Selective excretion of anti-inflammatory cytokine Interleukin-10 in a superantigen-inducing neonatal infectious disease

Neonatal toxic shock syndrome (TSS)-like exanthematous disease (NTED) is an emerging neonatal infectious disease caused by TSS toxin-1 (TSST-1). Although NTED and TSS are caused by the same superantigenic exotoxin, NTED is less severe than TSS. The mechanism of this reduced severity in NTED has not been elucidated. Thirteen patients with NTED were enrolled in the study. We investigated serum cytokine profile using a cytometric bead array system with a cytokine panel. Expression of Vβ2 and CD45RO in CD4⁺ T cells was investigated in mononuclear cells by using flowcytometry. Ten patients with other bacterial infections and eight patients without any infections were also enrolled as control groups. The mean serum level of IL-10 was 1209.9 pg/mL in patients with NTED at the time of admission into the study. The other inhibitory cytokine, IL-4, exhibited a minimum level. The high level of IL-10 rapidly decreased within 3–9 days of the onset of NTED. The cytokine profile of NTED, with its high IL-10 level, was clearly different from that of the other bacterial infections. The increased level of IL-10 seems to be related to the reduced severity of NTED. Th2 shift is not thought to be the cause of this IL-10 excretion.     

Is Urinary Lipoarabinomannan the Result of Renal Tuberculosis? Assessment of the Renal Histology in an Autopsy Cohort of Ugandan HIV-Infected Adults

Objective

The detection of urinary lipoarabinomannan (LAM), a mycobacterial cell wall component, is used to diagnose tuberculosis (TB). How LAM enters the urine is not known. To investigate if urinary LAM-positivity is the result of renal TB infection we correlated the outcomes of urinary LAM-antigen testing to renal histology in an autopsy cohort of hospitalized, Ugandan, HIV-infected adults.

Methods

We performed a complete autopsy, including renal sampling, in HIV-infected adults that died during hospitalization after written informed consent was obtained from the next of kin. Urine was collected postmortem through post-mortem catheterisation or by bladder puncture and tested for LAM with both a lateral flow assay (LFA) and an ELISA assay. Two pathologists assessed the kidney histology. We correlated the LAM-assay results and the histology findings.

Results

Of the 13/36 (36%) patients with a positive urinary LAM ELISA and/or LFA, 8/13 (62%) had renal TB. The remaining 5 LAM-positive patients had disseminated TB without renal involvement. Of the 23 LAM-negative patients, 3 had disseminated TB without renal involvement. The remaining LAM-negative patients had no TB infection and died mostly of fungal and bacterial infections. LAM LFA had a sensitivity of 81% and specificity of 100% to diagnose TB at any location, and the LAM ELISA a sensitivity of 63% and a specificity of 100%. 54% (7/13) LAM LFA-positive patients were not on anti-TB treatment at the time of death.

Conclusion

Renal TB infection explained LAM-positivity in the majority of patients. Patients with disseminated TB without renal involvement can also be diagnosed with LAM. This suggests that other mechanisms that lead to urinary LAM-positivity exist in a minority of patients.     

CRUMPLED LEAF (CRL) homologs of Physcomitrella patens are involved in the complete separation of dividing plastids

Plastid division is controlled by numerous nuclear genes. Arabidopsis thaliana CRUMPLED LEAF (AtCRL) is a plastid division-related gene, and the crl mutant exhibits a dwarf phenotype with abnormal cell division and a significant reduction in plastid numbers. However, the function of AtCRL is not fully understood. Here, we identified and characterized two AtCRL homologs, PpCRL1 and PpCRL2, in the moss Physcomitrella patens. PpCRL1 and PpCRL2 shared 77% amino acid identity with each other and 47% identity with AtCRL. Single PpCRL1 or -2 gene knockout (KO) mutants could not be distinguished from the wild-type mosses, but PpCRL1 and -2 double KO mutants displayed growth retardation of protonemata and gametophores and harbored approximately 10 large chloroplasts per cell. This indicates that PpCRL1 and PpCRL2 have redundant functions in chloroplast division and plant growth. Unlike the A. thaliana crl mutants, however, the PpCRL double KO mutants did not display abnormal orientation of the cell division plane. Complementation experiments showed that AtCRL partially rescued the defects in chloroplast size and number of the PpCRL double KO mutant. This suggests that PpCRL has a similar, but not identical, function to AtCRL. Time-lapse microscopic observation of the double PpCRL KO mutants revealed that some dumbbell-shaped chloroplasts failed to complete division at the late stage of plastid division; enlarged chloroplasts were thus generated. This strongly suggests that PpCRLs are involved in the complete separation of dividing chloroplasts.     

Observation of yawn-like behavior in a dugong (Dugong dugon)

Journal of Ethology - Yawning is an involuntary action that occurs in three phases: (1) slow mouth opening accompanied by inhalation, (2) maintaining the maximum mouth size, and (3) quick closure...     

Degradation of ester linkages in rice straw components by Sphingobium species recovered from the sea bottom using a non-secretory tannase-family α/β hydrolase

Microbial decomposition of allochthonous plant components imported into the aquatic environment is one of the vital steps of the carbon cycle on earth. To expand the knowledge of the biodegradation of complex plant materials in aquatic environments, we recovered a sunken wood from the bottom of Otsuchi Bay, situated in northeastern Japan in 2012. We isolated Sphingobium with high ferulic acid esterase activity. The strain, designated as OW59, grew on various aromatic compounds and sugars, occurring naturally in terrestrial plants. A genomic study of the strain suggested its role in degrading hemicelluloses. We identified a gene encoding a non-secretory tannase-family α/β hydrolase, which exhibited ferulic acid esterase activity. This enzyme shares the consensus catalytic triad (Ser-His-Asp) within the tannase family block X in the ESTHER database. The molecules, which had the same calculated elemental compositions, were produced consistently in both the enzymatic and microbial degradation of rice straw crude extracts. The non-secretory tannase-family α/β hydrolase activity may confer an important phenotypic feature on the strain to accelerate plant biomass degradation. Our study provides insights into the underlying biodegradation process of terrestrial plant polymers in aquatic environments.     

