Chromatin Bodies Research Articles

A Review of Autoimmune Disease Hypotheses with Introduction of the "Nucleolus" Hypothesis.

Numerous hypotheses have been proposed in order to explain the complexity of autoimmune diseases. These hypotheses provide frameworks towards understanding the relations between triggers, autoantigen development, symptoms, and demographics. However, testing and refining these hypotheses are difficult tasks since autoimmune diseases have a potentially overwhelming number of variables due to the influence on autoimmune diseases from environmental factors, genetics, and epigenetics. Typically, the hypotheses are narrow in scope, for example, explaining the diseases in terms of genetics without defining detailed roles for environmental factors or epigenetics. Here, we present a brief review of the major hypotheses of autoimmune diseases including a new one related to the consequences of abnormal nucleolar interactions with chromatin, the "nucleolus" hypothesis which was originally termed the "inactive X chromosome and nucleolus nexus" hypothesis. Indeed, the dynamic nucleolus can expand as part of a cellular stress response and potentially engulf portions of chromatin, leading to disruption of the chromatin. The inactive X chromosome (a.k.a. the Barr body) is particularly vulnerable due to its close proximity to the nucleolus. In addition, the polyamines, present at high levels in the nucleolus, are also suspected of contributing to the development of autoantigens.

Double minute chromosomes in acute myeloid leukemia, myelodysplastic syndromes, and chronic myelomonocytic leukemia are associated with micronuclei, MYC or MLL amplification, and complex karyotype

Double minute chromosomes (dmin) are small, paired chromatin bodies that lack a centromere and represent a form of extrachromosomal gene amplification. Dmin are rare in myeloid neoplasms and are generally associated with a poor prognosis. Most studies of dmin in myeloid neoplasms are case reports or small series. In the current study, we present the clinicopathologic and cytogenetic features of 22 patients with myeloid neoplasms harboring dmin. These neoplasms included acute myeloid leukemia (AML) (n = 18), myelodysplastic syndrome (MDS) (n = 3), and chronic myelomonocytic leukemia (CMML) (n = 1). The AML cases consisted of AML with myelodysplasia-related changes (n = 13) and therapy-related AML (n = 5). Dmin were detected in initial pre-therapy samples in 14 patients with AML or CMML; they were acquired during the disease course in 8 patients who had AML or MDS. The presence of dmin was associated with micronuclei (18/18; 100%), complex karyotype (17/22; 77.3%), and amplification of MYC (12/16; 75%) or MLL (4/16; 25%). Immunohistochemical staining for MYC performed on bone marrow core biopsy or clot sections revealed increased MYC protein in all 19 cases tested. Except for one patient, most patients failed to respond to risk-adapted chemotherapies. At last follow up, all patients had died of disease after a median of 5 months following dmin detection. In conclusion, dmin in myeloid neoplasms commonly harbor MYC or MLL gene amplification and manifest as micronuclei within leukemic blasts. Dmin are often associated with myelodysplasia or therapy-related disease, and complex karyotypes.

Mechanobiology of Chromatin and the Nuclear Interior

The view of the cell nucleus has evolved from an isolated, static organelle to a dynamic structure integrated with other mechanical elements of the cell. Both dynamics and integration appear to contribute to a mechanical regulation of genome expression. Here, we review physical structures inside the nucleus at different length scales and the dynamic reorganization modulated by cellular forces. First, we discuss nuclear organization focusing on self-assembly and disassembly of DNA structures and various nuclear bodies. We then discuss the importance of connections from the chromatin fiber through the nuclear envelope to the rest of the cell as they relate to mechanobiology. Finally, we discuss how cell stimulation, both chemical and physical, can alter nuclear structures and ultimately cellular function in healthy cells and in some model diseases. The view of chromatin and nuclear bodies as mechanical entities integrated with force generation from the cytoskeleton combines polymer physics with cell biology and medicine.

Spermatogenesis Studies Reveal a Distinct Nonsense-Mediated mRNA Decay (NMD) Mechanism for mRNAs with Long 3'UTRs.

Spermatogenesis Studies Reveal a Distinct Nonsense-Mediated mRNA Decay (NMD) Mechanism for mRNAs with Long 3'UTRs.

