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S Shen

Publications and source records attributed to S Shen.

At least 55 records · Page 3Linked to original sources

Comparison of the 5' leader sequences of North American isolates of reference and field strains of porcine reproductive and respiratory syndrome virus (PRRSV).

The 5' leader is documented to be an important regulatory element in many (+) ssRNAvirus genome. To understand the significance of the 5' leader RNA of PRRSV, we determined the complete leader sequences of fifteen different North American strains of PRRSV and predicted their secondary structures. Viruses analysed included three reference strains and nine field strains originating from different geographic locations. To further examine the leader region, one of the field strains was adapted to grow in tissue culture, and three clones were isolated. We also predicted the secondary structures of two European strains based on their published sequences. The predicted RNA secondary structures of the leader sequences suggested the existence of three conserved domains formed by the 5' region of the leader among the North American strains, two of which were conserved in the European strains. A variable structural domain was predicted from the 3' region of the leader sequences of the North American strains, where all tissue culture-adapted isolates were characterized by a stem-loop while field isolates were characterized by an internal bulge within the stem-loop.

5' Untranslated Regions↗

Increased IGFR activity and glucose transport in cultured skeletal muscle from insulin receptor null mice.

We have studied the role of the insulin receptor (IR) in metabolic and growth-promoting effects of insulin on primary cultures of skeletal muscle derived from the limb muscle of IR null mice. Cultures of IR null skeletal muscle displayed normal morphology and spontaneous contractile activity. Expression of muscle-differentiating proteins was slightly reduced in myoblasts and myotubes of the IR null skeletal muscle cells, whereas that of the Na+/K+ pump appeared to be unchanged. Insulin-like growth factor receptor (IGFR) expression was higher in myoblasts from IR knockout (IRKO) than from IR wild-type (IRWT) mice but was essentially unchanged in myotubes. Expression of the GLUT-1 and GLUT-4 transporters appeared to be higher in IRKO than in IRWT myoblasts and was significantly greater in myotubes from IRKO than from IRWT cultures. Consistent with GLUT expression, both basal and insulin or insulin-like growth factor I (IGF-I)-stimulated glucose uptakes were higher in IR null skeletal myotubes than in wild-type skeletal myotubes. Interestingly, autophosphorylation of IGFR induced by insulin and IGF-I was markedly increased in IR null skeletal myotubes. These results indicate that, in the absence of IR, there is a compensatory increase in basal as well as in insulin- and IGF-I-induced glucose transport, the former being mediated via increased activation of the IGF-I receptor.

Animals↗

Adolescent alcohol expectancies in offspring from families at high risk for developing alcoholism.

OBJECTIVE: The present study investigated alcohol expectancies derived from the Alcohol Expectancy Questionnaire (AEQ) in parents and their adolescent offspring. It was of interest to determine whether alcohol expectancies would differ by risk status, and whether those differences were influenced by parental beliefs. METHOD: Children/ adolescents aged 8 to 18, from families at high risk for developing alcoholism (n = 69; 37 males) and from low-risk control families (n = 46; 25 males), were evaluated annually. At every assessment, each child and one parent were administered the AEQ and interviewed to determine drinking status. Data for two time points approximately 3 years apart were analyzed. RESULTS: In early adolescence, high-risk offspring expected more improvement in social functioning when under the influence of alcohol than did low-risk controls. However, by age 16, risk group differences were not seen. Higher scores on two of the AEQ scales (Social Behavior and Relaxation) predicted the age of onset for regular drinking, whereas one scale (Social Behavior) predicted drinking behavior. In addition, high-risk offspring were found to have beliefs about the effects of alcohol that were similar to those of their parents, in contrast to low-risk offspring and their parents, who displayed significant negative correlations. CONCLUSIONS: This report confirms previous studies relating alcohol expectancies to drinking behavior (frequency, quantity per occasion, social consequences). Alcohol expectancies also were found to predict the age of onset to begin regular drinking in the combined group of adolescents studied, although risk differences in age of onset were not influenced by differing expectations concerning the effects of alcohol. These results suggest that the risk differences in expectancies that were seen in young adolescents (approximately age 13) may be due to the transmission of parental beliefs to their offspring. The absence of risk differences by late adolescence (approximately age 16) suggests that other factors (e.g., peer influences or experience drinking alcohol) also play a role.

