Neural Control of Interlimb Coordination and Gait Timing in Bipeds and Quadrupeds

1) A large body of behavioral data conceming animal and human gaits and gait transitions is simulated as emergent properties of a central pattern generator (CPG) model. The CPG model incorporates neurons obeying Hodgkin-Huxley type dynamics that interact via an on-center off-surround anatomy whose excitatory signals operate on a faster time scale than their inhibitory signals. A descending cornmand or arousal signal called a GO signal activates the gaits and controL their transitions. The GO signal and the CPG model are compared with neural data from globus pallidus and spinal cord, among other brain structures. 2) Data from human bimanual finger coordination tasks are simulated in which anti-phase oscillations at low frequencies spontaneously switch to in-phase oscillations at high frequencies, in-phase oscillations can be performed both at low and high frequencies, phase fluctuations occur at the anti-phase in-phase transition, and a "seagull effect" of larger errors occurs at intermediate phases. When driven by environmental patterns with intermediate phase relationships, the model's output exhibits a tendency to slip toward purely in-phase and anti-phase relationships as observed in humans subjects. 3) Quadruped vertebrate gaits, including the amble, the walk, all three pairwise gaits (trot, pace, and gallop) and the pronk are simulated. Rapid gait transitions are simulated in the order--walk, trot, pace, and gallop--that occurs in the cat, along with the observed increase in oscillation frequency. 4) Precise control of quadruped gait switching is achieved in the model by using GO-dependent modulation of the model's inhibitory interactions. This generates a different functional connectivity in a single CPG at different arousal levels. Such task-specific modulation of functional connectivity in neural pattern generators has been experimentally reported in invertebrates. Phase-dependent modulation of reflex gain has been observed in cats. A role for state-dependent modulation is herein predicted to occur in vertebrates for precise control of phase transitions from one gait to another. 5) The primary human gaits (the walk and the run) and elephant gaits (the amble and the walk) are sirnulated. Although these two gaits are qualitatively different, they both have the same limb order and may exhibit oscillation frequencies that overlap. The CPG model simulates the walk and the run by generating oscillations which exhibit the same phase relationships. but qualitatively different waveform shapes, at different GO signal levels. The fraction of each cycle that activity is above threshold quantitatively distinguishes the two gaits, much as the duty cycles of the feet are longer in the walk than in the run. 6) A key model properly concerns the ability of a single model CPG, that obeys a fixed set of opponent processing equations to generate both in-phase and anti-phase oscillations at different arousal levels. Phase transitions from either in-phase to anti-phase oscillations, or from anti-phase to in-phase oscillations, can occur in different parameter ranges, as the GO signal increases.

Pathophysiology of feline hyperadrenocorticism clinical. Case presentation

Hyperadrenocorticism is a rare endocrine disease in the cat; it is characterized by elevated blood cortisol level that generates numerous clinical signs including hyperglycemia, polyuria, polydipsia, polyphagia and skin diseases. The average age of onset is around 10 years. This disease usually occurs link with other endocrine disorders such as diabetes mellitus.The disease can be produced by functional alteration of the pituitary gland or the adrenal. A case report, with differential diagnosis and review of the literature, is presented.

The clinical significance of cathepsin S expression in human astrocytomas

Early local invasion by astrocytoma. cells results in tumor recurrence even after apparent total surgical resection, leading to the poor prognosis associated with malignant astrocytomas. Proteolytic enzymes have been implicated in facilitating tumor cell invasion and the current study was designed to characterize the expression of the cysteine proteinase cathepsin S (CatS) in astrocytomas and examine its potential role in invasion. Immunohistochemical analysis of biopsies demonstrated that CatS was expressed in astrocytoma cells but absent from normal astrocytes, oligodendrocytes, neurones and endothelial cells. Microglial cells and macrophages were also positive. Assays of specific activity in 59 astrocytoma biopsies confirmed CatS expression and in addition demonstrated that the highest levels of activity were expressed in grade IV tumors. CatS activity was also present in astrocytoma cells in vitro and the extracellular levels of activity were highest in cultures derived from grade IV tumors. In vitro invasion assays were carried out using the U251MG cell line and the invasion rate was reduced by up to 61% in the presence of the selective CatS inhibitor 4-Morpholineurea-LeuHomoPhe-vinylsulphone. We conclude that CatS expression is up-regulated in astrocytoma. cells and provide evidence for a potential role for CatS in invasion.

