Phyllosphere microbial associations improve plant reproductive success.

The above-ground (phyllosphere) plant microbiome is increasingly recognized as an important component of plant health. We hypothesized that phyllosphere bacterial recruitment may be disrupted in a greenhouse setting, and that adding a bacterial amendment would therefore benefit the health and growth of host plants. Using a newly developed synthetic phyllosphere bacterial microbiome for tomato (Solanum lycopersicum), we tested this hypothesis across multiple trials by manipulating microbial inoculation of leaves and measuring subsequent plant growth and reproductive success, comparing results from plants grown in both greenhouse and field settings. We confirmed that greenhouse-grown plants have a relatively depauperate phyllosphere bacterial microbiome, which both makes them an ideal system for testing the impact of phyllosphere communities on plant health and important targets for microbial amendments as we move towards increased agricultural sustainability. We find that the addition of the synthetic microbial community early in greenhouse growth leads to an increase in fruit production in this setting, implicating the phyllosphere microbiome as a key component of plant fitness and emphasizing the role that these bacterial microbiomes likely play in the ecology and evolution of plant communities.

Conspecific versus heterospecific transmission shapes host specialization of the phyllosphere microbiome.

In disease ecology, pathogen transmission among conspecific versus heterospecific hosts is known to shape pathogen specialization and virulence, but we do not yet know if similar effects occur at the microbiome level. We tested this idea by experimentally passaging leaf-associated microbiomes either within conspecific or across heterospecific plant hosts. Although conspecific transmission results in persistent host-filtering effects and more within-microbiome network connections, heterospecific transmission results in weaker host-filtering effects but higher levels of interconnectivity. When transplanted onto novel plants, heterospecific lines are less differentiated by host species than conspecific lines, suggesting a shift toward microbiome generalism. Finally, conspecific lines from tomato exhibit a competitive advantage on tomato hosts against those passaged on bean or pepper, suggesting microbiome-level host specialization. Overall, we find that transmission mode and previous host history shape microbiome diversity, with repeated conspecific transmission driving microbiome specialization and repeated heterospecific transmission promoting microbiome generalism.

Bifenthrin, a Ubiquitous Contaminant, Impairs the Development and Behavior of the Threatened Longfin Smelt during Early Life Stages.

The Longfin Smelt (Spirinchus thaleichthys) population in the San Franscisco Bay/Sacramento-San Joaquin Delta (Bay-Delta) has declined to ∼1% of its pre-1980s abundance and, as a result, is listed as threatened under the California Endangered Species Act. The reasons for this decline are multiple and complex, including the impacts of contaminants. Because the spawning and rearing seasons of Longfin Smelt coincide with the rainy season, during which concentrations of contaminants increase due to runoff, we hypothesized that early life stages may be particularly affected by those contaminants. Bifenthrin, a pyrethroid insecticide commonly used in agricultural and urban sectors, is of concern. Concentrations measured in the Bay-Delta have been shown to disrupt the behavior, development, and endocrine system of other fish species. The objective of the present work was to assess the impact of bifenthrin on the early developmental stages of Longfin Smelt. For this, embryos were exposed to 2, 10, 100, and 500 ng/L bifenthrin from fertilization to hatch, and larvae were exposed to 2, 10, and 100 ng/L bifenthrin from one day before to 3 days post-hatch. We assessed effects on size at hatch, yolk sac volume, locomotory behavior, and upper thermal susceptibility (via cardiac endpoints). Exposure to these environmentally relevant concentrations of bifenthrin did not significantly affect the cardiac function of larval Longfin Smelt; however, exposures altered their behavior and resulted in smaller hatchlings with reduced yolk sac volumes. This study shows that bifenthrin affects the fitness-determinant traits of Longfin Smelt early life stages and could contribute to the observed population decline.

Plant neighborhood shapes diversity and reduces interspecific variation of the phyllosphere microbiome.

Microbial communities associated with plant leaf surfaces (i.e., the phyllosphere) are increasingly recognized for their role in plant health. While accumulating evidence suggests a role for host filtering of its microbiota, far less is known about how community composition is shaped by dispersal, including from neighboring plants. We experimentally manipulated the local plant neighborhood within which tomato, pepper, or bean plants were grown in a 3-month field trial. Focal plants were grown in the presence of con- or hetero-specific neighbors (or no neighbors) in a fully factorial combination. At 30-day intervals, focal plants were harvested and replaced with a new age- and species-matched cohort while allowing neighborhood plants to continue growing. Bacterial community profiling revealed that the strength of host filtering effects (i.e., interspecific differences in composition) decreased over time. In contrast, the strength of neighborhood effects increased over time, suggesting dispersal from neighboring plants becomes more important as neighboring plant biomass increases. We next implemented a cross-inoculation study in the greenhouse using inoculum generated from the field plants to directly test host filtering of microbiomes while controlling for directionality and source of dispersal. This experiment further demonstrated that focal host species, the host from which the microbiome came, and in one case the donor hosts' neighbors, contribute to variation in phyllosphere bacterial composition. Overall, our results suggest that local dispersal is a key factor in phyllosphere assembly, and that demographic factors such as nearby neighbor identity and biomass or age are important determinants of phyllosphere microbiome diversity.

