“山水林田湖草沙生命共同体”耦合框架、模型与展望

“山水林田湖草沙生命共同体”系统保护与修复是我国生态文明建设的重要内容。明确生命共同体的耦合机制,是科学地进行生态保护和修复工作的关键。针对当前生命共同体耦合机制不清、理论和方法不健全的问题,从耦合的视角出发,在小流域尺度上单一生态系统内部生态要素的耦合、流域尺度上不同生态系统之间的耦合、区域尺度上人与自然的耦合三个方面进行整合,在此基础上探讨了多尺度山水林田湖草沙耦合理论,提出了一般性的山水林田湖草沙耦合理论框架。梳理并比较了当前主要的生态系统模型、景观模型、统计学模型以及复合生态系统的多模型耦合方法,综合提出了一个适用于"山水林田湖草沙生命共同体"耦合研究方法。对进一步完善山水林田湖草沙一体化保护修复提出了建议,包括：一是构建多源信息数据库,推进定量化耦合机制研究;二是开展全生命周期监测与评估,探索适应性治理路径;三是强化多元主体参与,完善协同保护机制。     

Novel molecular variants of the Na-Cl cotransporter gene are responsible for Gitelman syndrome.

A hereditary defect of the distal tubule accounts for the clinical features of Gitelman syndrome (GS), an autosomal recessive disease characterized by hypokalemia, hypomagnesemia, metabolic alkalosis, and hypocalciuria. Recently, we cloned the cDNA coding for the human Na-Cl thiazide-sensitive cotransporter (TSC; also known as ¿NCCT¿ or ¿SLC12A3¿) as a possible candidate for GS, and Simon et al., independently, described mutations in patients with GS. Now, we show 12 additional mutations consistent with a loss of function of the Na-Cl cotransporter in GS. Two missense replacements, R209W and P349L, are common to both studies and could represent ancient mutations. The other mutations include three deletions, two insertions, and six missense mutations. When all mutations from both studies are considered, missense mutations seem to be more frequently localized within the intracellular domains of the molecule, rather than in transmembrane or extracellular domains. One family, previously reported as a GS form with dominant inheritance, has proved to be recessive, with the affected child being a compound heterozygote. A highly informative intragenic tetranucleotide marker, useful for molecular diagnostic studies, has been identified at the acceptor splice site of exon 9.     

Bilateral detection thresholds in dextrals and sinistrals reflect the more sensitive side of the nose, which is not lateralized [published erratum appears in Chem Senses 1998 Dec;23(6):761]

Several fundamental questions remain enigmatic concerning human olfactory sensitivity, including (i) whether detection threshold differences exist between the two sides of the nose (and, if so, whether such differences are influenced by handedness) and (ii) whether bilateral (i.e. binasal) stimulation leads to lower thresholds than unilateral stimulation (and, if so, whether the degree of facilitation is inversely related to general olfactory ability). In this study, and well-validated single staircase procedure was used to establish bilateral and unilateral detection thresholds for the cranial nerve I stimulant phenyl ethyl alcohol in 130 right- and 33 left-handed subjects. No differences in sensitivity between the left and right sides of the nose were observed in either group. Bilateral thresholds were lower, on average, than unilateral thresholds when the latter were categorized in terms of left and right nares. However, the bilateral thresholds did not differ significantly from those of the side of the nose with the lower threshold. Overall smell ability, as measured by the University of Pennsylvania Smell Identification Test, did not interact with any of the test measures. These data imply that (i) the left and right sides of the nose do not systematically differ in detection threshold sensitivity for either dextrals or sinistrals and (ii) if central integration of left:right olfactory threshold sensitivity occurs, its effects do not exceed the function of the better side of the nose.      

云南瓶尔小草属一新种

Ophioglossum yongrenense Ching ex Z. R. He et W. M. Chu, sp. nov.Species nova aspectu inter O. kawamuram Tagawa et O. parvum Nishida et Kurita Japonicae, differt a priore frondibus pro parte laminis sterilibus praeditis (in illa frondibus omnino laminis sterilibus non praeditis), a posteriore frondibus pro parte laminis sterilibus non praeditis (in O. parvo Nishida et Kurita frondibus omino laminis sterilibus praeditis).……     

Polypharmacy in the management of patients with schizophrenia on risperidone in a tertiary-care hospital in Malaysia

