Miracle-dz/UniFAR-FTUs huggingface dataset:
Multiple sclerosis. Interactions between oligodendrocytes and hypertrophic astrocytes and their occurrence in other, nondemyelinating conditions.

BACKGROUND The proliferation of oligodendrocytes and their association with hypertrophic astrocytes has been previously described in resolving multiple sclerosis (MS) lesions. EXPERIMENTAL DESIGN Central nervous system lesions of different ages were examined from 9 cases of MS with clinical histories ranging from 8 weeks to 13 years and in a variety of non-MS conditions. RESULTS In MS, these associations were found to occur most frequently in acute, actively demyelinating (as opposed to resolving) lesions. They also occurred, albeit rarely, in chronic active and chronic silent MS plaques and in areas showing remyelination or normal myelination adjacent to lesions. Immunocytochemistry revealed that the oligodendrocytes occurred in increased numbers and displayed enhanced reactivity for HNK-1, similar to previous studies that claimed such cells to be of recent origin. Ultrastructurally, hypertrophic astrocytes in the lesion center usually possessed no formed bundles of intermediate filaments, but rather displayed a finely granular cytoplasm. Towards the perimeter, they contained bundles of filaments and showed increased staining with anti-glial fibrillary acidic protein antibody. The interactions involved the close apposition to, and internalization of oligodendrocytes by astrocytes, between which membrane specializations occurred, suggestive of an adhesion event. Identical glial associations were also seen in various non-MS conditions. In most of the latter cases, there was evidence of central nervous system inflammation and/or destruction. CONCLUSIONS These observations underscore the increased frequency of the glial cell phenomenon in active MS lesions, its ubiquity in diseases of different etiologies and the need for careful scrutiny of control central nervous system tissue in assessing the specificity of phenomena attributed to MS. It is suggested that these glial associations may represent a transient protective mechanism and may be related to local cytokine production.
Characterization of CD8+ cytotoxic T-lymphocyte responses after genetic immunization with retrovirus vectors expressing different forms of the hepatitis B virus core and e antigens

Cytotoxic T-lymphocyte (CTL) activity appears to play an important role in resolving hepatitis B virus (HBV) infection, and the ability to induce such responses remains an important goal for developing effective immunotherapeutics. A panel of recombinant retrovirus vectors expressing different forms of the HBV core antigen (HBcAg) or e antigen (eAg) were found to induce antigen-specific major histocompatibility complex-restricted CTL responses in both mice and macaques. In addition, a novel retrovirus vector expressing an HBcAg-neomycin phosphotransferase II (HBc-Neo) fusion protein [LHBc-NEO(6A3)], which allows the measurement of the anti-Neo antibody response as a means of directly tracking biological activity of the vector, was generated. Doses greater than 10(7) CFU were necessary to induce CTL responses in H-2(k) mice. Intramuscular injections with 10(8) CFU of the LHBc-NEO(6A3) retrovirus vector into rhesus monkeys induced HBc/eAg-specific antibody production and CD8+ CTLs. The CTL response from one of the two responder rhesus monkeys was directed against a 9-residue peptide, GELMTLATW, at positions 63 to 71 of the HBc/eAg sequence. The CTL response is long lived, being detectable as late as 16 weeks after immunization, and can be boosted upon reimmunization. The potent ability of recombinant retrovirus vectors to induce HBcAg- and eAg-specific CTL responses may prove beneficial as a therapeutic treatment for chronic hepatitis B infection.
Water ways: exploring water through metaphoric imagery, discussion and action

This case study was unique in its focus on an environmental education curriculum for older adults. It followed from previous studies in exploring the instructional and research potential of metaphor and environmental orientation. Environmental orientations towards water were examined among a group of retirees before, during and after a workshop which incorporated instructional metaphor as a teaching strategy. The study demonstrated that, at least for some participants, the use of metaphor from a variety of orientations has the potential to increase participants’ appreciation of alternative ways of relating to the environment. Overall, the use of metaphor appears to have contributed positively to most participants’ understanding of water issues. As an educational tool instructional metaphor was useful in group discussion as a catalyst for conversation about how participants view, understand and relate to water. As a research technique metaphoric interviewing was useful to help draw out the accumulated knowledge and experiences of older adults.
Developmental brain abnormalities in the offspring of schizophrenic mothers. II. Structural brain characteristics of schizophrenia and schizotypal personality disorder.

