Miracle-dz/UniFAR-FTUs huggingface dataset:
Structure-based virtual screening and molecular dynamics simulation of SARS-CoV-2 Guanine-N7 methyltransferase (nsp14) for identifying antiviral inhibitors against COVID-19

Abstract The recent pandemic caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) calls the whole world into a medical emergency. For tackling Coronavirus Disease 2019 (COVID-19), researchers from around the world are swiftly working on designing and identifying inhibitors against all possible viral key protein targets. One of the attractive drug targets is guanine-N7 methyltransferase which plays the main role in capping the 5′-ends of viral genomic RNA and sub genomic RNAs, to escape the host’s innate immunity. We performed homology modeling and molecular dynamic (MD) simulation, in order to understand the molecular architecture of Guanosine-P3-Adenosine-5’,5’-Triphosphate (G3A) binding with C-terminal N7-MTase domain of nsp14 from SARS-CoV-2. The residue Asn388 is highly conserved in present both in N7-MTase from SARS-CoV and SARS-CoV-2 and displays a unique function in G3A binding. For an in-depth understanding of these substrate specificities, we tried to screen and identify inhibitors from the Traditional Chinese Medicine (TCM) database. The combination of several computational approaches, including screening, MM/GBSA, MD simulations, and PCA calculations, provides the screened compounds that readily interact with the G3A binding site of homology modeled N7-MTase domain. Compounds from this screening will have strong potency towards inhibiting the substrate-binding and efficiently hinder the viral 5’-end RNA capping mechanism. We strongly believe the final compounds can become COVID-19 therapeutics, with huge international support. The focus of this study is to screen for antiviral inhibitors blocking guanine-N7 methyltransferase (N7-MTase), one of the key drug targets involved in the first methylation step of the SARS-CoV-2 RNA capping mechanism. Compounds binding the substrate-binding site can interfere with enzyme catalysis and impede 5’-end cap formation, which is crucial to mimic host RNA and evade host cellular immune responses. Therefore, our study proposes the top hit compounds from the Traditional Chinese Medicine (TCM) database using a combination of several computational approaches. Communicated by Ramaswamy H. Sarma.
A Drug Holiday Reduces the Frequency and Severity of Medication‐Related Osteonecrosis of the Jaw in a Minipig Model

Treatment of medication‐related osteonecrosis of the jaw (MRONJ) is challenging and no clear consensus has been achieved. This study investigated preventive measures recommended for tooth extractions under antiresorptive (AR) treatment and the role of discontinuation of AR therapy to avoid the onset of MRONJ in a minipig model. Thirty‐six Göttingen minipigs were divided into four groups. Group 1 (negative control): tooth extractions but no zoledronate (ZOL). Group 2 (positive control): weekly ZOL infusions for 12 weeks followed by tooth extractions without wound management followed by 8 weeks of ZOL treatment. Group 3: weekly ZOL infusions for 12 weeks followed by tooth extractions; surgical wound management (resection of sharp bone edges, mucoperiosteal coverage); and continuation of ZOL infusions for 8 weeks plus antibiotic treatment. Group 4: 12 weeks of ZOL infusions followed by a drug holiday for 6 weeks. Tooth extractions with preventive wound management followed by antibiotic treatment for 8 weeks but no ZOL infusions. Jawbones were subjected to macroscopic, radiological (CT and micro‐CT) and histopathological investigations. No clinical cases of MRONJ were observed in the negative group, in the positive control all animals developed MRONJ. Group 3 developed MRONJ in 83% of cases. With a drug holiday, 40% developed MRONJ in areas of tooth extraction. This is the first large animal model that reduces the occurrence of MRONJ following tooth extraction by the implementation of a drug holiday combined with antibiotic prophylaxis and smoothening of sharp bony edges. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.
Social and Psychological Capital for the Start-Up of Social Enterprises With a Migratory Background