Adolescent↗

PKCdelta activation: a divergence point in the signaling of insulin and IGF-1-induced proliferation of skin keratinocytes.

Insulin and insulin-like growth factor-1 (IGF-1) are members of the family of the insulin family of growth factors, which activate similar cellular downstream pathways. In this study, we analyzed the effects of insulin and IGF-1 on the proliferation of murine skin keratinocytes in an attempt to determine whether these hormones trigger the same signaling pathways. Increasing doses of insulin and IGF-1 promote keratinocyte proliferation in an additive manner. We identified downstream pathways specifically involved in insulin signaling that are known to play a role in skin physiology; these include activation of the Na+/K+ pump and protein kinase C (PKC). Insulin, but not IGF-1, stimulated Na+/K+ pump activity. Furthermore, ouabain, a specific Na+/K+ pump inhibitor, abolished the proliferative effect of insulin but not that of IGF-1. Insulin and IGF-1 also differentially regulated PKC activation. Insulin, but not IGF-1, specifically activated and translocated the PKCB isoform to the membrane fraction. There was no effect on PKC isoforms alpha, eta, epsilon, and zeta, which are expressed in skin. PKC8 overexpression increased keratinocyte proliferation and Na+/K+ pump activity to a degree similar to that induced by insulin but had no affect on IGF-1-induced proliferation. Furthermore, a dominant negative form of PKCdelta abolished the effects of insulin on both proliferation and Na+/K+ pump activity but did not abrogate induction of keratinocyte proliferation induced by other growth factors. These data indicate that though insulin or IGF-1 stimulation induce keratinocyte proliferation, only insulin action is specifically mediated via PKC8 and involves activation of the Na+/K+ pump.

Animals↗

Radioimmunotherapy with (111)In/(90)Y-2IT-BAD-m170 for metastatic prostate cancer.

PURPOSE: Over 31,000 Americans die of androgen-independent metastatic prostate cancer each year. New strategies that do not involve hormonal manipulation but instead recognize the biochemical and molecular characteristics of prostate cancer are needed. Radioimmunotherapy (RIT) uses a tumor-specific monoclonal antibody to deliver systemic, targeted radiation to cancer. The objectives of this Phase I study of (111)In-2IT-BAD-m170 (for imaging) and (90)Y-2IT-BAD-m170 (for therapy) were to determine the toxicity and maximum tolerated dose (MTD), the specificity for targeting metastatic prostate cancer, and the efficacy for palliation of pain. EXPERIMENTAL DESIGN: M170 is a mouse monoclonal antibody that targets adenocarcinomas. Patients with adequate renal and liver function, rising prostate-specific antigen, and androgen-independent metastatic prostate cancer were eligible. After estimation of dosimetry and pharmacokinetics with (111)In-2IT-BAD-m170, a single dose of (90)Y-2IT-BAD-m170 (0.185, 0.370, 0.555, or 0.740 GBq/m(2)) was administered to cohorts of three patients. Pain was assessed objectively by questionnaires before and for 8 weeks after RIT; weekly prostate-specific antigen levels were obtained for 2 months after RIT. RESULTS: The MTD of (90)Y-2IT-BAD-m170 was 0.740 GBq/m(2) for patients that had up to 10% of the axial skeleton involved with prostate cancer. Toxicity was almost exclusively confined to reversible myelosuppression. Metastatic prostate cancer was targeted by (111)In-2IT-BAD-m170 in all 17 patients. The mean radiation dose delivered to 39 bone and 18 nodal metastases by (90)Y-2IT-BAD-m170 was 10.5 Gy/GBq (range 2.8-25.1). Thirteen of 17 patients reported pain before (90)Y-2IT-BAD-m170; 7 of these 13 had a partial or complete resolution of pain that lasted an average of 4.3 weeks. CONCLUSIONS: This study determined the MTD of (111)In/(90)Y-2IT-BAD-m170 in patients with metastatic prostate cancer. The drugs were well tolerated, targeted metastases, and temporarily palliated pain.

Adenocarcinoma↗

Metabolite production in patients with lymphoma after radiometal-labeled antibody administration.

