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PubMed1991

Validation of the TNM classification (4th edn) for lung cancer: first results of a prospective study of 1086 patients with surgical treatment.

For the purpose of testing the validity of the new TNM classification (fourth edition) for lung cancer, data from 1086 patients with surgical treatment were analysed prospectively. Several items were examined: (1) the agreement between clinical (TNM) and pathologically confirmed classification (pTNM); (2) the value of the various diagnostic tests in estimating the pathologically confirmed classification; (3) the influence of the TNM definitions on separating distinct prognostic groups. With regard to the primary tumour (T), clinical and pathological classification were identical in 64% of the cases. With regard to lymph node involvement (N), the agreement was 48%, for distant metastasis 90% and for the staging 55%. As for the primary tumour (T), the accuracy of radiography (59%) was nearly identical with that of computed tomography (58%). Both these diagnostic techniques were less precise in determining the extent of lymph node involvement (computed tomography 50% correct assessments, radiography 43%). The statistically significant differences in the prognoses for the various pT, pN and pM categories as well as for the pathological stages and the categories of the new R classification could be confirmed. The new 1987 TNM definitions for lung cancer make possible international conformity; the classification is also practically useful and the prognostic relevance improved. The new classifications thus provide a more reliable basis for establishing guidelines for individual oncological therapy strategies and for the exchange of information between different centres on the progress made in diagnosis and therapy of lung cancer.

Carcinoma, Bronchogenic↗
PubMed1995

Solid-state nuclear magnetic resonance analysis of the conformation of an inhibitor bound to thermolysin.

A number of structural experimental methods are available to determine the receptor-bound conformation of ligands as part of the process of rational drug design, including X-ray diffraction and solution-state NMR. Not all receptor/ligand systems are amenable to these types of analyses due to difficulties in sample preparation or inherent limitations of the methods. Rotational echo double-resonance (REDOR) NMR is a solid-state, magic angle-spinning technique that measures the dipolar coupling between specifically labeled nuclei and enables the determination of internuclear distance. In previous studies of helical peptides, we have verified the ability of REDOR NMR to measure distances accurately and precisely. In this study we use REDOR and double REDOR to measure distances between backbone atoms in a phosphonamidate transition-state inhibitor bound to thermolysin. The 31P-13C', 31P-15N, and 31P-13C alpha distances (3.61 +/- 0.10, 3.89 +/- 0.12, and 5.37 +/- 0.13 A, respectively) measured in a complex of Cbz-GlyP-[1-13C]Leu-[15N,2-13C]Ala and the enzyme are consistent with those observed by X-ray diffraction in other comparable thermolysin/inhibitor complexes (average values of 3.58 +/- 0.04, 3.91 +/- 0.13, and 5.17 +/- 0.18 A, respectively). These results demonstrate that REDOR NMR is a viable alternative to more traditional methods such as X-ray diffraction, transferred NOESY, and isotope-edited NOESY for characterizing the receptor-bound conformation of ligands.

Amino Acid Sequence↗
PubMed2006

Children facing a family member's acute illness: a review of intervention studies.

BACKGROUND: A review of psycho-educational intervention studies to benefit children adapting to a close (parent, sibling, or grandparent) family member's serious illness was conducted. OBJECTIVES: To review the literature on studies addressing this topic, critique research methods, describe clinical outcomes, and make recommendations for future research efforts. DATA SOURCES: Research citations from 1990 to 2005 from Medline, CINAHL, Health Source: Nursing/Academic Edition, PsycARTICLES, and PsycINFO databases were identified. REVIEW METHODS: Citations were reviewed and evaluated for sample, design, theoretical framework, intervention, threats to validity, and outcomes. Reviewed studies were limited to those that included statistical analysis to evaluate interventions and outcomes. RESULTS: Six studies were reviewed. Positive outcomes were reported for all of the interventional strategies used in the studies. Reviewed studies generally lacked a theoretical framework and a control group, were generally composed of small convenience samples, and primarily used non-tested investigator instruments. They were diverse in terms of intervention length and intensity, and measured short-term outcomes related to participant program satisfaction, rather than participant cognitive and behavioral change. CONCLUSIONS: The paucity of interventional studies and lack of systematic empirical precision to evaluate intervention effectiveness necessitates future studies that are methodologically rigorous.

