Damaged DNA-binding protein 2 (DDB2) protects against UV irradiation in human cells and Drosophila

<p>Abstract</p> <p>Background</p> <p>We observed previously that cisplatin-resistant HeLa cells were cross-resistant to UV light due to accumulation of DDB2, a protein implicated in DNA repair. More recently, we found that cFLIP, which represents an anti-apoptotic protein whose level is induced by DDB2, was implicated in preventing apoptosis induced by death-receptor signaling. In the present study, we investigated whether DDB2 has a protective role against UV irradiation and whether cFLIP is also involved in this process.</p> <p>Methods</p> <p>We explored the role of DDB2 in mediating UV resistance in both human cells and Drosophila. To do so, DDB2 was overexpressed by using a full-length open reading frame cDNA. Conversely, DDB2 and cFLIP were suppressed by using antisense oligonucleotides. Cell survival was measured using a colony forming assay. Apoptosis was monitored by examination of nuclear morphology, as well as by flow cytometry and Western blot analyses. A transcription reporter assay was also used to assess transcription of cFLIP.</p> <p>Results</p> <p>We first observed that the cFLIP protein was upregulated in UV-resistant HeLa cells. In addition, the cFLIP protein could be induced by stable expression of DDB2 in these cells. Notably, the anti-apoptotic effect of DDB2 against UV irradiation was largely attenuated by knockdown of cFLIP with antisense oligonucleotides in HeLa cells. Moreover, overexpression of DDB2 did not protect against UV in VA13 and XP-A cell lines which both lack cFLIP. Interestingly, ectopic expression of human DDB2 in <it>Drosophila </it>dramatically inhibited UV-induced fly death compared to control GFP expression. On the other hand, expression of DDB2 failed to rescue a different type of apoptosis induced by the genes <it>Reaper </it>or <it>eiger</it>.</p> <p>Conclusion</p> <p>Our results show that DDB2 protects against UV stress in a cFLIP-dependent manner. In addition, the protective role of DDB2 against UV irradiation was found to be conserved in divergent living organisms such as human and <it>Drosophila</it>. In addition, UV irradiation may activate a cFLIP-regulated apoptotic pathway in certain cells.</p

Neurological abnormalities and neurocognitive functions in healthy elder people: A structural equation modeling analysis

Background/Aims: Neurological abnormalities have been reported in normal aging population. However, most of them were limited to extrapyramidal signs and soft signs such as motor coordination and sensory integration have received much less attention. Very little is known about the relationship between neurological soft signs and neurocognitive function in healthy elder people. The current study aimed to examine the underlying relationships between neurological soft signs and neurocognition in a group of healthy elderly

Evidence in cortical folding patterns for prenatal predispositions to hallucinations in schizophrenia.

All perception is a construction of the brain from sensory input. Our first perceptions begin during gestation, making fetal brain development fundamental to how we experience a diverse world. Hallucinations are percepts without origin in physical reality that occur in health and disease. Despite longstanding research on the brain structures supporting hallucinations and on perinatal contributions to the pathophysiology of schizophrenia, what links these two distinct lines of research remains unclear. Sulcal patterns derived from structural magnetic resonance (MR) images can provide a proxy in adulthood for early brain development. We studied two independent datasets of patients with schizophrenia who underwent clinical assessment and 3T MR imaging from the United Kingdom and Shanghai, China (n = 181 combined) and 63 healthy controls from Shanghai. Participants were stratified into those with (n = 79 UK; n = 22 Shanghai) and without (n = 43 UK; n = 37 Shanghai) hallucinations from the PANSS P3 scores for hallucinatory behaviour. We quantified the length, depth, and asymmetry indices of the paracingulate and superior temporal sulci (PCS, STS), which have previously been associated with hallucinations in schizophrenia, and constructed cortical folding covariance matrices organized by large-scale functional networks. In both ethnic groups, we demonstrated a significantly shorter left PCS in patients with hallucinations compared to those without, and to healthy controls. Reduced PCS length and STS depth corresponded to focal deviations in their geometry and to significantly increased covariance within and between areas of the salience and auditory networks. The discovery of neurodevelopmental alterations contributing to hallucinations establishes testable models for these enigmatic, sometimes highly distressing, perceptions and provides mechanistic insight into the pathological consequences of prenatal origins

