Synchrony and idiosyncrasy in the gut microbiome of wild baboons.

Human gut microbial dynamics are highly individualized, making it challenging to link microbiota to health and to design universal microbiome therapies. This individuality is typically attributed to variation in host genetics, diets, environments and medications but it could also emerge from fundamental ecological forces that shape microbiota more generally. Here, we leverage extensive gut microbial time series from wild baboons-hosts who experience little interindividual dietary and environmental heterogeneity-to test whether gut microbial dynamics are synchronized across hosts or largely idiosyncratic. Despite their shared lifestyles, baboon microbiota were only weakly synchronized. The strongest synchrony occurred among baboons living in the same social group, probably because group members range over the same habitat and simultaneously encounter the same sources of food and water. However, this synchrony was modest compared to each host's personalized dynamics. In support, host-specific factors, especially host identity, explained, on average, more than three times the deviance in longitudinal dynamics compared to factors shared with social group members and ten times the deviance of factors shared across the host population. These results contribute to mounting evidence that highly idiosyncratic gut microbiomes are not an artefact of modern human environments and that synchronizing forces in the gut microbiome (for example, shared environments, diets and microbial dispersal) are not strong enough to overwhelm key drivers of microbiome personalization, such as host genetics, priority effects, horizontal gene transfer and functional redundancy.

Gut microbiome heritability is nearly universal but environmentally contingent.

Relatives have more similar gut microbiomes than nonrelatives, but the degree to which this similarity results from shared genotypes versus shared environments has been controversial. Here, we leveraged 16,234 gut microbiome profiles, collected over 14 years from 585 wild baboons, to reveal that host genetic effects on the gut microbiome are nearly universal. Controlling for diet, age, and socioecological variation, 97% of microbiome phenotypes were significantly heritable, including several reported as heritable in humans. Heritability was typically low (mean = 0.068) but was systematically greater in the dry season, with low diet diversity, and in older hosts. We show that longitudinal profiles and large sample sizes are crucial to quantifying microbiome heritability, and indicate scope for selection on microbiome characteristics as a host phenotype.

A comparison of dominance rank metrics reveals multiple competitive landscapes in an animal society.

Across group-living animals, linear dominance hierarchies lead to disparities in access to resources, health outcomes and reproductive performance. Studies of how dominance rank predicts these traits typically employ one of several dominance rank metrics without examining the assumptions each metric makes about its underlying competitive processes. Here, we compare the ability of two dominance rank metrics-simple ordinal rank and proportional or 'standardized' rank-to predict 20 traits in a wild baboon population in Amboseli, Kenya. We propose that simple ordinal rank best predicts traits when competition is density-dependent, whereas proportional rank best predicts traits when competition is density-independent. We found that for 75% of traits (15/20), one rank metric performed better than the other. Strikingly, all male traits were best predicted by simple ordinal rank, whereas female traits were evenly split between proportional and simple ordinal rank. Hence, male and female traits are shaped by different competitive processes: males are largely driven by density-dependent resource access (e.g. access to oestrous females), whereas females are shaped by both density-independent (e.g. distributed food resources) and density-dependent resource access. This method of comparing how different rank metrics predict traits can be used to distinguish between different competitive processes operating in animal societies.

Noninvasive measurement of mucosal immunity in a free-ranging baboon population.

Ecoimmunological patterns and processes remain understudied in wild primates, in part because of the lack of noninvasive methods to measure immunity. Secretory immunoglobulin A (sIgA) is the most abundant antibody present at mammalian mucosal surfaces and provides an important first line of defense against pathogens. Recent studies show that sIgA can be measured noninvasively in feces and is a good marker of mucosal immunity. Here we validated a commercial ELISA kit to measure fecal IgA in baboons, tested the robustness of its results to variation in collection and storage conditions, and developed a cost-effective in-house ELISA for baboon fecal IgA. Using data from the custom ELISA, we assessed the relationship between fecal IgA concentrations and gastrointestinal parasite burden, and tested how sex, age, and reproductive effort predict fecal IgA in wild baboons. We find that IgA concentrations can be measured in baboon feces using an in-house ELISA and are highly correlated to the values obtained with a commercial kit. Fecal IgA concentrations are stable when extracts are stored for up to 22 months at -20°C. Fecal IgA concentrations were negatively correlated with parasite egg counts (Trichuris trichiura), but not parasite richness. Fecal IgA did not vary between the sexes, but for males, concentrations were higher in adults versus adolescents. Lactating females had significantly lower fecal IgA than pregnant females, but neither pregnant nor lactating female concentrations differed significantly from cycling females. Males who engaged in more mate-guarding exhibited similar IgA concentrations to those who engaged in little mate-guarding. These patterns may reflect the low energetic costs of mucosal immunity, or the complex dependence of IgA excretion on individual condition. Adding a noninvasive measure of mucosal immunity will promote a better understanding of how ecology modulates possible tradeoffs between the immune system and other energetically costly processes in the wild.

