Emergence of B.1.524(G) SARS-CoV-2 in Malaysia during the third COVID-19 epidemic wave

The COVID-19 pandemic first emerged in Malaysia in Jan 2020. As of 12th Sept 2021, 1,979,698 COVID-19 cases that occurred over three major epidemic waves were confirmed. The virus contributing to the three epidemic waves has not been well-studied. We sequenced the genome of 22 SARS-CoV-2 strains detected in Malaysia during the second and the ongoing third wave of the COVID-19 epidemic. Detailed phylogenetic and genetic variation analyses of the SARS-CoV-2 isolate genomes were performed using these newly determined sequences and all other available sequences. Results from the analyses suggested multiple independent introductions of SARS-CoV-2 into Malaysia. A new B.1.524(G) lineage with S-D614G mutation was detected in Sabah, East Malaysia and Selangor, Peninsular Malaysia on 7th October 2020 and 14th October 2020, respectively. This new B.1.524(G) group was not the direct descendant of any of the previously detected lineages. The new B.1.524(G) carried a set of genetic variations, including A701V (position variant frequency = 0.0007) in Spike protein and a novel G114T mutation at the 5’UTR. The biological importance of the specific mutations remained unknown. The sequential appearance of the mutations, however, suggests that the spread of the new B.1.524(G) lineages likely begun in Sabah and then spread to Selangor. The findings presented here support the importance of SARS-CoV-2 full genome sequencing as a tool to establish an epidemiological link between cases or clusters of COVID-19 worldwide.

Primary Immune Thrombocytopenia and Essential Thrombocythemia: So Different and yet Somehow Similar—Cases Series and a Review of the Literature

This article collects several published cases in which immune thrombocytopenic purpura (ITP) is followed by essential thrombocythemia (ET) and vice versa. This surprising clinical condition is possible, but very rare and difficult to diagnose and manage. We have made an attempt to analyse the possible causes of the sequential appearance of ITP and ET taking into consideration the following: alteration of the thrombopoietin (TPO) receptor, the role of autoimmunity and inflammation, and cytokine modulation. A better understanding of these interactions may provide opportunities to determine predisposing factors and aid in finding new treatment modalities both for ITP and ET patients.

Chemoprevention of Pancreatic Cancer by Inhibition of Glutathione-S Transferase P1

Pancreatic cancer is among the most refractory malignancies with poor prognosis. Thus, preventive approaches, in addition to the development of novel therapeutic strategies are essential for this type of cancer. KRAS mutations occur very early in the development of pancreatic cancers and could be targeted for its prevention, yet specific inhibitors for mutated KRAS are lacking. Accordingly, Glutathione-S Transferase p1 (GSTP1), which we recently found to be an autocrine stimulator of mutated KRAS signaling, is predicted to be an alternative target for chemoprevention of pancreatic cancer. In this study, chemopreventive effects of O-Hexadecyl-γ-glutamyl-S-benzyl-cysteinyl-D-phenyl glycine-Ethylester (HGBPE), which we previously synthesized to inhibit GSTP1 activity, was analyzed for its effect on the prevention of a rat pancreatic carcinogenesis model induced by 7,12-dimethyl-benzanthracene (DMBA). Rats administered with DMBA were grouped into five cohorts. In the treated group I, which was treated neither with HGBPE nor vehicle, sequential appearance of precancerous lesions, ductal complexes, and adenocarcinoma was confirmed as previously reported. We also confirmed in this group that mutations of KRAS and expression of GSTP1 simultaneously occurred in the ductal complex. To rats of groups II and IV, HGBPE was administered, and vehicle to those of group III and V. In groups of II and IV, the incidence of both ductal complex and adenocarcinoma were significantly lower than those in groups III and V. These data clearly suggest the efficacy of HGBP as a potential chemopreventive agent for pancreatic cancer.

