Deciphering the effects of gene deletion on yeast longevity using network and machine learning approaches

Longevity is one of the most basic and one of the most essential properties of all living organisms. Identification of genes that regulate longevity would increase understanding of the mechanisms of aging, so as to help facilitate anti-aging intervention and extend the life span. In this study, based on the network features and the biochemical/physicochemical features of the deletion network and deletion genes, as well as their functional features, a two-layer model was developed for predicting the deletion effects on yeast longevity. The first stage of our prediction approach was to identify whether the deletion of one gene would change the life span of yeast; if it did, the second stage of our procedure would automatically proceed to predict whether the deletion of one gene would increase or decrease the life span. It was observed by analyzing the predicted results that the functional features (such as mitochondrial function and chromatin silencing), the network features (such as the edge density and edge weight density of the deletion network), and the local centrality of deletion gene, would have important impact for predicting the deletion effects on longevity. It is anticipated that our model may become a useful tool for studying longevity from the angle of genes and networks. Moreover, it has not escaped our notice that, after some modification, the current model can also be used to study many other phenotype prediction problems from the angle of systems biology.     

A review of animal phosphofructokinase isozymes with an emphasis on their physiological role

Phosphofructokinase (PFK) isozymes and their physiological significance have been the focus of extensive research. The majority of this work has been centered around the PFK isozymes of rat, human and rabbit tissues. Consequently, this review emphasizes these studies. Additionally, a review of PFK isozymes in chickens, mice, guinea pig, and pig is presented. The relationship of the properties of each PFK isozyme in different tissues to the rates of glycolysis and/or gluconeogenesis in those tissues is discussed where possible. Moreover, the contribution of the different PFK isoenzymes to alterations of the glycolytic rate in various tissues is discussed in relationship to variations in nutritional, hormonal, developmental or pathological status of the animal.     

A general review of competition genetic effects with an emphasis on swine breeding

A review of previous studies is presented on estimates of genetic parameters and responses to selection with traditional breeding approaches, on correlations between agonistic behavior and growth performance, and on theoretical frameworks for selection incorporating interactions among individuals and on practical methods for incorporating competition effects in breeding programs.     

Objective detection of apoptosis in rat renal tissue sections using light microscopy and free image analysis software with subsequent machine learning: Detection of apoptosis in renal tissue

Objective

The current study proposes an automated machine learning approach for the quantification of cells in cell death pathways according to DNA fragmentation.

Quantifying uncertainty in predictions of invasiveness, with emphasis on weed risk assessment

Using the Australian Weed Risk Assessment (WRA) model as an example, we applied a combination of bootstrapping and Bayesian techniques as a means of explicitly estimating the posterior probability of weediness as a function of an import risk assessment model screening score. Our approach provides estimates of uncertainty around model predictions, after correcting for verification bias arising from the original training dataset having a higher proportion of weed species than would be the norm, and incorporates uncertainty in current knowledge of the prior (base-rate) probability of weediness. The results confirm the high sensitivity of the posterior probability of weediness to the base-rate probability of weediness of plants proposed for importation, and demonstrate how uncertainty in this base-rate probability manifests itself in uncertainty surrounding predicted probabilities of weediness. This quantitative estimate of the weediness probability posed by taxa classified using the WRA model, including estimates of uncertainty around this probability for a given WRA score, would enable bio-economic modelling to contribute to the decision process, should this avenue be pursued. Regardless of whether or not this avenue is explored, the explicit estimates of uncertainty around weed classifications will enable managers to make better informed decisions regarding risk. When viewed in terms of likelihood of weed introduction, the current WRA model outcomes of ‘accept’, ‘further evaluate’ or ‘reject’, whilst not always accurate in terms of weed classification, appear consistent with a high-expected cost of mistakenly introducing a weed. The methods presented have wider application to the quantitative prediction of invasive species for situations where the base-rate probability of invasiveness is subject to uncertainty, and the accuracy of the screening test imperfect.     

A framework for feature extraction from hospital medical data with applications in risk prediction

Background

Feature engineering is a time consuming component of predictive modeling. We propose a versatile platform to automatically extract features for risk prediction, based on a pre-defined and extensible entity schema. The extraction is independent of disease type or risk prediction task. We contrast auto-extracted features to baselines generated from the Elixhauser comorbidities.

