Introducing a Pictographic Language for Envisioning a Rich Variety of Enactive Systems with Different Degrees of Complexity

Notwithstanding the considerable amount of progress that has been made in recent years, the parallel fields of cognitive science and cognitive systems lack a unifying methodology for describing, understanding, simulating and implementing advanced cognitive behaviours. Growing interest in ’enactivism’ - as pioneered by the Chilean biologists Humberto Maturana and Francisco Varela - may lead to new perspectives in these areas, but a common framework for expressing many of the key concepts is still missing. This paper attempts to lay a tentative foundation in that direction by extending Maturana and Varela’s pictographic depictions of autopoietic unities to create a rich visual language for envisioning a wide range of enactive systems - natural or artificial - with different degrees of complexity. It is shown how such a diagrammatic taxonomy can help in the comprehension of important relationships between a variety of complex concepts from a pan-theoretic perspective. In conclusion, it is claimed that visual language is not only valuable for teaching and learning, but also offers important insights into the design and implementation of future advanced robotic systems

Serotonin and corticosterone rhythms in mice exposed to cigarette smoke and in patients with COPD:implication for COPD-associated neuropathogenesis

The circadian timing system controls daily rhythms of physiology and behavior, and disruption of clock function can trigger stressful life events. Daily exposure to cigarette smoke (CS) can lead to alteration in diverse biological and physiological processes. Smoking is associated with mood disorders, including depression and anxiety. Patients with chronic obstructive pulmonary disease (COPD) have abnormal circadian rhythms, reflected by daily changes in respiratory symptoms and lung function. Corticosterone (CORT) is an adrenal steroid that plays a considerable role in stress and anti-inflammatory responses. Serotonin (5-hydroxytryptamine; 5HT) is a neurohormone, which plays a role in sleep/wake regulation and affective disorders. Secretion of stress hormones (CORT and 5HT) is under the control of the circadian clock in the suprachiasmatic nucleus. Since smoking is a contributing factor in the development of COPD, we hypothesize that CS can affect circadian rhythms of CORT and 5HT secretion leading to sleep and mood disorders in smokers and patients with COPD. We measured the daily rhythms of plasma CORT and 5HT in mice following acute (3 d), sub-chronic (10 d) or chronic (6 mo) CS exposure and in plasma from non-smokers, smokers and patients with COPD. Acute and chronic CS exposure affected both the timing (peak phase) and amplitude of the daily rhythm of plasma CORT and 5HT in mice. Acute CS appeared to have subtle time-dependent effects on CORT levels but more pronounced effects on 5HT. As compared with CORT, plasma 5HT was slightly elevated in smokers but was reduced in patients with COPD. Thus, the effects of CS on plasma 5HT were consistent between mice and patients with COPD. Together, these data reveal a significant impact of CS exposure on rhythms of stress hormone secretion and subsequent detrimental effects on cognitive function, depression-like behavior, mood/anxiety and sleep quality in smokers and patients with COPD

Type and extent of trans-disciplinary co-operation to improve food security, health and household environment in low and middle income countries: systematic review

Acknowledgements: We are grateful to Dr Steve Turner and Dr Adam Price for their insightful comments that improved the manuscript. We would like to thank Heather Clark and Bimbola Kalejaiye for their help in data extraction. We are also grateful to Melanie Bickerton and Dr Amudha Poobalan for their systematic review advice.Peer reviewedPublisher PD

The relationship between puberty and social emotion processing

The social brain undergoes developmental change during adolescence, and pubertal hormones are hypothesized to contribute to this development. We used fMRI to explore how pubertal indicators (salivary concentrations of testosterone, oestradiol and DHEA; pubertal stage; menarcheal status) relate to brain activity during a social emotion task. Forty-two females aged 11.1 to 13.7 years underwent fMRI scanning while reading scenarios pertaining either to social emotions, which require the representation of another person’s mental states, or to basic emotions, which do not. Pubertal stage and menarcheal status were used to assign girls to early or late puberty groups. Across the entire sample, the contrast between social versus basic emotion resulted in activity within the social brain network, including dorsomedial prefrontal cortex (DMPFC), the posterior superior temporal sulcus, and the anterior temporal cortex (ATC) in both hemispheres. Increased hormone levels (independent of age) were associated with higher left ATC activity during social emotion processing. More advanced age (independent of hormone levels) was associated with lower DMPFC activity during social emotion processing. Our results suggest functionally dissociable effects of pubertal hormones and age on the adolescent social brain

