Miracle-dz/UniFAR-FTUs huggingface dataset:
Condensin II Regulates Interphase Chromatin Organization Through the Mrg-Binding Motif of Cap-H2

The spatial organization of the genome within the eukaryotic nucleus is a dynamic process that plays a central role in cellular processes such as gene expression, DNA replication, and chromosome segregation. Condensins are conserved multi-subunit protein complexes that contribute to chromosome organization by regulating chromosome compaction and homolog pairing. Previous work in our laboratory has shown that the Cap-H2 subunit of condensin II physically and genetically interacts with the Drosophila homolog of human MORF4-related gene on chromosome 15 (MRG15). Like Cap-H2, Mrg15 is required for interphase chromosome compaction and homolog pairing. However, the mechanism by which Mrg15 and Cap-H2 cooperate to maintain interphase chromatin organization remains unclear. Here, we show that Cap-H2 localizes to interband regions on polytene chromosomes and co-localizes with Mrg15 at regions of active transcription across the genome. We show that co-localization of Cap-H2 on polytene chromosomes is partially dependent on Mrg15. We have identified a binding motif within Cap-H2 that is essential for its interaction with Mrg15, and have found that mutation of this motif results in loss of localization of Cap-H2 on polytene chromosomes and results in partial suppression of Cap-H2-mediated compaction and homolog unpairing. Our data are consistent with a model in which Mrg15 acts as a loading factor to facilitate Cap-H2 binding to chromatin and mediate changes in chromatin organization.
Ethanol Self-Administration Restores Withdrawal-Associated Deficiencies in Accumbal Dopamine and 5-Hydroxytryptamine Release in Dependent Rats

Basal forebrain dopamine (DA) and 5-HT neurotransmission has been implicated in the mediation of the acute reinforcing actions of ethanol. Neuroadaptation theories predict that compensatory changes in neurochemical systems that are activated by alcohol acutely may underlie symptoms of withdrawal after chronic administration. To test this hypothesis, the release of DA and 5-HT was monitored by microdialysis in the nucleus accumbens of dependent male Wistar rats at the end of a 3–5 week ethanol (8.7% w/v) liquid diet regimen, during 8 hr of withdrawal, and during renewed availability of ethanol involving (1) the opportunity to operantly self-administer ethanol (10% w/v) for 60 min, followed by (2) unlimited access to the ethanol-liquid diet. Results were compared to control groups pair-fed with ethanol-free liquid diet and trained to self-administer either ethanol or water. In nondependent rats, operant ethanol self-administration increased both DA and 5-HT release in the NAC. Withdrawal from the chronic ethanol diet produced a progressive suppression in the release of these transmitters over the 8 hr withdrawal period. Self-administration of ethanol reinstated and maintained DA release at prewithdrawal levels but failed to completely restore 5-HT efflux. 5-HT levels recovered rapidly, however, within 1 hr of reexposure to ethanol liquid diet. These findings suggest that deficits in accumbal monoamine release may contribute to the negative affective consequences ethanol withdrawal and, thereby, motivate ethanol-seeking behavior in dependent subjects.
Betel quid chewing in rural Bangladesh: prevalence, predictors and relationship to blood pressure.

BACKGROUND Betel quid is chewed by 600 million people worldwide and it has been linked to obesity and cardiovascular disease. The purpose of our study was to examine the prevalence and predictors of betel quid chewing in a rural area of Bangladesh, and determine its effects on body mass index (BMI) and blood pressure. METHODS In this population-based prospective study, we analysed data on 19 934 Bangladeshi adults. Linear and multivariate logistic regression was used to determine the socio-demographic predictors of betel quid chewing and the effect of betel quid on change in BMI and on systolic and diastolic blood pressure, pulse pressure, arterial pressure, overweight or obesity, and hypertension. RESULTS At baseline, betel quid was chewed by 33.2% of the cohort (35.5% of men, 31.6% of women). In a subsample in which we collected methods of use, 17.5% chewed it without tobacco and 82.5% chewed it with tobacco. In multivariate analysis, betel quid chewing was associated with female sex, older age, tobacco smoking and lower socio-economic status, as measured by fewer years of formal education and not owning land. Betel quid was chewed more times per day among women and older persons. At follow-up, persons who chewed betel quid without tobacco had higher systolic blood pressure, diastolic blood pressure and arterial pressure in comparison with never users. After controlling for other explanatory variables, chewing betel quid without tobacco was associated with general hypertension [odds ratio (OR) 1.48, 95% confidence interval (CI) 1.04-2.10] and systolic hypertension (OR 1.55, 95% CI 1.01-2.37). We did not observe associations of betel quid chewing with BMI or overweight. CONCLUSIONS Betel quid chewing is likely contributing to high blood pressure in Bangladesh, particularly among women.
Intrauterine fetal demise following laser treatment in twin-to-twin transfusion syndrome.

