Inheritance through the cytoplasm

Most heritable information in eukaryotic cells is encoded in the nuclear genome, with inheritance patterns following classic Mendelian segregation. Genomes residing in the cytoplasm, however, prove to be a peculiar exception to this rule. Cytoplasmic genetic elements are generally maternally inherited, although there are several exceptions where these are paternally, biparentally or doubly-uniparentally inherited. In this review, we examine the diversity and peculiarities of cytoplasmically inherited genomes, and the broad evolutionary consequences that non-Mendelian inheritance brings. We first explore the origins of vertical transmission and uniparental inheritance, before detailing the vast diversity of cytoplasmic inheritance systems across Eukaryota. We then describe the evolution of genomic organisation across lineages, how this process has been shaped by interactions with the nuclear genome and population genetics dynamics. Finally, we discuss how both nuclear and cytoplasmic genomes have evolved to co-inhabit the same host cell via one of the longest symbiotic processes, and all the opportunities for intergenomic conflict that arise due to divergence in inheritance patterns. In sum, we cannot understand the evolution of eukaryotes without understanding hereditary symbiosis

The Perceptions on Male Circumcision as a Preventive Measure Against HIV Infection and Considerations in Scaling up of the Services: A Qualitative Study Among Police Officers in Dar es Salaam, Tanzania.

\ud In recent randomized controlled trials, male circumcision has been proven to complement the available biomedical interventions in decreasing HIV transmission from infected women to uninfected men. Consequently, Tanzania is striving to scale-up safe medical male circumcision to reduce HIV transmission. However, there is a need to investigate the perceptions of male circumcision in Tanzania using specific populations. The purpose of the present study was to assess the perceptions of male circumcision in a cohort of police officers that also served as a source of volunteers for a phase I/II HIV vaccine (HIVIS-03) trial in Dar es Salaam, Tanzania. In-depth interviews with 24 men and 10 women were conducted. Content analysis informed by the socio-ecological model was used to analyze the data. Informants perceived male circumcision as a health-promoting practice that may prevent HIV transmission and other sexually transmitted infections. They reported male circumcision promotes sexual pleasure, confidence and hygiene or sexual cleanliness. They added that it is a religious ritual and a cultural practice that enhances the recognition of manhood in the community. However, informants were concerned about the cost involved in male circumcision and cleanliness of instruments used in medical and traditional male circumcision. They also expressed confusion about the shame of undergoing circumcision at an advanced age and pain that could emanate after circumcision. The participants advocated for health policies that promote medical male circumcision at childhood, specifically along with the vaccination program. The perceived benefit of male circumcision as a preventive strategy to HIV and other sexually transmitted infections is important. However, there is a need to ensure that male circumcision is conducted under hygienic conditions. Integrating male circumcision service in the routine childhood vaccination program may increase its coverage at early childhood. The findings from this investigation provide contextual understanding that may assist in scaling-up male circumcision in Tanzania.\u

Phantom evaluation of a cardiac SPECT/VCT system that uses a common set of solid-state detectors for both emission and transmission scans

We developed a cardiac SPECT system (X-ACT) with low dose volume CT transmission-based attenuation correction (AC). Three solid-state detectors are configured to form a triple-head system for emission scans and reconfigured to form a 69-cm field-of-view detector arc for transmission scans. A near mono-energetic transmission line source is produced from the collimated fluorescence x-ray emitted from a lead target when the target is illuminated by a narrow polychromatic x-ray beam from an x-ray tube. Transmission scans can be completed in 1 min with insignificant patient dose (deep dose equivalent <5 μSv). We used phantom studies to evaluate (1) the accuracy of the reconstructed attenuation maps, (2) the effect of AC on image uniformity, and (3) the effect of AC on defect contrast (DC). The phantoms we used included an ACR phantom, an anthropomorphic phantom with a uniform cardiac insert, and an anthropomorphic phantom with two defects in the cardiac insert. The reconstructed attenuation coefficient of water at 140 keV was .150 ± .003/cm in the uniform region of the ACR phantom, .151 ± .003/cm and .151 ± .002/cm in the liver and cardiac regions of the anthropomorphic phantom. The ACR phantom images with AC showed correction of the bowing effect due to attenuation in the images without AC (NC). The 17-segment scores of the images of the uniform cardiac insert were 78.3 ± 6.5 before and 87.9 ± 3.3 after AC (average ± standard deviation). The inferior-to-anterior wall ratio and the septal-to-lateral wall ratio were .99 and 1.16 before and 1.02 and 1.00 after AC. The DC of the two defects was .528 and .156 before and .628 and .173 after AC. The X-ACT system generated accurate attenuation maps with 1-minute transmission scans. AC improved image quality and uniformity over NC

