A graph theoretical approach to experimental prioritization in genome-scale investigations.

The goal of systems biology is to gain a network level understanding of how gene interactions influence biological states, and ultimately inform upon human disease. Given the scale and scope of systems biology studies, resource constraints often limit researchers when validating genome-wide phenomena and potentially lead to an incomplete understanding of the underlying mechanisms. Further, prioritization strategies are often biased towards known entities (e.g. previously studied genes/proteins with commercially available reagents), and other technical issues that limit experimental breadth. Here, heterogeneous biological information is modeled as an association graph to which a high-performance minimum dominating set solver is applied to maximize coverage across the graph, and thus increase the breadth of experimentation. First, we tested our model on retrieval of existing gene functional annotations and demonstrated that minimum dominating set returns more diverse terms when compared to other computational methods. Next, we utilized our heterogenous network and minimum dominating set solver to assist in the process of identifying understudied genes to be interrogated by the International Mouse Phenotyping Consortium. Using an unbiased algorithmic strategy, poorly studied genes are prioritized from the remaining thousands of genes yet to be characterized. This method is tunable and extensible with the potential to incorporate additional user-defined prioritizing information. The minimum dominating set approach can be applied to any biological network in order to identify a tractable subset of features to test experimentally or to assist in prioritizing candidate genes associated with human disease.

Administration of thimerosal-containing vaccines to infant rhesus macaques does not result in autism-like behavior or neuropathology.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder. Some anecdotal reports suggest that ASD is related to exposure to ethyl mercury, in the form of the vaccine preservative, thimerosal, and/or receiving the measles, mumps, rubella (MMR) vaccine. Using infant rhesus macaques receiving thimerosal-containing vaccines (TCVs) following the recommended pediatric vaccine schedules from the 1990s and 2008, we examined behavior, and neuropathology in three brain regions found to exhibit neuropathology in postmortem ASD brains. No neuronal cellular or protein changes in the cerebellum, hippocampus, or amygdala were observed in animals following the 1990s or 2008 vaccine schedules. Analysis of social behavior in juvenile animals indicated that there were no significant differences in negative behaviors between animals in the control and experimental groups. These data indicate that administration of TCVs and/or the MMR vaccine to rhesus macaques does not result in neuropathological abnormalities, or aberrant behaviors, like those observed in ASD.

Routine Trimming and Therapeutic Farriery in Foals.

Hoof care in the first few months of life is serious business and should never be taken lightly. Farriery plays a vital role in both the development of the hoof and the conformation of the limb. Management of the feet and limbs during this period will often dictate the success of the foal as a sales yearling or mature sound athlete. A sound foot care program is time-consuming, whereas assembly-line trimming is quick and easy, but the former is much more beneficial.

Maximizing Sensory Dynamic Range by Tuning the Cortical State to Criticality.

Modulation of interactions among neurons can manifest as dramatic changes in the state of population dynamics in cerebral cortex. How such transitions in cortical state impact the information processing performed by cortical circuits is not clear. Here we performed experiments and computational modeling to determine how somatosensory dynamic range depends on cortical state. We used microelectrode arrays to record ongoing and whisker stimulus-evoked population spiking activity in somatosensory cortex of urethane anesthetized rats. We observed a continuum of different cortical states; at one extreme population activity exhibited small scale variability and was weakly correlated, the other extreme had large scale fluctuations and strong correlations. In experiments, shifts along the continuum often occurred naturally, without direct manipulation. In addition, in both the experiment and the model we directly tuned the cortical state by manipulating inhibitory synaptic interactions. Our principal finding was that somatosensory dynamic range was maximized in a specific cortical state, called criticality, near the tipping point midway between the ends of the continuum. The optimal cortical state was uniquely characterized by scale-free ongoing population dynamics and moderate correlations, in line with theoretical predictions about criticality. However, to reproduce our experimental findings, we found that existing theory required modifications which account for activity-dependent depression. In conclusion, our experiments indicate that in vivo sensory dynamic range is maximized near criticality and our model revealed an unanticipated role for activity-dependent depression in this basic principle of cortical function.

A Comparative Study of Gene Co-Expression Thresholding Algorithms.

