Rhabdomyolysis and Acute Kidney Injury Requiring Dialysis as a Result of Concomitant Use of Atypical Neuroleptics and Synthetic Cannabinoids

The use of synthetic cannabinoids (SCBs) is associated with many severe adverse effects that are not observed with marijuana use. We report a unique case of a patient who developed rhabdomyolysis and acute kidney injury (AKI) requiring dialysis after use of SCBs combined with quetiapine. Causes for the different adverse effects profile between SCBs and marijuana are not defined yet. Cases reported in literature with SCBs use have been associated with reversible AKI characterized by acute tubular necrosis and interstitial nephritis. Recent studies have showed the involvement of cytochromes P450s (CYPs) in biotransformation of SCBs. The use of quetiapine which is a substrate of the CYP3A4 and is excreted (73%) as urine metabolites may worsen the side effect profiles of both quetiapine and K2. SCBs use should be included in the differential diagnosis of AKI and serum Creatinine Phosphokinase (CPK) level should be monitored. Further research is needed to identify the mechanism of SCBs nephrotoxicity

Case Report Rhabdomyolysis and Acute Kidney Injury Requiring Dialysis as a Result of Concomitant Use of Atypical Neuroleptics and Synthetic Cannabinoids

The use of synthetic cannabinoids (SCBs) is associated with many severe adverse effects that are not observed with marijuana use. We report a unique case of a patient who developed rhabdomyolysis and acute kidney injury (AKI) requiring dialysis after use of SCBs combined with quetiapine. Causes for the different adverse effects profile between SCBs and marijuana are not defined yet. Cases reported in literature with SCBs use have been associated with reversible AKI characterized by acute tubular necrosis and interstitial nephritis. Recent studies have showed the involvement of cytochromes P450s (CYPs) in biotransformation of SCBs. The use of quetiapine which is a substrate of the CYP3A4 and is excreted (73%) as urine metabolites may worsen the side effect profiles of both quetiapine and K2. SCBs use should be included in the differential diagnosis of AKI and serum Creatinine Phosphokinase (CPK) level should be monitored. Further research is needed to identify the mechanism of SCBs nephrotoxicity

Composition and characteristics of soil microbial communities in cotton fields with different incidences of Verticillium wilt

Soil microorganisms could affect the growth of plants and play an important role in indicating the change of soil environment. Cotton Verticillium wilt is a serious soil borne disease. This study aimed to analyze the community characteristics of soil microorganisms in cotton fields with different incidences of Verticillium wilt, so as to provide theoretical guidance for the prevention and control of soil borne diseases of cotton. Through the analysis of soil microbial communities in six fields, the results showed that there was no difference in fungal and bacterial alpha-diversity index before cotton planting, while there were differences in rhizosphere of diseased plants. For fungal beta diversity indexes, there were significant differences in these six fields. There was no significant difference for bacterial beta diversity indexes before cotton planting, while there was a certain difference in the rhizosphere of diseased cotton plants. The composition of fungi and bacteria in different fields was roughly the same at the genus level, but the abundances of the same genus varied greatly between different fields. Before cotton planting, there were 61 fungi (genera) and 126 bacteria (genera) with different abundances in the six fields. Pseudomonas, Sphingomonas and Burkholderia had higher abundances in the fields with less incidence. This study will provide a theoretical basis for microbial control of Cotton Verticillium wilt

Characterization and Distribution of the autB Gene in Neisseria meningitidis

We aimed to investigate and understand the characterization and distribution of the autB gene in Neisseria meningitidis in China. autB is flanked by two conservative genes, smpB and glcD, and it can be present in the majority of meningococcal isolates, but not in 053442 of clonal complex 4821 (CC4821) which contains a 968 bp sequence. In this study, we sequenced the intervenient region between smpB and glcD in 178 Chinese N. meningitidis strains isolated from both patients and carriers. There were 110 serogroupable strains, other 68 were non-groupable (NG). Ninety nine of the 178 strains were clustered into 13 CCs, the remaining 79 were unassigned (UA). CC4821 is one of the dominant CCs in China. Forty of the 42 CC4821 strains and 26 of the 79 UA strains were autB-null, while the remaining 12 CCs were autB-positive. According to the N-terminal sequence, most (97/112) of the autB-positive strains were clustered into AutB1 and the remaining 15 were AutB2. The autB gene and its flanking intergenic sequences was superseded by a perfectly conservative sequence of an identical 968 bp in all of the autB-null N. meningitidis strains which had no identity with the relatively conservative intergenic sequences that flanked the autB gene in autB-positive strains. There was a 10 bp DNA uptake sequence (DUS) at the beginning of the interval 968 bp sequence in the autB-null strains while there was a 9 bp Haemophilus-specific uptake sequence (hUS) at the beginning of the partial holB gene and at the end of the partial tmk gene in autB-positive strains, holB and tmk gene were flanking the autB gene in Haemophilus. In conclusion, not all pathogenic N. meningitidis strains especially CC4821 possess the autB gene in China and the corresponding spacer region of the autB-null strains was not homologous to that found in autB-positive strains. There's a hypothesis that the DUS and hUS are likely to play a key part in the mechanism of uptake or loss of the autB gene