Student's Perception of the Impact of E-learning on Dental Education.

AIM: The aim of this study is to assess the influence of e-learning on dental education as perceived by predoctoral dental students. MATERIALS AND METHODS: In an institutional review board (IRB) approved protocol, a 14-question survey was created and electronically distributed to second-, third-, and fourth-year dental students. The participation was considered voluntary and all responses were anonymous. RESULTS: The survey targeted 1,130 predoctoral students, of which 255 (22.6%) responded. Of the respondents, 124 students (48.6%) preferred traditional lecture mixed with online learning, while 46 students (18%) preferred only the traditional lecture style. The top three electronic resources/applications, which students perceived as having the greatest impact on their learning, were: YouTube, Bone Box, and Google. The responses also indicated that 76.5% of the students gave high credibility (scores of 4 and 5) to electronic resources recommended by faculties. Sixty percent of students spent 1 to more than 4 hours per day on electronic resources for academic performance. The most important factor for online applications influencing academic performance was "organization and logic of content" (54%). E-learning had a significant perceived effect (scores of 4/5) on didactic understanding (65.1%) and on clinical understanding (71.4%). Students observed that faculties estimated to be under 50 years of age were more likely to incorporate e-learning into courses (52.6%) and more likely to use social media for communication (41.6%). CONCLUSION: The results indicate that e-learning may successfully be used in a dental school's curriculum to enhance students' perceptions of fundamental concepts and to enable students to apply this knowledge to clinical cases. CLINICAL SIGNIFICANCE: E-learning has recently been proposed as a basic supplementary tool to enhance medical and dental education. It is crucial to determine dental students' preferences regarding social media, online applications, and databases in order to incorporate e-learning into dental school courses.

Decreased Reoperations and Improved Outcomes With Reverse Total Shoulder Arthroplasty in Comparison to Hemiarthroplasty for Geriatric Proximal Humerus Fractures: A Systematic Review and Meta-Analysis.

OBJECTIVES: We sought to compare range of motion, clinical outcome scores, and complications after reverse total shoulder arthroplasty (RSA) and hemiarthroplasty (HA) in geriatric patients with acute proximal humerus fractures. DATA SOURCES: We searched MEDLINE (1946-2017), EMBASE (1947-2017), the Cochrane Central Register of Controlled Trials (1898-2017) and ClinicalTrials.gov in October 2017. No limits were used in the database search. We also manually reviewed reference lists of included studies. We did not restrict studies based on language. STUDY SELECTION: We included all randomized controlled trials and cohort studies in which the study population had a mean age of 65 years or older, received RSA or HA to treat an acute proximal humerus fracture, and had a minimum follow-up of 6 months. DATA EXTRACTION: Two independent reviewers used a standardized data collection form to extract relevant information from included studies. Discrepancies were resolved by a consensus or a third party if consensus could not be reached. Study authors were contacted for missing or incomplete data. DATA SYNTHESIS: Using a random effects model, we calculated mean differences (MD) and standardized mean differences (SMD) for continuous outcomes; we calculated relative risk for dichotomous outcomes. RESULTS: Fifteen studies were included in the meta-analysis, including 421 patients treated with RSA and 492 treated with HA for a total of 913 patients. Compared with HA, the RSA group had significantly improved pain scores (SMD = 0.74, P < 0.001), outcome scores (SMD = 0.63, P < 0.001), and forward flexion (MD = 24.3 degrees, P < 0.001). Compared with RSA, the HA group had a significantly increased risk of reoperation (relative risk = 2.8, P = 0.02). There were no differences between the groups with regard to external rotation (P = 0.31) or deep infection (P = 0.90). CONCLUSIONS: Aggregating available research suggests that RSA results in improved range of motion, clinical outcome scores, and rates of all-cause reoperation with no difference in infection rates. Using RSA for the treatment of acute proximal humerus fractures in the elderly population may result in improved short- and medium-term outcomes compared with HA. Future work should evaluate long-term outcomes to see if the benefits of RSA persist. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

CanDiD: A Framework for Linking Executive Function and Education.

