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Stability and change in personality disorder features: the Longitudinal Study of Personality Disorders.

BACKGROUND: There exists no empirical literature documenting the long-term longitudinal stability of personality pathology comparable to that available for normal personality. A number of test-retest studies have usefully established the short-term reliability of Axis II measures. However, the test-retest design is methodologically inadequate for resolving issues related to the long-term stability of personality disorder (PD). This prospective longitudinal study evaluated the stability of PD features in multiwave perspective. METHODS: Subjects (N = 250) drawn from a nonclinical university population were examined for PD features at 3 different time points using the International Personality Disorders Examination (IPDE) and the Millon Clinical Multiaxial Inventory II (MCMI-II) during a study period of 4 years. RESULTS: Features of PD displayed considerable evidence of stability for individual differences and group means, at the dimensional level of analysis, on both the IPDE and the MCMI-II. Both measures revealed modest declines in PD features over time; however, the observed changes were associated with relatively small effect sizes. CONCLUSION: Features of PD, viewed from a dimensional perspective, seem to be relatively stable in terms of individual differences and group means based on both clinical interview and self-administered PD assessments.

Analysis of Variance↗

Epoxide adducts at the guanine residue within single-stranded DNA chains: reactivity and stability studies.

Emphasis was placed in this work on the assessment of structural and biological features of nucleobase adducts that result from the reaction of DNA with epoxide derivatives. Thus we have prepared and characterized a set of site-specifically modified oligonucleotides at N7-position of a guanine residue, upon reaction with diepoxibutane, with the purpose of further investigating some of their biochemical features. The stability of the lesion-containing DNA fragments has also been investigated and clearly shows that the latter modified oligomers may be used as substrates for in vitro enzymatic assays, aimed at determining the biological effects within cell of these chemically induced DNA damage.

Butanes↗

Individual growth curve analysis illuminates stability and change in personality disorder features: the longitudinal study of personality disorders.

BACKGROUND: The long-term stability of personality pathology remains an open question. Its resolution will come from prospective, multiwave longitudinal studies using blinded assessments of personality disorders (PD). Informative analysis of multiwave data requires the application of statistical procedures, such as individual growth curve modeling, that can detect and describe individual change appropriately over time. The Longitudinal Study of Personality Disorders, which meets contemporary methodological design criteria, provides the data for this investigation of PD stability and change from an individual growth curve perspective. METHODS: Two hundred fifty subjects were examined for PD features at 3 different time points using the International Personality Disorders Examination during a 4-year study. Stability and change in PD features over time were examined using individual growth modeling. RESULTS: Fitting of unconditional growth models indicated that statistically significant variation in PD features existed across time in the elevation and rate of change of the individual PD growth trajectories. Fitting of additional conditional growth models, in which the individual elevation and rate-of-change growth parameters were predicted by subjects' study group membership (no PD vs possible PD), sex, and age at entry into the study, showed that study group membership predicted the elevation and rate of change of the individual growth curves. Comorbid Axis I psychopathology and treatment during the study period were related to elevations of the individual growth trajectories, but not to rates of change. CONCLUSIONS: From the perspective of individual growth curve analysis, PD features show considerable variability across individuals over time. This fine-grained analysis of individual growth trajectories provides compelling evidence of change in PD features over time and does not support the assumption that PD features are traitlike, enduring, and stable over time.

Adolescent↗

Locomotor decoupling and the origin of hominin bipedalism.

Theoretical adaptive landscapes and mathematical representations of key constraints of evolutionary and primate biology are used to propose a new hypothesis for the origin of hominin bipedalism. These constraints suggest that the selective pressure that produced this novel form of locomotion was the need for effective suspensory and terrestrial movement. This testable hypothesis, termed the Decoupling Hypothesis, posits that bipedalism is an adaptation that enables the shoulder to maintain a high degree of mobility, a feature important to suspensory behaviors, in the face of significant demands for a high degree of stability, a feature important for highly effective terrestrial quadrupedism.

