Flow arrest during carotid artery stenting with a distal embolic protection device: A single-center experience and clinical implications.

Objective: We aimed to investigate the incidence of flow arrest during carotid artery stenting (CAS) with filter-type embolic protection device (EPD), identify any predisposing factors for those situations, and contemplate intraprocedural precautionary steps. Methods: CAS was performed in 128 patients with 132 arteries using filter-type EPD. The characteristics of treated patients and arteries were compared between groups with and without flow arrest. Results: The incidence of flow arrest during CAS with filter-type EPD was 17.4%. In flow arrest group, cases of vulnerable plaques (p=0.02) and symptomatic lesions (p=0.01) were significantly more common, and there were more cases of debris captured by EPD in a planar pattern (p<0.01). Vulnerable plaques were significantly more common in the procedures showing a planar pattern than in the cases with other patterns (p<0.01). Flow arrest group showed a significantly higher rate of ischemic complications (p<0.05), although there were no significant periprocedural neurological changes. The planar pattern of captured debris in filter-type EPD was the only significant risk factor for flow arrest (adjusted odds ratio 88.44, 95% confidence interval 15.21-514.45, p<0.05). Conclusions: Flow arrest during CAS with filter-type EPD is not uncommon and associated with increased ischemic complications. Symptomatic stenoses and vulnerable plaque are related to this event. The planar pattern of captured debris on the EPD was the only significant risk factor for the flow arrest. Clinicians must pay attention to the occurrence of flow arrest and react quickly when performing CAS.

Optimal target blood pressure for the primary prevention of hemorrhagic stroke: a nationwide observational study.

Background: There are few reports on the preventative value of intensive blood pressure (BP) management for stroke, especially hemorrhagic stroke (HS), after new criteria for hypertension (HTN) were announced by the American College of Cardiology/American Heart Association in 2017. Aims: This study aimed to identify the optimal BP for the primary prevention of HS in a healthy population aged between 20 and 65 years. Methods: We conducted a 10-year observational study on the risk of HS, subclassified as intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH) according to BP categories (e.g., low normal BP, high normal BP, elevated BP, stage 1 HTN, and stage 2 HTN) using the National Health Insurance Service Database. Results: Out of 8,327,751 participants who underwent a health checkup in 2008, 949,550 were included in this study and observed from 2009 to 2018. The risk of ICH was significantly increased in men with stage 2 HTN {adjusted hazard ratio [aHR] 2.002 [95% confidence interval (CI) 1.203-3.332]} and in women with stage 1 HTN [aHR 2.021 (95% CI, 1.251-3.263)]. The risk of SAH was significantly increased in both men [aHR 1.637 (95% CI, 1.066-2.514)] and women [aHR 4.217 (95% CI, 2.648-6.715)] with stage 1 HTN. Additionally, the risk of HS was significantly increased in men with stage 2 HTN [aHR 3.034 (95% CI, 2.161-4.260)] and in women with stage 1 HTN [aHR 2.976 (95% CI, 2.222-3.986)]. Conclusion: To prevent primary HS, including ICH and SAH, BP management is recommended for adults under the age of 65 years with stage 1 HTN.

Single-Cell Detection of Erwinia amylovora Using Bio-Functionalized SIS Sensor.

Herein, we developed a bio-functionalized solution-immersed silicon (SIS) sensor at the single-cell level to identify Erwinia amylovora (E. amylovora), a highly infectious bacterial pathogen responsible for fire blight, which is notorious for its rapid spread and destructive impact on apple and pear orchards. This method allows for ultra-sensitive measurements without pre-amplification or labeling compared to conventional methods. To detect a single cell of E. amylovora, we used Lipopolysaccharide Transporter E (LptE), which is involved in the assembly of lipopolysaccharide (LPS) at the surface of the outer membrane of E. amylovora, as a capture agent. We confirmed that LptE interacts with E. amylovora via LPS through in-house ELISA analysis, then used it to construct the sensor chip by immobilizing the capture molecule on the sensor surface modified with 3'-Aminopropyl triethoxysilane (APTES) and glutaraldehyde (GA). The LptE-based SIS sensor exhibited the sensitive and specific detection of the target bacterial cell in real time. The dose-response curve shows a linearity (R2 > 0.992) with wide dynamic ranges from 1 to 107 cells/mL for the target bacterial pathogen. The sensor showed the value change (dΨ) of approximately 0.008° for growing overlayer thickness induced from a single-cell E. amylovora, while no change in the control bacterial cell (Bacillus subtilis) was observed, or negligible change, if any. Furthermore, the bacterial sensor demonstrated a potential for the continuous detection of E. amylovora through simple surface regeneration, enabling its reusability. Taken together, our system has the potential to be applied in fields where early symptoms are not observed and where single-cell or ultra-sensitive detection is required, such as plant bacterial pathogen detection, foodborne pathogen monitoring and analysis, and pathogenic microbial diagnosis.

