The effect of modulating the quantity of enzymes in a model ethanol pathway on metabolic flux in Synechocystis sp. PCC 6803
Synthetic metabolism allows new metabolic capabilities to be introduced into strains for biotechnology applications. Such engineered metabolic pathways are unlikely to function optimally as initially designed and native metabolism may not efficiently support the introduced pathway without further intervention. To develop our understanding of optimal metabolic engineering strategies, a two-enzyme ethanol pathway consisting of pyruvate decarboxylase and acetaldehyde reductase was introduced into Synechocystis sp. PCC 6803. We characteriseda new set of ribosome binding site sequences in Synechocystis sp. PCC 6803 providing a range of translation strengths for different genes under test. The effect of ribosome-bindingsite sequence, operon design and modifications to native metabolism on pathway flux was analysed by HPLC. The accumulation of all introduced proteins was also quantified using selected reaction monitoring mass spectrometry. Pathway productivity was more strongly dependent on the accumulation of pyruvate decarboxylase than acetaldehyde reductase. In fact, abolishment of reductase over-expression resulted in the greatest ethanol productivity, most likely because strains harbouringsingle-gene constructs accumulated more pyruvate decarboxylase than strains carrying any of the multi-gene constructs. Overall, several lessons were learned. Firstly, the expression level of the first gene in anyoperon influenced the expression level of subsequent genes, demonstrating that translational coupling can also occur in cyanobacteria. Longer operons resulted in lower protein abundance for proximally-encoded cistrons. And, implementation of metabolic engineering strategies that have previously been shown to enhance the growth or yield of pyruvate dependent products, through co-expression with pyruvate kinase and/or fructose-1,6-bisphosphatase/sedoheptulose-1,7-bisphosphatase, indicated that other factors had greater control over growth and metabolic flux under the tested conditions.
Bartasun et al. (2019) The effect of modulating the quantity of enzymes in a model ethanol pathway on metabolic flux in Synechocystis sp. PCC 6803. PeerJ 7:e7529 https://doi.org/10.7717/peerj.7529
Endogenous testosterone correlates with parochial altruism in relation to costly punishment in different social settings
Testosterone plays a key role in shaping human social behavior. Recent findings have linked testosterone to altruistic behavior in economic decision tasks depending on group membership and intergroup competition. The preferential treatment of ingroup members, while aggression and discrimination is directed towards outgroup members, has been referred to as parochial altruism. Here we investigated in two consecutive studies, whether testosterone is associated with parochial altruism depending on individual tendency for costly punishment. In the first study, 61 men performed a single-shot ultimatum game (UG) in a minimal group context, in which they interacted with members of an ingroup and outgroup. In the second study, 34 men performed a single-shot UG in a more realistic group context, in which they responded to the proposals of supporters of six political parties during the German election year 2017. Political parties varied in their social distance to the participants’ favorite party as indicated by an individual ranking. Participants of study 2 also performed a cued recall task, in which they had to decide whether they had already encountered a face during the previous UG (old-new decision). In order to make the UG data of study 2 most comparable to the data of study 1, the rejection rates of several parties were combined according to the social distance ranking they achieved. Parties ranked 1 to 3 formed the relatively close and favored ‘ingroup’ that shared similar political values with the participant (e.g., left wing parties), while the ‘outgroup’ consisted of parties ranked from 4 to 6 with more distant or even antagonistic political views (e.g., conservative to right wing parties). In both studies, results showed a parochial pattern with higher rejection rates made in response to outgroup compared to ingroup offers. Interestingly, across studies higher salivary testosterone was associated with higher rejection rates related to unfair outgroup offers in comparison to the unfair offers made by ingroup members. The present findings suggest that latent intergroup biases during decision-making may be positively related to endogenous testosterone. Similar to previous evidence that already indicated a role of testosterone in shaping male parochial altruism in male soccer fans, these data underscore the general, yet rather subtle role of male testosterone also in other social settings.
