Depression in Rheumatoid Arthritis and an Estimation of the Bi-directional Association of Depression and Disease Burden: A Dissertation

Depression is a common comorbidity in rheumatoid arthritis (RA), yet it may not be adequately recognized during routine clinical care. RA symptoms may confer a risk for depression, and vice versa; depression may affect RA disease activity and response to treatment. The study aims were to compare patient- and physician-reported depression measures, evaluate the temporal bi-directional association between RA disease activity and depressive symptomology, and assess depression as a moderator of RA treatment. Patients were identified using a national RA registry sample (Consortium of Rheumatology Researchers of North America; CORRONA). Depression prevalence and incidence rates were estimated, and concordance and disagreement using measures reported separately by patients and physicians, as well as baseline cross-sectional associations between RA disease and a history of depression. A survival analysis was conducted to temporally predict the incident onset of self-reported depressive symptoms using the different metrics of RA disease activity. Also, mixed effects models were used to assess prospective changes in RA disease activity by prevalent and incident depressive symptom status. Lastly, logistic regression models compared the likelihood of clinical response to RA treatment during follow-up in those with and without depression when starting biologic disease modifying anti-rheumatic drug (DMARD) therapy. Patient-reported depression rates were much higher and significantly different from physician based comorbidity estimates. Patient and physician RA disease activity measures were associated with an increased risk for depression onset, but not laboratory-reported serum biomarkers. Similarly, depression was temporally associated with significantly slower rates of decline regarding every patient-reported disease activity measure, some physician-reported metrics, but not acute phase reactants. Moreover, there was a significantly lower probability of achieving clinical remission among those with depression on a biologic DMARD after 6 months and an analogous effect at 12-months that was slightly lower in magnitude, which did not reach statistical significance. Rheumatologists under-reported the occurrence of prevalent and incident depressive symptoms, and thus are likely unaware of its presence in their RA patients. Further, the results suggest the bi-directional effects between these conditions are related to the cognitive and behavioral aspects of depression and their interactions with disease activity, rather than shared immunological mechanisms in the context of cell-mediated immunity. When also considering the impact on clinical response to biologic DMARDS, the findings collectively imply that rheumatologists must address any challenges due to depression to provide the best care to their patients

Design and Analysis of the Sphinx-NG CubeSat

This project continues the development of the Attitude Determination and Control (ADC) subsystem for a three-unit CubeSat in a high-altitude, polar, sun-synchronous orbit mission to perform solar and extraterrestrial X-ray spectroscopy. The previously outlined list of sensors and actuators were evaluated and updated. The performance of algorithms used for detumble, initial attitude determination, and attitude maintenance was improved by using MATLAB® and Systems Tool Kit (STK) simulations. Additionally, a low- cost, prototype ADC test bed was constructed which will be used by future teams to test and verify the selected ADC hardware. Finally, a detailed MATLAB® code guide, derivations of ADC algorithms, and recommendations were developed to assist future CubeSat ADC teams

Relationships between pig birth weight and expression of the immediate early gene EGR-1 in umbilical cord Wharton's jelly