Clinical Outcomes of Coil Embolization for Unruptured Intracranial Aneurysms Categorized by Region and Hospital Size : A Nationwide Cohort Study in Korea.

OBJECTIVE: To analyze the outcomes of coil embolization (CE) for unruptured intracranial aneurysm (UIA) according to region and hospital size based on National Health Insurance Service data in South Korea. METHODS: The incidence of complications, including intracranial hemorrhage (ICRH) and cerebral infarction (CI), occurring within 3 months and the 1-year mortality rates in UIA patients who underwent CE in 2018 were analyzed. Hospitals were classified as tertiary referral general hospitals (TRGHs), general hospitals (GHs) or semigeneral hospitals (sGHs) according to their size, and the administrative districts of South Korea were divided into 15 regions. RESULTS: In 2018, 8425 (TRGHs, 4438; GHs, 3617; sGHs, 370) CEs were performed for UIAs. Complications occurred in 5.69% of patients seen at TRGHs, 13.48% at GHs, and 20.45% at sGHs. The complication rate in TRGHs was significantly lower than that in GHs (p=0.039) or sGHs (p=0.005), and that in GHs was significantly lower than that in sGHs (p=0.030). The mortality rates in TRGHs, GHs, and sGHs were 0.81%, 2.16%, and 3.92%, respectively, with no significant difference. Despite no significant difference in the mortality rates, the complication rate significantly increased as the number of CE procedures per hospital decreased (p=0.001; rho=-0.635). Among the hospitals where more than 30 CEs were performed for UIAs, the incidence of CIs (p=0.096, rho=-0.205) and the mortality rates (3 months, p=0.048, rho=-0.243; 1 year, p=0.009, rho=-0.315) significantly decreased as the number of CEs that were performed increased and no significant difference in the incidence of post-CE ICRH was observed. CONCLUSION: The complication rate in patients who underwent CE for UIA increased as the hospital size and physicians' experience in conducting CEs decreased. We recommend nationwide quality control policies CEs for UIAs.

Plastid methylerythritol phosphate pathway participates in the hypersensitive response-related cell death in Nicotiana benthamiana.

Programmed cell death (PCD), a characteristic feature of hypersensitive response (HR) in plants, is an important cellular process often associated with the defense response against pathogens. Here, the involvement of LytB, a gene encoding 4-hydroxy-3-methylbut-2-enyl diphosphate reductase that participates in the final step of the plastid methylerythritol phosphate (MEP) pathway, in plant HR cell death was studied. In Nicotiana benthmiana plants, silencing of the NbLytB gene using virus-induced gene silencing (VIGS) caused plant growth retardation and albino leaves with severely malformed chloroplasts. In NbLytB-silenced plants, HR-related cell death mediated by the expression of either the human proapoptotic protein gene Bax or an R gene with its cognate Avr effector gene was inhibited, whereas that induced by the nonhost pathogen Pseudomonas syringae pv. syringae 61 was enhanced. To dissect the isoprenoid pathway and avoid the pleiotropic effects of VIGS, chemical inhibitors that specifically inhibit isoprenoid biosynthesis in plants were employed. Treatment of N. benthamiana plants with fosmidomycin, a specific inhibitor of the plastid MEP pathway, effectively inhibited HR-related PCD, whereas treatment with mevinolin (a cytoplasmic mevalonate pathway inhibitor) and fluridone (a carotenoid biosynthesis inhibitor) did not. Together, these results suggest that the MEP pathway as well as reactive oxygen species (ROS) generation in the chloroplast play an important role in HR-related PCD, which is not displaced by the cytosolic isoprenoid biosynthesis pathway.

