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[Effect of emotional stress on sleep dynamics in cats].

Emotional stress was developed in cats by putting them in one cage with dogs for 24 hours. Then the 24 hours sleep-walking cycles records revealed prolonged REM stage in day time or at night in five animals out of seven, and in six animals a general increase of REM sleep duration over 24 hours. Simultaneously, in six animals the length of drowsiness and of deep slow-wave sleep stages was reduced. Increased overall sleep duration in the 24 hours was recorded in five cats. Sleep changes dynamics analysis reveals three stages: 1) sharp shift of all sleep parameters--27%, 2) deviation in sleep parameters--34% and 3) returning to basic sleep parameters--in 38%. The conclusion is drawn that sleep disorders may be used as an index of higher nervous activity disturbance in waking state.

Animals↗
PubMed2026

Maternal redd1 mRNA decline triggers mTORC1 activation during the blastula-gastrula transition in zebrafish embryos.

During early metazoan development, maternal mRNAs and proteins stored in the egg sustain initial cellular functions. After the blastula stage, developmental control shifts to zygotic gene expression, and maternal transcripts are progressively degraded. Although mTORC1 is a central regulator of global mRNA translation and cell growth, its role in controlling maternal mRNA translation prior to gastrulation remains poorly understood. In zebrafish embryos, the mTORC1 inhibitor redd1 is abundantly expressed after fertilization but decreases following the maternal-to-zygotic transition (MZT), inversely correlating with mTORC1 activity. Overexpression of redd1 suppresses mTORC1, impairs gastrulation, and reduces translation of 5'TOP mRNAs and key regulatory genes, underscoring the necessity of relieving mTORC1 inhibition after the blastula stage. To investigate redd1 translation under conditions of low mTORC1 activity, we injected reporter mRNAs containing its 5' and 3' UTRs. The 3'UTR promoted polyadenylation and enhanced translation, while both UTRs enabled efficient reporter expression despite mTORC1 suppression, indicating that redd1 mRNA is translated independently of canonical mTORC1 pathways. Similarly, maternal mRNAs such as nanog, myca, pou5f3, and ccnb1, as well as the early zygotic transcript dharma, are translated through mTORC1-independent mechanisms. Together, these findings reveal a transient phase of mTORC1 suppression in early zebrafish embryos and demonstrate that select maternal and zygotic mRNAs bypass this regulation to ensure proper developmental progression.

Animals↗
PubMed1979

Stage of palate closure as one indication of "liability" to cleft palate.

A new inbred mouse strain, SW/Fr, developed from a random-bred SW stock has a 6% incidence of spontaneous cleft palate without cleft lip. SW/Fr mice close their palates comparatively late in development. After cortisone treatment, the mean of the distribution (mean time to reach palate stage 5) is shifted towards later gestational ages. There is no change in the variance of the distribution. These data lend further support to the hypothesis that cleft palate in mice may fit a model where a continuous distribution is separated into discontinuous parts by a developmental threshold, and that time of palate closure is an important component of liability to cleft palate.

Animals↗
PubMed2026

A novel urease-producing strain effectively induces cadmium biomineralization under low-temperature stress.

Microbially induced carbonate precipitation (MICP) has been widely used to immobilize Cadmium (Cd) in contaminated soils in mining-affected regions. However, its remediation efficacy under low-temperature stress, as well as the nucleation process that regulates Cd biomineralization via carbonate precipitation by psychrophilic bacteria, has yet to be investigated. Here, we isolated Pseudomonas sp. J-6, a novel urease-producing strain from tailings in high-altitude cold regions, exhibiting unparalleled cold adaptability at 5 °C and achieving 95.85 % Cd removal efficiency by MICP at 10 °C. Furthermore, the coprecipitation process of Ca1-xCdxCO3 was clarified through the continuous observation of the precipitates after the low-temperature MICP reaction. The crystal morphology transitioned from loose vaterite in the early stage to a dense square-block morphology in the middle stage. Cd2+ progressively shifted from a surface-bound state to lattice incorporation, ultimately resulting in the formation of stable Cd-substituted calcite crystals. In this process, low temperatures led to the formation of larger, highly ordered Cd-substituted calcite crystals, thereby strengthening Cd sequestration and its long-term stability. In addition, under low-temperature stress, Pseudomonas sp. J-6 induced MICP reaction decreased the bioavailable Cd in alpine slag soil by 44.85 % and enhanced physical properties. In the freeze-thaw cycles, the remediation efficiency remained stable. This study clarified the biomineralization potential in high-altitude cryogenic environments and the nucleation process of Cd biomineralization by psychrophilic bacteria-induced carbonate precipitation, filling a critical research gap in its application under extreme conditions and highlighting its promise for sustainable remediation of heavy metal pollution under low-temperature stress.

