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Aims/Background The prognostic significance of body composition variables has become a popular area of research over the recent years. This study aimed to determine whether adipose tissue variables and sarcobesity index measured by computed tomography (CT) could predict cardiopulmonary exercise testing (CPET) performance and long-term mortality in patients undergoing major colorectal surgery. Methods The Strengthening the Reporting of Cohort Studies in Surgery (STROCSS) statement standards were followed to conduct a retrospective cohort study of consecutive patients who had CPET prior to major colorectal surgery between January 2011 and January 2017. Receiver Operating Characteristic curve analysis was conducted to assess the discriminative performances of adipose tissue variables. The association between CT-derived adipose tissue variables (sarcobesity index, visceral adipose tissue, subcutaneous adipose tissue, and total adipose tissue) and CPET performance and mortality were assessed using regression analyses. Results 457 patients were included. Total adipose tissue evaluated via 2-dimensional (2D) and 3-dimensional (3D) approaches predicted oxygen uptake ( V̇ O 2 ) Rest, V̇ O 2 anaerobic threshold (AT), ventilatory equivalents for carbon dioxide ( V̇ E/ V̇ CO 2 ) AT, ventilatory equivalents for oxygen ( V̇ E/ V̇ O 2 ) AT, V̇ O 2 peak, exercise time, maximum work, peak metabolic equivalents (METS), peak respiratory rate (RER), and peak oxygen pulse. Sarcobesity index (2D and 3D) predicted V̇ O 2 Rest, V̇ O 2 AT, V̇ E/ V̇ CO 2 AT, V̇ O 2 peak, maximum work, peak METS, maximum heart rate, and peak RER. Neither total adipose tissue nor sarcobesity index (2D and 3D) predicted 1-year, 3-year, or 5-year mortality. There was no difference in the discriminative performance of adipose tissue variables in predicting mortality. Conclusion The CPET performance may be predicted by radiologically measured adipose tissue variables and sarcobesity index. However, the prognostic value of the variables may not be significant in this setting.

Restricted sugar and ketogenic diets can alter energy balance/metabolism, but decreased energy intake may be compensated by reduced expenditure. In healthy adults, randomization to restricting free sugars or overall carbohydrates (ketogenic diet) for 12 weeks reduces fat mass without changing energy expenditure versus control. Free-sugar restriction minimally affects metabolism or gut microbiome but decreases low-density lipoprotein cholesterol (LDL-C). In contrast, a ketogenic diet decreases glucose tolerance, increases skeletal muscle PDK4, and reduces AMPK and GLUT4 levels. By week 4, the ketogenic diet reduces fasting glucose and increases apolipoprotein B, C-reactive protein, and postprandial glycerol concentrations. However, despite sustained ketosis, these effects are no longer apparent by week 12, when gut microbial beta diversity is altered, possibly reflective of longer-term adjustments to the ketogenic diet and/or energy balance. These data demonstrate that restricting free sugars or overall carbohydrates reduces energy intake without altering physical activity, but with divergent effects on glucose tolerance, lipoprotein profiles, and gut microbiome., Competing Interests: Declaration of interests P.D.C. is a co-founder and CTO of SeqBiome Ltd. J.T.G. has received research funding from BBSRC, MRC, Cancer Research UK, the British Heart Foundation, Clasado Biosciences, Lucozade Ribena Suntory, Arla Foods Ingredients, the Cosun Nutrition Center, and the Fruit Juice Science Center; is a scientific advisory board member to ZOE; and has completed paid consultancy for 6d Sports Nutrition, The Dairy Council, PepsiCo, Violicom Medical, Tour Racing Ltd., and SVGC. J.A.B. is an investigator on research grants funded by BBSRC, MRC, the British Heart Foundation, Rare Disease Foundation, EU Hydration Institute, GlaxoSmithKline, Nestlé, Lucozade Ribena Suntory, Arla Foods, Cosun Nutrition Center, American Academy of Sleep Medicine Foundation, and Salus Optima (L3M Technologies Ltd.); has completed paid consultancy for PepsiCo, Kellogg’s, SVGC, and Salus Optima (L3M Technologies Ltd.); is Company Director of Metabolic Solutions Ltd.; receives an annual honorarium as a member of the academic advisory board for the International Olympic Committee Diploma in Sports Nutrition; and receives an annual stipend as Editor-in-Chief of International Journal of Sport Nutrition & Exercise Metabolism., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Logged and disturbed forests are often viewed as degraded and depauperate environments compared with primary forest. However, they are dynamic ecosystems 1 that provide refugia for large amounts of biodiversity 2,3 , so we cannot afford to underestimate their conservation value 4 . Here we present empirically defined thresholds for categorizing the conservation value of logged forests, using one of the most comprehensive assessments of taxon responses to habitat degradation in any tropical forest environment. We analysed the impact of logging intensity on the individual occurrence patterns of 1,681 taxa belonging to 86 taxonomic orders and 126 functional groups in Sabah, Malaysia. Our results demonstrate the existence of two conservation-relevant thresholds. First, lightly logged forests (<29% biomass removal) retain high conservation value and a largely intact functional composition, and are therefore likely to recover their pre-logging values if allowed to undergo natural regeneration. Second, the most extreme impacts occur in heavily degraded forests with more than two-thirds (>68%) of their biomass removed, and these are likely to require more expensive measures to recover their biodiversity value. Overall, our data confirm that primary forests are irreplaceable 5 , but they also reinforce the message that logged forests retain considerable conservation value that should not be overlooked., (© 2024. The Author(s).)