Adaptation, Biological↗

Multilocular cystic nephroma: MR imaging appearance with current techniques, including gadolinium enhancement.

The purpose of the study was to define the MRI appearance of multilocular cystic nephroma (MLCN), using current MR techniques, including gadolinium (Gd)-enhanced sequences. Seven patients with MLCN underwent MR imaging with the following sequences: T1-weighted spin echo with fat suppression (T1FS, five patients), T1-weighted spoiled gradient echo (SGE, seven patients), T2-weighted fast spin echo (two patients), and Gd-enhanced T1FS (seven patients) and SGE (seven patients). MLCN was histologically proven by resection of the mass in six patients and by observation of typical imaging features with stability in appearance over a 6-month period in one patient. Lesion morphology and signal intensity (SI) features were retrospectively evaluated. MRI features of MLCN included a solitary cystic lesion with thin internal septations in six patients and a cluster of closely grouped cysts similar in size in one patient. Individual cystic spaces demonstrated SI, varying from low to high on T1-weighted images in three patients and demonstrated low-to-intermediate SI in four patients. Herniation of the lesions into the renal collecting system and thin enhancing septa were demonstrated in all patients. A complex cystic renal lesion with enhancing septa and herniation into the renal collecting system are the characteristic MR findings of MLCN. The direct multiplanar capability of MR may optimally show the relationship of MLCN to the renal pelvis and, thus, facilitate correct diagnosis.

Adult↗

The Escherichia coli unc transcription terminator enhances expression of uncC, encoding the epsilon subunit of F1-ATPase, from plasmids by stabilizing the transcript.

The effect of the unc transcription terminator on expression of uncC, encoding the epsilon subunit of Escherichia coli F1-ATPase, from plasmids was studied. The cloned sequence in pTK1 included the uncC ribosome binding site, the uncC structural gene, and the unc transcription terminator. The cloned region in pSD37 was similar, but lacked the unc transcription terminator. Transformants carrying pTK1 produced the epsilon subunit of F1-ATPase, encoded by uncC, in 10-fold greater abundance than transformants carrying pSD37. Northern blots revealed similar differences in the steady-state uncC mRNA levels. The half-life of the message transcribed from pTK1 was 90-100 seconds, while that from pSD37 was 25-30 seconds. These studies indicate the importance of message stabilization through features at the 3' end of the transcript in ensuring adequate production of epsilon. We have exploited this stabilization to develop a simple, efficient, and gentle method of purifying the overproduced epsilon subunit.

Blotting, Northern↗

Origin of the magic numbers of water clusters with an excess electron.

Electron-bound water clusters [e(-)(H(2)O)(n)] show very strong peaks in mass spectra for n=2, 6, 7, and (11), which are called magic numbers. The origin of the magic numbers has been an enigma for the last two decades. Although the magic numbers have often been conjectured to arise from the intrinsic properties of electron-bound water clusters, we attributed them not to their intrinsic properties but to the particularly weak stability of the corresponding neutral water clusters (H(2)O)(n=2,6,7, and (11)). As the cluster size increases; this nonsmooth characteristic feature in stability of neutral water clusters is contrasted to the smooth increase in stability of e(-)-water clusters. As the magic number clusters have significant positive adiabatic electron affinities, their abundant distributions in atmosphere could play a significant role in atmospheric thermodynamics.

Journal Article↗

Sterically stabilized BGTC-based lipoplexes: structural features and gene transfection into the mouse airways in vivo.

