The tetratricopeptide repeats of receptors involved in protein translocation across membranes

Transport of polypeptides across membranes is a general and essential process in every cell. This process is utilized by molecular machines composed of soluble and membrane-inserted proteins. At least one component of the molecular transport machines present in different membranes contains a subunit with a domain composed of 3 tetratricopeptide repeat (TPR) motifs. These domains are important for protein-protein interaction, for example, recognition of chaperones. To understand the evolution of these TPR domain-containing receptors involved in protein translocation, we inferred their phylogenetic relationships. We show that the evolutionary rate of these TPR domains is reduced when compared with the remaining sequence. The reduction is explained by the interaction of the TPR domains with their substrates. Based on the TPR tree, we propose that Sec72 recognizes Hsp70 and that Tom34 recognizes Hsp90. The phylogeny can further be used to assign the localization of the Toc64 isoforms to mitochondria or chloroplasts. Our findings are discussed in the context of the evolutionary development of translocation systems with focus on the occurrence of Hsp70/Hsp90-recognizing TPR domains in these machineries.     

Size and placement of developing anterior teeth in immature Neanderthal mandibles from Dederiyeh Cave,Syria: Implications for emergence of the modern human chin

Evolutionary and functional significance of the human chin has long been explored from various perspectives including masticatory biomechanics, speech, and anterior tooth size. Recent ontogenetic studies have indicated that the spatial position of internally forming anterior teeth partially constrains adult mandibular symphyseal morphology. The present study therefore preliminarily examined the size and placement of developing anterior teeth in immature Neanderthal mandibles of Dederiyeh 1 and 2, compared with similarly‐aged modern humans (N = 16) and chimpanzees (N = 7) whose incisors are comparatively small and large among extant hominids, respectively. The Dederiyeh 1 mandible is described as slightly presenting a mental trigone and attendant mental fossa, whereas Dederiyeh 2 completely lacks such chin‐associated configurations. Results showed that, despite symphyseal size being within the modern human range, both Dederiyeh mandibles accommodated overall larger anterior dentition and displayed a remarkably wide bicanine space compared to those of modern humans. Dederiyeh 2 had comparatively thicker deciduous incisor roots and more enlarged permanent incisor crypts than Dederiyeh 1, but both Dederiyeh individuals exhibited a total dental size mostly intermediate between modern humans and chimpanzees. These findings potentially imply that the large deciduous/permanent incisors collectively distended the labial alveolar bone, obscuring an incipient mental trigone. It is therefore hypothesized that the appearance of chin‐associated features, particularly of the mental trigone and fossa, can be accounted for partly by developmental relationships between the sizes of the available mandibular space and anterior teeth. This hypothesis must be, however, further addressed with more referential samples in future studies. Am J Phys Anthropol 156:482–488, 2015. © 2014 Wiley Periodicals, Inc.     

Monte Carlo simulation of the dose distribution of ICRP adult reference computational phantoms for acquisitions with a 320 detector-row cone-beam CT scanner

PurposeThe purpose of this study was to develop and validate a Monte Carlo (MC) simulation tool for patient dose assessment for a 320 detector-row CT scanner, based on the recommendations of International Commission on Radiological Protection (ICRP). Additionally, the simulation was applied on four clinical acquisition protocols, with and without automatic tube current modulation (TCM).MethodsThe MC simulation was based on EGS4 code and was developed specifically for a 320 detector-row cone-beam CT scanner. The ICRP adult reference phantoms were used as patient models. Dose measurements were performed free-in-air and also in four CTDI phantoms: 150 mm and 350 mm long CT head and CT body phantoms. The MC program was validated by comparing simulations results with these actual measurements acquired under the same conditions. The measurements agreed with the simulations across all conditions within 5%. Patient dose assessment was performed for four clinical axial acquisitions using the ICRP adult reference phantoms, one of them using TCM.ResultsThe results were nearly always lower than those obtained from other dose calculator tools or published in other studies, which were obtained using mathematical phantoms in different CT systems. For the protocol with TCM organ doses were reduced by between 28 and 36%, compared to the results obtained using a fixed mA value.ConclusionsThe developed simulation program provides a useful tool for assessing doses in a 320 detector-row cone-beam CT scanner using ICRP adult reference computational phantoms and is ready to be applied to more complex protocols.     

