Interleukin 1β‐converting enzyme (ICE)‐like proteases (caspases) play an important role in programmed cell death (apoptosis), and elucidating the consequences of their proteolytic activity is central to our understanding of the molecular mechanisms of cell death. Diverse structural and regulatory proteins and enzymes, including protein kinase Cδ, the retinoblastoma protein (a protein involved in cell survival), the DNA repair enzyme DNA‐dependent protein kinase and the nuclear lamins, undergo specific and limited endoproteolytic cleavage by various caspases during apoptosis. Since individual caspases can (...) cleave multiple substrates, the consequences of cleavage of only a single substrate are still poorly understood. Nevertheless, proteolytic activation of protein kinase Cδ may be an important early step in the cell death pathway, and cleavage of the retinoblastoma protein could suppress its cell survival function, whereas proteolytic inactivation of DNA repair enzymes might compromise the ability of the cell to reverse DNA fragmentation. On the other hand, cleavages of nuclear and cytoplasmic structural proteins (e.g. the lamins and Gas2) appear to be required for or contribute to the dramatic rearrangements in cellular architecture that are necessary for the completion of the cell death process. An emerging theme is that parallel and sequential proteolytic activation and inactivation of key protein substrates occurs during the multiple steps of apoptosis. (shrink)

A central source of socially meaningful signals is the face, which can be visually analyzed to understand a person's emotions, intentions, beliefs, and desires, along with information about that person's social status, approachability, age, and gender. This article reviews the neural basis of the perception of such signals in humans, focusing on facial expression and gaze, and touching on lesser-studied signals such as pupil dilation and blushing. It discusses the involvement of structures such as the insula, orbitofrontal cortex, amygdala, and (...) superior temporal gyrus, which are studied in some detail with respect to how they process social stimuli. It reveals that social perception also involves information from other modalities and depends on the context in which signals occur. (shrink)

We discuss anatomical data that may represent the substrate for very diverse input to a single folium, indirectly supporting the notion of a laterolateral beam spreading along the long axis of a folium. We also raise the question of whether the more linear body representation in somatosensory cortico-ponto-cerebellar pathways represent an adaptation to sequential processing of information from contiguous body parts.

Over many centuries, the homing pigeon has been selectively bred for returning home from a distant location. As a result of this strong selective pressure, homing pigeons have developed an excellent spatial navigation system. This system passes through the hippocampal formation, which shares many striking similarities to the mammalian hippocampus; there are a host of shared neuropeptides, interconnections, and its role in the storage and manipulation of spatial maps. There are some notable differences as well: there are unique connectivity patterns (...) and spatial encoding strategies. This review summarizes the comparisons between the avian and mammalian hippocampal systems, and the responses of single neurons in several general categories: location and place cells responding in specific areas, path and goal cells responding between goal locations, context-dependent cells that respond before or during a task, and pattern, grid, and boundary cells that increase firing at stable intervals. Head-direction cells, responding to a specific compass direction, are found in mammals and other birds but not to date in pigeons. By studying an animal that evolved under significant adaptive pressure to quickly develop a complex and efficient spatial memory system, we may better understand the comparative neurology of neurospatial systems, and plot new and potentially fruitful avenues of comparative research in the future. (shrink)

Many enzymes are inhibited by their own substrates, leading to velocity curves that rise to a maximum and then descend as the substrate concentration increases. Substrate inhibition is often regarded as a biochemical oddity and experimental annoyance. We show, using several case studies, that substrate inhibition often has important biological functions. In each case we discuss, the biological significance is different. Substrate inhibition of tyrosine hydroxylase results in a steady synthesis of dopamine despite large fluctuations in (...) tyrosine due to meals. Substrate inhibition of acetylcholinesterase enhances the neural signal and allows rapid signal termination. Substrate inhibition of phosphofructokinase ensures that resources are not devoted to manufacturing ATP when it is plentiful. In folate metabolism, substrate inhibition maintains reactions rates in the face of substantial folate deprivation. Substrate inhibition of DNA methyltransferase serves to faithfully copy DNA methylation patterns when cells divide while preventing de novo methylation of methyl‐free promoter regions. (shrink)