BACKGROUND: Colloidal stability of lipid/DNA aggregates is a major requirement for cationic lipid-mediated transfection which is particularly difficult to fulfil at the high DNA concentrations used for in vivo gene delivery. Thus, we have investigated the potential of poly(ethyleneglycol) (PEG) conjugates for steric stabilization of lipoplexes formed by bis(guanidinium)-tren-cholesterol/dioleoyl phosphatidylethanolamine (BGTC/DOPE) liposomes, a class of cationic liposomes we have developed over the past few years. METHODS AND RESULTS: We demonstrate that adequate lipophilic PEG derivatives can stabilize BGTC/DOPE lipoplexes formed at high DNA concentration. We also report the results of cryotransmission electron microscopy studies indicating that PEG-stabilized lipoplexes form DNA-coated structures which assemble into clusters exhibiting various complex morphologies. Finally, we report data from in vivo transfection experiments suggesting that PEG-mediated colloidal stabilization of concentrated lipoplex solutions may allow enhanced transfection of the mouse airways via intranasal administration. CONCLUSION: Our results represent an important step towards the design of multimodular BGTC-based systems for improved in vivo gene transfection.

Animals↗

The paleobiology of Amphipithecidae, South Asian late Eocene primates.

Analysis of the teeth, orbital, and gnathic regions of the skull, and fragmentary postcranial bones provides evidence for reconstructing a behavioral profile of Amphipithecidae: Pondaungia, Amphipithecus, Myanmarpithecus (late middle Eocene, Myanmar) and Siamopithecus (late Eocene, Thailand). At 5-8 kg, Pondaungia, Amphipithecus, and Siamopithecus are perhaps the largest known Eocene primates. The dental and mandibular anatomy suggest that large-bodied amphipithecids were hard-object feeders. The shape of the mandibular corpus and stiffened symphysis suggest an ability to resist large internal loads during chewing and to recruit significant amounts of muscle forces from both the chewing and non-chewing sides of the jaw so as to increase bite force during mastication. The large spatulate upper central incisor of Pondaungia and projecting robust canines of all the larger amphipithecids suggest that incisal food preparation was important. The molars of Siamopithecus, Amphipithecus, and Pondaungia have weak shearing crests. This, and the thick molar enamel found in Pondaungia, suggests a diet of seeds and other hard objects low in fiber. In contrast, Myanmarpithecus was smaller, about 1-2 kg; its cheek teeth suggest a frugivorous diet and do not imply seed eating. Postcranial bones (humerus, ulna, and calcaneus) of a single large amphipithecid individual from Myanmar suggest an arboreal quadrupedal locomotor style like that of howler monkeys or lorises. The humeral head is rounded, proximally oriented, and the tuberosities are low indicating an extremely mobile glenohumeral joint. The great thickness of the midshaft cortical bone of the humerus implies enhanced ability to resist bending and torsion, as seen among slow moving primate quadrupeds. The elbow joint exhibits articular features for enhanced stability in habitually flexed positions, features also commonly found in slow moving arboreal quadrupeds. The short distal load arm of the calcaneus is consistent with, but not exclusive to, slow, arboreal quadrupedalism, and suggests no reliance on habitual leaping.

Animals↗

B-chronic lymphocytic leukaemia patients with stable benign disease show a distinctive membrane phenotype.

The circulating B cells of 98 patients with B-CLL were analysed with a panel of conventional markers and monoclonal antibodies including RFA-1 and RFA-4. A subgroup of patients was defined with a distinctive double membrane marker phenotype (RFA-1+, RFA-4+). These patients showed features of clinical stability. Their physical signs, haematological features and lymphocyte counts remained unchanged for 5-10 years: therefore, the RFA-1+, RFA-4+ membrane phenotype appears to identify a subgroup of B-CLL patients with a particularly non-progressive disease.

Aged↗

Dataset Readiness Assessment With Large Language Model (DRAFT-LLM): A Multi-Axis Audit Guided by LLM.

