Bats Use Magnetite to Detect the Earth's Magnetic Field

While the role of magnetic cues for compass orientation has been confirmed in numerous animals, the mechanism of detection is still debated. Two hypotheses have been proposed, one based on a light dependent mechanism, apparently used by birds and another based on a “compass organelle” containing the iron oxide particles magnetite (Fe3O4). Bats have recently been shown to use magnetic cues for compass orientation but the method by which they detect the Earth's magnetic field remains unknown. Here we use the classic “Kalmijn-Blakemore” pulse re-magnetization experiment, whereby the polarity of cellular magnetite is reversed. The results demonstrate that the big brown bat Eptesicus fuscus uses single domain magnetite to detect the Earths magnetic field and the response indicates a polarity based receptor. Polarity detection is a prerequisite for the use of magnetite as a compass and suggests that big brown bats use magnetite to detect the magnetic field as a compass. Our results indicate the possibility that sensory cells in bats contain freely rotating magnetite particles, which appears not to be the case in birds. It is crucial that the ultrastructure of the magnetite containing magnetoreceptors is described for our understanding of magnetoreception in animals

Radiation-Induced Cognitive Decline: Challenges and Solutions

Parisa Shamsesfandabadi,1 Arpeet Patel,2 Yun Liang,1 Matthew J Shepard,3 Rodney E Wegner1 1Radiation Oncology department, Allegheny Health Network, Pittsburgh, PA, USA; 2Drexel University College of Medicine, Philadelphia, PA, USA; 3Neurosurgery Department, Allegheny Health Network, Pittsburgh, PA, USACorrespondence: Parisa Shamsesfandabadi, Email [email protected]: Radiation therapy, a common treatment for central nervous system cancers, can negatively impact cognitive function, resulting in radiation-induced cognitive decline (RICD). RICD involves a decline in cognitive abilities such as memory and attention, likely due to damage to brain white matter, inflammation, and oxidative stress. The multifactorial nature of RICD poses challenges including different mechanisms of injury (neurogenesis, oxidative stress and neuroinflammation, dendritic structure alterations and vascular effects) and confounding factors like advanced age, and pre-existing conditions. Despite these challenges, several potential solutions exist. Neuroprotective agents like antioxidants can mitigate radiation damage, while cognitive rehabilitation techniques such as cognitive training and memory strategies improve cognitive function. Advanced imaging techniques like magnetic resonance imaging (MRI) help identify vulnerable brain areas, and proton therapy offers precise targeting of cancer cells, sparing healthy tissue. Multidisciplinary care teams are crucial for managing RICD’s cognitive and psychological effects. Personalized medicine, using genetic and molecular data, can identify high-risk patients and tailor treatments accordingly. Emerging therapies, including stem cell therapy and regenerative medicine, offer hope for repairing or replacing damaged brain tissue. Addressing RICD is vital for cancer survivors, necessitating consideration of cognitive function and provision of appropriate support and resources for those experiencing cognitive decline.Keywords: radiation therapy, radiation-induced cognitive decline, RICD, cognitive decline, cognitive function, central nervous system cancer

Sequence variation of Epstein-Barr virus: viral types, geography, codon usage and diseases

138 new Epstein-Barr virus (EBV) genome sequences have been determined. 125 of these and 116 from previous reports were combined to produce a multiple sequence alignment of 241 EBV genomes, which we have used to analyze variation within the viral genome. The type 1/type2 classification of EBV remains the major form of variation and is defined mostly by EBNA2 and EBNA3, but the type 2 SNPs at the EBNA3 locus extend into the adjacent gp350 and gp42 genes, whose products mediate infection of B cells by EBV. A small insertion within the BART miRNA region of the genome was present in 21 EBV strains. EBV from saliva of USA patients with chronic active EBV infection aligned with the wild type EBV genome, with no evidence of WZhet rearrangements. The V3 polymorphism in the Zp promoter for BZLF1 was found to be frequent in nasopharyngeal carcinoma cases both from Hong Kong and Indonesia. Codon usage was found to differ between latent and lytic cycle EBV genes and the main forms of variation of the EBNA1 protein have been identified.IMPORTANCE Epstein-Barr virus causes most cases of infectious mononucleosis and post-transplant lymphoproliferative disease. It contributes to several types of cancer including Hodgkin's lymphoma, Burkitt's lymphoma, diffuse large B cell lymphoma, nasopharyngeal carcinoma and gastric carcinoma. EBV genome variation is important because some of the diseases associated with EBV have very different incidences in different populations and geographic regions - differences in the EBV genome might contribute to these diseases. Some specific EBV genome alterations that appear to be significant in EBV associated cancers are already known and current efforts to make an EBV vaccine and antiviral drugs should also take account of sequence differences in the proteins used as targets

