The purpose of the United Nations-guided process to establish Sustainable Development Goals is to galvanize governments and civil society to rise to the interlinked environmental, societal, and economic challenges we face in the Anthropocene. We argue that the process of setting Sustainable Development Goals should take three key aspects into consideration. First, it should embrace an integrated social-ecological system perspective and acknowledge the key dynamics that such systems entail, including the role of ecosystems in sustaining human wellbeing, multiple cross-scale interactions, and uncertain thresholds. Second, the process needs to address trade-offs between the ambition of goals and the feasibility in reaching them, recognizing biophysical, social, and political constraints. Third, the goal-setting exercise and the management of goal implementation need to be guided by existing knowledge about the principles, dynamics, and constraints of social change processes at all scales, from the individual to the global. Combining these three aspects will increase the chances of establishing and achieving effective Sustainable Development Goals.

Microbes in the gastrointestinal tract are under selective pressure to manipulate host eating behavior to increase their fitness, sometimes at the expense of host fitness. Microbes may do this through two potential strategies: (i) generating cravings for foods that they specialize on or foods that suppress their competitors, or (ii) inducing dysphoria until we eat foods that enhance their fitness. We review several potential mechanisms for microbial control over eating behavior including microbial influence on reward and satiety pathways, production of toxins that alter mood, changes to receptors including taste receptors, and hijacking of the vagus nerve, the neural axis between the gut and the brain. We also review the evidence for alternative explanations for cravings and unhealthy eating behavior. Because microbiota are easily manipulatable by prebiotics, probiotics, antibiotics, fecal transplants, and dietary changes, altering our microbiota offers a tractable approach to otherwise intractable problems of obesity and unhealthy eating.

Background: Carriers of the APOE ε4 allele are at increased risk of developing Alzheimer’s disease (AD), and have been shown to have reduced cerebral metabolic rate of glucose (CMRgl) in the same brain areas frequently affected in AD. These individuals also exhibit reduced plasma levels of apolipoprotein E (apoE) attributed to a specific decrease in the apoE4 isoform as determined by quantification of individual apoE isoforms in APOE ε4 heterozygotes. Whether low plasma apoE levels are associated with structural and functional brain measurements and cognitive performance remains to be investigated.

Methods: Using quantitative mass spectrometry we quantified the plasma levels of total apoE and the individual apoE3 and apoE4 isoforms in 128 cognitively normal APOE ε3/ε4 individuals included in the Arizona APOE cohort. All included individuals had undergone extensive neuropsychological testing and 25 had in addition undergone FDG-PET and MRI to determine CMRgl and regional gray matter volume (GMV).

Results: Our results demonstrated higher apoE4 levels in females versus males and an age-dependent increase in the apoE3 isoform levels in females only. Importantly, a higher relative ratio of apoE4 over apoE3 was associated with GMV loss in the right posterior cingulate and with reduced CMRgl bilaterally in the anterior cingulate and in the right hippocampal area. Additional exploratory analysis revealed several negative associations between total plasma apoE, individual apoE isoform levels, GMV and CMRgl predominantly in the frontal, occipital and temporal areas. Finally, our results indicated only weak associations between apoE plasma levels and cognitive performance which further appear to be affected by sex.

Conclusions: Our study proposes a sex-dependent and age-dependent variation in plasma apoE isoform levels and concludes that peripheral apoE levels are associated with GMV, CMRgl and possibly cognitive performance in cognitively healthy individuals with a genetic predisposition to AD.

Background: We introduced a hypometabolic convergence index (HCI) to characterize in a single measurement the extent to which a person’s fluorodeoxyglucose positron emission tomogram (FDG PET) corresponds to that in Alzheimer’s disease (AD). Apolipoprotein E ε4 (APOE ε4) gene dose is associated with three levels of risk for late-onset AD. We explored the association between gene dose and HCI in cognitively normal ε4 homozygotes, heterozygotes, and non-carriers.

Methods: An algorithm was used to characterize and compare AD-related HCIs in cognitively normal individuals, including 36 ε4 homozygotes, 46 heterozygotes, and 78 non-carriers.

Results: These three groups differed significantly in their HCIs (ANOVA, p = 0.004), and there was a significant association between HCIs and gene dose (linear trend, p = 0.001).

Conclusions: The HCI is associated with three levels of genetic risk for late-onset AD. This supports the possibility of using a single FDG PET measurement to help in the preclinical detection and tracking of AD.

Background: Medical and public health scientists are using evolution to devise new strategies to solve major health problems. But based on a 2003 survey, medical curricula may not adequately prepare physicians to evaluate and extend these advances. This study assessed the change in coverage of evolution in North American medical schools since 2003 and identified opportunities for enriching medical education.