Development and Optimization of Vibration-Damped Tool Holders for High Length-to-Diameter Boring Operations

AbstractWhen the length-to-diameter ratio of a boring bar becomes too high, the vibration problem becomes excessive. This paper discusses the design and optimization of tuned mass dampers (TMDs) for vibration-damped boring bars. A typical TMD for a boring bar consists of a high-density mass, rubber elements, and viscous damping fluid. The TMD is mounted as close to the free end of the boring bar as possible for maximizing the damping effect. The different tuning strategies are related to the different types of vibrations that are observed in machining operations. It is shown that the classical tuning with minimized magnitude of the frequency response function will give the shortest settling time for free vibrations, while tuning for maximized negative real part of the frequency response function will give the highest resistance to regenerative chatter. For suppressing regenerative chatters, the internal damping in the material in the boring bar body is of minor importance for boring bars with TMDs, but of high importance for conventional undamped boring bars. The paper presents design solutions for TMDs in boring bars.

Cells With Chromosomal Aberrations Trigger Neoplastic Transformations in Humans.

Human population cytogenetic studies have revealed that a majority of persons who are prone to developing malignant features possess chromatin bodies termed as marker dots (MDs) measuring nearly 2 to 3 microns. These MDs are seen emanating from certain specific chromosomes, which may be early indicators of neoplastic transformation within cells.

Shugoshin forms a specialized chromatin domain at subtelomeres that regulates transcription and replication timing.

A chromosome is composed of structurally and functionally distinct domains. However, the molecular mechanisms underlying the formation of chromatin structure and the function of subtelomeres, the telomere-adjacent regions, remain obscure. Here we report the roles of the conserved centromeric protein Shugoshin 2 (Sgo2) in defining chromatin structure and functions of the subtelomeres in the fission yeast Schizosaccharomyces pombe. We show that Sgo2 localizes at the subtelomeres preferentially during G2 phase and is essential for the formation of a highly condensed subtelomeric chromatin body ‘knob'. Furthermore, the absence of Sgo2 leads to the derepression of the subtelomeric genes and premature DNA replication at the subtelomeric late origins. Thus, the subtelomeric specialized chromatin domain organized by Sgo2 represses both transcription and replication to ensure proper gene expression and replication timing.

Cytological studies on induced mitogynogenesis in Japanese flounder Paralichthys olivaceus (Temminck et Schlegel).

The effect of hydrostatic pressure treatment on the induction of mitogynogenesis in the eggs of Japanese flounder Paralichthys olivaceus (Temminck et Schlegel) by using heterospecific sperm were studied. Before treatment, the eggs were at metaphase of the first mitosis. The spindle was disassembled by the treatment and then resembled in its pretreatment position, and the chromosomes were rearranged, i.e., the first mitosis was not blocked. During the second mitotic cycle, only a monopolar spindle was assembled in each blastomere and the chromosomes doubled, but cell cleavage was blocked. In the third cycle, mitosis proceeded normally with a bipolar spindle in each blastomere. Flow cytometric analysis of ploidy demonstrated that mitogynogenetic larvae were all diploid. The ultraviolet light-irradiated sperm of the red sea bream (Pagrus major) was condensed, formed a dense chromatin body, and randomly entered one blastomere.

Do the presence of Barr bodies in male jail inmates indicates criminality: A pilot study

Background:Cytogenetic studies from past decades have shown that interphase cells of female cats contain a densely stained chromatin mass in their nuclei called as Barr bodies (BBs) named after the scientist Murray Barr. BBs are unique chromatin structures formed due to the condensation of the X-chromosome. Many psychopathic disorders originate from defective genes including the multiple X syndromes. Males with extra X-chromosome generally present with severe personality disorder. The present study was conducted to determine the presence of extra X-chromosome in male jail inmates through the detection of BB in peripheral blood and buccal smear.Materials and Methods:Study included 100 male subjects (fifty jail inmates and fifty controls), after obtaining the consent, peripheral blood smears (PBS) and buccal smears (BS) were prepared and stained using Leishman's and cresyl violet stain respectively. One hundred neutrophils in PBS and epithelial cells in BS were screened for detection of the BB; accumulated data were tabulated and statistically analyzed using t-test and Chi-square test.Results:60% of cases in PBS and 36% in BS showed positivity for the presence of BB in jail inmates as compared to 14% of cases in PBS and none in BS were positive for BB in controls.Conclusion:Presence of BB in male suggests increased likelihood of criminal tendencies. Further studies are to be carried out to compare the results with karyotyping.

