5′-Adenosine Monophosphate-Induced Hypothermia Attenuates Brain Ischemia/Reperfusion Injury in a Rat Model by Inhibiting the Inflammatory Response

Hypothermia treatment is a promising therapeutic strategy for brain injury. We previously demonstrated that 5′-adenosine monophosphate (5′-AMP), a ribonucleic acid nucleotide, produces reversible deep hypothermia in rats when the ambient temperature is appropriately controlled. Thus, we hypothesized that 5′-AMP-induced hypothermia (AIH) may attenuate brain ischemia/reperfusion injury. Transient cerebral ischemia was induced by using the middle cerebral artery occlusion (MCAO) model in rats. Rats that underwent AIH treatment exhibited a significant reduction in neutrophil elastase infiltration into neuronal cells and matrix metalloproteinase 9 (MMP-9), interleukin-1 receptor (IL-1R), tumor necrosis factor receptor (TNFR), and Toll-like receptor (TLR) protein expression in the infarcted area compared to euthermic controls. AIH treatment also decreased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling- (TUNEL-) positive neuronal cells. The overall infarct volume was significantly smaller in AIH-treated rats, and neurological function was improved. By contrast, rats with ischemic brain injury that were administered 5′-AMP without inducing hypothermia had ischemia/reperfusion injuries similar to those in euthermic controls. Thus, the neuroprotective effects of AIH were primarily related to hypothermia

P-P' Strings in M(atrix) Theory

We study the off-diagonal blocks in the M(atrix) model that are supposed to correspond to open strings stretched between a Dp-brane and a Dp'-brane. It is shown that the spectrum, including the quantum numbers, of the zero modes in the off-diagonal blocks can be determined from the index theorem and unbroken supersymmetry, and indeed reproduces string theory predictions for p-p' strings. Previously the matrix description of a longitudinal fivebrane needed to introduce extra degrees of freedom corresponding to 0-4 strings by hand. We show that they are naturally associated with the off-diagonal zero modes, and the supersymmetry transformation laws and low energy effective action postulated for them are now derivable from the M(atrix) theory.Comment: minor modification, references added. 21 pages, Latex, minor modification mad

Targeting Lactobacillus johnsonii to reverse chronic kidney disease.

Accumulated evidence suggested that gut microbial dysbiosis interplayed with progressive chronic kidney disease (CKD). However, no available therapy is effective in suppressing progressive CKD. Here, using microbiomics in 480 participants including healthy controls and patients with stage 1-5 CKD, we identified an elongation taxonomic chain Bacilli-Lactobacillales-Lactobacillaceae-Lactobacillus-Lactobacillus johnsonii correlated with patients with CKD progression, whose abundance strongly correlated with clinical kidney markers. L. johnsonii abundance reduced with progressive CKD in rats with adenine-induced CKD. L. johnsonii supplementation ameliorated kidney lesion. Serum indole-3-aldehyde (IAld), whose level strongly negatively correlated with creatinine level in CKD rats, decreased in serum of rats induced using unilateral ureteral obstruction (UUO) and 5/6 nephrectomy (NX) as well as late CKD patients. Treatment with IAld dampened kidney lesion through suppressing aryl hydrocarbon receptor (AHR) signal in rats with CKD or UUO, and in cultured 1-hydroxypyrene-induced HK-2 cells. Renoprotective effect of IAld was partially diminished in AHR deficiency mice and HK-2 cells. Our further data showed that treatment with L. johnsonii attenuated kidney lesion by suppressing AHR signal via increasing serum IAld level. Taken together, targeting L. johnsonii might reverse patients with CKD. This study provides a deeper understanding of how microbial-produced tryptophan metabolism affects host disease and discovers potential pathways for prophylactic and therapeutic treatments for CKD patients

Radiality of definable sets

In this article we use techniques developed by Hrushovski-Loeser to study certain metric properties of the Berkovich analytification of a finite morphism of smooth connected projective curves. In recent work, M. Temkin proved a radiality statement for the topological ramification locus associated to such finite morphisms. We generalize this result in two directions. We prove a radiality statement for a more general class of sets which we call definable sets. In another direction, we show that the result of Temkin can be obtained in families

A simulation study on the measurement of D0-D0bar mixing parameter y at BES-III

We established a method on measuring the \dzdzb mixing parameter $y$ for BESIII experiment at the BEPCII $e^+e^-$ collider. In this method, the doubly tagged $\psi(3770) \to D^0 \overline{D^0}$ events, with one $D$ decays to CP-eigenstates and the other $D$ decays semileptonically, are used to reconstruct the signals. Since this analysis requires good $e/\pi$ separation, a likelihood approach, which combines the $dE/dx$, time of flight and the electromagnetic shower detectors information, is used for particle identification. We estimate the sensitivity of the measurement of $y$ to be 0.007 based on a $20fb^{-1}$ fully simulated MC sample.Comment: 6 pages, 7 figure

The Immune Factors Involved in the Pathogenesis, Diagnosis, and Treatment of Sjogren's Syndrome

Sjogren's syndrome (SS) is a systemic, autoimmune disorder characterized by salivary insufficiency and lymphocytic infiltration of the exocrine glands. Even though the mechanism of its pathology and progression has been researched ever since its discovery, the roles of different parts of immune system remain inconclusive. There is no straightforward and simple theory for the pathogenesis and diagnosis of Sjogren’s syndrome because of the multiple kinds and functions of autoantibodies, changing proportion of different T-lymphocyte subsets with the progression of disease, unsuspected abilities of B lymphocytes discovered recently, crosstalk between cytokines connecting the factors mentioned previously, and genetic predisposition that contributes to the initiation of this disease. On the other hand, the number of significant reports and open-label studies of B-cell depletion therapy showing clinical efficacy in sjogren’s syndrome has continued to accumulate, which provides a promising future for the patients. In a word, further elucidation of the role of different components of the immune system will open avenues for better diagnosis and treatment of SS, whose current management is still mainly supportive