The close association between executive functions (EFs) and educational achievement has led to the idea that targeted EF training might facilitate learning and goal-directed behavior in the classroom. The evidence that training interventions have long-lasting and transferable effects is however decidedly mixed (Melby-Lervåg and Hulme, 2013; Simons et al., 2016). The goal of the current paper is to propose a new CanDiD framework for re-thinking EF and its links to education. Based on findings from basic EF research, the proposed CanDiD framework highlights dynamic and contextual influences on EF and emphasizes the importance of development and individual differences for understanding these effects. Implications for remedial interventions and curriculum design are discussed.

Ventral striatal activity links adversity and reward processing in children.

Adversity impacts many aspects of psychological and physical development including reward-based learning and decision-making. Mechanisms relating adversity and reward processing in children, however, remain unclear. Here, we show that adversity is associated with potentiated learning from positive outcomes and impulsive decision-making, but unrelated to learning from negative outcomes. We then show via functional magnetic resonance imaging that the link between adversity and reward processing is partially mediated by differences in ventral striatal response to rewards. The findings suggest that early-life adversity is associated with alterations in the brain's sensitivity to rewards accounting, in part, for the link between adversity and altered reward processing in children.

Complex sources of variance in female dominance rank in a nepotistic society.

Many mammalian societies are structured by dominance hierarchies, and an individual's position within this hierarchy can influence reproduction, behaviour, physiology and health. In nepotistic hierarchies, which are common in cercopithecine primates and also seen in spotted hyaenas, Crocuta crocuta, adult daughters are expected to rank immediately below their mother, and in reverse age order (a phenomenon known as 'youngest ascendancy'). This pattern is well described, but few studies have systematically examined the frequency or causes of departures from the expected pattern. Using a longitudinal data set from a natural population of yellow baboons, Papio cynocephalus, we measured the influence of maternal kin, paternal kin and group size on female rank positions at two life history milestones, menarche and first live birth. At menarche, most females (73%) ranked adjacent to their family members (i.e. the female held an ordinal rank in consecutive order with other members of her maternal family); however, only 33% of females showed youngest ascendancy within their matriline at menarche. By the time they experienced their first live birth, many females had improved their dominance rank: 78% ranked adjacent to their family members and 49% showed youngest ascendancy within their matriline. The presence of mothers and maternal sisters exerted a powerful influence on rank outcomes. However, the presence of fathers, brothers and paternal siblings did not produce a clear effect on female dominance rank in our analyses, perhaps because females in our data set co-resided with variable numbers and types of paternal and male relatives. Our results also raise the possibility that female body size or competitive ability may influence dominance rank, even in this classically nepotistic species. In total, our analyses reveal that the predictors of dominance rank in nepotistic rank systems are much more complex than previously thought.

Multi-decadal survival of an Antarctic nematode, Plectus murrayi, in a -20°C stored moss sample.

It is not clear for how long Antarctic soil nematodes might tolerate freezing. Samples of the Antarctic moss, Bryum argenteum, were collected on 1 October 1983 at Langhovde, Soya coast, eastern Antarctica and were stored at -20°C. After 25.5 years of storage, living nematodes were recovered from the samples and were identified as Plectus murrayi by morphological examination and nucleotide sequencing of ribosomal RNA loci. The nematodes can grow and reproduce in a water agar plate with bacteria (mainly Pseudomonas sp.) cultured from the moss extract. They showed freezing tolerance at -20°C and -80°C and their survival rate after exposure to -20°C, but not -80°C, was increased if they were initially frozen slowly at a high sub-zero temperature. They also showed some ability to tolerate desiccation stress.

Quantitative analysis of deuterium in zircaloy using double-pulse laser-induced breakdown spectrometry (LIBS) and helium gas plasma without a sample chamber.