Wegner on Hallucinations, Inconsistency, and the Illusion of Free Will. Some Critical Remarks

Wegner's argument on the illusory nature of conscious will, as developed in The Illusion of Conscious Will (2002) and other publications, has had major impact. Based on empirical data, he develops a theory of apparent mental causation in order to explain the occurrence of the illusion of conscious will. Part of the evidence for his argument is derived from a specific interpretation of the phenomenon of auditory verbal hallucinations as they may occur in schizophrenia. The aim of this paper is to evaluate the validity of the evidence on auditory verbal hallucinations as employed by Wegner. I conclude that auditory hallucinations do not provide solid evidence for Wegner's theory. Moreover, the phenomena in schizophrenia provide, in fact, an argument against part of Wegner's theory of apparent mental causation. © 2010 The Author(s)

Stereotactic body radiotherapy in the treatment of Pancreatic Adenocarcinoma in elderly patients

Background: Treatment of pancreatic adenocarcinoma in the elderly is often complicated by comorbidities that preclude surgery, chemotherapy and/or conventional external beam radiation therapy (EBRT). Stereotactic body radiotherapy (SBRT) has thus garnered interest in this setting.Methods: A retrospective review of 26 patients of age ≥ 80 with pancreatic adenocarcinoma treated with definitive SBRT+/-chemotherapy from 2007-2011 was performed. Twenty-seven percent of patients were stage I, 38% were stage II, 27% were stage III and 8% were stage IV. Patients most commonly received 24 Gy/1 fraction or 30-36 Gy/3 fractions. Kaplan-Meier was used to estimate overall survival (OS), local control (LC), cause specific survival (CSS) and freedom-from-metastatic disease (FFMD).Results: The median age was 86 (range 80-91), and median follow-up was 11.6 months (3.5-24.6). The median planning target volume was 21.48 cm3 (6.1-85.09). Median OS was 7.6 months with 6/12 month OS rates of 65.4%/34.6%, respectively. Median LC was 11.5 months, 6-month and 12-month actuarial LC rates were 60.1% and 41.2%, respectively. There were no independent predictors for LC, but there was a trend for improved LC with prescription dose greater than 20 Gy (p = 0.063). Median CSS was 6.3 months, and 6-month and 12-month actuarial CSS were 53.8% and 23.1%, respectively. Median FFMD was 8.4 months, and 6-month and 12-month actuarial rates were 62.0% and 41.4%, respectively. Nine patients (47%) had local failures, 11 (58%) had distant metastasis, and 7 (37%) had both. There were no acute or late grade 3+ toxicities.Conclusions: Definitive SBRT is feasible, safe and effective in elderly patients who have unresectable disease, have comorbidities precluding surgery or decline surgery. © 2013 Kim et al.; licensee BioMed Central Ltd

Transforaminal interbody debridement and fusion with antibiotic-impregnated bone graft to treat pyogenic discitis and vertebral osteomyelitis: a comparative study in Asian population

Study Design A retrospective cohort study. Purpose To evaluate whether using antibiotic-impregnated bone graft (AIBG) enhances infection control and shortens the postoperative course of pyogenic discitis and vertebral osteomyelitis (PDVO). Overview of Literature Surgical treatment of PDVO is indicated for neurological deficit, instability, unknown pathogen, or poorly controlled infection. The posterior-only approach is effective but requires 4–6 weeks of antibiotic treatment postoperatively. We hypothesized that AIBG used in an all-posterior approach could enhance infection control and shorten the postoperative course of PDVO. Methods Thirty patients with PDVO of the lumbar or thoracic spine treated with transforaminal interbody debridement and fusion (TIDF) with AIBG between March 2014 and May 2022 were reviewed (AIBG group). For comparative analysis, 28 PDVO patients who underwent TIDF without AIBG between January 2009 and June 2011 were enrolled (non-AIBG group). The minimum follow-up duration was 2 years. Clinical characteristics and surgical indications were comparable in the two groups. C-reactive protein (CRP) levels and the postoperative antibiotics course were compared between the two groups. Results Surgical treatment for PDVO resulted in clinical improvement and adequate infection control. Despite the shorter postoperative intravenous antibiotic duration (mean: 19.0 days vs. 39.8 days), the AIBG group had significantly lower CRP levels at postoperative 4 and 6 weeks. The mean Visual Analog Scale pain scores improved from 7.3 preoperatively to 2.2 at 6 weeks postoperatively. The average angle correction at the last follow-up was 7.9°. Conclusions TIDF with AIBG for PDVO can achieve local infection control with a faster reduction in CRP levels, leading to a shorter antibiotic duration

Loss of neuropeptide signalling alters temporal expression of mouse suprachiasmatic neuronal state and excitability