UNLABELLED: Radiometal-labeled monoclonal antibodies are retained longer in tumors than iodinated antibodies, leading to their increased use for radioimmunotherapy. Dissociation of radioiodine from the antibody during metabolism has been documented. We now report metabolites in the plasma of lymphoma patients given 111In- and 90Y-2-iminothiolane-2-[p-(bromoacetamido)benzyl]-1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid-Lym-1 (111In/90Y-2IT-BAD-Lym-1). METHODS: Nineteen patients with non-Hodgkin's lymphoma (NHL) received 111In- and 90Y-2IT-BAD-Lym-1; 111In was used as a surrogate tracer for 90Y, which emits no gamma-photon. Plasma was obtained up to 7 d and analyzed by high-performance liquid chromatography to determine the fraction of radiolabel associated with monomeric antibody, metabolites, and complexed antibody. Planar images of conjugate views were acquired up to 7 d and used to quantitate 111In in organs and tumors. RESULTS: Metabolites and complexes were observed in the plasma of every patient who received 111In-2IT-BAD-Lym-1. At 3 d, the mean percentages of 111In in the patients' plasma in monomeric, metabolite, and complexed forms were 54%, 36%, and 10%, respectively. Metabolites of 90Y-2IT-BAD-Lym-1 were formed to a similar extent. In comparison, in groups of breast and prostate cancer patients who received the radioimmunoconjugate 111In-2IT-BAD-m170, 91% and 94% of 111In in the patients' plasma were in monomeric form, respectively. Metabolites and complexes of 111In-2IT-BAD-Lym-1 contributed a mean 10% of the total area under the time-activity curve (AUC) for blood. Little formation of metabolites and complexes occurred in vitro in NHL patient or volunteer plasma or in Raji cell culture. The clinical and in vitro data supported the processing of 111In/90Y-2IT-BAD-Lym-1 in the hepatocytes as the dominant mechanism for the production of metabolites. CONCLUSION: Metabolites of 111In/90Y-2IT-BAD-Lym-1 accounted for 10% of blood AUC in patients. The therapeutic index was adversely affected by metabolism of 111In/90Y-2IT-BAD-Lym-1 to the extent that the tumor specificity of the radioactive metabolites was lost.

Adult↗

[Changes of crop yields and soil fertility under long-term application of fertilizer and recycled nutrients in manure on a black soil].

The results from a field experiment over thirteen years on a black soil in Northeast China indicated that nitrogen fertilizer increased crop yields by 724 kg.hm-2 per year on average, with an increase rate of 27.5% and about 9.4 kg increased yield from 1 kg applied N. In the early stage, the crop yields almost gave no response to phosphorus fertilizer, owing to the high level of soil available phosphorus at the beginning of the experiment. The average increase of crop yields by phosphorus in thirteen years was only 241 kg.hm-2 per year, with an increase rate of 7%, about 12.7 kg increased yield from 1 kg applied P. Annual application of recycled pig manure made by 80% of harvested grain fed to pigs and the stolks as bedding materials could increase crop yields by 268, 258 and 255 kg.hm-2 per year with an increase rate of 9.8%, 7.6% and 7.0%, based on no fertilizer, with N and with P and N, respectively. There was a trend that the effect of recycled manure on crop yield was gradually increased during the period of experiment, implying the existence of accumulative residual effect from the manure.

Agriculture↗

Conformational studies of cyclopropane carboxaldehydehyde from temperature-dependent FT-IR spectra of xenon solutions.

Variable temperature ( -60 to 100 degrees C) studies of the infrared spectra (3,500-400 cm(-1) of cyclopropane carboxaldehyde. c-C3H5CHO, dissolved in liquid xenon have been recorded. Utilizing several doublets due to the syn and anti conformers. the enthalpy difference has been determined to be 95 +/- 8 cm(-1) (1.14 +/- 0.10 kJ/mol) with the (anti conformer (oxygen atom trans to the three-member ring) the more stable rotamer. From this deltaH value, along with assigned torsional transitions for both the anti and svi, conformers, the potential function governing the conformational interchange has been estimated. Using the new infrared data from the xenon solution, along with some additional Raman data, and ab initio predictions from MP2/6-31G(d) calculations some reassignments of the fundamentals have been made. Ab initio calculations have been carried out with several different basis sets upto 6-311 +/- +G(d,p) with full electron correlation by the perturbation method to second order from which structural parameters and conformational stabilities have been determined. From all of the ab initio calculations, the syn conformer is predicted to be the more stable which is at variance with the experimental results. The spectroscopic and theoretical results are compared to the corresponding quantities for some similar molecules.

