SEARCH · PubMed Health

Results for “reverse engineering”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 325 records · Page 18Linked to original sources

PubMed2003

In vivo model for cross-species porcine endogenous retrovirus transmission using tissue engineered pulmonary arteries.

OBJECTIVE: Acellularised porcine scaffolds have been successfully used for cardiovascular tissue engineering. However, there is concern about the possibility of porcine endogenous retrovirus (PERV) transmission. In this study we developed an in vivo model for cross-species PERV transmission. METHODS: In vitro autologous repopulated porcine pulmonary arteries (n=6) were implanted in sheep in orthotopic position. Blood samples were collected regularly up to 6 months after implantation and tested for PERV by means of polymerase chain reaction and reverse transcriptase-polymerase chain reaction. Explanted tissue engineered pulmonary arteries were tested for PERV sequences. RESULTS: PERV DNA was detectable in acellularised porcine scaffolds. No PERV sequences were detectable 6 months after implantation of in vitro repopulated acellularised porcine pulmonary arteries and in all tested peripheral blood samples. CONCLUSIONS: Acellularised porcine matrix scaffolds can be used for cardiovascular tissue engineering of autologous grafts without risk of PERV transmission.

Animals↗

PubMed2002

Are beta-sheet breaker peptides dissolving the therapeutic problem of Alzheimer's disease?

Alzheimer's disease (AD) is a neurodegenerative disorder for which there is no cure or effective treatment. One of the major neuropathological signatures of AD is the deposition of amyloid plaques in the brain of affected people. Although the role of these structures in the pathogenesis of the disease is not fully understood, recent findings have provided evidence that amyloid may be a key player in the disease. Therefore, preventing and reversing cerebral amyloid deposition have become an attractive therapeutic strategy for AD. We have engineered synthetic beta-sheet breaker peptides to bind soluble amyloid peptide and prevent and reverse its conversion to the beta-sheet rich aggregated structure, precursor of the amyloid plaques. Results in vitro, in cell culture and in vivo suggest that beta-sheet breaker peptides might be candidates for an AD-therapy focused to reduce amyloid deposition.

Aged↗

PubMed2026

The future of TCR-Treg therapies is renewables.

Cell therapy has longstanding roots in haematopoietic stem cell transplantation and early immune cell transfers in infectious disease and transplantation, where patient- or donor-derived cells have achieved therapeutic benefit in selected contexts. The modern era has been driven largely by oncology, with engineered modalities such as tumour-infiltrating lymphocytes, CAR-T cells and TCR-engineered T cells delivering transformative responses but requiring complex, costly manufacturing. These platforms are now being adapted for autoimmune diseases to induce durable, antigen-specific immune tolerance, yet broad application is limited by safety concerns, process complexity and access. Non-engineered cell therapies for autoimmunity, including mesenchymal stem cells, polyclonal regulatory T cells and tolerogenic dendritic cells, have shown acceptable safety and proof-of-principle for immune re-education, but clinical responses have been modest and inconsistent, with limited scalability. Engineered approaches such as CAR-T cells can induce reversible B cell depletion in B cell-mediated rheumatic diseases but only addresses antibody-driven pathology and not T cell-mediated autoimmunity. TCR-engineered Tregs have emerged as a promising antigen-specific strategy, offering localized, antigen-linked suppression with bystander tolerance. Preclinical and early clinical data suggest superior potency, stability and disease control compared with polyclonal Tregs at similar or lower doses, but translation is constrained by the rarity and fragility of Tregs and by labour-intensive, CAR-T-like manufacturing. This review highlights emerging solutions for closed, automated and decentralised production, and discusses allogeneic approaches using gene-edited or banked Tregs with HLA engineering or matching. Together, these advances support the development of scalable, "off-the-shelf" TCR-Treg products with potential to provide safe, affordable tolerance-restoring therapies for autoimmune disease.

Humans↗

PubMed2003

New building blocks for the assembly of sequence selective molecular zippers.

Synthetic H-bonded molecular zippers contain no sequence information that can be used to engineer the selective binding interactions characteristic of biopolymers; reversing the sense of the amide bonds in the two binding partners generates a new orthogonal recognition motif and the mutually complementary binding partners form complexes an order of magnitude more stable than the corresponding mismatch complexes.