Substrate independence and mind-body functionalism claim that thinking does not depend on any particular kind of physical implementation. But real-world information processing depends on energy, and energy depends on material substrates. Biological evidence for these claims comes from ecology and neuroscience, while computational evidence comes from neuromorphic computing and deep learning. Attention to energy requirements undermines the use of substrate independence to support claims about the feasibility of artificial intelligence, the moral standing of robots, the possibility that we (...) may be living in a computer simulation, the plausibility of transferring minds into computers, and the autonomy of psychology from neuroscience. (shrink)

We use the phrase "moral intuition" to describe the appearance in consciousness of moral judgments or assessments without any awareness of having gone through a conscious reasoning process that produces this assessment. This paper investigates the neural substrates of moral intuition. We propose that moral intuitions are part of a larger set of social intuitions that guide us through complex, highly uncertain and rapidly changing social interactions. Such intuitions are shaped by learning. The neural substrates for moral intuition include fronto-insular, (...) cingulate, and orbito-frontal cortices and associated subcortical structure such as the septum, basil ganglia and amygdala. Understanding the role of these structures undercuts many philosophical doctrines concerning the status of moral intuitions, but vindicates the claim that they can sometimes play a legitimate role in moral decision-making. (shrink)

In this essay we will use mind as the term to designate the totality and manner in which our thoughts take place. We use the term brain to refer to the underlying mechanics, the substrate and the manner in which it supports the operations needed to carry out thoughts.

Recent neural models clarify many properties of mental imagery as part of the process whereby bottom-up visual information is influenced by top-down expectations, and how these expectations control visual attention. Volitional signals can transform modulatory top-down signals into supra-threshold imagery. Visual hallucinations can occur when the normal control of these volitional signals is lost.

W artykule rozważana jest koncepcja nagiego substratu w kontekście problemu indywiduacji. Głównym celem tekstu jest obrona teorii nagiego substratu (TNS) przed klasycznymi oraz współczesnymi zarzutami. Tok rozważań jest następujący: Autor we wstępie definiuje problem jednostkowienia i systematyzuje obecną dyskusję nad tym zagadnieniem. Następnie skupia się na porównaniu teorii wiązki i teorii nagiego substratu, ujętych jako alternatywne wyjaśnienia jednostkowości przedmiotów. Celem porównania dwóch teorii jest przedstawienie motywacji stojących za przyjęciem TNS. Głównym elementem tekstu jest punkt 2, w którym analizuje podstawowe założenia (...) TNS oraz odpiera wytaczane wobec niej zarzuty. Autor wykazuje, że warunkiem możliwości przezwyciężenia zarzutów z przeludnienia i regresu jest modyfikacja TNS i postulat teorii identyczności. (shrink)

Building on the content, developmental, and neurological evidence that there are numerous parallels between waking cognition and dreaming, this article argues that the likely neural substrate that supports dreaming, which was discovered through converging lesion and neuroimaging studies, may be a subsystem of the waking default network, which is active during mind wandering, daydreaming, and simulation. Support for this hypothesis would strengthen the case for a more general neurocognitive theory of dreaming that starts with established findings and concepts derived (...) from studies of waking cognition and neurocognition. If this theory is correct, then dreaming may be the quintessential cognitive simulation because it is often highly complex, often includes a vivid sensory environment, unfolds over a duration of a few minutes to a half hour, and is usually experienced as real while it is happening. (shrink)