Citation: Morton, J. M., Rathbun, T., & Davis, D. L. (2016). Relationships between pig birth weight and expression of the immediate early gene EGR-1 in umbilical cord Wharton's jelly. Journal of Animal Science, 94, 149-149. doi:10.2527/msasas2016-317In humans the expression of EGR-1 in umbilical cord Wharton’s jelly has been related to birth weight. In umbilical cords of small for gestational age (SGA) babies the expression of EGR-1 is increased compared to normal weight contemporaries. Expression of EGR-1 appears to indicate prenatal programming resulting from growth restriction. It is known that SGA babies develop slower compared to normal sized babies and in many ways are comparable to small birth weight pigs. Therefore we investigated whether EGR-1 expression in pig umbilical cord Wharton’s jelly is related to birth and weaning weights. Fifty-seven umbilical cords were collected from 5 litters (PIC; 326 × 1050), along with birth and weaning weights. Wharton’s jelly tissue was snap frozen and stored (?80°C) until RNA was extracted (Trizol method), RNA quantity determined using the Nanodrop method and quality was evaluated with an Agilent Bioanalyzer. Quantitative PCR was used to determine expression of EGR-1 compared to 18S and the data converted to relative expression using RNA from newborn pig testis as a calibrator. Birth weight (P < 0.003) and wean weight at d 21 (P < 0.026) were correlated negatively with EGR-1 expression. Larger pigs had decreased expression of EGR-1 compared to smaller pigs. The umbilical cords from the 14 pigs with the lowest expression of EGR-1 (bottom quartile) included only one pig with a birth weight < 1.11 kg while the top quartile included 9 pigs weighing less than 1.11 kg at birth (P < 0.002, chi square). In response to rising global demands for pork, swine producers have increased litter sizes and this has resulted in more small pigs at birth. We have identified that pigs with a birth weight below 1.11 kg have increased mortality rates by weaning age (3–4 wk). These pigs do not grow as well as their heavier contemporaries and result in lower value carcasses. Expression of EGR-1 in umbilical cords of low birth weight pigs appears to reflect prenatal programming comparable to that identified in SGA babies

Cj0596 is a periplasmic peptidyl prolyl cis-trans isomerase involved in Campylobacter jejuni motility, invasion, and colonization

Abstract Background Campylobacter jejuni is a gastrointestinal pathogen of humans, but part of the normal flora of poultry, and therefore grows well at the respective body temperatures of 37°C and 42°C. Proteomic studies on temperature regulation in C. jejuni strain 81–176 revealed the upregulation at 37°C of Cj0596, a predicted periplasmic chaperone that is similar to proteins involved in outer membrane protein folding and virulence in other bacteria. Results The cj0596 gene was highly conserved in 24 strains and species of Campylobacter, implying the importance of this gene. To study the role that Cj0596 plays in C. jejuni pathogenesis, a mutant derivative of strain 81–176 was constructed in which the cj0596 gene was precisely deleted. A revertant of this mutant was isolated by restoring the gene to its original chromosomal location using streptomycin counterselection. The cj0596 mutant strain demonstrated a slightly decreased growth rate and lower final growth yield, yet was more motile and more invasive of human intestinal epithelial cells than wild-type. In either single or mixed infections, the mutant was less able to colonize mice than 81–176. The cj0596 mutant also expressed altered levels of several proteins. Conclusion Mutation of cj0596 has an effect on phenotypes related to C. jejuni pathogenesis, probably due to its role in the proper folding of critical outer membrane proteins.</p

The augmentation of retinogeniculate communication during thalamic burst mode

Retinal signals are transmitted to cortex via neurons in the lateral geniculate nucleus (LGN), where they are processed in burst or tonic response mode. Burst mode occurs when LGN neurons are sufficiently hyperpolarized for T-Type Ca(2+) channels to de-inactivate, allowing them to open in response to depolarization which can trigger a high-frequency sequence of Na(+)-based spikes (i.e. burst). In contrast, T-type channels are inactivated during tonic mode and do not contribute to spiking. Although burst mode is commonly associated with sleep and the disruption of retinogeniculate communication, bursts can also be triggered by visual stimulation, thereby transforming the retinal signals relayed to the cortex.To determine how burst mode affects retinogeniculate communication, we made recordings from monosynaptically connected retinal ganglion cells and LGN neurons in male/female cats during visual stimulation. Our results reveal a robust augmentation of retinal signals within the LGN during burst mode. Specifically, retinal spikes were more effective and often triggered multiple LGN spikes during periods likely to have increased T-Type Ca(2+) channel activity. Consistent with the biophysical properties of T-Type Ca(2+) channels, analysis revealed that effect magnitude was correlated with the duration of the preceding thalamic interspike interval and occurred even in the absence of classically defined bursts. Importantly, the augmentation of geniculate responses to retinal input was not associated with a degradation of visual signals. Together, these results indicate a graded nature of response mode and suggest that, under certain conditions, bursts facilitate the transmission of visual information to the cortex by amplifying retinal signals.SIGNIFICANCE STATEMENTThe thalamus is the gateway for retinal information traveling to the cortex. The lateral geniculate nucleus (LGN), like all thalamic nuclei, has two classically defined categories of spikes-tonic and burst-that differ in their underlying cellular mechanisms. Here we compare retinogeniculate communication during burst and tonic response modes. Our results show that retinogeniculate communication is enhanced during burst mode and visually evoked thalamic bursts, thereby augmenting retinal signals transmitted to cortex. Further, our results demonstrate that the influence of burst mode on retinogeniculate communication is graded and can be measured even in the absence of classically defined thalamic bursts