This article details the Dataset Readiness Assessment for Training (DRAFT), a systematic method for determining whether a high-dimensional biological dataset is suitable for developing reliable, equitable (i.e., the extent to which model performance, error patterns, and potential benefits or harms are evaluated and found to be acceptably distributed across relevant demographic, biological, clinical, and contextual subgroups), and scientifically meaningful machine-learning models, and DRAFT Large Language Model (DRAFT-LLM), its optional human-in-the-loop extension for calibrating study-specific audits through structured, critically reviewed LLM guidance. Standard model validation often fails to detect when apparent performance is driven by spurious correlations, technical artifacts, or hidden stratification, leading to irreproducible and inequitable findings. DRAFT-LLM addresses this gap by shifting the focus from model tuning to structured dataset auditing, organized around Support Protocols 1 to 4 that capture the scientific intent, data structure, and governance constraints of a given study. These Support Protocols: (1) elicit and formalize investigator input into a study intake and dataset card; (2) compute standardized dataset statistics and structural summaries suitable for downstream analysis and LLM context; (3) configure the language model using form-based responses, safety guardrails, and governance rules; and (4) generate personalized instructions, prompts, and code templates for running DRAFT audits. Basic Protocols 1 to 3 are instantiated from this support layer for generalization, equity, and stability: they are reusable execution patterns whose concrete behavior is determined by the cards, statistics, and configurations defined in the Support Protocols. DRAFT-LLM and DRAFT are demonstrated in this article through an end-to-end case study on The Cancer Genome Atlas (TCGA). © 2026 Wiley Periodicals LLC. Support Protocol 1: Study intake and dataset card construction Support Protocol 2: Dataset structure and advanced summary statistics for LLM context Support Protocol 3: LLM configuration using structured form responses Support Protocol 4: Generation of personalized instructions for DRAFT audits Basic Protocol 1: Generalization audit Basic Protocol 2: Equity audit Basic Protocol 3: Stability audit.

Large Language Models↗

Self-immolative nitrogen mustards prodrugs cleavable by carboxypeptidase G2 (CPG2) showing large cytotoxicity differentials in GDEPT.

Nineteen novel potential self-immolative prodrugs and their corresponding drugs have been synthesized for gene-directed enzyme prodrug therapy (GDEPT) with carboxypeptidase G2 (CPG2) as the activating enzyme. The compounds are derived from o- and p-amino and p-methylamino aniline nitrogen mustards. Their aqueous stability, kinetics of drug release by CPG2, and cytotoxicity in the colon carcinoma cell line WiDr, expressing either surface-tethered CPG2 (stCPG2(Q)3) or control beta-galactosidase, are assessed. The effect of various structural features on stability, kinetics of activation, and biological activity is discussed. The p-methylamino prodrugs are the most stable compounds from this series, with the largest cytotoxicity differentials between CPG2-expressing and nonexpressing cells. The most potent compounds in all series are prodrugs of bis-iodo nitrogen mustards. 4-[N-[4'-Bis(2' '-iodoethyl)aminophenyl]-N'-methylcarbamoyloxymethyl]phenylcarbamoyl-l-glutamic acid, compound 39b, is 124-fold more cytotoxic to WiDr cells expressing CPG2 than to cells expressing beta-galactosidase. An additional six compounds show better cytotoxicity differential than the published N-[4-[(2-chloroethyl)(2-mesyloxyethyl)amino]benzoyl]-l-glutamic acid (CMDA) prodrug.

Aniline Mustard↗

Recent progress on collagen triple helix structure, stability and assembly.

Collagen is the major structural protein in skin, bone, tendon, cartilage and blood vessels. Its triple helical structure has been long studied by fibre diffraction. More recently, single crystal X-ray diffraction on collagen-like polypeptide models has allowed a significantly improved description of the triple helix and it has shed light on the relationships between triple helix features and stability. This review outlines the current knowledge regarding collagen triple helix structure, stability, and assembly, with a particular emphasis on the latest structural results.

Animals↗

Stabilized isoporphyrin intermediates in the inactivation of horseradish peroxidase by alkylhydrazines.