The highest number of forcibly displaced people has been currently recorded due to war, poverty, and climate change. Recently, a process that recognizes refugees as reliable interlocutors for the improvement of reception policies has started. Refugees are therefore encouraged to start up social enterprises aimed at fostering newcomers’ social integration to participate to such a phenomenon. Positive Psychology, with its focus on human strengths, allows to identify the resources that pushed refugees to turn the difficulties they faced during the journey and the resettlement process into resources for themselves and for the resettlement community. The following paper explores in particular the interplay between social and psychological capital that is at the base of a similar social entrepreneurship project through a case study. A qualitative research has been carried out within a social enterprise with a migratory background to analyze the internal and relational resources that brought founders to start up the venture. Results show that while social and psychological capital were independently activated to start from scratch in the resettlement community, they occurred in interrelation in a subsequent phase when participants transformed their direct experiences related to migration into the human capital of their enterprise.
How Would Capital Account Liberalization Affect China's Capital Flows and the Renminbi Real Exchange Rates?

In this paper we study the determinants of gross capital flows, project the size of China's international investment positions in 2020 and analyse the implications for the renminbi real exchange rates. We assume in this exercise that the renminbi will have largely achieved capital account convertibility by the end of this decade, a timetable consistent with recent proposals by the People's Bank of China. Our analysis shows that China's gross international investment positions would grow significantly, and inflows and outflows would become much more balanced. The private sector would turn its net liability position into a balanced position, and the official sector would reduce its net asset position significantly, relative to the countryi¦s GDP. Because of the increasing importance of private sector foreign claims and the decreasing importance of official foreign reserves, China would be able to earn higher net investment incomes from abroad. Overall, China would continue to be a net creditor, with the net foreign asset position as a share of GDP remaining largely stable through this decade. These findings suggest that the renminbi real exchange rate would not be particularly sensitive to capital account liberalisation as capital flows are expected to be two-sided. The renminbi real exchange rate would likely be on a path of moderate appreciation as China is expected to maintain a sizeable growth differential with its trading partners.
Patterns of Secondary Sexual Size Dimorphism in New World Myotis and a Test of Rensch's Rule

For bats, when secondary sexual dimorphism is significant, females typically are larger than males. Moreover, in mammals, variation in the degree of sexual dimorphism often follows an allometric relationship whereby differences vary with body size (Rensch's rule). We examined sexual dimorphism across the New World clade of Myotis regarding species-specific and clade-wide patterns of body, cranium, and wing size, Rensch's rule and degree to which such morphological variation is related to phylogeny. Size differences were common with significant cases of both male-biased and female-biased sexual dimorphism. In more than half the cases, females were larger than males. Variation in degree of dimorphism exhibited an allometric pattern. Nonetheless, slope of the relationship between size and degree of dimorphism was no different from unity (i.e., isometry), failing to support Rensch's rule. There was a strong and significant relationship between phylogeny and morphological variation but not between phylogeny and degree of dimorphism. Patterns suggest that differences between males and females enhance aerodynamic capabilities of females whereby larger mothers can overcome constraints on flight due to the mass of large fetuses and newborns.
Liver Injury in Critically Ill and Non-critically Ill COVID-19 Patients: A Multicenter, Retrospective, Observational Study