The thresholding problem is studied in the context of graph theoretical analysis of gene co-expression data. A number of thresholding methodologies are described, implemented, and tested over a large collection of graphs derived from real high-throughput biological data. Comparative results are presented and discussed.

Seminar: Scalable Preprocessing Tools for Exposomic Data Analysis.

BACKGROUND: The exposome serves as a popular framework in which to study exposures from chemical and nonchemical stressors across the life course and the differing roles that these exposures can play in human health. As a result, data relevant to the exposome have been used as a resource in the quest to untangle complicated health trajectories and help connect the dots from exposures to adverse outcome pathways. OBJECTIVES: The primary aim of this methods seminar is to clarify and review preprocessing techniques critical for accurate and effective external exposomic data analysis. Scalability is emphasized through an application of highly innovative combinatorial techniques coupled with more traditional statistical strategies. The Public Health Exposome is used as an archetypical model. The novelty and innovation of this seminar's focus stem from its methodical, comprehensive treatment of preprocessing and its demonstration of the positive effects preprocessing can have on downstream analytics. DISCUSSION: State-of-the-art technologies are described for data harmonization and to mitigate noise, which can stymie downstream interpretation, and to select key exposomic features, without which analytics may lose focus. A main task is the reduction of multicollinearity, a particularly formidable problem that frequently arises from repeated measurements of similar events taken at various times and from multiple sources. Empirical results highlight the effectiveness of a carefully planned preprocessing workflow as demonstrated in the context of more highly concentrated variable lists, improved correlational distributions, and enhanced downstream analytics for latent relationship discovery. The nascent field of exposome science can be characterized by the need to analyze and interpret a complex confluence of highly inhomogeneous spatial and temporal data, which may present formidable challenges to even the most powerful analytical tools. A systematic approach to preprocessing can therefore provide an essential first step in the application of modern computer and data science methods. https://doi.org/10.1289/EHP12901.

Farriery for the hoof with a sheared heel.

Sheared heels develop as an adaptation-distortion of the hoof capsule as a result of an abnormal strike and loading pattern of the foot, which is generally a consequence of limb conformation. The growth rate around the circumference of the hoof should be approximately uniform, but regional disturbances in growth rate can occur to either increase or decrease growth. The primary conformational trait that is observed in horses that develop sheared heels is a rotational deformity of the distal limb and a narrow chest. Farriery is directed toward improving the hoof capsule distortion and decreasing the forces on the displaced side of the foot.

Farriery for the hoof with a high heel or club foot.

A club foot or flexural deformity may affect a horse at any stage of life from neonate through adulthood. The emphasis of this article is on defining and recommending the appropriate farriery for flexural deformities involving the deep digital flexor tendon and the distal interphalangeal joint. Clinical management of the flexural deformity is influenced by the severity, duration, and etiology of the club foot as well as the degree and source of lameness. Also discussed is the management of mismatched hoof angles, which remains a controversial subject for both farrier and veterinarian.

Farriery for hoof wall defects: quarter cracks and toe cracks.

Conditions that result in the loss of the structural integrity of the hoof wall, such as quarter and toe cracks, are not uncommon and usually manifest in lameness. The successful management of these problems involves identifying and addressing the underlying causes, stabilization of the foot, and committed follow-up.

Nonseptic diseases associated with the hoof complex: keratoma, white line disease, canker, and neoplasia.

This article addresses nonseptic diseases associated with the hoof complex, namely keratoma, white line disease, canker, and neoplasia. Keratoma is an uncommon cause of lameness, which may be surgically removed. White line disease, a keratolytic process on the solar surface of the hoof, is treated with therapeutic farriery and resection of the hoof wall when appropriate. Equine canker is an infectious process that results in development of a chronic hypertrophy of the horn-producing tissues. Neoplasia involving the equine foot is rare, and melanoma is the most common type of neoplasm reported.

Septic diseases associated with the hoof complex: abscesses, punctures wounds, and infection of the lateral cartilage.

Hoof abscesses are probably the most common cause of acute severe lameness in horses encountered by veterinarians and farriers. Most affected horses show sudden, severe (acute) lameness; the degree of lameness varies from being subtle in the early stages to non-weight bearing. There is still debate between the veterinary and farrier professions as to who should treat a hoof abscess and the best method to resolve the abscess. Puncture wounds to the sole of the foot can introduce bacteria and debris to the solar surface of the distal phalanx and produce a fracture or a septic pedal osteitis.