A crucial safety measure to be strictly observed in the operation of heavy-water nuclear power plants is the mandatory regular inspection of the concentration of deuterium penetrated into the zircaloy fuel vessels. The existing standard method requires a tedious, destructive, and costly sample preparation process involving the removal of the remaining fuel in the vessel and melting away part of the zircaloy pipe. An alternative method of orthogonal dual-pulse laser-induced breakdown spectrometry (LIBS) is proposed by employing flowing atmospheric helium gas without the use of a sample chamber. The special setup of ps and ns laser systems, operated for the separate ablation of the sample target and the generation of helium gas plasma, respectively, with properly controlled relative timing, has succeeded in producing the desired sharp D I 656.10 nm emission line with effective suppression of the interfering H I 656.28 nm emission by operating the ps ablation laser at very low output energy of 26 mJ and 1 µs ahead of the helium plasma generation. Under this optimal experimental condition, a linear calibration line is attained with practically zero intercept and a 20 µg/g detection limit for D analysis of zircaloy sample while creating a crater only 10 µm in diameter. Therefore, this method promises its potential application for the practical, in situ, and virtually nondestructive quantitative microarea analysis of D, thereby supporting the more-efficient operation and maintenance of heavy-water nuclear power plants. Furthermore, it will also meet the anticipated needs of future nuclear fusion power plants, as well as other important fields of application in the foreseeable future.

Life at the top: rank and stress in wild male baboons.

In social hierarchies, dominant individuals experience reproductive and health benefits, but the costs of social dominance remain a topic of debate. Prevailing hypotheses predict that higher-ranking males experience higher testosterone and glucocorticoid (stress hormone) levels than lower-ranking males when hierarchies are unstable but not otherwise. In this long-term study of rank-related stress in a natural population of savannah baboons (Papio cynocephalus), high-ranking males had higher testosterone and lower glucocorticoid levels than other males, regardless of hierarchy stability. The singular exception was for the highest-ranking (alpha) males, who exhibited both high testosterone and high glucocorticoid levels. In particular, alpha males exhibited much higher stress hormone levels than second-ranking (beta) males, suggesting that being at the very top may be more costly than previously thought.

Combination joint-preserving surgery for forefoot deformity in patients with rheumatoid arthritis.

Proximal osteotomies for forefoot deformity in patients with rheumatoid arthritis have hitherto not been described. We evaluated combination joint-preserving surgery involving three different proximal osteotomies for such deformities. A total of 30 patients (39 feet) with a mean age of 55.6 years (45 to 67) underwent combined first tarsometatarsal fusion and distal realignment, shortening oblique osteotomies of the bases of the second to fourth metatarsals and a fifth-ray osteotomy. The mean follow-up was 36 months (24 to 68). The mean foot function index scores for pain, disability and activity subscales were 18, 23, and 16 respectively. The mean Japanese Society for Surgery of the Foot score improved significantly from 52.2 (41 to 68) to 89.6 (78 to 97). Post-operatively, 14 patients had forefoot stiffness, but had no disability. Most patients reported highly satisfactory walking ability. Residual deformity and callosities were absent. The mean hallux valgus and intermetatarsal angles decreased from 47.0 degrees (20 degrees to 67 degrees) to 9.0 degrees (2 degrees to 23 degrees) and from 14.1 degrees (9 degrees to 20 degrees) to 4.6 degrees (1 degree to 10 degrees), respectively. Four patients had further surgery including removal of hardware in three and a fifth-ray osteotomy in one. With good peri-operative medical management of rheumatoid arthritis, surgical repositioning of the metatarsophalangeal joint by metatarsal shortening and consequent relaxing of surrounding soft tissues can be successful. In early to intermediate stages of the disease, it can be performed in preference to joint-sacrificing procedures.

Impairment of conditioned freezing to tone, but not to context, in Fyn-transgenic mice: relationship to NMDA receptor subunit 2B function.

