Genomic structure of human lysosomal glycosylasparaginase

AbstractThe gene structure of the human lysosomal enzyme glycosylasparaginase was determined. The gene spans 13 kb and consists of 9 exons. Both 5′ and 3′ untranslated regions of the gene are uninterrupted by introns. A number of transcriptional elements were identified in the 5′ upstream sequence that includes two putative CAAT boxes followed by TATA-like sequences together with two AP-2 binding sites and one for Sp1. A 100 bp CpG island and several ETF binding sites were also found. Additional AP-2 and Sp1 binding sites are present in the first intron. Two polyadenylation sites are present and appear to be functional. The major known glycosylasparaginase gene defect G488→C, which causes the lysosomal storage disease aspartylglycosaminuria (AGU) in Finland, is located in exon 4. Exon 5 encodes the post-translational cleavage site for the formation of the mature α/β subunits of the enzyme as well as a recently proposed active site threonine, Thr206

In Situ Observation of Dicalcium Phosphate Monohydrate Formation and Phase Transformation

Calcium orthophosphates (CaPs), as important minerals in biomineralization and biomedicine, have attracted wide attention. Dicalcium phosphate monohydrate (DCPM, CaHPO4·H2O), the recently discovered crystalline CaP phase, has a higher metastability than dihydrate (DCPD, CaHPO4·2H2O) and anhydrate (DCPA, CaHPO4), which may lead to many potential applications in functional biomaterial development. However, the preparation of large-sized DCPM and the underlying mechanisms of its formation and phase evolution remain unclear. Herein, for the first time, we propose a method to prepare micrometer-sized DCPM under an acidic water–methanol mixture and using in situ time-resolved atomic force microscopy further explore its crystallization via dissolution of an acidic amorphous calcium phosphate. In support of the potential role of DCPM as the biomaterial, we demonstrate that DCPM can quickly evolve into more stable octacalcium phosphate in a near-physiological solution. This work provides a mechanistic understanding of the formation and phase transformation of DCPM, which may serve as a basis for subsequent synthesis and application of DCPM as functional biomaterials

Direct Observation of Alginate-Promoted Soil Phosphorus Availability

Phosphorus (P) is a nonrenewable resource with low availability in soils and thus can be a yield-limiting factor for food production. Alginate from brown algae has been proved to be a promising fertilizer additive to promote P utilization efficiency so as to achieve sustainable P management. However, there has been a lack of direct observation of how alginate promotes P availability due to the complexity of the soil system. Here, by combining in situ atomic force microscopy (AFM) and Raman spectroscopy, we in real time observed the nanoscale phase transformation kinetics of amorphous P-bearing minerals (APM) (Fe–P and Ca–P) prepared with the addition of alginate before (treatment II) and after (treatment I) the synthesis of APM. The surface of crystalline P-bearing minerals (CPM) derived from the phase transformation of APM without alginate addition showed obvious nanoscale etch pits after exposure to alginate-bearing solutions at mineral–water interfaces, indicating the solubilization of coprecipitated P, which was then quantified through batch dissolution experiments. Overall, the results revealed that alginate delayed the phase transformation of APM and enhanced the dissolution of CPM in a concentration-dependent or polymerization degree-dependent manner to retain plant-available forms of P. In addition, treatment II could more significantly delay the phase transformation than treatment I. AFM-based dynamic force spectroscopy (DFS) suggested that, consistent with the formation of molecular organomineral bonding, alginate with a higher polymerization degree had a higher binding energy to P-bearing minerals, which would contribute to APM stabilization and CPM dissolution through stronger alginate–mineral interactions. These findings provide direct evidence for the P availability-promoting effect of alginate as an additive as well as some guidance for the better design of P fertilizer additives to achieve sustainable P management in agriculture

Direct Nanoscale Imaging of Calcium Oxalate Crystallization on Brushite Reveals the Mechanisms Underlying Stone Formation