The Arabidopsis cyclophilin CYP18-1 facilitates PRP18 dephosphorylation and the splicing of introns retained under heat stress.

In plants, heat stress induces changes in alternative splicing, including intron retention; these events can rapidly alter proteins or downregulate protein activity, producing nonfunctional isoforms or inducing nonsense-mediated decay of messenger RNA (mRNA). Nuclear cyclophilins (CYPs) are accessory proteins in the spliceosome complexes of multicellular eukaryotes. However, whether plant CYPs are involved in pre-mRNA splicing remain unknown. Here, we found that Arabidopsis thaliana CYP18-1 is necessary for the efficient removal of introns that are retained in response to heat stress during germination. CYP18-1 interacts with Step II splicing factors (PRP18a, PRP22, and SWELLMAP1) and associates with the U2 and U5 small nuclear RNAs in response to heat stress. CYP18-1 binds to phospho-PRP18a, and increasing concentrations of CYP18-1 are associated with increasing dephosphorylation of PRP18a. Furthermore, interaction and protoplast transfection assays revealed that CYP18-1 and the PP2A-type phosphatase PP2A B'η co-regulate PRP18a dephosphorylation. RNA-seq and RT-qPCR analysis confirmed that CYP18-1 is essential for splicing introns that are retained under heat stress. Overall, we reveal the mechanism of action by which CYP18-1 activates the dephosphorylation of PRP18 and show that CYP18-1 is crucial for the efficient splicing of retained introns and rapid responses to heat stress in plants.

Temporally distinct regulatory pathways coordinate thermo-responsive storage organ formation in potato.

Tuberization is an important developmental process in potatoes, but it is highly affected by environmental conditions. Temperature is a major environmental factor affecting tuberization, with high temperatures suppressing tuber development. However, the temporal aspects of thermo-responsive tuberization remain elusive. In this study, we show that FT homolog StSP6A is suppressed by temporally distinct regulatory pathways. Experiments using StSP6A-overexpressing plants show that post-transcriptional regulation plays a major role at the early stage, while transcriptional regulation is an important late-stage factor, suppressing StSP6A at high temperatures in leaves. Overexpression of StSP6A in leaves restores tuber formation but does not recover tuber yield at the late stage, possibly because of suppressed sugar transport at high temperatures. Transcriptome analyses lead to the identification of potential regulators that may be involved in thermo-responsive tuberization at different stages. Our work shows that potato has temporally distinct molecular mechanisms that finely control tuber development at high temperatures.

Construction of SARS-CoV-2 virus-like particles in plant.

The pandemic of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused a public health emergency, and research on the development of various types of vaccines is rapidly progressing at an unprecedented development speed internationally. Some vaccines have already been approved for emergency use and are being supplied to people around the world, but there are still many ongoing efforts to create new vaccines. Virus-like particles (VLPs) enable the construction of promising platforms in the field of vaccine development. Here, we demonstrate that non-infectious SARS-CoV-2 VLPs can be successfully assembled by co-expressing three important viral proteins membrane (M), envelop (E) and nucleocapsid (N) in plants. Plant-derived VLPs were purified by sedimentation through a sucrose cushion. The shape and size of plant-derived VLPs are similar to native SARS-CoV-2 VLPs without spike. Although the assembled VLPs do not have S protein spikes, they could be developed as formulations that can improve the immunogenicity of vaccines including S antigens, and further could be used as platforms that can carry S antigens of concern for various mutations.

Accuracy evaluation of surface registration algorithm using normal distribution transform in stereotactic body radiotherapy/radiosurgery: A phantom study.

