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PubMed2025

Hidden diversity in Enterococcus faecalis revealed by CRISPR2 screening: eco-evolutionary insights into a novel subspecies.

Enterococcus faecalis is a commensal bacterium that colonizes the gut of humans and animals and is a major opportunistic pathogen, known for causing multidrug-resistant healthcare-associated infections (HAIs). Its ability to thrive in diverse environments and disseminate antimicrobial resistance genes (ARGs) across ecological niches highlights the importance of understanding its ecological, evolutionary, and epidemiological dynamics. The CRISPR2 locus has been used as a valuable marker for assessing clonality and phylogenetic relationships in E. faecalis. In this study, we identified a group of E. faecalis strains lacking CRISPR2, forming a distinct, well-supported clade. We demonstrate that this clade meets the genomic criteria for classification as a novel subspecies, here referred to as "subspecies B." Through a comprehensive pangenome analysis and comparative genomics, we explored the adaptive ecological traits underlying this diversification process, identifying clade-specific features and their predicted functional roles. Our findings suggest that the frequent isolation of subspecies B from meat products and processing facilities may reflect dissemination routes involving environmental contamination (e.g., water, plants, soil) from avian species. The absence of key virulence traits required for pathogenicity in mammals, particularly humans, and the lack of clinically relevant resistance determinants indicate that subspecies B currently poses minimal threat to public health compared with the broadly disseminated "subspecies A." Nevertheless, the unclear potential for genetic exchange between these subspecies and the frequent association of subspecies B with food sources calls for continued genomic surveillance of E. faecalis from a One Health perspective to detect and mitigate the emergence of high-risk variants in advance.IMPORTANCEExploring intraspecific genetic variability in generalist bacteria with pathogenic potential, such as Enterococcus faecalis, is a key to uncovering stable evolutionary trends. By screening the CRISPR2 locus across a representative set of genomes from diverse sources, this study reveals a previously unrecognized lineage within the population structure of E. faecalis, associated with underexplored nonhuman and nonhospital reservoirs. These findings broaden our knowledge of the species' genetic landscape and shed light on its adaptive strategies and patterns of ecological dissemination. By bridging phylogenetic patterns with variation in genetic defense systems and accessory traits, the study generates testable hypotheses about the genomic determinants and corresponding selective pressures that shape the species' behavior and long-term dissemination. This work offers new perspectives on the eco-evolutionary dynamics of E. faecalis and highlights the value of genomic surveillance beyond clinical settings, in alignment with One Health principles.

Enterococcus faecalis↗
PubMed1987

Identification of chromaffin granule-binding proteins. Relationship of the chromobindins to calelectrin, synhibin, and the tyrosine kinase substrates p35 and p36.

At least 23 soluble proteins (chromobindins) bind to chromaffin granule membranes in the presence of Ca2+. In order to further the identification of the chromobindins and to determine the roles they may play in exocytosis or other aspects of chromaffin cell biology, several of these proteins were compared to other known membrane-binding proteins. Chromobindin 4 was identified as a 32-kDa protein called calelectrin or endonexin. Immunologically related proteins were detected in bovine brain and human platelets. Chromobindin 20 was identified as a 67-kDa variant of calelectrin and was found to have the activities of the synexin inhibitory protein, synhibin. Chromobindin 8 was identified as p36, a substrate for the tyrosine-specific kinase, pp60v-src. Chromobindin 8 was also demonstrated to undergo phosphorylation predominantly on alkali-sensitive sites during stimulation of the chromaffin cell with 20 microM nicotine. Chromobindin 6 was identified as p35, a substrate for the tyrosine kinase activity associated with the epidermal growth factor receptor. Chromobindin 9, which is known to be a substrate for protein kinase C (Ca2+/phospholipid-dependent enzyme), was found to be immunologically related to p35 and may be a precursor of chromobindin 6. The identification of these proteins from the chromaffin system may be useful in the characterization of similar, complex groups of membrane-binding proteins that have been observed in other systems.

Amino Acids↗
PubMed1987

[Pathomorphology of malignant skin lymphomas].