OBJECTIVE To evaluate the incidence, risk factors and consequences of intrauterine fetal demise (IUFD) of at least one twin in twin-to-twin transfusion syndrome (TTTS) treated by laser. DESIGN Retrospective analysis. SETTING Experience of a single centre between 1999 and 2004. POPULATION A subgroup of 45 cases with fetal demise of one or both twins from a series of 120 cases of TTTS treated by laser. METHODS All cases were entered prospectively into a dedicated database and the results were analysed retrospectively. MAIN OUTCOME MEASURES Fetal demise prognostic factors, survival, fetal anaemia, brain lesions, neonatal death and intact survival. RESULTS IUFD of one twin occurred in 40 of 120 cases (19 donors and 21 recipients). IUFD of both twins occurred in another five cases. From these 40 cases, miscarriage occurred in two and pregnancy termination was requested in another two cases because of antenatal brain lesions. Two neonates died and two presented severe morbidity, survivors were therefore neurologically normal at 6-44 months of life in 89% (32/36) of the cases. Univariate analysis showed that preoperative abnormal umbilical artery Doppler in the donor before laser treatment and in the recipient following laser treatment was associated with their demise. Incomplete coagulation was suspected in cases where anaemia or cerebral lesions developed following the death of the first twin (10). CONCLUSIONS IUFD of one or both twins occurred in 45 of 120 (38%) cases of severe TTTS treated by laser. In these, separation of the placental circulations was incomplete in at least 22% (10/45) of the cases. Umbilical artery Doppler abnormalities before laser were found to be risk factors for the donors' demise following the procedure.
Patterns of cerebral gray and white matter alterations in preterm subjects by magnetic resonance imaging

Preterm birth is frequently associated with an increased risk of neurodevelopmental difficulties and of cognitive, behavioural and emotional problems during childhood. The present thesis comprises two MRI studies that demonstrated patterns of cerebral gray matter (GM) and white matter (WM) alterations and their cognitive correlates in children and adolescents who were born preterm.Our first study provided evidence of the persistence of diffuse WM abnormalities in adolescents who were born very preterm, and underlines their high frequency. The individual voxel-based morphometry analysis approach demonstrated that 80% of preterm subjects had WM abnormalities, the most frequently affected areas being the centrum semiovale and the posterior periventricular regions. These results suggest that WM reductions are common, even in those preterm subjects without motor impairment and who receive normal schooling. Volumetric and MRI-related cognitive outcomes suggest that cognitive processing speed is persistently impaired following early brain damage, despite the existence of developmental plasticity. Although the nature of the relationship between diffuse WM injury and cognitive/behavioural deficits is complex and not entirely understood, the results of our first study suggest that WM abnormalities are related with worse Performance IQ scores and slower processing speed. So, we can affirm that diffuse WM loss in preterm children plays an important role in long-term cognitive impairment. Our second study focussed on the investigation of preterm children with a low risk either of neurological deficit or of developmental difficulties. While the neurodevelopmental and cognitive outcome of high-risk preterm samples is well known, little research has been conducted into low-risk preterms, such as those born between 30-34 weeks of GA, with uncomplicated perinatal histories, normal cranial ultrasound scans and no obvious neurodevelopmental deficits. To our knowledge, this is the first study to investigate the brain volume characteristics of a low-risk preterm sample in childhood using an MRI approach and the first attempt to relate these measures to cognitive performance. This study demonstrated that low-risk preterm children are characterized by the presence of regional cortical GM volume reductions in the parietal and temporal lobes which correlate strongly with IQ. Moreover, preterm children also showed WM volume reductions that were concomitant with the GM loss in the parietal and temporal regions compared to full-terms.In summary, the body of results derived from this thesis provides evidence that preterm birth is associated with brain abnormalities and cognitive impairment in middle childhood and adolescence. Future studies are required to assess the impact of cognitive and behavioural function in middle childhood on later outcomes in preterm samples with low risk of neurodevelopmental deficits.
Therapeutic aspects of c-MYC signaling in inflammatory and cancerous colonic diseases