Objectives: To evaluate whether computed tomography (CT)-derived psoas major muscle measurements could predict preoperative cardiopulmonary exercise testing (CPET) performance and long-term mortality in patients undergoing major colorectal surgery and to compare predictive performance of psoas muscle measurements using 2D approach and 3D approach., Methods: A retrospective cohort study compliant with STROCSS standards was conducted. Consecutive patients undergoing major colorectal surgery between January 2011 and January 2017 following CPET as part of their preoperative assessment were included. Regression analyses were modelled to investigate association between the CT-derived psoas major muscle mass variables [total psoas muscle area (TPMA), total psoas muscle volume (TPMV) and psoas muscle index (PMI)] and CPET performance and mortality (1-year and 5-year). Discriminative performances of the variables were evaluated using Receiver Operating Characteristic (ROC) curve analysis., Results: A total of 457 eligible patients were included. The median TPMA and TPMV were 21 ​cm 2 (IQR: 15-27) and 274 ​cm 3 (IQR: 201-362), respectively. The median PMI measured via 2D and 3D approaches were 7 ​cm 2 /m 2 (IQR: 6-9) and 99 ​cm 3 /m 2 (IQR: 76-120), respectively. The risks of 1-year and 5-year mortality were 7.4% and 27.1%, respectively. Regression analyses showed TPMA, TPMV, and PMI can predict preoperative CPET performance and long-term mortality. However, ROC curve analyses showed no significant difference in predictive performance amongst TPMA, TPMV, and PMI., Conclusion: Radiologically-measured psoas muscle mass variables may predict preoperative CPET performance and may be helpful with informing more objective selection of patients for preoperative CPET and prehabilitation., Competing Interests: Declaration of competing interest Damian M. Bailey is Editor-in-Chief of Experimental Physiology, Chair of the Life Sciences Working Group, a member of the Human Spaceflight and Exploration Science Advisory Committee to the European Space Agency, a member of the Space Exploration Advisory Committee to the UK Space Agency, and a member of the National Cardiovascular Network for Wales and South East Wales Vascular Network. Damian M. Bailey is also affiliated to the companies FloTBI Inc. and Bexorg Inc., focused on the technological development of novel biomarkers of brain injury in humans. All other authors declare no conflict of interest., (Copyright © 2024 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.)

An often-quoted statement attributed to Wolfgang Pauli is that God made the bulk, but the surface was invented by the devil. Although humorous, the statement really reflects frustration in developing a detailed picture of a surface. In the last several decades, that frustration has begun to abate with numerous techniques providing clues to interactions and reactions at surfaces. Often these techniques require considerable prior knowledge. Complex mixtures on irregular or soft surfaces-complex interfaces-thus represent the last frontier. Two optical techniques: sum frequency generation (SFG) and second harmonic generation (SHG) are beginning to lift the veil on complex interfaces. Of these techniques, SFG with one excitation in the infrared has the potential to provide exquisite molecular- and moiety-specific vibrational data. This Perspective is intended both to aid newcomers in gaining traction in this field and to demonstrate the impact of high-phase resolution. It starts with a basic description of light-induced surface polarization that is at the heart of SFG. The sum frequency is generated when the input fields are sufficiently intense that the interaction is nonlinear. This nonlinearity represents a challenge for disentangling data to reveal the molecular-level picture. Three, high-phase-resolution methods that reveal interactions at the surface are described., (2023 Published under an exclusive license by the AVS.)

The extent to which patients with an abdominal aortic aneurysm (AAA) should exercise remains unclear, given theoretical concerns over the perceived risk of blood pressure-induced rupture, which is often catastrophic. This is especially pertinent during cardiopulmonary exercise testing, when patients are required to perform incremental exercise to symptom-limited exhaustion for the determination of cardiorespiratory fitness. This multimodal metric is being used increasingly as a complementary diagnostic tool to inform risk stratification and subsequent management of patients undergoing AAA surgery. In this review, we bring together a multidisciplinary group of physiologists, exercise scientists, anaesthetists, radiologists and surgeons to challenge the enduring 'myth' that AAA patients should be fearful of and avoid rigorous exercise. On the contrary, by appraising fundamental vascular mechanobiological forces associated with exercise, in conjunction with 'methodological' recommendations for risk mitigation specific to this patient population, we highlight that the benefits conferred by cardiopulmonary exercise testing and exercise training across the continuum of intensity far outweigh the short-term risks posed by potential AAA rupture., (© 2023 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Background: To what extent sex-related differences in cardiorespiratory fitness (CRF) impact postoperative patient mortality and corresponding implications for surgical risk stratification remains to be established., Methods: To examine this, we recruited 640 patients (366 males vs. 274 females) who underwent cardiopulmonary exercise testing prior to elective colorectal surgery. Patients were defined high risk if peak oxygen uptake was <14.3 mL kg -1  min -1 and ventilatory equivalent for carbon dioxide at 'anaerobic threshold' >34. Between-sex CRF and mortality was assessed, and sex-specific CRF thresholds predictive of mortality was calculated., Results: Seventeen percent of deaths were attributed to sub-threshold CRF, which was higher than established risk factors for cardiovascular disease (CVD). The group (independent of sex) exhibited a 5-fold higher mortality (high vs. low risk patients hazard ratio = 4.80, 95% confidence interval 2.73-8.45, p < 0.001). Females exhibited 39% lower CRF (p < 0.001) with more classified high risk than males (36 vs. 23%, p = 0.001), yet mortality was not different (p = 0.544). Upon reformulation of sex-specific CRF thresholds, lower cut-offs for mortality were observed in females, and consequently, fewer (20%) were stratified with sub-threshold CRF compared to the original 36% (p < 0.001)., Conclusions: Low CRF accounted for more deaths than traditional CVD risk factors, and when CRF was considered relative to sex, the disproportionate number of females stratified unfit was corrected. These findings support clinical consideration of 'sex-specific' CRF thresholds to better inform postoperative mortality and improve surgical risk stratification., (© 2023 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Purpose: To determine the effects of dietary sugar or carbohydrate restriction on physical activity energy expenditure, energy intake, and physiological outcomes across 24 h., Methods: In a randomized, open-label crossover design, twenty-five healthy men (n = 10) and women (n = 15) consumed three diets over a 24-h period: moderate carbohydrate and sugar content (MODSUG = 50% carbohydrate [20% sugars], 15% protein, 35% fat); low sugar content (LOWSUG = 50% carbohydrate [< 5% sugars], 15% protein, 35% fat); and low carbohydrate content (LOWCHO = 8% carbohydrate [< 5% sugars], 15% protein, 77% fat). Postprandial metabolic responses to a prescribed breakfast (20% EI) were monitored under laboratory conditions before an ad libitum test lunch, with subsequent diet and physical activity monitoring under free-living conditions until blood sample collection the following morning., Results: The MODSUG, LOWSUG and LOWCHO diets resulted in similar mean [95%CI] rates of both physical activity energy expenditure (771 [624, 919] vs. 677 [565, 789] vs. 802 [614, 991] kcal·d -1 ; p = 0.29] and energy intake (2071 [1794, 2347] vs. 2195 [1918, 2473] vs. 2194 [1890, 2498] kcal·d -1 ; P = 0.34), respectively. The LOWCHO condition elicited the lowest glycaemic and insulinaemic responses to breakfast (P < 0.01) but the highest 24-h increase in LDL-cholesterol concentrations (P < 0.001), with no differences between the MODSUG and LOWSUG treatments. Leptin concentrations decreased over 24-h of consuming LOWCHO relative to LOWSUG (p < 0.01)., Conclusion: When energy density is controlled for, restricting either sugar or total dietary carbohydrate does not modulate physical activity level or energy intake over a 24-h period (~ 19-h free-living) despite substantial metabolic changes., Clinical Trials Registration Id: NCT03509610, https://clinicaltrials.gov/show/NCT03509610., (© 2022. The Author(s).)