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition

Broad targeting of resistance to apoptosis in cancer

Apoptosis or programmed cell death is natural way of removing aged cells from the body. Most of the anti-cancer therapies trigger apoptosis induction and related cell death networks to eliminate malignant cells. However, in cancer, de-regulated apoptotic signaling, particularly the activation of an anti-apoptotic systems, allows cancer cells to escape this program leading to uncontrolled proliferation resulting in tumor survival, therapeutic resistance and recurrence of cancer. This resistance is a complicated phenomenon that emanates from the interactions of various molecules and signaling pathways. In this comprehensive review we discuss the various factors contributing to apoptosis resistance in cancers. The key resistance targets that are discussed include (1) Bcl-2 and Mcl-1 proteins; (2) autophagy processes; (3) necrosis and necroptosis; (4) heat shock protein signaling; (5) the proteasome pathway; (6) epigenetic mechanisms; and (7) aberrant nuclear export signaling. The shortcomings of current therapeutic modalities are highlighted and a broad spectrum strategy using approaches including (a) gossypol; (b) epigallocatechin-3-gallate; (c) UMI-77 (d) triptolide and (e) selinexor that can be used to overcome cell death resistance is presented. This review provides a roadmap for the design of successful anti-cancer strategies that overcome resistance to apoptosis for better therapeutic outcome in patients with cancer

Impacts of High-Protein Oral Nutritional Supplements Among Malnourished Men and Women with Sarcopenia: A Multicenter, Randomized, Double-Blinded, Controlled Trial.

BACKGROUND: Recent evidence suggests that nutritional interventions may improve muscle outcomes in malnutrition and sarcopenia. OBJECTIVES: We evaluated the effects of 2 high-quality oral nutritional supplements (ONS) differing in amount and type of key nutrients in older adult men and women. DESIGN: A multicenter, randomized, double-blinded, controlled clinical trial. PARTICIPANTS: Malnourished and sarcopenic men and women, 65 years and older (n = 330). INTERVENTION: A 24-week intervention period with 2 energy-rich (330 kcal) ONS treatment groups: Control ONS (CONS, 14 g protein; 147 IU vitamin D3) versus Experimental ONS (EONS, 20 g protein; 499 IU vitamin D3; 1.5 g CaHMB) taken twice daily. Both ONS also contained other vitamins, minerals, and nutrients in varying amounts. MEASUREMENTS: Isokinetic peak torque (PT, Nm) leg strength, grip strength (kg), and gait speed (m·s-1) were assessed at baseline and 12 and 24 weeks. Left and right leg muscle mass (LMM, kg) were assessed by dual-energy x-ray absorptiometry (DXA). Muscle quality (MQ) was leg strength expressed relative to the tested LMM (Nm·kg-1). Subgroup analyses were performed: severe sarcopenia (low skeletal mass index, low grip strength [ CONS, P = .032) in those with normal grip strength. There were no treatment differences based on sarcopenic severity for either grip strength or gait speed. CONCLUSION: ONS improved strength outcomes in malnourished older adults with sarcopenia. In those with mild-moderate sarcopenia, but not severe sarcopenia, consumption of the EONS improved leg muscle strength and quality compared with the standard CONS

Bayesian Modeling of Perceived Surface Slant from Actively-Generated and Passively-Observed Optic Flow