Acute Disease↗
PubMed1999

Automated semantic indexing of imaging reports to support retrieval of medical images in the multimedia electronic medical record.

This paper describes preliminary work evaluating automated semantic indexing of radiology imaging reports to represent images stored in the Image Engine multimedia medical record system at the University of Pittsburgh Medical Center. The authors used the SAPHIRE indexing system to automatically identify important biomedical concepts within radiology reports and represent these concepts with terms from the 1998 edition of the U.S. National Library of Medicine's Unified Medical Language System (UMLS) Metathesaurus. This automated UMLS indexing was then compared with manual UMLS indexing of the same reports. Human indexing identified appropriate UMLS Metathesaurus descriptors for 81% of the important biomedical concepts contained in the report set. SAPHIRE automatically identified UMLS Metathesaurus descriptors for 64% of the important biomedical concepts contained in the report set. The overall conclusions of this pilot study were that the UMLS metathesaurus provided adequate coverage of the majority of the important concepts contained within the radiology report test set and that SAPHIRE could automatically identify and translate almost two thirds of these concepts into appropriate UMLS descriptors. Further work is required to improve both the recall and precision of this automated concept extraction process.

Abstracting and Indexing↗
PubMed2005

Search for testicular cancer gene hits dead-end.

Testicular germ cell tumors (TGCTs) are the first tumors where the cell of origin, and the time of transformation were precisely defined. TGCTs in mice originate from primordial germ cells (PGCs) and develop within the testis during fetal development. TGCTs occur at an appreciable frequency (5%) only in the 129 family of inbred strains of laboratory mice, suggesting strong genetic control. These developmental and genetic properties make the 129 strains an exceptional model system to dissect TGCT pathogenesis. Ter is one of the most potent cancer modifiers genes known; it is a single gene mutation that causes progressive loss of PGCs on all inbred strain backgrounds and dramatically increased susceptibility to spontaneous TGCTs only on the 129 background. We recently showed that inactivation of the Dead end gene causes the Ter phenotype. Sequence analysis of Dead end encoded protein indicates it is homologous to factors involved in gene editing. The identity of Ter as Dead end and its function in PGCs will help clarify the role of editing in PGC biology and elucidate the causes of TGCTs in mice and humans.

Animals↗
PubMed2005

The incidence of autism in Olmsted County, Minnesota, 1976-1997: results from a population-based study.

OBJECTIVE: To determine the incidence of autism among children in Olmsted County, Minnesota. DESIGN: Through the Rochester Epidemiology Project, all inpatient and outpatient diagnoses are indexed for computerized retrieval. This computerized diagnostic index was used to identify children with any developmental disorder. A glossary of symptoms of autism was used to review medical and school records of these children for symptoms consistent with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for autistic disorder. SETTING: Olmsted County, Minnesota. Subjects All residents of Olmsted County 21 years or younger between 1976 and 1997. Main Outcome Measure The incidence of research-identified autism based on DSM-IV criteria for autistic disorder. RESULTS: The age-adjusted incidence of research-identified autism was 5.5 (95% confidence interval, 1.4-9.5) per 100 000 children from 1980 to 1983 and 44.9 (95% confidence interval, 32.9-56.9) from 1995 to 1997 (8.2-fold increase). This increase was confined to children younger than 10 years who were born after 1987. CONCLUSIONS: The incidence of research-identified autism increased in Olmsted County from 1976 to 1997, with the increase occurring among young children after the introduction of broader, more precise diagnostic criteria, increased availability of services, and increased awareness of autism. Although it is possible that unidentified environmental factors have contributed to an increase in autism, the timing of the increase suggests that it may be due to improved awareness, changes in diagnostic criteria, and availability of services, leading to identification of previously unrecognized young children with autism.

Adolescent↗
PubMed2004

[What wrist fracture did Pouteau actually describe?].