PURPOSE: To evaluate a feasibility of normal distribution transform (NDT) algorithm compared with the iterative closest point (ICP) method as a useful surface registration in stereotactic body radiotherapy (SBRT)/stereotactic radiosurgery (SRS). METHODS: Point cloud images using the 3D triangulation technology were obtained from a depth camera-based optical imaging (OSI) system equipped in a radiosurgery room. Two surface registration algorithms, NDT and ICP, were used to measure and compare the discrepancy values between the reference and the current surfaces during the positioning of the patient. The performance evaluation was investigated by calculating the registration error and root-mean-square (RMS) values for the surface model, reposition, and target accuracy, which were analyzed statistically using a paired t-test. RESULTS: For surface model accuracy, the average of the registration error and RMS values were measured as 3.56 ± 2.20 mm and 6.98 ± 1.89 mm for ICP method, and 1.76 ± 1.32 mm and 3.58 ± 1.30 mm for NDT method (p < 0.05). For reposition accuracy, the average registration error and RMS values were calculated as 1.41 ± 0.98 mm and 2.53 ± 1.64 mm using ICP method, and 0.92 ± 0.61 mm and 1.75 ± 0.80 mm using NDT method (p = 0.005). The overall target accuracy using the NDT method reduced the average of the reposition error and overall RMS value by 0.71 and 1.32 mm, respectively, compared to the ICP method (p = 0.03). CONCLUSIONS: We found that the surface registration algorithm based on NDT method provides more reliable accuracy in the values of surface model, reposition, and target accuracies than the classic ICP method. The NDT method in OSI systems offers reasonable accuracy in SBRT/SRS.

Complete genome sequence and genome organization of scorzonera virus A (SCoVA), a novel member of the genus Potyvirus.

The complete genomic sequence of scorzonera virus A (SCoVA) from a Scorzonera austriaca Willd. plant in South Korea was determined by high-throughput sequencing and confirmed by Sanger sequencing. The SCoVA genome contains 9867 nucleotides, excluding the 3'-terminal poly(A) tail. The SCoVA genome structure is typical of potyviruses and contains a single open reading frame encoding a large putative polyprotein of 3168 amino acids. Pairwise comparison analysis of the complete genome and polyprotein sequences of SCoVA with those of other potyviruses showed that they shared the highest nucleotide and amino acid sequences identity (54.47% and 49.57%, respectively) with those of lettuce mosaic virus (GenBank accession number KJ161185). Phylogenetic analysis of the amino acid sequence of the polyprotein confirmed that SCoVA belongs to the genus Potyvirus. These findings suggest that SCoVA should be considered a novel member of the genus Potyvirus, family Potyviridae.

Complete genome sequence of platycodon closterovirus 1, a novel putative member of the genus Closterovirus.

A new member of the genus Closterovirus was detected in Platycodon grandiflorus using high-throughput RNA sequencing analysis. The complete genome sequence of this new virus isolate, tentatively named "platycodon closterovirus 1" (PlaCV1), comprises 16,771 nucleotides with nine predicted open reading frames (ORFs) having the typical closterovirus genome organization. PlaCV1 shares 37%-50% nucleotide sequence identity with other known closterovirus genome sequences. The putative RNA-dependent RNA polymerase (RdRp), heat shock protein 70-like protein (HSP70h), viral heat shock protein 90-like protein (HSP90h), minor coat protein (CPm), and coat protein (CP) show 47-68%, 39-66%, 24-52%, 21-57%, and 16-35% amino acid sequence identity, respectively, to homologous proteins in previously identified closteroviruses, suggesting that it represents a distinct, new species in the genus. Phylogenetic analysis of HSP70h sequences places PlaCV1 alongside other members of the genus Closterovirus in the family Closteroviridae. To our knowledge, this study is the first report of the complete genome sequence of PlaCV1 infecting P. grandiflorus in the Republic of Korea.

Complete genome sequence of artemisia virus B, a new polerovirus infecting Artemisia princeps in South Korea.

The complete genome sequence of a new polerovirus found naturally infecting Artemisia princeps, artemisia virus B (ArtVB), was determined using high-throughput sequencing. The ArtVB genome comprises 6,141 nucleotides and contains six putative open reading frames (ORF0 to ORF5) with a genome structure typical of poleroviruses. A multiple sequence alignment showed that the complete ArtVB genome shares 50.98% nucleotide sequence identity with ixeridium yellow mottle virus 1 (IxYMaV-1, GenBank accession no. KT868949). ArtVB shares the highest amino acid sequence identity in P0 and P3-P5 (21.54%-51.69%) with other known poleroviruses. Phylogenetic analysis indicated that ArtVB should be considered a member of a new species within the genus Polerovirus, family Luteoviridae.

Detection of Rhodococcus fascians, the Causative Agent of Lily Fasciation in South Korea.