The present study was conducted primarily to determine the occurrence of polypharmacy in patients with schizophrenia on risperidone. The secondary aim was to ascertain the incidence of inappropriate prescribing with anticholinergics. A retrospective review of the medical records of all patients who were being followed up at the out-patient clinic of a tertiary-care hospital in Malaysia was conducted. Only patients who were being prescribed risperidone between 1 June 2008 and 31 December 2008 were included in the study. Demographic data such as patient’s age, gender and race were obtained from the patient’s medical records. In total, 113 patients met the selection criteria. Polypharmacy was found to occur in 34 patients (30.09%), with the majority (76.47%) being on two antipsychotics. In total, 27 patients (34.18%) on monotherapy with risperidone were prescribed an anticholinergic on scheduled dosing, while 19 patients (24.05%) were prescribed it on an as-needed basis. Of the patients on polypharmacy, 26 (76.47%) were on scheduled dosing of anticholinergics, while three (8.82%) were taking the medication on an as-needed basis. Polypharmacy should be avoided, and the use of anticholinergics should be closely reviewed. By adopting more efficient prescribing practices, costs can be reduced and financial resources can instead be channelled towards more beneficial areas for the patients.     

Analysis of Uromodulin Polymerization Provides New Insights into the Mechanisms Regulating ZP Domain-mediated Protein Assembly

Uromodulin is the most abundant protein secreted in urine, in which it is found as a high-molecular-weight polymer. Polymerization occurs via its zona pellucida (ZP) domain, a conserved module shared by many extracellular eukaryotic proteins that are able to assemble into matrices. In this work, we identified two motifs in uromodulin, mapping in the linker region of the ZP domain and in between protein cleavage and glycosylphosphatidylinositol (GPI)-anchoring sites, which regulate its polymerization. Indeed, mutations in either module led to premature intracellular polymerization of a soluble uromodulin isoform, demonstrating the inhibitory role of these motifs for ZP domain-mediated protein assembly. Proteolytic cleavage separating the external motif from the mature monomer is necessary to release the inhibitory function and allow protein polymerization. Moreover, we report absent or abnormal assembly into filaments of GPI-anchored uromodulin mutated in either the internal or the external motif. This effect is due to altered processing on the plasma membrane, demonstrating that the presence of the two modules has not only an inhibitory function but also can positively regulate protein polymerization. Our data expand previous knowledge on the control of ZP domain function and suggest a common mechanism regulating polymerization of ZP domain proteins.     

Identification of a new locus for medullary cystic disease, on chromosome 16p12.

Autosomal dominant medullary cystic disease (ADMCKD) is an interstitial nephropathy that has morphologic and clinical features similar to autosomal recessive nephronophthisis. The typical renal dysfunction associated with ADMCKD results mainly from a defect in urinary concentration ability, although results of urinalysis are normal. Recently, a locus on chromosome 1 was associated with ADMCKD, in DNA from two large Cypriot families, and genetic heterogeneity was inferred. We describe the genomewide linkage mapping of a new locus for medullary cystic disease, ADMCKD2, on chromosome 16p12 in a four-generation Italian pedigree. The family with ADMCKD2 fulfills the typical diagnostic criteria of ADMCKD, complicated by hyperuricemia and gouty arthritis. Marker D16S3036 shows a maximum two-point LOD score of 3.68, and the defined critical region spans 10.5 cM, between D16S500 and SCNN1B1-2. Candidate genes included in the critical region are discussed.     

The MRX complex regulates Exo1 resection activity by altering DNA end structure

Homologous recombination is triggered by nucleolytic degradation (resection) of DNA double‐strand breaks (DSBs). DSB resection requires the Mre11‐Rad50‐Xrs2 (MRX) complex, which promotes the activity of Exo1 nuclease through a poorly understood mechanism. Here, we describe the Mre11‐R10T mutant variant that accelerates DSB resection compared to wild‐type Mre11 by potentiating Exo1‐mediated processing. This increased Exo1 resection activity leads to a decreased association of the Ku complex to DSBs and an enhanced DSB resection in G1, indicating that Exo1 has a direct function in preventing Ku association with DSBs. Molecular dynamics simulations show that rotation of the Mre11 capping domains is able to induce unwinding of double‐strand DNA (dsDNA). The R10T substitution causes altered orientation of the Mre11 capping domain that leads to persistent melting of the dsDNA end. We propose that MRX creates a specific DNA end structure that promotes Exo1 resection activity by facilitating the persistence of this nuclease on the DSB ends, uncovering a novel MRX function in DSB resection.