Whole-brain 3D perfusion MRI at 3.0 T using CASL with a separate labeling coil.

A variety of continuous and pulsed arterial spin labeling (ASL) perfusion MRI techniques have been demonstrated in recent years. One of the reasons these methods are still not routinely used is the limited extent of the imaging region. Of the ASL methods proposed to date, continuous ASL (CASL) with a separate labeling coil is particularly attractive for whole-brain studies at high fields. This approach can provide an increased signal-to-noise ratio (SNR) in perfusion images because there are no magnetization transfer (MT) effects, and lessen concerns regarding RF power deposition at high field because it uses a local labeling coil. In this work, we demonstrate CASL whole-brain quantitative perfusion imaging at 3.0 T using a combination of strategies: 3D volume acquisition, background tissue signal suppression, and a separate labeling coil. The results show that this approach can be used to acquire perfusion images in all brain regions with good sensitivity. Further, it is shown that the method can be performed safely on humans without exceeding the current RF power deposition limits. The current method can be extended to higher fields, and further improved by the use of multiple receiver coils and parallel imaging techniques to reduce scan time or provide increased resolution.     

病人付费增加了中国医疗体制面临的挑战

编辑：你好。刘涛的述评（见本刊2006，4期，200页）在病人零付费问题上没有充分考虑医疗保健的政策选择问题。中国先前的情况表明，如需自己支付医药费，病人会减少看病次数，随之导致人民生活质量更差，现在的证据证实了这一点。在中国，老年人40％不看病和75％不住院的原因是由于医疗费用（病人付费）。另外，有人指出病人付费导致医疗不公平现象更加严重。进一步危害包括拖延老年病人病情造成人为的花费，以及延误治疗以增加长期的治疗费用。     

Congenital heart disease in Ceylon

An analysis of 555 consecutive cases of congenital heart disease in Ceylon has shown that for the whole series interatrial septal defect is the commonest cardiac lesion; next is interventricular septal defect, followed by persistent ductus arteriosus. Interventricular and interatrial septal defects are equally common among all the patients below 16 years of age, but interventricular septal defects are commonest among those below 11 years. Persistent truncus arteriosus is unusually common, while coarctation of the aorta and congenital aortic stenosis are rare, as compared with series reported from other places.     

A new begomovirus–betasatellite complex is associated with chilli leaf curl disease in Sri Lanka

Leaf curl disease of chilli (LCDC) is a major constraint in production of chilli in the Indian subcontinent. The objective of this study was to identify the begomovirus species occurring in chilli in Sri Lanka, where the LCDC was initially recorded in 1938. The virus samples were collected from the North Central Province, the major chilli growing region in Sri Lanka with a history of epidemic prevalence of LCDC. The virus could be readily transmitted by Bemisia tabaci to chilli, tomato and tobacco, where vein clearing followed by leaf curl developed. The genome analysis of two isolates obtained from two distantly located fields showing 100 % LCDC, revealed that the DNA-A genome (2754 nucleotides) shared 89.5 % sequence identity with each other and 68.80–84.40 % sequence identity with the other begomoviruses occurring in the Indian subcontinent. The closest identity (84.40 %) of the virus isolates was with Tomato leaf curl Sri Lanka virus (ToLCLKV). The results support that a new begomovirus species is affecting chilli in Sri Lanka and the name Chilli leaf curl Sri Lanka virus (ChiLCSLV) is proposed. Recombination analysis indicated that ChiLCSLV was a recombinant virus potentially originated from the begomoviruses prevailing in southern India and Sri Lanka. The genome of betasatellite associated with the two isolates consisted of 1366 and 1371 nucleotides and shared 95.2 % sequence identity with each other and 41.50–73.70 % sequence identity with the other betasatellite species. The results suggest that a new begomovirus betasatellite, Chilli leaf curl Sri Lanka betasatellite is associated with LCDC in Sri Lanka. This study demonstrates a new species of begomovirus and betasatellite complex is occurring in chilli in Sri Lanka and further shows that diverse begomovirus species are affecting chilli production in the Indian subcontinent.     

