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Meiotic recombination and DNA synthesis in a new cell cycle mutant of Saccharomyces cerevisiae.

Vegetative cells carrying the new temperature-sensitive mutation cdc40 arrest at the restrictive temperature with a medial nuclear division phenotype. DNA replication is observed under these conditions, but most cells remain sensitive to hydroxyurea and do not complete the ongoing cell cycle if the drug is present during release from the temperature block. It is suggested that the cdc40 lesion affects an essential function in DNA synthesis. Normal meiosis is observed at the permissive temperature in cdc40 homozygotes. At the restrictive temperature, a full round of premeiotic DNA replication is observed, but neither commitment to recombination nor later meiotic events occur. Meiotic cells that are already committed to the recombination process at the permissive temperature do not complete it if transferred to the restrictive temperature before recombination is realized. These temperature shift-up experiments demonstrate that the CDC40 function is required for the completion of recombination events, as well as for the earlier stage of recombination commitment. Temperature shift-down experiments with cdc40 homozygotes suggest that meiotic segregation depends on the final events of recombination rather than on commitment to recombination.

Cell Cycle

Repeat angiography in temporal contusions.

In the diagnosis of a temporal contusion bilater filling of the Sylvian vessels permits adequate comparison between the two sides. Such a comparison is important since even at a large contusion with marked upward or medial displacement of the Sylvian vessels no corresponding shift of the midline structure may exist in the acute stage. With increasing interval between trauma and angiography a shift may develop reflecting the true size of the lesion.

Cerebral Angiography

Timing of oocyte maturation in the mouse and its relevance to radiation-induced cell killing and mutational sensitivity.

Timing oocyte development by labeling the zona pellucida indicates that it takes 6 weeks (possibly a few days more) for a stage 3b oocyte to reach ovulation. Thus the shift in mutation frequency with time after irradiation occurs in an oocyte stage that is comparable in all mammals so far investigated, and in the mouse low-mutational sensitivity is not restricted to the arrested dictyate oocyte stage. Some oocytes with nuclear morphology similar to the arrested human oocytes give low mutation rates. Degree of chromosome condensation in early oocytes does not appear to be a reliable criterion of oocyte sensitivity to either cell killing or mutation induction, and genetic data on mouse oocytes may be more generally applicable than commonly thought.

Animals

Acetylcholinesterase isozymes in developing mouse tissues.

Several isozymes of acetylcholinesterase are separated by 10% acrylamide gel electrophoresis of mouse blood, brain, heart, muscle and tongue tissues. Two isozymes migrating near the origin are described which show changes in relative activity during development. The faster of the two bands is proportionately higher in concentration in embryonic tissues and is highly specific for the acetylthiocholine iodide substrate. This isozyme corresponds to the erythrocyte membrane AChE in electrophortic mobility and substrate specificity. The slower of the two bands is predominant in adult tissues and exhibits considerable cross reaction with the butyrylthiocholine iodide substrate. During embryonic and postnatal developmental stages there is a gradual shift from the faster migrating isozyme toward a predominance of the slower migrating isozyme.

Acetylcholinesterase

[A new image-processing system designed for densitometry and pattern analysis of microscopic specimen. Application to the automated recognition and counting of cells in the various phases of the mitotic cycle (author's transl)].

A new image analysing system, designed for microphotometric measurement and pattern recognition has been applied in the discrimination of cells from the various phases of the mitotic cycle. The data acquisition procedure is controlled by a programmable electronic unit and involves the combination of the shifting of the microscope moving stages and the scanning of the successive fields by a mechanical device. The data processing is achieved by a computer. The preliminary results we obtained have shown that such a system allows the automatic recognition and counting of the M, G1, S and G2 cells as also the G0 resting cells. The most useful parameters of the cell proliferation kinetics are thus obtained from a single specimen of a cell population.

Cell Count

Effect of human serum thymic factor on immature T lymphocytes in acute leukemia and other hematologic malignancies.

