Aversion learning techniques to evaluate dairy cattle handling practices

Fear of humans is a source of stress for Holstein dairy cattle and can result when animals are handled aversively. We used aversion learning techniques to determine which handling practices cattle find most aversive. In an aversion race, the cows are repeatedly walked down a race and treatments applied when they reached the end; the time and force required for cows to walk down the race are measured. The animal learns to associate walking down the race with the treatment received; if the treatment is aversive, the animal will take more time and require more force to reach the end of the race than if the treatment is positive. In experiment 1, 54 cows were assigned to four treatments (hit/shout, brushing, control, and food). Treatments of 2-min duration were applied three times a day for 4 days. Cows on the hit/shout treatment took more time and required more force to walk through the race than cows on other treatments, while brushed cows took longer to move through the race than cows given food. In experiment 2, 60 cows were assigned to five treatments (electric prod, shouting, hitting, tail twist, and control). Treatments of 1-min duration were applied three times a day for 3 days. Cows on the shout and electric prod treatments took more time and required more force to walk down the race than cows on the control treatment. In experiment 3, thirty-six 1-1.5-year-old heifers were assigned to three treatments (hand feeding, gentling, or control) applied as in experiment 2. Treatments did not affect the time or force required to walk down the race. The aversion race successfully discriminated between handling treatments that differ greatly in aversiveness but lacked sensitivity to distinguish between treatments that were similar. Although many procedural factors must be considered, aversion learning techniques are an effective method to determine which handling practices cattle find aversive or rewarding.     

Emotional reactions to odours in Parkinson's disease A clinical application of ethological methods

The behavioral reactions of 24 Parkinson patients to six kinds of odours were analyzed in relation to the subjective assessments of the odours. The reactions of the patients were normal in character, but reduced in intensity for two of the six odours. This was attributed primarily not to motor retardation but to impaired subjective perception.     

Emotional and behavioral reactions to facially deformed patients before and after craniofacial surgery

The present experiment investigated whether observers' emotional and behavioral reactions to facially deformed patients could be substantially improved by surgical procedures conducted by well-trained specialists in an experienced multidisciplinary team. Also investigated was the hypothesis that emotional states mediate the effects of physical attractiveness and facial deformity on social interaction. Twenty patients between the ages of 3 months and 17 years were randomly selected from over 2000 patients' files of Kenneth E. Salyer of Dallas, Texas. Patient diagnoses included facial clefts, hypertelorism, Treacher Collins syndrome, and craniofacial dysostoses (Crouzon's and Apert's syndromes). Rigorously standardized photographs of patients taken before and after surgery were shown to 22 "naive" raters ranging in age from 18 to 54 years. Raters were asked to predict their emotional and behavioral responses to the patients. These ratings indicated that observers' behavioral reactions to facially deformed children and adolescents would be more positive following craniofacial surgery. Similarly, the ratings indicated that observers' emotional reactions to these patients would be more positive following surgery. The results are discussed in terms of current sociopsychologic theoretical models for the effects of attractiveness on social interaction. A new model is presented that implicates induced emotional states as a mediating process in explaining the effects of attractiveness and facial deformity on the quality of social interactions. Limitations of the current investigation and directions for future research are also discussed.     

Functional neuroimaging of emotional learning and autonomic reactions

This article provides a selective overview of the functional neuroimaging literature with an emphasis on emotional activation processes. Emotions are fast and flexible response systems that provide basic tendencies for adaptive action. From the range of involved component functions, we first discuss selected automatic mechanisms that control basic adaptational changes. Second, we illustrate how neuroimaging work has contributed to the mapping of the network components associated with basic emotion families (fear, anger, disgust, happiness), and secondary dimensional concepts that organise the meaning space for subjective experience and verbal labels (emotional valence, activity/intensity, approach/withdrawal, etc.). Third, results and methodological difficulties are discussed in view of own neuroimaging experiments that investigated the component functions involved in emotional learning. The amygdala, prefrontal cortex, and striatum form a network of reciprocal connections that show topographically distinct patterns of activity as a correlate of up and down regulation processes during an emotional episode. Emotional modulations of other brain systems have attracted recent research interests. Emotional neuroimaging calls for more representative designs that highlight the modulatory influences of regulation strategies and socio-cultural factors responsible for inhibitory control and extinction. We conclude by emphasising the relevance of the temporal process dynamics of emotional activations that may provide improved prediction of individual differences in emotionality.     

