An axonemal intron splicing program sustains Plasmodium male development.

Differentiation of male gametocytes into flagellated fertile male gametes relies on the assembly of axoneme, a major component of male development for mosquito transmission of the malaria parasite. RNA-binding protein (RBP)-mediated post-transcriptional regulation of mRNA plays important roles in eukaryotic sexual development, including the development of female Plasmodium. However, the role of RBP in defining the Plasmodium male transcriptome and its function in male gametogenesis remains incompletely understood. Here, we performed genome-wide screening for gender-specific RBPs and identified an undescribed male-specific RBP gene Rbpm1 in the Plasmodium. RBPm1 is localized in the nucleus of male gametocytes. RBPm1-deficient parasites fail to assemble the axoneme for male gametogenesis and thus mosquito transmission. RBPm1 interacts with the spliceosome E complex and regulates the splicing initiation of certain introns in a group of 26 axonemal genes. RBPm1 deficiency results in intron retention and protein loss of these axonemal genes. Intron deletion restores axonemal protein expression and partially rectifies axonemal defects in RBPm1-null gametocytes. Further splicing assays in both reporter and endogenous genes exhibit stringent recognition of the axonemal introns by RBPm1. The splicing activator RBPm1 and its target introns constitute an axonemal intron splicing program in the post-transcriptional regulation essential for Plasmodium male development.

Short-term steaming during processing impacts the quality of Citri Reticulatae 'Chachi' peel.

Citrus peel is a commonly used food-medicine material in the production of fast-moving consumer goods (FMCGs). For instance, Ganpu tea is manufactured by combining the peel of Citri Reticulatae 'Chachi' (PCRC) with Pu-erh tea. The alleviated irritation of PCRC through years of aging makes Citri reticulatae Pericarpium a traditional Chinese medicine. Herein, we introduced short-term steaming into the processing of PCRC to favor the quick removal of its irritation while retaining its food-medicine properties. Sensory evaluation and volatile component analysis showed that 60-s steaming reduced irritation of freshly prepared PCRC. Biological evaluations indicated no effects of steaming on the neuroprotective activity of PCRC. The process increased the contents of several bioactive ingredients, including hesperidin, nobiletin, tangeretin, and synephrine. In addition, physical indications of accelerating PCRC aging were observed. Taken together, our findings suggest that short-term steaming may offer a promising new possibility for enhancing the quality of citrus peel.

EB1 decoration of microtubule lattice facilitates spindle-kinetochore lateral attachment in Plasmodium male gametogenesis.

Faithful chromosome segregation of 8 duplicated haploid genomes into 8 daughter gametes is essential for male gametogenesis and mosquito transmission of Plasmodium. Plasmodium undergoes endomitosis in this multinucleated cell division, which is highly reliant on proper spindle-kinetochore attachment. However, the mechanisms underlying the spindle-kinetochore attachment remain elusive. End-binding proteins (EBs) are conserved microtubule (MT) plus-end binding proteins and play an important role in regulating MT plus-end dynamics. Here, we report that the Plasmodium EB1 is an orthologue distinct from the canonical eukaryotic EB1. Both in vitro and in vivo assays reveal that the Plasmodium EB1 losses MT plus-end tracking but possesses MT-lattice affinity. This MT-binding feature of Plasmodium EB1 is contributed by both CH domain and linker region. EB1-deficient parasites produce male gametocytes that develop to the anucleated male gametes, leading to defective mosquito transmission. EB1 is localized at the nucleoplasm of male gametocytes. During the gametogenesis, EB1 decorates the full-length of spindle MTs and regulates spindle structure. The kinetochores attach to spindle MTs laterally throughout endomitosis and this attachment is EB1-dependent. Consequently, impaired spindle-kinetochore attachment is observed in EB1-deficient parasites. These results indicate that a parasite-specific EB1 with MT-lattice binding affinity fulfills the spindle-kinetochore lateral attachment in male gametogenesis.

Myricetin Inhibits α-Synuclein Amyloid Aggregation by Delaying the Liquid-to-Solid Phase Transition.

The aggregation of α-synuclein (α-Syn) is a critical pathological hallmark of Parkinson's disease (PD). Prevention of α-Syn aggregation has become a key strategy for treating PD. Recent studies have suggested that α-Syn undergoes liquid-liquid phase separation (LLPS) to facilitate nucleation and amyloid formation. Here, we examined the modulation of α-Syn aggregation by myricetin, a polyhydroxyflavonol compound, under the conditions of LLPS. Unexpectedly, neither the initial morphology nor the phase-separated fraction of α-Syn was altered by myricetin. However, the dynamics of α-Syn condensates decreased upon myricetin binding. Further studies showed that myricetin dose-dependently inhibits amyloid aggregation in the condensates by delaying the liquid-to-solid phase transition. In addition, myricetin could disassemble the preformed α-Syn amyloid aggregates matured from the condensates. Together, our study shows that myricetin inhibits α-Syn amyloid aggregation in the condensates by retarding the liquid-to-solid phase transition and reveals that α-Syn phase transition can be targeted to inhibit amyloid aggregation.

α-Synuclein phase separation and amyloid aggregation are modulated by C-terminal truncations.