In 37 patients with acute leukemia and in 13 patients with other hematologic malignancies, E-rosette formation of peripheral blood mononuclear cells, before and after incubation with human serum thymic factor, was studied. This assay showed that incubation with thymic factor caused a clear-cut increase of E-rosette-forming cells in 8 of the 37 acute leukemia patients. Among the 13 patients with other hematologic malignancies, a similar effect was observed in two with pediatric Hodgkin's disease and in one adult with Waldenström's macroglobulinemia. These results support the contention that a significant percentage of the so-called "null" cells circulating in the blood of the above-mentioned patients were, in fact, immature T cells (T0 lymphocytes) that were shifted to a more mature stage (T1) by thymic factor.

Child

[Immunoglobulin level in viral hepatitis patients].

The results of studying the dynamics of serum immunoglobulins in patients with viral hepatitis varying in severity are presented. At the acute stage of the disease pronounced shifts in the content of all the three classes of immunoglobulins were found to occur in the patients irrespective of their age. Higher levels of IgM detected in women seem to be due to the physiological peculiarities of the female organism. Gamma globulin prophylaxis, when carried out at the incubation period, has been shown to exert a negative influence on humoral immunity.

Adolescent

Body surface potential distribution following the production of right bundle branch block in dogs. Effects of breakthrough and right ventricular excitation on the body surface potentials.

Right bundle branch block (RBBB) was produced in five dogs by incising the main right bundle branch. Body surface isopotential maps of each of these dogs were obtained from 85 thoracic electrocardiograms using a mini-computer technique. In addition, the epicardial activaton process was obtained from the same dog, and were correlated with the map pattern. Following the incision, the following characteristic changes in the map pattern occurred: The ventricular activation was prolonged in RBBB as compared with normal. During the early stage of ventricular excitation, the maximum was shifted leftward due to the activation wavefronts in the left ventricle in contrast to the double septal activation in the control. A localized lower potential area (a concavity) which appears in the middle stage of activation within the anterior positivity as an initial representation of breakthrough was also shifted left-and-downward and delayed in appearance. The sudden change in the potential distribution subsequently observed occurred quite differently. The terminal excitation was characterized by the maximum occurring over the right chest in RBBB in contrast to the left chest in control. These changes in the pattern of the potential distribution were compatible with the changes in the ventricular excitation process. This result may be applied to human RBBB map interpretation.

Action Potentials

Twenty-four-hour recording in REM-narcoleptics with special reference to nocturnal sleep disruption.

Twenty narcoleptic patients and ten age-matched normals were polygraphically monitored for 58 consecutive hours. All subjects were on regimented sleep (hours between 2230 and 0700). Group A (11 patients and 10 normals) had enforced wakefulness during the day whereas Group B (9 patients) were permitted to sleep (mean = 2 1/2 hr.). On day 2, all subjects were permitted to sleep for 15-min periods every 2 hr. In narcoloptics, sleep recordings demonstrated a reduction of sleep latency, an increase of stage 1, and a decrease in stages 3 and 4 compared to normals, but total REM time and percentage of REM sleep were similar. Groups A and B showed no difference in the incidence of nocturnal awakenings. REM cyclic periodicity was larger in narcoleptics who also demonstrated a REM-sleep fragmentation. This fragmentation became more pronounced as time passed, with several shifts from REM to wakefulness and stage 1. Narcoleptics present REM onset sleep period but also show an inability to remain in REM sleep.

Adult

Immunocytochemistry of the pituitary glycoprotein hormones.

