Retroviral restriction factor TRIM5alpha is a trimer

The retrovirus restriction factor TRIM5alpha targets the viral capsid soon after entry. Here we show that the TRIM5alpha protein oligomerizes into trimers. The TRIM5alpha coiled-coil and B30.2(SPRY) domains make important contributions to the formation and/or stability of the trimers. A functionally defective TRIM5alpha mutant with the RING and B-box 2 domains deleted can form heterotrimers with wild-type TRIM5alpha, accounting for the observed dominant-negative activity of the mutant protein. Trimerization potentially allows TRIM5alpha to interact with threefold pseudosymmetrical structures on retroviral capsids.     

MicroRNA‐31a‐5p from aging BMSCs links bone formation and resorption in the aged bone marrow microenvironment

The alteration of age‐related molecules in the bone marrow microenvironment is one of the driving forces in osteoporosis. These molecules inhibit bone formation and promote bone resorption by regulating osteoblastic and osteoclastic activity, contributing to age‐related bone loss. Here, we observed that the level of microRNA‐31a‐5p (miR‐31a‐5p) was significantly increased in bone marrow stromal cells (BMSCs) from aged rats, and these BMSCs demonstrated increased adipogenesis and aging phenotypes as well as decreased osteogenesis and stemness. We used the gain‐of‐function and knockdown approach to delineate the roles of miR‐31a‐5p in osteogenic differentiation by assessing the decrease of special AT‐rich sequence‐binding protein 2 (SATB2) levels and the aging of BMSCs by regulating the decline of E2F2 and recruiting senescence‐associated heterochromatin foci (SAHF). Notably, expression of miR‐31a‐5p, which promotes osteoclastogenesis and bone resorption, was markedly higher in BMSCs‐derived exosomes from aged rats compared to those from young rats, and suppression of exosomal miR‐31a‐5p inhibited the differentiation and function of osteoclasts, as shown by elevated RhoA activity. Moreover, using antagomiR‐31a‐5p, we observed that, in the bone marrow microenvironment, inhibition of miR‐31a‐5p prevented bone loss and decreased the osteoclastic activity of aged rats. Collectively, our results reveal that miR‐31a‐5p acts as a key modulator in the age‐related bone marrow microenvironment by influencing osteoblastic and osteoclastic differentiation and that it may be a potential therapeutic target for age‐related osteoporosis.     

OhsR acts as an organic peroxide-sensing transcriptional activator using an <Emphasis Type="Italic">S</Emphasis>-mycothiolation mechanism in <Emphasis Type="Italic">Corynebacterium glutamicum</Emphasis>

Background

Corynebacterium glutamicum is a well-known producer of various l-amino acids in industry. During the fermenting process, C. glutamicum unavoidably encounters oxidative stress due to a specific reactive oxygen species (ROS) produced by consistent adverse conditions. To combat the ROS, C. glutamicum has developed many common disulfide bond-based regulatory devices to control a specific set of antioxidant genes. However, nothing is known about the mixed disulfide between the protein thiol groups and the mycothiol (MSH) (S-mycothiolation)-based sensor. In addition, no OhrR (organic hydroperoxide resistance regulator) homologs and none of the organic hydroperoxide reductase (Ohr) sensors have been described in the alkyl hydroperoxide reductase CF-missing C. glutamicum, while organic hydroperoxides (OHPs)-specific Ohr was a core detoxification system.

Results

In this study, we showed that the C. glutamicum OhsR acted as an OHPs sensor that activated ohr expression. OhsR conferred resistance to cumene hydroperoxide (CHP) and t-butyl hydroperoxide but not H₂O₂, hypochlorous acid, and diamide; this outcome was substantiated by the fact that the ohsR-deficient mutant was sensitive to OHPs but not inorganic peroxides. The DNA binding activity of OhsR was specifically activated by CHP. Mutational analysis of the two cysteines (Cys125 and Cys261) showed that Cys125 was primarily responsible for the activation of DNA binding. The oxidation of Cys125 produced a sulfenic acid (C125-SOH) that subsequently reacted with MSH to generate S-mycothiolation that was required to activate the ohr expression. Therefore, OhsR regulated the ohr expression using an S-mycothiolation mechanism in vivo.