BACKGROUND We examined differences in ventricular and sulcal cerebrospinal fluid-to-brain ratios as a function of lifetime psychiatric diagnosis in the offspring of schizophrenic mothers (high-risk sample) and in the offspring of normal parents (low-risk sample). METHODS We used a cohort analytic study of 17 high-risk individuals with schizophrenia, 31 high-risk individuals with schizotypal personality disorder, 33 high-risk individuals with nonschizophrenia-spectrum psychiatric disorders, 45 high-risk individuals with no disorders, 31 low-risk individuals with psychiatric disorders of all types, and 46 low-risk individuals with no disorders, evaluated initially in 1962 when they were a mean age of 15 years, and reexamined from 1986 through 1989 with psychiatric interviews and computed tomographic scans of the brain. RESULTS High-risk individuals with schizophrenia and schizotypal personality disorder evidenced an equivalent degree of cortical sulcal enlargement, and both groups evidenced significantly greater sulcal enlargement than did high-risk individuals with nonschizophrenia-spectrum disorders and no disorders and low-risk individuals with psychiatric disorders and no disorders. High-risk individuals with schizophrenia evidenced significantly greater ventricular enlargement than did high-risk and low-risk subjects with other disorders and no disorders, including those with schizotypal personality disorder. These differences were independent of age, gender, history of substance dependence, and history of organic brain syndromes and head injuries. CONCLUSIONS Among the offspring of schizophrenic parents, cortical abnormalities are expressed equally across the range of syndromes in the schizophrenia spectrum. Subcortical abnormalities (ie, ventricular enlargement) are more pronounced in the more severe syndrome (ie, schizophrenia).
Characterization of the hormone responsive element involved in the regulation of the progesterone receptor gene.

The transcription of the progesterone receptor gene is induced by estrogens and decreased by progestins. Studies were performed to define the regions of the gene and the molecular mechanisms involved. No hormonal regulation could be observed using 5′ flanking regions of the gene up to −2762 in front of a heterologous gene. Estrogen and progestin regulation could be observed only when using fragments of the gene extending down to +788. Progressive deletions from the 5′ and 3′ ends, site‐directed mutagenesis and DNase protection experiments with purified estrogen receptor suggested that the biologically active estrogen responsive element (ERE) is present at +698/+723, overlapping the initiation of translation. An oligonucleotide was synthesized bearing this ERE and shown to impart estrogen inducibility to a heterologous gene. Its regulation by anti‐estrogens corresponded to that of the in situ progesterone receptor gene since tamoxifen was a partial agonist whereas ICI 164384 was a full antagonist. This ERE also mediated down‐regulation by progestins in the presence of the progesterone receptor, even though it has no progesterone receptor binding ability. DNase footprinting showed that this effect was not due to a decrease of estrogen receptor affinity for the ERE in the presence of progesterone receptor. Finally, use of deletion mutants of the progesterone receptor showed that the steroid binding and the DNA binding domains were necessary for down‐regulation whereas deletions of various parts of the N‐terminal domain were without effect.
An Entamoeba histolytica LINE/SINE Pair Inserts at Common Target Sites Cleaved by the Restriction Enzyme-Like LINE-Encoded Endonuclease