Background:  In the United Kingdom, the most common surgical approach for repair of open abdominal aortic aneurysms (AAAs) is transperitoneal (TP). However, retroperitoneal (RP) approach is favored in those with more complex vascular anatomy often requiring a cross-clamp on the aorta superior to the renal arteries. This study compared these approaches in patients matched on all major demographic, comorbid, anatomic, and physiological variables., Methods:  Fifty-seven patients (TP: n  = 24; RP: n  = 33) unsuitable for endovascular aneurysm repair underwent preoperative cardiopulmonary exercise testing prior to open AAA repair. The surgical approach undertaken was dictated by individual surgeon preference. Postoperative mortality, complications, and length of hospital stay (LoS) were recorded. Patients were further stratified according to infrarenal (IR) or suprarenal/supraceliac (SR/SC) surgical clamping. Systemic inflammation (C-reactive protein) and renal function (serum creatinine and estimated glomerular filtration rate) were recorded., Results:  Twenty-three (96%) of TP patients only required an IR clamp compared with 12 (36%) in the RP group. Postoperative systemic inflammation was lower in RP patients ( p  = 0.002 vs. TP) and fewer reported pulmonary/gastrointestinal complications whereas renal impairment was more marked in those receiving SR/SC clamps ( p  < 0.001 vs. IR clamp). RP patients were defined by lower LoS ( p  = 0.001), while mid-/long-term mortality was low/comparable with TP, resulting in considerable cost savings., Conclusion:  Despite the demands of more complicated vascular anatomy, the clinical and economic benefits highlighted by these findings justify the more routine adoption of the RP approach for complex AAA repair., Competing Interests: The authors declare no conflict of interest related to this article., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Background: Initial clinical evaluation (ICE) is traditionally considered a useful screening tool to identify frail patients during the preoperative assessment. However, emerging evidence supports the more objective assessment of cardiorespiratory fitness (CRF) via cardiopulmonary exercise testing (CPET) to improve surgical risk stratification. Herein, we compared both subjective and objective assessment approaches to highlight the interpretive idiosyncrasies., Methods: As part of routine preoperative patient contact, patients scheduled for major surgery were prospectively "eyeballed" (ICE) by two experienced clinicians before more detailed history taking that also included the American Society of Anesthesiologists score classification. Each patient was subjectively judged to be either "frail" or "not frail" by ICE and "fit" or "unfit" from a thorough review of the medical notes. Subjective data were compared against the more objective validated assessment of postoperative outcomes using established CPET "cut-off" metrics incorporating peak pulmonary oxygen uptake, V̇O 2PEAK at the anaerobic threshold (V̇O 2 -AT), and ventilatory equivalent for carbon dioxide that collectively informed risk stratification. These data were retrospectively extracted from a single-center prospective National Health Service database. Data were analyzed using the Chi-square automatic interaction detection decision tree method., Results: A total of 127 patients were examined that comprised 58% male and 42% female patients aged 69 ± 10 years with a body mass index of 29 ± 7 kg/m 2 . Patients were poorly conditioned with a V̇O 2PEAK almost 20% lower than predicted for age, sex-matched healthy controls with 35% exhibiting a V̇O 2 -AT < 11 ml/kg/min. Disagreement existed between the subjective assessments of risk with ∼34% of patients classified as not frail on ICE were considered unfit by notes review (p < .0001). Furthermore, ∼35% of patients considered not frail on ICE and ∼31% of patients considered fit by notes review exhibited a V̇O 2 -AT < 11 ml/kg/min, and of these, ∼28% and ∼19% were classified as intermediate to high risk., Conclusions: These findings highlight the interpretive limitations associated with the subjective assessment of patient frailty with surgical risk classification underestimated in up to a third of patients compared to the validated assessment of CRF. They reinforce the benefits of a more objective and integrated approach offered by CPET that may help us to improve perioperative risk assessment and better direct critical care provision in patients scheduled for "high-stakes" surgery including open thoracoabdominal aortic aneurysm repair., (© 2022 The Authors. Journal of Cardiac Surgery published by Wiley Periodicals LLC.)

New Findings: What is the topic of this review? The relationships and physiological mechanisms underlying the clinical benefits of cardiorespiratory fitness (CRF) in patients undergoing major intra-abdominal surgery. What advances does it highlight? Elevated CRF reduces postoperative morbidity/mortality, thus highlighting the importance of CRF as an independent risk factor. The vascular protection afforded by exercise prehabilitation can further improve surgical risk stratification and postoperative outcomes., Abstract: Surgery accounts for 7.7% of all deaths globally and the number of procedures is increasing annually. A patient's 'fitness for surgery' describes the ability to tolerate a physiological insult, fundamental to risk assessment and care planning. We have evolved as obligate aerobes that rely on oxygen (O 2 ). Systemic O 2 consumption can be measured via cardiopulmonary exercise testing (CPET) providing objective metrics of cardiorespiratory fitness (CRF). Impaired CRF is an independent risk factor for mortality and morbidity. The perioperative period is associated with increased O 2 demand, which if not met leads to O 2 deficit, the magnitude and duration of which dictates organ failure and ultimately death. CRF is by far the greatest modifiable risk factor, and optimal exercise interventions are currently under investigation in patient prehabilitation programmes. However, current practice demonstrates potential for up to 60% of patients, who undergo preoperative CPET, to have their fitness incorrectly stratified. To optimise this work we must improve the detection of CRF and reduce potential for interpretive error that may misinform risk classification and subsequent patient care, better quantify risk by expressing the power of CRF to predict mortality and morbidity compared to traditional cardiovascular risk factors, and improve patient interventions with the capacity to further enhance vascular adaptation. Thus, a better understanding of CRF, used to determine fitness for surgery, will enable both clinicians and exercise physiologists to further refine patient care and management to improve survival., (© 2022 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

This study investigated whether carbohydrate-energy replacement immediately after prolonged endurance exercise attenuates insulin sensitivity the following morning, and whether exercise improves insulin sensitivity the following morning independent of an exercise-induced carbohydrate deficit. Oral glucose tolerance and whole-body insulin sensitivity were compared the morning after 3 evening conditions, involving (1) treadmill exercise followed by a carbohydrate replacement drink (200 or 150 g maltodextrin for males and females, respectively; CHO-replace ); (2) treadmill exercise followed by a non-caloric, taste-matched placebo ( CHO-deficit ); or (3) seated rest with no drink provided ( Rest ). Treadmill exercise involved 90 minutes at ∼80% age-predicted maximum heart rate. Seven males and 2 females (aged 23 ± 1 years; body mass index 24.0 ± 2.7 kg·m -2 ) completed all conditions in a randomised order. Matsuda index improved by 22% (2.2 [0.3, 4.0] au, p  = 0.03) and HOMA2-IR improved by 10% (-0.04 [-0.08, 0.00] au, p  = 0.04) in CHO-deficit versus CHO-replace , without corresponding changes in postprandial glycaemia. Outcomes were similar between Rest and other conditions. These data suggest that improvements to insulin sensitivity in healthy populations following acute moderate/vigorous intensity endurance exercise may be dependent on the presence of a carbohydrate-energy deficit. Novelty: Restoration of carbohydrate balance following acute endurance exercise attenuated whole-body insulin sensitivity. Exercise per se failed to enhance whole-body insulin sensitivity. Maximising or prolonging the post-exercise carbohydrate deficit may enhance acute benefits to insulin sensitivity.