We previously demonstrated that transgenic mice overexpressing Fyn tyrosine kinase exhibit higher seizure susceptibility and enhanced tyrosine phosphorylation of several proteins, including the N-methyl-D-aspartate (NMDA) receptor subunit 2B (NR2B). In the present study, we analysed behavioural phenotypes, especially conditioned fear responses, of Fyn-transgenic (TG) mice to better understand the role of Fyn in learned emotional behaviour. Tone-dependent conditioned freezing was significantly attenuated in Fyn-TG mice, whereas context-dependent freezing was unaffected. Neither massed nor spaced conditioning ameliorated the attenuation of tone-dependent freezing. However, the selective NR2B antagonist ifenprodil, when administered before conditioning, restored tone-dependent freezing in Fyn-TG mice at a dose that did not affect freezing in wild-type (WT) mice. These results suggest that impairment of tone-dependent conditioned freezing in Fyn-TG mice is caused by disruption of the NR2B-containing NMDA receptor function. Tyrosine phosphorylation of brain proteins, including NR2B, was enhanced in Fyn-TG mice compared with that in WT mice. We also found that ifenprodil significantly suppressed the enhanced tyrosine phosphorylation. Thus, our data support the notion that NMDA receptor activity is tightly correlated with protein tyrosine phosphorylation, and Fyn might be one key molecule that controls tone-dependent conditioned freezing through the regulation of NMDA receptor function.

Efficacy of immunoliposomes on cancer models in a cell-surface-antigen-density-dependent manner.

We have recently established a cancer-reactive human monoclonal antibody, GAH, with a positive ratio of over 90% against stomach cancer. GAH was formulated as polyethyleneglycol (PEG)-modified immunoliposomal doxorubicin (DXR) (ILD) and its efficacy was examined against gastrointestinal human cancers. In in vitro studies, a comparison of ILD with PEG-modified liposomal DXR (LD) demonstrated that ILD had dose-dependent cytotoxicity for GAH-reactive B37 cancer cells, but not LD. In concordance with this result, microscopic observations showed that ILD was bound to and GAH-dependently internalised by B37 cells. In in vivo studies, ILD exhibited significantly greater antitumour activity on cancer xenograft models than LD or free DXR. The relation between efficacy and antigen density was examined on 10 xenograft models bearing cancer cells with varying GAH reactivity. Immunoliposomal doxorubicin therapeutic activity correlated with the antigen density, with a minimum number being required. Also, ILD revealed strong antitumour activity on cancers with low sensitivity to DXR or LD, suggesting that ILD overcame the DXR resistance of antigen-positive cancer cells. Thus, these results show that GAH endows liposomes with targeting activity, resulting in strong efficacy against gastrointestinal cancers.

Comparison of two intracranial self-stimulation (ICSS) paradigms in C57BL/6 mice: head-dipping and place-learning.

A variety of intracranial self-stimulation (ICSS) paradigms have been utilized for investigations of reward. Among them, nose-poking and spatial-preference paradigms are known to be relatively more resistant to the effects of drug-induced motor-deficits in rat studies, although these two ICSS paradigms have not been directly compared in previous studies. In the present study, head-dipping and place-learning (forms of nose-poking and spatial-preference tasks, respectively) paradigms with lateral hypothalamus stimulation were systematically analyzed using C57BL/6 mice in the presence and absence of two motor-deficit-inducing drugs: tolperisone and harmaline. Rapid acquisition and rapid extinction patterns of ICSS responding were observed in the head-dipping and place-learning paradigms. In contrast to these pre-drug similarities in responding, dramatic differences were noted after drug administration. Tolperisone significantly reduced head-dipping but not place-learning ICSS responding. Similarly, reduction of ICSS responding after harmaline was more pronounced in the head-dipping task. Therefore, the place-learning paradigm may be superior for the assessment of reward values under motor-deficit-inducing conditions in C57BL/6 mice. The relative benefits and disadvantages of both ICSS paradigms are discussed. Combinations of complementary ICSS paradigms using mice may be useful for further investigations of the molecular bases of reward.

Defective plasmid partition in ftsH mutants of Escherichia coli.