Cathepsin S expression: An independent prognostic factor in glioblastoma tumours - A pilot Study

Cysteine proteinases have been implicated in astrocytoma invasion. We recently demonstrated that cathepsin S (CatS) expression is up-regulated in astrocytomas and provided evidence for a potential role in astrocytoma invasion (Flannery et al., Am J Path 2003;163(1):175–82). We aimed to evaluate the significance of CatS in human astrocytoma progression and as a prognostic marker. Frozen tissue homogenates from 71 patients with astrocytomas and 3 normal brain specimens were subjected to ELISA analyses. Immunohistochemical analysis of CatS expression was performed on 126 paraffin-embedded tumour samples. Fifty-one astrocytoma cases were suitable for both frozen tissue and paraffin tissue analysis. ELISA revealed minimal expression of CatS in normal brain homogenates. CatS expression was increased in grade IV tumours whereas astrocytoma grades I–III exhibited lower values. Immunohistochemical analysis revealed a similar pattern of expression. Moreover, high-CatS immunohistochemical scores in glioblastomas were associated with significantly shorter survival (10 vs. 5 months, p = 0.014). With forced inclusion of patient age, radiation dose and Karnofsky score in the Cox multivariate model, CatS score was found to be an independent predictor of survival. CatS expression in astrocytomas is associated with tumour progression and poor outcome in glioblastomas. CatS may serve as a useful prognostic indicator and potential target for anti-invasive therapy.

Detection of cathepsin S cysteine protease in human brain tumour microdialysates in vivo.

Microdialysis enables the chemistry of extracellular ?uid in body tissues to be measured. Extracellular proteases such as the cysteine protease, cathepsin S (CatS), are thought to facilitate astrocytoma invasion. Microdialysates obtained from human brain tumoursin vivo were subjected to cathepsin S activity and ELISA assays. Cathepsin S ELISA expression was detected in ?ve out of 10 tumour microdialysates, while activity was detected in ?ve out of 11 tumour microdialysates. Cathepsin S expression was also detected in microdialysate from the normal brain control although no activity was found in the same sample. While some re?nements to the technique are necessary, the authors demonstrate the feasibility and safety of microdialysis in human astrocytomasin vivo. Characterisation of the extracellular environment of brain tumoursin vivo using microdialysis may be a useful tool to identify the protease pro?le of brain tumours.

Inhibition of cathepsin L-like proteases by cathepsin V propeptide

The N-terminal propeptide domains of several cathepsin L-like cysteine proteases have been shown to possess potent inhibitory activity. Here we report the first kinetic characterisation of the inhibition properties of the cathepsin V propeptide (CatV PP). Using a facile recombinant approach we demonstrate expression, purification and evaluation of the CatV PP. This propeptide was found to behave as a tight-binding inhibitor against CatV (K (i) 10.2 nm). It also functions as an inhibitor against other members of the CatL-like subclass (CatL, 9.8 nm; CatS, 10.7 nm; and CatK, 149 nm) and had no discernible effects upon the more distantly related CatB.

Discovery of novel cathepsin S inhibitors by pharmacophore-based virtual high-throughput screening

The cysteine protease cathepsin S (CatS) is involved in the pathogenesis of autoimmune disorders, atherosclerosis, and obesity. Therefore, it represents a promising pharmacological target for drug development. We generated ligand-based and structure-based pharmacophore models for noncovalent and covalent CatS inhibitors to perform virtual high-throughput screening of chemical databases in order to discover novel scaffolds for CatS inhibitors. An in vitro evaluation of the resulting 15 structures revealed seven CatS inhibitors with kinetic constants in the low micromolar range. These compounds can be subjected to further chemical modifications to obtain drugs for the treatment of autoimmune disorders and atherosclerosis.