Pro-Inflammatory Interleukin-18 is Associated with Hepatic Steatosis and Elevated Liver Enzymes in People with HIV Monoinfection.

People with HIV (PWH) are at an increased risk of developing nonalcoholic fatty liver disease (NAFLD). Interleukin (IL)-18 is regulated by inflammasomes in response to pathogens and danger signals and has been implicated in both the pathogenesis of NAFLD and HIV disease progression. We hypothesized that increased IL-18 may be associated with NAFLD and liver injury in PWH. This was an observational study of 125 PWH and 59 individuals without HIV in the Boston area. Participants with known hepatitis B, hepatitis C, and excessive alcohol use were excluded. IL-18 was measured in serum by enzyme-linked immunosorbent assay. Liver lipid content was assessed by liver-to-spleen computed tomography (CT) attenuation ratio. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and IL-18 levels were higher in PWH than in controls. In PWH, log10 IL-18 was associated with log10AST (r = 0.34, p = .0001), log10ALT (r = 0.33, p = .0002), log10HIV RNA (r = 0.29, p = .002), and inversely associated with liver-to-spleen ratio (r = -0.24, p = .02). In addition, log10 IL-18 was associated with log10 triglycerides (r = 0.26, p = .003), log10 MCP-1 (monocyte chemoattractant protein-1; r = 0.33, p = .0004), log10caspase-1 (r = 0.35, p < .0001), log10LPS (r = 0.28, p = .004), and inversely associated with high-density lipoprotein (r = -0.28, p = .002), and CD4+/CD8+ T cell ratio (r = -0.24, p = .007). In controls without HIV, log10 IL-18 was also associated with log10ALT (r = 0.44, p = .0005). After adjusting for potential confounders, the relationships between IL-18 and AST (p = .004) and ALT (p = .003) remained significant, and the relationship between IL-18 and liver-to-spleen ratio (p = .02). Increased inflammasome activation and subsequent monocyte recruitment in PWH may contribute to the development and progression of NAFLD. Clinical Trials Registration. NCT00455793.

Implementation of Routine Cognitive Screening in the Preoperative Assessment Clinic.

Traditional systems of anesthesia evaluation do not routinely incorporate cognitive screening into preoperative assessments of vital organ systems. Increasing recognition of the importance of preoperative cognitive assessment of the elderly surgical patient has resulted in a "call to action" from experts in this area. A paradigm shift will be necessary to make this screening routine and not just a research tool. We describe our preliminary experience with developing a training program and implementing routine cognitive screening in a preoperative evaluation clinic. We outline a process showing our successful clinical implementation of sustainable cognitive stratification and documentation of routine cognitive screening.

The Feasibility of At-Home iPad Cognitive Testing For Use in Clinical Trials.

BACKGROUND: Technological advances now make it feasible to administer cognitive assessments at-home on mobile and touch-screen devices such as an iPad or tablet computer. Validation of these techniques is necessary to assess their utility in clinical trials. OBJECTIVES: We used a Computerized Cognitive Composite for Preclinical Alzheimer's Disease (C3-PAD) developed for iPad 1) to determine the feasibility of performing the C3-PAD at home by older individuals without the presence of a trained psychometrician; 2) to explore the reliability of in-clinic compared to at-home C3-PAD performance and 3) to examine the comparability of C3-PAD performance to standardized neuropsychological tests. DESIGN SETTING PARTICIPANTS: Forty-nine cognitively normal older individuals (mean age, 71.467.7 years; 20% non-Caucasian) were recruited from research centers at the Massachusetts General Hospital and Brigham and Women's Hospital. Participants made two in-clinic visits one-week apart and took five 30-minute alternate versions of the C3-PAD at-home measuring episodic memory, reaction time and working memory. MEASUREMENTS: A reliability analysis explored equivalence of the six alternate C3-PAD test versions. A feasibility assessment calculated the percentage of individuals who completed all at-home tests correctly, in contrast to incomplete assessments. Correlational analyses examined the association between C3-PAD-clinic compared to C3-PAD-home assessments and between C3-PAD performance and standardized paper and pencil tests. RESULTS: Excellent reliability was observed among the 6 C3-PAD alternate versions (Cronbach alpha coefficient=0.93). A total of 28 of 49 participants completed all at-home sessions correctly and 48 of 49 completed four out of five correctly. There were no significant differences in participant age, sex or education between complete and incomplete at-home assessments. A single in-clinic C3-PAD assessment and the at-home C3-PAD assessments were highly associated with each other (r2=0.508, p<0.0001), suggesting that at-home tests provide reliable data as in-clinic assessments. There was also a moderate association between the at-home C3-PAD assessments and the in-clinic standardized paper and pencil tests covering similar cognitive domains (r2= 0.168, p< 0.003). CONCLUSIONS: Reliable and valid cognitive data can be obtained from the C3-PAD assessments in the home environment. With initial in-clinic training, a high percentage of older individuals completed at-home assessments correctly. At-home cognitive testing shows promise for inclusion into clinical trial designs.

