Amino acid sequence of Aphanothece sacrum Ferredoxin II (minor component). Structural characteristics and evolutionary implications.
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The definition of chronic depression necessarily calls for a review of the concept of recovery which in psychopathology is not clearly and univocally defined. The percentage of chronic evolution among depressive patients either as a persistence of depressive symptoms or as an impairment of social and professional role, ranges from 12 to 15%. Chronic depression raises psychopathologic and nosographic problems as well as clinical ones. In fact chronic depressives are often not correctly diagnosed, inadequately treated and destined to be affected by an over increasing inability. The chronic evolution of depression may result as a concurrence of several factors: a neurotic personality, an inadequate antidepressant maintenance treatment, an inappropriated use of minor tranquillizers as the only treatment. The occurrence of physical impairement, the continuous nature of depression and the resistance of antidepressant treatment may be also considered. Moreover the psychodynamic mechanisms aroused by the depressive experience and the secondary advantages of the illness may plan an effective role maintaining depressive symptomatology.
Lineage switch (LS), defined as a change in leukemic lineage during the disease course, is a rare but clinically significant event in acute leukemia and is typically associated with poor prognosis. Although LS has been increasingly reported following targeted immunotherapies, the clonal mechanisms underlying this phenomenon remain incompletely understood, particularly in cases without KMT2A rearrangement. We report a case of LS from B-precursor acute lymphoblastic leukemia (BCP-ALL) to acute myeloid leukemia (AML) following treatment with the CD22-targeted antibody-drug conjugate inotuzumab ozogamicin. To elucidate the clonal architecture underlying LS, targeted next-generation sequencing was performed on bone marrow samples obtained at multiple time points throughout the disease course. Genomic analysis demonstrated that the lymphoid and myeloid disease phases shared ancestral genetic alterations but displayed distinct mutational profiles. At the time of LS, TP53 and SMC1A mutations newly emerged, whereas only a subset of mutations detected at ALL relapse was retained. These findings suggest that the AML phase most likely resulted from the selective expansion of a genetically distinct subclone derived from a common progenitor, rather than the direct transdifferentiation of the dominant ALL clone, consistent with immunotherapy-driven clonal selection. Longitudinal genomic profiling revealed stepwise clonal evolution during disease progression, supporting a model of immunotherapy-driven clonal selection leading to LS. This case provides molecular evidence suggesting that immune-targeted therapy can promote expansion of minor pre-existing subclones with alternative lineage potential within a common progenitor even in non-KMT2A-rearranged leukemia. Our findings highlight the importance of comprehensive genomic monitoring during immunotherapy to identify therapy-resistant subclones and better understand mechanisms of lineage plasticity in acute leukemia.
From October 1st 1970 to October 1st 1975, electrical and clinical post-operative observation of 1.700 operations under E.C.C. allowed record of E.E.G. and thus study incidents depending of cerebral embolism during their formation. 18 cases have been seen during E.C.C. and 2 at the stop of E.C.C. In 9 cases, it was an air embolus, in 4 others an atheromatous embolus. In the 7 remaining cases, origin of the embolus is uncertain, but probably gaseous. Semiology of the accident is first only E.E.G. In 10 cases, signs were minor, and moderate in 10 others, preceding a late but hard clinical symptomatology, frequently characterized by a delayed advent of epilepsy crisis. Later on, an annoying evolution of the accident was seen in 4 cases (1 death, 3 lasting neurologic deficiency). For the treatment, many observations confirm the highly beneficient part of early hyperbaric oxygen.
The form of the bacteriophage T4 prehead is described by its icosahedral symmetry, its diameter, and its length. We show how each of these parameters is regulated during prehead formation and ascribe specific form-determining functions to the prehead proteins. The major protein of the head shell can assemble in several different forms. The structure produced in vivo depends on the rate of synthesis of the major protein relative to the rates of synthesis of minor shell proteins and the major core protein. From our observations, we propose a model for form determination of the prehead and suggest a pathway for the evolution of its prolate shape.
Studying one hundred cases of simple gonarthrosis we found only one supra trochlear femoral erosion (STFE). Such a lesion was discovered in 14 cases among 150 chondrocalcinosis with arthrosic lesions. The cases involving STFE trend to a commun marked chondro-osteolytic evolution. The caracteristic patella sizes show clearly that STFE is not in relation with en anomaly of patella (patella alta...). The upper osteophyte of the patella presents only a minor importance in the formation of STFE. This STFE formation begins probably with a progressive chondro-osteolysis of patella and trochlea. Then, appears a progressive nipping between the upper point of patella and the supra trochlear femoral bone.
If the social pressure exerted against a minority is overwhelming (slavery, concentration camps) no cultural efforts of the slaves or prisoners can be expected. Absence of any pressure is not conducive to high achievements either. A moderate degree of social pressure especially when combined with a possibility of social acceptance will stimulate minority people to perform well and to try to achieve status and acceptance. The cultural climate in which persons belonging to the minority grew up often determines their choice of endeavor in which to prove themselves and to achieve. Arthur Toynbee's thesis of the importance of Challenge and Response for the evolution of civilisations and Hans Selye's concept of Stress in biology are related to the proposed hypothesis. The author shows the usefulness of his hypothesis on examples from the history of Blacks in America and of the Jews.