Amino Acid Motifs↗

PubMed1983

The iceperson cometh: cryonics, law and medicine.

The "New Biology" has already made profound impact on the law. Cryonics and genetic engineering represent technological triumphs. The natural, organic process of dying is being replaced by a humanly engineered technological process for living. The dying phase of life is prolonged until biological knowledge is available to reverse the dying phase and restore the living phase. Both cryonics and genetic engineering in their attempts to replace the organic process with the technological process disturb the delicate balance of the triad of life which each individual experiences--faith, health, and justice. Since law is a basic tool to achieve justice among human beings, how should it respond to the health argument of the cryonics' physician who views death as a disease which is curable? How should the law respond to the faith questions surrounding the cryonics patient? What am I? A block of ice. Who am I? A living, comatose patient or a dormant, static body with the possibility of a reverter. Why am I? A new human being now endowed with immortality through the triumph of life over death founded on man's current faith in the God called Technology. Cryonics through its unbalancing of the traditional triad of life poses formidable challenges to the major institutions of faith, health and justice. The practitioners in these institutions: clergy, physicians and lawyers must now reassess the rules of the game of life be they religious, medical or legal. This article offers insights to begin this reassessment.

Death↗

PubMed2004

[Subcloning of human neurotrophin-3 gene and construction of its genetically engineered cell model].

OBJECTIVE: To subclone human neurotrophin-3 gene (NT3) and transfer this gene into human bone marrow mesenchymal stem cells (BM-MSCs) to construct genetically engineered cells that produce NT3 in vitro. METHODS: Human BM-MSCs were cultured in low-glucose DMEM supplemented with 10% fetal bovine serum and 10 ng/ml epidermal growth factor. Flow cytometry (FCM) was used to examine the phenotypes of the cells. The eukaryotic expression vector pcDNA3.1(+)/NT3 was constructed and transferred into human BM-MSCs in vitro via liposomes. The genetically engineered BM-MSCs were selected several times with G418 and the clones were obtained and then amplified, followed by extraction of the RNA for detection of NT3 gene expression by reverse transcriptional (RT) PCR. The biological activity of the genetically engineered cells was examined by the collecting the supernatant of the culture medium for incubation of guinea pig cochlea hair cells. RESULTS: The cultured cells expressed CD13, CD29 and CD59, but no7 CD11, CD14, CD31, CD34, CD45, CD80, CD86, CD117 or HLA-DR. The BM-MSCs genetically modified with pcDNA3.1(+)/NT3 not only expressed and produced NT3, but also promoted the survival of the guinea pig cochlea hair cells in vitro. CONCLUSION: It is possible to construct the genetically engineered BM-MSCs that excrete NT3 in vitro.

Animals↗

PubMed1987

Effects of engineering complementary charged residues into the hydrophobic subunit interface of tyrosyl-tRNA synthetase. Appendix: Kinetic analysis of dimeric enzymes that reversibly dissociate into inactive subunits.

Wild-type tyrosyl-tRNA synthetase (TyrTS) from Bacillus stearothermophilus is a symmetrical dimer. Four different heterodimeric enzymes have been produced by site-directed mutagenesis at the subunit interface so that the monomers are linked by a potential salt bridge in a hydrophobic environment. The two Phe-164 residues of wild-type TyrTS are on the axis of symmetry and interact in a hydrophobic region of the subunit interface. Mutation of Phe-164 to aspartate or glutamate in full-length TyrTS and to lysine or arginine in an active truncated enzyme (delta TyrTS) induces reversible dissociation of the enzyme into inactive monomers. Mixing mutants in equimolar amounts produces four different heterodimers: TyrTS(Asp-164)-delta TyrTS(Lys-164); TyrTS(Asp-164)-delta TyrTS(Arg-164); TyrTS(Glu-164)-delta TyrTS(Lys-164); TyrTS(Glu-164)-delta TyrTS(Arg-164). A general method is derived for analyzing the kinetics of dimeric enzymes that reversibly dissociate into inactive subunits. Application to mutants of TyrTS allows estimation of dissociation constants (Kd values) for the dimers. At pH 7.8, the heterodimers have Kd values of 6-14 microM, whereas for homodimers Kd = 120-4000 microM. These values decrease to about 30 microM for homodimers of TyrTS(Asp-164), TyrTS(Glu-164), and delta TyrTS(Lys-164) when the pH favors uncharged forms of the side chains at position 164. Each of the four salt bridges engineered into the hydrophobic subunit interface of TyrTS appears, therefore, to be weak. These engineered salt bridges may be compared with naturally occurring ones. In the latter, there are complementary interactions between the charges in the salt bridge with polar groups in the protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acyl-tRNA Synthetases↗

PubMed1996

The mechanism of velocity modulated allosteric regulation in D-3-phosphoglycerate dehydrogenase. Cross-linking adjacent regulatory domains with engineered disulfides mimics effector binding.