Colonic inflammation is required to heal infections, wounds, and maintain tissue homeostasis. As the seventh hallmark of cancer, however, it may affect all phases of tumor development, including tumor initiation, promotion, invasion and metastatic dissemination, and also evasion immune surveillance. Inflammation acts as a cellular stressor and may trigger DNA damage or genetic instability, and, further, chronic inflammation can provoke genetic mutations and epigenetic mechanisms that promote malignant cell transformation. Both sporadical and colitis-associated colorectal carcinogenesis are multi-step, complex processes arising from the uncontrolled proliferation and spreading of malignantly transformed cell clones with the obvious ability to evade the host’s protective immunity. In cells upon DNA damage several proto-oncogenes, including c-MYC are activated in parelell with the inactivation of tumor suppressor genes. The target genes of the c-MYC protein participate in different cellular functions, including cell cycle, survival, protein synthesis, cell adhesion, and micro-RNA expression. The transcriptional program regulated by c-MYC is context dependent, therefore the final cellular response to elevated c-MYC levels may range from increased proliferation to augmented apoptosis. Considering physiological intestinal homeostasis, c-MYC displays a fundamental role in the regulation of cell proliferation and crypt cell number. However, c-MYC gene is frequently deregulated in inflammation, and overexpressed in both sporadic and colitis-associated colon adenocarcinomas. Recent results demonstrated that endogenous c-MYC is essential for efficient induction of p53-dependent apoptosis following DNA damage, but c-MYC function is also involved in and regulated by autophagy-related mechanisms, while its expression is affected by DNA-methylation, or histone acetylation. Molecules directly targeting c-MYC, or agents acting on other genes involved in the c-MYC pathway could be selected for combined regiments. However, due to its context-dependent cellular function, it is clinically essential to consider which cytotoxic drugs are used in combination with c-MYC targeted agents in various tissues. Increasing our knowledge about MYC-dependent pathways might provide direction to novel anti-inflammatory and colorectal cancer therapies.
Autoantibodies to phospholipid-binding plasma proteins: a new view of lupus anticoagulants and other "antiphospholipid" autoantibodies.

L UPUS ANTICOAGULANTS, and “antiphospholipid” autoantibodies in general, are of considerable clinical importance because of their strong association with thrombosis, recurrent fetal loss, and thrombocytopenia, ie, the “antiphospholipid” antibody syndrome. ’ This review focuses on recent evidence that “antiphospholipid” autoantibodies are not directed against anionic phospholipids, as has previously been thought, but are part of a larger group of autoantibodies against certain phospholipid-binding plasma proteins. At present, the most common and best characterized antigenic targets are &glycoprotein I (P2GPI)’-* and prothr~mbin. ~”~ Other phospholipid-binding proteins, particularly protein C and protein S,” may be important targets as well. Autoantibodies with these specificities differ from acquired coagulation factor inhibitors in that they preferentially bind antigens that are immobilized on anionic phospholipid membranes or certain synthetic surfaces. In most instances, antibody binding to the antigens in the fluid-phase is weak or nondetectable. Thus, such autoantibodies usually do not decrease plasma antigen levels. Although direct evidence for a pathophysiologic role of “antiphospholipid” autoantibodies is lacking, it is hypothesized that autoantibodies to phospholipid-binding proteins contribute directly to a thrombotic diathesis by interfering with hemostatic reactions that occur on anionic phospholipid membranes in vivo. Interestingly, the effect of autoantibodies on target antigen function may vary. For example, certain antibodies to P2GPI enhance its activity,””’ whereas antibodies to phospholipid-bound activated protein C are inhibitory. ” Taken together, these new observations explain much of the confusion regarding the laboratory tests used to detect “ antiphospholipid” antibodies and are providing key insights into the pathophysiology of the “antiphospholipid” antibody syndrome.
Characterization of HCV Interactions with Toll-Like Receptors and RIG-I in Liver Cells