The so-called " Pouteau-Colles" fracture was never specifically described by Pouteau. This surgeon from Lyons wrote a paper published in his posthumous works in 1783. The author was allowed access to an original edition of the paper at the "Ancienne Ecole de Médecine Navale de Rochefort". When reading this paper, it seems that Pouteau described a great variety of different kinds of forearm fractures. His original contribution was to define the mechanism of injury as occurring during a fall on the outstretched hand as opposed to direct injury. Pouteau presents a hypothetical muscular theory of fracture pattern etiology, but one that is useful in the understanding of the displacemnt of the bone fragments. He questions the principal role attributed to sprains and luxations at this time in the differential diagnosis of forearm injury. He described four clinical signs to diagnose, at a glance, which bone was injured, the site of the fracture, its displacements and mechanism of inury. Pouteau also presented a precise method of reduction and an original system of immobilisation, able to accomodate secondary displacements and avoid complications that were not fully recognised at that time, namely compartment syndrome and nosocomial infection. Pouteau simply concludes with a question concerning the future methods needed to reduce bony collapse and to fill the bone defects. In order to render special homage to this visionary surgeon, the author propose to attribute to the nosologic entity "fore-arm bone fractures" the qualificative of "Pouteau's fractures", or to associate to every fracture of the fore-arm described by any other author the name of the Lyons surgeon!

Colles' Fracture↗
PubMed2006

High precision variational calculations for the Born-Oppenheimer energies of the ground state of the hydrogen molecule.

Born-Oppenheimer approximation Hylleraas variational calculations with up to 7034 expansion terms are reported for the 1sigma(g)+ ground state of neutral hydrogen at various internuclear distances. The nonrelativistic energy is calculated to be -1.174 475 714 220(1) hartree at R = 1.4 bohr, which is four orders of magnitude better than the best previous Hylleraas calculation, that of Wolniewicz [J. Chem. Phys. 103, 1792 (1995)]. This result agrees well with the best previous variational energy, -1.174 475 714 216 hartree, of Cencek (personal communication), obtained using explicitly correlated Gaussians (ECGs) [Cencek and Rychlewski, J. Chem. Phys. 98, 1252 (1993); Cencek et al., ibid. 95, 2572 (1995); Rychlewski, Adv. Quantum Chem. 31, 173 (1998)]. The uncertainty in our result is also discussed. The nonrelativistic energy is calculated to be -1.174 475 931 399(1) hartree at the equilibrium R = 1.4011 bohr distance. This result also agrees well with the best previous variational energy, -1.174 475 931 389 hartree, of Cencek and Rychlewski [Rychlewski, Handbook of Molecular Physics and Quantum Chemistry, edited by S. Wilson (Wiley, New York, 2003), Vol. 2, pp. 199-218; Rychlewski, Explicitly Correlated Wave Functions in Chemistry and Physics Theory and Applications, edited by J. Rychlewski (Kluwer Academic, Dordrecht, 2003), pp. 91-147.], obtained using ECGs.

Journal Article↗
PubMed2004

The Molecular Pages of the mesotelencephalic dopamine consortium (DopaNet).

BACKGROUND: DopaNet http://www.dopanet.org is a Systems Biology initiative that aims to investigate precisely and quantitatively all the aspects of neurotransmission in a specific neuronal system, the mesotelencephalic dopamine system. The project should lead to large-scale models of molecular and cellular processes involved in neuronal signaling. A prerequisite is the proper storage of knowledge coming from the literature. METHODS: DopaNet Molecular Pages are highly structured descriptions of quantitative parameters related to a specific molecular complex involved in neuronal signal processing. A Molecular Page is built by maintainers who are experts in the field, and responsible for the quality of the page content. Each piece of data is identified by a specific ontology code, annotated (method of acquisition, species, etc.) and linked to the relevant bibliography. The Molecular Pages are stored as XML files, and processed through the DopaNet Web Service, which provides functionalities to edit the Molecular Pages, to cross-link the Pages and generate the public display, and to search them. CONCLUSIONS: DopaNet Molecular Pages are one of the core resources of the DopaNet project but should be of widespread utility in the field of Systems Neurobiology.

Animals↗
PubMed1999

Mouse testicular extracts process DNA double-strand breaks efficiently by DNA end-to-end joining.