On-demand semiconductor single-photon source with near-unity indistinguishability

Single photon sources based on semiconductor quantum dots offer distinct advantages for quantum information, including a scalable solid-state platform, ultrabrightness, and interconnectivity with matter qubits. A key prerequisite for their use in optical quantum computing and solid-state networks is a high level of efficiency and indistinguishability. Pulsed resonance fluorescence (RF) has been anticipated as the optimum condition for the deterministic generation of high-quality photons with vanishing effects of dephasing. Here, we generate pulsed RF single photons on demand from a single, microcavity-embedded quantum dot under s-shell excitation with 3-ps laser pulses. The pi-pulse excited RF photons have less than 0.3% background contributions and a vanishing two-photon emission probability. Non-postselective Hong-Ou-Mandel interference between two successively emitted photons is observed with a visibility of 0.97(2), comparable to trapped atoms and ions. Two single photons are further used to implement a high-fidelity quantum controlled-NOT gate.Comment: 11 pages, 11 figure

Umbilical hernia rupture with evisceration of omentum from massive ascites: a case report

<p>Abstract</p> <p>Introduction</p> <p>The incidence of hernias is increased in patients with alcoholic liver disease with ascites. To the best of our knowledge, this is the first report of an acute rise in intra-abdominal pressure from straining for stool as the cause of a ruptured umbilical hernia.</p> <p>Case presentation</p> <p>An 81-year-old Caucasian man with a history of alcoholic liver disease presented to our emergency department with an erythematous umbilical hernia and clear, yellow discharge from the umbilicus. On straining for stool, after initial clinical assessment, our patient noted a gush of fluid and evisceration of omentum from the umbilical hernia. An urgent laparotomy was performed with excision of the umbilicus and devitalized omentum.</p> <p>Conclusion</p> <p>We report the case of a patient with a history of alcoholic liver disease with ascites. Ascites causes a chronic increase in intra-abdominal pressure. A sudden increase in intra-abdominal pressure, such as coughing, vomiting, gastroscopy or, as in this case, straining for stool can cause rupture of an umbilical hernia. The presence of discoloration, ulceration or a rapid increase in size of the umbilical hernia signals impending rupture and should prompt the physician to reduce the intra-abdominal pressure.</p

Improving motivation through real-time fMRI-based self-regulation of the nucleus accumbens.

OBJECTIVE: Impaired nucleus accumbens (NAcc) activation is associated with amotivation and anhedonia, which are resistant to treatment with antipsychotics and antidepressants in schizophrenia. In this study, healthy participants were trained to self-regulate the activation of their NAcc, a brain region that plays an important role in motivation, using real-time functional magnetic resonance imaging (fMRI) neurofeedback. METHOD: The experimental group (N = 19) received feedback from the NAcc, whereas the control group (N = 5) received "sham" feedback from the posterior parahippocampal gyrus, a control brain region not normally related to motivation. All participants were trained to use mental strategies to regulate their NAcc activations in a 3T MRI scanner. RESULTS: For the learning effect of NAcc regulation, we found that the majority of participants (74%) in the experimental group successfully learned to self-regulate the NAcc. They also showed improved behavioral performance in motivation and decreased functional connectivity between the NAcc and the ventral medial prefrontal cortex and an increase in small-world properties in the reward circuit after training, indicating improved information integration in reward processing. However, improvement in motivation and modification of function connectivity were not observed in the sham control group and the participants who failed to self-regulate the NAcc in the experimental group. Self-regulation was influenced by the baseline motivation. CONCLUSIONS: These findings suggest that the NAcc could be self-regulated using real-time fMRI neurofeedback and can result in improved motivation in cognitive tasks. (PsycINFO Database Recor

Distribution of HLA-A, -B and -DRB1 Genes and Haplotypes in the Tujia Population Living in the Wufeng Region of Hubei Province, China

