Inferring functional modules of protein families with probabilistic topic models

Background  

Genome and metagenome studies have identified thousands of protein families whose functions are poorly understood and for which techniques for functional characterization provide only partial information. For such proteins, the genome context can give further information about their functional context.     

GnRH or eCG treatment fails to restore reproductive function in GnRH immunized ewes

This study was designed to evaluate the potential of using eCG or GnRH in restoring reproductive functions in GnRH immunized ewes. Thirty-three multiparous Kivircik ewes were randomly assigned into either control group (n=11) or immunization group (n=22). Ewes were immunized against GnRH by injecting with a cocktail of ovalbumin-LHRH-7 (ovalbumin-GnRH-7) and thioredoxin-LHRH-7 (thioredoxin-GnRH-7) fusion proteins generated by recombinant DNA technology in April. 500 IU eCG or 0.008 mg GnRH analogue was used to induce ovulations. Serum GnRH antibodies were present in animals of the immunized group beginning the second week after the first immunization and maintained throughout the study (14 months). Immunization caused anestrus in immunized ewes. eCG or GnRH analogue administration given after 14 days progestagen (20 mg fluorogestone acetate, FGA) treatment during breeding season (mid July) did not induce ovulation in these ewes. Two more attempts with single or multiple eCG injections failed to induce ovulation in this group as well. It appears that the gonadotropin stimulation was not of adequate time since neither eCG nor GnRH administration was able to restore reproductive function in immunized animals. The immunization effect lasted more than a year. These results suggest that GnRH immunization exerts its effect via the hypothalamo-pituitary axis and that more than such stimulation is required to overcome the reproductive suppression.     

聚酸酐控释制剂的研究进展

聚酸酐材料是一种良好的生物可降解材料,它可以作为药物载体将药物递送入人体的各个器官,如脑、骨骼、血管等,也可作为基因的载体对患者进行基因治疗。聚酸酐的合成工艺简单、成本低廉,可以满足不同的用途。它奇在人体内降解为对人体无害的二元酸而排除体内,具有良好的生物相容性。文中综述了聚酸酐的合成,聚酸酐控释制剂的制备工艺、降解、体内安全性和临床应用方面的研究进展,并提出了今后的发展方向。聚酸酐在医学方面的研究和应用必将日益广泛。     

Intracellular fate of Francisella tularensis within arthropod-derived cells

Since transmission of Francisella tularensis into the mammalian host occurs via arthropod vectors such as ticks, mosquitoes, horseflies and deerflies, recent studies have established Drosophila melanogaster as an arthropod vector model system. Nothing is known about the intracellular fate of F. tularensis within arthropod‐derived cells, and the role of this host‐parasite adaptation in the evolution of this pathogen to infect mammals. In this report, we explored intracellular trafficking of F. tularensis ssp. novicida in D. melanogaster‐derived S2 cells. First, we show that similar to the F. tularensis ssp. holarctica‐derived LVS strain, F. tularensis ssp. novicida is highly infectious, replicates exponentially within S2 cells and within adult flies, and is fatal to adult fruit flies in a dose‐dependent manner, while the iglC, iglD and mglA mutants are defective. Using electron and fluorescence microscopy‐based phagosome integrity assays, we show that the wild‐type strain escapes into the cytosol of S2 cells within 30–60 min post infection and by 6 h, 90% were cytosolic. In contrast, approximately 40–50% of the iglC and iglD mutants escape into the cytosol by 6 h while the other subpopulation becomes enclosed within multilamellar vesicles (MLVs). Pre‐treatment of S2 cells with the autophagy inhibitor methyl adenine blocks formation of the MLVs and all the vacuolar subpopulation of the iglC and iglD mutant bacteria become enclosed within single membrane‐surrounded vacuoles. Endocytic trafficking studies of F. tularensis within S2 cells show transient colocalization of the bacterial phagosome with D. melanogaster LAMP2–GFP fusion but not with lysosomes pre‐loaded with fluorescent dextran. Our data show that MLVs harbouring the iglC mutant acquire Lamp2 and dextran while MLVs harbouring the iglD mutant exclude these late endosomal and lysosomal markers. Our data indicate crucial differences in the role of the pathogenicity island‐encoded proteins in modulating intracellular trafficking within human macrophages and arthropod vector‐derived cells.     