Rhodococcus fascians is an important pathogen that infects various herbaceous perennials and reduces their economic value. In this study, we examined R. fascians isolates carrying a virulence gene from symptomatic lily plants grown in South Korea. Phylogenetic analysis using the nucleotide sequences of 16S rRNA, vicA, and fasD led to the classification of the isolates into four different strains of R. fascians. Inoculation of Nicotiana benthamiana with these isolates slowed root growth and resulted in symptoms of leafy gall. These findings elucidate the diversification of domestic pathogenic R. fascians and may lead to an accurate causal diagnosis to help reduce economic losses in the bulb market.

Complete genome sequence and genome organization of achyranthes virus A, a novel member of the genus Potyvirus.

The complete genomic sequence of achyranthes virus A (AcVA), from an Achyranthes bidentata Blume plant in South Korea, was determined. The genomic RNA has 9491 nucleotides (nt), excluding the 3'-terminal poly(A) tail and contains an open reading frame typical of members of the genus Potyvirus, family Potyviridae, encoding a large putative polyprotein of 3103 amino acids (aa). Pairwise comparisons showed that the AcVA sequence shares 47.81-57.78% nt sequence identity at the complete genome level, 41.89-56.41% aa sequence identity at the polyprotein level, and 50-63.8% aa sequence identity at the coat protein level with other members of genus Potyvirus. These pairwise comparison values are below the species demarcation cutoff for the family Potyviridae. Our results therefore suggest that this virus should be regarded as a novel member of the genus Potyvirus, tentatively named "achyranthes virus A".

The prevalence of stroke according to indoor radon concentration in South Koreans: Nationwide cross section study.

To investigate the relationship between indoor radon level and stroke, which is a major factor for background radiation.This study combines 2 nationwide studies. Demographic characteristics and medical history of participants were obtained from Korean National Health and Nutrition Examination Survey (KNHANES) from 2007 to 2012. Participants over 40 years old and who completed the questionnaire were included in the study. Indoor radon concentration was analyzed using the mean value of winter housing radon concentration from 2012 to 2016 published by the National Institute of Environmental Research. The average values of each metropolitan city and province were assigned to the residence of the participant. To eliminate the potential confounding factors, participants' age, sex, hypertension, diabetes, dyslipidemia, ischemic heart disease, education level, occupation, smoking, drinking, exercise, and dietary intake were adjusted in multivariable logistic regression.Total of 28,557 participants were included in this study. Indoor radon levels were significantly higher in the participants with stroke, and the prevalence of stroke increased as indoor radon levels increased (P < .001, P for linear trend <.001). Indoor radon level was associated with stroke even after adjusting potential confounding factors (OR: 1.004 [95CI: 1.001-1.007], P = .010) and high radon exposure (indoor radon over 100Bq/m3) was also associated with stroke (OR: 1.242 [95CI: 1.069-1.444], P = .005). Trend analysis showed linear correlation of increased odds between radon quartile and stroke (P for linear trend < .001). In subgroup analysis, elevated indoor radon was most strongly associated in participants with age over 76(OR: 1.872[95%CI:1.320-2.654], P < .001).High indoor radon concentration may be associated with stroke. Specifically, elevated radon was associated with stroke in participants over 76 years old. In high-risk population, home modification to reduce indoor radon may help decreasing the risk of stroke.

PIN-mediated polar auxin transport facilitates root-obstacle avoidance.

Plants sense mechanical stimuli to recognise nearby obstacles and change their growth patterns to adapt to the surrounding environment. When roots encounter an obstacle, they rapidly bend away from the impenetrable surface and find the edge of the barrier. However, the molecular mechanisms underlying root-obstacle avoidance are largely unknown. Here, we demonstrate that PIN-FORMED (PIN)-mediated polar auxin transport facilitates root bending during obstacle avoidance. We analysed two types of bending after roots touched barriers. In auxin receptor mutants, the rate of root movement during first bending was largely delayed. Gravity-oriented second bending was also disturbed in these mutants. The reporter assays showed that asymmetrical auxin responses occurred in the roots during obstacle avoidance. Pharmacological analysis suggested that polar auxin transport mediates local auxin accumulation. We found that PINs are required for auxin-assisted root bending during obstacle avoidance. We propose that rapid root movement during obstacle avoidance is not just a passive but an active bending completed through polar auxin transport. Our findings suggest that auxin plays a role in thigmotropism during plant-obstacle interactions.