Background: Liver injury commonly occurs in patients with COVID-19. There is limited data describing the course of liver injury occurrence in patients with different disease severity, and the causes and risk factors are unknown. We aim to investigate the incidence, characteristics, risk factors, and clinical outcomes of liver injury in patients with COVID-19. Methods: This retrospective observational study was conducted in three hospitals (Zhejiang, China). From January 19, 2020 to February 20, 2020, patients confirmed with COVID-19 (≥18 years) and without liver injury were enrolled and divided into non-critically ill and critically ill groups. The incidence and characteristics of liver injury were compared between the two groups. Demographics, clinical characteristics, treatments, and treatment outcomes between patients with or without liver injury were compared within each group. The multivariable logistic regression model was used to explore the risk factors for liver injury. Results: The mean age of 131 enrolled patients was 51.2 years (standard deviation [SD]: 16.1 years), and 70 (53.4%) patients were male. A total of 76 patients developed liver injury (mild, 40.5%; moderate, 15.3%; severe, 2.3%) with a median occurrence time of 10.0 days. Critically ill patients had higher and earlier occurrence (81.5 vs. 51.9%, 12.0 vs. 5.0 days; p < 0.001), greater injury severity (p < 0.001), and slower recovery (50.0 vs. 61.1%) of liver function than non-critically ill patients. Multivariable regression showed that the number of concomitant medications (odds ratio [OR]: 1.12, 95% confidence interval [CI]: 1.05–1.21) and the combination treatment of lopinavir/ritonavir and arbidol (OR: 3.58, 95% CI: 1.44–9.52) were risk factors for liver injury in non-critically ill patients. The metabolism of arbidol can be significantly inhibited by lopinavir/ritonavir in vitro (p < 0.005), which may be the underlying cause of drug-related liver injury. Liver injury was related to increased length of hospital stay (mean difference [MD]: 3.2, 95% CI: 1.3–5.2) and viral shedding duration (MD: 3.0, 95% CI: 1.0–4.9). Conclusions: Critically ill patients with COVID-19 suffered earlier occurrence, greater injury severity, and slower recovery from liver injury than non-critically ill patients. Drug factors were related to liver injury in non-critically ill patients. Liver injury was related to prolonged hospital stay and viral shedding duration in patients with COVID-19. Clinical Trial Registration: World Health Organization International Clinical Trials Registry Platform, ChiCTR2000030593. Registered March 8, 2020.
Species diversity within the Helvella crispa group (Ascomycota: Helvellaceae) in China

The white saddle-mushroom, a well-known European species, has long been named as Helvella crispa in China. In this study, phylogenetic analyses of combined ITS, nrLSU, tef 1-α, rpb 2 and mcm 7 sequence data, showed that the Chinese H. crispa -like samples represent a species complex, which contains at least six phylogenetic species. Three of these species, H. involuta, H. orienticrispa and H. pseudoreflexa, are introduced as new species in this paper. The remaining two taxa are not described due to paucity of material. Among the six phylogenetic species, H. zhongtiaoensis is more closely related to European H. crispa than the remaining Chinese species. They are provided with descriptions, photographs and are compared with similar species. A key to the Chinese morphologically recognizable taxa of this complex is provided.
Mechanical and Enzyme Assisted Fractionation Process for a Sustainable Production of Black Soldier Fly (Hermetia illucens) Ingredients

This study aimed at effective fractionation of Hermetia illucens into lipid and protein, considering the insects' anatomy. A hybrid approach was developed, separating the exoskeleton by mechanical pressing and fractionating the slurry by sonication and enzymatic treatment. Microscopy showed that the peripheral fat bodies were tightly attached to muscle fibers. Blanching caused protein aggregation and entrapment of fat in the protein matrix, resulting in 25.0% loss in fat extraction, compared to only 3.3% loss for unblanched larvae. After centrifugation of the juice obtained from unblanched larvae a cream layer rich of lipids and proteins, a supernatant with soluble protein, and a pellet including mainly insoluble proteins were obtained. Blanched juice centrifugation formed a lipid fraction, a reduced cream layer, and more pellet. Whereas, sonication hardly affected the fractionation, enzymatic treatment resulted in solubilisation of pellet protein and an increased lipid layer. In conclusion, processing without blanching is very effective to extract more lipids (>80%) from whole larvae in the form of a cream layer, while blanched-enzymatic treatment allows the extraction of lipids in a clear lipid layer (>40%). In both cases, around 50% of protein was recovered in the residue and the other 50% mainly in the pellet after centrifugation.
Rye Living Mulch Effects on Soil Moisture and Weeds in Asparagus