Cyclopropanes↗

Overexpression of the human VPAC2 receptor in the suprachiasmatic nucleus alters the circadian phenotype of mice.

The neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) belong to a superfamily of structurally related peptide hormones that includes glucagon, glucagon-like peptides, secretin, and growth hormone-releasing hormone. Microinjection of VIP or PACAP into the rodent suprachiasmatic nucleus (SCN) phase shifts the circadian pacemaker and VIP antagonists, and antisense oligodeoxynucleotides have been shown to disrupt circadian function. VIP and PACAP have equal potency as agonists of the VPAC(2) receptor (VPAC(2)R), which is expressed abundantly in the SCN, in a circadian manner. To determine whether manipulating the level of expression of the VPAC(2)R can influence the control of the circadian clock, we have created transgenic mice overexpressing the human VPAC(2)R gene from a yeast artificial chromosome (YAC) construct. The YAC was modified by a strategy using homologous recombination to introduce (i) the HA epitope tag sequence (from influenza virus hemagglutinin) at the carboxyl terminus of the VPAC(2)R protein, (ii) the lacZ reporter gene, and (iii) a conditional centromere, enabling YAC DNA to be amplified in culture in the presence of galactose. High levels of lacZ expression were detected in the SCN, habenula, pancreas, and testis of the transgenic mice, with lower levels in the olfactory bulb and various hypothalamic areas. Transgenic mice resynchronized more quickly than wild-type controls to an advance of 8 h in the light-dark (LD) cycle and exhibited a significantly shorter circadian period in constant darkness (DD). These data suggest that the VPAC(2)R can influence the rhythmicity and photic entrainment of the circadian clock.

Amino Acid Sequence↗

Efficacy of muscarinic stimulation and mode of excitation-contraction coupling in bovine trachealis muscle.

We have compared the efficacy of cromakalim and nifedipine to inhibit acetylcholine (ACh) and pilocarpine-induced tonic contractions in control preparations and in tissues where a fraction of the muscarinic receptor population had been removed by alkylation with phenoxybenzamine (PBZ). Both agonists induced contractions by stimulating pharmacologically similar receptors, probably of the M3 muscarinic subtype. The receptor reserve was larger, and the coupling between stimulation and contraction (E-C coupling) more efficient when ACh was the stimulating agonist. For stimulations that produced equal levels of muscle response, cromakalim was more efficacious in inhibiting contractions induced by pilocarpine. The efficacy of cromakalim in relaxing contractions induced by ACh increased when the number of functional receptors decreased. Cromakalim and nifedipine decreased the efficiency of E-C coupling for ACh and pilocarpine. Cromakalim efficacy decreased in a sigmoid manner when stimulating concentrations of ACh (and receptor occupancy) increased, and there was an inverse relationship between receptor occupancy by ACh and cromakalim efficacy. In the presence of TEA, a K+ channel blocker, nifedipine almost completely inhibited contractions induced by the M3 muscarinic agonist bethanechol. These data indicate that in bovine tracheal smooth muscle, electro-mechanical coupling is an inherent part of muscarinic E-C coupling, but its functional expression is dependent upon the efficacy of stimulation. The data also suggest that the M3 receptor is coupled to a cellular pathway linked with the activation of K+ channels that exerts a potent functional antagonism against activation of voltage-dependent Ca2+ entry.

Acetylcholine↗

Factors predicting the onset of adolescent drinking in families at high risk for developing alcoholism.