Clinico-morphologic study of 52 biopsy samples from patients with primary lymphoproliferative skin diseases was performed. Criteria of differential diagnosis of these diseases are suggested based on the differentiation degree of lymphoid cells, their belonging to T and B cell immune systems, and the character of proliferation (poly- or monoclonal). Three morphologic variants of malignant skin lymphoma have been distinguished, (lymphoplasmocytic, prolymphocytic and immunoblastic) all of them being clinically and prognostically different. The so-called "primary reticulosis" of skin is considered as a reactive proliferation of lymphoid cells, that in a number of cases transforms into a malignant lymphoma.

B-Lymphocytes↗
PubMed1996

A novel gene expressed in rat ameloblasts codes for proteins with cell binding domains.

Two variants of an mRNA sequence are identified that are expressed at high levels in rat ameloblasts during the formation of the enamel matrix. The sequences contain open reading frames for 407 and 324 amino acid residues, respectively. The encoded proteins, which we call amelins, are rich in proline, glycine, leucine, and alanine residues and contain the peptide domain DGEA, an integrin recognition sequence. The sequences coding for the C-terminal 305 amino acid residues, the 3' nontranslated part, and a microsatellite repeat at the nontranslated 5' region are identical in both mRNA variants. The remaining 5' regions contain 338 nucleotides unique to the long variant, 54 common nucleotides, and 46 nucleotides present only in the short variant. Eleven nucleotides have the potential to code for 5 amino acids of both proteins in different reading frames. The reading frame of the longer variant includes codons for a typical N-terminal signal peptide. The amelins are likely to be constituents of the enamel matrix and the only proteins that have so far been implicated in binding interactions between the ameloblast surface and its extracellular matrix.

Ameloblasts↗
PubMedDate not supplied

The medicalization of normal variants: the case of mitral valve prolapse.

Mild mitral valve prolapse, hypoglycemia, irritable colon, and premenstrual syndrome are examples of anatomico-physiologic phenomena that largely overlap with normal. Such "overlap syndromes" become labeled disease entities by the medical community through a process called medicalization. This report uses mitral valve prolapse (MVP) to exemplify the effects of medicalization on patients, physicians, and society. Ascertainment bias and insufficient controlled clinical studies have led to the description of a clinical entity replete with false associations (e.g., mitral valve prolapse syndrome) and overly pessimistic prognostication (e.g., risk of sudden death or endocarditis), leading to clinical overreaction, overtreatment, and unnecessary induction of disability. Though some physical complications may be prevented by recognizing severe MVP, there is substantial risk of iatrogenic harm by attributing complex symptoms and illness behavior to mild MVP, which is probably a normal variant. A three-dimensional analysis of illness experience is presented that may be of use in conceptualizing the clinical approach to overlap syndromes such as mild MVP. Conservative criteria for the diagnosis of significant MVP have been developed at the National Institutes of Health. Treatment of patients with mild MVP must emphasize that it is a normal variant without serious consequences. Because the risks of overmedicalization are so substantial, the impact of diagnostic labels on individual patients and society must be analyzed continually.

Adult↗
PubMed2005

Deletion of the LMNA initiator codon leading to a neurogenic variant of autosomal dominant Emery-Dreifuss muscular dystrophy.

Mutations in the LMNA gene encoding the nuclear envelope protein, lamins A and C, have been associated with at least nine distinct disorders now called laminopathies, including Emery-Dreifuss muscular dystrophy and Charcot-Marie-Tooth type 2 disease. We identified a novel mutation in the 5' region of the LMNA gene -3del15, resulting in the loss of 15 nucleotides from -3 to +12, including the translation ATG initiator codon. The mutation segregates in a previously described family with a clinical phenotype that shared features of both Emery-Dreifuss muscular dystrophy and Charcot-Marie-Tooth type 2. Thus, the mutation with this unique phenotypical expression represents the first example for a link between the neurogenic and myogenic phenotypes and extends the clinical variability of laminopathies.

