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PubMed2000

Information content of protein sequences.

The complexity of large sets of non-redundant protein sequences is measured. This is done by estimating the Shannon entropy as well as applying compression algorithms to estimate the algorithmic complexity. The estimators are also applied to randomly generated surrogates of the protein data. Our results show that proteins are fairly close to random sequences. The entropy reduction due to correlations is only about 1%. However, precise estimations of the entropy of the source are not possible due to finite sample effects. Compression algorithms also indicate that the redundancy is in the order of 1%. These results confirm the idea that protein sequences can be regarded as slightly edited random strings. We discuss secondary structure and low-complexity regions as causes of the redundancy observed. The findings are related to numerical and biochemical experiments with random polypeptides.

Algorithms↗
PubMed2026

Beyond Earth: Recent Advancements in Microgravity Biomedical and Genetic Research in Saudi Arabia.

Microgravity research has emerged as a rapidly evolving field at the intersection of space medicine, genomics, biotechnology, and precision medicine. Exposure to the space environment induces complex physiological and molecular adaptations that affect multiple biological systems, including immune regulation, metabolism, musculoskeletal function, and gene expression. Recent advances in genomics, multi-omics technologies, artificial intelligence, and bioengineering have substantially improved our understanding of biological adaptation to spaceflight and expanded opportunities for translational biomedical research. This review summarizes recent advances in genetic and biomedical research under microgravity conditions, with particular emphasis on molecular mechanisms, omics technologies, genome editing, microbiome research, regenerative medicine, and personalized healthcare approaches. Major experimental platforms, landmark spaceflight studies, and translational applications in infectious diseases, cancer biology, aging, tissue engineering, and pharmaceutical development are discussed. The review also highlights Saudi Arabia's emerging contributions to genomic medicine and space biosciences through initiatives such as the Saudi Human Genome Program, the Saudi Pangenome Project, the Saudi Space Agency, and the BioGravity Initiative. Recent Saudi participation in human spaceflight and microgravity-associated biomedical research is discussed within the context of Vision 2030 and national investments in biotechnology and precision medicine. Collectively, advances in microgravity research are expected to contribute to the advancement of precision medicine and facilitate the development of innovative diagnostic and therapeutic strategies with significant implications for both human space exploration and terrestrial healthcare.

Humans↗
PubMed2026

Single-cell profiling of mitochondrial phenotyping-coupled mtDNA genotyping.

Simultaneously profiling mitochondrial DNA (mtDNA) heteroplasmy and phenotypic variability at the single-cell level remains a challenge due to the absence of integrated methods that map mitochondrial genotypes alongside their functional states. We introduce human single-cell mitochondrial phenotype-coupled mtDNA sequencing (scMPCDS), a platform that quantifies mtDNA mutations and heteroplasmy together with mitochondrial membrane potential and reactive oxygen species within individual cells. Unlike bulk sequencing or separate single-omics techniques, scMPCDS directly correlates mitochondrial genomic instability with functional outcomes. Using this approach, we demonstrate that DdCBE-mediated mtDNA editing induces cell-specific off-target mutations in the mitochondrial genome, which coincide with diverse phenotypic changes. Applying scMPCDS to HeLa cells and clear cell renal cell carcinoma tissues, we identify single-cell subpopulations exhibiting distinct mtDNA mutation burdens and altered bioenergetic profiles, implicating potential mitochondrial heterogeneity-driven tumor evolution. Overall, scMPCDS serves as a versatile tool to unravel mitochondrial genotype-phenotype relationships at the single-cell level in both normal and disease states, thereby advancing precise mitochondrial diagnostics and therapeutics.

Humans↗
PubMed1986

Mutational specificity of a proof-reading defective Escherichia coli dnaQ49 mutator.