A deep learning approach to evaluate the feasibility of enzymatic reactions generated by retrobiosynthesis

Retrobiosynthesis allows the designing of novel biosynthetic pathways for the production of chemicals and materials through metabolic engineering, but generates a large number of reactions beyond the experimental feasibility. Thus, an effective method that can reduce a large number of the initially predicted enzymatic reactions has been needed. Here, we present Deep learning-based Reaction Feasibility Checker (DeepRFC) to classify the feasibility of a given enzymatic reaction with high performance and speed. DeepRFC is designed to receive Simplified Molecular-Input Line-Entry System (SMILES) strings of a reactant pair, which is defined as a substrate and a product of a reaction, as an input, and evaluates whether the input reaction is feasible. A deep neural network is selected for DeepRFC as it leads to better classification performance than five other representative machine learning methods examined. For validation, the performance of DeepRFC is compared with another in-house reaction feasibility checker that uses the concept of reaction similarity. Finally, the use of DeepRFC is demonstrated for the retrobiosynthesis-based design of novel one-carbon assimilation pathways. DeepRFC will allow retrobiosynthesis to be more practical for metabolic engineering applications by efficiently screening a large number of retrobiosynthesis-derived enzymatic reactions. DeepRFC is freely available at https://bitbucket.org/kaistsystemsbiology/deeprfc .     

Predicting adverse drug reactions through interpretable deep learning framework

Background

Adverse drug reactions (ADRs) are unintended and harmful reactions caused by normal uses of drugs. Predicting and preventing ADRs in the early stage of the drug development pipeline can help to enhance drug safety and reduce financial costs.

Methods

In this paper, we developed machine learning models including a deep learning framework which can simultaneously predict ADRs and identify the molecular substructures associated with those ADRs without defining the substructures a-priori.

Results

We evaluated the performance of our model with ten different state-of-the-art fingerprint models and found that neural fingerprints from the deep learning model outperformed all other methods in predicting ADRs. Via feature analysis on drug structures, we identified important molecular substructures that are associated with specific ADRs and assessed their associations via statistical analysis.

Conclusions

The deep learning model with feature analysis, substructure identification, and statistical assessment provides a promising solution for identifying risky components within molecular structures and can potentially help to improve drug safety evaluation.

     

Emotional and cognitive reinforcement of rat hippocampal long-term potentiation by different learning paradigms

In earlier studies we have shown that a protein-synthesis-independent, early, long-term potentiaton (early-LTP) that lasts up to 4-5 hours can be transformed (reinforced) into a protein-synthesis-dependent late-LTP that lasts > or = 8 hours by either an emotional challenge (e.g. swim stress) or mastering a cognitive task (e.g. spatial learning). In the present study we show that LTP-reinforcement by spatial training depends on the specific constraints of the learning paradigm. In a holeboard paradigm,LTP-reinforcement is related to the formation of a lasting reference memory whereas water-maze training gives more heterogenous results. Thus, cognitive aspects interfere with emotionally challenging components of the latter paradigm. These data indicate that different spatial-learning tasks are weighted distinctly by the animal. Thus, we show that aspects of specific spatial learning paradigms such as shifts of attention and emotional content directly influence functional plasticity and memory formation.     

Impairment of Emotional Memory and Ability to Identify Emotional States in Patients with Parkinson's Disease

Parkinson's disease (PD) is characterized not only by a progressive movement disorder but also by a variety of mental disorders, which can be arbitrarily divided into cognitive and emotional–personality disorders. The aim of this investigation was to study the relationship between cognitive and emotional–personality disturbances in patients with PD during learning of emotionally significant words and visual recognition of emotional states. The volume and stability of recall of neutral and expressive words were significantly lower in patients than in healthy subjects, whereas the parameters of word recognition were similar in both groups. Unlike in healthy subjects, the characteristics of recall of neutral and expressive words in patients did not differ considerably. Patients with PD significantly more often incorrectly interpreted emotional states shown in pictures, particularly negative emotions. Deficit in retention of expressive words and recognition of emotional states correlated with the severity of motor and cognitive disorders, particularly of attention and executive dysfunction. The results of our study can be explained by a dissociation of the cognitive and motivational–affective functions in PD because of a disconnection between the basal ganglia, the limbic structures, and the frontal cortex. This dissociation tended to increase with progress of the disease.     