Tails of animal attraction: Incorporating the feline into the family

Increased urbanization and female employment have led to the cat overtaking the dog as the companion animal of preference. However, thisarticle looks beyond lifestyle changes as reasons for the popularity of the cat. The article explores the emotional consumer-socialization processinvolving the incorporation of the cat into the family. Subjective personal introspection (SPI) and supporting vignettes of female humans in theirfamilies (all of which were high-involvement owners) explore the hows and whys of feline incorporation. The study identifies several categories ofincorporation. The findings suggest that this complex process involves many factors — namely, consumer socialization, intergenerationalinfluence, brand loyalty, commitment, near-instant loyalty, immediacy, distress, anthropomorphism, and nostalgia. These factors underpin theintimacy and care the human–feline relationship expresses. The ability for humans and cats to bond in a way that fosters emotional intimacy canbe considered one of the purest forms of relationships.© 2007 Published by Elsevier Inc.

The effect of animals on human health and well-being

Substantial sums of money are invested annually in preventative medicine and therapeutic treatment for people with a wide range of physical and psychological health problems, sometimes to no avail. There is now mounting evidence to suggest that companion animals, such as dogs and cats, can enhance the health of their human owners and may thus contribute significantly to the health expenditure of our country. This paper explores the evidence that pets can contribute to human health and well-being. The article initially concentrates on the value of animals for short- and long-term physical health, before exploring the relationship between animals and psychological health, focusing on the ability of dogs, cats, and other species to aid the disabled and serve as a "therapist" to those in institutional settings. The paper also discusses the evidence for the ability of dogs to facilitate the diagnosis and treatment of specific chronic diseases, notably cancer, epilepsy, and diabetes. Mechanisms underlying the ability of animals to promote human health are discussed within a theoretical framework. Whereas the evidence for a direct causal association between human well-being and companion animals is not conclusive, the literature reviewed is largely supportive of the widely held, and long-standing, belief that "pets are good for us." © 2009 The Society for the Psychological Study of Social Issues.

Lateralized behaviour in the domestic cat, Felis silvestris catus

Lateralized behaviour in the felids has been subject to little investigation. We examined the paw use of 42 domestic cats on three tasks designed to determine whether the animals performed asymmetrical motor behaviour. The influence of the cats' sex and age on their paw preferences was also explored. The distribution of the cats' paw preferences differed significantly between the three tasks. Task 1, the most complex exercise involving retrieval of a food treat from an empty jar, encouraged the most apparent display of lateralized behaviour, with all but one animal showing a strong preference to use either their left or right paw consistently. Tasks 2 (an exercise involving reaching for a toy suspended overhead) and 3 (a challenge involving reaching for a toy moving along the ground) encouraged ambilateral motor performance. Lateralized behaviour was strongly sex related. Male and female cats showed paw preferences at the level of the population, but in opposite directions. Females had a greater preference for using their right paw; males were more inclined to adopt their left paw. Feline age was unrelated to either strength or direction of preferred paw use. Overall, the findings suggest that there are two distinct populations of paw preference in the cat that cluster strongly around the animals' sex. The results also point to a relationship between lateralized behaviour and task complexity. More apparent patterns of lateralized behaviour were evident on more complex manipulatory tasks, hinting at functional brain specialization in this species. © 2009 The Association for the Study of Animal Behaviour.

Dogs as a diagnostic tool for ill-health in humans

Researchers have long reported that dogs and cats improve the physical and psychological health of their human caregivers, and while it is still inconclusive, a substantial amount of research now lends support for the commonly held view that "pets are good for us." Recently, studies have directed attention toward exploring the use of animals, most notably dogs, in the detection of disease and other types of health problems in people. This article reviews the evidence for dogs' ability to detect ill health in humans, focusing specifically on the detection of cancer, epileptic seizures, and hypoglycemia. The author describes the research carried out in this area and evaluates it in an effort to determine whether dogs have a role to play in modern health care as an "alert" tool or screening system for ill health. Where necessary, the author has highlighted weaknesses in the work and proposed directions for future studies.