The dnaQ (mutD) gene product which encodes the epsilon-subunit of the DNA polymerase III holoenzyme has a central role in controlling the fidelity of DNA replication because both mutD5 and dnaQ49 mutations severely decrease the 3'-5' exonucleolytic editing capacity. It is shown in this paper that more than 95% of all dnaQ49-induced base pair substitutions are transversions of the types G:C-T:A and A:T-T:A. Not only is this unusual mutational specificity precisely that observed recently for a number of potent carcinogens such as benzo(a) pyrene diolepoxide (BPDE) and aflatoxin B1 (AFB1), which are dependent on the SOS system to mutagenize bacteria, but it is also seen for the constitutively expressed SOS mutator activity in E. coli tif-1 strains as well as for the SOS mutator activity mediated gap filling of apurinic sites. Because the G:C-T:A and A:T-T:A transversions can either result from the insertion of an adenine across from apurinic sites or arise due to the incorporation of syn-adenine opposite a purine base, we postulate that the DNA polymerase III holoenzyme also has a reduced discrimination ability in a dnaQ49 background. The introduction of a lexA (Ind-) allele, which prevents the expression of SOS functions, led to a significant reduction in the dnaQ49-caused mutator effect. Both, the mutational specificity observed and the partial lexA+ dependence of the mutator effect provoke a reanalysis of the hypothesis that the DNA polymerase III holoenzyme can be converted into the postulated but until now unidentified SOS polymerase.

Anticodon↗
PubMed2001

Determination of measurement uncertainty for the determination of triazines in groundwater from validation data.

Laboratories are increasingly urged to submit full uncertainties of their analytical results rather than only standard deviations. The determination of measurement uncertainties in compliance with the Guide to the Expression of Uncertainty in Measurement (GUM) is demonstrated using the validation approach explicitly endorsed by the recent edition of the EURACHEM guide for the determination of measurement uncertainty. Measurement uncertainty was split into uncertainty of the sample mass, uncertainty of the concentration of the stock standard solution, uncertainty of the calibration and uncertainty connected to within- and between-series precision. Uncertainties of sample mass and of the concentration of the stock standard solution were 0.26 and 1.14% for all analytes, which is negligible compared with the contributions of precision and calibration. Uncertainty of calibration was estimated from the calibration graph. Relative uncertainty of calibration was found to be strongly concentration dependent and to be the main uncertainty contribution below 0.2 microgram L-1. Precision was split into within-series and between-series standard deviation, which dominate the combined standard uncertainty at higher concentrations. The results obtained from these calculations are compared with results for a certified reference material and with the performance in an interlaboratory comparison. It was found that all results agreed within their uncertainty with the target values, showing that the estimated uncertainties are realistic.

Journal Article↗
PubMed2005

Aberrant IgM signaling promotes survival of transitional T1 B cells and prevents tolerance induction in lupus-prone New Zealand black mice.

New Zealand Black (NZB) mice develop a lupus-like syndrome. Although the precise immune defects leading to autoantibody production in these mice have not been characterized, they possess a number of immunologic abnormalities suggesting that B cell tolerance may be defective. In the bone marrow, immature self-reactive B cells that have failed to edit their receptors undergo apoptosis as a consequence of Ig receptor engagement. Splenic transitional T1 B cells are recent bone marrow emigrants that retain these signaling properties, ensuring that B cells recognizing self-Ags expressed only in the periphery are deleted from the naive B cell repertoire. In this study we report that this mechanism of tolerance is defective in NZB mice. We show that NZB T1 B cells are resistant to apoptosis after IgM cross-linking in vitro. Although extensive IgM cross-linking usually leads to deletion of T1 B cells, in NZB T1 B cells we found that it prevents mitochondrial membrane damage, inhibits activation of caspase-3, and promotes cell survival. Increased survival of NZB T1 B cells was associated with aberrant up-regulation of Bcl-2 after Ig receptor engagement. We also show that there is a markedly increased proportion of NZB T1 B cells that express elevated levels of Bcl-2 in vivo and provide evidence that up-regulation of Bcl-2 follows encounter with self-Ag in vivo. Thus, we propose that aberrant cell signaling in NZB T1 B cells leads to the survival of autoreactive B cells, which predisposes NZB mice to the development of autoimmunity.