Livingmulchesgrowingbelowasparagus(Asparagusofficinales)ferncanimprove soil health and suppress weeds but may also suppress asparagus through competition for water or nutrients. The central objective of this research was to test whether cereal rye (Secale cereale) living mulch, in combination with overhead irrigation, could provide comparable weed suppression to standard residual herbicides without reducing asparagus yields. Afield experiment was conducted from 2008 to 2010 in a mature asparagus planting on sandy soils in western Michigan to evaluate the effects of irrigation (none vs. overhead) and weed management systems (standard herbicides vs. rye living mulch) on weed suppression, soil moisture content, and asparagus yield. Rye living mulch and herbicide treatments were established immediately after asparagus harvest in late June of each year. Rye living mulch reduced soil-available water in early August by 26% to 52% compared with herbicide treatments but had no detectable effect on asparagus yields. Compared with herbicide treatments, rye living mulch reduced fall-germinating weed emergence and resulted in lower densities of horseweed (Conyza canadensis) during asparagus harvest. However, in 2 of 3 years, the living mulch system resulted in higher densities of summer annual weeds—including Powell amaranth (Amaranthus powellii) and longspine sandbur (Cenchrus longispinus)—during the fern growth period com- pared with herbicide treatments. After 3 years, the density of summer annual weeds was more than 10-fold greater in rye living mulch treatments compared with standard residual herbicidestreatments. Ourresults suggest that1)soil-improving ryecovercrops can partially suppress weeds but may also compete with asparagus for soil moisture in dry years unless irrigation is used; and 2) successful use of rye living mulches for weed management will depend on identification of complementary weed management practices to avoid build-up of the summer annual weed seedbank.
Seed growth of desi and kabuli chickpea (Cicer arietinum L.) in a short-season Mediterranean-type environment

The influence of terminal drought on the seed growth of 3 chickpea (Cicer arietinum L.) genotypes was examined in a field experiment at Merredin, Western Australia. Tyson, a small-seeded desi cultivar, ICCV88201, a desi breeding line (sister line to the recently released Sona cultivar) with medium-sized seed, and Kaniva, a kabuli cultivar with large seed, were grown under rainfed and irrigated conditions. In the rainfed plots, leaf water potential had decreased from above –1.2 MPa to about –2.5 MPa and net photosynthesis from 21 to 29 µmol CO2/m2. s to below 10 µmol CO2/m2.s, by the time seed filling commenced. Rainfed plants had significantly fewer pods than irrigated plants, regardless of genotype. In rainfed plants average seed weight was reduced by 19, 23 and 34% and yield by 74, 52 and 72% in Tyson, ICCV88201, and Kaniva respectively. Individual pods were tagged at pod set on previously-selected representative plants and were weighed separately from the rest of the plant over 6 subsequent harvests so that the rate and duration of seed fill could be measured. Genotypic differences in the maximum rate of seed fill were found to exist in chickpea. In both irrigated and rainfed conditions, Kaniva had the highest maximum rate of seed fill followed by ICCV88201 and Tyson. Both the rate and duration of seed growth were reduced in the rainfed plants, regardless of genotype. Reductions in the dry weight of the pod shell suggest that the remobilisation of dry matter from the pod may contribute 9–15% of the seed weight in rainfed chickpea.
Organization Capital

We develop a firm-specific measure of the most important intangible asset - organization capital - and document that organization capital is associated with five years of future operating and stock return performance, after controlling for other factors. Thus, our organization capital measure captures firms' fundamental ability to generate abnormal performance. We also find that executive compensation is positively associated with our measure of organization capital, showing that the measure indeed reflects managerial ability.
EVALUATING THE PERFORMANCE OF AUSTRALIAN ANNUAL MEDICS IN SUB-TROPICAL AND SUB-HUMID ECOLOGICAL ZONES OF PAKISTAN

The study was conducted to test the performance of Medicago varieties in sub-tropical and sub-humid ecological zones of Pakistan on the basis of dry matter accumulation, root nodulation and nitrogen fixation. For this purpose, certified uninoculated seeds of Medicago varieties were sown in the first week of October 2005 at National Agricultural Research Centre (NARC), Islamabad. The study reveals that Medicago blancheana, var. SA-3410 and Medicago rugosa Var.SA-5814 were densely covered with active nodules. Both varieties also had the highest N-content in their tissues. Medicago arabica var. SA-2355, var. SA 2041, M. liltoralis var „SA-2144‟ M. murex var. SA-4000, M. polymorpha var. SA-2167, var. SA3836, M. rotata var-2145, M. Scutellata var. SA-2082 and var. SA-7620 yielded more than 5 t. ha -1 dry matter. Hence, these varieties were regarded as promising for rangelands and marginal croplands located in sub-humid and sub-tropical ecological zones of Pakistan.
The effect of zinc bacitracin on the physiology of broilers fed plant and animal protein diets.

