Notes

Climbing Innate Guidance from the Genomics Age.
The structural identification of impurities in cephalosporins has been reported. However, to the best of our knowledge, there was no report on the impurities of cefsulodin sodium, which is necessary for the quality control. Thus, the aim of this study was to separate and characterize the impurities in cefsulodin sodium raw material using liquid chromatography/tandem mass spectrometry (LC/MS/MS).

The analytes were separated on a Kromasil 100-5C18 column (4.6mm × 250 mm, 5μm) using a gradient elution with a mobile phase consisting of 1% ammonium sulphate aqueous solution and acetonitrile in the first dimension. The separation in the second dimension was carried on a Shimadzu Shim-pack GISS C18 column (50 mm × 2.1mm, 1.9μm) with a mobile phase consisting of 10 mM ammonium formate solution and methanol.

The fragmentation behaviors of cefsulodin and its impurities were studied and the structures of the impurities were deduced based on the MS
data. The structures of ten unknown impurities were proposed based on the work carried out in this study. The degradation behaviors of cefsulodin sodium were also studied. This revealed that cefsulodin sodium should be stored in a dry, cool and dark closed container.

Based on the characterization of impurities, this study not only revealed the mechanism by which impurities were produced, thus providing guidance to pharmaceutical companies for manufacturing process improvement and impurity control, but also provided a scientific basis for further improvement of official monographs in pharmacopoeias.
Based on the characterization of impurities, this study not only revealed the mechanism by which impurities were produced, thus providing guidance to pharmaceutical companies for manufacturing process improvement and impurity control, but also provided a scientific basis for further improvement of official monographs in pharmacopoeias.Lymphangioleiomyomatosis (LAM) is a rare systemic disease of women of reproductive age characterized by proliferation of abnormal smooth muscle like cells (LAM cells). Patients with LAM characteristically present with chronic dyspnea and cough and less commonly with spontaneous pneumothorax. Manifestation of extrapulmonary LAM as an initial presenting symptom is rare with a renal angiomyolipoma and lymphangioleiomyoma being most common. Although histologic findings of LAM are well-described, the cytological features; however, have been described only in few case reports, which focus on pulmonary LAM. Here, we report a case where initial diagnosis of LAM was made on pelvic "lymph node" fine needle aspiration (FNA) and biopsy in otherwise asymptomatic 25-year-old female, leading to further investigation and detection of developing cystic lung lesions. FNA cytology from the pelvic "lymph node" yielded proliferation of spindle cells without cytologic atypia. This case presented both clinical and histopathologic challenge, requiring clinical correlation and immunohistochemical staining for diagnosis. While rare, it is important to consider LAM in the differential diagnosis of spindle cell lesions in aspirate from nodules around vascular bundles in women of reproductive age even without history of lung lesion.MicroRNAs constitute a class of endogenous, non-coding RNAs that influence various processes within the cell. By base-pairing to partially-complementary sites located in the 3' untranslated region of target messenger RNAs, microRNAs participate in post-transcriptional regulation of the majority of human protein-coding genes. Their dysregulation has been related to many pathological processes and diseases. Thus, an in-depth understanding of the microRNA mechanisms of action is crucial. Here, we present a new concept of probe design to achieve an efficient and sequence-independent miRNA-mRNA cross-linking. The new strategy is based on the utilization of a controlled mixture of probes for a chosen miRNA, in which a trioxsalen moiety is introduced at the N4 -position of a selected cytidine through short oligoethylene glycol-based linkers. In vitro photo-cross-linking experiments with mini-libraries of probes for microRNAs of interest showed variable cross-linking efficiencies, demonstrating a general applicability of the presented approach.Acetic acid stress represents a frequent challenge to counteract for yeast cells under several environmental conditions and industrial bioprocesses. The molecular mechanisms underlying its response have been mostly elucidated in the budding yeast Saccharomyces cerevisiae, where acetic acid can be either a physiological substrate or a stressor. This review will focus on acetic acid stress and its response in the context of cellular transport, pH homeostasis, metabolism and stress-signalling pathways. This information has been integrated with the results obtained by multi-omics, synthetic biology and metabolic engineering approaches aimed to identify major cellular players involved in acetic acid tolerance. In the production of biofuels and renewable chemicals from lignocellulosic biomass, the improvement of acetic acid tolerance is a key factor. In this view, how this knowledge could be used to contribute to the development and competitiveness of yeast cell factories for sustainable applications will be also discussed.Pseudomonas aeruginosa produces phenazine-1-carboxylic acid (PCA) and pyocyanin (PYO), which aid its anaerobic survival by mediating electron transfer to distant oxygen. These natural secondary metabolites are being explored in biotechnology to mediate electron transfer to the anode of bioelectrochemical systems. A major challenge is that only a small fraction of electrons from microbial substrate conversion is recovered. It remained unclear whether phenazines can re-enter the cell and thus, if the electrons accessed by the phenazines arise mainly from cytoplasmic or periplasmic pathways. Here, we prove that the periplasmic glucose dehydrogenase (Gcd) of P. aeruginosa and P. click here putida is involved in the reduction of natural phenazines. PYO displayed a 60-fold faster enzymatic reduction than PCA; PCA was, however, more stable for long-term electron shuttling to the anode. Evaluation of a Gcd knockout and overexpression strain showed that up to 9% of the anodic current can be designated to this enzymatic reaction.
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