Adult↗
PubMed2001

Rare variant of the intrasoleus musculocutaneous perforator: clinical considerations in raising a free peroneal osteocutaneous flap.

To improve the stability of the cutaneous portion of the vascularized free peroneal osteocutaneous flap (the so-called peroneal flap), various anatomic studies have been conducted, and a reliable notion of the course of cutaneous perforators has been provided; however, anatomic anomalies have occasionally been observed. The authors encountered a rare type of cutaneous perforator in the distal third of the lower leg. It was located under the inferior surface of the flexor hallucis longus muscle, after running in the soleus muscle parallel to the fibula, and then joined the posterior tibial artery. Since absolutely definite diagnostic methods have not been established for the course of the cutaneous perforator, surgery with the possibility of secondary anastomosis, always with a separate peroneal flap, should be a consideration.

Arteries↗
PubMedDate not supplied

[New variant of glucose-6-phosphate dehydrogenase (G-6-PD "Kaluga") from erythrocytes of a patient with chronic nonspherocytic hemolytic anemia].

Properties of a new form of glucose-6-phosphate dehydrogenase (G6PD) from erythrocytes, called "Kaluga", are described. The enzyme was isolated from erythrocytes of a patient with chronic non-spherocytic hemolytic anemia; in the blood cells 20% of the G6PD activity was maintained as compared with normal state. The partially purified enzyme was shown to be unstable in electrophoresis, it possessed a biphase type of pH-optima; Km value for NADP was decreased for glucose-6-phosphate Km value was normal. The thermostability of G6PD was normal at 46 within 1 hr.

Anemia, Hemolytic, Congenital Nonspherocytic↗
PubMed2005

New concepts for distinguishing the hidden patterns of linkage disequilibrium which underlie association between genotypes and complex phenotypes.

A disappointing feature of conventional methods for detecting association between DNA variation and a phenotype of interest is that they tell us little about the hidden pattern of linkage disequilibrium (LD) with the functional variant that is actually responsible for the association. This limitation applies to case-control studies and also to the transmission/disequilibrium test (TDT) and other family-based association methods. Here we present a fresh perspective on genetic association based on two novel concepts called 'LD squares' and 'equirisk alleles'. These describe and characterize the different patterns of gametic LD which underlie genetic association. These concepts lead to a general principle - the Equi-Risk Allele Segregation Principle - which captures the way in which underlying LD patterns affect the transmission patterns of genetic variants associated with a phenotype. This provides a basis for distinguishing the hidden LD patterns and might help to locate the functional variants responsible for the association.

Alleles↗
PubMed1992

The A1 (B) phenomenon: a monoclonal anti-B (BS-85) demonstrates low levels of B determinants on A1 red cells.

A monoclonal anti-B (BS 85) that reacts strongly with red cells from weak B variants (B3, Bint and Bv) has demonstrated the presence of a trace of B on A1 red cells. The agglutination of group A1 red cells by an anti-B antibody is called the A1 (B) phenomenon and is the converse of the B(A) phenomenon seen with certain monoclonal anti-A antibodies. Fragile A1 (B) agglutination is best seen by spin-tube techniques and A1 red cells negative in saline tests are agglutinated by albumin and protease enzyme-enhanced tests, but no reactions are seen with A2 red cells. The A1 (B) reaction is specifically inhibited by B substance, and D-galactose and the galactose-containing sugars melibiose and lactose. Red cells from B variants showed differential inhibition patterns with various sugars. A1 transferase levels were normal even in the strongest A1 (B) reactive blood samples, although the plasma H transferase levels and H status of these red cells were elevated. This is in contrast to the B(A) phenomenon which is associated with elevated levels of B transferase. It is suggested that A1(B) overlapping specificity can occur because of a combination of higher H activity (and thus more H sites) together with normal levels of A transferase activity as they are 20% higher than normal levels of B transferase. The production of anti-B reagents free of the A1 (B) phenomenon with BS-85 is achieved by suitable dilution using quality control tests with protease-treated A1 red cells.(ABSTRACT TRUNCATED AT 250 WORDS)

ABO Blood-Group System↗
PubMed2003

Review of chromophobe renal cell carcinoma with focus on clinical and pathobiological aspects.