Callus stimulation in distraction osteogenesis

Distraction osteogenesis has been described as in vivo tissue engineering. The ability to stimulate this process for the repair of bony defects or lengthening of congenitally shortened facial structures is likely to significantly impact the field of craniofacial surgery. The purpose of this study was to determine whether mechanical stimulation of the distracted rabbit mandible would accelerate the maturation of the bony callus when applied during the early consolidation period. Twenty adult New Zealand White rabbits underwent unilateral mandibular osteotomy. A uni-directional internal distractor device (Synthes, Paoli, Pa.) was positioned along a plane perpendicular to the line of osteotomy. After a 7-day latency period, distraction was commenced at a rate of 1.0 mm/day for 12 days in all animals. In a control group of 10 rabbits, a consolidation period of 8 weeks was observed before they were killed. In the experimental group of 10 rabbits, daily alternate compression and distraction of 1 mm (sequential compression and distraction) was performed for 3 weeks followed by a 5-week period of rigid fixation. Each animal received a dose of a fluorescent label at three different time points during the study: at the end of the distraction period, 3 weeks after the completion of the distraction phase, and 3 days before it was killed. All animals were killed 8 weeks after the completion of the distraction phase. Undecalcified histologic analysis and 3-point bending tests to failure were performed on the extracted mandibles. The results of the experimental and control groups were compared.Four animals in the control group and three animals in the experimental group were excluded from the study because of screw loosening resulting in distractor dislodgment or because of infection. On histologic analysis, cortical thickness at the center of the callus was found to be significantly greater in the experimental group compared with the control group when normalized to the contralateral hemimandible (83 percent versus 49 percent, respectively; p < 0.007). The ratio of cortical to cancellous bone in the distracted callus was uniformly found to be greater in the experimental specimens. The mineral apposition rate was calculated by using fluorescence microscopy and found to be significantly greater in the experimental group both during the period of sequential compression and distraction (3.2 microm/day versus 2.1 microm/day, p = 0.02) and after the period of sequential compression and distraction (1.4 microm/day versus 1.1 microm/day, p = 0.006). Mechanical testing revealed no significant differences in bending strength or stiffness between experimental or control groups (p = 0.54 and 0.47, respectively). This study has demonstrated that daily alternating compression and distraction of 1 mm amplitude during the early consolidation period has a stimulatory impact on callus formation with respect to osteoblastic activity, remodeling, and maturation of bone. Optimal timing and amplitude of sequential movement, long-term biomechanical differences, and molecular pathways have yet to be elucidated.     

PGE(2) stimulates VEGF expression in endothelial cells via ERK2/JNK1 signaling pathways

Vascular endothelial growth factor (VEGF) plays an essential role in the initiation and regulation of angiogenesis-a crucial component of wound healing and cancer growth. Prostaglandins (PGs) stimulate angiogenesis but the precise mechanisms of their pro-angiogenic actions remain unexplained. We investigated whether prostaglandin E(2) (PGE(2)) can induce VEGF expression in rat gastric microvascular endothelial cells (RGMEC) and the signaling pathway(s) involved. We demonstrated that PGE(2) significantly increased ERK2 and JNK1 activation and VEGF mRNA and protein expression. Incubation of RGMEC with PD 98059 (MEK kinase inhibitor) significantly reduced PGE(2)-induced ERK2 activity, VEGF mRNA and protein expression. Furthermore, PD 98059 treatment almost completely abolished JNK1 activation. Our data suggest that PGE(2)-stimulates VEGF expression in RGMEC via transactivation of JNK1 by ERK2. One potential implication of this finding is that increased PG levels in cancers could facilitate tumor growth by stimulating VEGF synthesis and angiogenesis.     

Arterial anatomy of the lower lip: a cadaveric study

The aim of the study was to investigate the arterial anatomy of the lower lip. The location, course, length, and diameter of the inferior labial artery and the sublabial artery were revealed by bilateral meticulous anatomic dissections in 14 adult male preserved cadaver heads. Another cadaver head was used for silicone rubber injection to fill the regional arterial tree. The inferior labial artery was the main artery of the lower lip and in all cases branched off the facial artery. The mean length of the inferior labial artery was found to be 52.3 mm (range, 16 to 98 mm). The mean distance of the origin of the inferior labial artery from the labial commissura was 23.9 mm. The mean external diameter of the inferior labial artery at the origin was 1.2 mm. The sublabial artery was present in 10 (71 percent) of the cadavers. Mean measurements of this artery were 1 mm for diameter, 23.4 mm for length, and 27.6 mm for distance from the labial commissura. The sublabial artery may originate from the facial artery or the inferior labial artery. This study found that this region does not have a constant arterial distribution, the inferior labial artery and the sublabial artery (if it exists) can be in different locations unilaterally or bilaterally, and the diameter and the length may vary.