Loss of the DNA-binding domain of the farnesoid X receptor gene causes severe liver and kidney injuries.

Farnesoid X receptor (FXR) regulates bile acid synthesis, lipid metabolism, and glucose homeostasis in metabolic organs. FXR-knockout (FXR-KO) mice lacking the last exon of the FXR gene develop normally and display no prenatal and early postnatal lethality, whereas human patients with mutations in the DNA-binding domain of the FXR gene develop severe hepatic dysfunction. In this study, we generated novel FXR-KO mice lacking the DNA-binding domain of the FXR gene using CRISPR-Cas9 technology and evaluated their phenotypes. Similar to the aforementioned FXR-KO mice, our novel mice showed elevated serum levels of total bile acids and total cholesterol. However, they were obviously short-lived, showing severe liver and renal pathologies at an early age. These results indicate that FXR, including its unknown isoforms, has more significant functions in multiple organs than previously reported. Thus, the novel FXR-KO mice could lead to a new aspect that requires reworking of previous knowledge of FXR in the liver and renal function.

Histological evidence for the cardiac safety of high-dose pegylated liposomal doxorubicin in a patient with HIV-associated Kaposi sarcoma: a case report and literature review.

BACKGROUND: Pegylated liposomal doxorubicin plays an important role in the treatment of patients with severe refractory human immunodeficiency virus (HIV)-associated Kaposi sarcoma (KS). High cumulative doses of conventional doxorubicin exceeding 500 mg/m2 are known to cause cardiac toxicity. However, the safe cumulative dose of pegylated liposomal doxorubicin is unclear. CASE PRESENTATION: A 40-year-old Japanese man with HIV infection presented with pain, edema, and multiple skin nodules on both legs which worsened over several months. He was diagnosed with HIV-associated KS. He received long-term pegylated liposomal doxorubicin combined with antiretroviral therapy for advanced, progressive KS. The cumulative dose of pegylated liposomal doxorubicin reached 980 mg/m2. The patient's left ventricular ejection fraction remained unchanged from baseline during treatment. After he died as a result of cachexia and wasting, caused by recurrent sepsis and advanced KS, an autopsy specimen of his heart revealed little or no evidence of histological cardiac damage. We also conducted a literature review focusing on histological changes of the myocardium in patients treated with a cumulative dose of pegylated liposomal doxorubicin exceeding 500 mg/m2. CONCLUSIONS: This case report and literature review suggest that high (> 500 mg/m2) cumulative doses of pegylated liposomal doxorubicin may be used without significant histological/clinical cardiac toxicity in patients with HIV-associated KS.

Campylobacter fetus meningitis associated with eating habits of raw meat and raw liver in a healthy patient: A case report and literature review.

Meningitis caused by the zoonotic pathogen Campylobacter fetus in immunocompetent adults is rare. We report a 48-year-old Japanese woman with no underlying disease who was found to have meningitis caused by C. fetus. Both C. fetus subsp. fetus and C. fetus subsp. venerealis were isolated from the cerebrospinal fluid culture. The mode of infection in our patient was considered to be associated with the consumption of raw beef and raw cattle liver on a regular basis. Public awareness and education to avoid the consumption of raw or undercooked meat might help prevent C. fetus meningitis.

Selective bond breaking of CO2 in phase-locked two-color intense laser fields: laser field intensity dependence.

Selective bond breaking of CO2 in phase-locked ω-2ω two-color intense laser fields (λ = 800 nm and 400 nm, total field intensity I ∼ 1014 W cm-2) has been investigated by coincidence momentum imaging. The CO+ and O+ fragment ions produced by two-body Coulomb explosion, CO22+ → CO+ + O+, exhibit asymmetric distributions along the laser polarization direction, showing that one of the two equivalent C-O bonds is selectively broken by the laser fields. At a field intensity higher than 2 × 1014 W cm-2, the largest fragment asymmetry is observed when the relative phase ϕ between the ω and 2ω laser fields is ∼0 and π. On the other hand, an increase of the asymmetry and a shift of the phase providing the largest asymmetry are observed at lower field intensities. The selective bond breaking and its dependence on the laser field intensity are discussed in terms of a mechanism involving deformation of the potential energy surfaces and electron recollision in intense laser fields.

Dissection of barley chromosomes 1H and 6H by the gametocidal system.

We dissected barley chromosomes 1H and 6H added to common wheat by the gametocidal system and identified structural changes of the chromosomes by fluorescence in situ hybridization and genomic in situ hybridization. We found five aberrations of chromosome 1H, all of which lacked the long arm: one small fragment with the subtelomeric HvT01 sequence, one terminal deletion, and three telocentric chromosomes of the short arm. We established 33 dissection lines carrying single aberrant 6H chromosomes, of which 15 were deletions, 16 were translocations and two were isochromosomes. We conducted PCR analysis of the aberrant barley chromosomes using 75 and 81 EST markers specific to chromosomes 1H and 6H, respectively. This enabled us to construct a cytological map of chromosome 6H and to compare it to the previously reported genetic map and also to the physical map, which were released by the International Barley Genome Sequencing Consortium. The marker orders on the three maps were largely in agreement. The cytological map had better resolution in the proximal region of chromosome 6H than the corresponding genetic map. We discuss some of the discrepancies in marker order between the three maps that might be due to intraspecific polymorphism and gene duplication, as well as to technical problems inherent in the physical mapping process.