In this task, you're given a paragraph from the research paper and your task is to generate a suitable title for the research paper based on the given paper. Under 100 words is a good title length.

Ex Input:
A new porcine coronavirus SADS-CoV was recently identified from suckling piglets 20 with severe diarrhea in southern China and its genome sequence is most identical (~95% 21 identity) to that of bat α-coronavirus HKU2. It again indicates bats are the natural 22 reservoir of many coronaviruses that have great potential for cross-species transmission 23 to animals and humans by recombination and/or mutation. Here we report the cryo-EM 24 structures of HKU2 and SADS-CoV spike glycoprotein trimers at 2.38 Å and 2.83 Å 25 resolution, respectively. HKU2 and SADS-CoV spikes exhibit very high structural 26 similarity, with subtle differences mainly distributed in the NTD and CTD of the S1 27 subunit responsible for cell attachment and receptor binding. We systematically 28 analyzed and compared the NTD, CTD, SD1 and SD2 domains of the S1 subunit and 29 the S2 subunit of HKU2 spike with those of α-, β-, γ-, and δ-coronavirus spikes. The 30 results show that the NTD and CTD of HKU2/SADS-CoV are probably the most 31 ancestral in the evolution of spike. Although the S2 subunit mediating membrane fusion 32 is highly conserved, the connecting region after fusion peptide in HKU2/SADS-CoV 33 S2 subunit also adopts a conformation distinct from other coronaviruses. These results 34 structurally demonstrate a close evolutionary relationship between HKU2 /SADS-CoV 35 and β-coronavirus spikes and provide new insights into the evolution and cross-species 36 transmission of coronaviruses. : bioRxiv preprint 39 Coronaviruses, categorized into the order Nidovirales family Coronaviridae and 40 subfamily Coronavirinae, are a large group of viral pathogens with a wide host range 1 . 41 Their infections in humans, other mammals and birds can cause respiratory, hepatic, 42 enteric and neurological diseases with varying severity 2 . The severe acute respiratory 43 syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus 44 (MERS-CoV) have posed severe threats to human health in the 21 st century 1,3 . In the 45 meantime, coronaviruses infecting domestic animals also bring substantial economic 46 losses 4 . For example, the swine acute diarrhea syndrome coronavirus (SADS-CoV) 47 (also known as SeACoV and PEAV) isolated in 2017 caused outbreaks of severe watery 48 diarrhea of suckling piglets with a mortality up to 90% in several commercial pig farms 49 in Guangdong Province of China 5-10 . SADS-CoV is an α-coronavirus and other 50 representative members in the α-genus are porcine epidemic diarrhea virus 51 (PEDV), porcine transmissible gastroenteritis coronavirus (TGEV), porcine respiratory 52 coronavirus (PRCV), human NL63 and 229E coronaviruses (HCoV-NL63 and HCoV-53 229E) 1 . Representative members in other three genera include mouse hepatitis 54 coronavirus (MHV), bovine coronavirus (BCoV), SARS-CoV, MERS-CoV, HCoV-55 OC43 and HCoV-HKU1 in the β-genus, avian infectious bronchitis virus (IBV) in the 56 γ-genus and porcine deltacoronavirus (PdCoV) in the δ-genus 1 . 57 Cross-species transmission promoted by genetic recombination and/or mutations 58 underlies the host range expansion of coronaviruses 3,11-13 . Bats are the natural reservoir 59 of more than 30 different α-and β-coronaviruses that have great potential for 60 interspecies transmission by recombination and/or mutation 12,14-16 . Data on genetic 61 evolution, receptor binding and pathogenesis have demonstrated that human SARS-62 CoV and MERS-CoV most likely originate from bats 1 . Palm civets and dromedary 63 camels are the intermediate hosts of SARS-CoV and MERS-CoV from bats to humans 1 , 64 respectively. The newly identified porcine SADS-CoV isolates are also found to share 65 ~95% sequence identity with Rhinolophus bat coronavirus HKU2, and this further 66 stressed the severe results of coronavirus spillover from bats to domestic animals 5-10 .

Ex Output:
Cryo-EM structures of HKU2 and SADS-CoV spike 1 glycoproteins and insights into coronavirus evolution 2 3 4


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Simple Summary: Rearing of replacement female calves on a dairy farm is of critical importance to maintain herd sizes, improve the genetic quality of the herd, and remain economically sustainable. A 2-year investment period is needed for replacement female heifers to grow before entering the milking herd. The management of replacements over this 2-year period can vary greatly among operations, making it difficult to compare producers' cost to benchmark. The objective of this project was to develop a model to calculate the cost of rearing a replacement heifer from birth to weaning under different housing, milk source, allotments, and labor and health management decisions to be used as a dairy farm decision support tool. We calculated the cost for management options with general cost values. We found that the average feed cost represented 46% of the total cost while labor, and fixed and variable costs represented 33%, 9%, and 12%, respectively. The total cost increased as milk allotment increased, but cost per Kg of gain decreased. The ranges in total cost within each management scenario often exceed the difference in cost from one scenario to the next. In conclusion, variable costs have the potential to vary among operations, playing a major role in the total cost of rearing replacements from birth to weaning. Abstract: Dairy calves are raised in various housing and feeding environments on dairy farms around North America. The objective of this study was to develop a simulation model to calculate the cost of raising replacement dairy heifers using different inputs that reflect different management decisions and evaluate their influence on the total cost. In this simulation, 84 calves were modeled between 0-2 months of age to reflect a 1000 heifer herd. The decisions associated with housing, liquid diet source and allowance, labor utilization, and health were calculated. Costs and biological responses were reflective of published surveys, literature, and market conditions. A 10,000-iteration economic simulation was used for each management scenario using @Risk and PrecisionTree add-ons (Palisade Corporation, Ithaca, NY, USA) to account for variation in pre-weaning mortality rate, weaning age, and disease prevalence. As milk allotment increased, total feed cost increased. Feeding calves a higher allowance of milk resulted in a lower cost per kg of gain. Average feed cost percentage of the total cost was 46% (min, max: 33%, 59%) while labor, and fixed and variable cost represented 33% (20%, 45%), 9% (2%, 12%), and 12% (10%, 14%), respectively. Total pre-weaning costs ranged from $258.56 to $582.98 per calf across all management scenarios and milk allotments. project administration, J.H.C.C. The authors would like to thank Dannon for their continued support of this project.