Cytoplasmic Polyadenylation Element Binding Protein Deficiency Stimulates PTEN and Stat3 mRNA Translation and Induces Hepatic Insulin Resistance

The cytoplasmic polyadenylation element binding protein CPEB1 (CPEB) regulates germ cell development, synaptic plasticity, and cellular senescence. A microarray analysis of mRNAs regulated by CPEB unexpectedly showed that several encoded proteins are involved in insulin signaling. An investigation of Cpeb1 knockout mice revealed that the expression of two particular negative regulators of insulin action, PTEN and Stat3, were aberrantly increased. Insulin signaling to Akt was attenuated in livers of CPEB–deficient mice, suggesting that they might be defective in regulating glucose homeostasis. Indeed, when the Cpeb1 knockout mice were fed a high-fat diet, their livers became insulin-resistant. Analysis of HepG2 cells, a human liver cell line, depleted of CPEB demonstrated that this protein directly regulates the translation of PTEN and Stat3 mRNAs. Our results show that CPEB regulated translation is a key process involved in insulin signaling

Boron microlocalization in oral mucosal tissue: implications for boron neutron capture therapy

Clinical studies of the treatment of glioma and cutaneous melanoma using boron neutron capture therapy (BNCT) are currently taking place in the USA, Europe and Japan. New BNCT clinical facilities are under construction in Finland, Sweden, England and California. The observation of transient acute effects in the oral mucosa of a number of glioma patients involved in the American clinical trials, suggests that radiation damage of the oral mucosa could be a potential complication in future BNCT clinical protocols, involving higher doses and larger irradiation field sizes. The present investigation is the first to use a high resolution surface analytical technique to relate the microdistribution of boron-10 (10B) in the oral mucosa to the biological effectiveness of the 10B(n,α)7Li neutron capture reaction in this tissue. The two boron delivery agents used clinically in Europe/Japan and the USA, borocaptate sodium (BSH) and p-boronophenylalanine (BPA), respectively, were evaluated using a rat ventral tongue model. 10B concentrations in various regions of the tongue mucosa were estimated using ion microscopy. In the epithelium, levels of 10B were appreciably lower after the administration of BSH than was the case after BPA. The epithelium:blood 10B partition ratios were 0.2:1 and 1:1 for BSH and BPA respectively. The 10B content of the lamina propria was higher than that measured in the epithelium for both BSH and BPA. The difference was most marked for BSH, where 10B levels were a factor of six higher in the lamina propria than in the epithelium. The concentration of 10B was also measured in blood vessel walls where relatively low levels of accumulation of BSH, as compared with BPA, was demonstrated in blood vessel endothelial cells and muscle. Vessel wall:blood 10B partition ratios were 0.3:1 and 0.9:1 for BSH and BPA respectively. Evaluation of tongue mucosal response (ulceration) to BNC irradiation indicated a considerably reduced radiation sensitivity using BSH as the boron delivery agent relative to BPA. The compound biological effectiveness (CBE) factor for BSH was estimated at 0.29 ± 0.02. This compares with a previously published CBE factor for BPA of 4.87 ± 0.16. It was concluded that variations in the microdistribution profile of 10B, using the two boron delivery agents, had a significant effect on the response of oral mucosa to BNC irradiation. From a clinical perspective, based on the findings of the present study, it is probable that potential radiation-induced oral mucositis will be restricted to BNCT protocols involving BPA. However, a thorough high resolution analysis of 10B microdistribution in human oral mucosal tissue, using a technique such as ion microscopy, is a prerequisite for the use of experimentally derived CBE factors in clinical BNCT. © 2000 Cancer Research Campaig

Solid state quantum memory using the 31P nuclear spin

The transfer of information between different physical forms is a central theme in communication and computation, for example between processing entities and memory. Nowhere is this more crucial than in quantum computation, where great effort must be taken to protect the integrity of a fragile quantum bit. Nuclear spins are known to benefit from long coherence times compared to electron spins, but are slow to manipulate and suffer from weak thermal polarisation. A powerful model for quantum computation is thus one in which electron spins are used for processing and readout while nuclear spins are used for storage. Here we demonstrate the coherent transfer of a superposition state in an electron spin 'processing' qubit to a nuclear spin 'memory' qubit, using a combination of microwave and radiofrequency pulses applied to 31P donors in an isotopically pure 28Si crystal. The electron spin state can be stored in the nuclear spin on a timescale that is long compared with the electron decoherence time and then coherently transferred back to the electron spin, thus demonstrating the 31P nuclear spin as a solid-state quantum memory. The overall store/readout fidelity is about 90%, attributed to systematic imperfections in radiofrequency pulses which can be improved through the use of composite pulses. We apply dynamic decoupling to protect the nuclear spin quantum memory element from sources of decoherence. The coherence lifetime of the quantum memory element is found to exceed one second at 5.5K.Comment: v2: Tomography added and storage of general initial state