Animals↗
PubMed1998

A brief history of printing of lithographic medical books in modern times.

A large number of lithographic medical books came out within about 100 years after the introduction of lithography technique from the west. There are about 1000 extant lithographic medical books among which 500 still extant as lithographic edition in our country. The development of lithographic medical book could be divided into three stages: the embryonic stage, the prosperous stage and the devlined stage. In spite of the shortcomings that the printing was not exquisite and the textual proofreading was not precise, the value of these lithographic medical books could not be underrated in preserving the medical documents, spreading the medical knowledge and promoting the confluence of TCM and western medicine.

China↗
PubMed2006

Simple pulse-acquire NMR methods for the quantitative analysis of calcium, magnesium and sodium in human serum.

Simple pulse-acquire NMR methods are presented for accurate quantitation of calcium (Ca(2+)), magnesium (Mg(2+)) and sodium (Na(+)) in human serum. Ca(2+) and Mg(2+) can be determined simultaneously by (1)H NMR via their EDTA (ethylenediaminetetraacetic acid) complexes. Spectra are acquired before and after addition of EDTA, and the difference spectrum is used for integration of the signals from the complexes relative to an internal reference. Serum sodium can also be determined through pulse-acquire (23)Na NMR by integration of the free sodium signal relative to a reference signal (Na(+)+EDTA in a coaxial capillary tube). The method shows excellent accuracy and precision for all three metal ions. Slow chemical exchange between complexed and free EDTA at the natural pH of serum does not limit the accuracy of the determination of Ca(2+) and Mg(2+), and the large errors associated with spin-echo spectral editing methods are avoided.

Calcium↗
PubMed2002

[Acceptance of van Swieten's liquor in Japan].

Carl Peter Thunberg, a Swedish medical doctor and botanist who visited Japan in 1775 as a medical doctor attached to the Dutch Trade House in Dejima, Nagasaki, taught the treatment of syphilis using mercury water to Japanese doctors and interpreters. This therapy is based on the oral administration of a 0.014% solution of mercuric chloride and was published in 1754 by Gerard van Swieten in Vienna, who questioned the utility of the conventional salivation therapy. The dose was set taking safety into account. Kogyu Yoshio, a Japanese-Dutch interpreter, had already read about it in a book written by J. J. Plenck, when he was taught about the therapy by Thunberg. He recorded Thunberg's teachings in his book "Komohijiki", presenting details of various formulations, including a high-dose formulation. The mercury therapy was subsequently spread across the country by medical doctors who learned Western medicine through the Dutch. In the 1820's, Genshin Udagawa, who read a number of Western medical books, published books on Western drugs. In these books, G. Udagawa included precise information on "Swieten Yakushu-hu (medicated alcohol)", including information on the dosage, formulation, mode of usage, and precautions for use. The maximum dose of mercuric chloride established chloride established by van Swieten was included in the Japanese Pharmacopoeia up to its 5th edition.

Alcohols↗
PubMed2026

Spacer-engineered donor DNA enhances CRISPR-Cas9-mediated knockin to establish a chemical knockdown platform for endogenous proteins.

Precise installation of functional protein domains at endogenous loci is a powerful approach for interrogating protein functions, but its broad application is limited by the low efficiency of homology-directed repair (HDR)-mediated knockin during Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9 gene editing. Here, we investigated a simple donor DNA engineering strategy that enhances HDR-mediated gene knockin by appending additional gRNA-recognizable spacer sequences to donor templates. Systematic analysis of linear dsDNA and plasmid donors showed that spacer position, length, and orientation influenced HDR efficiency, and that spacer-containing donors improved knockin across multiple genomic loci, insertion sizes, cell types and delivery modalities. Mechanistic analyses revealed that spacer-containing donors formed stable complexes with Cas9/gRNA and showed increased nuclear localization, supporting nuclear delivery as a key contributor to improved editing outcomes. We then applied this gene-editing strategy to establish a chemical knockdown platform by installing drug-responsive degrons at endogenous loci, generating cell lines in which GSK3β or Lin28A protein could be rapidly, potently and reversibly depleted by drug treatment. These platforms enable selective modulation of endogenous proteins and reveal cellular responses that may differ from those obtained using conventional genetic perturbation. Together, this work establishes a readily implementable framework that integrates improved gene editing with on-demand chemical knockdown of endogenous proteins.