Reimers et al. (2019) Endogenous testosterone correlates with parochial altruism in relation to costly punishment in different social settings. PeerJ 7:e7537 https://doi.org/10.7717/peerj.7537
A real-world study on clinical predictors of relapse after hospitalized detoxification in a Chinese cohort with alcohol dependence
Background The relapse rate of alcohol dependence (AD) after detoxification is high, but few studies have investigated the clinical predictors of relapse after hospitalized detoxification in real-world clinical practice, especially among Chinese patients. Methods This longitudinal cohort study followed up 122 AD patients who were discharged from January 1, 2016 to January 30, 2018 from their most recent hospitalization for detoxification. These patients were interviewed by telephone from May 20, 2017, to June 30, 2018, at least 6 months after discharge. During the interview, the relapse were assessed by using a revised Chinese version of the Alcohol Use Disorder Identification Test. Candidate predictors, such as therapeutic modalities during hospitalization and at discharge, medical history data related to alcohol use, and demographic information, were obtained from the medical records in the hospital information system. Results During the 6–24 months (with a median of 9 months) follow-up period, the relapse rate was 53.3%. Individuals with a college education level and those who had not been treated with the brief comprehensive cognitive-motivational-behavioural intervention (CCMBI) were more likely than their counterparts to relapse after hospitalized detoxification, and their adjusted HRs (95% CIs) were 1.85 (1.09, 3.16) and 2.00 (1.16, 3.46), respectively. The CCMBI use predicted a reduction in the relapse rate by approximately one-fifth. Conclusion Undergoing the CCMBI during detoxification hospitalization and having less than a college-level education could predict a reduced risk of AD relapse. These findings provide useful information both for further clinical research and for real-world practice.
Tao et al. (2019) A real-world study on clinical predictors of relapse after hospitalized detoxification in a Chinese cohort with alcohol dependence. PeerJ 7:e7547 https://doi.org/10.7717/peerj.7547
HiLDA: a statistical approach to investigate differences in mutational signatures
We propose a hierarchical latent Dirichlet allocation model (HiLDA) for characterizing somatic mutation data in cancer. The method allows us to infer mutational patterns and their relative frequencies in a set of tumor mutational catalogs and to compare the estimated frequencies between tumor sets. We apply our method to two datasets, one containing somatic mutations in colon cancer by the time of occurrence, before or after tumor initiation, and the second containing somatic mutations in esophageal cancer by sex, age, smoking status, and tumor site. In colon cancer, the relative frequencies of mutational patterns were found significantly associated with the time of occurrence of mutations. In esophageal cancer, the relative frequencies were significantly associated with the tumor site. Our novel method provides higher statistical power for detecting differences in mutational signatures.
Yang et al. (2019) HiLDA: a statistical approach to investigate differences in mutational signatures. PeerJ 7:e7557 https://doi.org/10.7717/peerj.7557
Nicotinamide riboside exerts protective effect against aging-induced NAFLD-like hepatic dysfunction in mice
Background & Aims Aging is one of the risk factors of non-alcoholic fatty liver disease (NAFLD). Yet, the mechanism underlying the aging-associated NAFLD-like syndrome is not fully understood. Nicotinamide adenine dinucleotide (NAD), a ubiquitous coenzyme, has protective effects against aging. Here, we investigated the actions of NAD precursors nicotinamide riboside (NR) on the development of aging-induced NAFLD. Methods NR supplemented food (2.5 g/kg food) was applied to aged mice for three months while normal chow to the other groups. Body weight, food intake, liver weight and fat pat mass were measured. The serum concentrations of lipid content, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and NAD were determined by biochemical assays. Pathological assessment and immunohistochemistry analysis of hepatic tissues were used to evaluate the effect of NR on NAFLD development and inflammatory infiltration. Results NR repletion significantly reduced fat pat mass in aged mice, while not altered the body weight, food intake, and liver weight. NR repletion significantly rescued the NAD reduction in aged mice. The total cholesterol and triglyceride levels could be lowered by NR repletion in aged mice. The AST level was also significantly reduced by NR repletion in aged group, while the ALT level lowered but without significance. Notably, moderate NAFLD phenotypes, including steatosis and hepatic fibrosis could be markedly corrected by NR repletion. In addition, Kupffer cells accumulated and inflammatory infiltration could also be remarkably reversed by NR repletion in aged mice. Conclusion Aging was associated with NAFLD-like phenotypes in mice, which could be reversed by oral NR repletion. Therefore, oral NR uptake might be a promising strategy to halt the progression of NAFLD.
