Dark matter physics, flavor physics and LHC constraints in the dark matter model with a bottom partner

In the scenario that a dark matter (DM) is a weakly interacting massive particle, there are many possibilities of the interactions with the Standard Model (SM) particles to achieve the relic density of DM. In this paper, we consider one simple DM model where the DM candidate is a complex scalar and interacts with the SM particles via exchange of the Higgs particle and an extra quark, named bottom partner. The extra quark carries the same quantum number as the right-handed down-type quarks and has Yukawa couplings with the DM candidate and the right-handed down-type quarks. The Yukawa interactions are not only relevant to the thermal relic density of the DM, but also contribute to the flavor physics, such as the $\Delta F=2$ processes. In addition, the flavor alignment of the Yukawa couplings is related to the decay modes of the extra quark. Then, we can find the explicit correlations among the physical observables in DM physics, flavor physics and the signals at the LHC. Based on the numerical analyses of the thermal relic density, the direct detection of the DM and the current LHC bounds using the latest results, we survey our predictions for the $\Delta F=2$ processes. We investigate the perturbative bound on the Yukawa coupling, as well. Study of a fermionic DM model with extra scalar quarks is also given for comparison.Comment: 18 pages, 8 figures, 2 tables; some typos corrected, version published in JHE

Cisplatin, rather than oxaliplatin, increases paracellular permeability of LLC-PK1 cells via activating protein kinase C

The clinical use of cisplatin is limited by its adverse events, particularly serious nephrotoxicity. It was clarified that cisplatin is transported by a kidney-specific organic cation transporter (OCT2). OCT2 also mediates the uptake of oxaliplatin into renal proximal tubular cells; however, this agent does not lead nephrotoxicity. In the present study, we carried out comparative experiments with cisplatin and oxaliplatin using porcine kidney LLC-PK1 cell monolayers. In the fluorescein-labeled isothiocyanate-dextran flux assay, the basolateral application of cisplatin, but not oxaliplatin, resulted in an increase in the paracellular permeability of cell monolayers. Even though the cellular accumulation of platinum at 50 μM oxaliplatin could reach the same level at 30 μM cisplatin, oxaliplatin did not induce hyper-permeability in cell monolayers. Cisplatin, but not oxaliplatin, significantly activated PKC. In addition, the combination of PKC inhibitors recovered the increase in paracellular permeability. In conclusion, pharmacodynamic mechanisms via PKC could explain the difference in nephrotoxicity between cisplatin and oxaliplatin

Effect of riboflavin deficiency on development of the cerebral cortex in Slc52a3 knockout mice

Riboflavin transporter 3 (RFVT3), encoded by the SLC52A3 gene, is important for riboflavin homeostasis in the small intestine, kidney, and placenta. Our previous study demonstrated that Slc52a3 knockout (Slc52a3−/−) mice exhibited neonatal lethality and metabolic disorder due to riboflavin deficiency. Here, we investigated the influence of Slc52a3 gene disruption on brain development using Slc52a3−/− embryos. Slc52a3−/− mice at postnatal day 0 showed hypoplasia of the brain and reduced thickness of cortical layers. At embryonic day 13.5, the formation of Tuj1+ neurons and Tbr2+ intermediate neural progenitors was significantly decreased; no significant difference was observed in the total number and proliferative rate of Pax6+ radial glia. Importantly, the hypoplastic phenotype was rescued upon riboflavin supplementation. Thus, it can be concluded that RFVT3 contributes to riboflavin homeostasis in embryos and that riboflavin itself is required during embryonic development of the cerebral cortex in mice

Arachidonic acid containing phosphatidylcholine increases due to microglial activation in ipsilateral spinal dorsal horn following spared sciatic nerve injury