DNA double-strand break (DSB) processing was studied in mouse testicular extracts using a defined DSB created by cleaving supercoiled pUC12 DNA at a unique site as the substrate, and analysing the processed DNA by gel electrophoresis. Our results demonstrated that enzymatic activity in the extracts promoted multimerization of DNA and suppressed its circularization. This was distinctly different from T4 DNA ligase activity in the control and therefore the process must be more complex than simple ligation. Efficiency of this end-to-end joining was ATP and Mg(2+)-dependent and was much higher with cohesive (especially with 5') than with blunt ends. On recleaving, the joining was predominantly faithful, especially for cohesive ends; but a detectable fraction of DNA had undergone end-processed joining causing junctional deletions, mostly with blunt ends. Redigestion of end-joined products from time course experiments established that the end-deleted joining occurred concurrent to the faithful joining. Junctional segments were cloned and their restriction analysis confirmed the presence of large deletions from both the sides. These results suggested the association of an end-processing activity (exonuclease/helicase + flap endonuclease) along with the end-joining ligase(s). Suppression of end-edited joining on lowering the reaction temperature to 17 degrees or 14 degrees C, despite efficient faithful joining, indicated that this enzymatic activity is retarded at low temperature. Though the efficiency and fidelity of joining were termini-dependent, the orientation of joining was random. Lack of preference for homologous ends (H:H or T:T), as well as efficient joining of heterologous DNA (pUC12/pBR322) having two different blunt termini, showed that the end joining could occur independent of extensive/terminal homology. Retention of radioactivity on end joining of (alpha-32P)dCTP end-filled cohesive termini, and lack of their junctional cleavability, apparently due to restriction site duplication, suggested direct double strand ligation. Thus it is demonstrated that mouse male germ cells possess an efficient DNA end-joining activity, involving either a major pathway of precise joining, or a minor end-deleted joining, and it seems to be achieved by a multienzymatic complex as suggested also for somatic cells by others. These results show that mammalian male germ cells that are proficient in homologous recombination utilize nonhomologous end-joining (NHEJ) mechanism for DSB processing and therefore NHEJ is a conserved, universal pathway for the vital function of DSB repair.

Adenosine Triphosphate↗
PubMed1988

The fidelity of base selection by the polymerase subunit of DNA polymerase III holoenzyme.

In common with other DNA polymerases, DNA polymerase III holoenzyme of E. coli selects the biologically correct base pair with remarkable accuracy. DNA polymerase III is particularly useful for mechanistic studies because the polymerase and editing activities reside on separate subunits. To investigate the biochemical mechanism for base insertion fidelity, we have used a gel electrophoresis assay to measure kinetic parameters for the incorporation of correct and incorrect nucleotides by the polymerase (alpha) subunit of DNA polymerase III. As judged by this assay, base selection contributes a factor of roughly 10(4)-10(5) to the overall fidelity of genome duplication. The accuracy of base selection is determined mainly by the differential KM of the enzyme for correct vs. incorrect deoxynucleoside triphosphate. The misinsertion of G opposite template A is relatively efficient, comparable to that found for G opposite T. Based on a variety of other work, the G:A pair may require a special correction mechanism, possibly because of a syn-anti pairing approximating Watson-Crick geometry. We suggest that precise recognition of the equivalent geometry of the Watson-Crick base pairs may be the most critical feature for base selection.

DNA Polymerase III↗
PubMed2026

Cross-target and cell-preferential CRISPR-Cas9 inhibition with carbohydrate-tagged oligonucleotides.

Precise control of clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) activity is important for limiting off-target effects and chromosomal rearrangements. Existing inhibitors, including anti-CRISPR proteins and spacer-targeting oligonucleotides, can be constrained by immunogenicity, target-sequence dependence, or delivery challenges. Here, we developed single-stranded DNA oligonucleotides that target conserved regions of the Streptococcus pyogenes Cas9 single-guide RNA (sgRNA) scaffold rather than the variable spacer. Screening identified single-stranded DNA 7 (ssDNA7), which targets stem-loop-1 and the adjacent linker and inhibits Cas9 activity across multiple tested spacer sequences and genomic loci without redesigning the inhibitor. Carbohydrate conjugation improved oligonucleotide stability and preferentially enhanced inhibitory activity in selected liver-derived or cancer cell models. Amplicon sequencing confirmed inhibition of endogenous editing in multiple cell models and normal liver-derived organoids, and supported cell-preferential inhibition in matched cell comparisons. These findings establish sgRNA-scaffold targeting as a strategy for cross-target inhibition of Cas9 and show that carbohydrate conjugation can tune its cellular activity.

CRISPR-Cas9↗
PubMed1997

Characterization of the low molecular weight photosystem II reaction center subunits and their light-induced modifications by mass spectrometry.