Results

Hospital medical records was transformed to event sequences, to which filters were applied to extract feature sets capturing diversity in temporal scales and data types. The features were evaluated on a readmission prediction task, comparing with baseline feature sets generated from the Elixhauser comorbidities. The prediction model was through logistic regression with elastic net regularization. Predictions horizons of 1, 2, 3, 6, 12 months were considered for four diverse diseases: diabetes, COPD, mental disorders and pneumonia, with derivation and validation cohorts defined on non-overlapping data-collection periods.For unplanned readmissions, auto-extracted feature set using socio-demographic information and medical records, outperformed baselines derived from the socio-demographic information and Elixhauser comorbidities, over 20 settings (5 prediction horizons over 4 diseases). In particular over 30-day prediction, the AUCs are: COPD—baseline: 0.60 (95% CI: 0.57, 0.63), auto-extracted: 0.67 (0.64, 0.70); diabetes—baseline: 0.60 (0.58, 0.63), auto-extracted: 0.67 (0.64, 0.69); mental disorders—baseline: 0.57 (0.54, 0.60), auto-extracted: 0.69 (0.64,0.70); pneumonia—baseline: 0.61 (0.59, 0.63), auto-extracted: 0.70 (0.67, 0.72).

Conclusions

The advantages of auto-extracted standard features from complex medical records, in a disease and task agnostic manner were demonstrated. Auto-extracted features have good predictive power over multiple time horizons. Such feature sets have potential to form the foundation of complex automated analytic tasks.

Electronic supplementary material

The online version of this article (doi:10.1186/s12859-014-0425-8) contains supplementary material, which is available to authorized users.     

The promise of machine learning in predicting treatment outcomes in psychiatry

For many years, psychiatrists have tried to understand factors involved in response to medications or psychotherapies, in order to personalize their treatment choices. There is now a broad and growing interest in the idea that we can develop models to personalize treatment decisions using new statistical approaches from the field of machine learning and applying them to larger volumes of data. In this pursuit, there has been a paradigm shift away from experimental studies to confirm or refute specific hypotheses towards a focus on the overall explanatory power of a predictive model when tested on new, unseen datasets. In this paper, we review key studies using machine learning to predict treatment outcomes in psychiatry, ranging from medications and psychotherapies to digital interventions and neurobiological treatments. Next, we focus on some new sources of data that are being used for the development of predictive models based on machine learning, such as electronic health records, smartphone and social media data, and on the potential utility of data from genetics, electrophysiology, neuroimaging and cognitive testing. Finally, we discuss how far the field has come towards implementing prediction tools in real‐world clinical practice. Relatively few retrospective studies to‐date include appropriate external validation procedures, and there are even fewer prospective studies testing the clinical feasibility and effectiveness of predictive models. Applications of machine learning in psychiatry face some of the same ethical challenges posed by these techniques in other areas of medicine or computer science, which we discuss here. In short, machine learning is a nascent but important approach to improve the effectiveness of mental health care, and several prospective clinical studies suggest that it may be working already.     

A historical review of cellular calcium handling,with emphasis on mitochondria

Calcium ions are of central importance in cellular physiology, as they carry the signal activating cells to perform their programmed function. Ca²⁺ is particularly suitable for this role because of its chemical properties and because its free concentration gradient between the extra cellular and the cytosolic concentrations is very high, about four orders of magnitude. The cytosolic concentration of Ca²⁺ is regulated by binding and chelation by various substances and by transport across plasma and intracellular membranes. Various channels, transport ATPases, uniporters, and antiporters in the plasma mem brane, endoplasmic and sarcoplasmic reticulum, and mitochondria are responsible for the transport of Ca²⁺ .The regulation of these transport systems is the subject of an increasing number of studies. In this short review, we focus on the mitochondrial transporters, i.e. the calcium uniporter used for Ca²⁺ uptake, and the antiporters used for the efflux, i.e. the Ca²⁺/Na⁺ antiporter in mitochondria and the plasma membrane of excitable cells,and the Ca²⁺/nH⁺ antiporter in liver and some other mitochondrial types. Mitochondria are of special interest in that Ca²⁺ stimulates respiration and oxidative phosphorylation to meet the energy needs of activated cells. The studies on Ca²⁺ and mitochondria began in the fifties, but interest in mito chondrial Ca²⁺ handling faded in the late seventies since it had become apparent that mitochondria in resting cells contain very low Ca²⁺. Interest increased again in the nineties also because it was discovered that mitochondria and Ca²⁺ had a central role in apoptosis and necrosis. This is of special interest in calcium overload and oxidative stress conditions, when the opening of the mitochondrial permeability transition pore is stimulated.Translated from Biokhimiya,Vol. 70, No. 2, 2005, pp. 231–239.Original Russian Text Copyright © 2005 by Saris, Carafoli.This revised version was published online in April 2005 with corrections to the post codes.     