Emotional Reactions to Disfigurement from Cancer Therapy

Disfigurement not only produces current anxieties but reactivates childhood conflicts. The emotional reaction depends upon the disturbance to the patient''s major adaptations to life as well as the meaning of the organ to the patient. Fear of isolation and rejection by others may be more terrifying than fear of death. Emotional reactions include regression with marked dependency, anxiety, depression, hostility and, if severe, paranoid states, hypochondriasis, denial, counterphobic behaviour, obsessive-compulsive reactions and schizophrenic reactions. Management basically involves early establishment of a positive doctor-patient relationship. In such a relationship the physican should educate his patient, undercut guilt, accept transient regression and expression of anger, set limits on counterphobic behaviour, either support or gently question denial of reality, and support, without being overly sympathetic, a depressed patient. The nurse, social worker, psychiatrist and the patient''s family may be valuable members of the therapy team. Disfigurements of various body areas pose individual problems of management.     

Bilateral Skin Conductance Responses to Emotional Faces

Skin conductance responses (SCR) measure objective arousal in response to emotionally-relevant stimuli. Central nervous system influence on SCR is exerted differentially by the two hemispheres. Differences between SCR recordings from the left and right hands may therefore be expected. This study focused on emotionally expressive faces, known to be processed differently by the two hemispheres. Faces depicting neutral, happy, sad, angry, fearful or disgusted expressions were presented in two tasks, one with an explicit emotion judgment and the other with an age judgment. We found stronger responses to sad and happy faces compared with neutral from the left hand during the implicit task, and stronger responses to negative emotions compared with neutral from the right hand during the explicit task. Our results suggest that basic social stimuli generate distinct responses on the two hands, no doubt related to the lateralization of social function in the brain.     

Antiluteolytic strategies to improve fertility in cattle.

During early pregnancy, a "critical period" may be defined between Days 15 and 17. Embryonic mortality associated with this period causes significant economic losses to the cattle industry. During this period, the endometrium will follow a default program to release luteolytic pulses of PGF2alpha, unless the conceptus sends appropriate antiluteolytic signals to block PGF2alpha, production. Maintenance of pregnancy is dependent on a successful blockage of endometrial PGF2alpha production. Biology of the critical period is complex and multifactorial. Endocrine, cellular and molecular factors, both from maternal and conceptus origins act in concert to determine whether luteolysis or maintenance of pregnancy will prevail. Understanding the influences of such factors in the biology of the critical period allowed researchers to produce a series of strategies aiming to favor maintenance of pregnancy in lieu of luteolysis. Strategies include hormonal and nutritional manipulations to decrease plasma concentrations of estradiol 17beta (E2) while increasing those of progesterone (P4), and inhibiting the PGF2alpha-synthesizing enzymatic machinery in the endometrium during the critical period. Experimental results indicate that use of such strategies has improved pregnancy rates following artificial insemination and embryo transfer programs.     

Dietary manipulations to improve embryonic survival in cattle

High-producing dairy cows are subfertile. Hormonal and metabolic responses associated with homeorrhetic and homeostatic regulatory responses to partition nutrients for lactation, coupled with management, contribute to the reduction in fertility. Systems of reproductive management partially restore herd reproductive performance and provide a basis to access the impact of targeted nutritional strategies to further improve postpartum health and reproduction. Increasing the number of days feeding prepartum diets with a negative dietary cation-anion difference (DCAD), combined with adequate energy, protein, amino acids, and trace/macrominerals, improves the subsequent pregnancy rate. Likewise, supplementation of organic Se in the transition period and lactation improves immune function, uterine health, and subsequent reproductive performance under conditions of Se insufficiency. A basic understanding of the regulatory processes between nutrient partitioning and reproduction has led to the development of dietary strategies that benefit both lactation and reproduction. Postpartum increases in dietary nonstructural carbohydrates (i.e., glucogenic diets) increases ovarian activity in either intensive or extensive systems. Furthermore, sequential feeding of glucogenic-lipogenic diets enhances the proportion of cows pregnant by 120 d of lactation. Fatty acids of the n-6 and n-3 families act as nutraceuticals, altering innate immune responses and subsequent gene expression within the uterus to complement the sequential processes of follicle and embryo development and survival of the embryo and fetus. Selective or sequential feeding of lipogenic diets can benefit reproductive and immunological responses of lactating dairy cows and extensively managed beef cows.