Beryllium-10 surface exposure dating of offset moraines on one branch of the Karakorum Fault west of the Gar basin yields a long-term (140- to 20-thousand-year) right-lateral slip rate of ~10.7 ± 0.7 ...millimeters per year. This rate is 10 times larger than that inferred from recent InSAR analyses (~1 ± 3 millimeters per year) that span ~8 years and sample all branches of the fault. The difference in slip-rate determinations suggests that large rate fluctuations may exist over centennial or millennial time scales. Such fluctuations would be consistent with mechanical coupling between the seismogenic, brittle-creep, and ductile shear sections of faults that reach deep into the crust.
Middle East respiratory syndrome coronavirus (MERS-CoV) causes a zoonotic respiratory disease of global public health concern, and dromedary camels are the only proven source of zoonotic infection. ...Although MERS-CoV infection is ubiquitous in dromedaries across Africa as well as in the Arabian Peninsula, zoonotic disease appears confined to the Arabian Peninsula. MERS-CoVs from Africa have hitherto been poorly studied. We genetically and phenotypically characterized MERS-CoV from dromedaries sampled in Morocco, Burkina Faso, Nigeria, and Ethiopia. Viruses from Africa (clade C) are phylogenetically distinct from contemporary viruses from the Arabian Peninsula (clades A and B) but remain antigenically similar in microneutralization tests. Viruses from West (Nigeria, Burkina Faso) and North (Morocco) Africa form a subclade, C1, that shares clade-defining genetic signatures including deletions in the accessory gene ORF4b. Compared with human and camel MERS-CoV from Saudi Arabia, virus isolates from Burkina Faso (BF785) and Nigeria (Nig1657) had lower virus replication competence in Calu-3 cells and in ex vivo cultures of human bronchus and lung. BF785 replicated to lower titer in lungs of human DPP4-transduced mice. A reverse genetics-derived recombinant MERS-CoV (EMC) lacking ORF4b elicited higher type I and III IFN responses than the isogenic EMC virus in Calu-3 cells. However, ORF4b deletions may not be the major determinant of the reduced replication competence of BF785 and Nig1657. Genetic and phenotypic differences in West African viruses may be relevant to zoonotic potential. There is an urgent need for studies of MERS-CoV at the animal–human interface.
The presence of ~NS‐trending rifts within the Tibetan Plateau attests that it is undergoing ~EW extension. In southern Tibet, the total extension rate, distributed across seven main rifts over a ...distance of ~1,000 km, has been inferred to amount to about half of the shortening rate across the Himalayas. Quantifying the late Quaternary extension rates across the largest rift (Yadong‐Gulu rift YGR) is important to understand Tibetan deformation and to discuss the high plateau evolution during the later stages of continental collision. We performed 10Be surface‐exposure cosmogenic nuclide dating of 57 samples from three fluvial surfaces and two moraines that are vertically offset by the normal faults bounding the northern YGR. After carefully assessing individual ages at each site, to elucidate scatter in the age distributions, we obtained ~EW extension rates of up to 3–6 mm/yr near the northern end of the rift (Gulu) and of only 1.3 ± 0.3 mm/yr in the south (Yangbajing). The fast rates in the north may be influenced by dextral slip along the Beng Co fault, whose rate ought to be at least 6.0 ± 1.8 mm/yr. The total late Quaternary extension rate of 9 ± 2 mm/yr we infer across southern Tibet between ~81°E and 92°E, assuming similar rates across each rift, is similar to earlier, qualitative inferences and consistent with recent geodetic results. Distinct deformation rates north and south of the Bangong‐Nujiang suture may reflect significant differences between the extensional kinematics and mechanisms across the Qiangtang and Lhasa blocks.
Key Points
Extension rates along Yadong‐Gulu rift decrease from north (3–6 mm/yr) to south (~1.3 mm/yr) due to Beng Co dextral faulting
The post‐250 ka extension rate across the ~1,000 km stretch of South Tibet north of Nepal is 9 ± 2 mm/yr, consistent with geodetic rates
The causes and mechanisms of eastward extension south and north of the Bangong‐Nujiang suture are different
Thrusting implication in the crustal thickening history of eastern Tibet is highly debated. The ∼250 km‐long Muli thrust of the Yalong thrust belt in SE Tibet is a major Miocene structure with a ...pronounced topographic step (∼2,000 m). Using thermo‐kinematic modeling based on thermochronology data, we constrain the crustal geometry of the thrust as being steep (>70°) at the surface, in agreement with field observations, and flattening at depth (≥20 km) on an intra‐crustal décollement. Thrusting motion on the fault shows a velocity of 0.2 ± 0.06 km/Ma since 50 Ma, followed by an acceleration at a rate of 0.6 ± 0.08 km/Ma starting at 12.5 ± 1 Ma, yielding a total of ∼15 km of exhumed crust. Deeper, deformation may be localized through a ductile shear zone, and be related to the ∼15 km Moho step and shear wave velocity contrast imaged by tomography beneath the Yalong thrust belt.