Development of a psychometrically equivalent short form of the Face-Name Associative Memory Exam for use along the early Alzheimer's disease trajectory.

Neuropsychologists are developing more challenging and specific tests to detect early and subtle changes in cognition related to preclinical Alzheimer's disease (AD). The 16-item Face-Name Associative Memory Exam (FNAME-16) is a challenging paired associative memory test able to detect subtle memory changes associated with biomarker evidence of preclinical AD. However, as individuals progress along the AD trajectory, measures that are sensitive at the preclinical stage may become too challenging by the stage of Mild Cognitive Impairment (MCI). Our goal was to develop a modified version of the face-name and face-occupation paired associative memory task (FNAME-12) with fewer stimuli and additional learning trials suitable for use in MCI. We administered the FNAME-12A, an alternate version FNAME 12B, the original FNAME-16, and a series of other neuropsychological measures to 65 clinically normal (CN) older adults (aged 65 to 85) and a subsample characterized by MCI (n = 18). The FNAME-12 exhibited psychometric equivalence with the FNAME-16 (r = .77, p < .001) and was correlated with other measures of episodic and semantic memory. The alternate form, FNAME-12B, was highly correlated with FNAME-12A (r = .76, p < .001). Mean performance on the FNAME 12A, stratified by education, was generated. The task could be completed by our MCI group yet remained challenging in the CN group, providing evidence for its utility along the AD trajectory.

Evolutionary origin of bipolar disorder-revised: EOBD-R.

The hypothesis of the evolutionary origin of bipolar disorder (EOBD) synthesized ideas about the biological clock and seasonal shifts in mood (Rosenthal, Wehr) with theorizing that bipolar disorder descends from a pyknic (compact, cold-adapted) group (Kretchmer). The hypothesis suggested that bipolar behaviors evolved in the northern temperate zone as highly derived adaptations to the selective pressures of severe climatic conditions during the Pleistocene. Given evidence of Neandertal contributions to the human genome, the hypothesis is extended (EOBD-R) to suggest Neandertal as the ancestral source for bipolar vulnerability genes (susceptibility alleles). The EOBD-R hypothesis explains and integrates existing observations: bipolar disorder has the epidemiology of an adaptation; it is correlated with a cold-adapted build, and its moods vary according to light and season. Since the hypothesis was first published, data consistent with it have continued to appear. Individuals with seasonal affective disorder, which is related to bipolar disorder, have been shown to manifest a biological signal of season change similar to that found in hibernating animals. The involvement of the circadian gene network in the pathophysiology of bipolar disorder has been confirmed. Because selective pressures during the Pleistocene would have been greatest for women of reproductive age, they are expected to manifest winter depression more than males or younger females, which is the case. (This sex difference is also found in hibernating mammals.) Because it is hypothesized that the evolution of bipolar disorder took place in the northern temperate zone during the Pleistocene, it is not expected that individuals of African descent, lacking Neandertal genes, will manifest circular bipolar I disorder, and in fact, the incidence of bipolar disorder among black individuals is less than among whites. A definitive test of the hypothesis is proposed: It is predicted that the bipolar and Neandertal genomes will be more similar than the modern human and Neandertal genomes, and the modern human and San and Yoruba genomes will be more similar than the bipolar and San and Yoruba genomes. Failure to confirm these predictions will falsify the EOBD-R hypothesis. The EOBD-R hypothesis has important implications in the search for bipolar vulnerability genes and our understanding of ourselves and our Neandertal ancestor. At a practical level, confirmation of the EOBD-R hypothesis will boost interest and research in the prevention and management of bipolar symptoms by manipulation of ambient light.