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At least 19 recordsLinked to original sources
PubMed2026

Partial enumeration of extreme rays in metabolic networks using bit pattern trees.

Extreme ray analysis of metabolic networks, even though very powerful, is currently limited to smaller metabolic networks. Some approaches to generating partial sets of extreme rays exist, but the computational efficiency of the so-called double-description method is yet to be exploited. Previous work highlighted the possibility of sampling within its iterations, enabling partial enumeration for double-description based methods. However, these approaches severely lack computational efficiency to be a suitable alternative. In this work, the highly efficient bit pattern trees are used within the sampling framework to significantly enhance its output and speed. Combined with the recent revision of the Canonical Basis Approach (CBA), our approach outperforms the other tested methods under the reported benchmark conditions even for a full enumeration study, requiring only half the computation time. In addition, a filter setting allows the memory demand to be scaled down while retaining high efficiency. However, some issues with the combinatorial explosion of candidates still persist and are further investigated. This study therefore puts forward a novel, double description-based alternative to partial enumeration of extreme rays. Further improvements in memory efficiency would allow this promising approach to scale powerful extreme ray-based analyses to genome-scale metabolic networks.

constraint-based modelling↗
PubMed2026

Transposon insertion sequencing of Pseudomonas aeruginosa identifies multiple intersecting pathways essential for extreme colistin resistance.

Colistin is used to treat antibiotic resistant gram-negative infections, including those caused by Pseudomonas aeruginosa (Pa). Using a diverse collection of clinical isolates, we identified BWH047, a colistin-resistant isolate with an extremely high minimum inhibitory concentration (MIC, 1280 µg/mL). To characterize the genes conditionally essential for colistin resistance in BWH047, we employed transposon insertion sequencing and identified 20 gene candidates. In-frame deletion validated 75% of the candidates and identified genes in several new pathways that contribute to colistin resistance in Pa, including algU and wapH. We also identified several candidate genes from previously reported colistin resistance pathways (e.g., arn, pmrAB). We further investigated the impact of a colistin resistance-associated inner membrane DedA-family undecaprenyl phosphate flippase, which we named DpcA (DedA of Pseudomonas necessary for colistin resistance A). Deletion of dpcA in BWH047 restored sensitivity to colistin (MIC = 0.5 µg/mL) and resulted in several unique changes to the structure of lipopolysaccharide (LPS), including production of decreased amounts of the colistin resistance-conferring 4-amino-4-deoxy-L-arabinose (L-Ara4N) modification on lipid A. This work represents a robust analysis of colistin resistance in Pa and identifies intersecting pathways that contribute to extreme phenotypic resistance.

Pseudomonas aeruginosa↗
PubMed1979

Central locomotor programming in the rabbit.

In decorticate, unanaesthetized and curarized rabbit preparations, with both hindlimbs deafferented, locomotor-like discharges were recorded from nerves to flexors and extensors and their time patterns were compared. The bursts of rhythmic activities recorded from nerves to several flexor muscles acting at either joint were shown to be synchronous, with no differences in their time of onset. The same was true for the extensors. Nerves to bifunctional muscles (biceps posterior, semi-tendinosus and tenuissimus) acting on two consecutive joints (knee flexors, hip extensors) could display two consecutive bursts in each locomotor cycle, one being pure flexor and the other an extensor discharge. It is shown here that this functional bivalence is programmed centrally and can be modulated, i.e. the relative importance of the flexor and the extensor bursts can be changed in a predictable way through afferent (proprioceptive or cutaneous) influences, or through activation of the descending monoaminergic pathways. In extreme cases, complete functional reversal was observed in these bifunctional muscle nerves.

Action Potentials↗
PubMed2024

A case of Ph+ acute lymphoblastic leukemia and EGFR mutant lung adenocarcinoma synchronous overlap: may one TKI drug solve two diseases?

BACKGROUND: Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) refers to ALL patients with t(9;22) cytogenetic abnormalities, accounting for about 25% of ALL. Lung adenocarcinoma (LUAD) is the most common pathological type of non-small-cell lung cancer, which has a frequency of approximately 45% cases with mutations in EGFR. Both Ph+ ALL and EGFR mutant LUAD are involved in the pathogenesis of the abnormal activation of the tyrosine kinase pathway. Although the second primary hematological malignancy after the treatment of solid tumors is common in clinics, the synchronous multiple primary malignant tumors of hematological malignancy overlap solid tumors are uncommon, even both tumors involved in the pathogenesis of the abnormal activation of the tyrosine kinase pathway are extremely rare. CASE PRESENTATION: An 84-year-old man with fatigue and dizziness was diagnosed with Ph+ ALL. Meanwhile, a chest CT indicated a space-occupying lesions, characterized by the presence of void, in the right lower lope with the enlargement of mediastinal lymph node and right pleural effusion. After a few weeks, the patient was diagnosed with LUAD with EGFR exon 19 mutation. Both tyrosine kinase inhibitors (TKI) (Flumatinib) and EGFR-TKI (Oxertinib) was used for the patients, and finally have controlled both diseases. CONCLUSION: As far as we know, we for the first time reported a case of Ph+ ALL and EGFR mutant LUAD synchronous overlap, of which pathogenesis is related to abnormal tyrosine kinase activation. This patient was successfully treated with two different TKIs without serious adverse events.