Ex Output:
An Economic Analysis of the Costs Associated with Pre-Weaning Management Strategies for Dairy Heifers


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Background. T cell immunoglobulin mucin domain-1 (TIM-1) is a phosphatidylserine (PS) 28 receptor, mediating filovirus entry into cells through interactions with PS on virions. TIM-1 29 expression has been implicated in Ebola virus (EBOV) pathogenesis; however, it remains 30 unclear whether this is due to TIM-1 serving as a filovirus receptor in vivo or, as others have 31 suggested, TIM-1 induces a cytokine storm elicited by T cell/virion interactions. Here, we use a 32 BSL2 model virus that expresses EBOV glycoprotein and demonstrate the importance of TIM-1 33 as a virus receptor late during in vivo infection. 34 Methodology/Principal findings. We used an infectious, recombinant vesicular stomatitis virus 35 expressing EBOV glycoprotein (EBOV GP/rVSV) to assess the role of TIM-1 during in vivo 36 infection. TIM-1-sufficient or TIM-1-deficient BALB/c interferon α/β receptor -/mice were 37 challenged with EBOV GP/rVSV-GFP or G/rVSV-GFP. While G/rVSV caused profound 38 morbidity and mortality in both mouse strains, TIM-1-deficient mice had significantly better 39 survival than TIM-1-expressing mice following EBOV GP/rVSV challenge. EBOV GP/rVSV 40 load in spleen was high and unaffected by expression of TIM-1. However, infectious virus in 41 serum, liver, kidney and adrenal gland was reduced late in infection in the TIM-1-deficient mice, 42 suggesting that virus entry via this receptor contributes to virus load. Consistent with higher 43 virus loads, proinflammatory chemokines trended higher in organs from infected TIM-1-44 sufficient mice compared to the TIM-1-deficient mice, but proinflammatory cytokines were more 45 modestly affected. To assess the role of T cells in EBOV GP/rVSV pathogenesis, T cells were 46 depleted in TIM-1-sufficient and -deficient mice and the mice were challenged with virus. 47 Depletion of T cells did not alter the pathogenic consequences of virus infection. 48 . CC-BY 4.0 International license is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/466102 doi: bioRxiv preprint Conclusions. Our studies provide evidence that at late times during EBOV GP/rVSV infection, 49 TIM-1 increased virus load and associated mortality, consistent with an important role of this 50 receptor in virus entry. This work suggests that inhibitors which block TIM-1/virus interaction 51 may serve as effective antivirals, reducing virus load at late times during EBOV infection. 52 53 Author summary 54 T cell immunoglobulin mucin domain-1 (TIM-1) is one of a number of phosphatidylserine (PS) 55 receptors that mediate clearance of apoptotic bodies by binding PS on the surface of dead or 56 dying cells. Enveloped viruses mimic apoptotic bodies by exposing PS on the outer leaflet of the 57 viral membrane. While TIM-1 has been shown to serve as an adherence factor/receptor for 58 filoviruses in tissue culture, limited studies have investigated the role of TIM-1 as a receptor in 59 vivo. Here, we sought to determine if TIM-1 was critical for Ebola virus glycoprotein-mediated 60 infection using a BSL2 model virus. We demonstrate that loss of TIM-1 expression results in 61 decreased virus load late during infection and significantly reduced virus-elicited mortality. 62 These findings provide evidence that TIM-1 serves as an important receptor for Ebola virus in 63 vivo. Blocking TIM-1/EBOV interactions may be effective antiviral strategy to reduce viral load 64 and pathogenicity at late times of EBOV infection. 65 66 . CC-BY 4.0 International license is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/466102 doi: bioRxiv preprint 129 for maEBOV we observed that EBOV GP/rVSV was less pathogenic in TIM-1-deficient mice 130 compared to control mice. The impact of the loss of TIM-1 was specific for EBOV GP-131 expressing virus since wild-type VSV was equally virulent in TIM-1-deficient and TIM-1-132 sufficient mice over a wide range of challenge doses. Importantly, reduced mortality observed 133 in the virus-infected TIM-1 -/mice was associated with lower virus load at late time points 134 during infection in multiple tissues previously appreciated to be important in EBOV 135 . CC-BY 4.0 International license is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. It . https://doi.org/10.1101/466102 doi: bioRxiv preprint 157 Havcr1, were replaced with a LacZ gene, generating a TIM-1-null mouse (TIM-1 -/-) BALB/c 158 IFN-αβ receptor-deficient (Ifnar -/-) mice were a kind gift from Dr. Joan Durbin, NYU Langone 159 . CC-BY 4.0 International license is made available under a

Ex Output:

2 3 TIM-1 SERVES AS A NONREDUNDANT RECEPTOR FOR EBOLA 4 VIRUS, ENHANCING VIREMIA AND PATHOGENESIS 5 6