The 2017 Mw 7.3 Sarpol Zahāb Earthquake, Iran: A compact blind shallow-dipping thrust event in the mountain front fault basement

The 12 November 2017 Mw 7.3 Sarpol Zahāb earthquake is one of the largest events to have occurred in the north-western Zagros fold-and-thrust belt during the instrumental period. We use teleseismic and synthetic aperture radar data to study the earthquake source parameters, rupture process and active tectonic characteristics of the event. We find that both data sets individually produce remarkably similar slip distribution, indicative of buried faulting that is consistent with the lack of significant surface rupture. Through the joint inversion of satellite radar and teleseismic data, we find that the rupture propagated rapidly (~3.2 km/s) and asymmetrically along strike to the south, but relatively slowly (~1.5 km/s) in the updip direction, and formed a single large-slip asperity with a peak slip value close to 5 m. Given the regional tectonic context of the distribution of known faults and lithologies, we suggest that the maximum slip is either located in the lowest sedimentary cover or the uppermost basement of the Mountain Front Fault

The 2017 Mw 7.3 Sarpol Zahāb Earthquake, Iran: A compact blind shallow-dipping thrust event in the mountain front fault basement

The 12 November 2017 Mw 7.3 Sarpol Zahāb earthquake is one of the largest events to have occurred in the north-western Zagros fold-and-thrust belt during the instrumental period. We use teleseismic and synthetic aperture radar data to study the earthquake source parameters, rupture process and active tectonic characteristics of the event. We find that both data sets individually produce remarkably similar slip distribution, indicative of buried faulting that is consistent with the lack of significant surface rupture. Through the joint inversion of satellite radar and teleseismic data, we find that the rupture propagated rapidly (~3.2 km/s) and asymmetrically along strike to the south, but relatively slowly (~1.5 km/s) in the updip direction, and formed a single large-slip asperity with a peak slip value close to 5 m. Given the regional tectonic context of the distribution of known faults and lithologies, we suggest that the maximum slip is either located in the lowest sedimentary cover or the uppermost basement of the Mountain Front Fault

Cytokines induced memory-like NK cells engineered to express CD19 CAR exhibit enhanced responses against B cell malignancies

CD19 chimeric antigen receptor (CAR) engineered NK cells have been used for treating patients with relapsed and/or refractory B cell malignancies and show encouraging outcomes and safety profile. However, the poor persistence of NK cells remains a major challenge for CAR NK cell therapy. Memory-like NK cells (MLNK) induced by IL-12, IL-15, and IL-18 have shown enhanced and prolonged responses to tumor re-stimulation, making them an attractive candidate for adoptive cellular immunotherapy. Here, we show efficient and stable gene delivery of CD19 CAR to memory-like NK cells using retroviral vectors with transduction efficiency comparable to those achieved with conventional NK cells. Analysis of surface molecules revealed a distinct phenotypic profile in CAR engineered memory-like NK cells (CAR MLNK), as evidenced by increased expression of CD94 and downregulation of NKp30 as well as KIR2DL1. Compared to conventional CAR NK cells, CAR MLNK cells exhibited significantly increased IFN-γ production and degranulation in response to CD19+ target cells, resulting in enhanced cytotoxic activity against CD19+ leukemia cells and lymphoma cells. Furthermore, memory properties induced by IL-12/-15/-18 improved the in vivo persistence of CAR MLNK cells and significantly suppressed tumor growth in a exnograft mouse model of lymphoma, leading to prolonged survival of CD19+ tumor-bearing mouse. Altogether, our data indicate that CD19 CAR engineered memory-like NK cells exhibited superior persistence and antitumor activity against CD19+ tumors, which might be an attractive approach for treating patient with relapse or refractory B cell malignancies

ZEB2 Mediates Multiple Pathways Regulating Cell Proliferation, Migration, Invasion, and Apoptosis in Glioma