ABSTRACT The non-long-terminal-repeat (non-LTR) retrotransposons (also called long interspersed repetitive elements [LINEs]) are among the oldest retroelements. Here we describe the properties of such an element from a primitive protozoan parasite, Entamoeba histolytica, that infects the human gut. This 4.8-kb element, called EhLINE1, is present in about 140 copies dispersed throughout the genome. The element belongs to the R4 clade of non-LTR elements. It has a centrally located reverse transcriptase domain and a restriction enzyme-like endonuclease (EN) domain at the carboxy terminus. We have cloned and expressed a 794-bp fragment containing the EN domain in Escherichia coli. The purified protein could nick supercoiled pBluescript DNA to yield open circular and linear DNAs. The conserved PDX12-14D motif was required for activity. Genomic sequences flanking the sites of insertion of EhLINE1 and the putative partner short interspersed repetitive element (SINE), EhSINE1, were analyzed. Both elements resulted in short target site duplications (TSD) upon insertion. A common feature was the presence of a short T-rich stretch just upstream of the TSD in most insertion sites. By sequence analysis an empty target site in the E. histolytica genome, known to be occupied by EhSINE1, was identified. When a 176-bp fragment containing the empty site was used as a substrate for EN, it was prominently nicked on the bottom strand at the precise point of insertion of EhSINE1, showing that this SINE could use the LINE-encoded endonuclease for its insertion. The nick on the bottom strand was toward the right of the TSD, which is uncommon. The lack of strict target site-specificity of the restriction enzyme-like EN encoded by EhLINE1 is also exceptional. A model for retrotransposition of EhLINE1/SINE1 is presented.
Word recognition in continuous speech with background noise based on posterior probability measure

To overcome the issues of speech recognition, most of the existing research work considers pre-treatment techniques (noise reduction, end point detection) combined with the training models and pattern recognition techniques. To find the target word in a predefined speech sentence, various similarity measure techniques have been developed. However, the existence of background noise in speech signal degrades the performance of the system in terms of target word identification. In this paper, a novel technique for Word Recognition in Continuous Speech with Background Noise (WRBN) is proposed which differentiates the background noise from speech signal. The proposed technique uses Posterior Probability Measure (PPM), used in image processing for target localisation. Unlike PPM, background speech components which participate actively in mismatching or misidentification, have not been considered in the literature.
Does connection with @realDonaldTrump affect stock prices?

This study investigates whether investors react to signals of an association between a firm and Donald Trump indicated by tweets containing both words 'Trump' (or '@realDonaldTrump') and a S&P500 firm name. Our results reveal that a large number of such tweets ignite speculations about a political connection between a firm and the US's President, thus affecting investors' trading behaviors. In particular, a rise in these tweets induces significant increases in trading volatility and trading volume. However, we do not find such great impacts on stock returns, suggesting that the speculations are more likely to spread among small non-institutional investors. Further investigations show that sentiments embedded in these tweets have limited influence. There is evidence of a changing market behavior towards such tweets centered by the President's inauguration.
Protection against FIV challenge infection by genetic vaccination using minimalistic DNA constructs for FIV env gene and feline IL-12 expression

ObjectiveTo evaluate the efficacy of a genetic vaccination protocol based on minimalistic, immunogenic defined gene expression (MIDGE) vectors coding for domains of the feline immunodeficiency virus (FIV) env gene and feline IL-12. MethodsThree groups of four cats each were immunized three times within 6 weeks by the ballistic transfer of gold particles coated with MIDGE vectors. Group 1 received non-coated gold beads, groups 2 and 3 MIDGE vectors expressing FIV surface plus part of the transmembrane protein. In addition, group 3 received feline IL-12 DNA. All cats were challenged by intraperitoneal injection of 25 TCID50 of infectious FIV Z2. The following criteria were monitored: clinical signs, antibodies to transmembrane protein, antibodies to whole FIV, haematological parameters and kinetics of CD4 and CD8 cells, FIV proviral load (determined by quantitative polymerase chain reaction; PCR) and cytotoxic T lymphocyte (CTL) activity (in selected cats). ResultsNone of the cats developed a detectable antibody response during immunizations. Four weeks after challenge exposure, all cats in group 1 (control) and group 2 (FIV surface-transmembrane protein) had seroconverted and showed a high proviral load until week 19 (end of experiment). In contrast, only one of four cats in group 3 (surface-transmembrane protein and IL-12) showed antibodies; it was provirus positive at reduced virus load. Short-lived CTL activity was found in two cats in group 3. ConclusionGenetic vaccination using a MIDGE-based construct for the expression of the surface-transmembrane protein domain of FIV env and feline IL-12 DNA led to protection against homologous virus challenge in three out of four vaccinated cats.
Functional interaction between APOE4 and LDL receptor isoforms in Alzheimer’s disease