CRISPR-Cas9↗
PubMed2006

Structural and optical properties of highly hydroxylated fullerenes: stability of molecular domains on the C60 surface.

The excitation spectra and the structural properties of highly hydroxylated C(60)(OH)(x) fullerenes (so-called fullerenols) are analyzed by comparing optical absorption experiments on dilute fullerenol-water solutions with semiempirical and density functional theory electronic structure calculations. The optical spectrum of fullerenol molecules with 24-28 OH attached to the carbon surface is characterized by the existence of broad bands with reduced intensities near the ultraviolet region (below approximately 500 nm) together with a complete absence of optical transitions in the visible part of the spectra, contrasting with the intense absorption observed in C(60) solutions. Our theoretical calculations of the absorption spectra, performed within the framework of the semiempirical Zerner intermediate neglect of diatomic differential overlap method [Reviews in Computational Chemistry II, edited by K. B. Lipkowitz and D. B. Boyd (VCH, Weinheim, 1991), Chap. 8, pp. 313-316] for various gas-phase-like C(60)(OH)(26) isomers, reveal that the excitation spectra of fullerenol molecules strongly depend on the degree of surface functionalization, the precise distribution of the OH groups on the carbon structure, and the presence of impurities in the samples. Interestingly, we have surprisingly found that low energy atomic configurations are obtained when the OH groups segregate on the C(60) surface forming molecular domains of different sizes. This patchy behavior for the hydroxyl molecules on the carbon surface leads in general to the formation of fullerene compounds with closed electronic shells, large highest occupied molecular orbital-lowest unoccupied molecular orbital energy gaps, and existence of an excitation spectrum that accounts for the main qualitative features observed in the experimental data.

Journal Article↗
PubMed2002

Indexing of Internet resources in order to improve the provision of problem-relevant medical information.

Due to the information overload and the unstructured access to (medical) information of the internet, it isn't hardly possible to find problem-relevant medical information in an appropriate time (e.g. during a consultation). The web offers a mixture of web pages, forums, newsgroups and databases. The search for problem-relevant information for a certain knowledge area encounters on two basic problems. On the one hand, you have to find in the jungle of the information, relevant resources for your individual clinical case (treatment, diagnosis, therapeutic option etc..). The second problem consists of being able to judge the quality of individual contents of inteernet pages. On the basis of the different informational needs of health care professionals and patients a catalog with inteernet resources was created to tumor diseases such as lung cancer (small cell and non-small cell carcinoma), colorectal cancer and thyroid cancer. Explicit and implicit metainformation, if available, such as the title of the document, language, date or keywords are stored in the database. The database entries are editorially revised, so that further specific metainformation is available for the information retrieval. Our pragmatic approach of searching, editing, and archiving of internet content is still necessary since most of the web documents are based on HTML, which doesn't allow for structuring (medical) information and assigning metainformation sufficiently. The use of specific metainformation is crucial in order to improve the recall and precision of internet searches. In the future, XML and related technologies (RDF) will meet these requirements.

Abstracting and Indexing↗
PubMed1998

Stage classifications of pancreatic cancer: comparison of the Japanese and UICC classifications and proposal for a new staging system. Union Internationale Contre le Cancer.