The development of rapidly progressive glomerulonephritis associated with both antineutrophil cytoplasmic antibody-associated vasculitis and anti-glomerular basement membrane nephritis in the course of nontuberculous mycobacterium infection: a case report

Background Antineutrophil cytoplasmic antibodies (ANCA) and Anti-glomerular basement membrane (GBM) antibodies often induce rapidly progressive glomerulonephritis (RPGN). Some reports have demonstrated RPGN with the sequential appearance of ANCA then anti-GBM antibodies, suggesting that ANCA may induce the development of anti-GBM antibodies. Whereas, many reports have shown that the development of ANCA is associated with various infectious diseases, such as non-tuberculous mycobacterial infection. Case presentation A 65-year-old woman with pulmonary non-tuberculous mycobacterial (NTM) infection was monitored without treatment. One year later, serum myeloperoxidase (MPO)- ANCA were elevated (14.1 U/mL (normal value < 3.0 U/ml)). A high fever and RPGN appeared 1 year later, and serum MPO-ANCAs were 94.1 U/mL. Anti-GBM antibodies were also detected. A renal biopsy revealed crescentic glomerulonephritis with linear deposits of IgG and C3c along the GBM and interstitial inflammation with endarteritis of arterioles. The diagnosis was RPGN associated with anti-GBM nephritis and ANCA-associated vasculitis. Conclusion This report shows that preceding NTM infection may have induced ANCA and anti-GBM antibodies and caused the development of RPGN.

UHT Metamorphism Peaking Above 1100 °C with Slow Cooling: Insights from Pelitic Granulites in the Jining Complex, North China Craton

The peak temperature and duration of ultrahigh-temperature (UHT) metamorphism are critical to identify and understand its tectonic environment. The UHT metamorphism of the Jining complex in the Khondalite Belt, North China Craton is controversial on the peak temperature, time and tectonic setting. A representative sapphirine-bearing granulite sample is selected from the classic Tianpishan outcrop for addressing the metamorphic evolution and timing. The rock is markedly heterogeneous on centimetre scale and can be divided into melanocratic domains rich in sillimanite (MD-s) or rich in orthopyroxene (MD-o), and leucocratic domains (LD). On the basis of detailed petrographic analyses and phase equilibria modelling using THERMOCALC, all three types of domains record peak temperatures of 1120–1140 °C and a series of post-peak cooling stages at 0·8–0·9 GPa to the fluid-absent solidus (∼890 °C), followed by sub-solidus decompression. The peak temperature for MD-s is constrained by the coexistence of sillimanite-I + sapphirine + spinel + quartz, where sillimanite-I contains densely exsolved aciculae of hematite, yielding reintegrated Fe2O3 contents up to 2·1–2·3 wt %. The post-peak cooling evolution involves the sequential appearance of K-feldspar, sillimanite-II + garnet, orthopyroxene and biotite, where sillimanite-II is exsolution-free and contains variable Fe2O3 contents of 1·3–1·8 wt %. The peak temperature for MD-o is constrained by the sapphirine + orthopyroxene assemblage, where orthopyroxene has a maximum AlIV of 0·22 (Al2O3 = 9·5 wt %) in the core. The cooling evolution involves the sequential appearance of K-feldspar, garnet and biotite, and the decreasing AlIV (0·22→0·17) from core to rim in orthopyroxene. The peak temperature for LD is constrained by the inferred K-feldspar-absent assemblage and the maximum anorthite content of 0·11 in K-feldspar. The cooling evolution involves the crystallization of segregated melts, exsolution of supra-solvus ternary feldspars and growth of biotite. The Al in orthopyroxene, Fe2O3 in sillimanite and anorthite in K-feldspar are good indicators for constraining extreme UHT conditions although they depend differently on bulk-rock compositions. In-situ SHRIMP U–Pb dating of metamorphic zircon indicates that the UHT metamorphism may have occurred at &gt;1·94 Ga and the cooling under UHT conditions lasted over 40 Ma. The extreme UHT metamorphism in the Jining complex is interpreted to be triggered by the advective heating of intraplate hyperthermal mafic magmas together with a plume-related hot mantle upwelling, following an orogenic crustal thickening event.

Low rate of somatic mutations in a long-lived oak tree

Because plants do not possess a proper germline, deleterious somatic mutations can be passed to gametes and a large number of cell divisions separating zygote from gamete formation in long-lived plants may lead to many mutations. We sequenced the genome of two terminal branches of a 234-year-old oak tree and found few fixed somatic single-nucleotide variants (SNVs), whose sequential appearance in the tree could be traced along nested sectors of younger branches. Our data suggest that stem cells of shoot meristems are robustly protected from accumulation of mutations in trees.