Background: Multiple genes have been provisionally associated with Alzheimer’s disease, including the coding polymorphisms in exons 8 and 13 in the low density lipoprotein receptor gene (LDLR), situated on chromosome 19p13.2. Methods: The sample groups consisted of 180 AD patients and 141 control spouses. We carried out genotyping of LDLR8 and LDLR13. Results: The LDLR8 GG genotype was common, found in 84% of the unaffected control subjects and 91% of the AD patients in our study. There was a ninefold elevation in risk associated with GG:CC versus A– and T– among APOE4+ subjects when compared with APOE4− subjects (odds ratio 9.3; 95% confidence interval 1.8 to 48.2). With the additional information on LDLR polymorphism, we defined an overall 12 fold elevation in risk for APOE4 in combination with LDLR GG:CC (11.9; 2.8 to 50.0; Fisher’s exact test, p = 0.0002; standard power 0.999), compared with other subjects lacking all three of these polymorphisms. Conclusion: These results imply a functional interaction between ApoE and LDL receptor proteins that determines risk for Alzheimer’s disease.
The calpain‐system of Drosophila melanogaster: coming of age

Drosophila melanogaster is one of the most popular and powerful model organisms that helpour understanding of mammalian (human) life processes at the molecular level. Calpains are Ca2+‐activated cytoplasmic proteases thought to play multiple roles in intracellular signal processing by limited proteolysis of target substrate proteins, thereby changing their function. The calpain superfamily consists of 14 genes in mammals, but only 4 genes in Drosophila. One may assume that the calpain system, i.e. recognizing calpain‐dependent life processes and identifying the substrates cleaved while exerting their functions, would prove easier to solve in Drosophila than in mammals. Recently, major progress has been made in characterizing Drosophila Calpain A, Calpain B and Calpain C. The fourth member, Calpain D (or SOL), was analyzed earlier. At this juncture, it seems justifiable to summarize our knowledge about the Drosophila enzymes, in comparison to the ubiquitous mammalian ones, as regards structure–function relations, mode of activation by Ca2+ and other factors, inhibition, potential targeting, expression pattern in vivo, etc. Equipped with all this information, we may now embark on the genetic modification of family members, interpreting mutant phenotypes in terms of the cell biology of calpains. BioEssays 26:1088–1096, 2004. © 2004 Wiley Periodicals, Inc.
Immunohistochemical and Ultrastructural Investigation of Neural Differentiation in Ewing Sarcoma/PNET of Bone and Soft Tissues

The authors evaluated the role of immunohistochemistry and electron microscopy in defining neural differentiation in 28 cases of Ewing sarcoma/ PNET. The panel of primary antibodies used included vimentin, MIC-2, NSE, S-100 protein, leu7, neurofilaments, GFAP, and chromogranin A. Cases were considered undifferentiated when neural markers were absent, poorly differentiated if one neural marker was present, and well differentiated if two or more markers were observed. Cases were also evaluated for the presence of cytoplasmic processes, microtubules, and neurosecretory granules as ultrastructural features of neural differentiation: the tumor was classified as well differentiated if two of these features were present; and poorly differentiated if one was evident; all other cases were considered undifferentiated. According to immunohistochemistry, 10 cases (35.7%) were undifferentiated, 12 cases (42.9%) were poorly differentiated, and 6 (21.4%) were well differentiated. According to the ultrastructural analysis, 10 tumors were undifferentiated (35.7%), 14 poorly differentiated (50%), and 4 well differentiated (14.3%). The overall concordance between the two techniques was low (35.7%), and both modalities were concordant in classifying only 1 well-differentiated, 5 poorly differentiated, and 4 undifferentiated tumors. In conclusion, the authors suggest that investigations devoted to test the prognostic significance of neural differentiation in these neoplasms should employ both immunohistochemistry and electron microscopy, separately and in combination, to assess what is the most effective choice for predicting the clinical course.
Role of Oxidative Stress in Development of Complications in Diabetes