The storage sites of the pituitary glycoprotein hormones were identified with the use of electron microscopic immunocytochemical techniques and antisera to the beta (beta) chains of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and thyroid-stimulating hormone (TSH). The TSH cells in normal rats is ovoid or angular and contains small granules 60-160 nm in diameter. In TSH cells hypertrophied 45 days after thyroidectomy, staining is in globular patches in granules or diffusely distributed in the expanded profiles of dilated rough endoplasmic reticulum. The gonadotrophs (FSH and LH cells) exhibited three different morphologies. Type I cells are ovoid with a population of large granules and a population of small granules. Staining for FSHbeta or LHbeta was intense and specific only in the large granules (diameter of 400 nm or greater). Type II cells are angular or stellate and contain numerous secretory granules averaging 200-220 nm in diameter. They predominate during stages in the estrous cycle when FSH or LH secretion is high. Type III cells look like adrenocorticotropin (ACTH) cells in that they are stellate with peripherally arranged granules. They generally stain only with anti-FSHbeta and their staining can not be abolished by the addition of 100 ng ACTH. In preliminary quantitative studies of cycling females, we found that on serial sections FSH cells and LH cells show similar shifts to a more angular population of cells during stages of active secretion. However, the shifts are not in phase with one another. Furthermore, there are at least 1.5 times more FSH cells than LH cells at all stages of the cycle. Our collection of serial cells shows that some cells (usually type I or II) stain for both gonadotropic hormones, whereas others (usually type II or III) contain only one.

Animals

Circulating Tumor DNA in Bladder Cancer: Current Clinical Evidence and Emerging Multi-Omics Perspectives-A Narrative Review.

Background: Circulating tumor DNA (ctDNA) analysis has emerged as a promising tool for real-time disease monitoring in muscle-invasive bladder cancer (MIBC). This narrative review summarizes current clinical evidence regarding ctDNA across disease stages. Methods: We examine recent translational and clinical findings, incorporating key prospective data from practice-changing trials, as well as insights into minimal residual disease (MRD) detection, treatment escalation and de-escalation strategies, and systemic barriers to adoption. Results: Postoperative ctDNA positivity consistently identifies patients with molecular residual disease (MRD) who face a substantially higher risk of recurrence and mortality, frequently preceding radiographic relapse by several months. Prospective evidence now validates ctDNA as a predictive biomarker to guide adjuvant immunotherapy escalation, while sustained ctDNA negativity correlates with high long-term disease-free survival. Beyond plasma ctDNA, emerging multi-compartment liquid biopsies-integrating urinary tumor DNA (utDNA)-demonstrate enhanced sensitivity, particularly in bladder-sparing and local surveillance settings. Furthermore, integrating genomic ctDNA profiling with novel post-transcriptional layers like epitranscriptomics offers a functional framework to capture tumor adaptation under therapeutic pressure. However, clinical translation remains constrained by a lack of assay harmonization, variable analytical sensitivity, and the need for standardized intervention thresholds. Conclusions: Longitudinal liquid biopsies are rapidly shifting MIBC management from static, stage-based paradigms toward dynamic, molecularly informed precision oncology. While ctDNA-guided strategies show robust clinical utility, prospective interventional validation and technical standardization are required before widespread routine integration.

biomarkers

[Heat sensitivity of starred sturgeon follicles at different stages of their maturation period].

The influence of sharp temperature shift and proportioned keeping of the sevryuga females at a low temperature on the oocyte maturation and ovulation has been studied. The reaction of the follicles to similar influences was shown to differ at different stages of the period of maturation inertia: the follicles remained intact at the stages prior to the germinal vesicle (oocyte nucleus) breakdown, were damaged in a part of females at the prometa- and metaphase I and in the most females at the prometa- and metaphase II. The injection of triiodothyronine to the females subjected to cooling at different stages of the period of maturation inertia exerted no effect on the oocyte ovulation and the egg fertilizability.

Animals

Reframing early gastric carcinogenesis through lineage, niche, and evolution.