Methods: In 2013, curriculum deans for all North American medical schools were invited to rate curricular coverage and perceived importance of 12 core principles, the extent of anticipated controversy from adding evolution, and the usefulness of 13 teaching resources. Differences between schools were assessed by Pearson’s chi-square test, Student’s t-test, and Spearman’s correlation. Open-ended questions sought insight into perceived barriers and benefits.

Results: Despite repeated follow-up, 60 schools (39%) responded to the survey. There was no evidence of sample bias. The three evolutionary principles rated most important were antibiotic resistance, environmental mismatch, and somatic selection in cancer. While importance and coverage of principles were correlated (r = 0.76, P < 0.01), coverage (at least moderate) lagged behind importance (at least moderate) by an average of 21% (SD = 6%). Compared to 2003, a range of evolutionary principles were covered by 4 to 74% more schools. Nearly half (48%) of responders anticipated igniting controversy at their medical school if they added evolution to their curriculum. The teaching resources ranked most useful were model test questions and answers, case studies, and model curricula for existing courses/rotations. Limited resources (faculty expertise) were cited as the major barrier to adding more evolution, but benefits included a deeper understanding and improved patient care.

Conclusion: North American medical schools have increased the evolution content in their curricula over the past decade. However, coverage is not commensurate with importance. At a few medical schools, anticipated controversy impedes teaching more evolution. Efforts to improve evolution education in medical schools should be directed toward boosting faculty expertise and crafting resources that can be easily integrated into existing curricula.

Introduction: Abundance of immune cells has been shown to have prognostic and predictive significance in many tumor types. Beyond abundance, the spatial organization of immune cells in relation to cancer cells may also have significant functional and clinical implications. However there is a lack of systematic methods to quantify spatial associations between immune and cancer cells.

Methods: We applied ecological measures of species interactions to digital pathology images for investigating the spatial associations of immune and cancer cells in breast cancer. We used the Morisita-Horn similarity index, an ecological measure of community structure and predator–prey interactions, to quantify the extent to which cancer cells and immune cells colocalize in whole-tumor histology sections. We related this index to disease-specific survival of 486 women with breast cancer and validated our findings in a set of 516 patients from different hospitals.

Results: Colocalization of immune cells with cancer cells was significantly associated with a disease-specific survival benefit for all breast cancers combined. In HER2-positive subtypes, the prognostic value of immune-cancer cell colocalization was highly significant and exceeded those of known clinical variables. Furthermore, colocalization was a significant predictive factor for long-term outcome following chemotherapy and radiotherapy in HER2 and Luminal A subtypes, independent of and stronger than all known clinical variables.

Conclusions: Our study demonstrates how ecological methods applied to the tumor microenvironment using routine histology can provide reproducible, quantitative biomarkers for identifying high-risk breast cancer patients. We found that the clinical value of immune-cancer interaction patterns is highly subtype-specific but substantial and independent to known clinicopathologic variables that mostly focused on cancer itself. Our approach can be developed into computer-assisted prediction based on histology samples that are already routinely collected.

The apolipoprotein E (APOE) e4 genotype is a powerful risk factor for late-onset Alzheimer’s disease (AD). In the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort, we previously reported significant baseline structural differences in APOE e4 carriers relative to non-carriers, involving the left hippocampus more than the right—a difference more pronounced in e4 homozygotes than heterozygotes. We now examine the longitudinal effects of APOE genotype on hippocampal morphometry at 6-, 12- and 24-months, in the ADNI cohort. We employed a new automated surface registration system based on conformal geometry and tensor-based morphometry. Among different hippocampal surfaces, we computed high-order correspondences, using a novel inverse-consistent surface-based fluid registration method and multivariate statistics consisting of multivariate tensor-based morphometry (mTBM) and radial distance. At each time point, using Hotelling’s T² test, we found significant morphological deformation in APOE e4 carriers relative to non-carriers in the full cohort as well as in the non-demented (pooled MCI and control) subjects at each follow-up interval. In the complete ADNI cohort, we found greater atrophy of the left hippocampus than the right, and this asymmetry was more pronounced in e4 homozygotes than heterozygotes. These findings, combined with our earlier investigations, demonstrate an e4 dose effect on accelerated hippocampal atrophy, and support the enrichment of prevention trial cohorts with e4 carriers.