It is unclear whether neuromuscular electrical stimulation (NMES) has meaningful metabolic effects when users have the opportunity to self-select the intensity to one that can be comfortably tolerated. Nine healthy men aged 28 ± 9 y (mean ± SD) with a body mass index 22.3 ± 2.3 kg/m 2 completed 3 trials involving a 2-h oral glucose tolerance test whilst, in a randomised counterbalanced order, (1) sitting motionless (SIT), (2) standing motionless (STAND); and (3) sitting motionless with NMES of quadriceps and calves at a self-selected tolerable intensity. The mean (95% confidence interval [CI]) total energy expenditure was greater in the NMES trial (221 [180-262] kcal/2 h) and STAND trial (178 [164-191] kcal/2 h) than during SIT (159 [150-167] kcal/2 h) (both, p < 0.05). This was primarily driven by an increase in carbohydrate oxidation in the NMES and STAND trials compared with the SIT trial ( p < 0.05). Postprandial insulin iAUC was lower in both NMES and STAND compared with SIT (16.4 [7.7-25.1], 17 [7-27] and 22.6 [10.8-34.4] nmol·120 min/L, respectively; both, p < 0.05). Compared with sitting, both NMES and STAND increased energy expenditure and whole-body carbohydrate oxidation and reduced postprandial insulin concentrations in healthy men, with more pronounced effects seen with NMES. Self-selected NMES is a potential strategy for improving metabolic health. This trial is registered at ClinicalTrials.gov (ID: NCT04389736). Novelty: NMES at a comfortable intensity enhances energy expenditure and carbohydrate oxidation, and reduces postprandial insulinemia. Thus, self-selected NMES represents a potential strategy to improve metabolic health.

Single atom (SA), noble metal catalysts are of interest due to high projected catalytic activity while minimizing cost. Common issues facing many synthesis methodologies include complicated processes, low yields of SA product, and production of mixtures of SA and nanoparticles (NPs). Herein we report a simple, room-temperature synthesis of single Pt-atom decorated, anatase Fe-doped TiO 2 particles that leverages the Fe dopant as an engineered defect site to photodeposit and stabilize atomically dispersed Pt. Both particle morphology and Fe dopant location are based on thermodynamic principles (Gibbs-Wulff construction). CO-DRIFTS (diffuse reflectance infrared Fourier transform spectroscopy) reveals absence of bridge-bonded CO signal, confirming atomically dispersed Pt. XAS (X-ray absorption spectroscopy) of both Pt and Fe indicates Fe-O-Pt bonding that persists through catalytic cycling. Mass balance indicates that the Pt loading on single particles is 2.5 wt % Pt; the single Pt-atom decorated nanoparticle yield is 17%. Pt-containing particles show more than an order-of-magnitude increased photooxidation efficiency relative to particles containing only Fe. High single-atom-Pt yield, ease of synthesis, and high catalytic activity demonstrate the utility and promise of this method. The principles of this photodeposition synthesis allow for its generalizability toward other SA metals of catalytic interest.

This study investigated metabolic, endocrine, appetite and mood responses to a maximal eating occasion in fourteen men (mean: age 28 (sd 5) years, body mass 77·2 (sd 6·6) kg and BMI 24·2 (sd 2·2) kg/m2) who completed two trials in a randomised crossover design. On each occasion, participants ate a homogenous mixed-macronutrient meal (pizza). On one occasion, they ate until 'comfortably full' (ad libitum) and on the other, until they 'could not eat another bite' (maximal). Mean energy intake was double in the maximal (13 024 (95 % CI 10 964, 15 084) kJ; 3113 (95 % CI 2620, 3605) kcal) compared with the ad libitum trial (6627 (95 % CI 5708, 7547) kJ; 1584 (95 % CI 1364, 1804) kcal). Serum insulin incremental AUC (iAUC) increased approximately 1·5-fold in the maximal compared with ad libitum trial (mean: ad libitum 43·8 (95 % CI 28·3, 59·3) nmol/l × 240 min and maximal 67·7 (95 % CI 47·0, 88·5) nmol/l × 240 min, P < 0·01), but glucose iAUC did not differ between trials (ad libitum 94·3 (95 % CI 30·3, 158·2) mmol/l × 240 min and maximal 126·5 (95 % CI 76·9, 176·0) mmol/l × 240 min, P = 0·19). TAG iAUC was approximately 1·5-fold greater in the maximal v. ad libitum trial (ad libitum 98·6 (95 % CI 69·9, 127·2) mmol/l × 240 min and maximal 146·4 (95 % CI 88·6, 204·1) mmol/l × 240 min, P < 0·01). Total glucagon-like peptide-1, glucose-dependent insulinotropic peptide and peptide tyrosine-tyrosine iAUC were greater in the maximal compared with ad libitum trial (P < 0·05). Total ghrelin concentrations decreased to a similar extent, but AUC was slightly lower in the maximal v. ad libitum trial (P = 0·02). There were marked differences on appetite and mood between trials, most notably maximal eating caused a prolonged increase in lethargy. Healthy men have the capacity to eat twice the energy content required to achieve comfortable fullness at a single meal. Postprandial glycaemia is well regulated following initial overeating, with elevated postprandial insulinaemia probably contributing.