Plain Language Summary
The India‐Eurasia collision (∼50 million years ago Ma) led to the formation of the Tibetan Plateau, the world's largest and highest orogenic plateau. The formation and evolution of such a unique geological feature has been one of the main controversies in Earth Sciences for decades, especially regarding the role of faulting in the thickening of the crust. Here, we present 3D thermo‐kinematic models of thermochronology data allowing to constrain the exhumation history of the Muli thrust fault, a ∼250 km‐long major structure of the SE Tibetan margin, linked to significant steps in surface topography and in crustal boundary at depth (Moho). We constrain a steep fault (>70°) within the upper crust, consistent with field observations, that flattens at depth (≥20 km). The Muli thrust presents rapid thrusting motion (0.6 ± 0.08 km/Ma) that initiated at ∼12.5 Ma, following a slower phase (0.2 ± 0.06 km/Ma) since 50 Ma, with total rock exhumation of ∼15 km. This underlines the important role of thrust faulting in the thickening of the SE Tibetan crust.
Key Points
Thermo‐kinematic modeling of Muli thrust, a major thrust fault of SE Tibetan Plateau
15 km crust exhumation in 50 Ma on a high‐angle (>70°) ramp—décollement fault linked to thickening of SE Tibetan crust
Fault related to significant Moho step and shear wave velocity contrast in deep crust suggests entire crust implication
Genetic recombination has frequently been observed in coronaviruses. Here, we sequenced multiple complete genomes of dromedary camel coronavirus HKU23 (DcCoV-HKU23) from Nigeria, Morocco, and ...Ethiopia and identified several genomic positions indicative of cross-species virus recombination events among other betacoronaviruses of the subgenus Embecovirus (clade A beta-CoVs). Recombinant fragments of a rabbit coronavirus (RbCoV-HKU14) were identified at the hemagglutinin esterase gene position. Homolog fragments of a rodent CoV were also observed at 8.9-kDa open reading frame 4a at the 3' end of the spike gene. The patterns of recombination differed geographically across the African region, highlighting a mosaic structure of DcCoV-HKU23 genomes circulating in dromedaries. Our results highlighted active recombination of coronaviruses circulating in dromedaries and are also relevant to the emergence and evolution of other betacoronaviruses, including Middle East respiratory syndrome coronavirus (MERS-CoV).
Genetic recombination is often demonstrated in coronaviruses and can result in host range expansion or alteration in tissue tropism. Here, we showed interspecies events of recombination of an endemic dromedary camel coronavirus, HKU23, with other clade A betacoronaviruses. Our results supported the possibility that the zoonotic pathogen MERS-CoV, which also cocirculates in the same camel species, may have undergone similar recombination events facilitating its emergence or may do so in its future evolution.
The intestinal mucus layer plays a key role in the maintenance of host-microbiota homeostasis. To document the crosstalk between the host and microbiota, we used gnotobiotic models to study the ...influence of two major commensal bacteria, Bacteroides thetaiotaomicron and Faecalibacterium prausnitzii, on this intestinal mucus layer. B. thetaiotaomicron is known to use polysaccharides from mucus, but its effect on goblet cells has not been addressed so far. F. prausnitzii is of particular physiological importance because it can be considered as a sensor and a marker of human health. We determined whether B. thetaiotaomicron affected goblet cell differentiation, mucin synthesis and glycosylation in the colonic epithelium. We then investigated how F. prausnitzii influenced the colonic epithelial responses to B. thetaiotaomicron.
B. thetaiotaomicron, an acetate producer, increased goblet cell differentiation, expression of mucus-related genes and the ratio of sialylated to sulfated mucins in mono-associated rats. B. thetaiotaomicron, therefore, stimulates the secretory lineage, favoring mucus production. When B. thetaiotaomicron was associated with F. prausnitzii, an acetate consumer and a butyrate producer, the effects on goblet cells and mucin glycosylation were diminished. F. prausnitzii, by attenuating the effects of B. thetaiotaomicron on mucus, may help the epithelium to maintain appropriate proportions of different cell types of the secretory lineage. Using a mucus-producing cell line, we showed that acetate up-regulated KLF4, a transcription factor involved in goblet cell differentiation.
B. thetaiotaomicron and F. prausnitzii, which are metabolically complementary, modulate, in vivo, the intestinal mucus barrier by modifying goblet cells and mucin glycosylation. Our study reveals the importance of the balance between two main commensal bacteria in maintaining colonic epithelial homeostasis via their respective effects on mucus.
Significance
The absence of zoonotic MERS-CoV in Africa in spite of an abundance of MERS-CoV–infected dromedaries has remained an enigma. We demonstrate that geographically and genetically distinct ...viruses from Africa have low replication competence in the human lung, providing a possible explanation for the absence of severe MERS disease in Africa. The findings suggest that MERS-CoV now entrenched in the Arabian Peninsula has acquired increased pathogenic potential for humans. We demonstrate that the spike protein contributes to this phenotypic difference. If pathogenic clade B viruses from the Arabian Peninsula are introduced into Africa, they are likely to become dominant, as they have in the Arabian Peninsula, and to be associated with adverse health impacts in Africa and increased pandemic threat.