Effect of Cystone on urinary composition and stone formation over a one year period

Kidney stones are a common problem for which inadequate prevention exists. We recruited ten recurrent kidney stone formers with documented calcium oxalate stones into a two phased study to assess safety and effectiveness of Cystone^®, an herbal treatment for prevention of kidney stones. The first phase was a randomized double-blinded 12 week cross over study assessing the effect of Cystone^® vs. placebo on urinary supersaturation. The second phase was an open label one year study of Cystone^® to determine if renal stone burden decreased, as assessed by quantitative and subjective assessment of CT. Results revealed no statistically significant effect of Cystone^® on urinary composition short (6 weeks) or long (52 weeks) term. Average renal stone burden increased rather than decreased on Cystone^®. Therefore, this study does not support the efficacy of Cystone^® to treat calcium oxalate stone formers. Future studies will be needed to assess effects on stone passage, or on other stone types.     

Efficient synthesis of new tetradentate ligands with potential applications for 64Cu PET-imaging

We wish to report the synthesis of new tetradentate ligands in less than 3 h in good to excellent yields from a commercially available compound using microwave-assisted technology. First tests of complexation showed a high ability of these ligands to chelate ⁶⁴Cu(II) in very diluted medium. These new systems have the potential to be used for nuclear medicine and particularly for PET-imaging.     

Notch signaling and Notch signaling modifiers

Originally discovered nearly a century ago, the Notch signaling pathway is critical for virtually all developmental programs and modulates an astounding variety of pathogenic processes. The DSL (Delta, Serrate, LAG-2 family) proteins have long been considered canonical activators of the core Notch pathway. More recently, a wide and expanding network of non-canonical extracellular factors has also been shown to modulate Notch signaling, conferring newly appreciated complexity to this evolutionarily conserved signal transduction system. Here, I review current concepts in Notch signaling, with a focus on work from the last decade elucidating novel extracellular proteins that up- or down-regulate signal potency.     

肾综合征出血热胸部并发症的CT表现

目的：总结肾综合征出血热（EHF）胸部并发症的CT表现和探讨胸部CT表现对肾综合征出血热的诊断价值。方法：分析60例经HFRS-IgM阳性确诊的HFRS的胸部螺旋cT表现,其中轻型5例、中型20例、重型28例、危重型7例。结果：肺部感染22例,肺水肿12例,胸腔积液4l例,心包积液17例,其中,心包积液合并肺水肿者4例,肺部感染并胸腔积液者4例,胸腔积液合并下肺局部膨胀不全18例,胸部CT检查正常8例。结论：肾综舍征出血热,胸部并发症发生几率较高,以胸腔积液及胸腔积液并下肺膨胀不全发生几率最高,HFRS的胸部CT表现对于临床有很好的治疗意义,早期CT检查可准确显示肾综合征出血热病人胸部改变的特征。     

Four-dimensional imaging of transvacuolar strand dynamics in tobacco BY-2 cells

The vacuole is a characteristic organelle of plant cells and fulfills several important functions related to metabolism and growth of the cell. To shed light on the details of vacuolar structural changes in plant cells, we explored the three-dimensional organization and dynamics of living Nicotiana tabacum L. cv. Bright Yellow 2 cell vacuoles by real-time confocal time-lapse imaging. For imaging, the cells were pulse-labeled with the amphipathic styryl dye FM1-43 (N-(3-triethylammoniumpropyl)-4-(4-(dibutylamino)styryl)pyridinium dibromide), which is delivered to the plant vacuole by endocytic uptake and then incubated overnight. Imaging of the membrane-labeled vacuole revealed a complex vacuole morphology underlaid by constant remodeling. The vacuole is traversed by multiple transvacuolar strands which move along each other and fuse in multiple manners. New strands were created by fission of large membrane sheets. Endocytic vesicle trafficking was followed within the dynamic transvacuolar strands. The movement occurred in a stop-and-go fashion with an average vesicle velocity of 0.46 microm/s and a peak velocity of 0.82 microm/s. Transvacuolar-strand reduction and creation is a characteristic event observed during mitosis. Here we propose a mechanistic model for the alteration of the number of transvacuolar strands, on the basis of their fusion and fission.