<i>Drosophila S6 Kinase Like</i> Inhibits Neuromuscular Junction Growth by Downregulating the BMP Receptor Thickveins

<div><p>Synaptic connections must be precisely controlled to ensure proper neural circuit formation. In <i>Drosophila melanogaster</i>, bone morphogenetic protein (BMP) promotes growth of the neuromuscular junction (NMJ) by binding and activating the BMP ligand receptors wishful thinking (Wit) and thickveins (Tkv) expressed in motor neurons. We report here that an evolutionally conserved, previously uncharacterized member of the S6 kinase (S6K) family S6K like (S6KL) acts as a negative regulator of BMP signaling. <i>S6KL</i> null mutants were viable and fertile but exhibited more satellite boutons, fewer and larger synaptic vesicles, larger spontaneous miniature excitatory junctional potential (mEJP) amplitudes, and reduced synaptic endocytosis at the NMJ terminals. Reducing the gene dose by half of <i>tkv</i> in <i>S6KL</i> mutant background reversed the NMJ overgrowth phenotype. The NMJ phenotypes of <i>S6KL</i> mutants were accompanied by an elevated level of Tkv protein and phosphorylated Mad, an effector of the BMP signaling pathway, in the nervous system. In addition, Tkv physically interacted with S6KL in cultured S2 cells. Furthermore, knockdown of S6KL enhanced Tkv expression, while S6KL overexpression downregulated Tkv in cultured S2 cells. This latter effect was blocked by the proteasome inhibitor MG132. Our results together demonstrate for the first time that S6KL regulates synaptic development and function by facilitating proteasomal degradation of the BMP receptor Tkv.</p></div

Genetic interactions between <i>S6KL</i> and components of the BMP signaling pathway in regulating NMJ growth.

<p>(A–H) Confocal images of NMJ 4 synapses of different genotypes co-stained with anti-HRP (green) and anti-CSP (magenta): WT (A), <i>S6KL</i>^<i>140</i> (B), <i>S6KL</i>^<i>140</i><i>; tkv</i>^<i>7</i><i>/+</i> (C), <i>tkv</i>^<i>7</i><i>/tkv</i>^{<i>k16713</i>} (D), <i>S6KL</i>^<i>140</i><i>; tkv</i>^<i>7</i><i>/tkv</i>^{<i>k16713</i>} (E), <i>S6KL</i>^<i>140</i><i>/+</i> (F), <i>dad</i>^<i>J1E4</i><i>/+</i> (G), and <i>S6KL</i>^<i>140</i><i>/+; dad</i>^<i>J1E4</i><i>/+</i> (H). Scale bar, 5 μm. (I–L) Confocal images of NMJ 4 terminals co-labeled with anti-pMad (green) and anti-HRP (magenta) in WT (I), <i>tkv</i>^<i>7</i><i>/+</i> (J), <i>S6KL</i>^<i>140</i> (K), and <i>S6KL</i>^<i>140</i><i>; tkv</i>^<i>7</i><i>/+</i> (L) larvae. (M) Quantifications of synaptic bouton numbers in different genotypes including wild type (n = 17), <i>S6KL</i>^<i>140</i> (n = 19), <i>tkv</i>^<i>7</i><i>/tkv</i>^{<i>k16713</i>} (n = 17), <i>S6KL</i>^<i>140</i><i>; tkv</i>^<i>7</i><i>/tkv</i>^{<i>k16713</i>} (n = 10), <i>tkv</i>^<i>7</i><i>/+</i> (n = 16), <i>S6KL</i>^<i>140</i><i>; tkv</i>^<i>7</i><i>/+</i> (n = 19), <i>S6KL</i>^<i>140</i><i>/+</i> (n = 19), <i>dad</i>^<i>J1E4</i><i>/+</i> (n = 10), and <i>S6KL</i>^<i>140</i><i>/+; dad</i>^<i>J1E4</i><i>/+</i> (n = 22). (N) Quantification of the relative fluorescence intensities of pMad in NMJ terminals of different genotypes. n = 8, 9, 8, and 8 for wild type, <i>tkv</i>^<i>7</i><i>/+</i>, <i>S6KL</i>^<i>140</i>, and <i>S6KL</i>^<i>140</i><i>; tkv</i>^<i>7</i><i>/+</i>, respectively. **<i>p</i><0.01 by one-way ANOVA with Tukey post hoc test; error bars indicate SEM. (O) Western results of larval brains from wild-type control and <i>S6KL</i>^<i>140</i> mutants. Actin was used as a loading control. (P) Quantification of the relative protein levels of pMad and Mad in the larval brains of wild type and <i>S6KL</i>^<i>140</i> mutants. The level of pMad but not Mad was increased in <i>S6KL</i> mutants. <i>n</i> = 3, **<i>p</i><0.01 by Student’s <i>t</i>-tests; error bars indicate SEM.</p