Background and Aim The aim of this study was to examine the mechanisms of IFN induction and viral escape. In order to accomplish the goal we compared our new hepatoma cell line LH86, which has intact TLR3 and RIG-I expression and responds to HCV by inducing IFN, with Huh7.5 cells which lack those features. Methods The initial interaction of LH86 cells, Huh7.5 cells or their transfected counter parts (LH86 siRIG-I, siTLR3 or siTLR7 and Huh7.5 RIG-I, TLR3 or TLR7) after infection with HCV (strain JFH-1) was studied by measuring the expression levels of IFNβ, TRAIL, DR4, DR5 and their correlation to viral replication. Results HCV replicating RNA induces IFN in LH86 cells. The IFN induction system is functional in LH86, and the expression of the RIG-I and TLR3 in LH86 is comparable to the primary hepatocytes. Both proteins appear to play important roles in suppression of viral replication. We found that innate immunity against HCV is associated with the induction of apoptosis by RIG-I through the TRAIL pathway and the establishment of an antiviral state by TLR3. HCV envelope proteins interfere with the expression of TLR3 and RIG-I. Conclusion These findings correlate with the lower expression level of PRRs in HCV chronic patients and highlight the importance of the PRRs in the initial interaction of the virus and its host cells. This work represents a novel mechanism of viral pathogenesis for HCV and demonstrates the role of PRRs in viral infection.
Quality of life and psychiatric sequelae following aneurysmal subarachnoid haemorrhage: does neuroendocrine dysfunction play a role?

Objective Patients who have sustained aneurysmal subarachnoid haemorrhage (SAH) often suffer persistent impairments in their quality of life (QoL) and psychological disturbances despite a good neurological outcome. In the light of the high prevalence of partial hypopituitarism in SAH survivors demonstrated in recent investigations, we aimed to determine whether neuroendocrine dysfunction has an impact on QoL and neurobehavioural symptoms in these patients.
Space-time block codes versus space-time trellis codes

Two outstanding examples of transmit diversity schemes for the multiple-antenna flat-fading channel are space-time block coding (STBC) and space-time trellis coding (STTC). We compare the performance of STBC and STTC in terms of the frame error rate keeping the transmit power, spectral efficiency and number of trellis states fixed. We discover that a simple concatenation of space-time block codes with traditional AWGN (additive white Gaussian noise) trellis codes outperforms some of the best known space-time trellis codes at SNRs (signal to noise ratios) of interest. Our result holds for a small number of trellis states with one or two receive antennas, and is useful for the design and implementation of multiple-antenna wireless systems.
Physics-Based Person Tracking Using Simplified Lower-Body Dynamics

We introduce a physics-based model for 3D person tracking. Based on a biomechanical characterization of lower-body dynamics, the model captures important physical properties of bipedal locomotion such as balance and ground contact, generalizes naturally to variations in style due to changes in speed, step-length, and mass, and avoids common problems such as footskate that arise with existing trackers. The model dynamics comprises a two degree-of-freedom representation of human locomotion with inelastic ground contact. A stochastic controller generates impulsive forces during the toe-off stage of walking and spring-like forces between the legs. A higher-dimensional kinematic observation model is then conditioned on the underlying dynamics. We use the model for tracking walking people from video, including examples with turning, occlusion, and varying gait.
Mucosal Transcriptomics Implicates Under Expression of BRINP3 in the Pathogenesis of Ulcerative Colitis