A New Species of Giant Sengi or Elephant-Shrew (Genus \u3cem\u3eRhynchocyon\u3c/em\u3e) Highlights the Exceptional Biodiversity of the Udzungwa Mountains of Tanzania

A new species of sengi, or elephant-shrew, is described. It was discovered in the northern Udzungwa Mountains of Tanzania in 2005. Sengis (Order Macroscelidea, super-cohort Afrotheria) include four genera and 15 species of mammals that are endemic to Africa. This discovery is a significant contribution to the systematics of this small order. Based on 49 camera trap images, 40 sightings and five voucher specimens, the new sengi is diurnal and distinguished from the other three species of Rhynchocyon by a grizzled grey face, pale yellow to cream chest and chin, orange-rufous sides, maroon back and jet-black lower rump and thighs. The body weight of the new species is about 700 g, which is 25–50% greater than any other giant sengi. The new Rhynchocyon is only known from two populations that cover about 300 km2 of montane forest. It has an estimated density of 50–80 individuals km−2. This discovery has important implications for the conservation of the high biodiversity that is found in the forests of the Eastern Arc Mountains

Advances in studying phasic dopamine signaling in brain reward mechanisms

The last sixty years of research has provided extraordinary advances of our knowledge of the reward system. Since its discovery as a neurotransmitter by Carlsson and colleagues (1), dopamine (DA) has emerged as an important mediator of reward processing. As a result, a number of electrochemical techniques have been developed to measure DA in the brain. Together, these techniques have begun to elucidate the complex roles of tonic and phasic DA signaling in reward processing and addiction. In this review, we will first provide a guide for the most commonly used electrochemical methods for DA detection and describe their utility in furthering our knowledge about DA's role in reward and addiction. Second, we will review the value of common in vitro and in vivo preparations and describe their ability to address different types of questions. Last, we will review recent data that has provided new mechanistic insight of in vivo phasic DA signaling and its role in reward processing and reward-mediated behavior

Data-driven curation, learning and analysis for inferring evolving IoT botnets in the wild

The insecurity of the Internet-of-Things (IoT) paradigm continues to wreak havoc in consumer and critical infrastructure realms. Several challenges impede addressing IoT security at large, including, the lack of IoT-centric data that can be collected, analyzed and correlated, due to the highly heterogeneous nature of such devices and their widespread deployments in Internet-wide environments. To this end, this paper explores macroscopic, passive empirical data to shed light on this evolving threat phenomena. This not only aims at classifying and inferring Internet-scale compromised IoT devices by solely observing such one-way network traffic, but also endeavors to uncover, track and report on orchestrated "in the wild" IoT botnets. Initially, to prepare the effective utilization of such data, a novel probabilistic model is designed and developed to cleanse such traffic from noise samples (i.e., misconfiguration traffic). Subsequently, several shallow and deep learning models are evaluated to ultimately design and develop a multi-window convolution neural network trained on active and passive measurements to accurately identify compromised IoT devices. Consequently, to infer orchestrated and unsolicited activities that have been generated by well-coordinated IoT botnets, hierarchical agglomerative clustering is deployed by scrutinizing a set of innovative and efficient network feature sets. By analyzing 3.6 TB of recent darknet traffic, the proposed approach uncovers a momentous 440,000 compromised IoT devices and generates evidence-based artifacts related to 350 IoT botnets. While some of these detected botnets refer to previously documented campaigns such as the Hide and Seek, Hajime and Fbot, other events illustrate evolving threats such as those with cryptojacking capabilities and those that are targeting industrial control system communication and control services