Overgrown NMJs in <i>S6KL</i> mutants.

<p>(A–F) Representative NMJ 4 synapses from different genotypes double-stained with anti-HRP recognizing neuronal plasma membrane (green) and an antibody against CSP (magenta), a synaptic vesicle protein. Insets show higher-magnification images of terminal boutons. The genotypes are: (A) Wild type, (B) homozygous <i>S6KL</i>^<i>140</i> mutants, (C) hemizygous <i>S6KL</i>^<i>140</i><i>/Df(1)ED741</i> mutants, (D) neuronal rescue of <i>S6KL</i>^<i>140</i> by overexpression of S6KL under the control of <i>elav-Gal4</i> (<i>S6KL</i>^<i>140</i><i>elav-Gal4/S6KL</i>^<i>140</i><i>; UAS-S6KL/+</i>), (E) Muscular rescue of <i>S6KL</i>^<i>140</i> by overexpression of S6KL under the control of <i>Mhc-Gal4</i> (<i>S6KL</i>^<i>140</i>; <i>UAS-S6KL/Mhc-Gal4</i>), and (F) Neuronal rescue of <i>S6KL</i>^<i>140</i> by overexpression of the kinase dead S6KL (S6KL^K193Q) under the control of <i>elav-Gal4</i> (<i>S6KL</i>^<i>140</i><i>elav-Gal4/ S6KL</i>^<i>140</i><i>; UAS-S6KL</i>^<i>K193Q</i><i>/+</i>). Satellite boutons are indicated by arrows in B. Insets D and F show Western results of larvae brain extracts using anti-S6KL and anti-actin antibodies. Scale bar, 5 μm. (G, H) Statistical results of the number of total boutons (G) and satellite boutons (H) in different genotypes. <i>n</i> = 17, 19, 15, 16, 19 and 18 NMJs for wild type, <i>S6KL</i>^<i>140</i>, <i>S6KL</i>^<i>140</i><i>/Df(1)ED7413</i>, <i>S6KL</i>^<i>140</i><i>elav-Gal4/S6KL</i>^<i>140</i><i>; UAS-S6KL/+</i>, <i>S6KL</i>^<i>140</i>; <i>UAS-S6KL/Mhc-Gal4</i>, and <i>S6KL</i>^<i>140</i><i>elav-Gal4/S6KL</i>^<i>140</i><i>; UAS-S6KL</i>^<i>K193Q</i><i>/+</i>, respectively. ***<i>p</i><0.001 by one-way ANOVA with Tukey post hoc test; error bars indicate SEM.</p

S6KL functions presynaptically in regulating NMJ growth.

<p>(A–E) Representative NMJ4 synapses from different genotypes doubly stained with anti-HRP (green) and anti-CSP (magenta). (A) wild type, (B) <i>elav-Gal4/+; UAS-S6KL/+</i>, (C) <i>C57-Gal4/UAS-S6KL</i>, (D) <i>elav-Gal4/+; S6KL RNAi/+</i>, and (E) <i>S6KL RNAi/+; C57-Gal4/+</i>. Scale bar, 5 μm. (F, G) Statistical results of the number of boutons (F) and satellite boutons (G) in different genotypes. <i>n</i> >16 for each genotype; ***<i>p</i> < 0.001 by one-way ANOVA with Tukey post hoc test; error bars indicate SEM.</p