Early gastric cancer is still commonly conceptualized as the endpoint of a linear sequence from chronic gastritis to intestinal metaplasia, dysplasia, and invasion. Yet recent single-cell, spatial, genomic, and functional studies indicate that this model incompletely captures the biology of early gastric carcinogenesis. Malignant potential is established progressively within a precancerous gastric field already shaped by somatic evolution, chronic inflammatory injury, and epithelial lineage distortion. Within this field, progression is concentrated in a restricted set of precursor states, particularly incomplete, hybrid, and stem-like metaplastic populations that display plasticity, persistence, and increasing compatibility with a supportive microenvironment. Fibroblast niche remodeling, immune protection loss, endothelial rewiring, genomic instability, epigenetic drift, and selective retention of advantageous molecular alterations further promote malignant commitment. In parallel, diffuse gastric cancer appears to follow a distinct route that may arise independently of conventional intestinal metaplasia through E-cadherin-deficient epithelial transformation and downstream chromatin reprogramming. Here, we synthesize recent evidence to propose an updated framework for early gastric carcinogenesis based on field evolution, lineage instability, ecosystem support, and pathway divergence. Rather than replacing the classical Correa cascade, this framework seeks to refine it by shifting the unit of risk assessment from histologic stage alone to biologically defined precursor states shaped by lineage instability, clonal persistence, niche permissiveness, and pathway-specific molecular constraints. This perspective shifts the emphasis of prevention from detecting smaller cancers to identifying and intercepting biologically committed precursor states before invasion occurs.

Humans

Polytene chromosomes of Oxytricha: biochemical and morphological changes during macronuclear development in a ciliated protozoan.

After conjugation in the ciliated protozoan, Oxytricha, polytene chromosomes are formed during the development of a macronucleus from a micronucleus. Here we report a microscopic study of these chromosomes and an analysis of their DNA. The polytene chromosomes of Oxytricha bear a strong morphological resemblance to the polytene chromosomes of the Dipteran salivary gland. The nucleus of a developing macronuclear anlage contains 120 +/- 2 polytene chromosomes and each chromosome has an average of 81 hands; a total of about 10,000 bands per nucleus. At a later stage in development, the number of bands per chromosome is reduced by a factor of four, presumably due to fusion of adjacent bands. The polytene chromosomes then break up into their constituent bands, each of which is encased in a vesicle. There are about 2,700 vesicles per nucleus.--During the growth of polytene chromosomes, there is a change in the relative proportion of sequences in the DNA. The DNA from polytene nuclei has a buoyant density of 1.695 g/cc, significantly lighter than the density of the original micronuclear DNA (1.698 G/cc to 1.702 g/cc). We interpret this buoyant density change to be the result of differential replication of DNA sequences during polytene chromosome growth. A second change in DNA composition occurs after the polytene stage of development, shown by a shift in buoyant density to 1.701 g/cc in the DNA of the mature macronucleus. During this second process, the molecular weight of the DNA is reduced from greater than 50 x 10(6) daltons to about 2 x 10(6) daltons.

Animals

Hydrogen-supported biodefluorination of unsaturated perfluorinated carboxylic acids.

PFMeUPA (i.e., (E)-perfluoro(4-methylpent-2-enoic acid) is a unsaturated perfluorohexanoic acid wtih emerging concern due to its potential to cause developmental toxicity. Here, we investigate the sustainable biological treatment of PFMeUPA under anoxic conditions by delineating batch degradation potential and continuous-flow reactor dynamics using hydrogen (H2) as the sole electron donor. In batch assays inoculated with anaerobic digestion sludge, an enriched hydrogenotrophic consortium achieved near-complete removal of 50 μM PFMeUPA over 90-days with a stoichiometric release of 125 μM fluoride (F-), representing a 26% defluorination extent that corresponds to the cleavage of two C-F bonds per molecule. The continuous-flow H₂-based membrane biofilm reactor (MBfR) harboring this enriched anaerobic biofilm was operated for 130 days, achieving 100% removal of 5 μM PFMeUPA and 20% of defluorination at a hydraulic retention time (HRT) = 6 h. Transformation product identification using high-resolution mass spectrometry suggests dominance of reductive defluorination and a shift toward hydrogenated byproducts at later stages. Metagenomic results indicate the enrichment of microbial taxa including Hydrogenophaga (hp_bin.22) and and Azonexus (hp_bin.19) genomes, which carry genes for hydrogen metabolism (hoxH) and fluoride efflux pumps (crcB). This work demonstrates the feasibility of hydrogen-supported biological treatment for unsaturated perfluorinated carboxylic acids from contaminated water. SYNOPSIS: We demonstrate reductive defluorination of branched PFAS by a H2-fed biofilm, with co-occurring hydrogenase and fluoride exporter genes in Hydrogenophaga and Azonexus as potential biodefluorination biomarkers.