Nϵ-(carboxymethyl)lysine, Nϵ-(carboxymethyl)hydroxylysine, and the fluorescent cross-link pentosidine are formed by sequential glycation and oxidation reactions between reducing sugars and proteins. These compounds, termed glycoxidation products, accumulate in tissue collagen with age and at an accelerated rate in diabetes. Although glycoxidation products are present in only trace concentrations, even in diabetic collagen, studies on glycation and oxidation of model proteins in vitro suggest that these products are biomarkers of more extensive underlying glycative and oxidative damage to the protein. Possible sources of oxidative stress and damage to proteins in diabetes include free radicals generated by autoxidation reactions of sugars and sugar adducts to protein and by autoxidation of unsaturated lipids in plasma and membrane proteins. The oxidative stress may be amplified by a continuing cycle of metabolic stress, tissue damage, and cell death, leading to increased free radical production and compromised free radical inhibitory and scavenger systems, which further exacerbate the oxidative stress. Structural characterization of the cross-links and other products accumulating in collagen in diabetes is needed to gain a better understanding of the relationship between oxidative stress and the development of complications in diabetes. Such studies may lead to therapeutic approaches for limiting the damage from glycation and oxidation reactions and for complementing existing therapy for treatment of the complications of diabetes.
Big men and atrial fibrillation: effects of body size and weight gain on risk of atrial fibrillation in men.

AIMS Obesity is a recognized risk factor for atrial fibrillation (AF), partly because of the association between body mass index (BMI) and atrial volume. We aimed to determine whether other factors relating to body size were related to AF. METHODS AND RESULTS Data were derived from a random population sample of 6903 men (mean age 51.5 years) who underwent a single midlife evaluation as part of the multifactor Swedish Primary Prevention Study. A total of 1253 men (18.2%) had a subsequent hospital discharge diagnosis (principal or secondary) of AF during a maximum follow-up of 34.3 years. Body surface area (BSA) at age 20 (calculated from recalled weight and measured height) was strongly related to subsequent AF (P < 0.0001), as were midlife BMI and weight gain from age 20 to midlife (P < 0.0001). In a Cox regression model which adjusted for midlife BMI, weight gain and other risk factors, hazard ratios (HR) [95% confidence intervals (CI)] for AF for the second, third, and fourth quartile of BSA at age 20, compared with the lowest quartile, were 1.47 (95% CI, 1.22-1.76), 1.66 (95% CI, 1.38-2.00), and 2.22 (95% CI, 1.82-2.70) (P for trend <0.0001). CONCLUSION Large body size in youth, in an era when obesity was rare, as well as weight gain from age 20 to midlife, were both independently related to the development of AF. Given the current trends not only for obesity but also for height, a substantial increase in the incidence of AF is likely.
Combination therapy with sirolimus and mycophenolate mofetil: effects on the kidney and on transforming growth factor-&bgr;11

Sirolimus (SRL) is not nephrotoxic, but it has been shown to increase transforming growth factor (TGF)-&bgr;. We investigated the effect of combining mycophenolate mofetil (MMF) with SRL on renal structure and function and on TGF-&bgr;1. Rats treated with vehicle (VH), MMF 10 mg/kg/d, SRL 0.3 mg/kg/d, or SRL+MMF were killed at 28 days. The physiologic and histologic changes and expression of TGF-&bgr;1, plasminogen activator inhibitor-1, and extracellular matrix proteins were studied. Although SRL alone did not alter renal function and structure, it increased TGF-&bgr;1 mRNA by 44% and protein by 48% (P <0.05 vs. VH). Treatment with MMF did not affect TGF-&bgr;1. When combined with SRL, MMF decreased TGF-&bgr;1 expression to VH levels. A similar trend was observed with plasminogen activator inhibitor-1 and extracellular matrix proteins. The long-term consequence of increased TGF-&bgr; in SRL-treated kidneys remains unknown. However, because MMF can reverse this trend, SRL and MMF combination therapy may be protective.