Environmental conditions play a major role in shaping the spatial distributions of pathogens, which in turn can drive local adaptation and divergence in host genetic diversity. Haemosporidians, such as Plasmodium (malaria), are a strong selective force, impacting survival and fitness of hosts, with geographic distributions largely determined by habitat suitability for their insect vectors. Here, we have tested whether patterns of fine-scale local adaptation to malaria are replicated across discrete, ecologically differing island populations of Berthelot's pipits Anthus berthelotii . We sequenced TLR4, an innate immunity gene that is potentially under positive selection in Berthelot's pipits, and two SNPs previously identified as being associated with malaria infection in a genome-wide association study (GWAS) in Berthelot's pipits in the Canary Islands. We determined the environmental predictors of malaria infection, using these to estimate variation in malaria risk on Porto Santo, and found some congruence with previously identified environmental risk factors on Tenerife. We also found a negative association between malaria infection and a TLR4 variant in Tenerife. In contrast, one of the GWAS SNPs showed an association with malaria risk in Porto Santo, but in the opposite direction to that found in the Canary Islands GWAS. Together, these findings suggest that disease-driven local adaptation may be an important factor in shaping variation among island populations., Competing Interests: None declared., (© 2019 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Surgery for radical treatment of esophageal cancer (EC) carries significant inherent risk. The objective identification of patients who are at high risk of complications is of importance. In this study the prognostic value of cardiopulmonary fitness variables (CPF) derived from cardiopulmonary exercise testing (CPET) was assessed in patients undergoing potentially curative surgery for EC within an enhanced recovery program. OC patients underwent preoperative CPET using automated breath-by-breath respiratory gas analysis, with measurements taken during a ramped exercise test on a bicycle. The prognostic value of V ˙ O 2 Peak , Anaerobic Threshold (AT) and VE/VCO 2 derived from CPET were studied in relation to post-operative morbidity, which was collected prospectively, and overall survival. Consecutive 120 patients were included for analysis (median age 65 years, 100 male, 75 neoadjuvant therapy). Median AT in the cohort developing major morbidity (Clavien-Dindo classification >2) was 10.4 mL/kg/min compared with 11.3 mL/kg/min with no major morbidity (P = 0.048). Median V ˙ O 2 Peak in the cohort developing major morbidity was 17.0 mL/kg/min compared with 18.7 mL/kg/min in the cohort (P = 0.009). V ˙ O 2 Peak optimum cut-off was 17.0 mL/kg/min (sensitivity 70%, specificity 53%) and for AT was 10.5 mL/kg/min (sensitivity 60%, specificity 44%). Multivariable analysis revealed V ˙ O 2 Peak to be the only independent factor to predict major morbidity (OR 0.85, 95% CI 0.75-0.97, P = 0.018). Cumulative survival was associated with operative morbidity severity (χ 2  = 4.892, df = 1, P = 0.027). These results indicate that V ˙ O 2 Peak as derived from CPET is a significant predictor of major morbidity after oesophagectomy highlighting the physiological importance of cardiopulmonary fitness., (© 2019 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Approximately 50% of prostate cancers harbor the TMPRSS2:ERG fusion, resulting in elevated expression of the ERG transcription factor. Despite the identification of this subclass of prostate cancers, no personalized therapeutic strategies have achieved clinical implementation. Kinases are attractive therapeutic targets as signaling networks are commonly perturbed in cancers. The impact of elevated ERG expression on kinase signaling networks in prostate cancer has not been investigated. Resolution of this issue may identify novel therapeutic approaches for ERG-positive prostate cancers. In this study, we used quantitative mass spectrometry-based kinomic profiling to identify ERG-mediated changes to cellular signaling networks. We identified 76 kinases that were differentially expressed and/or phosphorylated in DU145 cells engineered to express ERG. In particular, the Traf2 and Nck-interacting kinase (TNIK) was markedly upregulated and phosphorylated on multiple sites upon ERG overexpression. Importantly, TNIK has not previously been implicated in prostate cancer. To validate the clinical relevance of these findings, we characterized expression of TNIK and TNIK phosphorylated at serine 764 (pS764) in a localized prostate cancer patient cohort and showed that nuclear enrichment of TNIK (pS764) was significantly positively correlated with ERG expression. Moreover, TNIK protein levels were dependent upon ERG expression in VCaP cells and primary cells established from a prostate cancer patient-derived xenograft. Furthermore, reduction of TNIK expression and activity by silencing TNIK expression or using the TNIK inhibitor NCB-0846 reduced cell viability, colony formation and anchorage independent growth. Therefore, TNIK represents a novel and actionable therapeutic target for ERG-positive prostate cancers that could be exploited to develop new treatments for these patients., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Research has previously shown that adding consistent stereoscopic information to self-motion displays can improve the vection in depth induced in physically stationary observers. In some past studies, the simulated eye-separation was always close to the observer's actual eye-separation, as the aim was to examine vection under ecological viewing conditions that provided consistent binocular and monocular self-motion information. The present study investigated whether large discrepancies between the observer's simulated and physical eye-separations would alter the vection-inducing potential of stereoscopic optic flow (either helping, hindering, or preventing the induction of vection). Our self-motion displays simulated eye-separations of 0 cm (the non-stereoscopic control), 3.25 cm (reduced from normal), 6.5 cm (approximately normal), and 13 cm (exaggerated relative to normal). The rated strength of vection in depth was found to increase systematically with the simulated eye-separation. While vection was the strongest in the 13-cm condition (stronger than even the 6.5-cm condition), the 3.25-cm condition still produced superior vection to the 0-cm control (i.e., it had significantly stronger vection ratings and shorter onset latencies). Perceptions of scene depth and object motion-in-depth speed were also found to increase with the simulated eye-separation. As expected based on the findings of previous studies, correlational analyses suggested that the stereoscopic advantage for vection (found for all of our non-zero eye-separation conditions) was due to the increase in perceived motion-in-depth.

Metabarcoding has been used in a range of ecological applications such as taxonomic assignment, dietary analysis and the analysis of environmental DNA. However, after a decade of use in these applications there is little consensus on the extent to which proportions of reads generated corresponds to the original proportions of species in a community. To quantify our current understanding, we conducted a structured review and meta-analysis. The analysis suggests that a weak quantitative relationship may exist between the biomass and sequences produced (slope = 0.52 ± 0.34, p < 0.01), albeit with a large degree of uncertainty. None of the tested moderators, sequencing platform type, the number of species used in a trial or the source of DNA, were able to explain the variance. Our current understanding of the factors affecting the quantitative performance of metabarcoding is still limited: additional research is required before metabarcoding can be confidently utilized for quantitative applications. Until then, we advocate the inclusion of mock communities when metabarcoding as this facilitates direct assessment of the quantitative ability of any given study., (© 2018 The Authors. Molecular Ecology Published by John Wiley & Sons Ltd.)