BACKGROUND: The aim of the present study was to analyze the expression of Zinc finger E-box Binding homeobox 2 (ZEB2) in glioma and to explore the molecular mechanisms of ZEB2 that regulate cell proliferation, migration, invasion, and apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: Expression of ZEB2 in 90 clinicopathologically characterized glioma patients was analyzed by immunohistochemistry. Furthermore, siRNA targeting ZEB2 was transfected into U251 and U87 glioma cell lines in vitro and proliferation, migration, invasion, and apoptosis were examined separately by MTT assay, Transwell chamber assay, flow cytometry, and western blot. RESULTS: The expression level of ZEB2 protein was significantly increased in glioma tissues compared to normal brain tissues (P<0.001). In addition, high levels of ZEB2 protein were positively correlated with pathology grade classification (P = 0.024) of glioma patients. Knockdown of ZEB2 by siRNA suppressed cell proliferation, migration and invasion, as well as induced cell apoptosis in glioma cells. Furthermore, ZEB2 downregulation was accompanied by decreased expression of CDK4/6, Cyclin D1, Cyclin E, E2F1, and c-myc, while p15 and p21 were upregulated. Lowered expression of ZEB2 enhanced E-cadherin levels but also inhibited β-Catenin, Vimentin, N-cadherin, and Snail expression. Several apoptosis-related regulators such as Caspase-3, Caspase-6, Caspase-9, and Cleaved-PARP were activated while PARP was inhibited after ZEB2 siRNA treatment. CONCLUSION: Overexpression of ZEB2 is an unfavorable factor that may facilitate glioma progression. Knockdown ZEB2 expression by siRNA suppressed cell proliferation, migration, invasion and promoted cell apoptosis in glioma cells

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Genome-Wide Screening for Pathogenic Proteins and microRNAs Associated with Parasite&ndash;Host Interactions in Trypanosoma brucei

Tsetse flies are a type of blood-sucking insect living in diverse locations in sub-Saharan Africa. These insects can transmit the unicellular parasite Trypanosoma brucei (T. brucei) which causes African trypanosomiasis in mammals. There remain huge unmet needs for prevention, early detection, and effective treatments for this disease. Currently, few studies have investigated the molecular mechanisms of parasite&ndash;host interactions underlying African trypanosomiasis, mainly due to a lack of understanding of the T. brucei genome. In this study, we dissected the genomic and transcriptomic profiles of T. brucei by annotating the genome and analyzing the gene expression. We found about 5% of T. brucei proteins in the human proteome, while more than 80% of T. brucei protein in other trypanosomes. Sequence alignment analysis showed that 142 protein homologs were shared among T. brucei and mammalian genomes. We identified several novel proteins with pathogenic potential supported by their molecular functions in T. brucei, including 24 RNA-binding proteins and six variant surface glycoproteins. In addition, 26 novel microRNAs were characterized, among which five miRNAs were not found in the mammalian genomes. Topology analysis of the miRNA-gene network revealed three genes (RPS27A, UBA52 and GAPDH) involved in the regulation of critical pathways related to the development of African trypanosomiasis. In conclusion, our work opens a new door to understanding the parasite&ndash;host interaction mechanisms by resolving the genome and transcriptome of T. brucei

Oxygen Plasma Technology-Assisted Preparation of Three-Dimensional Reduced Graphene Oxide/Polypyrrole/Strontium Composite Scaffold for Repair of Bone Defects Caused by Osteoporosis

Repairs of bone defects caused by osteoporosis have always relied on bone tissue engineering. However, the preparation of composite tissue engineering scaffolds with a three-dimensional (3D) macroporous structure poses huge challenges in achieving osteoconduction and osteoinduction for repairing bone defects caused by osteoporosis. In the current study, a three-dimensional macroporous (150–300 μm) reduced graphene oxide/polypyrrole composite scaffold modified by strontium (Sr) (3D rGO/PPY/Sr) was successfully prepared using the oxygen plasma technology-assisted method, which is simple, safe, and inexpensive. The findings of the MTT assay and AO/EB fluorescence double staining showed that 3D rGO/PPY/Sr has a good biocompatibility and effectively promoted MC3T3-E1 cell proliferation. Furthermore, the ALP assay and alizarin red staining showed that 3D rGO/PPY/Sr increased the expression levels of ALP activity and the formation of calcified nodules. The desirable biocompatibility, osteoconduction, and osteoinduction abilities, assure that the 3D macroporous rGO/PPY/Sr composite scaffold offers promising potential for use in the repair of bone defects caused by osteoporosis in bone tissue engineering