BACKGROUND: With a longitudinal prospective design, the purpose of this study was 1) to assess, with survival analysis, the age of onset of drinking in relation to family history of alcoholism; 2) to examine the importance of selected neurobiological and psychosocial risk factors in predicting the onset to drink; and 3) to determine if the age of onset of substance dependence problems differed by risk group status. METHODS: One hundred twenty-five children and adolescents were evaluated annually (N = 638 evaluations), providing up to seven annual waves of longitudinal data. Survival analyses were performed to determine the age of onset of regular drinking and the age of onset for substance abuse/dependence. The age of onset of regular drinking outcome was modeled using familial density of alcoholism and four factors, which included neurobiological indices of development (postural sway and P300), personality characteristics, academic achievement, self-esteem, and trait anxiety. RESULTS: High-risk children/adolescents showed a significantly earlier age of onset of drinking and an earlier age of onset for substance abuse problems. Familial density of alcoholism predicted an earlier onset of drinking, as did having deficits in reading achievement, reduced P300 (visual and auditory), and greater postural sway for age. Higher scores on the Extraversion scale of the Junior version of the Eysenck Personality Inventory also predicted an earlier onset of drinking. CONCLUSIONS: Familial density of alcoholism (number of alcoholic first- and second-degree relatives) is an important predictor of adolescent alcohol initiation. Evidence is presented suggesting that part of the familial/genetic variation in outcome may be due to neurobiological factors and temperament.

Adolescent↗

Perceptual alternation in obsessive compulsive disorder--implications for a role of the cortico-striatal circuitry in mediating awareness.

Mounting evidence suggests that obsessive compulsive disorder (OCD) results from functional aberrations of the fronto-striatal circuitry. However, empirical studies of the behavioral manifestations of OCD have been relatively lacking. The present study employs a behavioral task that allows a quantitative measure of how alternative percepts are formed from one moment to another, a process mimicking the brain state in which different thoughts and imageries compete for access to awareness. Eighteen patients with OCD, 12 with generalized anxiety disorder, and 18 normal subjects participated in the experiment, in which they viewed one of the three Schröder staircases and responded by pressing a key to each perceptual reversal. The results demonstrate that the patients with OCD have a higher perceptual alternation rate than the normal controls. Moreover, the frequency of perceptual alternation is significantly correlated with the Yale-Brown obsessive compulsive and the Hamilton anxiety scores. The increase in the frequency of perceptual reversals cannot easily be accounted for by learning or by different patterns of eye fixations on the task. These results provide further evidence that an impairment of the inhibitory function of the cortico-striatal circuitry might underlie the etiology of OCD. The implications of the results for a general role of the cortico-striatal circuitry in mediating awareness are discussed.

Adult↗

Life expectancy, antagonistic pleiotropy, and the testis of dogs and men.

BACKGROUND: Prostate cancer and benign prostatic hyperplasia are important age-related prostatic diseases that are under the influence of testicular hormones. However, the disparity between male and female life expectancy within the human population cannot be explained solely by the prevalence of prostatic disease-related mortality. The purpose of this paper is to explore the possibility that the testis exerts a detrimental effect on life span. METHODS: First, we review previously published and unpublished data on the influence of the testis on the life span of dogs and men. Aging in pet dogs and men is then discussed in terms of evolutionary theory, emphasizing the significance of a prolonged postreproductive life span and possible consequences of late-acting deleterious genes in these two species. Finally, we present preliminary data that orchiectomy can reduce DNA damage within the brain of elderly male dogs. RESULTS AND CONCLUSIONS Taken together, these observations raise the intriguing possibility that interventions to antagonize the testis might have much broader therapeutic applications that will extend well beyond the treatment of prostate cancer.

Adolescent↗

Developmental changes in postural sway in children at high and low risk for developing alcohol-related disorders.

BACKGROUND: To utilize the power of latent growth analysis to evaluate changes in postural sway during development in children who are either at high or low risk for developing alcoholism. METHODS: A total of 629 assessments of postural sway have been performed in children and adolescents (n = 126) who were evaluated annually over a 7-year period. RESULTS: Latent curve models indicated that these children/adolescents show a linear decrease in sway with age. Moreover, significantly different rates of change in the amount of sway between high- and low-risk offspring were seen. With the exception of one of the four stances tested, high-risk boys consistently showed a slower rate of improvement with respect to the amount of sway exhibited compared to low-risk boys. In girls, similar rates of improvement with age were seen in high- and low-risk individuals, though in one stance the high-risk girls showed a deterioration (greater sway with increasing age). CONCLUSIONS: Previous reports of increased postural sway in high-risk offspring most likely reflect a developmental delay (high-risk children have greater sway than is appropriate for their age based on normative values by age).

Adolescent↗

Determination of the complete nucleotide sequence of a vaccine strain of porcine reproductive and respiratory syndrome virus and identification of the Nsp2 gene with a unique insertion.