The reaction of horseradish peroxidase with alkylhydrazines results in delta-meso-alkylation of the prosthetic heme group and enzyme inactivation (Ator, M. A., David, S. K., and Ortiz de Montellano, P. R. (1987) J. Biol. Chem. 262, 14954-14960). As reported here, enzyme inactivation is associated with the accumulation of intermediates that absorb at approximately 835 nm. The properties of these intermediates, including their collapse to give meso-alkylhemes, identify them as isoporphyrins. The t1/2 values for inactivation and formation of the isoporphyrin intermediate at 25 degrees C are, respectively, 11.6 and 12.5 min for methylhydrazine (2.0 mM), 8.7 and 7.2 min for ethylhydrazine (1.0 mM), and 30 and 25 s for phenylethylhydrazine (50 microM). The isoporphyrin intermediates are surprisingly long-lived, with half-lives (35 degrees C, pH 7.0) of 9, 28, 96, and 450 min for, respectively, the phenylethyl, methyl, n-butyl, and ethyl analogues. pH studies show that protonation of a group with pKa = 5.0-6.5 accelerates isoporphyrin decay and decreases steady state isoporphyrin accumulation. Horseradish peroxidase reconstituted with delta-meso-methylheme, unlike horseradish peroxidase with a heme that has a larger meso-substituent, is catalytically active but is more sensitive to H2O2-mediated degradation of the prosthetic group than is the native enzyme. The delta-meso-methylheme prosthetic group is converted in the reaction with H2O2 to a biliverdin-like product. The results implicate highly stabilized isoporphyrin intermediates in the inactivation of horseradish peroxidase by alkylhydrazines and indicate that inactivation by the meso-alkyl groups is due to steric interference with electron delivery to the heme edge rather than to intrinsic electronic consequences of meso-alkylation. The structural features that stabilize the cationic isoporphyrins may also be involved in stabilization of the Compound I porphyrin radical cation.

Alkylation↗

Use of Ammophila arenaria for Dune Stabilization in South Africa and Its Current Distribution-Perceptions and Problems.

/ This paper examines the use of the European dune pioneer plant Ammophila arenaria (marram or European beach grass) for dune stabilization in South Africa in the past and present, its present distribution in South Africa, and the perceptions of coastal management agencies and the public about its further use. The planting of A. arenaria became the most important means of dune stabilization, by human intervention, along the South African Cape coast in this century. Its modern distribution from the semiarid west coast to the subtropical shores of the Eastern Cape extends through various climatic zones. Although historical data are missing for some areas, there is no indication of its unaided spread. A. arenaria occurs at most sites because of its prior planting. The South African climate appears to affect its vigor. However, concern about the use of the alien grass has been raised since it has proved to be a highly invasive species in other parts of the world, particularly along the North American west coast and in Tasmania. While the CSIR (Council of Scientific and Industrial Research) promotes its use, CNC (Cape Nature Conservation) follows a policy that restricts the use of any alien plant, including A. arenaria, and requests further research on its invasive properties. Although a questionnaire survey shows that stabilization sites featuring large areas of A. arenaria are accepted by the South African public, current coastal management practices need to be analyzed critically. A thorough investigation of the potential invasiveness of A. arenaria on South African coastal dunes will be essential and shed new light on the American A. arenaria problem.KEY WORDS: Ammophila arenaria; Marram; European beach grass; Dune stabilization; South Africa; Coastal managementhttp://link.springer-ny.com/link/service/journals/00267/bibs/24n4p467.html</HEA

Journal Article↗

Protective effects of rilmenidine and AGN 192403 on oxidative cytotoxicity and mitochondrial inhibitor-induced cytotoxicity in astrocytes.