Rapid rule out of myocardial infarction with the use of copeptin as a biomarker for cardiac injury

Copeptin is a non‐specific marker of an endogenous stress response. A dual biomarker marker approach involving the simultaneous use of troponin and copeptin assays may assist early exclusion of acute coronary syndrome in Australian emergency departments. The utility and limitations of this approach are discussed.     

Improved nanocomposite of montmorillonite and hydroxyapatite for defluoridation of water

A novel hydroxyapatite montmorillonite (HAP-MMT) nanocomposite system was synthesized using a simple wet chemical in situ precipitation method. Neat nano hydroxyapatite (HAP) was also synthesized for comparison. The characterization of the materials was carried out using Fourier Transform Infrared Spectroscopy (FT-IR), Scanning Electron Microscopy (SEM), X-ray diffraction (XRD) and Brunauer–Emmett–Teller (BET) isotherms to study the functional groups, morphology, crystallinity and the surface area respectively. Batch adsorption studies and kinetic studies on fluoride adsorption were conducted for the HAP-MMT system and for neat HAP. The effect of parameters such as contact time, pH, initial concentration, temperature, and thermodynamic parameters and the effect of coexisting ions on fluoride adsorption by HAP-MMT were studied. Results of the isotherm experiments were fitted to four adsorption isotherm models namely Langmuir, Freundlich, Temkin and Dubinin Radushkevich. Fluoride adsorption over HAP-MMT fitted to the Freundlich adsorption isotherm model and showed more than two-fold improved adsorption capacity (16.7 mg g⁻¹) compared to neat HAP. The best-fitting kinetic model for both adsorbents was found to be pseudo second order. Calculated thermodynamic parameters indicated that the fluoride adsorption by HAP-MMT is more favorable compared to that on HAP within the temperature range of 27 °C–60 °C. Improved fluoride adsorption by HAP-MMT is attributed to the exfoliated nature of HAP-MMT. Gravity filtration studies carried out using a 1.5 ppm fluoride solution, which is closer to the ground water fluoride concentrations of Chronic Kidney Disease of unknown etiology (CKDu) affected areas in Sri Lanka, resulted in a 1600 ml g⁻¹ break through volume indicating the potential of HAP-MMT to be used in real applications.

A novel hydroxyapatite montmorillonite (HAP-MMT) nanocomposite was synthesized using a simple wet chemical in situ precipitation method. This nanocomposite showed improved adsorption properties towards fluoride ions in water.     

Molecular mechanisms for the regulation of histone mRNA stem-loop–binding protein by phosphorylation

