Grid technology for collaborative ontology development

In contrast with the centrally-organised curation of the Gene Ontology, many biological ontologies are developed by loosely-organised groups who develop their ontology remotely. These groups tend to be formed from scientists and bio-informaticians from research groups with a common interest, who want to create a resource that will be useful to the community, rather than being formally mandated. Until recently, technological support for bio-ontology development relied on stand-alone editors running on users’ desk- tops for creating new ontology versions (e.g. OBO-Edit, COBrA and Protégé) and on private email, email lists and perhaps Wikis for the distribution of ontology files and discussions. Clearly, much better use could be made of the storage, versioning and visualisation techniques being developed by the database and e- Science communities. BioSphere is an online ontology editor supporting multiple users and is underpinned by a server that stores versions (in OWL-XML) and provides a discussion portal

Stability and reachability analysis of a hybrid model of luminescence in the marine bacterium \u3ci\u3eVibrio fischeri\u3c/i\u3e

This paper addresses the mathematical modeling and analysis of the quorum sensing system found in unicellular bacteria that exhibit bioluminescence. The luminescence is governed by the expression of genes in the cell, which in turn is controlled by the density of cells in a population. The paper illustrates the application of standard tools in control theory and some recent tools in hybrid systems to the quorum sensing system, and demonstrates that bioluminescence can be modeled and understood as the output of a switched dynamical system

An intrinsic connection between COVID-19 and aging

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a rapidly spreading outbreak of coronavirus disease 2019 (the COVID-19 pandemic). COVID-19 has severely affected healthcare systems worldwide, as well as the global economy, and has significantly increased morbidity and mortality rates. The majority of COVID-19-related deaths occurred in older individuals, primarily among those with concomitant diseases, including metabolic, respiratory, and cardiovascular diseases. Aging hallmarks, such as cellular senescence, chronic inflammation, and genomic instability, partially explain the increased disease severity at the molecular level with advancing age. Other multifactorial considerations, including healthcare facilities, socioeconomic status, and dissemination of epidemic information, may help control morbidity in the elderly population. While the World Health Organization declared an end to the emergency status of COVID-19 in May 2023, physical and emotional impairments may persist after recovery from the virus. Precautions should therefore be taken to prevent future pandemics, and suitable emphasis should be placed on addressing persistent COVID-19 and preventing future pandemics

Cytotoxic and Apoptotic Effects of Pinostilbene and Bortezomib Combination Treatment on Human Multiple Myeloma Cells.

Multiple myeloma (MM) is a cancer of plasma cells in the bone marrow characterized by bone lesions, hypercalcemia, anemia, and renal failure. Bortezomib (BTZ), a common treatment for MM, is a proteasome inhibitor that induces apoptosis in MM cells. However, high doses of BTZ can be very toxic, signifying a need for a synergistic drug combination to improve treatment efficacy. Resveratrol (RES), a phenolic compound found in grapes, has been shown to inhibit MM cell growth. We sought to identify a synergistic combination of BTZ with a RES derivative and analyze the effects on reducing viability and inducing apoptosis in human MM cells. BTZ as well as RES and its derivatives pinostilbene (PIN) and piceatannol (PIC) decreased MM cell viability in a dose- and time-dependent manner and increased expression of cleaved proapoptotic proteins poly(ADP-ribose) polymerase 1 (PARP1) and caspase-3 in a dose-dependent manner. The combination of 5 nM BTZ and 5 μM PIN was identified to have synergistic cytotoxic effects in MM RPMI 8226 cells. MM RPMI 8226 cells treated with this combination for 24 h showed increased cleaved PARP1 and caspase-3 expression and higher percentages of apoptotic cells versus cells treated with the individual compounds alone. The treatment also showed increased apoptosis induction in MM RPMI 8226 cells co-cultured with human bone marrow stromal HS-5 cells in a Transwell model used to mimic the bone marrow microenvironment. Expression of oxidative stress defense proteins (catalase, thioredoxin, and superoxide dismutase) in RPMI 8226 cells were reduced after 24 h treatment, and cytotoxic effects of the treatment were ameliorated by antioxidant N-acetylcysteine (NAC), suggesting the treatment impacts antioxidant levels in RPMI 8226 cells. Our results suggest that this combination of BTZ and PIN decreases MM cell viability synergistically by inducing apoptosis and oxidative stress in MM cells

JCV GCN in a Natalizumab-Treated MS Patient is Associated With Mutations of the VP1 Capsid Gene

Objective: To describe the clinical, neuroimaging, immunologic, and virologic characteristics of JC virus-associated granule cell neuronopathy (JCV GCN) in a natalizumab-treated patient with multiple sclerosis (MS) who developed immune reconstitution inflammatory syndrome (IRIS) after natalizumab withdrawal. Methods: We obtained longitudinal clinical data as well as MRI and proton magnetic resonance spectroscopy from this patient with MS. We measured JCV-specific cellular immune response in his peripheral blood by intracellular cytokine staining and sequenced a fragment of JCV VP1 capsid gene detected in his CSF. We contrast our findings with the first recently reported case. Results: This patient presented with worsening cerebellar symptoms and progressive cerebellar atrophy without new MS lesions on MRI after 63 months of natalizumab monotherapy. JCV DNA was detected in his CSF by PCR and harbored novel GCN-type mutations in the VP1 gene. He developed IRIS upon discontinuation of natalizumab and plasma exchange, which manifested itself by a worsening of clinical symptoms and contrast enhancement in the cerebellum on MRI. Treatment with corticosteroids resulted in resolution of IRIS, as demonstrated by proton magnetic resonance spectroscopy. The patient had a strong JCV-specific T-cell response in his peripheral blood and remains alive after 15 months from onset of symptoms, although with significant disability. He did not have MS relapse on glatiramer acetate. Conclusions: JCV GCN should be considered in patients on natalizumab presenting with progressive cerebellar symptoms and cerebellar atrophy, and is associated with mutations in the JCV VP1 gene. Natalizumab withdrawal may be complicated by JCV GCN IRIS, and require treatment with corticosteroids