Conclusion

This is the first report demonstrating that the regulatory OhsR specifically sensed OHPs stress and responded to it by activating a specific ohr gene under its control using an S-mycothiolated mechanism.

     

Mapping QTL for Omega-3 Content in Hybrid Saline Tilapia

Tilapia is one of most important foodfish species. The low omega-3 to omega-6 fatty acid ratio in freshwater tilapia meat is disadvantageous for human health. Increasing omega-3 content is an important task in breeding to increase the nutritional value of tilapia. However, conventional breeding to increase omega-3 content is difficult and slow. To accelerate the increase of omega-3 through marker-assisted selection (MAS), we conducted QTL mapping for fatty acid contents and profiles in a F₂ family of saline tilapia generated by crossing red tilapia and Mozambique tilapia. The total omega-3 content in F₂ hybrid tilapia was 2.5 ± 1.0 mg/g, higher than that (2.00 mg/g) in freshwater tilapia. Genotyping by sequencing (GBS) technology was used to discover and genotype SNP markers, and microsatellites were also genotyped. We constructed a linkage map with 784 markers (151 microsatellites and 633 SNPs). The linkage map was 2076.7 cM long and consisted of 22 linkage groups. Significant and suggestive QTL for total lipid content were mapped on six linkage groups (LG3, -4, -6, -8, -13, and -15) and explained 5.8–8.3% of the phenotypic variance. QTL for omega-3 fatty acids were located on four LGs (LG11, -18, -19, and -20) and explained 5.0 to 7.5% of the phenotypic variance. Our data suggest that the total lipid and omega-3 fatty acid content were determined by multiple genes in tilapia. The markers flanking the QTL for omega-3 fatty acids can be used in MAS to accelerate the genetic improvements of these traits in salt-tolerant tilapia.     

Is the proportion of clonal species higher at higher latitudes in Australia?

We provide a large‐scale quantification of the relationship between latitude and the proportion of species with clonal reproduction. Parasite pressure is thought to be higher at low latitudes, while abiotic stress is thought to be higher at high latitudes. We therefore predicted that there would be a higher proportion of clonal species at high latitudes than at low latitudes. We collected data of 4386 native seed plant species from 446 genera and 99 families present in ABRSFlora of Australia. Species' occurrence records were taken from the Atlas of Living Australia, including 817 450 species‐site combinations spanning 34.5° of latitude. Logistic regression showed that the proportion of clonal species significantly increased with latitude, rising from 3.3% clonal species at 9.25°S to 26.7% clonal species at 43.75°S. The overall average proportion of clonal species in Australian seed plants was 9.4%. This study adds to our growing understanding of dramatic latitudinal gradients in the way plants grow and reproduce. It also reveals that Australian vegetation contains a relatively low proportion of clonally reproducing species.     

Optimization of Cell Disruption and Transesterification of Lipids from <Emphasis Type="Italic">Botryococcus braunii</Emphasis> LB572

Several methods including microwave, Frenchpress, autoclave, bead-beating, ultrasonication, and osmotic shock were compared to identify the most effective microalgal cell disruption method. Botryococcus braunii LB572 was cultured in 5 L flasks containing JM medium mixed with oceanic sediment extract for 13 days. Among the methods tested, enhanced lipid extraction was achieved through microwave treatment (2450MHz, 1250W at 150°C for 20 min). Oleic (C18:1), linolenic (C18:3), and palmitic acids (C16:0) were found to be the major fatty acids among the C14-C24 acids from extracted lipid. In addition, the optimal conditions of transesterification were as follows: 70 mL of methanol, 6 mL of sulfuric acid, 8 mL of chloroform, and boiling at 100°C for 30 min; 85.4% of C14-C24 FAME and 78.5% of C16-C18 FAME were esterified from transesterifiable lipids.     

