CRL Ubiquitin Ligases and DNA Damage Response

Cullin/RING ubiquitin ligases (CRL) comprise the largest subfamily of ubiquitin ligases. CRLs are involved in cell cycle regulation, DNA replication, DNA damage response (DDR), development, immune response, transcriptional regulation, circadian rhythm, viral infection, and protein quality control. One of the main functions of CRLs is to regulate the DDR, a fundamental signaling cascade that maintains genome integrity. In this review, we will discuss the regulation of CRL ubiquitin ligases and their roles in control of the DDR

Structure of human tryptophanyl-tRNA synthetase in complex with tRNA(Trp) reveals the molecular basis of tRNA recognition and specificity

Aminoacyl-tRNA synthetases (aaRSs) are a family of enzymes responsible for the covalent link of amino acids to their cognate tRNAs. The selectivity and species-specificity in the recognitions of both amino acid and tRNA by aaRSs play a vital role in maintaining the fidelity of protein synthesis. We report here the first crystal structure of human tryptophanyl-tRNA synthetase (hTrpRS) in complex with tRNA(Trp) and Trp which, together with biochemical data, reveals the molecular basis of a novel tRNA binding and recognition mechanism. hTrpRS recognizes the tRNA acceptor arm from the major groove; however, the 3′ end CCA of the tRNA makes a sharp turn to bind at the active site with a deformed conformation. The discriminator base A73 is specifically recognized by an α-helix of the unique N-terminal domain and the anticodon loop by an α-helix insertion of the C-terminal domain. The N-terminal domain appears to be involved in Trp activation, but not essential for tRNA binding and acylation. Structural and sequence comparisons suggest that this novel tRNA binding and recognition mechanism is very likely shared by other archaeal and eukaryotic TrpRSs, but not by bacterial TrpRSs. Our findings provide insights into the molecular basis of tRNA specificity and species-specificity

A peak capacitor current pulse-train controlled buck converter with fast transient response and a wide load range

It is known that ripple-based control of a switching dc-dc converter benefits from a faster transient response than a conventional PWM control switching dc-dc converter. However, ripple-based control switching dc-dc converters may suffer from fast-scale oscillation. In order to achieve fast transient response and ensure stable operation of a switching dc-dc converter over a wide load range, based on a conventional pulse train control technique, a peak capacitor current pulse train (PCC-PT) control technique is proposed in this paper. With a buck converter as an example, the operating modes, steady-state performance and transient respond performance of a PCC-PT controlled buck converter are presented and assessed. To eliminate fast-scale oscillation, circuit and control parameter design consideration are given. An accurate discrete iteration model of a PCC-PT controlled buck converter is established, based on which, the effects of circuit parameters on stability of converter operating in a DCM mode, mixed DCM-CCM mode, and CCM mode are studied. Simulation and experimental results are presented to verify the analysis results

Analyses of the Global Multilocus Genotypes of the Human Pathogenic Yeast Candida tropicalis

Candida tropicalis is a globally distributed human pathogenic yeast, especially prevalent in tropical and sub-tropical regions. Over the last several decades, a large number of studies have been published on the genetic diversity and molecular epidemiology of C. tropicalis from different parts of the world. However, the global pattern of genetic variation remains largely unknown. Here we analyzed the published multilocus sequence data at six loci for 876 isolates from 16 countries representing five continents. Our results showed that 280 of the 2677 (10.5%) analyzed nucleotides were polymorphic, resulting in a mean of 82 (a range of 38–150) genotypes per locus and a total of 633 combined diploid sequence types (DSTs). Among these, 93 combined DSTs were shared by 336 strains, including 10 by strains from different continents. Analysis of Molecular Variance (AMOVA) showed that 89% of the observed genetic variations were found within regional and national populations while < 10% was due to among-country separations. Pairwise geographic population analyses showed overall low but statistically significant genetic differentiation between most geographic populations, with the Singaporean and Indian populations being the most distinct from other populations. However, the Mantel test showed no significant correlation between genetic distance and geographic distance among the geographic populations. Consistent with high genetic variation within and limited variations among geographic populations, results from STRUCTURE analyses showed that the 876 isolates could be grouped into 15 genetic clusters, with each cluster having a broad geographic distribution. Together, our results suggest frequent gene flows among certain regional, national, and continental populations of C. tropicalis, resulting in abundant regional and national genetic diversities of this important human fungal pathogen

Hashimoto’s encephalopathy cases: Chinese experience

BACKGROUND: Hashimoto’s encephalopathy is a poorly understood syndrome consisting of heterogeneous neurological symptoms and high serum antithyroid antibody titers, typically responding to steroids. More clinical series studies are required to characterize the clinical, laboratory and imaging features, and outcomes, especially in the Chinese population. METHODS: We analyzed the clinical, laboratory, and imaging features and outcomes of thirteen consecutive patients with Hashimoto’s encephalopathy diagnosed in Xuan Wu Hospital, Beijing from 2005 to 2010 retrospectively. RESULTS: Cognitive impairment (84.6%) and psychiatric symptoms (38.5%) were the most frequent symptoms. Seizures (30.8%) and myoclonus (7.7%) were less common than previously described. Three (23.1%) patients showed abnormal signals in hippocampus or temporal lobe, which were believed related to their memory disorders or seizures. MRI changes showed resolution paralleling clinical improvement in one patient. Among eight patients who received steroid therapy, five patients recovered, one patient improved with residual deficits, and two patients relapsed or had no effect. Among five non-steroid treated patients, three patients experienced stable remission with antiepileptic drugs or general neurotrophic therapy, and two patients experienced continuous deterioration. CONCLUSIONS: Most patients with Hashimoto’s encephalopathy showed good response to steroids. Some patients improved without steroid therapy. Considering its reversible course, we recommend that Hashimoto’s encephalopathy should always be in the differential diagnosis while evaluating disorders of the central nervous system