Coronaviruses are pathogens of pandemic potential. Middle East respiratory syndrome coronavirus (MERS-CoV) causes a zoonotic respiratory disease of global public health concern, and dromedary camels are the only proven source of zoonotic infection. More than 70% of MERS-CoV–infected dromedaries are found in East, North, and West Africa, but zoonotic MERS disease is only reported from the Arabian Peninsula. We compared viral replication competence of clade A and B viruses from the Arabian Peninsula with genetically diverse clade C viruses found in East (Egypt, Kenya, and Ethiopia), North (Morocco), and West (Nigeria and Burkina Faso) Africa. Viruses from Africa had lower replication competence in ex vivo cultures of the human lung and in lungs of experimentally infected human-DPP4 (hDPP4) knockin mice. We used lentivirus pseudotypes expressing MERS-CoV spike from Saudi Arabian clade A prototype strain (EMC) or African clade C1.1 viruses and demonstrated that clade C1.1 spike was associated with reduced virus entry into the respiratory epithelial cell line Calu-3. Isogenic EMC viruses with spike protein from EMC or clade C1.1 generated by reverse genetics showed that the clade C1.1 spike was associated with reduced virus replication competence in Calu-3 cells in vitro, in ex vivo human bronchus, and in lungs of hDPP4 knockin mice in vivo. These findings may explain why zoonotic MERS disease has not been reported from Africa so far, despite exposure to and infection with MERS-CoV.
Field evidence for syn-deformation migmatization and crystallization along the Karakorum fault contradicts the study of Wang et al. (2012). The ages of such magmatic rocks provide minimum ages for ...the onset of deformation at ∼23Ma in North Ayilari and ∼19Ma in Tangtse. The onset of deformation at 12Ma in the Ayilari range inferred by Wang et al. (2012) from a muscovite Ar/Ar age is a cooling age, thus only a minimum age. The ∼60Ma granodiorite bodies, the ophiolitic rocks and the south Kailash thrust that are correlated across the fault to provide a 52±2km finite offset do not define reliable piercing points. Such observations as well as our previous work concur to show that the Karakorum fault initiated in the Oligo-Miocene, and has a long-term dextral slip-rate between 7.5 and 13mm/yr, approximately twice that proposed by Wang et al. (2012).
Middle East respiratory syndrome coronavirus (MERS-CoV) is enzootic in dromedary camels and causes zoonotic infection and disease in humans. Although over 80% of the global population of infected ...dromedary camels are found in Africa, zoonotic disease had only been reported in the Arabia Peninsula and travel-associated disease has been reported elsewhere. In this study, genetic diversity and molecular epidemiology of MERS-CoV in dromedary camels in Ethiopia were investigated during 2017-2020. Of 1766 nasal swab samples collected, 61 (3.5%) were detected positive for MERS-CoV RNA. Of 484 turbinate swab samples collected, 10 (2.1%) were detected positive for MERS-CoV RNA. Twenty-five whole genome sequences were obtained from these MERS-CoV positive samples. Phylogenetically, these Ethiopian camel-originated MERS-CoV belonged to clade C2, clustering with other East African camel strains. Virus sequences from camel herds clustered geographically while in an abattoir, two distinct phylogenetic clusters of MERS-CoVs were observed in two sequential sampling collections, which indicates the greater genetic diversity of MERS-CoV in abattoirs. In contrast to clade A and B viruses from the Arabian Peninsula, clade C camel-originated MERS-CoV from Ethiopia had various nucleotide insertions and deletions in non-structural gene nsp3, accessory genes ORF3 and ORF5 and structural gene N. This study demonstrates the genetic instability of MERS-CoV in dromedaries in East Africa, which indicates that the virus is still actively adapting to its camel host. The impact of the observed nucleotide insertions and deletions on virus evolution, viral fitness, and zoonotic potential deserves further study.
18F-FDG-PET/CT is recommended to improve the diagnosis of prosthetic valve infective endocarditis (PVIE) and is a major criterion in the ESC-2015 classification. However, there is little evidence for ...its usefulness in the follow-up of medically treated PVIE patients.
A monocentric retrospective analysis of patients hospitalized for PVIE between January 2013 and December 2019 who were not treated with surgery and who had at least two 18F-FDG-PET/CT examinations during their medical management.
Among 170 patients with PVIE, 117 were treated with antibiotic therapy but no surgery. Of these, 36 (31%) had at least two 18F-FDG-PET/CT examinations. At initial imaging, 28 patients had heterogeneous FDG uptake on their prosthetic valve and eight on their associated aortic graft. Hypermetabolism of spleen and bone marrow (HSBM) was observed in 18 and 19 patients, respectively. At the first follow-up 18F-FDG-PET/CT, 21 (58%) patients still had heterogeneous uptake, indicating persistent active endocarditis. HSBM was still present at the last follow-up imaging in four of the six patients with recurrent PVIE.
18F-FDG-PET/CT monitoring of medically treated patients with PVIE provides valuable additional information and prospective multicentric study should be conducted to assess its usefulness.
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