Buccal Smear Examination for Barr Bodies as Sex Determination Tool: Is it a Redundant Exercise?

Buccal Smear Examination for Barr Bodies as Sex Determination Tool: Is it a Redundant Exercise?

91 EMBRYO SUGAR CONSUMPTION DURING IN VITRO DEVELOPMENT

Despite the presence of glycogen and triglycerides as energy reserves in bovine embryos, the viability of embryonic cells in culture is maintained primarily by energetic substrates present in the culture medium. The aim of this experiment was evaluate the embryo metabolism during three important stages of development: Days 1 to 3, Days 3 to 5, and Days 5 to 7; before the formation of Barr body, before the differentiation into ICM and trophectoderm, and during the blastocyst formation, respectively. In this study, we evaluated some energetic substrates (Krebs cycle intermediates). For these analyses we chose to use proton magnetic resonance (H1-NMR) spectroscopy. Matured oocytes were purchased from DeSoto Biosciences (Seymour, TN, USA). The matured cumulus-oocyte complexes were fertilized in vitro according to our standard procedures (Rubessa et al. 2011 Theriogenology 76, 1347–1355). For each group (Days 1–3, 3–5, and 5–7), the zygotes were place in individual drops, and after 48 h of culture, they were placed into well of the well (WOW) culture. For the 3–5 and 5–7 groups, the zygotes were first place in 400 μL of SOF and then moved in a single drop. The 5–7 group was not placed in the WOW system. Zygotes were incubated in a humidified mixture of 5% CO2, 6% O2, and 88% N2 in air at 39°C. The embryos were scored for quality on the basis of morphological criteria. Samples of media (40 μL) were added to 560 μL of a stock solution prepared by dissolving 5.0 mg of sodium 3-(trimethylsilyl)-2,2′,3,3′-tetradeuteropropionate (TSP) in 50 mL of deuterium oxide. The TSP acted both as a chemical shift reference and as an internal standard for the purposes of quantitation. The resulting diluted samples were transferred to a 5-mm NMR tube. Samples were analysed on a Varian VNS-750 NB (750 MHz) spectrometer (Agilent Technologies, Santa Clara, CA, USA). A total of 30 embryos were evaluated, 10 per stage. Data were statistically analysed through an analysis of variance using the Generalized Linear Model (GLM) procedure (SPSS, version 18, 2009). Bonferroni’s post-hoc test was used to perform statistical multiple comparison. The α level was set at 0.05. All data were expressed as quadratic mean and mean standard error. The results, reported in Table 1, show that there was no statistical difference when we compare the lactate, myo-inositol, and pyruvate concentrations. However, there were significant differences when we focused on acetate and formate levels: after Day 3 the production of these two substrates significantly increased. Formate and acetate are important metabolites of the Krebs cycle. The changes of these two substrates are important signs that embryos start glycolysis after Day 3. Table 1.Quadratic means and mean standard errors of formate, lactate, myo-inositol, pyruvate, and acetate for Day 1–3, 3–5, 5–7, and control groups

Photodynamic therapy with a novel porphyrin-based photosensitizer against human gastric cancer.

The objective of the present study was to evaluate the effects of novel porphyrin-based photosensitizer meso-5-[ρ-diethylene triamine pentaacetic acid- aminophenyl]-10,15,20-triphenyl-porphyrin (DTP)-mediated photodynamic therapy (PDT) on the HGC27 and SNU-1 human gastric cancer cell lines. The absorption spectrum of DTP was analyzed using a microplate spectrophotometer. The HGC27 or SNU-1 cells were incubated with DTP and exposed to illumination by a 650-nm laser. The experiments were divided into four groups: A blank control, cells treated with DTP without light, cells exposed to laser light without DTP and cells treated with a combination of DTP and light together. The phototoxicity of DTP was analyzed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay. Cell apoptosis was detected by flow cytometry and Hoechst 33342 staining. In addition, the intracellular distribution of DTP was investigated by laser scanning confocal microscopy. DTP-PDT demonstrated marked phototoxicity towards HGC27- and SNU-1 cells. The rate of cell death increased significantly in a DTP concentration-dependent and light dose-dependent manner, with maximum mortality rates of 74.14 and 67.76%, respectively. There were significant differences between the therapeutic and control groups (P<0.01). In addition, the growth of cells treated with DTP or laser light alone was not inhibited. Further evaluation revealed that, following DTP-PDT, HGC27 and SNU-1 cells demonstrated notable apoptotic changes, including condensed chromatin, fragmented nuclei and apoptotic bodies, and the percentage of apoptotic cells was significantly higher than that of the control groups (P<0.01). Furthermore, confocal laser scanning microscopy revealed that DTP localized to the lysosomes but not mitochondria in the two types of tumor cell. In conclusion, significant phototoxicity and reduced cytotoxicity in dark conditions make the novel photosensitizer DTP a promising potential PDT drug for future use in the treatment of human gastric cancer.