The influence of expectation on spinal manipulation induced hypoalgesia: An experimental study in normal subjects

<p>Abstract</p> <p>Background</p> <p>The mechanisms thorough which spinal manipulative therapy (SMT) exerts clinical effects are not established. A prior study has suggested a dorsal horn modulated effect; however, the role of subject expectation was not considered. The purpose of the current study was to determine the effect of subject expectation on hypoalgesia associated with SMT.</p> <p>Methods</p> <p>Sixty healthy subjects agreed to participate and underwent quantitative sensory testing (QST) to their leg and low back. Next, participants were randomly assigned to receive a positive, negative, or neutral expectation instructional set regarding the effects of a specific SMT technique on pain perception. Following the instructional set, all subjects received SMT and underwent repeat QST.</p> <p>Results</p> <p>No interaction (p = 0.38) between group assignment and pain response was present in the lower extremity following SMT; however, a main effect (p < 0.01) for hypoalgesia was present. A significant interaction was present between change in pain perception and group assignment in the low back (p = 0.01) with participants receiving a negative expectation instructional set demonstrating significant hyperalgesia (p < 0.01).</p> <p>Conclusion</p> <p>The current study replicates prior findings of c- fiber mediated hypoalgesia in the lower extremity following SMT and this occurred regardless of expectation. A significant increase in pain perception occurred following SMT in the low back of participants receiving negative expectation suggesting a potential influence of expectation on SMT induced hypoalgesia in the body area to which the expectation is directed.</p

Stress-Induced C/EBP Homology Protein (CHOP) Represses MyoD Transcription to Delay Myoblast Differentiation

When mouse myoblasts or satellite cells differentiate in culture, the expression of myogenic regulatory factor, MyoD, is downregulated in a subset of cells that do not differentiate. The mechanism involved in the repression of MyoD expression remains largely unknown. Here we report that a stress-response pathway repressing MyoD transcription is transiently activated in mouse-derived C2C12 myoblasts growing under differentiation-promoting conditions. We show that phosphorylation of the α subunit of the translation initiation factor 2 (eIF2α) is followed by expression of C/EBP homology protein (CHOP) in some myoblasts. ShRNA-driven knockdown of CHOP expression caused earlier and more robust differentiation, whereas its constitutive expression delayed differentiation relative to wild type myoblasts. Cells expressing CHOP did not express the myogenic regulatory factors MyoD and myogenin. These results indicated that CHOP directly repressed the transcription of the MyoD gene. In support of this view, CHOP associated with upstream regulatory region of the MyoD gene and its activity reduced histone acetylation at the enhancer region of MyoD. CHOP interacted with histone deacetylase 1 (HDAC1) in cells. This protein complex may reduce histone acetylation when bound to MyoD regulatory regions. Overall, our results suggest that the activation of a stress pathway in myoblasts transiently downregulate the myogenic program

Toward a Comprehensive Approach to the Collection and Analysis of Pica Substances, with Emphasis on Geophagic Materials

Pica, the craving and subsequent consumption of non-food substances such as earth, charcoal, and raw starch, has been an enigma for more than 2000 years. Currently, there are little available data for testing major hypotheses about pica because of methodological limitations and lack of attention to the problem.In this paper we critically review procedures and guidelines for interviews and sample collection that are appropriate for a wide variety of pica substances. In addition, we outline methodologies for the physical, mineralogical, and chemical characterization of these substances, with particular focus on geophagic soils and clays. Many of these methods are standard procedures in anthropological, soil, or nutritional sciences, but have rarely or never been applied to the study of pica.Physical properties of geophagic materials including color, particle size distribution, consistency and dispersion/flocculation (coagulation) should be assessed by appropriate methods. Quantitative mineralogical analyses by X-ray diffraction should be made on bulk material as well as on separated clay fractions, and the various clay minerals should be characterized by a variety of supplementary tests. Concentrations of minerals should be determined using X-ray fluorescence for non-food substances and inductively coupled plasma-atomic emission spectroscopy for food-like substances. pH, salt content, cation exchange capacity, organic carbon content and labile forms of iron oxide should also be determined. Finally, analyses relating to biological interactions are recommended, including determination of the bioavailability of nutrients and other bioactive components from pica substances, as well as their detoxification capacities and parasitological profiles.This is the first review of appropriate methodologies for the study of human pica. The comprehensive and multi-disciplinary approach to the collection and analysis of pica substances detailed here is a necessary preliminary step to understanding the nutritional enigma of non-food consumption