In recent years, the concept of chromophobe renal cell carcinoma (RCC) has been established. Chromophobe RCCs account for about 4-6% of all renal tumors. Macroscopically, the cut surface of the tumor is generally grey-beige in color. Histologically, there are two variants (typical and eosinophilic). In the typical variant, large tumor cells with architecture of a compact tubulo-cystic pattern proliferate. The cytoplasm is abundant and shows a fine reticular translucent pattern. The cell border is thick, prominent and eosinophilic. In the eosinophilic variant, tumor cells are smaller and markedly eosinophilic, and a perinuclear halo is often seen. Histochemically, the tumor cells generally show a diffuse and strong reaction for Hale's colloidal iron staining. Ultrastructurally, tumor cells contain many cytoplasmic microvesicles (150-300 nm). In chromosomal analysis, a low chromosome number is characteristic of chromophobe RCCs, due to the frequent occurrence of a combined loss of chromosomes 1, 2, 6, 10, 13, 17, and 21. In differential diagnosis, histological distinction from oncocytomas, which share a common phenotype (intercalated cells of the collecting duct system), is most important. In this diagnostic setting, recent studies have given rise to several problems. Firstly, some cases of coexistent chromophobe RCC and oncocytoma (so-called renal oncocytosis) or cases of oncocytoma with metastasis have recently been reported. Secondly, the existence of chromophobe adenoma, which is the benign counterpart of chromophobe RCC, and an oncocytic variant of chromophobe RCC has recently been suggested. Therefore, further studies are needed to elucidate the relationship between chromophobe RCCs and oncocytomas, to confirm whether chromophobe adenoma actually exists or not, and to identify the key gene that causes chromophobe RCCs.

Carcinoma, Renal Cell↗
PubMed1999

Role of fibroblasts in HGF/SF-induced cohort migration of human colorectal carcinoma cells: fibroblasts stimulate migration associated with increased fibronectin production via upregulated TGF-beta1.

Carcinoma cells frequently invade the surrounding tissue as coherent clusters or nests of cells. We have called this type of movement "cohort migration." We have previously presented an in vitro two-dimensional cohort migration model, in which highly metastatic variant L-10 cells of human rectal adenocarcinoma cell line RCM-1 moved as coherent cell sheets when stimulated with 12-O-tetradecanoylphorbol-13-acetate (TPA) or hepatocyte growth factor/scatter factor (HGF/SF). Pericellular deposition of EDA-containing fibronectin (EDA+FN) was essential for TPA-induced cohort migration. In this study, we investigated how colon-derived fibroblasts could affect the induction of cohort migration of colorectal carcinoma cells by HGF/SF, since carcinoma cell-fibroblast interactions frequently regulate biological events during cancer cell invasion. Fibroblasts co-cultured with L-10 carcinoma cells stimulated HGF/SF-induced cohort migration of L-10 cells up to 2 to 3-fold. Conditioned medium (CM) from fibroblasts that were cultured alone was not effective but CM from fibroblasts cocultured with carcinoma cells enhanced HGF/SF-induced cohort migration, and this effect in CM was found to be mediated by TGF-beta1 upregulated in co-cultured conditions. Among the motogenic growth factors examined, only TGF-beta1 synergistically stimulated HGF/SF-induced L-10 cell cohort migration, although TGF-beta1 alone did not induce cohort migration. TGF-beta1 also exhibited synergistic effect in several other human colorectal carcinoma cell lines. The synergistic stimulation of L-10 cell cohort migration by HGF/SF and TGF-beta1 was associated with increased production of motility-enhancing EDA+FN by L-10 cells, and blocking FN with a specific antibody effectively inhibited the synergistic effect.

Adenocarcinoma↗
PubMed2000

Analysis of the human KCNH2(HERG) gene: identification and characterization of a novel mutation Y667X associated with long QT syndrome and a non-pathological 9 bp insertion.