D-3-Phosphoglycerate dehydrogenase (PGDH) (EC 1.1.1.95) from Escherichia coli is an allosterically regulated enzyme of the Vmax type. It is a tetramer of identical subunits and each subunit is made up of three identifiable domains, the cofactor binding domain, the substrate binding domain, and the regulatory domain. Each subunit contacts two other subunits through adjacent cofactor binding domains and through adjacent regulatory domains. L-Serine, the physiological effector, inhibits catalytic activity by apparently tethering regulatory domains from adjacent subunits together through the formation of hydrogen bonds to each subunit. This investigation demonstrates that cross-linking adjacent regulatory domains with engineered disulfides produces catalytic inhibition in the absence of inhibitor in a manner similar to that produced by the inhibitor. The inhibition due to cross-linking can be completely reversed in a concentration dependent manner by dithiothreitol. The active mutant enzyme, containing the engineered cysteines in the reduced state, retains its ability to be inhibited by L-serine, although at a 100-fold higher concentration. Hill plots of the serine inhibition of mutant and native enzyme indicate that the number of interacting sites remains at 2 in the mutant enzyme. The reversible inhibition of enzyme activity that results from tethering adjacent regulatory domains with engineered disulfides suggests that these domains move in some manner relative to one another during the active to inhibited state transition. These observations support the model which predicts that catalytic activity is regulated by the movement of rigid domains about flexible hinges and that effector binding prevents this by locking the regulatory domains in a state that produces an open active site cleft.

Allosteric Regulation↗

PubMed2004

Site-specific and reversible anchoring of active proteins onto cellulose using a cellulosome-like complex.

Protein engineering strategies facilitating controlled and spontaneous assembly of macromolecular complexes are of great interest for the design of artificial multi-enzyme systems of pre-defined composition. Here we have combined affinity proteins from different sources to achieve specific and reversible anchoring of affinity domain-tagged reporter proteins to a cellulose-anchored fusion protein. The design principle mimics the architecture of macromolecular cellulosome complexes produced by some cellulolytic microbes. A fusion protein between a cellulose-binding module (CBM1Cel6A) of the Trichoderma reesei cellobiohydrolase Cel6A and a five-domain staphylococcal protein A (SPA) was constructed to serve as platform for docking of easily detectable reporter proteins onto cellulose surfaces. In turn, the reporter proteins were produced as fusions to two copies of a SPA-binding affinity protein (an affibody denoted Z(SPA-1)), selected from a phage display library constructed by combinatorial protein engineering. In a series of experiments, involving repeated washing and low pH elution, affinity-tagged Enhanced Green Fluorescent Protein (EGFP) and Fusarium solani pisi lipase cutinase reporter proteins were both found to be specifically directed from solution to the same region of a cellulose filter paper where SPA-CBM1Cel6A fusion protein had been previously applied. This showed that the SPA-CBM1Cel6A fusion protein had been stably anchored to the cellulose surface without loss of binding capacity and that the interaction between SPA and the Z(SPA-1) affibody domains was selective. The generality of this biospecificity-driven system for assembly applications is discussed.

Cellulose↗

PubMed2005

Chemical genetic engineering of G protein-coupled receptor kinase 2.