In the 4th edition of General Rules for the Study of Pancreatic Cancer by the Japan Pancreas Society (JPS), published in 1993 (English version published in 1996), a system resembling the TNM classification by the Union Internationale Contre le Cancer (UICC) was adopted, based on the results of precise analysis of data from 11,317 cases of carcinoma of the pancreas registered by the JPS during the 10-year period from 1981 to 1990. We compare the two TNM classifications and staging groups, focusing on the simplicity and reproducibility of the diagnostic criteria and the reliability of predicting outcome. To compare the prognostic value of the two classification systems, we analyzed the published data on resected cases registered by Pancreatic Cancer Registration Committee of the JPS. The results showed that a major drawback of the JPS classification is that is difficult to apply and has poor reproducibility. Survival rates differed significantly among the four stages in the JPS classification, whereas the UICC staging system did not reflect differences in outcome among the four stages, especially between stages II and III. The prognostic value of the UICC T category is better than that of the JPS T category, whereas the N category of JPS has better prognostic value than that of the UICC system. Believing that a combination of the two systems would solve this problem, we propose a new TNM classification and stage-grouping system that draws on the merits of both. This new system may provide improvements in staging classification that will lead to the establishment of a more practical and universal staging system for ductal carcinoma of the pancreas.

Humans↗
PubMed1997

[Coding for clinical laboratory information].

The field of clinical laboratory tests is facing an increase in the number of test items as well as a corresponding diversification due to the demands of medical institutions as well as improvements in analytical techniques. To respond to this situation, medical institutions have been promoting systematization of their testing procedures; information exchange among the institutions has likewise expanded with the use of media such as on-line systems and internet. Standardization of interfaces has been proposed to secure a common framework compatible with different types of information. Some embodiments in this country includes; (1) Interface Standards on Clinical Laboratory Information For information exchange, the format and reporting comments used in the media systems were standardized under the sponsorship of The Medical Information System Development Center, with a publication issued on 1993. (2) Standardization of Laboratory Test Code Standardization of codes for information exchange has been established under the sponsorship of The Japan Society of Clinical Pathology (Laboratory Test Coding Committee), through the systematization of laboratory test code used in media systems. A publication entitled "Classification & Coding for Clinical Laboratory Tests (8th edition in 1992, 9th edition in 1994 and supplement in 1996)" has been issued. The system for "Classification & Coding for Clinical Laboratory Tests" is divided into 5 components; (1) analyte code, (2) identification code, (3) specimen code, (4) methodology code, and (5) data classification code. The Laboratory test codes are precisely classified by "(1) analyte code", and then are identified by combination of additional codes such as specimen and methodology codes. In this year, we are making a new easily-used-codes composed of 5 Arabic figures.

Clinical Laboratory Information Systems↗
PubMed2026

Tobamoviruses: Advances in Molecular Biology, Host Interactions and Integrated Disease Management.

Tobamoviruses (viruses in the genus Tobamovirus, family Virgaviridae) lead to major yield losses in economically important crops around the world. In this review, we go beyond the canonical gene expression framework by integrating recent discoveries of reverse open reading frames (rORFs) on the negative-strand RNA. These rORFs have only been experimentally validated in cucumber green mottle mosaic virus (CGMMV), with predicted sequence-conserved homologs across a subset of the genus, including TMV, ToBRFV, and PMMoV. However, they are not universally present in all tobamoviruses. We systematically dissect the infection cycle-from disassembly and replication to cell-to-cell and systemic movement-with an emphasis on the host factors hijacked at each stage. We synthesize current understanding of plant antiviral immunity, focusing on RNA silencing and NLR receptor-mediated resistance as two pillars of defense, along with the transcription factors and microRNAs that orchestrate these responses. We critically evaluate the experimental evidence for both plant defenses and viral counter-strategies, noting that many mechanistic models derive from limited model systems. We further characterize host genetic resistance and susceptibility factors applicable to crop breeding. These resources include dominant NLR and non-NLR resistance, as well as recessive resistance derived from modified host susceptibility genes. We address how viral mutations, recombination and fitness trade-offs undermine resistance durability. We then evaluate their practical deployment through conventional breeding, the exploitation of quantitative resistance, and genome editing, and outline associated agronomic drawbacks and regulatory constraints. Using ToBRFV as a case study, we analyze its epidemiological traits and assess the current arsenal of surveillance tools, from field diagnostics to remote sensing. Finally, we survey management strategies across a spectrum of maturity. Some approaches, including sanitation protocols and conventionally bred resistant cultivars, have proven effective under field conditions. The first dsRNA-based biopesticide has recently been registered in China, while other biological control agents and low-risk chemical approaches remain largely at the experimental stage. We also discuss the bottlenecks that impede lab-to-field transition and highlight promising solutions such as precision breeding and evolution-oriented cultivar deployment. By bridging molecular virology, epidemiology, and integrated disease management, this review provides a critical, bench-to-field framework for the sustainable control of tobamoviruses.