Effects of Salt Stress on Photosynthetic Pigments and Activity of Ribulose-1,5-bisphosphate Carboxylase/Oxygenase in <Emphasis Type="Italic">Kalidium foliatum</Emphasis>

The effects of NaCl and Na₂SO₄ on photosynthetic pigments, malondialdehyde (MDA), Rubisco activity and superoxide dismutase (SOD) activity were investigated in Kalidium foliatum (Pall.) Moq., which is distributed in the saline soil of Hetao irrigation area in Inner Mongolia China. The K. foliatum plants were treated with NaCl (0, 100, 250, 400 and 500 mM), Na₂SO₄ (0, 100, 250, 400 and 500 mM) and NaCl + Na₂SO₄ (1: 1, v/v) (0, 100, 250, 400 and 500 mM of Na⁺ concentration, 0, 50, 125, 200 and 250 mM of Cl^– and SO ₄ ^2– concentration) for 10 days. Content of chlorophylls and carotenoids were significantly higher than control at increasing NaCl and Na₂SO₄ concentration, in contrast, were significantly reduced by higher concentration of NaCl + Na₂SO₄. Rubisco activity reduced steadily at 100 and 250 mM NaCl, while increased at 400 and 500 mM NaCl. Rubisco activity was significantly higher than control at 100 mM Na₂SO₄, and was no more change under NaCl + Na₂SO₄ treatment. The SOD activity increased with increasing NaCl and Na₂SO₄, and increased at moderate NaCl + Na₂SO₄ treatment. MDA content was lower than control at 250 mM salt concentration. On the basis of the data obtained, K. foliatum showed resistance to salt such as Na⁺, Cl^–and SO ₄ ^2– , Rubisco activity in K. foliatum might be more sensitive to salt.     

Engineering Temperature‐Dependent Carrier Concentration in Bulk Composite Materials via Temperature‐Dependent Fermi Level Offset

Precise control of carrier concentration in both bulk and thin‐film materials is crucial for many solid‐state devices, including photovoltaic cells, superconductors, and high mobility transistors. For applications that span a wide temperature range (thermoelectric power generation being a prime example) the optimal carrier concentration varies as a function of temperature. This work presents a modified modulation doping method to engineer the temperature dependence of the carrier concentration by incorporating a nanosize secondary phase that controls the temperature‐dependent doping in the bulk matrix. This study demonstrates this technique by de‐doping the heavily defect‐doped degenerate semiconductor GeTe, thereby enhancing its average power factor by 100% at low temperatures, with no deterioration at high temperatures. This can be a general method to improve the average thermoelectric performance of many other materials.     

Professor Hu Zhihong: The New President of the Society for Invertebrate Pathology

正The Society for Invertebrate Pathology (SIP) is foremost in the world covering all aspects of related research in insect virology, bacteriology, mycology, parasitology and microbial control. The SIP has a wide scientific appeal with members from many countries spanning every continent in the globe. Election of members to the Society’s Governing     

Safety and Efficacy of Apatinib Combined with Temozolomide in Advanced Melanoma Patients after Conventional Treatment Failure

OBJECTIVE: Asian melanoma patients, predominantly comprised of acral and mucosal subtypes, might not benefit from immunotherapy and targeted therapy as much as Caucasian patients. Novel treatment strategies are demanded after conventional treatment failure. This was a prospective, single-arm, and single-center dose escalation study to investigate the safety and preliminary efficacy of apatinib combined with temozolomide in heavily treated advanced melanoma patients. METHODS: Patients were sequentially admitted to four dose-escalating groups of apatinib and temozolomide (three cases in each group) using a traditional 3?+?3 dose escalation design method. RESULTS: Twelve patients were enrolled between December 2016 and August 2017. Most patients with an acral or mucosal primary origin progressed after immunotherapy or targeted therapy. Dose escalation had been completed without dose-limiting toxicity. Common adverse events included hypertension, hand-foot syndrome, proteinuria, neutropenia, nausea, and fatigue. All adverse events were grade 1 or 2, while the maximum tolerated dose was not reached. Up to January 2018, 1 patient achieved partial response, 9 experienced stable disease, and 2 exhibited progressive disease. The objective response rate and disease control rate were 8.3% and 83%, respectively. CONCLUSIONS: In conclusion, apatinib combined with temozolomide was well tolerated and has demonstrated efficacy in advanced melanoma patients.