Han et al. (2019) Nicotinamide riboside exerts protective effect against aging-induced NAFLD-like hepatic dysfunction in mice. PeerJ 7:e7568 https://doi.org/10.7717/peerj.7568
Testing the function of dromaeosaurid (Dinosauria, Theropoda) ‘sickle claws’ through musculoskeletal modelling and optimization
Dromaeosaurids were a clade of bird-like, carnivorous dinosaurs that are well known for their characteristic morphology of pedal digit II, which bore an enlarged, sickle-shaped claw and permitted an extreme range of flexion–extension. Proposed functions for the claw often revolve around predation, but the exact manner of use varies widely. Musculoskeletal modelling provides an avenue to quantitatively investigate the biomechanics of this enigmatic system, and thereby test different behavioural hypotheses. Here, a musculoskeletal model of the hindlimb and pes of Deinonychus was developed, and mathematical optimization was used to assess the factors that maximize production of force at the claw tip. Optimization revealed that more crouched hindlimb postures (i.e., more flexed knees and ankles) and larger flexor muscle volumes consistently increased claw forces, although the optimal degree of digit flexion or extension depended on assumptions of muscle activity and fibre operating range. Interestingly, the magnitude of force capable of being produced at the claw tip was relatively small, arguing against regular transmission of a large proportion of body weight into a substrate principally via the claw tip. Such transmission would therefore likely have needed to occur via more proximal parts of the foot. Collectively, the results best support a grasping function for digit II (e.g., restraint of prey smaller than the dromaeosaurid’s own body size), although other behaviours involving flexed hindlimbs cannot be excluded.
Bishop (2019) Testing the function of dromaeosaurid (Dinosauria, Theropoda) ‘sickle claws’ through musculoskeletal modelling and optimization. PeerJ 7:e7577 https://doi.org/10.7717/peerj.7577
The association of wrist circumference with hypertension in northeastern Chinese residents in comparison with other anthropometric obesity indices
Background Wrist circumference (WrC) is an easily obtained measure in estimating the body frame and regional fat distribution, and has increasingly used as an obesity index. The aim of our study is to estimate the association of WrC with elevated blood pressure (BP) among northeastern Chinese community-dwelling residents, and compare the strength of this association to other anthropometric obesity indices. Methods A total of 2,331 adult participants (761 male participants, and 1,570 female participants) were included. WrC and other five generally used obesity indices, including body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR) and neck circumference (NC) were measured. Hypertension was defined as systolic blood pressure (SBP)/diastolic blood pressure (DBP) ≥140/90 mmHg or anti-hypertensive medication use. Multivariable linear and logistic regression models were performed to identify associations of BP and hypertension with per standard deviation (SD) increase of obesity indices. Areas under receiver operative characteristic curves (AUC) were calculated to compare the predicting capacity of WrC and other obesity indices on hypertension. Results All of the six obesity indices were positively associated with both SBP and DBP after adjustment for age and gender (P-values of associations of SBP with obesity indices were 0.043 for WrC, and <0.001 for other five indices; P-values of associations of DBP with obesity indices were 0.011 for WrC, 0.031 for WHR, and <0.001 for other four indices), while the association between SBP and WrC showed no statistically significant after further adjusted for life-style and metabolic risk factors (P-value was 0.062). The increases of both SBP and DBP per SD increase of BMI were the largest. The positive associations of five obesity indices but WHR with hypertension were observed after adjustment for all risk factors (P-values were 0.024 for WrC, 0.064 for WHR and <0.001 for other four indices). However, the odd ratios (OR) of WrC was the smallest, while BMI was the largest. Consistently, the AUC of BMI was the largest and statistically larger than that observed for WrC (P-value <0.001). Conclusions WrC was associated with hypertension among northeastern Chinese populations. However, the association was not stronger than the other generally used indices, particularly BMI.
Li et al. (2019) The association of wrist circumference with hypertension in northeastern Chinese residents in comparison with other anthropometric obesity indices. PeerJ 7:e7599 https://doi.org/10.7717/peerj.7599
OutbreakFinder: a visualization tool for rapid detection of bacterial strain clusters based on optimized multidimensional scaling
With the evolution of next generation sequencing (NGS) technologies, whole-genome sequencing of bacterial isolates is increasingly employed to investigate epidemiology. Phylogenetic analysis is the common method for using NGS data, usually for comparing closeness between bacterial isolates to detect probable outbreaks. However, interpreting a phylogenetic tree is not easy without training in evolutionary biology. Therefore, developing an easy-to-use tool that can assist people who wish to use a phylogenetic tree to investigate epidemiological relatedness is crucial. In this paper, we present a tool called OutbreakFinder that can accept a distance matrix in csv format; alignment files from Lyve-SET, Parsnp, and ClustalOmega; and a tree file in Newick format as inputs to compute a cluster-labeled two-dimensional plot based on multidimensional-scaling dimension reduction coupled with affinity propagation clustering. OutbreakFinder can be downloaded for free at https://github.com/skypes/Newton-method-MDS.