Aboveground Biomass and Soil Moisture as Affected by Short-Term Grazing Exclusion in Eastern Alpine Meadows of the Qinghai-Tibet Plateau, China

Heavy grazing substantially influences grassland vegetation and animal nutrition on the Qinghai-Tibet plateau (Guo et al. 2003). Degradation is characterized by a reduction in vegetation height, reduced ground cover decrease in species diversity (Wang et al. 2007). The objective of this study was to determine the effects of short-term exclusion from grazing on aboveground herbage, forage nutritive value, and soil moisture in an alpine meadow in the eastern zone of the plateau. Three farms, applying different intensity of grazing over the summer months, were compared

Modeling dust sources, transport, and radiative effects at different altitudes over the Tibetan Plateau

Mineral dust plays an important role in the climate of the Tibetan Plateau (TP) by modifying the radiation budget, cloud macro- and microphysics, precipitation, and snow albedo. Meanwhile, the TP, with the highest topography in the world, can affect intercontinental transport of dust plumes and induce typical distribution characteristics of dust at different altitudes. In this study, we conduct a quasi-global simulation to investigate the characteristics of dust source contribution and transport over the TP at different altitudes by using a fully coupled meteorology–chemistry model, the Weather Research and Forecasting model with chemistry (WRF-Chem), with a tracer-tagging technique. Generally, the simulation reasonably captures the spatial distribution of satellite-retrieved dust aerosol optical depth (AOD) at different altitudes. Model results show that dust particles are emitted into atmosphere through updrafts over major desert regions and then transported to the TP. The East Asian dust (mainly from the Gobi and Taklamakan deserts) is transported southward and is lifted up to the TP, contributing a mass loading of 50 mg m−2 at a height of 3 km and 5 mg m−2 at a height of 12 km over the northern slope of the TP. Dust from North Africa and the Middle East are concentrated over both of the northern and southern slopes below 6 km, where mass loadings range from 10 to 100 and 1 to 10 mg m−2 below 3 km and above 9 km, respectively. As the dust is transported to the north and over the TP, mass loadings are 5–10 mg m−2 above a height of 6 km. The dust mass flux carried from East Asia to the TP is 7.9 Tg yr−1, mostly occurring at heights of 3–6 km. The dust particles from North Africa and the Middle East are transported eastward following the westerly jet and then are carried into the TP at the west side with dust mass fluxes of 7.8 and 26.6 Tg yr−1, respectively. The maximum mass flux of the North African dust mainly occurs at 0–3 km (3.9 Tg yr−1), while the Middle Eastern dust occurs at 6–9 km (12.3 Tg yr−1). The dust outflow occurs on the east side (−17.89 Tg yr−1) and south side (−11.22 Tg yr−1) of the TP, with a peak value (8.7 Tg yr−1) at 6–9 km. Moreover, the dust (by mass) is concentrated within the size range of 1.25–5.0 µm and the dust (by particle number) is concentrated in the size range of 0.156–1.25 µm. Compared with other aerosols, the dust contributes to more than 50 % of the total AOD over the TP. The direct radiative forcing induced by the dust is −1.28 W m−2 at the top of the atmosphere (cooling), 0.41 W m−2 in the atmosphere (warming), and −1.68 W m−2 at the surface (cooling). Our quantitative analyses of the dust contributions from different source regions and the associated radiative forcing can help us to better understand the role of dust on the climate over the TP and surrounding regions

Heterogeneous ice nucleation correlates with bulk-like interfacial water

Establishing a direct correlation between interfacial water and heterogeneous ice nucleation (HIN) is essential for understanding the mechanism of ice nucleation. Here, we study the HIN efficiency of polyvinyl alcohol (PVA) surfaces with different densities of hydroxyl groups. We find that the HIN efficiency increases with the decrease of the hydroxyl group density. By explicitly considering that interfacial water molecules of PVA films consist of ‘tightly bound water’, ‘bound water’ and ‘bulk-like water’, we reveal that ‘bulk-like water’ can be correlated directly to the HIN efficiency of surfaces. As the density of hydroxyl groups decreases, ‘bulk-like water’ molecules can rearrange themselves with a reduced energy barrier into ice due to the diminishing constraint by the hydroxyl groups on the PVA surface. Our study not only provides a new strategy on experimentally controlling HIN efficiency but also gives another perspective in understanding the mechanism of ice nucleation, i.e., the phase change efficiency of ‘bulk-like’ interfacial water of a film is a predictor for the HIN efficiency of that film