Aneuploidy underlies brefeldin A-induced antifungal drug resistance in Cryptococcus neoformans

Cryptococcus neoformans is at the top of the list of “most wanted” human pathogens. Only three classes of antifungal drugs are available for the treatment of cryptococcosis. Studies on antifungal resistance mechanisms are limited to the investigation of how a particular antifungal drug induces resistance to a particular drug, and the impact of stresses other than antifungals on the development of antifungal resistance and even cross-resistance is largely unexplored. The endoplasmic reticulum (ER) is a ubiquitous subcellular organelle of eukaryotic cells. Brefeldin A (BFA) is a widely used chemical inducer of ER stress. Here, we found that both weak and strong selection by BFA caused aneuploidy formation in C. neoformans, mainly disomy of chromosome 1, chromosome 3, and chromosome 7. Disomy of chromosome 1 conferred cross-resistance to two classes of antifungal drugs: fluconazole and 5-flucytosine, as well as hypersensitivity to amphotericin B. However, drug resistance was unstable, due to the intrinsic instability of aneuploidy. We found overexpression of AFR1 on Chr1 and GEA2 on Chr3 phenocopied BFA resistance conferred by chromosome disomy. Overexpression of AFR1 also caused resistance to fluconazole and hypersensitivity to amphotericin B. Furthermore, a strain with a deletion of AFR1 failed to form chromosome 1 disomy upon BFA treatment. Transcriptome analysis indicated that chromosome 1 disomy simultaneously upregulated AFR1, ERG11, and other efflux and ERG genes. Thus, we posit that BFA has the potential to drive the rapid development of drug resistance and even cross-resistance in C. neoformans, with genome plasticity as the accomplice

Efficacy of calcein as a chemical marker of Potamocorbula laevis

IntroductionCalcein was used to develop a shell marking method for Potamocorbula laevis.MethodsThe suitable conditions for marking were investigated, including marking concentration, immersion time, and water temperature. The impacts and feasibility of the marking method were assessed based on the survival rate of P. laevis, the success rate of fluorescence marking, marking quality, and alterations in activities of antioxidant enzymes in the digestive gland of the experimental bivalves. Two concentrations of calcein (20 and 50 mg/L) were used and the immersion time included 1 and 2 h, respectively. The experiment was performed in two rounds, with water temperatures of 12.84 ± 0.09 and 24.18 ± 0.04 °C, respectively.Results and discussionThe results indicated that calcein did not significantly impact the survival of P. laevis after 7 d of recovery. The catalase activity and malondialdehyde content in low temperature-marked P. laevis showed significant decreases, and the relative abundances of certain fatty acids also exhibited significant changes within 2 h post exposure to 20 mg/L of calcein. However, these indicators returned to normal levels within 7 d. The marking impact of calcein was proportional to the calcein concentration and immersion time. Higher temperature generated a negative impact on the marking effect of 20 mg/L of calcein, while no obvious impacts were observed for 50 mg/L of calcein. The marking success rates and the recapture rates of P. laevis for in situ tests in the two experimental groups were both 100% and 4.44 ± 1.29% after one month. Also, the recapture marking rates and the marking good rates of the recaptured individuals were both 100%. There were no significant differences between these parameters for 50 and 75 mg/L of calcein. Given the cost and safety of labeling, a strategy in terms of an immersion in 50 mg/L of calcein for 2 h could be considered as an effective in situ labeling scheme for P. laevis. In conclusion, calcein can be employed as a marking method for P. laevis. These findings could be potentially beneficial for development of in situ labeling technology, proliferation as well as release of shellfish in tidal flats and resource conservation

UBR4 deficiency causes male sterility and testis abnormal in Drosophila

IntroductionIt has been established that UBR4 encodes E3 ubiquitin ligase, which determines the specificity of substrate binding during protein ubiquitination and has been associated with various functions of the nervous system but not the reproductive system. Herein, we explored the role of UBR4 on fertility with a Drosophila model.MethodsDifferent Ubr4 knockdown flies were established using the UAS/GAL4 activating sequence system. Fertility, hatchability, and testis morphology were studied, and bioinformatics analyses were conducted. Our results indicated that UBR4 deficiency could induce male sterility and influent egg hatchability in Drosophila.ResultsWe found that Ubr4 deficiency affected the testis during morphological analysis. Proteomics analysis indicated 188 upregulated proteins and 175 downregulated proteins in the testis of Ubr4 knockdown flies. Gene Ontology analysis revealed significant upregulation of CG11598 and Sfp65A, and downregulation of Pelota in Ubr4 knockdown flies. These proteins were involved in the biometabolic or reproductive process in Drosophila. These regulated proteins are important in testis generation and sperm storage promotion. Bioinformatics analysis verified that UBR4 was low expressed in cryptorchidism patients, which further supported the important role of UBR4 in male fertility.DiscussionOverall, our findings suggest that UBR4 deficiency could promote male infertility and may be involved in the protein modification of UBR4 by upregulating Sfp65A and CG11598, whereas downregulating Pelota protein expression