A sensitive and simple reverse phase HPLC purification scheme was developed for the rapid separation of the small protein subunits from photosystem II reaction center preparations. The precise molecular masses of the alpha- and beta-subunits of cytochrome b559 and the psbI gene product from pea plants, found to be 4394.6 +/- 0. 6, 9283.6 +/- 0.7, and 4209.5 +/- 0.5 Da, respectively, were then successfully determined for the first time by electrospray- and fast atom bombardment-mass spectrometry. Discrepancies between the molecular weights assigned and those calculated from the respective DNA sequences were observed for alpha- and beta-subunits of cytochrome b559. Currently, the nucleotide sequence of the psbI gene product from pea plants is not available. Application of novel mapping and sequencing strategies has assured the elucidation of full primary structures of all of the purified subunits. The modifications identified here include the post-translational processing of the initiating methionine on both subunits of cytochrome b559, NH2-terminal acetylation and an mRNA editing site at residue 26 (Ser --> Phe) on the beta-subunit, and retention of the NH2-terminal formyl-Met on the psbI gene product. In addition, specific oxidation of a single amino acid residue was identified on the psbI gene product and the beta-subunit purified from light-treated reaction center preparations. Overall, these studies provide the first detailed primary structural characterization of the small subunits of the reaction center complex and their associated light-induced modifications.

Amino Acid Sequence↗
PubMed1996

A single telomerase RNA is sufficient for the synthesis of variable telomeric DNA repeats in ciliates of the genus Paramecium.

Paramecium telomeric DNA consists largely of a random distribution of TTGGGG and TTTGGG repeats. Given the precise nature of other ciliate telomerases, it has been postulated that there are two distinct types of the Paramecium enzyme, each synthesizing perfect telomeric repeats: one with a template RNA that specifies the addition of TTTGGG and the second dictating the synthesis of TTGGGG repeats. We have cloned and sequenced telomerase RNA genes from Paramecium tetraurelia, P. primaurelia, P. multimicronucleatum, and P. caudatum. Surprisingly, a single gene encodes telomerase RNA in all four species, although an apparently nontranscribed pseudogene is also present in the genome of P. primaurelia. The overall lengths of the telomerase RNAs range between 202 and 209 nucleotides, and they can be folded into a conserved secondary structure similar to that derived for other ciliate RNAs. All Paramecium telomerase RNAs examined include a template specific for the synthesis of TTGGGG telomeric repeats, which has not been posttranscriptionally edited to account for the conventional synthesis of TTTGGG repeats. On the basis of these results, possible mechanisms for the synthesis of variable telomeric repeats by Paramecium telomerase are discussed.

Animals↗
PubMed1993

Accutracker II (version 30/23) ambulatory blood pressure monitor: clinical validation using the British Hypertension Society and Association for the Advancement of Medical Instrumentation standards.

OBJECTIVE: To assess the Accutracker II (version 30/23) ambulatory blood pressure monitor by nationally agreed protocols in order to resolve previous conflicting assessments, and to examine the feasibility of combining these protocols into one study. DESIGN: The protocols of the Association for the Advancement of Medical Instrumentation (AAMI) and the British Hypertension Society (BHS) were used simultaneously. SUBJECTS: Five normotensive subjects were used to assess interobserver variation; 30 subjects took part in the field evaluation and 85 in the laboratory evaluation. The latter subjects were selected to cover a wide range of blood pressures and differences in arm circumference. OUTCOME MEASUREMENTS: Classification of device accuracy according to the criteria of the BHS and AAMI protocols. RESULTS: Among 255 observations the mean +/- SD difference between blood pressure measurements by the Accutracker II and the observers was -2.2 +/- 0.8/-3.5 +/- 0.9 mmHg. There was a small but statistically significant difference between one device and the other two, but all three fulfilled the BHS criteria of 95% of measurements falling within 3 mmHg before and after use. In 30 24-h recordings > 80% of the programmed inflations produced valid recordings. Editing criteria accounted for the majority (55%) of invalid readings; weak Korotkoff sounds, imperfect electrocardiogram signals or movement artefact accounted for the remainder. CONCLUSIONS: Version 30/23 of the Accutracker II fulfilled the AAMI criteria; using the BHS system, it was graded A for systolic and C for diastolic blood pressure. Although both protocols were readily combined into one study, they do not assess exactly the same aspects of blood pressure measurement. Previous conflicting evaluations could be due to differences in applying the protocols or may result from modifications in production models. Posture may affect the rating given by the BHS protocol. Until there is general international agreement on the method used to validate ambulatory blood pressure monitors, simultaneous use of both the BHS and AAMI protocols is recommended. In future assessments or investigational use of any similar instruments the model used should be described precisely.