Divergent actions of long noncoding RNAs on X-chromosome remodelling in mammals and Drosophila achieve the same end result: dosage compensation.

Organisms with heterochromatic sex chromosomes need to compensate for differences in dosages of the sex chromosome-linked genes that have somatic functions. In-depth cytological and subsequent biochemical and molecular studies on dosage compensation started with Mary F. Lyon's proposal in early 1960s that the Barr body in female mammalian somatic cells represented one of the randomly inactivated and heterochromatinized X chromosomes. In contrast,Drosophila was soon shown to achieve dosage compensation through hypertranscription of single X in male whose chromatin remains more open.Identification of proteins that remodel chromatin either to cause one of the two X chromosomes in somatic cells of very early female mammalian embryos to become condensed and inactive or to remodel the single X in male Drosophila embryos to a more open state for hypertranscription provided important insights into the underlying cellular epigenetic processes.However, the most strikin g and unexpected discoveries were the identification of long noncoding RNAs (lncRNAs), X-inactive specific transcript (Xist) in mammals and roX1/2 in Drosophila, which were essential for achieving the contrasting chromatin organizations but leading to similar end result in terms of dosage compensation of X-linked genes in females and males. An overview of the processes of X inactivation or hyperactivation in mammals and Drosophila, respectively, and the roles played by Xist, roX1/2 and other lncRNAs in these events is presented.

A Case of Munchausen Syndrome by Proxy: Is it a Misdiagnosis?

Introduction : Child abuse is an area in Forensic Medicine where the diagnosis and management could be difficult. A deep history and close inward observation is a must where there is the slightest doubt of child abuse, in order to identify compounding factors and address accordingly. Here we report a case of repeated episodes of hematuria which was extensively investigated in three tertiary care hospitals revealing no cause, ultimately the mother being discovered as the culprit. Case report : A three year old boy who was extensively investigated for repeated episodes of gross hematuria since the age of seven months was admitted to Teaching Hospital, Peradeniya with another episode of gross hematuria. The child was clinically normal and investigations including blood, imaging studies and renal biopsy were unremarkable. Urine checked for bar bodies was positive. A case conference was held and it was decided to keep the child under parental custody under supervision of medico-legal authorities, while the mother is followed up at the psychiatry clinic for depression. Discussion : Munchausen syndrome (MS) by proxy is a psychiatric disorder which consists of fabricating or inducing illness in a child, usually by his mother, leading to unnecessary and potentially harmful medical investigations and/or treatment which are seen in this case as well. Thus this emphasizes the importance of thinking of MS, before going into potentially harmful investigations when the basic investigations are normal and identifying the importance of having an interlinked e database system in medical facilities in countries like Sri Lanka. Sri Lanka Journal of Forensic Medicine, Science & Law-December 2014-Vol.5 No.2; 3-7

Highly condensed chromatins are formed adjacent to subtelomeric and decondensed silent chromatin in fission yeast.

It is generally believed that silent chromatin is condensed and transcriptionally active chromatin is decondensed. However, little is known about the relationship between the condensation levels and gene expression. Here we report the condensation levels of interphase chromatin in the fission yeast Schizosaccharomyces pombe examined by super-resolution fluorescence microscopy. Unexpectedly, silent chromatin is less condensed than the euchromatin. Furthermore, the telomeric silent regions are flanked by highly condensed chromatin bodies, or ‘knobs'. Knob regions span ∼50 kb of sequence devoid of methylated histones. Knob condensation is independent of HP1 homologue Swi6 and other gene silencing factors. Disruption of methylation at lysine 36 of histone H3 (H3K36) eliminates knob formation and gene repression at the subtelomeric and adjacent knob regions. Thus, epigenetic marks at H3K36 play crucial roles in the formation of a unique chromatin structure and in gene regulation at those regions in S. pombe.