FtsH is an ATP-dependent protease that is essential for cell viability in Escherichia coli. The essential function of FtsH is to maintain the proper balance of biosynthesis of major membrane components, lipopolysaccharide and phospholipids. F plasmid uses a partitioning system and is localized at specific cell positions, which may be related to the cell envelope, to ensure accurate partitioning. We have examined the effects of ftsH mutations on the maintenance of a mini-F plasmid, and have found that temperature-sensitive ftsH mutants are defective in mini-F plasmid partition, but not replication, at permissive temperature for cell growth. A significant fraction of replicated plasmid molecules tend to localize close together on one side of the cell, which may result in failure to pass the plasmid to one of the two daughter cells upon cell division. By contrast, an ftsH null mutant carrying the suppressor mutation sfhC did not affect partitioning of the plasmid. The sfhC mutation also suppressed defective maintenance in temperature-sensitive ftsH mutants. Using this new phenotype caused by ftsH mutations, we also isolated a new temperature-sensitive ftsH mutant. Mutations in ftsH cause an increase in the lipopolysaccharide/ phospholipid ratio due to stabilization of the lpxC gene product, which is involved in lipopolysaccharide synthesis and is a substrate for proteolysis by the FtsH protease. It is likely that altered membrane structure affects the localization or activity of a putative plasmid partitioning apparatus located at positions equivalent to 1/4 and 3/4 of the cell length.

The effect of posterior tibial tendon dysfunction on hindfoot kinematics.

This biomechanical study investigated the functional role of the posterior tibial tendon (PTT) in acquired flatfoot mechanics. Acquired flatfoot deformity has been attributed to PTT dysfunction; however, the progression from acute dysfunction to end-stage deformity has not been fully demonstrated. Eight human cadaver lower leg and foot specimens were used in two phases of experimental testing. In Phase 1, intact (normal) specimens were loaded to simulate (a) heel strike, (b) stance, and (c) heel rise both with and without PTT function. Then, each specimen was subjected to a procedure designed to create a simulated flatfoot deformity. The resulting flattened feet were used in Phase 2 to examine the effect of restoring PTT function to a flatfoot model. During both phases of testing, the 3-D kinematic orientation of the hindfoot complex was recorded. Small but statistically significant changes in the angular orientation of the hindfoot complex were observed, during both Phase 1 and 2 testing, when comparing the effects of a functional and dysfunctional PTT. The greatest angular changes were recorded during heel rise. For the normal foot, the small changes observed in the orientation of the hindfoot complex following release of the PTT load suggest that the intact osteo-ligamentous structure of the hindfoot is initially able to maintain normal alignment following acute PTT dysfunction. Once the soft tissues have been weakened, as in our flatfoot model, the PTT had little effect in overcoming the soft tissue laxity to correct the position of the foot.

Differential effect of Fyn tyrosine kinase deletion on offensive and defensive aggression.

Fyn tyrosine kinase is highly expressed in the limbic system and mice lacking Fyn tyrosine kinase showed increased fearfulness in a variety of tests for anxiety-related behaviors. To investigate the possible role of Fyn tyrosine kinase in aggression, we assessed the aggressive behaviors of the mice lacking the Fyn tyrosine kinase using the resident-intruder and restraint-induced target biting paradigms. The percentage of Fyn-deficient mice that attacked an inanimate target in a restraint tube was higher than that of the control mice. On the contrary, in the resident-intruder paradigm, the percentage of Fyn-deficient mice that attacked the intruder was lower and the Fyn-deficient mice showed a longer latency to attack an intruder. These results suggest a distinct role of Fyn tyrosine kinase in enhancing the offensive aggression and decreasing the defensive aggression. A possible influence of anxiety-phenotype of the Fyn-deficient mice on their abnormal aggressive behavior was discussed.

Acoustic priming lowers the threshold for electrically induced seizures in mice inferior colliculus, but not in the deep layers of superior colliculus.

Mice become highly susceptible to audiogenic seizures (AGS) after exposing them to an intense noise in their early life (priming). To elucidate the brain mechanisms for this priming effect of AGS, we compared the threshold current intensities inducing AGS syndromes between primed (n=88) and non-primed (n=84) mice by electrically stimulating the central nucleus and external cortex of the inferior colliculus (CIC and ECIC), and the deep layers of the superior colliculus (DLSC). The threshold for wild running was significantly lower for the primed mice than for the control mice in the case of the CIC and ECIC, but not the DLSC. The current intensity for inducing clonic seizure was lower for the primed mice than for the control mice in the case of the ECIC. These results show that the inferior colliculus (IC) plays an important role in the priming effect of AGS in mice, but that the DLSC does not.