Oxidative stress and mitochondrial dysfunction are important aspects of pathogenesis, particularly in the brain, which is highly dependent on oxygen, and the protection of astrocytes is essential for neuroprotection. In this context, imidazoline drugs have been reported to be neuroprotective. Our recent study showed that imidazoline drugs, including guanabenz, inhibit the naphthazarin-induced oxidative cytotoxicity associated with lysosomal destabilization. We now report on a study into the protective effects of rilmenidine and AGN 192403, which have affinity for imidazoline-1 receptors, on the cytotoxicity induced by naphthazarin and inhibitors of mitochondrial respiration in astrocytes. Cytotoxicity was measured grossly by LDH release and by measuring changes in lysosomal membrane stability and features of mitochondrial membrane permeabilization. Naphthazarin-induced cytotoxicity was evidenced by the ordered development of lysosomal acridine orange relocation, decrease in mitochondrial potential, cytochrome c release, and caspase-9 activation, and was inhibited by guanabenz, rilmenidine, and AGN 192403. Antimycin A and rotenone induced mitochondrial dysfunction primarily, and their cytotoxicities were inhibited only by AGN 192403. Rilmenidine and guanabenz may have a lysosomal stabilizing effect, which underlies their protective effects. AGN 192403 might affect the mitochondrial cell death cascades, and had a novel protective effect on the cytotoxicity associated with mitochondrial dysfunction.

Animals↗

Amino acid sequence of the triple-helical domain of human collagen type VI.

The complete amino acid sequence of the triple-helical domain of human collagen VI was deduced from sequences of appropriate cDNA clones and confirmed to about 50% by Edman degradation of tryptic peptides. This domain consists of three different peptide segments containing some 335-336 amino acid residues originating from central portions of the alpha 1 (VI), alpha 2(VI), and alpha 3(VI) chains, respectively. Sequence identity in the X/Y positions of the Gly-X-Y repeats is rather low (10-15%) between the chains. Peculiar features of these sequences include 3 cysteine residues about 50 (alpha 3(VI)) and 89 (alpha 1(VI), alpha 2(VI)) residues away from the N-terminus and several Gly-X-Y interruptions clustered in the C-terminal two-thirds of the triple helix. These structures are presumably required for cross-linking collagen VI oligomers and for super-coiling of triple helices in the dimers. Other features include 11 Arg-Gly-Asp sequences, some of which are likely to be used as cell-binding sites, and four Asn-X-Thr sequences, allowing N-linked glycosylation along the triple helix. Junctional areas close to the helix contain short, cysteine-rich segments which may seal the triple-helical domain through disulfide bond formation, endowing it with high stability. These features, together with a low sequence homology to fiber-forming and basement-membrane collagens, document the unique character of collagen VI, whose triple helix is specifically adjusted for forming microfibrils in tissues.

Amino Acid Sequence↗

Structures and dynamics of the major G-quadruplex in the human PDGFR-&#x3b2; gene promoter: insights into vacancy G-quadruplex formation.

Overexpression of PDGFR-&#x3b2; (platelet-derived growth factor receptor beta) kinase contributes to diverse human diseases, including cancers, cardiovascular disorders, and fibrosis. G-quadruplexes (G4s) formed in the PDGFR-&#x3b2; promoter act as transcriptional repressors and represent attractive therapeutic targets. We previously reported that the major G4-forming region of the PDGFR-&#x3b2; promoter adopts a unique broken-strand G4, whereas truncation of this sequence generates a vacancy G4 (vG4) that can be filled-in by external guanine analogs or metabolites and further stabilized by small molecules, suggesting a potential regulatory mechanism and opportunity for selective drug targeting. However, the relationship between broken-strand G4s and vG4s remains unclear. Here, we demonstrate that the PDGFR-&#x3b2; promoter sequence forms a dynamic equilibrium between two broken-strand G4 conformations that interconvert on the millisecond timescale, with vG4 serving as an intermediate. We determined the high-resolution NMR structures of these interconverting G4s, which share a conserved vG4 core but differ in their intramolecular guanine "fill-in." Both conformations feature a stabilizing G-G capping base pair unique to the PDGFR-&#x3b2; promoter. These findings elucidate the structural details of broken-strand PDGFR-&#x3b2; promoter G4s and the mechanism of vG4 formation, providing critical insights for selective drug targeting and establishing a framework for rational design of small molecules to modulate PDGFR-&#x3b2; transcription.

G-Quadruplexes↗