We measured perceived depth from the optic flow (a) when showing a stationary physical or virtual object to observers who moved their head at a normal or slower speed, and (b) when simulating the same optic flow on a computer and presenting it to stationary observers. Our results show that perceived surface slant is systematically distorted, for both the active and the passive viewing of physical or virtual surfaces. These distortions are modulated by head translation speed, with perceived slant increasing directly with the local velocity gradient of the optic flow. This empirical result allows us to determine the relative merits of two alternative approaches aimed at explaining perceived surface slant in active vision: an “inverse optics” model that takes head motion information into account, and a probabilistic model that ignores extra-retinal signals. We compare these two approaches within the framework of the Bayesian theory. The “inverse optics” Bayesian model produces veridical slant estimates if the optic flow and the head translation velocity are measured with no error; because of the influence of a “prior” for flatness, the slant estimates become systematically biased as the measurement errors increase. The Bayesian model, which ignores the observer's motion, always produces distorted estimates of surface slant. Interestingly, the predictions of this second model, not those of the first one, are consistent with our empirical findings. The present results suggest that (a) in active vision perceived surface slant may be the product of probabilistic processes which do not guarantee the correct solution, and (b) extra-retinal signals may be mainly used for a better measurement of retinal information

Risk of tuberculosis in patients with diabetes: population based cohort study using the UK Clinical Practice Research Datalink.

BACKGROUND: Previous cohort studies demonstrate diabetes as a risk factor for tuberculosis (TB) disease. Public Health England has identified improved TB control as a priority area and has proposed a primary care-based screening program for latent TB. We investigated the association between diabetes and risk of tuberculosis in a UK General Practice cohort in order to identify potential high-risk groups appropriate for latent TB screening. METHODS: Using data from the UK Clinical Practice Research Datalink we constructed a cohort of patients with incident diabetes. We included 222,731 patients with diabetes diagnosed from 1990-2013 and 1,218,616 controls without diabetes at index date who were matched for age, sex and general practice. The effect of diabetes was explored using a Poisson analysis adjusted for age, ethnicity, body mass index, socioeconomic status, alcohol intake and smoking. We explored the effects of age, diabetes duration and severity. The effects of diabetes on risk of incident TB were explored across strata of chronic disease care defined by cholesterol and blood pressure measurement and influenza vaccination rates. RESULTS: During just under 7 million person-years of follow-up, 969 cases of TB were identified. The incidence of TB was higher amongst patients with diabetes compared with the unexposed group: 16.2 and 13.5 cases per 100,000 person-years, respectively. After adjustment for potential confounders the association between diabetes and TB remained (adjusted RR 1.30, 95 % CI 1.01 to 1.67, P = 0.04). There was no evidence that age, time since diagnosis and severity of diabetes affected the association between diabetes and TB. Diabetes patients with the lowest and highest rates of chronic disease management had a higher risk of TB (P <0.001 for all comparisons). CONCLUSIONS: Diabetes as an independent risk factor is associated with only a modest overall increased risk of TB in our UK General Practice cohort and is unlikely to be sufficient cause to screen for latent TB. Across different consulting patterns, diabetes patients accessing the least amount of chronic disease care are at highest risk for TB.This article presents independent research supported by a National Institute for Health Research (NIHR) In Practice Fellowship to LP (grant number NIHR/IPF/11/05). DAJM received Wellcome Trust funding (grant number 092691/Z/10/Z). LS is supported by a Wellcome Trust Senior Research Fellowship in Clinical Science

Birds of a Feather Flock Together: Experience-Driven Formation of Visual Object Categories in Human Ventral Temporal Cortex

The present functional magnetic resonance imaging study provides direct evidence on visual object-category formation in the human brain. Although brain imaging has demonstrated object-category specific representations in the occipitotemporal cortex, the crucial question of how the brain acquires this knowledge has remained unresolved. We designed a stimulus set consisting of six highly similar bird types that can hardly be distinguished without training. All bird types were morphed with one another to create different exemplars of each category. After visual training, fMRI showed that responses in the right fusiform gyrus were larger for bird types for which a discrete category-boundary was established as compared with not-trained bird types. Importantly, compared with not-trained bird types, right fusiform responses were smaller for visually similar birds to which subjects were exposed during training but for which no category-boundary was learned. These data provide evidence for experience-induced shaping of occipitotemporal responses that are involved in category learning in the human brain