TMV↗
PubMed2026

Uncovering phenotypic expansion in AXIN2-related disorders through precision animal modeling.

PURPOSE: Heterozygous pathogenic variants in AXIN2 (HGNC: 904) cause oligodontia-colorectal cancer syndrome. We identified 5 individuals with de novo heterozygous variants [NM_004655.4:c.196G>A p.(Glu66Lys), c.197A>G p.(Glu66Gly), and c.199G>A p.(Gly67Arg)] in AXIN2. Common phenotypes among these individuals included ectodermal dysplasia, global developmental delay, microcephaly, and limb, ophthalmologic, and genitourinary abnormalities. METHODS: Structural modeling was performed to predict the impact of these variants on AXIN2. A prime editing N1 screen of mouse embryos was performed to test whether the p.Glu66Lys variant produces a phenotype. Drosophila models were used to test the effect of this variant on Wnt signaling. RESULTS: Structural modeling suggests that these variants disrupt AXIN2 binding to tankyrase, which regulates AXIN2 levels through poly-ADP-ribosylation. Heterozygous (p.Glu66Lys) mouse embryos were perinatally lethal with soft palate clefts and skeletal abnormalities. Modeling of the p.Glu66Lys variant in the Drosophila wing suggests gain-of-function or dominant-negative activity compared to reference AXIN2. CONCLUSION: Specific variants in the tankyrase-binding domain of AXIN2 are pathogenic, leading to phenotypic expansion with potential context-dependent effects on AXIN2 function and Wnt signaling. The N1 modeling strategy used to demonstrate variant pathogenicity may be beneficial for resolving other heterozygous variants associated with congenital anomalies.

AXIN2↗
PubMed1993

Rule based artificial intelligence expert system for determination of upper extremity impairment rating.

Quantitative evaluation of upper extremity impairment, a percentage rating most often determined using a rule based procedure, has been implemented on a personal computer using an artificial intelligence, rule-based expert system (AI system). In this study, the rules given in Chapter 3 of the AMA Guides to the Evaluation of Permanent Impairment (Third Edition) were used to develop such an AI system for the Apple Macintosh. The program applies the rules from the Guides in a consistent and systematic fashion. It is faster and less error-prone than the manual method, and the results have a higher degree of precision, since intermediate values are not truncated.

Arm Injuries↗
PubMed2021

Functional impact of cancer-associated cohesin variants on gene expression and cellular identity.

Cohesin is a ring-shaped protein complex that controls dynamic chromosome structure. Cohesin activity is important for a variety of biological processes, including formation of DNA loops that regulate gene expression. The precise mechanisms by which cohesin shapes local chromosome structure and gene expression are not fully understood. Recurrent mutations in cohesin complex members have been reported in various cancers, though it is not clear whether many cohesin sequence variants have phenotypes and contribute to disease. Here, we utilized CRISPR/Cas9 genome editing to introduce a variety of cohesin sequence variants into murine embryonic stem cells and investigate their molecular and cellular consequences. Some of the cohesin variants tested caused changes to transcription, including altered expression of gene encoding lineage-specifying developmental regulators. Altered gene expression was also observed at insulated neighborhoods, where cohesin-mediated DNA loops constrain potential interactions between genes and enhancers. Furthermore, some cohesin variants altered the proliferation rate and differentiation potential of murine embryonic stem cells. This study provides a functional comparison of cohesin variants found in cancer within an isogenic system, revealing the relative roles of various cohesin perturbations on gene expression and maintenance of cellular identity.

Animals↗