The probiotic effects of Lactobacillus reuteri have been speculated to partly depend on its capacity to produce the antimicrobial substance reuterin during the reduction of glycerol in the gut. In this study, the potential of this process to protect human intestinal epithelial cells against infection with Salmonella enterica serovar Typhimurium was investigated. We used a three-dimensional (3-D) organotypic model of human colonic epithelium that was previously validated and applied to study interactions between S. Typhimurium and the intestinal epithelium that lead to enteric salmonellosis. Using this model system, we show that L. reuteri protects the intestinal cells against the early stages of Salmonella infection and that this effect is significantly increased when L. reuteri is stimulated to produce reuterin from glycerol. More specifically, the reuterin-containing ferment of L. reuteri caused a reduction in Salmonella adherence and invasion (1 log unit), and intracellular survival (2 log units). In contrast, the L. reuteri ferment without reuterin stimulated growth of the intracellular Salmonella population with 1 log unit. The short-term exposure to reuterin or the reuterin-containing ferment had no observed negative impact on intestinal epithelial cell health. However, long-term exposure (24 h) induced a complete loss of cell-cell contact within the epithelial aggregates and compromised cell viability. Collectively, these results shed light on a potential role for reuterin in inhibiting Salmonella-induced intestinal infections and may support the combined application of glycerol and L. reuteri. While future in vitro and in vivo studies of reuterin on intestinal health should fine-tune our understanding of the mechanistic effects, in particular in the presence of a complex gut microbiota, this the first report of a reuterin effect on the enteric infection process in any mammalian cell type.

Purpose: PET (positron emission tomography) imaging researches of functional metabolism using fluorodeoxyglucose ([superscript 18]F-FDG) of animal brain are important in neuroscience studies. FDG-PET imaging studies are often performed on groups of rats, so it is desirable to establish an objective voxel-based statistical methodology for group data analysis.

Material and Methods: This study establishes a statistical parametric mapping (SPM) toolbox (plug-ins) named spmratIHEP for voxel-wise analysis of FDG-PET images of rat brain, in which an FDG-PET template and an intracranial mask image of rat brain in Paxinos & Watson space were constructed, and the default settings were modified according to features of rat brain. Compared to previous studies, our constructed rat brain template comprises not only the cerebrum and cerebellum, but also the whole olfactory bulb which made the later cognitive studies much more exhaustive. And with an intracranial mask image in the template space, the brain tissues of individuals could be extracted automatically. Moreover, an atlas space is used for anatomically labeling the functional findings in the Paxinos & Watson space. In order to standardize the template image with the atlas accurately, a synthetic FDG-PET image with six main anatomy structures is constructed from the atlas, which performs as a target image in the co-registration.

Results: The spatial normalization procedure is evaluated, by which the individual rat brain images could be standardized into the Paxinos & Watson space successfully and the intracranial tissues could also be extracted accurately. The practical usability of this toolbox is evaluated using FDG-PET functional images from rats with left side middle cerebral artery occlusion (MCAO) in comparison to normal control rats. And the two-sample t-test statistical result is almost related to the left side MCA.

Conclusion: We established a toolbox of SPM8 named spmratIHEP for voxel-wise analysis of FDG-PET images of rat brain.

This study presents the first global transcriptional profiling and phenotypic characterization of the major human opportunistic fungal pathogen, Candida albicans, grown in spaceflight conditions. Microarray analysis revealed that C. albicans subjected to short-term spaceflight culture differentially regulated 452 genes compared to synchronous ground controls, which represented 8.3% of the analyzed ORFs. Spaceflight-cultured C. albicans–induced genes involved in cell aggregation (similar to flocculation), which was validated by microscopic and flow cytometry analysis. We also observed enhanced random budding of spaceflight-cultured cells as opposed to bipolar budding patterns for ground samples, in accordance with the gene expression data. Furthermore, genes involved in antifungal agent and stress resistance were differentially regulated in spaceflight, including induction of ABC transporters and members of the major facilitator family, downregulation of ergosterol-encoding genes, and upregulation of genes involved in oxidative stress resistance.

Finally, downregulation of genes involved in actin cytoskeleton was observed. Interestingly, the transcriptional regulator Cap1 and over 30% of the Cap1 regulon was differentially expressed in spaceflight-cultured C. albicans. A potential role for Cap1 in the spaceflight response of C. albicans is suggested, as this regulator is involved in random budding, cell aggregation, and oxidative stress resistance; all related to observed spaceflight-associated changes of C. albicans. While culture of C. albicans in microgravity potentiates a global change in gene expression that could induce a virulence-related phenotype, no increased virulence in a murine intraperitoneal (i.p.) infection model was observed under the conditions of this study. Collectively, our data represent an important basis for the assessment of the risk that commensal flora could play during human spaceflight missions. Furthermore, since the low fluid-shear environment of microgravity is relevant to physical forces encountered by pathogens during the infection process, insights gained from this study could identify novel infectious disease mechanisms, with downstream benefits for the general public.