Plant injury due to oxygen deficiency in the root environment of soilless culture: A review

The deficiency of oxygen concentration in root environment linked to waterlogging conditions caused important injuries for plants. These effects could be reproduced by oxygen deficient nutrient solution. This bibliographical synthesis has been centered on experimental results obtained on plants cultivated in soilless culture. This review paper presents a methodology used to study oxygen depletion in a nutrient solution and to calculate root respiration rates. The main factors influencing root respiration are reviewed as well as the consequences of oxygen deficiency on roots and shoots functioning. This study would not be complete without some information on the main mechanisms of plant adaptation to oxygen deficiency.     

Motor learning in man: A review of functional and clinical studies

This chapter reviews results of clinical and functional imaging studies which investigated the time-course of cortical and subcortical activation during the acquisition of motor a skill. During the early phases of learning by trial and error, activation in prefrontal areas, especially in the dorsolateral prefrontal cortex, is has been reported. The role of these areas is presumably related to explicit working memory and the establishment of a novel association between visual cues and motor commands. Furthermore, motor associated areas of the right hemisphere and distributed cerebellar areas reveal strong activation during the early motor learning. Activation in superior-posterior parietal cortex presumably arises from visuospatial processes, while sensory feedback is coded in the anterior-inferior parietal cortex and the neocerebellar structures. With practice, motor associated areas of the left-hemisphere reveal increased activity. This shift to the left hemisphere has been observed regardless of the hand used during training, indicating a left-hemispheric dominance in the storage of visuomotor skills. Concerning frontal areas, learned actions of sequential character are represented in the caudal part of the supplementary motor area (SMA proper), whereas the lateral premotor cortex appears to be responsible for the coding of the association between visuo-spatial information and motor commands. Functional imaging studies which investigated the activation patterns of motor learning under implicit conditions identified for the first, a motor circuit which includes lateral premotor cortex and SMA proper of the left hemisphere and primary motor cortex, for the second, a cognitive loop which consists of basal ganglia structures of the right hemisphere. Finally, activity patterns of intermanual transfer are discussed. After right-handed training, activity in motor associated areas maintains during performance of the mirror version, but is increased during the performance of the original-oriented version with the left hand. In contrary, increased activity during the mirror reversed action, but not during the original-oriented performance of the untrained right hand is observed after left-handed training. These results indicate the transfer of acquired right-handed information which reflects the mirror symmetry of the body, whereas spatial information is mainly transferred after left-handed training. Taken together, a combined approach of clinical lesion studies and functional imaging is a promising tool for identifying the cerebral regions involved in the process of motor learning and provides insight into the mechanisms underlying the generalisation of actions.     

A review on the genus Metarhizium as an entomopathogenic microbial biocontrol agent with emphasis on its use and utility in Mexico

Metarhizium is a genus of entomopathogenic fungi that was initially classified into three species and varieties. More recently, DNA sequencing has improved the phylogenetic resolution of Metarhizium which now includes 30 species. The insect host ranges vary within the genus and some species such as M. robertsii have broad host ranges, while others such as M. acridum show a narrow host range and are restricted to the order Orthoptera. Metarhizium spp. are ubiquitous naturally occurring soil inhabiting fungi, and some are rhizosphere colonisers and their diversity has been attributed to various selective factors (habitat type, climatic conditions, specific associations with plants and insect hosts). Metarhizium have been used for the biological control of insect pests that affect economically important agricultural crops and have been tested under laboratory and field conditions for the control of insect vectors of human disease, showing the effectiveness of the fungus against the target pest. In Mexico, Metarhizium species have been used for the control of insect pests such as the spittlebug (Hemiptera: Cercopidae), and locusts (Orthoptera) that affect crops such as corn, bean and sugarcane. Biosafety studies, such as dermal and intragastric tests in mammalian models have also been carried out to ensure safety to humans and other animals. Metarhizium shows great promise as an alternative to chemical insecticides that has relatively low impact on human health and the environment. Key features of Metarhizium for biocontrol of insects are outlined with special reference to their utility in Mexico.     