Cadmium↗
PubMed1979

[Dynamics of the total proteolytic activity and kinin system components of the blood in acute cholecystitis].

Under study was the dynamics of changes of the activity of components of the kinin system and proteolytic activity of blood in 32 patients with acute cholecystitis. The results have shown that cholecystic patients and patients with the diseases of biliary ducts, especially in the exacerbation stage, have pronounced shifts in the kinin system components and in the proteolytic activity of blood as a whole. In clinical conditions the proteolytic activity data can be used for determining the severity and development of acute cholecystitis. The use of protease inhibitors in the inflammation of the gallbladder and biliary ducts results in a decreased blood proteolytic activity and thereby contributes to more rapid recovery of patients with such disorders.

Acute Disease↗
PubMed1978

Effects of high ambient temperature on sleep in young men.

Each of 10 normal subjects had 4 nights of laboratory-monitored sleep, consisting of adjustment, baseline, high blanket temperature (HBT), and recovery nights. EEG-EOG recordings were made on each night; rectal temperature, heart rate, body weight, and ambient temperatures were monitored throughout the last 2 nights. On the HBT night, subjects had less total sleep time, more frequent and longer awakenings, greater shifting among sleep stages, decreased amounts of stage 1 REM and stages 3 + 4, and delayed onset of deep sleep (stages 3 and 4). Body temperature was elevated to a relatively constant level of 37 degrees C on the HBT night, but gradually decreased from 36 degrees C to 34.5 degrees C across the recovery night. Heart rate decreased at a linear rate on both the HBT and recovery nights, but was 15 beats/min faster on the former. Subjects experienced liquid loss of 1.25 kg on the HBT night, but had a full recovery by the following evening.

Adult↗
PubMed2026

Integrative multi-omics analysis reveals lipid/metabolite dysregulation and temporal decoupling in disease progression.

Our study presents and applies a metabolomics-driven multi-omics integration strategy to elucidate dynamic pathway interactions during disease progression. We analyzed longitudinal metabolomics datasets from a Duchenne muscular dystrophy (DMD) mouse model (6-30 weeks) and an acute Bothrops asper envenomation model (1-24 h) to contrast chronic versus acute inflammation. In the DMD model, we predicted phased cross-talk between sphingolipid metabolism and neurotrophin signaling: an early proteomic surge followed by lipid-mediated amplification and a late convergence at the protein level. Arginine and proline metabolism exhibited early metabolite accumulation preceding delayed inferred protein changes, consistent with impaired nitric oxide synthesis and argininemia-like effect. We also predicted late-stage activation of the AGE-RAGE pathway in DMD, likely triggered by ceramide buildup, and an autophagy-related lipid metabolic shift at mid-stage. In the envenomation model, tryptophan-kynurenine and nicotinamide pathways for NAD⁺ biosynthesis were rapidly perturbed at the metabolite level (1-3 h) but induced corresponding predicted enzymes only by 24 h. Thyroid hormone signaling showed an early coupling of substrate availability (tyrosine surge at 1 h) with predicted stress-response proteins and a second, delayed wave of inferred transcriptional regulators at 24 h. Acute envenomation also triggered immediate glycine/serine utilization possibly for antioxidant defense and glycerophospholipid breakdown (via phospholipase A₂), whereas chronic DMD showed sustained glycine/serine engagement and inferred, unresolved phospholipid perturbation without protein-level compensation, which may result from chronic oxidative stress. Overall, our integrative analysis revealed time-specific, multi-layer molecular perturbations distinguishing acute toxin injury from chronic muscle degeneration. Key metabolic control points (ceramide accumulation, arginine flux diversion, autophagy-lipid cross-talk, NAD⁺ salvage timing) were identified, highlighting potential targets for stage-specific therapeutic or nutritional interventions.

Animals↗
PubMed1979

Sensitivity patterns for the induction of homeotic shifts in a favorable strain of mice.