Proteasome subunit RPT2a promotes PTGS through repressing RNA quality control in Arabidopsis.

RNA quality control (RQC) and post-transcriptional gene silencing (PTGS) target and degrade aberrant endogenous RNAs and foreign RNAs, contributing to homeostasis of cellular RNAs. In plants, RQC and PTGS compete for foreign and selected endogenous RNAs; however, little is known about the mechanism interconnecting the two pathways. Using a reporter system designed for monitoring PTGS, we revealed that the 26S proteasome subunit RPT2a enhances transgene PTGS by promoting the accumulation of transgene-derived short interfering RNAs without affecting their biogenesis. RPT2a physically associated with a subset of RQC components and downregulated the protein level. Overexpression of the RQC components interfered with transgene silencing, and impairment of the RQC machinery reinforced transgene PTGS attenuated by rpt2a. Overall, we demonstrate that the 26S proteasome subunit RPT2a promotes PTGS by repressing the RQC machinery to control foreign RNAs.

Potential of Pantoea dispersa as an effective biocontrol agent for black rot in sweet potato.

Biocontrol offers a promising alternative to synthetic fungicides for the control of a variety of pre- and post-harvest diseases of crops. Black rot, which is caused by the pathogenic fungus Ceratocytis fimbriata, is the most destructive post-harvest disease of sweet potato, but little is currently known about potential biocontrol agents for this fungus. Here, we isolated several microorganisms from the tuberous roots and shoots of field-grown sweet potato plants, and analyzed their ribosomal RNA gene sequences. The microorganisms belonging to the genus Pantoea made up a major portion of the microbes residing within the sweet potato plants, and fluorescence microscopy showed these microbes colonized the intercellular spaces of the vascular tissue in the sweet potato stems. Four P. dispersa strains strongly inhibited C. fimbriata mycelium growth and spore germination, and altered the morphology of the fungal hyphae. The detection of dead C. fimbriata cells using Evans blue staining suggested that these P. dispersa strains have fungicidal rather than fungistatic activity. Furthermore, P. dispersa strains significantly inhibited C. fimbriata growth on the leaves and tuberous roots of a susceptible sweet potato cultivar ("Yulmi"). These findings suggest that P. dispersa strains could inhibit black rot in sweet potato plants, highlighting their potential as biocontrol agents.

Genomic detection and molecular characterization of two distinct isolates of cycas necrotic stunt virus from Paeonia suffruticosa and Daphne odora.

Complete genome sequences of two cycas necrotic stunt virus (CNSV) isolates from Paeonia suffruticosa and Daphne odora were determined. Phylogenetic trees and pairwise comparisons using complete RNA1- and RNA2-encoded polyproteins showed that the two CNSV isolates are divergent (83.19%-89.42% in polyprotein 1 and 73.61%-85.78% in polyprotein 2). A comparative analysis based on taxonomic criteria for the species demarcation of nepoviruses confirmed that they are not new species but distinct variants. This is the first report of the complete genome sequences of CNSV detected in P. suffruticosa and D. odora, and the first report of CNSV infecting P. suffruticosa.

A human pathogenic bacterium Shigella proliferates in plants through adoption of type III effectors for shigellosis.

Shigella, which infects primates, can be transmitted via fresh vegetables; however, its molecular interactions with plants have not been elucidated. Here, we show that four Shigella strains, Shigella boydii, Shigella sonnei, Shigella flexneri 2a, and S. flexneri 5a, proliferate at different levels in Arabidopsis thaliana. Microscopic studies revealed that these bacteria were present inside leaves and damaged plant cells. Green fluorescent protein (GFP)-tagged S. boydii and S. flexneri 5a colonized leaves only, whereas S. flexneri 2a colonized both leaves and roots. Using Shigella mutants lacking type III secretion systems (T3SSs), we found that T3SSs that regulate the pathogenesis of shigellosis in humans also play a central role in bacterial proliferation in Arabidopsis. Strikingly, the immunosuppressive activity of two T3S effectors, OspF and OspG, was required for proliferation of Shigella in Arabidopsis. Of note, delivery of OspF or OspG effectors inside plant cells upon Shigella inoculation was confirmed using a split GFP system. These findings demonstrate that the human pathogen Shigella can proliferate in plants by adapting immunosuppressive machinery used in the original host human.