Long QT (LQT) syndrome is a potentially life-threatening disorder, characterized by a distinct cardiac arrhythmia known as torsades de pointes. Mutations within a number of genes linked to the familial form, including that coding for a cardiac potassium channel called KCNH2 (HERG), have been described based on the characterized genomic organization. A standardized method was developed to screen the entire gene for gene variants. We report a single base pair substitution, introducing a premature STOP codon at codon 667 of the gene in a healthy individual with an extended QTc interval (460 msec). In vitro expression of the codon Y667X variant in Xenopus oocyte suggests that the autosomal dominant variant does not function in a dominant/negative manner and cannot co-assemble to form a channel, resulting in a reduction of the KCNH2 current, and an extension of the QT interval. This indicates that pathogenic LQT gene variants exist in the apparently normal population, the prognosis and clinical consequences of which remain to be determined. The assays described should facilitate future studies into this area.

Animals↗
PubMed2003

Carotid stenting in the bovine arch.

We report our experience in stent-supported angioplasty of the left internal carotid artery in patients with anomalous origin of the left common carotid, the so-called bovine arch, in which the right brachiocephalic and left carotid share a common trunk from the aortic arch. The occurrence of the anatomic variant is discussed, and techniques of femoral, brachial, and radial approaches are described.

Aged↗
PubMed1982

Avian and primate communication: the problem of natural categories.

To negotiate effectively with the world on the basis of experience, organisms must classify past events with rules about when to lump stimulus variants into perceptual categories and when to treat them separately. In nature, tactics for evading capture vary with the predator. Appropriately, adult monkey alarm calls are specifically linked to predator category. Linkages are less precise in one-month infants but they discriminate between major predator categories. Associations become more highly specified with experience. Birds discriminate innately between conspecific and alien songs, but vocal perception is subsequently enriched by experience. Monkeys also use special processing in categorizing their own vocal repertoire. In forming perceptual categories birds and monkeys evidently use species-specific predispositions that focus attention on biologically relevant stimuli and ensure commonality in rules used by species members in perceptual analysis. Thus animals are led to share natural perceptual categories to which meaningful communicative labels can be attached.

Animal Communication↗
PubMed2004

Partitioning of TSE infectivity during ethanol fractionation of human plasma.

The practice of validating processes for their capacity to inactivate a range of non-enveloped and enveloped viruses also provides confidence that plasma products will be safe from emerging viral pathogens with known aetiology. Of greater concern are diseases of unknown or poorly defined aetiology such as the group of neurological diseases collectively called the transmissible spongiform encephalopathies (TSEs), or prion diseases, for which the best known human disease is Creutzfeldt-Jakob Disease (CJD) and its variant form (vCJD). The goal of the current study was to investigate the potential for manufacturing steps used in the production of albumin and immunoglobulin products by Kistler-Nitschmann fractionation, and the utility of nanofiltration of immunoglobulin to remove TSE agents. Two different scrapie model systems were used. In the first system infectious material used for spiking was scrapie sheep brain homogenate with infectivity titres being measured in hamsters. In the second system purified scrapie agent was used (PrP fibrils) with Western blot analysis measuring reduction in the proteinase K resistant form being used as a measure of removal. The data demonstrated substantial removal of the infectious agent by the manufacturing process in both model systems although some differences were observed in partitioning of the two different infectious materials. The hamster infectivity studies were shown to be approximately 1000 fold more sensitive than the Western Blot assay. The data from both studies provide added confidence that these plasma products are safe with respect to their potential to transmit TSE.

Animals↗
PubMed2003

Vocal similarities and social bonds in Campbell's monkey (Cercopithecus campbelli).

This study examined variations of social call structures in female Campbell's monkeys. The comparison of frequency modulations using a similarity index revealed that each individual presented one to three variants. Some variants were shared by two to several individuals, often associated with play. On the contrary, vocal divergence was observed in a socially isolated animal and a negative correlation appeared between similarity index and the frequency of avoidance. This preliminary study gives the first evidence of variant sharing between group members in primates.

Animals↗