G protein-coupled receptor kinases (GRKs) play a pivotal role in receptor regulation. Efforts to study the acute effects of GRKs in intact cells have been limited by a lack of specific inhibitors. In the present study we have developed an engineered version of GRK2 that is specifically and reversibly inhibited by the substituted nucleotide analog 1-naphthyl-PP1 (1Na-PP1), and we explored GRK2 function in regulated internalization of the mu-opioid receptor (muOR). A previously described method that conferred analog sensitivity on various kinases, by introducing a space-creating mutation in the conserved active site, failed when applied to GRK2 because the corresponding mutation (L271G) rendered the mutant kinase (GRK2-as1) catalytically inactive. A sequence homology-based approach was used to design second-site suppressor mutations. A C221V second-site mutation produced a mutant kinase (GRK2-as5) with full functional activity and analog sensitivity as compared with wild-type GRK2 in vitro and in intact cells. The role of GRK2-as5 activity in the membrane trafficking of the muOR was also characterized. Morphine-induced internalization was completely blocked when GRK2-as5 activity was inhibited before morphine application. However, inhibition of GRK2-as5 during recycling and reinternalization of the muOR did not attenuate these processes. These results suggest there is a difference in the GRK requirement for initial ligand-induced internalization of a G protein-coupled receptor compared with subsequent rounds of reinternalization.

Adenosine Triphosphate↗

PubMed2000

Alleviation of murine leukemia virus repression in embryonic carcinoma cells by genetically engineered primer binding sites and artificial tRNA primers.

The primer binding site (PBS) plays pivotal roles during reverse transcription of retroviruses and also is the target of a cellular host defense impeding the transcription of murine leukemia virus (MLV) harboring a proline (pro) PBS in embryonic cells. Both the PBS and the tRNA primer are copied during reverse transcription and anneal as complementary DNA sequences creating the PBS of the integrated provirus. The pro PBS of MLV can be exchanged by PBS sequences matching endogenous or engineered tRNAs to allow replication of Akv MLV-derived vectors in fibroblasts. Here we use the PBS escape mutant B2 to demonstrate the capacity of the synthetic tRNA(B2) to function in reverse transcription in competition with endogenous tRNAs in fibroblasts and embryonic carcinoma (EC) cells. We further show symmetry between PBS and the primer by the ability of the synthetic tRNA(B2) to confer escape from EC repression of a PBS-Pro vector. Of a panel of vectors with the repressed pro PBS substituted for other natural or artificial PBS sequences, all except one efficiently expressed the neo marker gene when transferred to NIH/3T3 and EC cells, hence avoiding PBS-mediated silencing in EC cells. A non-natural PBS matching an artificially designed tRNA molecule conferred no further relief from repression than that attained with the B2 escape mutant or the natural alternative PBSs. Interestingly, a vector harboring a PBS matching tRNA(Lys1.2) suffered repression similar to the wild-type PBS-Pro but was partially rescued by a single point mutation of the PBS.

3T3 Cells↗

PubMed2001

Generation of a humanised single chain Fv (Scfv) derived from the monoclonal Eric-1 recognising the human neural cell adhesion molecule.

BACKGROUND: Murine monoclonal antibody (MoAb) ERIC-1 recognises an epitope on the neural cell adhesion molecule (NCAM) whose expression in paediatric and adult tissues is confined mainly to the brain, peripheral nerve, and adrenal medulla. Anti-NCAM antibodies have been used for the treatment and diagnosis of a number of tumours, including neuroblastoma. However, whole antibody exhibits poor penetration into solid tumour deposits and rapid systemic clearance upon repeated administration due to development of a human antimouse antibody (HAMA) response. PROCEDURE: To overcome these problems, recombinant DNA techniques have been used to humanise and assemble the ERIC-1 immunoglobulin variable heavy (VH) and light (VL) chains into a single chain Fv (scFv). RESULTS: Three humanised scFv clones were identified which differ from the predicted humanised sequence by occasional amino acid changes, but these maintain the same specificity as the original ERIC-1 MoAb. CONCLUSIONS: The humanised scFv may prove to be a useful reagents in the treatment and diagnosis of a variety of neuroectodermal tumours and can clearly form a suitable template for the generation of a fully humanised ERIC-1 MoAb.

Amino Acid Sequence↗

PubMed2000

Development of a plant-derived subunit vaccine candidate against hepatitis C virus.