Individual neurons of the hypothalamic suprachiasmatic nuclei (SCN) contain an intracellular molecular clock that drives these neurons to exhibit day-night variation in excitability. The neuropeptide vasoactive intestinal polypeptide (VIP) and its cognate receptor, VPAC2, are synthesized by SCN neurons and this intercellular VIP-VPAC2 receptor signal facilitates coordination of SCN neuronal activity and timekeeping. How the loss of VPAC2 receptor signalling affects the electrophysiological properties and states of SCN neurons as well as their responses to excitatory inputs is unclear. Here we used patch-clamp electrophysiology and made recordings of SCN neurons in brain slices prepared from transgenic animals that do not express VPAC2 receptors (Vipr2−/− mice) as well as animals that do (Vipr2+/+ mice). We report that while Vipr2+/+ neurons exhibit coordinated day-night variation in their electrical state, Vipr2−/− neurons lack this and instead manifest a range of states during both day and night. Further, at the population level, Vipr2+/+ neurons vary the membrane threshold potential at which they start to fire action potentials from day to night, while Vipr2−/− neurons do not. We provide evidence that Vipr2−/− neurons lack a component of voltage-gated sodium currents that contribute to SCN neuronal excitability. Moreover, we determine that this aberrant temporal control of neuronal state and excitability alters neuronal responses to a neurochemical mimic of the light-input pathway to the SCN. These results highlight the critical role VIP-VPAC2 receptor signalling plays in the temporal expression of individual neuronal states as well as appropriate ensemble activity and input gating of the SCN neural network

CMS physics technical design report : Addendum on high density QCD with heavy ions

Peer reviewe

Pathologic response with neoadjuvant chemotherapy and stereotactic body radiotherapy for borderline resectable and locally-advanced pancreatic cancer

Background: Neoadjuvant stereotactic body radiotherapy (SBRT) has potential applicability in the management of borderline resectable and locally-advanced pancreatic adenocarcinoma. In this series, we report the pathologic outcomes in the subset of patients who underwent surgery after neoadjuvant SBRT. Methods: Patients with borderline resectable or locally-advanced pancreatic adenocarcinoma who were treated with SBRT followed by resection were included. Chemotherapy was to the discretion of the medical oncologist and preceded SBRT for most patients. Results: Twelve patients met inclusion criteria. Most (92%) received neoadjuvant chemotherapy, and gemcitabine/capecitabine was most frequently utilized (n = 7). Most were treated with fractionated SBRT to 36 Gy/3 fractions (n = 7) and the remainder with single fraction to 24 Gy (n = 5). No grade 3+ acute toxicities attributable to SBRT were found. Two patients developed post-surgical vascular complications and one died secondary to this. The mean time to surgery after SBRT was 3.3 months. An R0 resection was performed in 92% of patients (n = 11/12). In 25% (n = 3/12) of patients, a complete pathologic response was achieved, and an additional 16.7% (n = 2/12) demonstrated <10% viable tumor cells. Kaplan-Meier estimated median progression free survival is 27.4 months. Overall survival is 92%, 64% and 51% at 1-, 2-, and 3-years. Conclusions: This study reports the pathologic response in patients treated with neoadjuvant chemotherapy and SBRT for borderline resectable and locally-advanced pancreatic cancer. In our experience, 92% achieved an R0 resection and 41.7% of patients demonstrated either complete or extensive pathologic response to treatment. The results of a phase II study of this novel approach will be forthcoming. © 2013 Rajagopalan et al.; licensee BioMed Central Ltd

Timed daily exercise remodels circadian rhythms in mice

Regular exercise is important for physical and mental health. An underexplored and intriguing property of exercise is its actions on the body’s 24 h or circadian rhythms. Molecular clock cells in the brain’s suprachiasmatic nuclei (SCN) use electrical and chemical signals to orchestrate their activity and convey time of day information to the rest of the brain and body. To date, the long-lasting effects of regular physical exercise on SCN clock cell coordination and communication remain unresolved. Utilizing mouse models in which SCN intercellular neuropeptide signaling is impaired as well as those with intact SCN neurochemical signaling, we examined how daily scheduled voluntary exercise (SVE) influenced behavioral rhythms and SCN molecular and neuronal activities. We show that in mice with disrupted neuropeptide signaling, SVE promotes SCN clock cell synchrony and robust 24 h rhythms in behavior. Interestingly, in both intact and neuropeptide signaling deficient animals, SVE reduces SCN neural activity and alters GABAergic signaling. These findings illustrate the potential utility of regular exercise as a long-lasting and effective non-invasive intervention in the elderly or mentally ill where circadian rhythms can be blunted and poorly aligned to the external world