Replication-dependent histone mRNAs end with a conserved stem loop that is recognized by stem-loop–binding protein (SLBP). The minimal RNA-processing domain of SLBP is phosphorylated at an internal threonine, and Drosophila SLBP (dSLBP) also is phosphorylated at four serines in its 18-aa C-terminal tail. We show that phosphorylation of dSLBP increases RNA-binding affinity dramatically, and we use structural and biophysical analyses of dSLBP and a crystal structure of human SLBP phosphorylated on the internal threonine to understand the striking improvement in RNA binding. Together these results suggest that, although the C-terminal tail of dSLBP does not contact the RNA, phosphorylation of the tail promotes SLBP conformations competent for RNA binding and thereby appears to reduce the entropic penalty for the association. Increased negative charge in this C-terminal tail balances positively charged residues, allowing a more compact ensemble of structures in the absence of RNA.Histone synthesis increases at the beginning of S-phase to package newly replicated DNA with histone proteins, but synthesis must be shut down rapidly and histone mRNA degraded at the end of DNA replication because of the toxicity of surplus histone proteins (1, 2). This cyclic demand for histones requires strict regulation, which is achieved mainly by controlling the synthesis and degradation of histone mRNA (3). Replication-dependent histone mRNAs are the only known cellular mRNAs that are not polyadenylated and instead end with a conserved stem loop (4). Histone mRNAs are generated from longer histone pre-mRNAs as a result of an endonucleolytic cleavage between the stem loop and a purine-rich downstream sequence termed the “histone downstream element” (HDE) (5).Stem-loop–binding protein (SLBP), also known as “hairpin-binding protein” (6), binds to the histone mRNA stem loop, and U7 small nuclear ribonucleoprotein binds to the HDE (7). Other factors, including the endonuclease CPSF-73, are involved in both polyadenylation and histone mRNA 3′-end processing (8–11). In mammalian nuclear extracts, SLBP is not absolutely required for the biochemical reaction of processing (12). In contrast, cleavage of histone pre-mRNA in Drosophila cells and nuclear extracts requires the binding of SLBP to the stem loop (10, 13).The minimal histone mRNA processing domain of Drosophila SLBP contains a 72-aa RNA-binding domain (RBD) unique to SLBPs and an 18-aa C-terminal region (Fig. 1A) (14). This RNA-processing domain (RPD) is necessary and sufficient for histone mRNA 3′-end processing in vitro (15). The RBDs of human SLBP (hSLBP) and Drosophila SLBP (dSLBP) are phosphorylated at a Thr residue in a conserved TPNK motif (16, 17). The recent crystal structure of hSLBP RBD in complex with histone mRNA stem loop and 3′ hExo, a 3′–5′ exonuclease required for histone mRNA degradation, provided the first molecular insights into the architecture of this complex, and revealed how the hSLBP RBD forms a new RNA-binding motif to interact with the stem-loop RNA (18). On the other hand, how SLBP alone interacts with the RNA or how this interaction might be affected by phosphorylation of the TPNK motif is not known.Open in a separate windowFig. 1.Schematic of the domain architecture of dSLBP (Upper) and amino acid sequence alignment of RPDs of Drosophila and human SLBP (Lower). Domains of SLBP include the N-terminal domain (NTD), RBD, and C-terminal region (C). Amino acid sequences are shown with the RBD sequence in the top two rows and the C-terminal region in the bottom row. T230 in the TPNK motif and phosphorylation sites in the C-terminal region are indicated with boldface and asterisks, respectively; the residues involved in RNA binding are shown in cyan; and acidic residues in the C-terminal region are shown in red.The C-terminal region of dSLBP contains a motif, SNSDSDSD, whose hyperphosphorylation is required for efficient processing of histone pre-mRNA (15). Despite the similarity of hSLBP and dSLBP RBDs (55% identical residues) and their ability to bind identical stem-loop RNA sequences, neither SLBP can substitute for the other to process histone pre-mRNA in nuclear extracts; in fact, hSLBP inhibits processing of Drosophila histone pre-mRNA (15). This incompatibility results from differences in the C-terminal region (Fig. 1). The sequence C-terminal to the RBD in hSLBP is required for processing, but it is longer, has no similarity to the Drosophila sequence, and lacks phosphorylation sites.Here we focused on dSLBP and showed that phosphorylation greatly increases dSLBP binding affinity for the histone mRNA stem loop. Mimicking phosphorylation of the dSLBP RPD by mutation of phosphorylation sites to Glu residues at both the TPNK motif and the C-terminal region also boosted binding affinity relative to the nonphosphorylated dSLBP RPD. Structural studies of both the human and Drosophila SLBP RPD indicated that phosphorylation of the TPNK motif stabilizes the RNA-binding domain, but the C-terminal region is flexible in the protein:RNA complex and does not contact the RNA. Instead, we show that the increased negative charge in the C-terminal region of the dSLBP RPD results in a more compact ensemble of protein conformations in the absence of RNA, thereby increasing RNA-binding affinity by reducing the entropy of the unbound protein.