BACKGROUND: The distribution of HLA alleles and haplotypes varies widely between different ethnic populations and geographic areas. Before any genetic marker can be used in a disease-associated study it is therefore essential to investigate allelic frequencies and establish a genetic database. METHODOLOGY/PRINCIPAL FINDINGS: This is the first report of HLA typing in the Tujia group using the Luminex HLA-SSO method HLA-A, -B and -DRB1 allelic distributions were determined in 124 unrelated healthy Tujia individuals, and haplotypic frequencies and linkage disequilibrium parameters were estimated using the maximum-likelihood method. In total 10 alleles were detected at the HLA-A locus, 21 alleles at the HLA-B locus and 14 alleles at the HLA-DRB1 locus. The most frequently observed alleles in the HLA-I group were HLA-A*02 (35.48%), A*11 (28.23%), A*24 (15.73%); HLA-B*40 (25.00%), B*46 (16.13%), and B*15 (15.73%). Among HLA-DRB1 alleles, high frequencies of HLA-DRB1*09 (25.81%) were observed, followed by HLA-DRB1*15 (12.9%), and DRB1*12 (10.89%). The two-locus haplotypes at the highest frequency were A*02-B*46A (8.47%), followed by A*11-B*40 (7.66%), A*02-B*40 (8.87%), A*11-B*15 (6.45%), A*02-B*15 (6.05%), B*40-DRB1*09 (9.27%) and B*46-DRB1*09 (6.45%). The most common three-locus haplotypes found in the Tujia population were A*02-B*46-DRB1*09 (4.84%) and A*02-B*40-DRB1*09 (4.03%). Fourteen two-loci haplotypes had significant linkage disequilibrium. Construction of a neighbor-joining phylogenetic tree and principal component analysis using the allelic frequencies at HLA-A was performed to compare the Tujia group and twelve other previously reported populations. The Tujia population in the Wufeng of Hubei Province had the closest genetic relationship with the central Han population, and then to the Shui, the Miao, the southern Han and the northern Han ethnic groups. CONCLUSIONS/SIGNIFICANCE: These results will become a valuable source of data for tracing population migration, planning clinical organ transplantation, carrying out HLA-linked disease-associated studies and forensic identification

The Pioneer Anomaly

Radio-metric Doppler tracking data received from the Pioneer 10 and 11 spacecraft from heliocentric distances of 20-70 AU has consistently indicated the presence of a small, anomalous, blue-shifted frequency drift uniformly changing with a rate of ~6 x 10^{-9} Hz/s. Ultimately, the drift was interpreted as a constant sunward deceleration of each particular spacecraft at the level of a_P = (8.74 +/- 1.33) x 10^{-10} m/s^2. This apparent violation of the Newton's gravitational inverse-square law has become known as the Pioneer anomaly; the nature of this anomaly remains unexplained. In this review, we summarize the current knowledge of the physical properties of the anomaly and the conditions that led to its detection and characterization. We review various mechanisms proposed to explain the anomaly and discuss the current state of efforts to determine its nature. A comprehensive new investigation of the anomalous behavior of the two Pioneers has begun recently. The new efforts rely on the much-extended set of radio-metric Doppler data for both spacecraft in conjunction with the newly available complete record of their telemetry files and a large archive of original project documentation. As the new study is yet to report its findings, this review provides the necessary background for the new results to appear in the near future. In particular, we provide a significant amount of information on the design, operations and behavior of the two Pioneers during their entire missions, including descriptions of various data formats and techniques used for their navigation and radio-science data analysis. As most of this information was recovered relatively recently, it was not used in the previous studies of the Pioneer anomaly, but it is critical for the new investigation.Comment: 165 pages, 40 figures, 16 tables; accepted for publication in Living Reviews in Relativit

Search for rare quark-annihilation decays, B --> Ds(*) Phi

We report on searches for B- --> Ds- Phi and B- --> Ds*- Phi. In the context of the Standard Model, these decays are expected to be highly suppressed since they proceed through annihilation of the b and u-bar quarks in the B- meson. Our results are based on 234 million Upsilon(4S) --> B Bbar decays collected with the BABAR detector at SLAC. We find no evidence for these decays, and we set Bayesian 90% confidence level upper limits on the branching fractions BF(B- --> Ds- Phi) Ds*- Phi)<1.2x10^(-5). These results are consistent with Standard Model expectations.Comment: 8 pages, 3 postscript figues, submitted to Phys. Rev. D (Rapid Communications