The equine practitioner-farrier relationship: building a partnership.

The importance of hoof care in maintaining the health and soundness of a horse cannot be overstated. The aphorism, "No foot, no horse" still holds true. For equine ambulatory practitioners, the time devoted to a thorough understanding of the equine digit and it's care is well worth the investment. The effort devoted to developing good relationships with individuals who will likely be responsible for implementing the changes suggested as a result of that understanding will be rewarded many times over in the course of the equine ambulatory practitioner's career.

Domination based classification algorithms for the controllability analysis of biological interaction networks.

Deciding the size of a minimum dominating set is a classic NP-complete problem. It has found increasing utility as the basis for classifying vertices in networks derived from protein-protein, noncoding RNA, metabolic, and other biological interaction data. In this context it can be helpful, for example, to identify those vertices that must be present in any minimum solution. Current classification methods, however, can require solving as many instances as there are vertices, rendering them computationally prohibitive in many applications. In an effort to address this shortcoming, new classification algorithms are derived and tested for efficiency and effectiveness. Results of performance comparisons on real-world biological networks are reported.

Farriery for chronic laminitis.

Laminitis is considered chronic once the distal phalanx has displaced within the hoof capsule. Chronic laminitis generally occurs as a direct sequel to acute laminitis. Clinical evaluation of chronic laminitis is best performed with a thorough clinical examination and radiography. The mainstay of hoof care is therapeutic farriery. In this article, the goals and principles of hoof care, the appropriate trim and various shoes that form the bulk of farriery for chronic laminitis, and surgical treatments are discussed.

Basic farriery for the performance horse.

Proper farriery promotes a healthy functional foot and biomechanical efficiency and prevents lameness. Because the equine veterinarian is responsible for the soundness of the horse, a working knowledge of farriery becomes essential. A thorough knowledge of traditional horseshoeing enables the veterinarian to interact with the farrier at the farrier's level; this ultimately enhances and promotes quality hoof care. This article focuses on fundamental farriery and recognizing subtle changes in hoof conformation that can be used to preserve the integrity of the hoof capsule, along with the structures enclosed within, and thus prevent lameness in the performance horse.

Millisecond, micron precision multi-whisker detector.

The neural mechanisms of somatosensory information processing in the rodent vibrissae system are a topic of intense debate and research. Certain hypotheses emphasize the importance of stick-slip whisker motion, high-frequency resonant vibrations, and/or the ability to decode complex textures. Other hypotheses focus on the importance of integrating information from multiple whiskers. Tests of the former require measurements of whisker motion that achieve high spatiotemporal accuracy without altering the mechanical properties of whiskers. Tests of the latter require the ability to monitor the motion of multiple whiskers simultaneously. Here we present a device that achieves both these requirements for two-dimensional whisker motion in the plane perpendicular to the whiskers. Moreover, the system we present is significantly less expensive (<$2.5 k) and simpler to build than alternative devices which achieve similar detection capabilities. Our system is based on two laser diodes and two linear cameras. It attains millisecond temporal precision and micron spatial resolution. We developed automated algorithms for processing the data collected by our device and benchmarked their performance against manual detection by human visual inspection. By this measure, our detection was successful with less than 10 µm deviation between the automated and manual detection, on average. Here, we demonstrate its utility in anesthetized rats by measuring the motion of multiple whiskers in response to an air puff.

Chronic laminitis: current treatment strategies.

Laminitis is divided into four different phases: developmental, acute, subacute, and chronic. The focus of this article is on treating the laminitic horse after the cessation of therapy for the acute phase, that is, usually 2 to 4 weeks after the onset of clinical signs.

Proper physiologic horseshoeing.

Adherence to the basic principles of physiologic horseshoeing is essential to maintaining hoof health and soundness. Most horses do not require special trimming or shoeing techniques. Becoming familiar with a few basic concepts can help the veterinarian to recognize when changes in trimming or shoeing might be expected to help the performance of a sound horse or might help to restore the performance of one that is lame. Sound physiologic horseshoeing can only be achieved by a thorough knowledge of, strict adherence to, and skillful application of basic principles, such as hoof angle, HPA, and mediolateral balance. Only then does the art of farriery truly approach being a science.