Humans↗
PubMed2025

Primulina pan-genome reveals differential gene retention following whole-genome duplications and provides insights into edaphic specialization.

Primulina, a genus of >200 species specialized to extreme soils, provides a model for edaphic adaptation. We assemble seven genomes and construct a pan-genome spanning nine species from karst, Danxia, and acidic soils. Comparative analyses reveal that karst-adapted species have smaller genomes. Two lineage-specific whole-genome duplications (WGDs) exhibit biased duplicate loss in large gene families but preferential retention of transcription factors, indicating combined adaptive and nonadaptive forces. Pan-genome analyses identify ion channel and transporter genes enriched in variant hotspots and under positive selection in karst lineages. Candidate genes for drought and salt stress tolerance include ABC transporters and ion channels. Notably, an ABC transporter shows positive selection in karst species and unique structural variation in non-karst species. Together, our findings show that genome downsizing, biased post-WGD retention, and evolution of ion-transport pathways shape adaptation to extreme soils. The Primulina pan-genome provides a resource for dissecting mechanisms underlying edaphic specialization.

Gene Duplication↗
PubMed2025

De novo transcriptome assembly and gene expression analysis of Cnidium officinale under high-temperature conditions.

BACKGROUND: The medicinal plant Cnidium officinale (CO) is widespread in Northeast Asia and vulnerable to heat stress. The naturally occurring composition of pharmacological ingredients of CO results in overall physiological consequences; therefore, it is crucial to have a comprehensive understanding of metabolic response to ambient heat in terms of acclimation to estimate how much CO is exposed to threatening environmental conditions. RESULTS: Transcriptome analysis is critical for understanding the consequences of long-term physiological adaptation of CO to abiotic stress. However, transcriptome analysis on this species, particularly under prolonged stress conditions, has remained limited. We employed a temperature gradient tunnel (TGT) to subject CO to high-temperature exposure for four months, enabling us to observe the cumulative effects of heat and assess its acclimation mechanisms. In the absence of genome sequencing data, we performed de novo transcriptome assembly and compared DEGs from temperature treatment plots of a TGT and a growth chamber (GC). Since interpreting transcriptomic data can be complex, we employed a sequential analytical approach, including DEG clustering, GO enrichment, KEGG pathway mapping, miRNA-target gene analysis, and multiple rounds of RNA sequencing validation. DEGs were classified into two categories: genes exhibiting significant fold changes and genes showing significant count changes rather than fold changes. Then, we analyzed the functional roles of DEGs to determine which pathways respond to ambient and stressful high temperatures and validated the findings through cross-comparison with GC. Additionally, we conducted miRNA analysis to investigate post-transcriptional regulation under high temperatures. CO grown under higher ambient temperatures exhibited slight upregulation of pathways related to protein stability and turnover, ABA biosynthesis, and energy production, such as photosynthesis and oxidative phosphorylation. However, under extreme heat stress, most metabolic pathways were downregulated except for those involved in transcription, translation, oxidative phosphorylation and the biosynthesis of cutin, suberin, and wax. CONCLUSION: This study demonstrated that proper clustering of genes based on expression levels and fold changes in two different experimental conditions, along with pathway mapping, may provide a comprehensive understanding of CO's response to heat stress. These insights could contribute to future research on heat tolerance and crop improvement.

Gene Expression Profiling↗
PubMed1979

Migration of a particulate radioactive tracer from the vagina to the peritoneal cavity and ovaries.

In this report we describe a radionuclide procedure designed to evaluate the migration of a particulate radioactive tracer from the vagina to the peritoneal cavity and ovaries, as well as the determination of the patency of the pathways between these two extremes of the female reproductive system. 99mTc-labelled human albumin microspheres (99mTc-HAM) were deposited in the posterior fornices of 24 patients a day before they were to undergo different gynaecological operations. During this period sequential images were obtained and after the operation radioactivity levels in the removed organs and tissues were counted with a scintillation detector. In 14 out of 21 cases, the ovaries and fallopian tubes were counted separately from the uterus. Nine were positive (radioactivity levels were sufficiently high in the tubes and ovaries) and 5 were negative (no substantial radioactivity levels could be detected in either the tubes or the ovaries). The 5 negative results all occurred in patients with proved tubal damage as a result of previous infection. All the results were either true positive or true negative, providing evidence of migration, or obstruction, of 99mTc-HAM from the vagina through the uterus and tubes to the peritoneal cavity and ovaries.