This paper examines the possibility that the linkage arrangements and regulatory properties of genes may be influenced by selection. A mathematical hypothesis is developed in order to show how selective properties of hemoglobin beta chains could have influenced the linkage and regulation of their structural genes. The hypothesis is applied to the case of mouse hemoglobin beta chains. In most mice, closely-linked pairs of loci (doublets) code for two structurally divergent beta chains in unequal amounts. Some mouse strains have singlet alleles, however, coding for another beta chain variant. With the mathematical hypothesis, one can show that selectively determined "evolutionary potentials" may have favored changes in proportions of major and minor chains produced by a doublet allele. In the extreme case, zero production of the minor chain may give a selective advantage, leading to a singlet; conversely, selection may favor linking another gene to the singlet locus to give a doublet. A specific prediction of the model is the stable maintenance under certain conditions of multiple alleles at regulatory loci. The concept of evolutionary potential thus suggests that selection could have influenced the evolution of genotypic fitnesses, in addition to causing changes in gene frequencies as in standard population genetics models
The lacrimals glands may be the focus of the pleomorphic tumours with the same property as the major and minor salivary glands. Their localisation causes different clinical and therapeutic consequences. The cylindromes or Adenoid Cystic Carcinoma are to be put on a parallel with the pleomorphic tumours, though the issue of the clinical evolution is very different for each of them.
In the previously published series of patients with generalized head and neck epidermoid carcinoma, a high dose combination of methotrexate (MTX) (0.4 mg/kg biw. i.v.) and bleomycin (BLM) (30 mg biw. iv) produced an objective remission rate of 60% with a median duration of 9 weeks. The disappointingly short duration of the remissions was tentatively related to the short period of treatment, which was limited to 5 weeks in order to keep the cumulative dosage of BLM below 300 mg. In the present study, covering 26 patients, a lower weekly dose was adopted (BLM 15 mg, MTX 0.6 mg/kg). 13 partial remissions were obtained with a median duration of 26 weeks; in 7 cases there was no evolution, in 6 cases progression of the tumor was registered, and there was one death from hematological toxicity. The major toxicity was leuko- and thrombopenia with one toxic death. Digestive and cutaneous side effects and fever were minor. There were 2 cases of major pulmonary toxicity, one of which was lethal. In conclusion, a combination of MTX and BLM at a relatively low dosage is active in disseminated head and neck carcinoma and appears to be compatible with longer maintenance of palliation in comparison with results obtained at a high dose level.
The authors present the case of a 14 year-old girl having the cervical deformity developed on the background of influenza and sore throat and was caused by an apparently minor sports injury, with vertebrocervical lesion and rupture of the inner wall of the jugular vein. The painful onset symptomatology, initially attributed to exacerbation of the anginous process and cervical adenitis, evolved towards phonation, deglutition, nervous and final respiratory disturbances. The progressive evolution and gravity of the clinical picture imposed craniocervical surgery, with exclusion of the lateral intramastoid sinus and resection of the extensive ectatic cervicoprevertebral pouch. The authors discuss the mechanism of the vascular lesion, the clinical picture, evolution, diagnosis and therapy, which totaly differed from classical descriptions of phlebectasia of the jugular vein.
Intracellular serine protease was isolated from stationary-grown Bacillus subtilis A-50 cells and purified to homogeneity. The molecular weight of the enzyme is 31,000 +/- 1,000, with an isoelectric point of 4.3. Its amino acid composition is characteristically enriched in glutamic acid content, differing from that of extra-cellular subtilisins. The enzyme is completely inhibited with phenylmethylsulfonyl fluoride and ethylenediaminetetraacetic acid. Intracellular protease possesses negligible activity towards bovine serum albumin and hemoglobin, but has 5- to 20-fold higher specific activity against p-nitroanilides of benzyloxycarbonyl tripeptides than subtilisin BPN'. Esterolytic activity of the enzyme is also higher than that of subtilisin BPN'. The enzyme is sequence homologous with secretory subtilisins throughout 50 determined NH2-terminal residues, indicating the presence of duplicated structural genes for serine proteases in the B. subtilis genome. The occurrence of two homologous genes in the cell might accelerate the evolution of serine protease not only by the loosening of selective constrainst, but also by creation of sequence variants by means of intragenic recombination. Three molecular forms of intracellular protease were found, two of them with NH2-terminal glutamic acid and one minor form, three residues longer, with asparagine as NH2 terminus. These data indicate the possible presence of an enzyme precursor proteolytically modified during cell growth.