The ontogenesis of lateralized behavior in the domestic cat, Felis silvestris catus

For the first time, the development of paw preferences in the domestic cat, Felis silvestris catus, is explored. Twelve cats were tested at ages 12 weeks, 6 months, and 1 year on a challenge requiring them to use one of their paws to retrieve food. To control for repeated testing of the same cats at different ages, the subjects' paw preferences were compared with those of cats tested just once, at 6 months (n = 11) or 1 year (n = 14) of age. Analysis revealed a significant effect of age on the distribution of cats' paw preferences. Cats were significantly more likely to be ambilateral than paw preferent at 12 weeks and at 6 months but more likely to display a lateral bias in paw use at 1 year. There was a significant positive correlation between cats' paw preferences at 6 months and at 1 year. Lateralized behavior was strongly sex related. Females had a greater preference for using their right paw; males were significantly more inclined to adopt their left. Analysis revealed no significant difference in the direction or strength of paw preferences of cats tested longitudinally or cross-sectionally at 6 months or 1 year of age. Findings indicate that cats develop paw preferences by 1 year and hint at a relative stability in preferred paw use over time. The strong sex effect observed strengthens the case for the influence of a biological mechanism in the emergence of motor asymmetry in cats.

Cowpox: reservoir hosts and geographic range

It is generally accepted that the reservoir hosts of cowpox virus are wild rodents, although direct evidence for this is lacking for much of the virus's geographic range. Here, through a combination of serology and PCR, we demonstrate conclusively that the main hosts in Great Britain are bank voles, wood mice and short-tailed field voles. However, we also suggest that wood mice may not be able to maintain infection alone, explaining the absence of cowpox from Ireland where voles are generally not found. Infection in wild rodents varies seasonally, and this variation probably underlies the marked seasonal incidence of infection in accidental hosts such as humans and domestic cats.

Prenatal and early sucking influences on dietary preference in newborn, weaning, and young adult cats

Early experiences are of potential importance in shaping long-term behavior. This study examined the relative influence of prenatal and/or early postnatal experience of chemosensory stimuli on subsequent olfactory and dietary preferences of cats as newborns, at 9-10 weeks, and at 6 months. Cats were exposed to vanillin or 4-ethylguaiacol via their mother's diet either prenatally, postnatally, perinatally (prenatal and postnatal), or experienced no exposure to the stimuli (control). Newborns were given a two-choice olfactory test between the familiar "odor" and no odor; 9-10 week olds were tested for their preference between two food treats, one flavored with the familiar stimulus and the other unflavored; at 6 months, cats were given a choice of two bowls of food, one flavored with the familiar stimulus and the other unflavored. At all ages, cats preferred the familiar, and avoided the unfamiliar, stimulus. Perinatal exposure exerted the strongest influence on preference. Prenatal exposure influenced preference at all ages and postnatal exposure exerted a stronger effect as the cat aged. We conclude that long-term chemosensory and dietary preferences of cats are influenced by prenatal and early (nursing) postnatal experience, supporting a natural and biologically relevant mechanism for the safe transmission of diet from mother to young. © The Author 2012. Published by Oxford University Press. All rights reserved.

A Cat's Lick: Democratisation and Minority Communities in the Post-Soviet Baltic

The research on Estonia, Latvia and Lithuania has pointed out some controversial social and political developments since the collapse of the Soviet Union. Crucially, there is a discrepancy between the governments' commitment to creating democratic political regimes, to ensuring harmonious social relations and to accommodating the ethno-cultural diversity of the resident communities. In reflecting on the legacies of the Soviet past, the book addresses the role non-titular populations have played in the process of democratisation and the relation between the states, societies and minorities in the post-Soviet Baltic states. The argument proceeds along three lines. Firstly, the book examines the institutional dimension of democratisation in the region, thereby addressing the processes of state- and nation-building as reflected in various policy-developments. Secondly, it compares the impact of ethno-cultural diversity on the development of the respective Baltic nation-states. The discussion makes clear that the framework of Baltic political communities was designed to suit the interests of the titular groups and thus resulted in the marginalisation of the minority communities. Thirdly, the book assesses the participation of minority communities in the development, criticism and improvement of state institutions and policies since independence. The analysis points out that, two decades after independence, the post-Soviet Baltic states and societies are seen by many members of the majority groups as primarily serving the interests of their ethnic community. In this situation, the members of the non-titular communities need to adapt to the majorities' perceptions in order to benefit from the achievements of democratisation.