Adult↗
PubMed1976

A study on the pathogenesis of postmastectomy lymphedema.

In order to study the causes of postmastectomy lymphedema, venography, lymphangiography and RISA absorption test were performed on the patients following radical mastectomy. Venous obstruction was a rare cause of postmastectomy lymphedema. Edema patterns in arm lymphangiography were observed in the patients with lymphedema and even in some of the non-edematous upper extremities. The finding of axillary lymphangiography was correlated with the degree of edema of the upper extremity. The absence of adequate lymphatic pathway across the axilla (type 2, collateral and type 3, blocking) was thought to provide the pathologic base for the postmastectomy lymphedema. RISA absorption test also provided precise information of the lymphatic flow in the extremity. It was lower in the patients with edema, as compared with the patients without edema.

Arm↗
PubMed1975

Utilization of adenosine for nucleotide synthesis in the erythrocytes of some animals.

Erythrocytes of human, monkey, dog, rat, mouse, guinea pig, hen, or frog were incubated with [U-14C]adenosine at a concentration of 0.23 muM, a level roughly corresponding to its plasma level in mammals. Direct utilization of adenosine by phosphorylation (the kinase pathway) and indirect utilization via hypoxanthine (the hypoxanthine pathway) were analyzed from the ratio of the specific radioactivities of nucleotide and base, as described previously (1,2). Both human and monkey cells efficiently utilized adenosine only by the kinase pathway, while rodent cells used the same route with an efficiency which varied with the species. Canine cells incorporated adenosine in extremely small amounts both by the kinase pathway and via the hypoxanthine pathway with a marked predominance of the former. Frog erythrocytes were similar to dog cells in mechanism of utilization, but the efficiency was of the same level as that of the primates. In contrast to other animals tested, the avian cells utilized twice as much adenosine via the hypoxanthine pathway as by the kinase pathway.

Adenosine↗
PubMed2025

Hypermethylation at 45S rDNA promoter in cancers.

The ribosomal genes (rDNA genes) encode 47S rRNA which accounts for up to 80% of all cellular RNA. At any given time, no more than 50% of rDNA genes are actively transcribed, and the other half is silent by forming heterochromatin structures through DNA methylation. In cancer cells, upregulation of ribosome biogenesis has been recognized as a hallmark feature, thus, the reduced methylation of rDNA promoter has been thought to support conformational changes of chromatin accessibility and the subsequent increase in rDNA transcription. However, an increase in the heterochromatin state through rDNA hypermethylation can be a protective mechanism teetering on the brink of a threshold where cancer cells rarely successfully proliferate. Hence, clarifying hypo- or hypermethylation of rDNA will unravel its additional cellular functions, including organization of genome architecture and regulation of gene expression, in response to growth signaling, cellular stressors, and carcinogenesis. Using the bisulfite-based quantitative real-time methylation-specific PCR (qMSP) method after ensuring unbiased amplification and complete bisulfite conversion of the minuscule DNA amount of 1 ng, we established that the rDNA promoter was significantly hypermethylated in 107 breast, 65 lung, and 135 colon tumour tissue samples (46.81%, 51.02% and 96.60%, respectively) as compared with their corresponding adjacent normal samples (26.84%, 38.26% and 77.52%, respectively; p < 0.0001). An excessive DNA input of 1 &#x3bc;g resulted in double-stranded rDNA remaining unconverted even after bisulfite conversion, hence the dramatic drop in the single-stranded DNA that strictly required for bisulfite conversion, and leading to an underestimation of rDNA promoter methylation, in other words, a faulty hypomethylation status of the rDNA promoter. Our results are in line with the hypothesis that an increase in rDNA methylation is a natural pathway protecting rDNA repeats that are extremely sensitive to DNA damage in cancer cells.

DNA Methylation↗
PubMed1977

Hepatic emboli following inferior vena caval ligation. Brief report.

Radionuclide venography performed by foot vein injection of 99mTc MAA and 99mTc DTPA in a 34-year-old man approximately one year after inferior vena caval ligation demonstrated an unusual collateral pathway between the veins of the lower extremities and the portal vein, and also evidence for multiple hepatic emboli. This is a newly recognized sequela of inferior vena caval ligation.

Adult↗
PubMed1976

Plasticity in the developing visual system: the effects of retinal lesions made in young rats.