A mixture of calcium oxalate and calcium phosphate is a source of chronic human disease, forming kidney stones. However, the mechanisms of pathological biomineralization and its modulation by natural inhibitors such as osteopontin (OPN) proteins are poorly defined at the nanoscale. Here, the in vitro formation of calcium oxalate monohydrate (COM) concretions having brushite nidi is observed using in situ atomic force microscopy (AFM) in a simulated acidic urinary milieu. We quantify the dissolution kinetics of the [101]_<i>Cc</i>, [1̅00]_<i>Cc</i>, and [101̅]_<i>Cc</i> steps on the brushite (CaHPO₄·2H₂O, DCPD) (010) surfaces by oxalate, two urinary constituents. In support of clinical observations, we further demonstrate the inhibitory effect of phosphorylated OPN peptides on the step retreat rates through step-specific interactions, this in turn regulating the kinetics of COM nucleation and aggregation at the expense of brushite crystals by means of the interfacial mineral replacement reactions. The definition of respective roles for DCPD and OPN peptides thereby offers general insights concerning the control of kidney stone formation and the mechanisms through which aberrant crystallization kinetics is inhibited

Controlled Preparation of Cross-Linked SnO₂ Hollow Nanotube Networks for Electrocatalytic CO₂ Reduction

The electrochemical system based on water, CO2, and electricity is the key technology to realize the coexistence and combination of renewable energy and fossil energy, which can convert CO2 molecules into high-value-added products under mild and controlled conditions, thus achieving carbon neutrality. Designing efficient electrocatalysts to realize highly active, selective, and stable CO2RR has become one of the vital issues. Particularly, the nanostructure design and interface adjustment of electrocatalysts have been regarded as the key points for improving their catalytic performance. Herein, a tin dioxide hollow nanotube (SnO2 HNT) catalyst with a three-dimensional cross-linked network structure has been fabricated by electrospinning and rapid-heating calcination. The morphology and component structure of SnO2 HNTs were analyzed by a series of characterizations. The performance in electrocatalytic carbon dioxide reduction reaction (eCO2RR) was further tested. Owing to the hollow nanostructure, the catalyst possessed a large specific surface area and abundant active sites, which greatly accelerated mass transport and electron mobility. During eCO2RR, SnO2 HNTs achieved a peak faraday efficiency value of 87.4% for C1 products at −1.1 V vs RHE, which significantly suppressed the occurrence of hydrogen evolution side reactions. In addition, compared with the commercial SnO2 nanoparticles or partially reduced Sn/SnO2, the catalytic activity and selectivity of CO2-to-formate conversion significantly increased under the same potential, indicating that the optimization of electronic/geometric structure for high-yield metal oxides can effectively improve the comprehensive performance of eCO2RR

Vincentz et al., 2017, PLoS Genetics.pdf

The left ventricle of the heart drives blood flow throughout the body. Impaired left ventricle function, associated either with heart failure or with certain, severe cardiac birth defects, constitutes a significant cause of mortality. Understanding how heart muscle grows is vital to developing improved treatments for these diseases. Unfortunately, genetic tools necessary to study the left ventricle have been lacking. Here we engineer the first mouse line to enable specific genetic study of the left ventricle. We show that, unlike in the adult heart, the embryonic left ventricle is remarkably tolerant of cell death, as remaining cells have the capacity to proliferate and to restore heart function. Conversely, disruption of two related genes, Hand1 and Hand2, within the left ventricle causes cells to assume the wrong identity, and to consequently overgrow and impair cardiac function. Ablation of these mutant cells rescues heart function. We conclude that selective removal of defective heart muscle and replacement with healthy cells may provide an effective therapy to treat heart failure. </div

MoS2 nanosheets supported on hollow carbon spheres as efficient catalysts for electrochemical hydrogen evolution reaction

Hybridizing structured carbon materials with MoS2 has been demonstrated to be an effective method to increase the electrochemical hydrogen evolution reaction (HER) activity and durability of MoS2. In this study, we report the growth of MoS2 nanosheets on the surface of uniform hollow carbon spheres (HCS) to form a hydrangea-like nanocomposite. The HCS were formed through carbonization of a phenol formaldehyde template, and the MoS2 nanosheets were grown on the HCS surfaces through a hydrothermal method. The nanocomposites have the advantages of significantly improved electrical conductivity, ease of varying the MoS2 loading, and minimizing stacking of MoS2 nanosheets, which are manifested by their remarkably improved HER performance. The well-tuned carbon−MoS2 composite shows a Tafel slope of 48.9 mV dec−1, an onset potential of −0.079 V (vs reversible hydrogen electrode), and an overpotential of 126 mV at the current density of 10 mA cm−2 after 1000 potential cycles.</p

