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A/J and C57BL/6 J (B6) mice share a mutation in Cdh23 (ahl allele) and are characterized by age-related hearing loss. However, hearing loss occurs much earlier in A/J mice at about four weeks of age. Recent study has revealed that a mutation in citrate synthase (Cs) is one of the main contributors, but the mechanism is largely unknown. In the present study, we showed that A/J mice displayed more severe degeneration of hair cells, spiral ganglion neurons, and stria vascularis in the cochleae compared with B6 mice. Moreover, messenger RNA accumulation levels of caspase-3 and caspase-9 in the inner ears of A/J mice were significantly higher than those in B6 mice at 2 and 8 weeks of age. Immunohistochemistry localized caspase-3 expression mainly to the hair cells, spiral ganglion neurons, and stria vascularis in cochleae. In vitro transfection with Cs short hairpin RNA (shRNA) alone or cotransfection with Cs shRNA and Cdh23 shRNA significantly increased the levels of caspase-3 in an inner ear cell line (HEI-OC1). Finally, a pan-caspase inhibitor Z-VAD-FMK could preserve the hearing of A/J mice by lowering about 15 decibels of the sound pressure level for the auditory-evoked brainstem response thresholds. In conclusion, our results suggest that caspase-mediated apoptosis in the cochleae, which may be related to a Cs mutation, contributes to the early onset of hearing loss in A/J mice.

Monosialoganglioside (GM1) has been considered to have a neurotrophic factor-like activity. Nerve growth factor (NGF), a member of the neurotrophin family, is essential for neuronal survival, differentiation and maturation. The aim of the present study was to investigate whether co-administration of GM1 and NGF reverses glutamate (Glu) neurotoxicity in primary cultured rat embryonic dorsal root ganglion (DRG) neurons. DRG neurons were exposed to Glu (2 mmol/1), Glu (2 mmol/1) plus GM1 (10 microg/ml), Glu (2 mmol/l) plus NGF (10 ng/ml), Glu (2 mmol/l) plus GM1 (5 microg/ml) and NGF (5 ng/ml) and then processed for detecting intracellular concentrations of Ca2+ ([Ca2+] i) by confocal laser scanning microscopy and growth-associated protein 43 (GAP43) mRNA by RT-PCR. The fluorescent intensity in Glu plus GM1 and NGF incubated neurons was the lowest as compared with that in other groups. The expression of GAP43 mRNA in Glu plus GM1 and NGF incubated neurons was the highest as compared with that in other groups. These results implicated that GM1 and NGF have synergistic neuroprotective effects on DRG neurons with excitotoxicity induced by Glu in vitro.

Recently Belle collaboration reported new measurements for the branching fractions with the first observing two processes of $$ \mathcal{B}\left({\Xi}_c^0\to \Lambda {K}_S^0\right) $$ B Ξ c 0 → Λ K S 0 , $$ \mathcal{B}\left({\Xi}_c^0\to {\Sigma}^0{K}_S^0\right) $$ B Ξ c 0 → Σ 0 K S 0 and updating data for $$ \mathcal{B}\left({\Xi}_c^0\to {\Sigma}^{+}{K}^{-}\right) $$ B Ξ c 0 → Σ + K − . Combined with other known data on charmless two body decays of anti-triplet charmed baryons, a lot of information can be derived with the assistance of SU(3) flavour symmetry. Using SU(3) relations between different decay modes, we can give some predictions based on the new measurements which can be tested with the high luminosity experiments in the future. More interestingly, we find that a global fit is now possible with the addition of new Belle data. In general, there are 18 complex SU(3) invariant amplitudes. We find that a scenario of all amplitudes being real can fit the data well with a χ2/d.o.f. only 0.773. This indicates that neglecting the phases of the amplitudes is a reasonable assumption. When more data become available, one may be able to get more information for phases in the amplitudes. We give several comments on the feature of global fit regarding the branching fractions, relations between different decays, and decays involving K0 and $$ \overline{K} $$ K ¯ 0. Many of the unknown branching fractions and polarization asymmetry parameters of anti-triplet charmed baryon for charmless two body decays are predicted to be accessible by experiments at Belle, Belle II, BES-III, and LHCb. The validity of SU(3) for charmless two body hadronic decays can be more accurately tested.

The aim of this study is to explore the relationship of intrapulmonary activation of nuclear factor-kappaB (NF-kappaB) and the expression of inducible nitric oxide synthase (iNOS) mRNA with pulmonary injury in rats with severe acute pancreatitis (SAP). Fifty-four Sprague Dawley rats were randomly divided into three groups: sham operation (control) group (n = 18), SAP group (n = 18), and pyrrolindine dithiocarbamate (PDTC) pretreated group (n = 18). A SAP model was induced by retrograde injected 5% sodium taurocholate into the bile-pancreatic duct (1 ml/kg). PDTC-pretreated SAP rats were given 100 mg/kg body weight PDTC intraperitoneally before pancreatitis was induced. Six rats from each group were sacrificed at 3, 6, and 12 h after modeling. Activation of NF-kappaB in pulmonary tissues and pancreas tissues was detected by immunohistochemical methods. Intrapulmonary expression of iNOSmRNA was assayed by fluorogenic quantitative reverse transcription polymerize chain reaction. The expression of NF-kappaB in the SAP group in pulmonary tissues was enhanced significantly at any measure point compared with control group (58.4 +/- 10.8 vs. 3.8 +/- 1.8, 119.8 +/- 17.8 vs. 5.2 +/- 2.4, and 90.2 +/- 14.4 vs. 4.7 +/- 2.2, P < 0.01). But the expressions of NF-kappaB in the PDTC group were significantly lower than those in SAP group (54.3 +/- 9.6 vs. 58.4 +/- 10.8, 93.9 +/- 7.9 vs. 119.8 +/- 17.8, and 82.2 +/- 13.3 vs. 90.2 +/- 14.4, P < 0.05). The number of positive cells in SAP group and PDTC group reached its peak at 6 h and then declined. The expression of iNOSmRNA in PDTC groups was significantly weaker than that in SAP group (2.0 +/- 0.8 vs. 2.2 +/- 1.9, 2.4 +/- 1.2 vs. 4.6 +/- 1.8, and 1.5 +/- 0.8 vs. 3.2 +/- 1.5, P < 0.05). The activation of NF-kappaB may be involved in the SAP lung injury through regulating the expression of iNOSmRNA. PDTC might inhibit the activation of NF-kappaB and then reduce the expression of iNOSmRNA and effectively alleviate the severity of lung injury.

Heavy charged gauge bosons are proposed in some theories beyond the standard model.We explore the discovery potential for W ′ → tb with top quark semi-leptonic decay at the LHC. We concentrate on the new physics signal search with the deviation from the standard model prediction if the resonance peak of W ′ cannot be observed directly. Signal events with two jets plus one charged lepton and missing energy are simulated, together with the dominant standard model backgrounds. In this paper, it is found that suitable cuts on the kinematic observables can effectively suppress the standard model backgrounds, so that it is possible to search for a W ′ signal at the LHC if its mass is less than 6.6 TeV.

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