This study presents the influence of zinc (Zn) bacitracin, a growth promoter on the physiology of broiler chickens fed plants and animal protein diets. The differential effect of the two diets on plasma lipid profiles (total cholesterol, triglycerol, high-density lipoprotein, (HDL) and low-density lipoprotein (LDL), mineral profiles, (including calcium to phosphorus ratio in the broiler chicken bones) and the plasma hormone profile (testosterone, oestrogen and progesterone levels) were investigated. Results showed a significant difference (P 0.05) when Zn bacitracin was added to the plant protein diet, while there was an increase in testosterone when Zn bacitracin was added to the animal protein diet. Broiler chickens fed with plant protein diet showed significantly higher Calcium levels in bones and claws (P<0.05). The inclusion of Zn bacitracin significantly lowered Ca levels in both diets. Phosphorus levels in bones and claws showed no significant differences. These results indicate that some parameters changed in tissues on inclusion of Zn bacitracin, but its negative effect on the physiology of broilers and the possible effect on humans need to be further investigated.
1 Large-Scale Mutant Analysis of Seed Development in Arabidopsis

With advances in DNA sequencing and reports of sequenced genomes appearing at an accelerating rate, one can easily forget an important principle that first guided research in molecular plant biology 25 years ago – that genomics and proteomics are most powerful when focused on model genetic organisms. It is therefore fitting that a book devoted to seed genomics should include several chapters on the use of genetic analysis to address fundamental questions in seed biology. My objective in this chapter is not to detail all of the seed mutants analyzed to date or to describe all of the biological questions that have been addressed with these mutants. Instead, I have chosen to focus on my own professional journey, spanning the past 35 years, to isolate and characterize large numbers of embryo-defective (emb) mutants in the model plant, Arabidopsis thaliana. This choice is justified by a quick look at the numbers involved. More embryo mutants have been isolated and characterized in Arabidopsis, and their genes identified, than in all other angiosperms combined. Any discussion of the strategies, procedures, and conclusions drawn from the analysis of large numbers of mutants defective in seed development must therefore focus on what has been accomplished in Arabidopsis. This work has been performed over several decades by dozens of individuals in my laboratory, along with scores of investigators throughout the Arabidopsis community. The results summarized in this chapter are a testament to their combined efforts and insights. Readers unfamiliar with basic features of seed development are referred to Chapters 2 and 3 of this book.
Breast-Milk Microbiota Linked to Celiac Disease Development in Children: A Pilot Study From the PreventCD Cohort

Celiac disease (CeD) is an immune-mediated disorder triggered by exposure to dietary gluten proteins in genetically predisposed individuals. In addition to the host genome, the microbiome has recently been linked to CeD risk and pathogenesis. To progress in our understanding of the role of breast milk microbiota profiles in CeD, we have analyzed samples from a sub-set of mothers (n = 49) included in the PreventCD project, whose children did or did not develop CeD. The results of the microbiota data analysis indicated that neither the BMI, HLA-DQ genotype, the CeD condition nor the gluten-free diet of the mothers could explain the human milk microbiota profiles. Nevertheless, we found that origin country, the offspring’s birth date and, consequently, the milk sampling date influenced the abundance and prevalence of microbes in human milk, undergoing a transition from an anaerobic to a more aerobic microbiota, including potential pathogenic species. Furthermore, certain microbial species were more abundant in milk samples from mothers whose children went on to develop CeD compared to those that remained healthy. These included increases in facultative methylotrophs such as Methylobacterium komagatae and Methylocapsa palsarum as well as in species such as Bacteroides vulgatus, that consumes fucosylated-oligosaccharides present in human milk, and other breast-abscess associated species. Theoretically, these microbiota components could be vertically transmitted from mothers-to-infants during breastfeeding, thereby influencing CeD risk.