Hydrogenotrophic biodefluorination

The convergent evolution of the pelvic suction cup: A unique key innovation in spiny-finned fishes.

Key innovations open ecological opportunities and can redirect evolutionary trajectories. In spiny-finned fishes, the pelvic suction cup-a fused adhesive structure formed from the pelvic fins and supported by a modified girdle-appears to be one such trait. Using a novel 960-species phylogeny spanning 940 exons and 67 newly sequenced snailfish genomes, we show that the suction cup evolved independently three times across lineages separated by over 100 million years. By enabling adhesion in high-energy habitats such as tide pools and waterfalls, the suction cup set the stage for body depression and accompanying shifts in scales, teeth, and clade-specific ecofunctional profiles. Comparative analyses reveal convergence in a distinctive region of morphospace and body-shape evolution accelerated two- to fivefold. Diversification analyses uncover heterogeneous but elevated rates, with a clear burst in rock-climbing gobies associated with suction cup evolution. By opening novel habitats and fostering phenotypic novelty, the suction cup emerges as a key innovation that reshaped spiny-finned fish evolution.

Animals

A low-cost signal averager and data-acquisition device.

A low-cost data-acquisition device, which can be used as a signal averager or temporary data buffer, is described. It consists of 1) an input stage built with a multiplexer, sample-and-hold amplifier, and an analog-to-digital converter; 2) a memory section made of static shift registers with recirculate capability; 3) an output stage built with a demultiplexer and a digital-to-analog converter and, 4) a control module which provides the logic signals to operate the machine. Basic diagrams are presented and several applications are described.

Electronics

Interpretation of the body surface isopotential maps of patients with right bundle branch block. Determination of the region of the delayed activation within the right ventricle.

Body surface isopotential maps were produced by computer processing of the 85 electrocardiograms obtained from the entire thorax of 28 patients with complete or incomplete right bundle branch block (RBBB). We divided the map patterns into the following 3 groups. Type I map pattern (10 cases): at the early stage of QRS, the maximum was located in the left chest. It shifted to the left from the normal position; at the instant of 44 msec, on the average, after the onset of QRS breakthrough minimum appeared over the left chest. Its appearance was delayed and its site shifted to the left as compared with the normal; at the late stage, the positive zone covered extensively the right chest and the right back; terminally, the maximum was positioned along the right parasternum. Type II map pattern (13 cases): at the early stage of QRS, the maximum was in the left chest as in Type I; breakthrough minimum appeared at 38 msec on the average, later than in the normal, but the site of breakthrough minimum varied from the left chest as in Type I to the midsternal region as in the normal; at the late stage, the positive zone covered the upper part of the right chest and the right back, less extensively than in Type I; the terminal maximum was in the upper sternal region. Type III map pattern (5 cases): the map pattern passed normally until the late stage, but thereafter a small positive zone survived over the upper sternal region. In Type I the delayed activation was presumed to occur all over the right ventricle, in Type II mainly over the smaller area of the right anterior free wall, and in Type III over the localized area of the outflow tract. Patients with complete RBBB showed Type I pattern. Patients with incomplete RBBB showed Type II or Type III pattern, although electrocardiograms failed to differentiate Type II patients from Type III patients. These findings suggest that the electrocardiographic pattern of incomplete RBBB probably arises from the various mechanisms.

Adult