A review of the hymenopterous natural enemies of cockroaches with emphasis on biological control

The biology and control potential of hymenopterous natural enemies of cockroaches in the familiesAmpulicidae, Evaniidae, Pteromalidae, Eulophidae, Eupelmidae, andEncyrtidae were reviewed. Emphasis was placed on parasitoids of major domiciliary cockroach species, especially those that have had experimental usage in integrated pest management programs. The most promising parasitoids wereAprostocetus hagenowii (Ratzeburg) againstPeriplaneta species, andComperia merceti (Compere) againstSupella longipalpa (F.). Future research should focus on practical augmentation techniques that will be compatible with other control methodologies in the urban environment.      

A flexible computational framework for detecting, characterizing, and interpreting statistical patterns of epistasis in genetic studies of human disease susceptibility

Detecting, characterizing, and interpreting gene-gene interactions or epistasis in studies of human disease susceptibility is both a mathematical and a computational challenge. To address this problem, we have previously developed a multifactor dimensionality reduction (MDR) method for collapsing high-dimensional genetic data into a single dimension (i.e. constructive induction) thus permitting interactions to be detected in relatively small sample sizes. In this paper, we describe a comprehensive and flexible framework for detecting and interpreting gene-gene interactions that utilizes advances in information theory for selecting interesting single-nucleotide polymorphisms (SNPs), MDR for constructive induction, machine learning methods for classification, and finally graphical models for interpretation. We illustrate the usefulness of this strategy using artificial datasets simulated from several different two-locus and three-locus epistasis models. We show that the accuracy, sensitivity, specificity, and precision of a na?ve Bayes classifier are significantly improved when SNPs are selected based on their information gain (i.e. class entropy removed) and reduced to a single attribute using MDR. We then apply this strategy to detecting, characterizing, and interpreting epistatic models in a genetic study (n = 500) of atrial fibrillation and show that both classification and model interpretation are significantly improved.     

Genetic associations of body composition,flexibility and injury risk with ACE,ACTN3 and COL5A1 polymorphisms in Korean ballerinas

[Purpose]

The purpose of this study was to exam the association of body composition, flexibility, and injury risk to genetic polymorphisms including ACE ID, ACTN3 RX, and COL5A1 polymorphisms in ballet dancers in Korea.

[Methods]

For the purpose of this study, elite ballerinas (n = 97) and normal female adults (n = 203) aged 18 to 39 were recruited and these participants were tested for body weight, height, body fat, fat free mass, flexibility, injury risks on the joints and gene polymorphisms (ACE, ACTN3, COL5A1 polymorphism).

[Results]

As results, the ACE DD genotype in ballerinas was associated with higher body fat and percentage of body fat than the ACE II and ID genotypes (p < 0.05). In the study on the ACTN3 polymorphism and ballerinas, the XX genotype in ballerinas had lower body weight and lower fat-free mass than the RR and RX genotype (p < 0.005). Also, the means of sit and reach test for flexibility was lower in the ACTN3 XX genotype of ballerinas than the RR and RX genotype of ballerinas (p < 0.05). Among the sports injuries, the ankle injury of the XX-genotyped ballerinas was in significantly more prevalence than the RR and XX-genotyped ballerinas (p < 0.05). According to the odd ratio analysis, XX-genotyped ballerinas have the injury risk on the ankle about 4.7 (95% CI: 1.6~13.4, p < 0.05) times more than the RR and RX-genotyped ballerinas. Meanwhile, the COL5A1 polymorphism in ballerinas has no association with any factors including flexibility and injury risks.

[Conclusion]

In conclusion, ACE polymorphism and ACTN3 polymorphism were associated with ballerinas'' performance capacity; COL5A1 was not associated with any factors of performance of Ballerinas. The results suggested that the ACE DD genotype is associated with high body fat, the ACTN3 XX genotype is associated with low fat-free mass, low flexibility, and higher risk of ankle-joint injury.     

