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Baricitinib therapy in COVID-19: A pilot study on safety and clinical impactDear Editor , 38.1 (37.7-38.7) 0.356 Breath rate N/min, median (IQR), 23 (19.5-24.2) 22 (19.7-24) 0.665 SpO2 (%),median (IQR) 91 (90-92.5) 92 (91.2-93) 0.157 PaO2/FiO2, median (IQR) 290 (199.2-292.2) 268.6 (264.4-295) 0.603 Pulse rate, median (IQR) 82 (73-88.3) 90 (87.2-94.5) 0.069 SBP mm/Hg, median (IQR) 120 (110-131.2) 105 (100-111.25) 0.003 DBP mm/Hg, median (IQR) 70 (60-80) 62.5 (60-66.25) 0.094 WBC (x10 9 /L), median (IQR) 7.8 (5.8-10.8) 8.2 (7.3-8.8) 0.908 Neutrophils (x10 9 /L), median (IQR) 6,5 (4.5-7.7) 6.9 (6.4-7.6) 0.707 Lymphocytes (x10 9 /L), median (IQR) 0.7 (0.7-1.2) 0.89 (0.7-0.9) 1.0 0 0 Hemoglobin (g/L), median (IQR) 118 (102-134.2) 125 (108-134) 0.568 Platelets (x10 9 /L), median (IQR) 203 (174-227) 366 (340-407) 0.0 0 0 ALT (U/L), median (IQR) 28.5 (23.5-52) 44 (37-50) 0.157 AST (U/L), median (IQR) 34 (26.2-48) 44 (34.7-47) 0.525 Creatinine (mg/dl), median (IQR)1.0 (0.9-1.1) 1.00 (0.9-1) 0.583 CRP (mg/dl), median (IQR) 8.2 (5.8-14.5) 3 (1.5-3.2) 0.002 Procalcitonin ng/ml, median (IQR) 0.7 (0.4-1.1) 1.2 (0.8-2.1) 0.902 MEWS, median (IQR) 3 ( 2-3.25) 3 (3-4) 0.544 Abbreviations and symbols: N = number;% = percentage; °C: grade Celsius; min = minute; SpO2 = peripheral capillary oxygen saturation; PaO2/FiO2 = ratio of arterial oxygen partial pressure to fractional inspired oxygen; SBP = systolic blood pressure; DBP = diastolic blood pressure; WBC = white blood cells; AST = serum glutamic oxaloacetic transaminase; ALT = serum alanine aminotransferase; MEWS = Modified Early Warning Score; IQR: Interquartile range.

ITP and dITP exist in all cells. dITP is potentially mutagenic, and the levels of these nucleotides are controlled by inosine triphosphate pyrophosphatase (EC 3.6.1.19). Here we report the cloning, expression, and characterization of a 21.5-kDa human inosine triphosphate pyrophosphatase (hITPase), an enzyme whose activity has been reported in many animal tissues and studied in populations but whose protein sequence has not been determined before. At the optimal pH of 10.0, recombinant hITPase hydrolyzed ITP, dITP, and xanthosine 5-triphosphate to their respective monophosphates whereas activity with other nucleoside triphosphates was low. K m values for ITP, dITP, and xanthosine 5-triphosphate were 0.51, 0.31, and 0.57 mM, respectively, and k cat values were 580, 360, and 640 s ؊1 , respectively. A divalent cation was absolutely required for activity. The gene encoding the hITPase cDNA sequence was localized by radiation hybrid mapping to chromosome 20p in the interval D20S113-D20S97, the same interval in which the ITPA inosine triphosphatase gene was previously localized. A BLAST search revealed the existence of many similar sequences in organisms ranging from bacteria to mammals. The function of this ubiquitous protein family is proposed to be the elimination of minor potentially mutagenic or clastogenic purine nucleoside triphosphates from the cell.

The VirB proteins of Agrobacterium tumefaciens form a transport pore to transfer DNA from bacteria to plants. The assembly of the transport pore will require interaction among the constituent proteins. The identification of proteins that interact with one another can provide clues to the assembly of the transport pore. We studied interaction among four putative transport pore proteins, VirB7, VirB8, VirB9 and VirB10. Using the yeast two-hybrid assay, we observed that VirB8, VirB9, and VirB10 interact with one another. In vitro studies using protein fusions demonstrated that VirB10 interacts with VirB9 and itself. These results suggest that the outer membrane VirB7-VirB9 complex interacts with the inner membrane proteins VirB8 and VirB10 for the assembly of the transport pore. Fusions that contain small, defined segments of the proteins were used to define the interaction domains of VirB8 and VirB9. All interaction domains of both proteins mapped to the N-terminal half of the proteins. Two separate domains at the N-and C-terminal ends of VirB9 are involved in its homotypic interaction, suggesting that VirB9 forms a higher oligomer. We observed that the alteration of serine at position 87 of VirB8 to leucine abolished its DNA transfer function. Studies on the interaction of the mutant protein with the other VirB proteins showed that the VirB8S87L mutant is defective in interaction with VirB9. The mutant, however, interacted efficiently with VirB8 and VirB10, suggesting that the VirB8-VirB9 interaction is essential for DNA transfer.