ABSTRACT This paper examines the rise and fall of the British popular microscopy movement during the decades surrounding the turn of the twentieth century. It highlights that what is currently understood as microscopy was actually two inter-related but distinct communities and argues that the recognized collapse of microscopical societies in the closing decades of the nineteenth century was the result of amateur specialization. It finds the roots of popular microscopy in the Working Men’s College movement and highlights how microscopy adopted (...) its Christian Socialist pedagogy of equality and fraternity, resulting in a radical scientific movement that both prized and encouraged publication by its amateur adherents, who often occupied the middle and working classes. It studies the taxonomic boundaries of this popular microscopy, particularly focusing on its relationship with the study of cryptogams or ‘lower plants’. It explores how its success combined with its radical approach to publication and self-sufficiency created the conditions for its collapse, as devotees established a range of successor communities that had tighter taxonomic bounds. Finally, it shows how the philosophy and practices of popular microscopy continued in these successor communities, focusing on the British expression of mycology, the study of fungi. (shrink)

In this commentary, I critically assess Rex Welshon’s position on the neural substrates of ownership unity. First, I comment on Welshon’s definition of ownership unity and underline some of the problems stemming from his phenomenological analysis. Second, I analyze Welshon’s proposal to establish a mechanistic relation between neural substrates and ownership unity. I show that it is insufficient and defend my own position on how neural mechanisms may give rise to whole subjects of experience, which I call the neuro-integrative account (...) of consciousness. Lastly, I comment on Welshon’s philosophical contribution and claim that it leaves the reader theoretically stranded. (shrink)

To find the neural substrates of consciousness, researchers compare subjects’ neural activity when they are aware of stimuli against neural activity when they are not aware. Ideally, to guarantee that the neural substrates of consciousness—and nothing but the neural substrates of consciousness—are isolated, the only difference between these two contrast conditions should be conscious awareness. Nevertheless, in practice, it is quite challenging to eliminate confounds and irrelevant differences between conscious and unconscious conditions. In particular, there is an often-neglected confound that (...) is crucial to eliminate from neuroimaging studies: task performance. Unless subjects’ task performance is matched (and hence perceptual signal processing is matched), researchers risk finding the neural correlates of perception, rather than conscious perception. Here, we discuss the theoretical motivations for the performance matching framework and review empirical demonstrations of, and theoretical inferences derived from, obtaining differences in consciousness while controlling for task performance. We summarize signal detection theoretic modeling frameworks that explain how it is that we can derive performance-matched differences in consciousness without the effect being trivially driven by differences in criterion setting, and also provide principles for designing experimental paradigms that yield performance-matched differences in awareness. Finally, we address potential technical and theoretical issues that stem from matching performance across conditions of awareness, and we introduce the notion of “triangulation” for designing comprehensive experimental sets that can better reveal the neural substrates of consciousness. (shrink)

BackgroundExercise is primarily sustained by energy derived from lipids, and glucose. Substrate utilization is the pattern by which these fuel sources are used during activity. There are many factors that influence substrate utilization. We aim to delineate the effect of exercise intensity and body composition on substrate utilization.ObjectiveThe objective of our study was to discern the differences in substrate utilization profiles during a maximal and submaximal graded exercise test, and to determine the extent to which body (...) composition influences substrate utilization during the exercise tests.MethodsA total of 27 male athletes, 32.5 ± 11 years of age, were recruited for this study. Body composition was analyzed using a bioelectrical impedance analyzer. Maximal and submaximal exercise tests were performed on a treadmill. A novel graded submaximal treadmill protocol was used for the submaximal test.ResultsAverage percent body fat was 15.8 ± 5%. Average maximal oxygen consumption was 47.6 ± 9 mL/kg/min, while the average exercise intensity at which participants were shifting to glucose predominance for energy during the maximal and submaximal tests were 76 ± 8.3% and 58.4 ± 21.1%, respectively. A paired-samples t-test was conducted to compare percent VO2max at crossover point in maximal and submaximal graded exercise tests. There was a significant difference in percent VO2max at the crossover point for maximal and submaximal tests. A linear regression was performed to elucidate the interaction between exercise intensity at the crossover point and body composition during a maximal and submaximal graded exercise test. There was a significant effect of PBF on percent VO2max at crossover point during the maximal graded exercise test [F = 9.10, P = 0.006] with an R2 of 0.245. However, there was no significant effect of PBF on percent VO2max at crossover point during the submaximal graded exercise test.ConclusionSubstrate utilization, represented by the crossover point, is dependent on the rate of increase in exercise intensity. At maximal efforts, the crossover to carbohydrates from fats as the predominant fuel source occurs at a significantly later stage of percent VO2max than at submaximal efforts. Furthermore, body composition represented by PBF is a significant predictor of substrate utilization during maximal efforts. Athletes with a relatively higher PBF are more likely to have increased lipid oxidation during high intensity exercises than those with a lower body fat percentage. (shrink)