The central visual pathways of the rat have been used as a model for investigating the significance of axonal interactions in mammalian neural development. Attention is restricted largely to the aberrant distribution of optic axons to the ipsilateral side of the brain and their distribution in the superior colliculus after early unilateral eye damage. The normal ipsilateral retinotectal pathway in pigmented rats appears as a series of patches located anteriorly and laterally in the stratum opticum, whereas in albino animals it is a small area lying anteromedially. In both, a few axons are often found at the extreme posterior border of the superior colliculus. After unilateral eye enucleation at birth, an aberrant ipsilateral pathway from the remaining eye arises at the optic chiasm. It originates from all parts of the retina and terminates in the ipsilateral superior colliculus in a topographic fashion such that the upper retina projects laterally and the lower retina, medially. The pathway is heaviest anteromedially (from lower temporal retina) and lightest posterolaterally (from upper nasal retina). There is always a heavy projection to the extreme posterior border of the superior colliculus. In only two animals of a large series was direct intertectal sprouting found. After partial retinal lesions, there is again an ipsilateral pathway from the unlesioned eye which fills the projection area of the lesion. As after total enucleation, the pathway arises from most of the ipsilateral retina, not just that region homotypic to the lesion site, being heaviest from the lower temporal and lightest (or deficient) from the upper retina. There is suggestion of ordering of the projection into the deafferented region in that the ipsilateral degeneration after lesions in the intact eye is compact but does not fill the gap in the crossed projection completely. There is also indication that some intact parts of the retina lesioned at birth may also project in an inappropriate retinotopic fashion to the deafferented region. The corticotectal pathway shows a normal map. Study of the ipsilateral retinotectal pathway indicates that the axons terminating at the extreme posterior border of the superior colliculus arise from the lower temporal retina. The results are interpreted as indicating that the aberrant uncrossed pathways after complete or local retinal lesions, compare very closely in most features. Both distribute to the deafferented area of the superior colliculus -- in one, this is the whole surface, while in the other it is a small area. The fact that in the latter case axons are ending in quite inappropriate parts of the tectal map, may be explained more simply in terms of interactions between adjacent axons in the optic pathway rather than by an hypothesis involving a change in the cell labels across the tectal map.

Age Factors↗
PubMed1977

Vestibular and somatosensory interaction in the cat vestibular nuclei.

The vestibular nuclei of cats were explored extracellulary with micropipettes to locate units with a resting discharge rate which responded to rotation in the horizontal plane. These units were examined for somatosensory input from neck and limbs. Fewer than half responded to somatosensory stimulation. The neck region was the body area most effective in influencing unitary activity. The response pattern most often noted was an increase and decrease in discharge frequency when the body was moved towards and away from the recording electrode respectively. Change in discharge rate was observed to be primarily dependant upon neck velocity and not upon absolute neck position. Half of the somatosensory units received input from either the forelimbs or the hindlimbs, while the remaining half responded to both.

Action Potentials↗
PubMed2026

ProMeta: a meta-learning framework for robust disease diagnosis and prediction from plasma proteomics.

MOTIVATION: The plasma proteome offers a dynamic window of human health, capturing the real-time intersections between genetics and physiology. However, the application of deep learning to proteomics is currently hindered by a reliance on large-scale labeled datasets, rendering standard models ineffective for rare or novel diseases where patient samples are inherently scarce. RESULTS: Here, we present ProMeta, a meta-learning framework designed to enable robust disease modeling under extreme data restrictions. By integrating knowledge-guided pathway encoding with bi-level meta-optimization, ProMeta projects unstructured proteomic profiles into biologically interpretable functional tokens. This architecture allows the model to learn a global initialization containing transferable biological priors from biobank-scale data, facilitating rapid adaptation to novel tasks. Through comprehensive benchmark experiments, ProMeta consistently outperformed transfer learning and traditional machine learning baselines in both disease diagnosis and prediction tasks. In the most challenging 4-shot scenarios (utilizing only 2 cases and 2 controls), the model achieved robust generalization with an average AUROC of &#x223c;0.69, representing a 24.6% relative improvement over the best-performing baseline methods. Mechanistic investigation revealed that ProMeta disentangles cases from controls in the latent space prior to task-specific adaptation, confirming the acquisition of universal biological rules rather than rote memorization. Furthermore, gradient-based interpretation identified disease-specific protein biomarkers and functional pathways consistent with known pathophysiology. Collectively, ProMeta overcomes the data-scarcity bottleneck in precision medicine, providing a scalable, interpretable framework for characterizing the full spectrum of human diseases, particularly for rare conditions lacking extensive clinical cohorts. AVAILABILITY AND IMPLEMENTATION: The source code of ProMeta is available at GitHub (https://github.com/lihan97/ProMeta).

Proteomics↗