The complete nucleotide sequence of the genomic RNA of a vaccine strain (SP) of porcine reproductive and respiratory syndrome virus (PRRSV) was determined. It shares approximately 94% identity of nucleotide sequence with two recently reported North American strains, 16244B and VR2332, but only 78% with a European strain, Lelystad virus (LV). Its genome is the longest among the four published complete sequences of PRRSV, due to an insertion in the Nsp2-encoding region. Compared to Nsp2 of the North American strains and the European strain, the predicted Nsp2 of strain SP contains 36 and 155 amino acid insertions, respectively, near the C-terminus, in addition to several highly variable regions. The insertion shows no homology with any equivalent arterivirus proteins. This high sequence disparity of Nsp2 among different PRRSV isolates suggested that it could be used as a marker to differentiate PRRSV genotypes. The 5' RACE and primer extension analysis of three North American strains demonstrated that the utmost 5'-end nucleotides are conserved among PRRSV strains isolated from two continents. The predicted polyprotein 1 a/b contains conserved proteinase, polymerase and helicase domains responsible for polyprotein processing, RNA transcription and replication.

Animals↗

Refined mapping of the human serotonin transporter (SLC6A4) gene within 17q11 adjacent to the CPD and NF1 genes.

The SLC6A4 gene encodes the serotonin transporter, the target of an important class of antidepressant drugs (serotonin selective reuptake inhibitors). Polymorphisms in the SLC6A4 gene have been reported to be associated with susceptibility to depression and other psychiatric disorders. We have constructed a 1 Mb YAC and PAC contig which harbours both the SLC6A4 and the carboxypeptidase D (CPD) genes. The order of loci within the contig was cen-D17S975-D17S1549-24R-D17S1294-SLC6A4-28L+ ++-(CPD, D17S2009, D17S2004)-D17S2120-ter. Both genes were deleted in one of 17 neurofibromatosis type 1 (NF1) patients carrying submicroscopic NF1 contiguous gene deletions.

Carboxypeptidases↗

Immobilization of Pseudomonas cepacia lipase in a phyllosilicate sol-gel matrix: effectiveness as a biocatalyst.

A novel procedure is described for immobilizing a lipase from Pseudomonas cepacia (PS-30) within a phyllosilicate sol-gel matrix. The method is based on cross-linking a phyllosilicate clay with silicate polymers produced by the controlled hydrolysis of tetramethyl orthosilicate (TMOS). The activity of the phyllosilicate sol-gel-immobilized lipase was dependent upon the type of alkylammonium salt, inorganic catalyst and volume ratio of phyllosilicate clay to TMOS used. Lipase PS-30 immobilized in this way was more stable and had higher activity compared with the free lipase. Studies on the lipase-catalysed esterification of lauric acid with octan-1-ol in iso-octane showed that under controlled water activity conditions the phyllosilicate sol-gel-immobilized lipase had better activity compared with other supported lipase preparations. In addition, the phyllosilicate sol-gel-immobilized lipase was reusable for at least five esterification cycles without significant loss of activity.

Catalysis↗

Conversion of compatible plant-pathogen interactions into incompatible interactions by expression of the Pseudomonas syringae pv. syringae 61 hrmA gene in transgenic tobacco plants.

The hrmA gene from Pseudomonas syringae pv. syringae has previously been shown to confer avirulence on the virulent bacterium P. syringae pv. tabaci in all examined tobacco cultivars. We expressed this gene in tobacco plants under the control of the tobacco Delta0. 3 TobRB7 promoter, which is induced upon nematode infection in tobacco roots (Opperman et al. 1994, Science, 263, 221-223). A basal level of hrmA expression in leaves of transgenic plants activated the expression of pathogenesis-related genes, and the transgenic plants exhibited high levels of resistance to multiple pathogens: tobacco vein mottling virus, tobacco etch virus, black shank fungus Phytophthora parasitica, and wild fire bacterium Pseudomonas syringae pv. tabaci. However, the hrmA transgenic plants were not significantly more resistant to root-knot nematodes. Our results suggest a potential use of controlled low-level expression of bacterial avr genes, such as hrmA, in plants to generate broad-spectrum resistance to bacterial, fungal and viral pathogens.

Animals↗