial fragmentation and lysosomal targeting of autophagosomes containing mitochondria as well as a later reduction of mitochondrial content in skeletal muscle along with mitochondrial oxidative stress in sciatic nerve. Thus, we have generated conditional MitoTimer mice and provided proof of principle evidence of their utility to simultaneously assess mitochondrial structure, oxidative stress, and mitophagy in vivo in a tissue-specific, controllable fashion.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Ischemia-reperfusion (IR) due to temporary restriction of blood flow causes tissue/organ damages under various disease conditions, including stroke, myocardial infarction, trauma, and orthopedic ...surgery. In the limbs, IR injury to motor nerves and muscle fibers causes reduced mobility and quality of life. Endurance exercise training has been shown to increase tissue resistance to numerous pathological insults. To elucidate the impact of endurance exercise training on IR injury in skeletal muscle, sedentary and exercise-trained mice (5 wk of voluntary running) were subjected to ischemia by unilateral application of a rubber band tourniquet above the femur for 1 h, followed by reperfusion. IR caused significant muscle injury and denervation at neuromuscular junction (NMJ) as early as 3 h after tourniquet release as well as depressed muscle strength and neuromuscular transmission in sedentary mice. Despite similar degrees of muscle atrophy and oxidative stress, exercise-trained mice had significantly reduced muscle injury and denervation at NMJ with improved regeneration and functional recovery following IR. Together, these data suggest that endurance exercise training preserves motor nerve and myofiber structure and function from IR injury and promote functional regeneration. NEW & NOTEWORTHY This work provides the first evidence that preemptive voluntary wheel running reduces neuromuscular dysfunction following ischemia-reperfusion injury in skeletal muscle. These findings may alter clinical practices in which a tourniquet is used to modulate blood flow.
Maternal micronutrient deficiencies in pregnancy can have profound effects on fetal development and pregnancy outcome. Plasma trace minerals including copper, zinc, selenium and iron have been shown ...to be extremely important in supporting reproduction. We sought to determine whether there is an association between maternal trace mineral status in early pregnancy and pregnancy complications using a prospective cohort study of 1065 pregnant Australian women who were recruited as part of the Screening for Pregnancy Endpoints (SCOPE) study in Adelaide. Copper, zinc, selenium and iron present in the plasma were measured using mass spectrometry in samples collected at 15±1 weeks’ gestation. After adjusting for covariates, women with lower plasma copper (<27.9μmol/L and 27.9–32.5μmol/L) had decreased risk for any pregnancy complication when compared with women with high plasma copper (>32.5μmol/L) (aRR=0.87; 95% CI=0.76, 0.99 and aRR=0.88; 95% CI=0.78, 1.00, respectively). This was also observed when adjusting for plasma zinc and selenium status (<27.9μmol/L: aRR=0.81; 95% CI=0.69, 0.96 and 27.9–32.5μmol/L: aRR=0.84; 95% CI=0.72, 0.98). Combined low copper and zinc status was also associated with a reduced risk of any pregnancy complication as compared with high copper and zinc status (aRR=0.80; 95% CI=0.70, 0.93). These results provide justification for further work into elucidating the mechanistic role of trace elements in early pregnancy, as well as their interactions in supporting successful pregnancy outcomes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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