Tsai et al. (2019) OutbreakFinder: a visualization tool for rapid detection of bacterial strain clusters based on optimized multidimensional scaling. PeerJ 7:e7600 https://doi.org/10.7717/peerj.7600
Healthy eating promoting in a Brazilian sports-oriented school: a pilot study
Background Adolescents, particularly athletes, have high exposure to ultra-processed foods, which could be harmful to their health and physical performance. School environments are capable of improving eating patterns. Our study is aimed at capturing changes in students’ food consumption three years after they enrolled at an experimental school, considered a model of health promotion in Rio de Janeiro city. We also aimed to depict the promising nature of the healthy eating promotion program implemented in the school and share the learnings from its implementation. Methods Our pilot study was a follow-up on the implementation of a school garden, experimental kitchen activities, and health promotion classes. We evaluated 83 adolescent athletes’ food consumption twice during the study: at its beginning (2013) and end (2016), by administering a food frequency questionnaire (FFQ) that inquired about the frequency of foods consumed in the past week. To evaluate how effectively the activities were established, integrated, and sustained in schools, the Garden Resources, Education, and Environment Nexus (GREEN) tool was used, and the school’s adherence to the school garden program was classified as high (scored 47 points out of 57). Results In 2013, 89 adolescents (mean ± SD 11.9 ± 0.4 years, 54% male) participated in the study, of which 83 continued until 2016 (14.8 ± 0.5 years, 55% male). In 2013, the mean frequency of raw salad and fruits consumption was 1.4 (CI [1.0–1.9]) and 4.3 (CI [3.8–4.9]) days per week, respectively. Three years later, the frequency of raw salad and fruits consumption was 2.2 (CI [1.6–2.7]) and 5.0 (4.5–5.5), respectively. Considering that five meals were offered at school (five days/week), it may be possible to assume that the program raised awareness on the importance of healthy eating. Conclusion Our results suggest that such integrated healthy eating promotion programs may improve adolescent athletes’ eating habits, by increasing the frequency of their consumption of unprocessed foods. This pilot study’s results inspired us to implement an expanded project at the municipal level. Since 2018, teachers who participated in this program are working with Rio de Janeiro’s Municipal Secretary of Education for Coordination of Curricular Projects. Some learnings from this pilot study on implementing the garden/experimental kitchen project in this school are being applied in 65 schools of the municipal network: joint activities must be fostered among students, teachers, and parents; healthy eating needs to be a respected value among adolescent athletes and become an example for parents and teachers.
Massarani et al. (2019) Healthy eating promoting in a Brazilian sports-oriented school: a pilot study. PeerJ 7:e7601 https://doi.org/10.7717/peerj.7601
Identification of hub genes and molecular mechanisms in infant acute lymphoblastic leukemia with MLL gene rearrangement
Infant acute lymphoblastic leukemia (ALL) with the mixed lineage leukemia (MLL) gene rearrangement (MLL-R) is considered a distinct leukemia from childhood or non-MLL-R infant ALL. To detect key genes and elucidate the molecular mechanisms of MLL-R infant ALL, microarray expression data were downloaded from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) between MLL-R and non-MLL-R infant ALL were identified. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out. Then, we constructed a protein-protein interaction (PPI) network and identified the hub genes. Finally, drug-gene interactions were mined. A total of 139 cases of MLL-R infant ALL including 77 (55.4%) fusions with AF4, 38 (27.3%) with ENL, 14 (10.1%) with AF9, and 10 (7.2%) other gene fusions were characterized. A total of 236 up-regulated and 84 down-regulated DEGs were identified. The up-regulated DEGs were mainly involved in homophilic cell adhesion, negative regulation of apoptotic process and cellular response to drug GO terms, while down-regulated DEGs were mainly enriched in extracellular matrix organization, protein kinase C signaling and neuron projection extension GO terms. The up-regulated DEGs were enriched in seven KEGG pathways, mainly involving transcriptional regulation and signaling pathways, and down-regulated DEGs were involved in three main KEGG pathways including Alzheimer’s disease, TGF-beta signaling pathway, and hematopoietic cell lineage. The PPI network included 297 nodes and 410 edges, with MYC, ALB, CD44, PTPRC and TNF identified as hub genes. Twenty-three drug-gene interactions including four up-regulated hub genes and 24 drugs were constructed by Drug Gene Interaction database (DGIdb). In conclusion, MYC, ALB, CD44, PTPRC and TNF may be potential bio-markers for the diagnosis and therapy of MLL-R infant ALL.
Zhang et al. (2019) Identification of hub genes and molecular mechanisms in infant acute lymphoblastic leukemia with MLL gene rearrangement. PeerJ 7:e7628 https://doi.org/10.7717/peerj.7628