The aggregation of α-synuclein (α-Syn) is a key pathological hallmark of Parkinson's disease (PD). α-Syn undergoes liquid-liquid phase separation (LLPS) to drive amyloid aggregation. How the LLPS of α-Syn is regulated remains largely unknown. Here, we discovered that the C-terminal region modulates α-Syn phase separation through electrostatic interactions. The wild-type (WT) and PD disease-related truncated α-Syn can co-exist in the condensates. The truncated α-Syn could dramatically promote WT α-Syn phase separation. Further studies demonstrated that the truncated α-Syn accelerated WT α-Syn turning to amyloid aggregates by modulation of phase separation. Together, our findings disclose the role of the C-terminal domain in the LLPS of α-Syn and pave the path for understanding the mechanism of truncated α-Syn in PD pathology.

Genome Sequence of Zymomonas mobilis subsp. mobilis NRRL B-1960.

Zymomonas mobilis subsp. mobilis is an efficient ethanol producer with application for industrial production of biofuel. To supplement existing Z. mobilis genomic resources and to facilitate genomic research, we used Oxford Nanopore and Illumina sequencing to assemble the complete genome of the beer spoilage isolate Z. mobilis subsp. mobilis strain NRRL B-1960.

Purification and sequence characterization of chondroitin sulfate and dermatan sulfate from fishes.

Chondroitin sulfate (CS) and dermatan sulfate (DS) were extracted and purified from skins or bones of salmon (Salmo salar), snakehead (Channa argus), monkfish (Lophius litulon) and skipjack tuna (Katsuwonus pelamis). Size, structural sequences and sulfate groups of oligosaccharides in the purified CS and DS could be characterized and identified using high performance liquid chromatography (HPLC) combined with Orbitrap mass spectrometry. CS and DS chain structure varies depending on origin, but motif structure appears consistent. Structures of CS and DS oligosaccharides with different size and sulfate groups were compared between fishes and other animals, and results showed that some minor differences of special structures could be identified by hydrophilic interaction chromatography-liquid chromatography-fourier transform-mass/mass spectrometry (HILIC-LC-FT-MS/MS). For example, data showed that salmon and skipjack CS had a higher percentage content of high-level sulfated oligosaccharides than that porcine CS. In addition, structural information of different origins of CS and DS was analyzed by principal component analysis (PCA) and results showed that CS and DS samples could be differentiated according to their molecular conformation and oligosaccharide fragments information. Understanding CS and DS structure derived from different origins may lead to the production of CS or DS with unique disaccharides or oligosaccharides sequence composition and biological functions.

[Analysis of factors related to mortality of critical patients with acute renal dysfunction].

OBJECTIVE: To investigate the high risk factors related to mortality rate of critical patients with acute renal dysfunction in intensive care unit (ICU). METHODS: The data of patients with acute renal dysfunction hospitalized in ICU of Peking union medical college hospital during August 1999 to May 2001 were retrospectively investigated and the high risk factors related to hospital mortality were analyzed. The statistical analysis methods were univariate and multivariate factors analysis. RESULTS: Among 1 218 critical patients hospitalized during August 1999 to May 2001, there were 149 patients with acute renal dysfunction. One hundred and thirty-five patients were investigated completely. Fifty-five (41 percent) died during the hospital stay. By univariate analysis, risk factors related to hospital mortality included acute physiology and chronic health evaluationII (APACHEII) score, the systemic inflammatory response syndrome, sepsis, severe sepsis, septic shock, chronic respiratory dysfunction, sepsis-related organ failure assessment (SOFA) score, acute respiratory dysfunction, coagulation dysfunction, central nerves system dysfunction, cardiovascular dysfunction, management of noradrenaline and continuous venovenous hemofiltration (CVVH). By multivariate analysis, only APACHEII score and management of noradrenaline and CVVH were determined as risk factors of hospital mortality independently. If the three factors were excluded, sepsis, central nerves system dysfunction, oliguria became the risk factors of mortality (all P<0.05). CONCLUSION: The prognosis of critical patients with the acute renal dysfunction correlate with degree of basic diseases. There include oliguresis, coagulation dysfunction, central nerves system dysfunction and sepsis. In spite of management of CVVH, acute renal dysfunction per se can affect the prognosis of the critical patients.

[The role of the static P-V curve under zero end-expiratory pressure in sustained inflation in patients with acute respiratory distress syndrome].

OBJECTIVE: To evaluate the value of static P-V curve under zero end-expiratory pressure (ZEEP) in predicting the effect of sustained inflation (SI) on hemodynamics, oxygenation and alveolar recruitment in patients with acute respiratory distress syndrome (ARDS). METHODS: Static P-V curve was measured under positive end-expiratory pressure (PEEP) in all the patients 2 h afer PEEP was applied. Patients who experienced more than 20% increase in PaO(2)/FiO(2) were considered as responders to SI. RESULTS: (1) The static P-V curves in responders consistently showed a concave pattern with c-2d >or= 0 cm H(2)O (1 cm H(2)O = 0.098 kpa) and c >or= 18 cm H(2)O, while those in non-responders showed a convex pattern with c-2d < 0 cm H(2)O or c < 18 cm H(2)O. (2) After SI, decrease of Q(s)/Q(t) (P = 0.006) was found in responders, but not in non-responders (P = 0.339). The amount of recruited volume was significantly higher in responders than in non-responders after SI [(241 +/- 111) ml vs (29 +/- 46) ml, P = 0.036]. CONCLUSION: The static P-V curves under ZEEP exhibited different patterns in responders and non-responders to SI in ARDS patients, and may be of value in predicting the response to SI.