In an effort to develop a prescreening system that is sensitive, is compatible with in-vivo administration of presumptive teratogens, and utilizes morphological endpoints, we are studying the induction of homeotic shifts in the axial skeleton. Our earlier work had demonstrated the existence of critical periods for certain such shifts, even though the (C57BL x NB)F1 hybrid used was not entirely suitable for this purpose. Using 100 R X-rays on successive days during the period of major organogenesis, we have now analyzed the sensitivity pattern of the BALB/c, since this strain normally straddles thresholds for the position of axial borders. Mortality, birthweight, and skeletal anomalies were analyzed, in addition to the homeotic shifts. --Day 9 1/4 postconception was clearly the most sensitive stage for the production of posterior shifts at the thoraco-lumbar border and the lumbo-sacral border, and for increases in the number of sternebrae and costo-sternal junctions. Anterior shift could be induced three days later, on day 12 1/4, but this was confined to only one of the four characters, the thoraco-lumbar border. There are a number of indications that, at given stages during the study period, BALB/c embryos correspond developmentally to chronologically somewhat earlier stages of two strains studied previously. The present results do not support the hypothesis that factors influencing the quantitative skeletal characters act by way of body size. --Since homeotic shifts can be produced by a number of mechanisms and are obvious indications that developmental interference has occurred, and since such shifts are easy to score and convenient to analyze quantitatively, our identification of a highly suitable strain and of stages of maximum sensitivity in this strain should aid in making the system useful in the prescreening for chemical teratogens.

Abnormalities, Drug-Induced↗
PubMed1976

Dose-related sleep disturbances induced by coffee and caffeine.

In a 13-night sleep laboratory study, each of 18 normal young adult males twice received 1 cup of warm water, 1-, 2-, and 4-cup equivalents of regular coffee, a 4-cup equivalent of decaffeinated coffee, and a 4-cup equivalent of caffeine. All beverages were administered 30 min before bedtime according to a balanced Latin-square design. Regular coffee produced dose-related changes in most standard electroencephalogram-electrooculogram (EEG-EOG) sleep parameters, and the 4-cup equivalents of regular coffee and caffeine produced equivalent effects. Decaffeinated coffee had no effect. Regular coffee and caffeine caused rapid eye movement (REM) sleep to shift to the early part of the night and stages 3 and 4 sleep to shift to the later part. Coffee also produced dose-related changes in several subjects estimates of sleep characteristics. These results suggest that coffee and caffeine may be used in normal subjects to induce symptoms mimicking those of insomnia. Such a tool should promote further understanding of insomnia.

Adult↗
PubMed2025

Proposal of real-world solutions for the implementation of predictive biomarker testing in patients with operable non-small cell lung cancer.

The implementation of biomarker testing for targeted therapies and immune checkpoint inhibitors is a cornerstone in the management of metastatic and locally advanced non-small cell lung cancer (NSCLC), playing a pivotal role in guiding treatment decisions and patient care. The emergence of precision medicine in the realm of operable NSCLC has been marked by the recent approvals of osimertinib, atezolizumab, nivolumab, pembrolizumab and alectinib for early-stage disease, signifying a shift towards more tailored therapeutic strategies. Concurrently, the landscape of this disease is rapidly evolving, with several further pending approvals and numerous clinical trials in progress. To harness the benefits of these innovative neo-adjuvant and adjuvant therapies, the integration of predictive biomarker testing into standard clinical protocols is imperative for patients with operable NSCLC. A multidisciplinary international consortium has identified three primary obstacles impeding the effective testing of patients with operable NSCLC. These challenges encompass the limited number of test requests by physicians, the inadequacy of tissue samples for comprehensive testing, and the prevalence of cost-reduction measures leading to suboptimal testing practices. This review delineates the aforementioned challenges and proposed solutions, and strategic recommendations aimed at enhancing the testing process. By addressing these issues, we strive to optimize patient outcomes in operable NSCLC, ensuring that individuals receive the most appropriate and effective care based on their unique disease profile.

Humans↗
PubMed1976

[Development of the neurosecretory system of the eyestalk of larval Astacus leptodactylus salinus (Crustacea Decapoda Reptania): photon microscopy].

Using the alcian blue-alcian yellow staining method, the neurosecretory system in the eyestalk of the Crayfish Astacus leptodactylus is studied during the period following the first, second, third and fourth moult after hatching. On the basis of their staining affinities, six different cell types are distinguishable, always spread over the four optic ganglia and varying in number depending upon the moment of sampling. A clearly recognizable sinus gland is present in the period following the third and fourth moult after hatching. During the successive stages, there occurs a shift in staining pattern of the sinus gland, which is also expressed by the variation in number of the various stained cell types.

Astacoidea↗
PubMed2026

NoisyFlow: differentially private optimal transport using neural networks for secure biomedical data sharing across multiple institutions.