New Findings: What is the central question of this study? To what extent cardiorespiratory fitness is impaired in patients with abdominal aortic aneurysmal (AAA) disease and corresponding implications for postoperative survival requires further investigation. What is the main finding and its importance? Cardiorespiratory fitness is impaired in patients with AAA disease. Patients with peak oxygen uptake of <13.1 ml O 2  kg -1  min -1 and ventilatory equivalent for carbon dioxide at anaerobic threshold ≥34 are associated with increased risk of postoperative mortality at 2 years. These findings demonstrate that cardiorespiratory fitness can predict mid-term postoperative survival in AAA patients, which may help to direct care provision., Abstract: Preoperative cardiopulmonary exercise testing is a standard assessment of cardiorespiratory fitness (CRF) and risk stratification. However, to what extent CRF is impaired in patients undergoing surgical repair of abdominal aortic aneurysm (AAA) disease and the corresponding implications for postoperative outcome requires further investigation. We measured CRF during an incremental exercise test to exhaustion using online respiratory gas analysis in patients with AAA disease (n = 124, aged 72 ± 7 years) and healthy sedentary control subjects (n = 104, aged 70 ± 7 years). Postoperative survival was examined for association with CRF, and threshold values were calculated for independent predictors of mortality. Patients who underwent preoperative cardiopulmonary exercise testing before surgical repair had lower CRF [age-adjusted mean difference of 12.5 ml O 2  kg -1  min -1 for peak oxygen uptake ( V ̇ O 2 peak ), P < 0.001 versus control subjects]. After multivariable analysis, both V ̇ O 2 peak and the ventilatory equivalent for carbon dioxide at anaerobic threshold ( V ̇ E / V ̇ C O 2 - AT ) were independent predictors of mid-term postoperative survival (2 years). Hazard ratios of 5.27 (95% confidence interval 1.62-17.14, P = 0.006) and 3.26 (95% confidence interval 1.00-10.59, P = 0.049) were observed for V ̇ O 2 peak  < 13.1 ml O 2  kg -1  min -1 and V ̇ E / V ̇ C O 2 - AT ≥ 34, respectively. Thus, CRF is lower in patients with AAA, and those with a V ̇ O 2 peak  < 13.1 ml O 2  kg -1  min -1 and V ̇ E / V ̇ C O 2 - AT ≥ 34 are associated with a markedly increased risk of postoperative mortality. Collectively, our findings demonstrate that CRF can predict mid-term postoperative survival in AAA patients, which may help to direct care provision., (© 2018 The Authors. Experimental Physiology © 2018 The Physiological Society.)

Importin 13 (IPO13) is a key member of the importin β superfamily, which can transport cargoes both into and out of the nucleus to contribute to a variety of important cellular processes. IPO13 is known to undergo phosphorylation, but the impact of this on function has not been investigated. Here, we show for the first time that IPO13 is phosphorylated by cAMP-dependent protein kinase A specifically at serine 193. Results from fluorescence recovery after photobleaching and fluorescence loss in photobleaching approaches establish that negative charge at serine 193 through phosphorylation or point mutation both reduces IPO13 nuclear import and increases its nuclear export. Importantly, phosphorylation also appears to enhance cargo interaction on the part of IPO13, with significant impact on localization, as shown for the Pax6 homeobox-containing transcription partner. This is the first report that IPO13 can be phosphorylated at Ser193 and that this modification regulates IPO13 subcellular localization and nucleocytoplasmic transport function, with important implications for IPO13's role in development and other processes., (© 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

Background: Cardiorespiratory fitness can inform patient care, although to what extent natural variation in CRF influences clinical practice remains to be established. We calculated natural variation for cardiopulmonary exercise test (CPET) metrics, which may have implications for fitness stratification., Methods: In a two-armed experiment, critical difference comprising analytical imprecision and biological variation was calculated for cardiorespiratory fitness and thus defined the magnitude of change required to claim a clinically meaningful change. This metric was retrospectively applied to 213 patients scheduled for colorectal surgery. These patients underwent CPET and the potential for misclassification of fitness was calculated. We created a model with boundaries inclusive of natural variation [critical difference applied to oxygen uptake at anaerobic threshold (V˙O 2 -AT): 11 ml O 2  kg -1  min -1 , peak oxygen uptake (V˙O 2 peak): 16 ml O 2  kg -1  min -1 , and ventilatory equivalent for carbon dioxide at AT (V̇ E /V̇CO 2 -AT): 36]., Results: The critical difference for V˙O 2 -AT, V˙O 2 peak, and V˙ E /V˙CO 2 -AT was 19%, 13%, and 10%, respectively, resulting in false negative and false positive rates of up to 28% and 32% for unfit patients. Our model identified boundaries for unfit and fit patients: AT <9.2 and ≥13.6 ml O 2  kg -1  min -1 , V˙O 2 peak <14.2 and ≥18.3 ml kg -1  min -1 , V˙ E /V˙CO 2 -AT ≥40.1 and <32.7, between which an area of indeterminate-fitness was established. With natural variation considered, up to 60% of patients presented with indeterminate-fitness., Conclusions: These findings support a reappraisal of current clinical interpretation of cardiorespiratory fitness highlighting the potential for incorrect fitness stratification when natural variation is not accounted for., (Copyright © 2018 British Journal of Anaesthesia. All rights reserved.)

Localized outbreaks of jellyfish, known as blooms, cause a variety of adverse ecological and economic effects. However, fundamental aspects of their ecology remain unknown. Notably, there is scant information on the role jellyfish occupy in food webs: in many ecosystems, few or no predators are known. To identify jellyfish consumers in the Irish Sea, we conducted a molecular gut content assessment of 50 potential predators using cnidarian-specific mtDNA primers and sequencing. We show that jellyfish predation may be more common than previously acknowledged: uncovering many previously unknown jellyfish predators. A substantial proportion of herring and whiting were found to have consumed jellyfish. Rare ingestion was also detected in a variety of other species. Given the phenology of jellyfish in the region, we suggest that the predation was probably targeting juvenile stages of the jellyfish life cycle., Competing Interests: We declare we have no competing interests.

