Genome-wide CRISPR Screens Reveal Host Factors Critical for SARS-CoV-2 Infection

1. Download : Download high-res image (212KB)
2. Download : Download full-size image

     

Environmental margin and island evolution in Middle Eastern populations of the Egyptian fruit bat

Here, we present a study of the population genetic architecture and microevolution of the Egyptian fruit bat (Rousettus aegyptiacus) at the environmental margins in the Middle East using mitochondrial sequences and nuclear microsatellites. In contrast to the rather homogenous population structure typical of cave‐dwelling bats in climax tropical ecosystems, a relatively pronounced isolation by distance and population diversification was observed. The evolution of this pattern could be ascribed to the complicated demographic history at higher latitudes related to the range margin fragmentation and complex geomorphology of the studied area. Lineages from East Africa and Arabia show divergent positions. Within the northwestern unit, the most marked pattern of the microsatellite data set is connected with insularity, as demonstrated by the separate status of populations from Saharan oases and Cyprus. These demes also exhibit a reduction in genetic variability, which is presumably connected with founder effects, drift and other potential factors related to island evolution as site‐specific selection. Genetic clustering indicates a semipermeability of the desert barriers in the Sahara and Arabian Peninsula and a corridor role of the Nile Valley. The results emphasize the role of the island environment in restricting the gene flow in megabats, which is also corroborated by biogeographic patterns within the family, and suggests the possibility of nascent island speciation on Cyprus. Demographic analyses suggest that the colonization of the region was connected to the spread of agricultural plants; therefore, the peripatric processes described above might be because of or strengthened by anthropogenic changes in the environment.     

The first lithic industry of mainland Southeast Asia: Evidence of the earliest hominin in a tropical context

Recent discoveries of ancient sites in mainland Southeast Asia confirm the presence of old lithic industries as early as 0.8 Ma, i.e., at the transition between the Early to Middle Pleistocene. Although these open-air sites still require geochronological and biostratigraphic precisions, they allow us to understand the oldest vestiges of human presence in the tropics and the technical orientations chosen by these hominins. This article aims to present an objective and critical synthesis of the material discovered at the main sites. Some sites in Cambodia and Thailand have been the subject of archaeological field missions by the Ministère de l’Europe et des Affaires Étrangères (MEAE). The diversity of lithic tool types and manufacture methods encountered from the Middle Pleistocene in peninsular Asia shows a technical variability that stands out as a counterexample to diffusionist hypotheses of a cultural fabrication inherited from the West. The diversity of production methods, tools, and raw material matrices remains incomparable to those encountered in the West, Africa, or South Asia. To date, only evidence from China has allowed us to put forward the hypothesis of a common technical basis that would have spread from its southern territories; however, this hypothesis is currently under debate. Researchers have proposed the idea of continuous technical progress and the shift from heavy industry to a lighter and polished stone in Southeast Asia. However, the omnipresence of the pebble prevents a clear conclusion because these technical objects from Southeast Asia are quite simply incommensurable; a chopper in these regions may not be comparable with another chopper from the terraces of the Garonne or the Roussillon in France, for example. In other words, these tools are above all ‘tropical’ tools, and they belong to a distant cognitive world(s) with specific use(s), gesture(s), and meaning(s), making it impossible for them to be compared or evaluated by our faculty of Western judgment.     

Cultural conservatism and variability in the Acheulian sequence of Gesher Benot Ya‘aqov

The Acheulian Technocomplex exhibits two phenomena: variability and conservatism. Variability is expressed in the composition and frequencies of tool types, particularly in the varying frequencies of bifaces (handaxes and cleavers). Conservatism is expressed in the continuous presence of bifaces along an immense time trajectory. The site of Gesher Benot Ya‘aqov (GBY) offers a unique opportunity to study aspects of variability and conservatism as a result of its long cultural-stratigraphic sequence containing superimposed lithic assemblages. This study explores aspects of variability and conservatism within the Acheulian lithic assemblages of GBY, with emphasis placed on the bifacial tools. While variability has been studied through a comparison of typological frequencies in a series of assemblages from the site, evidence for conservatism was examined in the production modes expressed by the reduction sequence of the bifaces. We demonstrate that while pronounced typological variability is observed among the GBY assemblages, they were all manufactured by the same technology. The technology, size, and morphology of the bifaces throughout the entire stratigraphic sequence of GBY reflect the strong conservatism of their makers. We conclude that the biface frequency cannot be considered as a chrono/cultural marker that might otherwise allow us to distinguish between different phases within the Acheulian. The variability observed within the assemblages is explained as a result of different activities, tasks, and functions, which were carried out at specific localities along the shores of the paleo-Hula Lake in the early Middle Pleistocene.     

Baicalin positively regulates osteoclast function by activating MAPK/Mitf signalling

Activation of osteoblasts in bone formation and osteoclasts in bone resorption is important during the bone fracture healing process. There has been a long interest in identifying and developing a natural therapy for bone fracture healing. In this study, we investigated the regulation of osteoclast differentiation by baicalin, which is a natural molecule extracted from Eucommiaulmoides (small tree native to China). It was determined that baicalin enhanced osteoclast maturation and bone resorption activity in a dose‐dependent manner. Moreover, this involves the activation of MAPK, increased Mitf nuclear translocation and up‐regulation of downstream osteoclast‐related target genes expression. The baicalin‐induced effect on osteoclast differentiation can be mimicked by specific inhibitors of p‐ERK (U0126) and the Mitf‐specific siRNA, respectively. Protein–ligand docking prediction identified that baicalin might bind to RANK, which is the upstream receptor of p‐ERK/Mitf signalling in osteoclasts. This indicated that RANK might be the binding target of baicalin. In sum, our findings revealed baicalin increased osteoclast maturation and function via p‐ERK/Mitf signalling. In addition, the results suggest that baicalin can potentially be used as a natural product for the treatment of bone fracture.     