Background:Mucosal abnormalities are potentially important in the primary pathogenesis of ulcerative colitis (UC). We investigated the mucosal transcriptomic expression profiles of biopsies from patients with UC and healthy controls, taken from macroscopically noninflamed tissue from the terminal ileum and 3 colonic locations with the objective of identifying abnormal molecules that might be involved in disease development. Methods:Whole-genome transcriptional analysis was performed on intestinal biopsies taken from 24 patients with UC, 26 healthy controls, and 14 patients with Crohn's disease. Differential gene expression analysis was performed at each tissue location separately, and results were then meta-analyzed. Significantly, differentially expressed genes were validated using quantitative polymerase chain reaction. The location of gene expression within the colon was determined using immunohistochemistry, subcellular fractionation, electron and confocal microscopy. DNA methylation was quantified by pyrosequencing. Results:Only 4 probes were abnormally expressed throughout the colon in patients with UC with Bone morphogenetic protein/Retinoic acid Inducible Neural-specific 3 (BRINP3) being the most significantly underexpressed. Attenuated expression of BRINP3 in UC was independent of current inflammation, unrelated to phenotype or treatment, and remained low at rebiopsy an average of 22 months later. BRINP3 is localized to the brush border of the colonic epithelium and expression is influenced by DNA methylation within its promoter. Conclusions:Genome-wide expression analysis of noninflamed mucosal biopsies from patients with UC identified BRINP3 as significantly underexpressed throughout the colon in a large subset of patients with UC. Low levels of this gene could predispose or contribute to the maintenance of the characteristic mucosal inflammation seen in this condition.
Calculus of Variations Equivariant gluing constructions of contact stationary

A contact-stationary Legendrian submanifold of S2n+1 is a Legendrian submanifold whose volume is stationary under contact deformations. The simplest contactstationary Legendrian submanifold (actually minimal Legendrian) is the real, equatorial n-sphere S0. This paper develops a method for constructing contact-stationary (but not minimal) Legendrian submanifolds of S2n+1 by gluing together configurations of sufficiently many U (n + 1)-rotated copies of S0. Two examples of the construction, corresponding to finite cyclic subgroups of U (n+1) are given. The resulting submanifolds are very symmetric; are geometrically akin to a ‘necklace’ of copies of S0 attached to each other by narrow necks and winding a large number of times around S2n+1 before closing up on themselves; and are topologically equivalent to S1 × Sn−1. Mathematics Subject Classification (2000) 58Jxx · 53Axx
Monetary Policy with a Wider Information Set: A Bayesian Model Averaging Approach

Monetary policy has been usually analyzed in the context of small macroeconomic models where central banks are allowed to exploit a limited amount of information. Under these frameworks, researchers typically derive the optimality of aggressive monetary rules, contrasting with the observed policy conservatism and interest rate smoothing. This paper allows the central bank to exploit a wider information set, while taking into account the associated model uncertainty, by employing Bayesian Model Averaging with Markov Chain Model Composition (MC³). In this enriched environment, we derive the optimality of smoother and more cautious policy rates, together with clear gains in macroeconomic efficiency.
Occurrence of Emerald Ash Borer (Coleoptera: Buprestidae) and Biotic Factors Affecting Its Immature Stages in the Russian Far East

ABSTRACT Field surveys were conducted from 2008 to 2011 in the Khabarovsk and Vladivostok regions of Russia to investigate the occurrence of emerald ash borer, Agrilus planipennis Fairmaire, and mortality factors affecting its immature stages. We found emerald ash borer infesting both introduced North American green ash (Fraxinus pennsylvanica Marshall) and native oriental ashes (F. mandshurica Rupr. and F. rhynchophylla Hance) in both regions. Emerald ash borer densities (larvae/m2 of phloem area) were markedly higher on green ash (11.3–76.7 in the Khabarovsk area and 77–245 in the Vladivostok area) than on artificially stressed Manchurian ash (2.2) or Oriental ash (10–59). Mortality of emerald ash borer larvae caused by different biotic factors (woodpecker predation, host plant resistance and/or undetermined diseases, and parasitism) varied with date, site, and ash species. In general, predation of emerald ash borer larvae by woodpeckers was low. While low rates (3–27%) of emerald ash borer larval mortality were caused by undetermined biotic factors on green ash between 2009 and 2011, higher rates (26–95%) of emerald ash borer larval mortality were caused by putative plant resistance in Oriental ash species in both regions. Little (<1%) parasitism of emerald ash borer larvae was observed in Khabarovsk; however, three hymenopteran parasitoids (Spathius sp., Atanycolus nigriventris Vojnovskaja-Krieger, and Tetrastichus planipennisi Yang) were observed attacking third - fourth instars of emerald ash borer in the Vladivostok area, parasitizing 0–8.3% of emerald ash borer larvae infesting Oriental ash trees and 7.3–62.7% of those on green ash trees (primarily by Spathius sp.) in two of the three study sites. Relevance of these findings to the classical biological control of emerald ash borer in newly invaded regions is discussed.