Importin 13 (Imp13) is a bidirectional nuclear transporter of proteins involved in a range of important cellular processes, with an N-terminally truncated inhibitory isoform (tImp13) specifically expressed in testis. To gain insight into tImp13 function, we performed a yeast-2-hybrid screen from a human testis cDNA library, identifying for the first time a suite of interactors with roles in diverse cellular process. We validated the interaction of tImp13 with Eukaryotic translation initiation factor 4γ2 (EIF4G2) and High mobility group containing protein 20A (HMG20A), benchmarking that with glucocorticoid receptor (GR), a known Imp13 interactor expressed in testis. Coimmunoprecipitation assays indicated association of both tImp13 and Imp13 with EIF4G2, HMG20A and GR. Quantitative confocal microscopic analysis revealed the ability of tImp13 to inhibit the nuclear localisation of EIF4G2, HMG20A and GR, as well as that of Imp13 to act as a nuclear exporter for both EIF4G2 and HMG20A, and as a nuclear importer for GR. The physiological relevance of these results was highlighted by the cytoplasmic localisation of EIF4G2, HMG20A and GR in pachytene spermatocytes/round spermatids in the murine testis where tImp13 is present at high levels, in contrast to the nuclear localisation of HMG20A and GR in spermatogonia, where tImp13 is largely absent. Interestingly, Imp13, EIF4G2, HMG20A and GR were found together in the acrosome vesicle of murine epididymal spermatozoa. Collectively, our findings show, for the first time, that tImp13 may have a functional role in the mature spermatozoa, in addition to that in the meiotic germ cells of the testis., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Although observer motions project different patterns of optic flow to our left and right eyes, there has been surprisingly little research into potential stereoscopic contributions to self-motion perception. This study investigated whether visually induced illusory self-motion (i.e., vection) is influenced by the addition of consistent stereoscopic information to radial, circular, and spiral (i.e., combined radial + circular) patterns of optic flow. Stereoscopic vection advantages were found for radial and spiral (but not circular) flows when monocular motion signals were strong. Under these conditions, stereoscopic benefits were greater for spiral flow than for radial flow. These effects can be explained by differences in the motion aftereffects generated by these displays, which suggest that the circular motion component in spiral flow selectively reduced adaptation to stereoscopic motion-in-depth. Stereoscopic vection advantages were not observed for circular flow when monocular motion signals were strong, but emerged when monocular motion signals were weakened. These findings show that stereoscopic information can contribute to visual self-motion perception in multiple ways.

Understanding the spatial scale at which selection acts upon adaptive genetic variation in natural populations is fundamental to our understanding of evolutionary ecology, and has important ramifications for conservation. The environmental factors to which individuals of a population are exposed can vary at fine spatial scales, potentially generating localized patterns of adaptation. Here, we compared patterns of neutral and major histocompatibility complex (MHC) variation within an island population of Berthelot's pipit (Anthus berthelotii) to assess whether landscape-level differences in pathogen-mediated selection generate fine-scale spatial structuring in these immune genes. Specifically, we tested for spatial associations between the distribution of avian malaria, and the factors previously shown to influence that distribution, and MHC variation within resident individuals. Although we found no overall genetic structure across the population for either neutral or MHC loci, we did find localized associations between environmental factors and MHC variation. One MHC class I allele (ANBE48) was directly associated with malaria infection risk, while the presence of the ANBE48 and ANBE38 alleles within individuals correlated (positively and negatively, respectively) with distance to the nearest poultry farm, an anthropogenic factor previously shown to be an important determinant of disease distribution in the study population. Our findings highlight the importance of considering small spatial scales when studying the patterns and processes involved in evolution at adaptive loci., (© 2016 The Authors. Molecular Ecology Published by John Wiley & Sons Ltd.)

Anthropogenic modification of habitats may reduce the resources available for native species, leading to population declines and extinction. These same habitats often have the highest richness of non-native species. This pattern may be explained if recently human-modified habitats provide novel resources that are more accessible to non-native species than native species. Using non-native birds in the Iberian Peninsula as a case study, we conduct a large-scale study to investigate whether non-native species are positively associated with human modified habitats, and to investigate whether this positive association may be driven by the presence of resources that are not fully exploited by native species. We do this by comparing the functional diversity and resource use of native and non-native bird communities in a recently human-modified habitat (rice fields) and in more traditional habitats in the Iberian Peninsula. The functional diversity of native bird communities was lower in rice fields, but non-native birds were positively associated with rice fields and plugged this gap. Differences in resource use between native and non-native species allowed non-native species to exploit resources that were plentiful in rice fields, supporting the role of underexploited resources in driving the positive association of non-native birds with rice fields. Our results provide a potential mechanism explaining the positive association of non-native species with anthropogenic habitats, and further work is needed to test if this applies more generally.

Invertebrates are dominant species in primary tropical rainforests, where their abundance and diversity contributes to the functioning and resilience of these globally important ecosystems. However, more than one-third of tropical forests have been logged, with dramatic impacts on rainforest biodiversity that may disrupt key ecosystem processes. We find that the contribution of invertebrates to three ecosystem processes operating at three trophic levels (litter decomposition, seed predation and removal, and invertebrate predation) is reduced by up to one-half following logging. These changes are associated with decreased abundance of key functional groups of termites, ants, beetles and earthworms, and an increase in the abundance of small mammals, amphibians and insectivorous birds in logged relative to primary forest. Our results suggest that ecosystem processes themselves have considerable resilience to logging, but the consistent decline of invertebrate functional importance is indicative of a human-induced shift in how these ecological processes operate in tropical rainforests.

Many of the world's languages face serious risk of extinction. Efforts to prevent this cultural loss are severely constrained by a poor understanding of the geographical patterns and drivers of extinction risk. We quantify the global distribution of language extinction risk-represented by small range and speaker population sizes and rapid declines in the number of speakers-and identify the underlying environmental and socioeconomic drivers. We show that both small range and speaker population sizes are associated with rapid declines in speaker numbers, causing 25% of existing languages to be threatened based on criteria used for species. Language range and population sizes are small in tropical and arctic regions, particularly in areas with high rainfall, high topographic heterogeneity and/or rapidly growing human populations. By contrast, recent speaker declines have mainly occurred at high latitudes and are strongly linked to high economic growth. Threatened languages are numerous in the tropics, the Himalayas and northwestern North America. These results indicate that small-population languages remaining in economically developed regions are seriously threatened by continued speaker declines. However, risks of future language losses are especially high in the tropics and in the Himalayas, as these regions harbour many small-population languages and are undergoing rapid economic growth.

How the environment influences the transmission and prevalence of disease in a population of hosts is a key aspect of disease ecology. The role that environmental factors play in host-pathogen systems has been well studied at large scales, that is, differences in pathogen pressures among separate populations of hosts or across land masses. However, despite considerable understanding of how environmental conditions vary at fine spatial scales, the effect of these parameters on host-pathogen dynamics at such scales has been largely overlooked. Here, we used a combination of molecular screening and GIS-based analysis to investigate how environmental factors determine the distribution of malaria across the landscape in a population of Berthelot's pipit (Anthus berthelotii, Bolle 1862) on the island of Tenerife (Canary Islands, Spain) using spatially explicit models that account for spatial autocorrelation. Minimum temperature of the coldest month was found to be the most important predictor of malaria infection at the landscape scale across this population. Additionally, anthropogenic factors such as distance to artificial water reservoirs and distance to poultry farms were important predictors of malaria. A model including these factors, and the interaction between distance to artificial water reservoirs and minimum temperature, best explained the distribution of malaria infection in this system. These results suggest that levels of malaria infection in this endemic species may be artificially elevated by the impact of humans. Studies such as the one described here improve our understanding of how environmental factors, and their heterogeneity, affect the distribution of pathogens within wild populations. The results demonstrate the importance of measuring fine-scale variation - and not just regional effects - to understand how environmental variation can influence wildlife diseases. Such understanding is important for predicting the future spread and impact of disease and may help inform disease management programmes as well as the conservation of specific host species., (© 2014 The Authors. Journal of Animal Ecology © 2014 British Ecological Society.)