MOTIVATION: Biomedical models improve when trained on data pooled across institutions, but sensitive patient records (e.g. genomics, clinical data, and medical images) are difficult to share due to privacy constraints. Moreover, data collected at different sites often have shifted distributions because of covariate differences (including batch effects), so privacy-preserving sharing alone cannot simply resolve cross-site mismatch. Methods that protect individuals while explicitly aligning distributions are needed to enable reliable multi-institutional analyses. RESULTS: We present NoisyFlow, a three-stage differentially private framework for cross-institutional harmonization under distribution shift. In stage I, each site learns a differentially private flow-based generator of its local labeled distribution. In stage II, it learns a neural optimal transport map to a shared reference distribution. In stage III, a central server composes the released models to generate reference-aligned pseudo-data for downstream analysis without accessing raw records. Across four biomedical settings spanning single-cell genomics, histopathology, neurogenomics, and wearable sensing, NoisyFlow reduces distribution shift while preserving downstream utility under formal differential privacy guarantees. AVAILABILITY AND IMPLEMENTATION: The implementation of NoisyFlow is available at https://github.com/gersteinlab/NoisyFlow.

Information Dissemination↗
PubMed2026

Integrative multi-omics analysis of metabolite-protein interaction networks across different stages of coronary heart disease.

To elucidate the molecular characteristics of synergistic interactions across the clinical stages of coronary heart disease (CHD)-specifically stable angina pectoris (SAP), unstable angina pectoris (UAP), and acute myocardial infarction (AMI)-through integrated metabolomic and proteomic analyses. Based on a cohort including SAP, UAP, AMI, and healthy controls, metabolomic and proteomic analyses were performed to identify differentially expressed molecules, followed by KEGG pathway enrichment analysis. Pathways co-enriched across both omics platforms were selected to construct metabolite-protein interaction networks. The number of pathways co-enriched in both metabolomic and proteomic analyses increased markedly with disease stage. Only two pathways (histidine metabolism and arginine and proline metabolism) were identified in the SAP stage; this number increased to five in the UAP stage (including ferroptosis and efferocytosis) and expanded to 25 in the AMI stage, encompassing three major functional modules: immune inflammation, metabolic reprogramming, and cell signaling. The core network exhibited a stepwise increase in connectivity, shifting from a sparse structure in the SAP stage to a highly interconnected architecture in the AMI stage, with L-glutamate and KNG1 identified as the central hubs in this cross-sectional network. In addition, CNDP1 exhibited a stage-dependent functional transition, shifting from downregulation in SAP to upregulation in AMI. In this cross-sectional analysis, metabolic dysregulation and immune activation exhibited stepwise increases in interconnectivity across the SAP, UAP, and AMI groups, with the most extensive crosstalk observed in the AMI stage-a network configuration consistent with a tightly coupled "molecular storm". These findings provide novel insights into stage-associated molecular signatures of CHD and identify candidate hub molecules for stage-oriented therapeutic investigation.

Humans↗
PubMed2026

Adjuvant CDK4/6 inhibitors in early-stage breast cancer: Clinical evidence and considerations for risk stratification and treatment selection.

Hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer is the most common biologic subtype and carries a persistent risk of recurrence, particularly in patients with high-risk, early-stage disease. Cyclin-dependent kinase 4 and 6 inhibitors, initially established as a standard component of first-line therapy in the metastatic setting based on improvements in progression-free and overall survival, have since been evaluated in the adjuvant setting. While adjuvant palbociclib did not improve invasive disease-free survival, the monarchE and NATALEE trials demonstrated that abemaciclib and ribociclib, respectively, reduce recurrence risk in patients with high-risk, early-stage disease, with emerging overall survival data further supporting their use. However, the absolute magnitude of benefit varies substantially with baseline risk, and treatment-related toxicity and adherence challenges must be considered, as approximately 20% to 25% of patients discontinue therapy before completion. The integration of these agents into clinical practice also intersects with ongoing efforts to deescalate axillary surgery, as treatment eligibility has been largely defined by anatomic staging, particularly nodal status. Available data suggest that the incremental impact of axillary surgery on identifying candidates for cyclin-dependent kinase 4 and 6 inhibition is modest, especially among the favorable-risk populations now eligible for surgical deescalation. As the field evolves, advances in molecular risk stratification, genomic profiling, and dynamic biomarkers are poised to shift treatment selection from anatomic staging toward biologically driven approaches. Multidisciplinary decision-making that integrates tumor biology, anticipated absolute benefit, toxicity, patient preferences, and surgical considerations will be essential to ensure individualized care.

Humans↗
PubMed1978

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↗
PubMed1979

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↗
PubMed1977

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↗