Peripheral nerve injury induces substantial molecular changes in the somatosensory system that leads to maladaptive plasticity and cause neuropathic pain. Understanding the molecular pathways responsible for the development of neuropathic pain is essential to the development of novel rationally designed therapeutics. Although lipids make up to half of the dry weight of the spinal cord, their relation with the development of neuropathic pain is poorly understood. We aimed to elucidate the regulation of spinal lipids in response to neuropathic peripheral nerve injury in mice by utilizing matrix-assisted laser desorption/ionization imaging mass spectrometry, which allows visualization of lipid distribution within the cord. We found that arachidonic acid (AA) containing [PC(diacyl-16:0/20:4)+K]+ was increased temporarily at superficial ipsilateral dorsal horn seven days after spared nerve injury (SNI). The spatiotemporal changes in lipid concentration resembled microglia activation as defined by ionized calcium binding adaptor molecule 1 (Iba1) immunohistochemistry. Suppression of microglial function through minocycline administration resulted in attenuation of hypersensitivity and reduces [PC(diacyl-16:0/20:4)+K]+ elevation in the spinal dorsal horn. These data suggested that AA containing [PC(diacyl-16:0/20:4)+K]+ is related to hypersensitivity evoked by SNI and implicate microglial cell activation in this lipid production

Taxanes and platinum derivatives impair Schwann cells via distinct mechanisms

Impairment of peripheral neurons by anti-cancer agents, including taxanes and platinum derivatives, has been considered to be a major cause of chemotherapy-induced peripheral neuropathy (CIPN), however, the precise underlying mechanisms are not fully understood. Here, we examined the direct effects of anti-cancer agents on Schwann cells. Exposure of primary cultured rat Schwann cells to paclitaxel (0.01 μM), cisplatin (1 μM), or oxaliplatin (3 μM) for 48 h induced cytotoxicity and reduced myelin basic protein expression at concentrations lower than those required to induce neurotoxicity in cultured rat dorsal root ganglion (DRG) neurons. Similarly, these anti-cancer drugs disrupted myelin formation in Schwann cell/DRG neuron co-cultures without affecting nerve axons. Cisplatin and oxaliplatin, but not paclitaxel, caused mitochondrial dysfunction in cultured Schwann cells. By contrast, paclitaxel led to dedifferentiation of Schwann cells into an immature state, characterized by increased expression of p75 and galectin-3. Consistent with in vitro findings, repeated injection of paclitaxel increased expression of p75 and galectin-3 in Schwann cells within the mouse sciatic nerve. These results suggest that taxanes and platinum derivatives impair Schwan cells by inducing dedifferentiation and mitochondrial dysfunction, respectively, which may be important in the development of CIPN in conjunction with their direct impairment in peripheral neurons

重傷外傷の認識が遅れ救急外来で緊急開腹術を行った１例

An８１-year-old man fell down and bruised his left abdomen. After a while the back pain got worse, and he admitted to the Emergency Department. At hospitals admission, several signs of shock were observed, and contrast-enhanced CT revealed a splenic injury. However, it took an hour and a half to diagnose and convene the trauma team because of the lack of information shared among medical staffs and the delay of the recognition as a severe traumatic injury. Since there was no available operation room at the time, nor there wasn’t time to transfer to another hospital, he was forced to undergo emergency open splenectomy at the Emergency Department. That decision saved his life as a result. In ２００２, it revealed that the deaths of about ４０％ of expired trauma patients who arrived at emergency centers were probably preventable. Since then, much progress has been made in establishing and generalizing the trauma care and evaluation guidelines. Our hospital is also making progress in organizing a trauma team and the massive transfusion protocol. However, even if they are well maintained, we won’t be able to decrease the number of preventable trauma deaths（PTD）unless we diagnose it. Improving clinical management as well as making efforts on teamwork, leads to a rapid definitive care in trauma patients

A different pathway in the endoplasmic reticulum stress-induced expression of human HRD1 and SEL1 genes

Human HRD1 and SEL1 are components of endoplasmic reticulum-associated degradation (ERAD), which is a retrograde transport mechanism from the ER to the cytosol for removing unfolded proteins. The expression of HRD1 and SEL1 was induced by ER stress-inducing agents and overexpression of both ER stress-responsive transcription factors, ATF6 and XBP1. Inhibition of IRE1 and ATF6 revealed that ER stress-induced HRD1 and SEL1 expressions are mediated by IRE1-XBP1- and ATF6-dependent pathways, respectively. These results suggest that the ER stress-induced ERAD gene expressions are mediated by different pathways, which are attributed to the differences in the promoter regions

Identification and characterization of plant Haspin kinase as a histone H3 threonine kinase

Kurihara, D., Matsunaga, S., Omura, T. et al. Identification and characterization of plant Haspin kinase as a histone H3 threonine kinase. BMC Plant Biol 11, 73 (2011). https://doi.org/10.1186/1471-2229-11-73