The making of a Barr body: the mosaic of factors that eXIST on the mammalian inactive X chromosome.

During X-chromosome inactivation (XCI), nearly an entire X chromosome is permanently silenced and converted into a Barr body, providing dosage compensation for eutherians between the sexes. XCI is facilitated by the upregulation of the long non-coding RNA gene, XIST, which coats its chromosome of origin, recruits heterochromatin factors, and silences gene expression. During XCI, at least two distinct types of heterochromatin are established, and in this review we discuss the enrichment of facultative heterochromatin marks such as H3K27me3, H2AK119ub, and macroH2A as well as pericentric heterochromatin marks such as HP1, H3K9me3, and H4K20me3. The extremely stable maintenance of silencing is a product of reinforcing interactions within and between these domains. This paper "Xplores" the current knowledge of the pathways involved in XCI, how the pathways interact, and the gaps in our understanding that need to be filled.

Of mice and cats (both calico): Mary F Lyon, FRS (1925-2014).

Of mice and cats (both calico): Mary F Lyon, FRS (1925-2014).

Clinical Neuropathology teaching case 3-2015: female or male brain? Anti-ubiquitin visualizes Barr bodies in hippocampal granule cells which allows the determination of gender in human brains.

No available.

Fine structure of the male genital system of the predatory mite Rhagidia halophila (Rhagidiidae, Prostigmata, Actinotrichida).

The male genital system of the actinotrichid mite Rhagidia halophila is described and compared with other mites and arachnids. The large testes are composed of germinal and glandular parts and produce numerous small sperm cells. The glandular parts are connected via a testicular bridge. Spermiogenesis occurs in cysts containing spermatids in equal stages of development. Cysts of spermatids are embedded in huge somatic cells. The nuclei of the spermatids loose their envelope. Mature sperm cells are simple exhibiting a ring-shaped chromatin body and lacking an acrosomal complex. They are most similar to the sperm cells of the related mite Linopodes motatorius. The spermatopositor contains the ejaculatory duct divided into a dorsal channel and a ventral channel that are connected via a narrow passage. At its distal end, the spermatopositor is divided into three eugenital lips. The function of the spermatopositor during deposition of the peculiar thread-like spermatophores is discussed. Details of the sensilla of the spermatopositor and the progenital lips are reported. The genital papillae located on the inner side of the progenital lips exhibit characteristics of cells performing transport of ions and/or water. The results confirm the overall similarity of actinotrichid genital systems, which is profoundly different from that of anactinotrichid mites. With reference to other Arachnida it is corroborated that testes and sperm structure of Actinotrichida are most similar to that of Solifugae. However, synapomorphies between sperm cells of Rhagidia and Solifugae that could suggest a closer relationship between these two taxa as was suggested in earlier studies were not recognizable. On the contrary, the sperm cells of Rh. halophila being devoid of an acrosomal complex appeared to be more apomorphic than those of many other actinotrichid mites as well as Solifugae.

Vertical structure and dominating factors of sand body during Late Triassic Chang 9 time of Yanchang Formation in Ordos Basin, NW China

Based on a synthetic geological study of drilling, well logging and core observations, two main genetic types of Chang 9 sand body in Odors Basin were recognized, which included two effects, that is, delta environment and tractive current effects that lead to the development of mouth bar, distal bar, sheet sand and other sand bodies of subaerial and subaqueous distributary channel, natural levee, flood fan and delta front, and shore-shallow lake environment and lake flow transformation effects that result in the development of sandy beach bar, sheet sand and other sand bodies. Chang 9 sand body mainly developed five basic vertical structures, namely box shape, campaniform, infundibuliform, finger and dentoid. The vertical stacking patterns of multilayer sand body was complex, and the common shapes included box shape + box shape, campaniform + campaniform, campaniform + box shape, infundibuliform + infundibuliform, campaniform + infundibuliform, box shape + campaniform, box shape + infundibuliform, and finger + finger. Based on the analysis on major dominating factors of vertical structure of sand body, sedimentary environment, sedimentary facies and rise, fall and cycle of base level are identified as the major geological factors that control the vertical structure of single sand body as well as vertical stacking patterns and distribution of multistory sand bodies.