An extended dose-response model for microbial responses to ionizing radiation

© 2017 Siasou, Johnson and Willey. An understanding of the environmental toxicology of ionizing radiation (IR) is needed because nuclear power production is expanding and there is increasing pressure to build nuclear waste repositories. The effects of IR in the environment have long been investigated but there have been fewer studies involving environmental microbiology than its importance to key ecosystems services demands. Here, we highlight some unique aspects of the relationship between microbes and IR and use them to suggest an extended dose-response model. At high doses, IR causes DNA damage and oxidative stress but some microbes have a remarkable capacity for DNA repair and are tolerant of oxidative stress. Not only is significant radioresistance increasingly being reported for microbes, but some microbes are even radiotrophic. The stressful radiative environment of the early Earth might help explain the existence of these traits, which challenge the assumptions of current dose response models for IR. We suggest that a perspective that takes into account these traits plus both dose and dose rate can be used to model an "effects landscape" that might provide insights for the environmental toxicology of IR to microbes. This might help to predict the effects of IR on key ecosystem processes and also be useful in understanding the environmental toxicology of IR in general

Digital tools in allergy and respiratory care

Patient care in the allergy and respiratory fields is advancing rapidly, offering the possibility of the inclusion of a variety of digital tools that aim to improve outcomes of care. Impaired access to several health care facilities during the COVID-19 pandemic has considerably increased the appetite and need for the inclusion of e-health tools amongst end-users. Consequently, a multitude of different e-health tools have been launched worldwide with various registration and access options, and with a wide range of offered benefits. From the perspective of both patients and healthcare providers (HCPs), as well as from a legal and device-related perspective, several features are important for the acceptance, effectiveness,and long-term use of e-health tools. Patients and physicians have different needs and expectations of how digital tools might be of help in the care pathway. There is a need for standardization by defining quality assurance criteria.Therefore, the Upper Airway Diseases Committee of the World Allergy Organization (WAO) has taken the initiative to define and propose criteria for quality, appeal, and applicability of e-health tools in the allergy and respiratory care fields from a patient, clinician, and academic perspective with the ultimate aim to improve patient health and outcomes of care

Role of Pelvic Lymph Node Dissection in Prostate Cancer Treatment

Pelvic lymph node dissection (PLND) is the most accurate and reliable staging procedure for detecting lymph node invasion (LNI) in prostate cancer. Recently, [11C]-choline positron emission tomography imaging and magnetic resonance imaging with lymphotropic superpara-magnetic nanoparticles have shown potential for detecting LNI but are still under investigation. The risk of LNI in low-risk groups could be underestimated by use of the current nomograms, which rely on data collected from patients who underwent only limited PLND. Extended PLND (ePLND) shows higher lymph node yield, which leads to the removal of more positive nodes and fewer missed positive nodes. It may be possible to refrain from performing PLND on low-risk patients with a prostate-specific antigen value <10 ng/ml and a biopsy Gleason score ≤6, but the risk of biopsy-related understaging should be kept in mind. Theoretically, meticulous ePLND may also impact prostate cancer survival by clearing low-volume diseases and occult micrometastasis even in pN0. The therapeutic role of PLND in prostate cancer patients is still an open question, especially in individuals with low-risk disease. Patients with intermediate- to high-risk disease are more likely to benefit from ePLND

Regulation of synaptic Rac1 activity, long-term potentiation maintenance, and learning and memory by BCR and ABR Rac GTPase-activating proteins

Rho family small GTPases are important regulators of neuronal development. Defective Rho regulation causes nervous system dysfunctions including mental retardation and Alzheimer's disease. Rac1, a member of the Rho family, regulates dendritic spines and excitatory synapses, but relatively little is known about how synaptic Rac1 is negatively regulated. Breakpoint cluster region (BCR) is a Rac GTPase-activating protein known to form a fusion protein with the c-Abl tyrosine kinase in Philadelphia chromosome-positive chronic myelogenous leukemia. Despite the fact that BCR mRNAs are abundantly expressed in the brain, the neural functions of BCR protein have remained obscure. We report here that BCR and its close relative active BCR-related (ABR) localize at excitatory synapses and directly interact with PSD-95, an abundant postsynaptic scaffolding protein. Mice deficient for BCR or ABR show enhanced basal Rac1 activity but only a small increase in spine density. Importantly, mice lacking BCR or ABR exhibit a marked decrease in the maintenance, but not induction, of long-term potentiation, and show impaired spatial and object recognition memory. These results suggest that BCR and ABR have novel roles in the regulation of synaptic Rac1 signaling, synaptic plasticity, and learning and memory, and that excessive Rac1 activity negatively affects synaptic and cognitive functions.This work was supported by the National Creative Research Initiative Program of the Korean Ministry of Education, Science and Technology (E.K.), Neuroscience Program Grant 2009-0081468 (S.-Y.C.), 21st Century Frontier R&D Program in Neuroscience Grant 2009K001284 (H.K.), Basic Science Research Program Grant R13-2008-009-01001-0 (Y.C.B.), and United States Public Health Service Grants HL071945 (J.G.) and HL060231 (J.G., N.H.)

14-3-3 Mediates Histone Cross-Talk during Transcription Elongation in Drosophila

Post-translational modifications of histone proteins modulate the binding of transcription regulators to chromatin. Studies in Drosophila have shown that the phosphorylation of histone H3 at Ser10 (H3S10ph) by JIL-1 is required specifically during early transcription elongation. 14-3-3 proteins bind H3 only when phosphorylated, providing mechanistic insights into the role of H3S10ph in transcription. Findings presented here show that 14-3-3 functions downstream of H3S10ph during transcription elongation. 14-3-3 proteins localize to active genes in a JIL-1–dependent manner. In the absence of 14-3-3, levels of actively elongating RNA polymerase II are severely diminished. 14-3-3 proteins interact with Elongator protein 3 (Elp3), an acetyltransferase that functions during transcription elongation. JIL-1 and 14-3-3 are required for Elp3 binding to chromatin, and in the absence of either protein, levels of H3K9 acetylation are significantly reduced. These results suggest that 14-3-3 proteins mediate cross-talk between histone phosphorylation and acetylation at a critical step in transcription elongation

HIV and COVID-19: two pandemics with significant (but different) central nervous system complications

Human immunodeficiency virus (HIV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause significant neurologic disease. Central nervous system (CNS) involvement of HIV has been extensively studied, with well-documented invasion of HIV into the brain in the initial stage of infection, while the acute effects of SARS-CoV-2 in the brain are unclear. Neuropathologic features of active HIV infection in the brain are well characterized whereas neuropathologic findings in acute COVID-19 are largely non-specific. On the other hand, neuropathologic substrates of chronic dysfunction in both infections, as HIV-associated neurocognitive disorders (HAND) and post-COVID conditions (PCC)/long COVID are unknown. Thus far, neuropathologic studies on patients with HAND in the era of combined antiretroviral therapy have been inconclusive, and autopsy studies on patients diagnosed with PCC have yet to be published. Further longitudinal, multidisciplinary studies on patients with HAND and PCC and neuropathologic studies in comparison to controls are warranted to help elucidate the mechanisms of CNS dysfunction in both conditions