Hepatitis C virus (HCV) is a major cause of acute and chronic hepatitis with over 180 million cases worldwide. Vaccine development for HCV has been difficult. Presently, the virus cannot be grown in tissue culture and there is no vaccine or effective therapy against this virus. In this research, we describe the development of an experimental plant-derived subunit vaccine against HCV. A tobamoviral vector was engineered to encode a consensus sequence of hypervariable region 1 (HVR1), a potential neutralizing epitope of HCV, genetically fused to the C-terminal of the B subunit of cholera toxin (CTB). This epitope was selected from among the amino acid sequences of HVR1 "mimotopes" previously derived by phage display technology. The nucleotide sequence encoding this epitope was designed utilizing optimal plant codons. This mimotope is capable of inducing cross-neutralizing antibodies against different variants of the virus. Plants infected with recombinant tobacco mosaic virus (TMV) engineered to express the HVR1/CTB chimeric protein, contained intact TMV particles and produced the HVR1 consensus peptide fused to the functionally active, pentameric B subunit of cholera toxin. Plant-derived HVR1/CTB reacted with HVR1-specific monoclonal antibodies and immune sera from individuals infected with virus from four of the major genotypes of HCV. Intranasal immunization of mice with a crude plant extract containing the recombinant HVR1/CTB protein elicited both anti-CTB serum antibody and anti-HVR1 serum antibody which specifically bound to HCV virus-like particles. Using plant-virus transient expression to produce this unique chimeric antigen will facilitate the development and production of an experimental HCV vaccine. A plant-derived recombinant HCV vaccine can potentially reduce expenses normally associated with production and delivery of conventional vaccines.

Administration, Intranasal↗

PubMed2003

Construction of an infectious chimeric classical swine fever virus containing the 5'UTR of bovine viral diarrhea virus, and its application as a universal internal positive control in real-time RT-PCR.

RT-PCR is used widely as a diagnostic method to detect and differentiate pestiviruses. The construction of two chimeric classical swine fever virus (CSFV) recombinants based on a marker virus constructed previously [J. Virol. 72 (1998) 5318-5322] is described. These viruses, termed vA187CAT_5UTRBVD and vA187CAT_IRESBVD, contain the entire 5' untranslated region (5'UTR) or the internal ribosome entry site (IRES) of bovine viral diarrhea virus (BVDV), respectively. Both chimeric viruses proved to be infectious in cell culture. Hence, the 5'UTR as well as the IRES element only of BVDV can substitute for the corresponding genome region of CSFV. Next, two sets of primers and corresponding dual-labeled TaqMan probes were designed; one detecting specifically a conserved but CSFV-specific area within the 5'UTR of wild-type CSFV, the other one targeting the CAT gene inserted in vA187CAT_5UTRBVD. The two primer/probe sets were combined in a closed-tube multiplex one-step RT-PCR. To monitor the entire extraction and detection process limited amounts of vA187CAT_5UTRBVD were added directly to clinical samples before RNA extraction. The multiplex RT-PCR proved to be as sensitive as the single primer/probe set method, but allowed the validation of each sample tested individually, based on the detection of the CAT marker gene. vA187CAT_5UTRBVD was also used successfully for foot-and-mouth disease virus (FMDV) TaqMan RT-PCR. Therefore, it is considered a universal internal positive control for RT-PCR assays to exclude loss of RNA during extraction, or failure of amplification due to inhibitory substances present in the sample.

5' Untranslated Regions↗

PubMed2004

Severe acute respiratory syndrome coronavirus pathogenesis, disease and vaccines: an update.

BACKGROUND: A novel coronavirus has recently been identified as the cause of severe acute respiratory syndrome (SARS-CoV). The ability of this family of positive strand RNA viruses to move between species and cause severe disease in humans, with the potential for pandemic spread, has been confirmed. METHODS: An understanding of the disease and its pathogenesis and the genetics of coronavirus infections, as well as strategies to treat or prevent coronavirus infections, are essential. The history of coronavirus vaccines and the occurrence of laboratory-associated SARS-CoV infections underscore the need for stably attenuated strains of SARS-CoV and other coronaviruses. RESULTS: Rapid progress has been made in understanding the clinical disease of SARS in adults and children. In adults, systemic infection with clinical and biochemical abnormalities, as well as respiratory infection, may be the rule. SARS is much milder in children younger than 12 years old than it is in adolescents and adults. In children age 12 years and younger, symptoms are generally nonspecific and cold-like. Numerous approaches to the development of SARS-CoV vaccines have been undertaken, and there is evidence that antibodies to the spike protein may be protective from replication and pathology in animal models. CONCLUSIONS: The availability of reverse genetic systems has made it possible to engineer and recover coronavirus variants that contain multiple genetically stable mutations that grow well in culture but are attenuated for replication, virulence or both. Such variants will be platforms for the safe growth of SARS-CoV and candidates for live attenuated vaccines.