Life history of the endangered Japanese striped loach,Cobitis kaibarai (Cypriniformes: Cobitidae), with special reference to its reproductive ecology and the influence of creek reshapings on its population density

In recent years, the biodiversity of freshwater fishes has been markedly decreasing worldwide because of anthropogenic activities. The Japanese striped loach, Cobitis kaibarai (Cypriniformes: Cobitidae), is a primary freshwater fish endemic to northern Kyushu, Japan. This species is designated as endangered IB class in the Red List by the Japan Ministry of the Environment. Its population is decreasing, possibly because of habitat loss and degradation. To conserve C. kaibarai populations, information on its basic ecology is necessary; nonetheless, its detailed life history and reproductive ecology have yet to be clarified. In this study, the authors conducted monthly capture–mark–recapture surveys and periodical observations to investigate the life history, spawning sites and season of C. kaibarai. They also evaluated the influence of creek reshaping (concrete revetment) on the C. kaibarai population in Saga Plain, northern Kyushu. Between 2015 and 2018, more individuals were captured during winter than summer. The average body width of females peaked in early June and small immatures were confirmed from July. Some individuals were captured across 15 or more months after their initial marking. In the survey of reproductive sites, eggs and larvae of C. kaibarai were found in shallow areas in mid-June; these were temporarily submerged following the increase in water level from early June. Therefore, C. kaibarai spawns in shallow areas during this season. Based on the capture–mark–recapture surveys, the estimated population density of C. kaibarai significantly decreased in a census site that had undergone creek reshaping, which contrasted with the results in a control site, where no significant difference was detected. The standard length of C. kaibarai increased following creek reshaping, suggesting that the proportion of C. kaibarai postponing spawning had increased, possibly because of degradation of spawning environments. The results of this study provide important ecological knowledge for the conservation of C. kaibarai and emphasize the importance of shallow waters for floodplain spawners.     

MTCL1 plays an essential role in maintaining Purkinje neuron axon initial segment

The axon initial segment (AIS) is a specialized domain essential for neuronal function, the formation of which begins with localization of an ankyrin-G (AnkG) scaffold. However, the mechanism directing and maintaining AnkG localization is largely unknown. In this study, we demonstrate that in vivo knockdown of microtubule cross-linking factor 1 (MTCL1) in cerebellar Purkinje cells causes loss of axonal polarity coupled with AnkG mislocalization. MTCL1 lacking MT-stabilizing activity failed to restore these defects, and stable MT bundles spanning the AIS were disorganized in knockdown cells. Interestingly, during early postnatal development, colocalization of MTCL1 with these stable MT bundles was observed prominently in the axon hillock and proximal axon. These results indicate that MTCL1-mediated formation of stable MT bundles is crucial for maintenance of AnkG localization. We also demonstrate that Mtcl1 gene disruption results in abnormal motor coordination with Purkinje cell degeneration, and provide evidence suggesting possible involvement of MTCL1 dysfunction in the pathogenesis of spinocerebellar ataxia.     

Discovery of (-)-6-[2-[4-(3-fluorophenyl)-4-hydroxy-1-piperidinyl]-1-hydroxyethyl]-3,4-dihydro-2(1H)-quinolinone--a potent NR2B-selective N-methyl D-aspartate (NMDA) antagonist for the treatment of pain

(-)-6-[2-[4-(3-Fluorophenyl)-4-hydroxy-1-piperidinyl]-1-hydroxyethyl]-3,4-dihydro-2(1H)-quinolinone was identified as an orally active NR2B-subunit selective N-methyl-d-aspartate (NMDA) receptor antagonist. It has very high selectivity for NR2B subunits containing NMDA receptors versus the HERG-channel inhibition (therapeutic index=4200 vs NR2B binding IC(50)). This compound has improved pharmacokinetic properties compared to the prototype CP-101,606.     

Carbohydrate-recognition domains of galectin-9 are involved in intermolecular interaction with galectin-9 itself and other members of the galectin family

Galectin-9 (Gal-9) is a tandem-repeat-type member of the galectin family associated with diverse biological processes, such as apoptosis, cell aggregation, and eosinophil chemoattraction. Although the detailed sugar-binding specificity of Gal-9 has been elucidated, molecular mechanisms that underlie these functions remain to be investigated. During the course of our binding study by affinity chromatography and surface plasmon resonance (SPR) analysis, we found that human Gal-9 interacts with immobilized Gal-9 in the protein-protein interaction mode. Interestingly, this intermolecular interaction strongly depended on the activity of the carbohydrate recognition domain (CRD), because the addition of potent saccharide inhibitors abolished the binding. The presence of multimers was also confirmed by Ferguson plot analysis of result of polyacrylamide gel electrophoresis and matrix-assisted laser-desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS). Moreover, this intermolecular interaction was observed between Gal-9 and other galectin members, such as Gal-3 and Gal-8, but not Gal-1. Because such properties have not been reported yet, they may explain an unidentified mechanism underlying the diverse functions of Gal-9.