Adolescent↗
PubMed2006

[Galen's "On the anatomy of veins and arteries" translation from the Greek text and discussion].

Galen's treatise "On the anatomy of veins and arteries" was translated literally from the Greek text (Kühn's edition, vol. 2, pp. 779-830) into Japanese, utilizing a knowledge of anatomy. The previous Latin and English translations, as well as the descriptions of the vascular system in the other Galenic texts such as "Anatomical Procedures" were utilized as references for the present translation. The present study has identified many branches of veins and arteries, and discussed the influence on anatomy until Vesalius. For example, Galen considered that the main trunk of the portal vein sent off 7 branches, and Avicenna's "Canon" and Mondino's "Anatomia" identified a trunk and 8 branches, whereas Vesalius found bifurcation of the portal vein as in the modern anatomy. As to the vein of the forearm, Galen found 3 superficial veins including the central largest one and Vesalius' "Tabulae anatomicae" depicted this arrangement of veins, whereas Vesalius' 'Fabrica" corrected this erroneous description, based on anatomical findings. The precise understanding of Galenic anatomy provides essential information to understand the developing process of Vesalius' anatomy.

Arteries↗
PubMed2005

The double-stranded RNA-binding motif, a versatile macromolecular docking platform.

The double-stranded RNA-binding motif (dsRBM) is an alphabetabetabetaalpha fold with a well-characterized function to bind structured RNA molecules. This motif is widely distributed in eukaryotic proteins, as well as in proteins from bacteria and viruses. dsRBM-containing proteins are involved in processes ranging from RNA editing to protein phosphorylation in translational control and contain a variable number of dsRBM domains. The structural work of the past five years has identified a common mode of RNA target recognition by dsRBMs and dissected this recognition into two functionally separated interaction modes. The first involves the recognition of specific moieties of the RNA A-form helix by two protein loops, while the second is based on the interaction between structural elements flanking the RNA duplex with the first helix of the dsRBM. The latter interaction can be tuned by other protein elements. Recent work has made clear that dsRBMs can also recognize non-RNA targets (proteins and DNA), and act in combination with other dsRBMs and non-dsRBM motifs to play a regulatory role in catalytic processes. The elucidation of functional networks coordinated by dsRBM folds will require information on the precise functional relationship between different dsRBMs and a clarification of the principles underlying dsRBM-protein recognition.

Amino Acid Sequence↗
PubMed2026

A CRISPR-Cas9 Toolkit Enabling Tunable Integration and Transient Homologous Recombination Enhancement in Yarrowia lipolytica.

Although the oleaginous yeast Yarrowia lipolytica is a promising microbial cell factory, its application remains constrained by inefficient homology-directed repair (HDR) and a lack of precise genomic integration tools. To address these limitations, we developed a comprehensive genetic toolkit featuring three synergistic advancements. First, we systematically identified 55 neutral integration sites with tunable expression profiles, enabling stable, position-independent gene integration with predictable transcriptional output across a 12.88-fold dynamic range. Second, we established a dual-readout high-throughput screening platform combining colony morphology analysis with hrGFP fluorescence. This approach accurately measures locus-specific homologous recombination (HR) efficiency while eliminating false positives by dominant non-homologous end joining (NHEJ). Third, we engineered a transient HR enhancement system by fusing the Sae2 exonuclease to Cas9 via a flexible (GGGGS)3 linker. This fusion significantly boosts HR efficiency and surpasses the cleavage activity of unmodified Cas9 without introducing permanent genomic modifications or compromising cellular fitness. Finally, HR efficiency for single-gene integration was increased from 46.5% to 77.5% while the dual-locus editing efficiency reached 64.1% when using 500-bp homology arms, and the engineered strains demonstrated improved genetic stability compared to those with constitutive HR enhancement.

Yarrowia↗