A key factor in oncogenesis is the transport into the nucleus of oncogenic signalling molecules, such as Gli1 (glioma-associated oncogene homologue 1), the central transcriptional activator in the Hedgehog signalling pathway. Little is known, however, how factors such as Gli are transported into the nucleus and how this may be regulated by interaction with other cellular factors, such as the negative regulator suppressor of fused (SuFu). In the present study we show for the first time that nuclear entry of Gli1 is regulated by a unique mechanism through mutually exclusive binding by its nuclear import factor Impβ1 (importin β1) and SuFu. Using quantitative live mammalian cell imaging, we show that nuclear accumulation of GFP-Gli1 fusion proteins, but not of a control protein, is specifically inhibited by co-expression of SuFu. Using a direct binding assay, we show that Impβ1 exhibits a high nanomolar affinity to Gli1, with specific knockdown of Impβ1 expression being able to inhibit Gli1 nuclear accumulation, thus implicating Impβ1 as the nuclear transporter for Gli1 for the first time. SuFu also binds to Gli1 with a high nanomolar affinity, intriguingly being able to compete with Impβ1 for binding to Gli1, through the fact that the sites for SuFu and Impβ1 binding overlap at the Gli1 N-terminus. The results indicate for the first time that the relative intracellular concentrations of SuFu and Impβ1 are likely to determine the localization of Gli1, with implications for its action in cancer, as well as in developmental systems.

Regulation of nuclear protein import is central to many cellular processes such as development, with a key mechanism being factors that retain cargoes in the cytoplasm that normally localize in the nucleus. The breast cancer antigen BRCA1-binding protein BRAP2 has been reported as a novel negative regulator of nuclear import of various nuclear localization signal (NLS)-containing viral and cellular proteins, but although implicated in differentiation pathways and highly expressed in tissues including testis, the gamut of targets for BRAP2 action in a developmental context is unknown. As a first step towards defining the BRAP2 interactome, we performed a yeast-2-hybrid screen to identify binding partners of BRAP2 in human testis. Here we report characterization for the first time of three of these: the high mobility group (HMG)-box-domain-containing chromatin component HMG20A, nuclear mitotic apparatus protein NuMA1 and synaptic nuclear envelope protein SYNE2. Co-immunoprecipitation experiments indicate association of BRAP2 with HMG20A, NuMA1, and SYNE2 in testis, underlining the physiological relevance of the interactions, with immunohistochemistry showing that where BRAP2 is co-expressed with HMG20A and NuMA1, both are present in the cytoplasm, in contrast to their nuclear localization in other testicular cell types. Importantly, quantitative confocal microscopic analysis of cultured cells indicates that ectopic expression of BRAP2 inhibits nuclear localization of HMG20A and NuMA1, and prevents nuclear envelope accumulation of SYNE2, the first report of BRAP2 altering localization of a non-nuclear protein. These results imply for the first time that BRAP2 may have an important role in modulating subcellular localization during testicular development., (Copyright © 2013 Elsevier B.V. All rights reserved.)

The effects of climate change on biodiversity should depend in part on climate displacement rate (climate-change velocity) and its interaction with species' capacity to migrate. We estimated Late Quaternary glacial-interglacial climate-change velocity by integrating macroclimatic shifts since the Last Glacial Maximum with topoclimatic gradients. Globally, areas with high velocities were associated with marked absences of small-ranged amphibians, mammals, and birds. The association between endemism and velocity was weakest in the highly vagile birds and strongest in the weakly dispersing amphibians, linking dispersal ability to extinction risk due to climate change. High velocity was also associated with low endemism at regional scales, especially in wet and aseasonal regions. Overall, we show that low-velocity areas are essential refuges for Earth's many small-ranged species.

In 1847, Karl Bergmann proposed that temperature gradients are the key to understanding geographic variation in the body sizes of warm-blooded animals. Yet both the geographic patterns of body-size variation and their underlying mechanisms remain controversial. Here, we conduct the first assemblage-level global examination of 'Bergmann's rule' within an entire animal class. We generate global maps of avian body size and demonstrate a general pattern of larger body sizes at high latitudes, conforming to Bergmann's rule. We also show, however, that median body size within assemblages is systematically large on islands and small in species-rich areas. Similarly, while spatial models show that temperature is the single strongest environmental correlate of body size, there are secondary correlations with resource availability and a strong pattern of decreasing body size with increasing species richness. Finally, our results suggest that geographic patterns of body size are caused both by adaptation within lineages, as invoked by Bergmann, and by taxonomic turnover among lineages. Taken together, these results indicate that while Bergmann's prediction based on physiological scaling is remarkably accurate, it is far from the full picture. Global patterns of body size in avian assemblages are driven by interactions between the physiological demands of the environment, resource availability, species richness and taxonomic turnover among lineages.

Despite its wide implications for many ecological issues, the global pattern of spatial turnover in the occurrence of species has been little studied, unlike the global pattern of species richness. Here, using a database on the breeding distributions of birds, we present the first global maps of variation in spatial turnover for an entire taxonomic class, a pattern that has to date remained largely a matter of conjecture, based on theoretical expectations and extrapolation of inconsistent patterns from different biogeographic realms. We use these maps to test four predictions from niche theory as to the form that this variation should take, namely that turnover should increase with species richness, towards lower latitudes, and with the steepness of environmental gradients and that variation in turnover is determined principally by rare (restricted) species. Contrary to prediction, we show that turnover is high both in areas of extremely low and high species richness, does not increase strongly towards the tropics, and is related both to average environmental conditions and spatial variation in those conditions. These results are closely associated with a further important and novel finding, namely that global patterns of spatial turnover are driven principally by widespread species rather than the restricted ones. This complements recent demonstrations that spatial patterns of species richness are also driven principally by widespread species, and thus provides an important contribution towards a unified model of how terrestrial biodiversity varies both within and between the Earth's major land masses.