Taxonomic significance of short forms of middle Permian Pseudoalbaillella Holdsworth and Jones, 1980 (Follicucullidae,Radiolaria)

Middle Permian Pseudoalbaillella from the Xiaodong area in South China were studied using fossil morphology. Short forms of Pseudoalbaillella fusiformis (Holdsworth and Jones), Pseudoalbaillella internata Wang, and Pseudoalbaillella monacantha (Ishiga and Imoto), characterized by a short and skirt-like pseudoabdomen, were confirmed. We conclude that the short forms were derived from their respective species by breaking off during disruptive processes. If this is true, there may be structurally weakened parts in the pseudoabdomen.     

QCT/FEA predictions of femoral stiffness are strongly affected by boundary condition modeling

Quantitative computed tomography-based finite element models of proximal femora must be validated with cadaveric experiments before using them to assess fracture risk in osteoporotic patients. During validation, it is essential to carefully assess whether the boundary condition (BC) modeling matches the experimental conditions. This study evaluated proximal femur stiffness results predicted by six different BC methods on a sample of 30 cadaveric femora and compared the predictions with experimental data. The average stiffness varied by 280% among the six BCs. Compared with experimental data, the predictions ranged from overestimating the average stiffness by 65% to underestimating it by 41%. In addition, we found that the BC that distributed the load to the contact surfaces similar to the expected contact mechanics predictions had the best agreement with experimental stiffness. We concluded that BC modeling introduced large variations in proximal femora stiffness predictions.     

Modulation of the immune response by Middle East respiratory syndrome coronavirus

Coronavirus (CoV) infections are commonly associated with respiratory and enteric disease in humans and animals. In 2012, a new human disease called Middle East respiratory syndrome (MERS) emerged in the Middle East. MERS was caused by a virus that was originally called human coronavirus-Erasmus Medical Center/2012 but was later renamed as Middle East respiratory syndrome coronavirus (MERS-CoV). MERS-CoV causes high fever, cough, acute respiratory tract infection, and multiorgan dysfunction that may eventually lead to the death of the infected individuals. The exact origin of MERS-CoV remains unknown, but the transmission pattern and evidence from virological studies suggest that dromedary camels are the major reservoir host, from which human infections may sporadically occur through the zoonotic transmission. Human to human transmission also occurs in healthcare facilities and communities. Recent studies on Middle Eastern respiratory continue to highlight the need for further understanding the virus-host interactions that govern disease severity and infection outcome. In this review, we have highlighted the major mechanisms of immune evasion strategies of MERS-CoV. We have demonstrated that M, 4a, 4b proteins and Plppro of MERS-CoV inhibit the type I interferon (IFN) and nuclear factor-κB signaling pathways and therefore facilitate innate immune evasion. In addition, nonstructural protein 4a (NSP4a), NSP4b, and NSP15 inhibit double-stranded RNA sensors. Therefore, the mentioned proteins limit early induction of IFN and cause rapid apoptosis of macrophages. MERS-CoV strongly inhibits the activation of T cells with downregulation of antigen presentation. In addition, uncontrolled secretion of interferon ɣ-induced protein 10 and monocyte chemoattractant protein-1 can suppress proliferation of human myeloid progenitor cells.     

Emergence,evolution, and vaccine production approaches of SARS-CoV-2 virus: Benefits of getting vaccinated and common questions

The emergence of coronavirus disease 2019 (COVID-19) pandemic in Wuhan city, China at the end of 2019 made it urgent to identify the origin of the causal pathogen and its molecular evolution, to appropriately design an effective vaccine. This study analyzes the evolutionary background of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or SARS-2) in accordance with its close relative SARS-CoV (SARS-1), which was emerged in 2002. A comparative genomic and proteomic study was conducted on SARS-2, SARS-1, and Middle East respiratory syndrome coronavirus (MERS), which was emerged in 2012. In silico analysis inferred the genetic variability among the tested viruses. The SARS-1 genome harbored 11 genes encoding 12 proteins, while SARS-2 genome contained only 10 genes encoding for 10 proteins. MERS genome contained 11 genes encoding 11 proteins. The analysis also revealed a slight variation in the whole genome size of SARS-2 comparing to its siblings resulting from sequential insertions and deletions (indels) throughout the viral genome particularly ORF1AB, spike, ORF10 and ORF8. The effective indels were observed in the gene encoding the spike protein that is responsible for viral attachment to the angiotensin-converting enzyme 2 (ACE2) cell receptor and initiating infection. These indels are responsible for the newly emerging COVID-19 variants αCoV, βCoV, γCoV and δCoV. Nowadays, few effective COVID-19 vaccines developed based on spike (S) glycoprotein were approved and become available worldwide. Currently available vaccines can relatively prevent the spread of COVID-19 and suppress the disease. The traditional (killed or attenuated virus vaccine and antibody-based vaccine) and innovated vaccine production technologies (RNA- and DNA-based vaccines and viral vectors) are summarized in this review. We finally highlight the most common questions related to COVID-19 disease and the benefits of getting vaccinated.