Adolescent↗

PubMed2025

Mapping early PRC2 nucleation sites upon Suz12 reintroduction reveals features of de novo Polycomb recruitment.

Polycomb domains safeguard cell identity by maintaining lineage-specific chromatin states enriched in repressive histone modifications, preserving the epigenetic memory of cell lineages. While Polycomb Repressive Complex 2 (PRC2) can re-establish its occupancy after perturbation, the mechanisms that guide de novo Polycomb recruitment remain unclear. To address this, we engineered an auxin-inducible degradation system to reversibly deplete and reintroduce the endogenous PRC2 core subunit Suz12 in mouse embryonic stem cells (mESCs). Genome-wide profiling at an early recovery time point revealed ~1,100 PRC2 nucleation sites, characterized by rapid Suz12 and histone H3K27me3 re-accumulation with strong signal, with minimal impact on gene expression. These sites were significantly enriched at bivalent promoters, coinciding with unmethylated CpG islands and chromatin states associated with developmental regulation, and were largely conserved in differentiated cells. Motif analysis identified G/C-rich DNA sequences associated with E2F and zinc-finger proteins, alongside strong co-occupancy with MTF2 and JARID2, two PRC2 cofactors previously implicated in Polycomb targeting. Notably, a subset of nucleation sites overlapped with long-range chromatin interaction anchors in histone H3K27me3 HiChIP datasets. These findings reveal that PRC2 de novo nucleation sites are associated with a combination of chromatin states, DNA sequence features, cofactor co-occupancy and spatial genome organization, suggesting that epigenetic memory can be re-established through defined genomic and chromatin features.

Epigenetic memory↗

PubMed2003

Self-organization from structural refrigeration.

The self-organization of a classical current is studied, in an exactly solvable model where both the quantum statistics over microhistories of particles, and the macroscopic phenomenology, can be computed in closed form. It is shown that for thermodynamically reversible systems, the Jaynes formulation of statistical mechanics naturally extends to include explicit macroscopic dynamics and heterogeneities in temperature, while preserving the structure of partition functions, effective potentials, and ground states of the equilibrium theory. Self-organization in such reversible systems is constrained by entropy transport through engine and refrigeration cycles, rather than by diffusion in gradients. Limitations in the ability to decompose such systems sensibly into components with additive entropies, and in the extrapolation of entropy functions from equilibrium forms, are discussed with examples.

Journal Article↗

PubMed2005

Multiple gene segments control the temperature sensitivity and attenuation phenotypes of ca B/Ann Arbor/1/66.

Cold-adapted (ca) B/Ann Arbor/1/66 is the influenza B virus strain master donor virus for FluMist, a live, attenuated, influenza virus vaccine licensed in 2003 in the United States. Each FluMist vaccine strain contains six gene segments of the master donor virus; these master donor gene segments control the vaccine's replication and attenuation. These gene segments also express characteristic biological traits in model systems. Unlike most virulent wild-type (wt) influenza B viruses, ca B/Ann Arbor/1/66 is temperature sensitive (ts) at 37 degrees C and attenuated (att) in the ferret model. In order to define the minimal genetic components of these phenotypes, the amino acid sequences of the internal genes of ca B/Ann Arbor/1/66 were aligned to those of other influenza B viruses. These analyses revealed eight unique amino acids in three proteins: two in the polymerase subunit PA, two in the M1 matrix protein, and four in the nucleoprotein (NP). Using reverse genetics, these eight wt amino acids were engineered into a plasmid-derived recombinant of ca B/Ann Arbor/1/66, and these changes reverted both the ts and the att phenotypes. A detailed mutational analysis revealed that a combination of two sites in NP (A114 and H410) and one in PA (M431) controlled expression of ts, whereas these same changes plus two additional residues in M1 (Q159 and V183) controlled the att phenotype. Transferring this genetic signature to the divergent wt B/Yamanashi/166/98 strain conferred both the ts and the att phenotypes on the recombinant, demonstrating that this small, complex, genetic signature encoded the essential elements for these traits.

Adaptation, Physiological↗