An adequate understanding of ‘the self’ and/or ‘primary-process consciousness’ should allow us to explain how affective experiences are created within the brain. Primitive emotional feelings appear to lie at the core of our beings, and the neural mechanisms that generate such states may constitute an essential foundation process for the evolution of higher, more rational, forms of consciousness. At present, abundant evidence indicates that affective states arise from the intrinsic neurodynamics of primitive self-centred emotional and motivational systems situated in subcortical (...) regions of the brain. Accordingly, a neural understanding of ‘the self’ may arise from a study of how various biological value-coding systems converge and interact with coherent brainstem representations of the body and nearby attentional/waking systems of the brain. Affective feelings may be caused by the neurodynamics of basic emotional circuits interacting with the neural schema of bodily action plans. One key brain area where such interactions occur is found within centromedial diencephalic midbrain areas such as the periventricular and periaqueductal gray and nearby tectal and tegmental zones. Here I will envision that a Simple Ego-type Life Form is instantiated in those circuits The ability of this ’primal SELF’ to resonate with primitive emotional values may help yield the raw subjectively experienced feelings of pleasure, lust, anger, hunger, desire, fear, loneliness and so forth. A study of such systems is a reasonable starting point for the neurological analysis of affective feelings, which may lie at the periconscious core of all other forms of animal consciousness. If such a neurodynamic process was an essential neural preadaptation for the emergence of higher levels of consciousness, it may help us close the explanatory gap between brain circuit states and the psychological nature of affective feelings. Thereby, it may also help us conceptualize the nature of psychological binding within higher forms of consciousness in new ways. (shrink)

The remodel the structure of chromatin (RSC) nucleosome remodeling complex is a conserved chromatin regulator with roles in chromatin organization, especially over nucleosome depleted regions therefore functioning in gene expression. Recent reports in Saccharomyces cerevisiae have identified specificities in RSC activity toward certain types of nucleosomes. RSC has now been shown to preferentially evict nucleosomes containing the histone variant H2A.Z in vitro. Furthermore, biochemical activities of distinct RSC complexes has been found to differ when their nucleosome substrate is partially (...) unraveled. Mammalian BAF complexes, the homologs of yeast RSC and SWI/SNF complexes, are also linked to nucleosomes with H2A.Z, but this relationship may be complex and extent of conservation remains to be determined. The interplay of remodelers with specific nucleosome substrates and regulation of remodeler outcomes by nucleosome composition are tantalizing questions given the wave of structural data emerging for RSC and other SWI/SNF family remodelers. (shrink)

Deciphering how DCAFs (DDB1‐CUL4 Associated Factors) modulate a broad spectrum of cellular processes, including cell cycle progression and maintenance of genomic integrity is critical to better understand cellular homeostasis and diseases. Cells contain more than 100 DCAFs that associate with the Cullin‐Ring Ubiquitin Ligase 4 (CRL4) complex that target specific protein substrates for degradation. DCAFs are thought to act as substrate receptors that dictate the specificity of the ubiquitination machinery (“catalytic DCAFs”). However, recent studies have suggested that some DCAFs (...) might play a different role by targeting CRL4 complexes to distinct cellular compartments (“structural DCAFs”). Once localized to their correct cellular domains, these CRLs dissociate from the structural DCAFs prior to their association with other, substrate‐specific catalytic DCAFs. Thus, we propose that DCAF switches can provide a mechanistic basis for the degradation of proteins that regulate cell growth and proliferation at precise points in space and time. (shrink)