环孢素A对大鼠肺缺血/再灌注损伤中细胞凋亡的影响

目的:探讨线粒体膜通透性转换孔(MPTP)抑制剂——环孢素A(CsA)对大鼠肺常温缺血/再灌注后细胞凋亡的影响。方法:健康SD大鼠30只,随机分为3组(n=10):假手术组、缺血/再灌注组(I/R组)和环孢素A干预组(CsA组)。复制在体肺缺血/再灌注损伤模型。采用原位缺口末端标记(TUNEL)法检测肺组织细胞凋亡,免疫组化技术检测肺组织细胞细胞色素C(CytC)的含量,以及分光光度计测定肺组织细胞caspase-3的活性。结果:I/R组肺组织细胞胞浆CytC的含量、caspase-3活性明显高于假手术组(P0.01),并观察到大量肺组织细胞凋亡的发生。CsA组与I/R组相比,CytC释放明显减少(P0.01),caspase-3活性减弱,细胞凋亡的发生率明显下降(P0.01)。结论:环孢素A可能通过抑制MPTP开放,减少缺血/再灌注后线粒体CytC的释放,从而减少肺组织细胞的凋亡。     

Assessment of heavy metal in the water,sediment, and two edible fish species of Jamshedpur Urban Agglomeration,India with special emphasis on human health risk

The city of Jamshedpur, nicknamed the “industrial capital of Jharkhand,” is one of the oldest industrial settlements in India, nestled amidst the mineral-rich Chota Nagpur plateau, with its diverse tribal population. Heavy metal contamination from industrialization and urbanization can pose a serious health risk to the resident population of the city. Metal concentrations in water and sediment of various water bodies (rivers, canals, and lakes) were determined using ICP-MS. Pollution indices indicate heavy metal contamination at Jamshedpur Urban Agglomeration, mainly because of Cr (23–1111.6 mg/kg), Hg (0.08–4.11 mg/kg), and Pb (5.2–248 mg/kg). Labeo rohita and Punitus sarara, the two popular edible fishes, also have high concentration of Cr, Hg, and Pb. Health risk to human population due to consumption of metal contaminated edible fishes (L. rohita and P. sarara) was determined by target hazard quotient (THQ) and hazard index (HI). THQ value of fish consumption (most popular protein supplement in the area) was found higher for Cr and Pb when compared with previous literature on fish consumption. Also, HI value ranged from 1.4 to 3.9, suggesting that the children have higher health risks than adults, due to consumption of metal contaminated fishes (especially L. rohita).     

A review on the present status and management of mangrove wetland habitat resources in Bangladesh with emphasis on mangrove fisheries and aquaculture

The mangrove forest of Bangladesh, the largest continuous mangrove bulk, is one of the most important features of the coastal area of the country. The existence of the mangrove has increased the values of other coastal and marine resources such as the coastal and marine fisheries by increasing productivity and supporting a wide biological diversity. The deltaic mangrove of Bangladesh is ecologically different from the other, mostly nondeltaic mangroves of the world and is unique also in its floral and faunal assemblage; therefore, a number of endangered plants and animals that are extinct from other parts of the world, are existing in Bangladesh mangrove. However, the mangrove has been under intensive pressure of exploitation for the last few decades which, in addition to direct clearance and conversion have placed the mangrove under extreme threat. Shrimp farming is the most destructive form of resource use the mangrove has been converted to, which contributed significantly to mangrove destruction with a corresponding loss of biological resources. Concerns have been raised among the ecologists, biologists, managers and policy makers since the early 1990s; deliberate destruction of mangrove and unplanned development of coastal aquaculture particularly shrimp aquaculture have been put under extreme criticism and the sustainability has been questioned. The present status of the mangrove resources including mangrove fisheries and aquaculture and management practices have been reviewed in this paper; impacts of different forms of human interventions and resource use have also been discussed. It is suggested that the management options and the policy aspects should be critically reviewed and amended accordingly; beneficiaries and stakeholders at all levels of resource exploitation must take part and contribute to conservation and management. An immediate need for mangrove conservation has been identified.