Experimental investigation of the hydrodynamic field around a half-cone woody debris jam on a bridge pier

A debris jam causes extra load and associated scour on a bridge pier, and this significantly affects the safety of the bridge. Laboratory experiments were conducted to investigate the flow field around half-cone shaped debris jams of equal size, following the geometry in previous field studies, but with different surface roughness. The debris jams were assembled using dowels or by 3D printing. The results indicate three zones were observed behind the debris jam: the wake dead zone, high shear transition zone, and accelerated high-speed zone. A debris jam enlarges the dead zone while Reynolds shear stress was greatest in the transition zone for all debris jam cases. Additionally, the drag coefficient of debris jams built by dowels was greater compared with the 3D-printed debris jam, attributed to the debris jam roughness. In summary, debris jams form the wake dead zone behind the pier, increase downward flow in front of the pier, and enhance flow acceleration around the pier, highlighting the potential hazards to bridge safety.</p

Datasheet1_Limb-salvage surgery versus extremity amputation for early-stage bone cancer in the extremities: a population-based study.docx

BackgroundMany attempts have been made to induce limb salvage as an alternative to amputation for primary bone cancer in the extremities, but efforts to establish its benefits over amputation yielded inconsistent results with regard to outcomes and functional recovery. This study aimed to investigate the prevalence and therapeutic efficiency of limb-salvage tumor resection in patients with primary bone cancer in the extremities, and to compare it with extremity amputation.MethodsPatients diagnosed with T1-T2/N0/M0 primary bone cancer in the extremities between 2004 and 2019 were retrospectively identified from the Surveillance, Epidemiology, and End Results program database. Cox regression models were used to test for statistical differences between overall survival (OS) and disease-specific survival (DSS). The cumulative mortality rates (CMRs) for non-cancer comorbidities were also estimated. The evidence level in this study was Level IV.ResultsA total of 2,852 patients with primary bone cancer in the extremities were included in this study, among which 707 died during the study period. Of the patients, 72.6% and 20.4% underwent limb-salvage resection and extremity amputation, respectively. In patients with T1/T2-stage bone tumors in the extremities, limb-salvage resection was associated with significantly better OS and DSS than extremity amputation (OS: adjusted HR, 0.63; 95% confidence interval [CI], 0.55–0.77; p ConclusionLimb-salvage resection exhibited excellent oncological superiority for T1/2-stage primary bone tumors in the extremities. We recommend that patients with resectable primary bone tumors in the extremities undergo limb-salvage surgery as the first choice of treatment.</p

Multifunctionality of Silicified Nanoshells at Cell Interfaces of <i>Oryza sativa</i>

The mimic and design of artificial nanoshell materials on individual cells have been explored in microbial and mammalian cells, and these synthetic interfacial materials can confer new and unique properties on living cells to resist various environmental stresses. However, no attempts have been made toward chemical nanoencapsulation of higher plant cells. Here, we cultivated rice (<i>Oryza sativa</i>) single cells whose cell walls were silicified identically by mimicking diatom biomineralization. Results show that the silica nanoshell at the cell interface is effective at adsorbing cadmium (Cd²⁺) ions by in situ noninvasive microtest technology to quantitatively measure Cd²⁺ ion fluxes, rapidly sequestering and immobilizing Cd ions in the silicified cell walls with adsorption fluxes 6- to 10-times greater than those of the unsilicified cell walls. This, therefore, confers increased Cd tolerance by inhibiting Cd ion uptake into cells. In addition, using in situ atomic force microscopy to probe cell mechanical properties, the cell walls are remarkably strong by virtue of the material properties of the silica nanoshells that physically protects the cells against mechanical challenges. Chemically silicified cells may have acquired a multifunctionality of co-optimized mechanical protection and heavy metal detoxification by organic–inorganic composite materials of the silicified cell walls