Influenza viruses type A isolated in 1968--1976 were found to have changes in the content of the antigenic determinant H3. The experiments showed that while in the viruses isolated in 1968--1972 the H3 antigen was dominating, in the A/Port Chalmers/1/73 virus and some viruses isolated in 1975--1976 this antigen became more and more minor. A correlation was observed between the content of H3 antigen in viruses and the capacity of anti-H3 antiserum to inhibit the infectious activity of viruses. The prepared monospecific serum to H3 antigen contained no antibody to the other two antigenic determinants of virus or to neuraminidase and host cell antigen and was completely free from inhibitors. The serum could be used in HI, CFT, and immunodiffusion tests for the analysis of the antigenic composition of newly isolated influenza viruses.
Radiation exposure from panoramic equipment can be reduced significantly by use of smaller film, adjustment of the beam height to the height of the smaller film, and careful positioning of patients. These techniques have no adverse effect on the quality of the diagnostic information needed in dentistry. In addition to describing methods of reducing exposures from panoramic machines, this study demonstrates that the use of a barrier collar during static, cephalometric examinations can appreciably reduce thyroid exposure. Since the objective is to obtain diagnostic information from the film without irradiating the thyroid, the application of a lead-impregnated collar is a minor inconvenience, easily borne by the patient and operator. It should be noted that the use of the collar during panoramic examinations affords little or no protection since the relative motion of the panoramic machine places the axis of movement inside the head and neck of the patient. While the evolution of diagnostic radiology may have reached a high level of technical refinement of equipment and film the clinician still must avoid unnecessary exposure for X-ray examinations and must carefully select the best type of examination to be used for each patient. For example, a complete panoramic examination to determine the position of a known unerupted third molar tooth is probably not an exercise of good judgment since other examinations, such as periapical, could yield the same information with less exposure. Decisions must be made with good judgment, value being placed on relative risks versus the benefits of diagnostic yield.
Recent theoretical and algorithmic advances in introgression detection, coupled with the growing availability of genome-scale data, have highlighted the widespread occurrence of interspecific gene flow across the tree of life. However, current methods largely depend on the molecular clock assumption-a questionable premise given empirical evidence of substitution rate variation across lineages. While such rate heterogeneity is known to compromise gene flow detection among divergent lineages, its impact on closely related taxa at shallow evolutionary timescales remains poorly understood, likely because these taxa are often assumed to adhere to a molecular clock. To address this gap, we combine theoretical analyses and simulations to evaluate the robustness of widely used site pattern methods (D-statistic and HyDe) to rate variation across phylogenetic timescales. Our results demonstrate that both methods exhibit high sensitivity to even minor deviations from the molecular clock at shallow timescales, complementing previous findings at deeper scales. Specifically, in young phylogenies (with an age of 3 × 105 generations) with small population sizes, weak (17% difference) and moderate (33% difference) rate variation can inflate false-positive rates up to 35% and 100%, respectively, using site pattern counts from a 500 Mb genome. Employing a more distant outgroup intensifies these spurious signals. Our study demonstrates that summary tests for introgression are pervasively vulnerable to minor rate variations and underscores the critical need for advanced methodologies to disentangle genuine introgression from false signals generated by rate heterogeneity.
A new method for the isolation of C6 and C7 by affinity chromatography of human serum with anti-C6 and anti-C7 coupled to Sepharose is described. C6 and C7 prepared by this method are hemolytically fully active, homogeneous proteins obtained in 25% yield. A comparison of the properties of isolated C6 and C7 gave the following results: The amino acid composition of the two proteins is very similar. The m.w. calculated from the amino acid content is 124,800 for C6 and 120,800 for C7. Both components are single chain glycoproteins migrating upon electrophoresis at pH 8.6 as beta 2-globulins, Both proteins are polymorphic as detected by isoelectrofocusing in polyacrylamide gels and range in their isoelectric points from pH 6.15 to 6.7. The UV spectra reveal only minor differences; the extinction coefficients are: EC6 = 1.71 cm2 X mg-1 and EC7 = 1.92 cm2 X mg-1. CD-spectra show 8% alpha-helix and 10% beta-structure for C6 and 10% alpha-helix and 14% beta-structure for C7. The structural similarities of C6 and C7 suggest their evolution from a common ancestral gene.
In a case of cervical adenocarcinoma in situ, accompanied by relatively minor squamous-cell dysplasia, the neoplastic glandular cells were associated with "abnormal" but not clearly cancerous surface cells of the endocervix. Measurements of the nuclear DNA of these cells revealed an aneuploid pattern similar to that of epidermoid dysplasias. It is suggested that endocervical dysplasia is a valid entity and represents a step in the evolution of cervical adenocarcinoma from reserve cells comparable to the position of epidermoid dysplasia in the genesis of epidermoid carcinoma.
The structure of the periostracum in the fresh-water mussel Amblema has been described using light microscopy, transmission elec;ron microscopy, and scanning electron microscopy. The structure and evolutive course of the periostracum was studied along its entire length, from the periostracal groove until it forms the tough outer covering of the shell. At least five structurally and functionally distinct regions were identified. In addition, the periostracum itself was seen to be a multilayered structure consisting of three major layers which are themselves subdivided into minor layers. From these morphological observations, a regulatory role for the various periostracal layers in mineral trapping, nucleation, and the subsequent formation of the prismatic and nacreous layers of the shell can be postulated.