Opioid-Prescribing Practices for Post-Operative Patients in Otolaryngology: A Multiphasic Quality Improvement Project in a Single Large Institution

Objectives: In otolaryngology, postoperative pain management lacks evidence-based guidelines. We investigated opioid prescription and consumption for common procedures to develop prescribing guidelines at our institution. Study Design: Prospective, survey study. Methods: Patients who underwent surgery between July and September were given surveys upon discharge and at first follow-up visit. We assessed opioid usage and pain using the visual analog scale and opioid consumption throughout the postoperative period. Opioid prescriptions were converted to a standardized unit of 5 mg Oxycodone pills for reporting. Four procedures (transoral robotic surgery resection [TORS], sialendoscopy, parathyroidectomy/thyroidectomy, and parotidectomy) were selected for isolated analysis. Results: Of the 80 surveys that met criteria for inclusion for analysis, a total of 1,954.0 pills were prescribed, with 300.3 pills (15.4%) reported having been used by patients, leaving 1,653.7 pills (84.5%) unused. TORS (n=12) average pills used: 4.9 ± 5.9 (95% CI: 1.6-8.3); total % pills unused: 89.3%. Sialendoscopy (n=13) average pills used: 4.2 ± 5.1 (95% CI: 1.1-7.4); total % pills unused: 72.5%. Parathyroidectomy/thyroidectomy (n=22) average pills used: 3.1 ± 4.4 (95% CI: 1.7-5.5); total % pills unused: 79.2%. Parotidectomy (n=12) average pills used: 1.3 ± 2.5 (95% CI: 0.7-4.3); total % pills unused: 94.7%. Conclusions: At our institution, opioids for ((postoperative otolaryngology)) patients’ pain management in otolaryngologic procedures were prescribed in excess with 84.5% reported as unused. Procedure-specific opioid diversion pool ranged from 72.5%-94.7%. Our findings provide a foundation for procedure-specific evidence-based opioid prescription guidelines

Detection of a Westward Hotspot Offset in the Atmosphere of a Hot Gas Giant CoRoT-2b

Short-period planets exhibit day-night temperature contrasts of hundreds to thousands of degrees K. They also exhibit eastward hotspot offsets whereby the hottest region on the planet is east of the substellar point; this has been widely interpreted as advection of heat due to eastward winds. We present thermal phase observations of the hot Jupiter CoRoT-2b obtained with the IRAC instrument on the Spitzer Space Telescope. These measurements show the most robust detection to date of a westward hotspot offset of 23 $\pm$ 4 degrees, in contrast with the nine other planets with equivalent measurements. The peculiar infrared flux map of CoRoT-2b may result from westward winds due to non-synchronous rotation magnetic effects, or partial cloud coverage, that obscures the emergent flux from the planet's eastern hemisphere. Non-synchronous rotation and magnetic effects may also explain the planet's anomalously large radius. On the other hand, partial cloud coverage could explain the featureless dayside emission spectrum of the planet. If CoRoT-2b is not tidally locked, then it means that our understanding of star-planet tidal interaction is incomplete. If the westward offset is due to magnetic effects, our result represents an opportunity to study an exoplanet's magnetic field. If it has Eastern clouds, then it means that our understanding of large-scale circulation on tidally locked planets is incomplete.Comment: 30 pages, 4 figures, 15 supplementary figure

Mixed Chamber Ensembles

Kennesaw State University School of Music presents Mixed Chamber Ensembles, 2:00 p.m. performance.https://digitalcommons.kennesaw.edu/musicprograms/1357/thumbnail.jp

Selective Oxidative Stress Induces Dual Damage to Telomeres and Mitochondria in Human T Cells

Oxidative stress caused by excess reactive oxygen species (ROS) accelerates telomere erosion and mitochondrial injury, leading to impaired cellular functions and cell death. Whether oxidative stress-mediated telomere erosion induces mitochondrial injury, or vice versa, in human T cells—the major effectors of host adaptive immunity against infection and malignancy—is poorly understood due to the pleiotropic effects of ROS. Here we employed a novel chemoptogenetic tool that selectively produces a single oxygen (1O2) only at telomeres or mitochondria in Jurkat T cells. We found that targeted 1O2 production at telomeres triggered not only telomeric DNA damage but also mitochondrial dysfunction, resulting in T cell apoptotic death. Conversely, targeted 1O2 formation at mitochondria induced not only mitochondrial injury but also telomeric DNA damage, leading to cellular crisis and apoptosis. Targeted oxidative stress at either telomeres or mitochondria increased ROS production, whereas blocking ROS formation during oxidative stress reversed the telomeric injury, mitochondrial dysfunction, and cellular apoptosis. Notably, the X-ray repair cross-complementing protein 1 (XRCC1) in the base excision repair (BER) pathway and multiple mitochondrial proteins in other cellular pathways were dysregulated by the targeted oxidative stress. By confining singlet 1O2 formation to a single organelle, this study suggests that oxidative stress induces dual injury in T cells via crosstalk between telomeres and mitochondria. Further identification of these oxidation pathways may offer a novel approach to preserve mitochondrial functions, protect telomere integrity, and maintain T cell survival, which can be exploited to combat various immune aging-associated diseases