Localization of HIV-1 RNA in mammalian nuclei

The Rev protein of human immunodeficiency virus type 1 (HIV-1) facilitates the nuclear export of unspliced and partially spliced viral RNAs. In the absence of Rev, these intron-containing HIV-1 RNAs are retained in the nucleus. The basis for nuclear retention is unclear and is an important aspect of Rev regulation. Here we use in situ hybridization and digital imaging microscopy to examine the intranuclear distributions of intron-containing HIV RNAs and to determine their spatial relationships to intranuclear structures. HeLa cells were transfected with an HIV-1 expression vector, and viral transcripts were localized using oligonucleotide probes specific for the unspliced or spliced forms of a particular viral RNA. In the absence of Rev, the unspliced viral RNAs were predominantly nuclear and had two distinct distributions. First, a population of viral transcripts was distributed as approximately 10-20 intranuclear punctate signals. Actinomycin D chase experiments indicate that these signals represent nascent transcripts. A second, stable population of viral transcripts was dispersed throughout the nucleoplasm excluding nucleoli. Rev promoted the export of this stable population of viral RNAs to the cytoplasm in a time-dependent fashion. Significantly, the distributions of neither the nascent nor the stable populations of viral RNAs coincided with intranuclear speckles in which splicing factors are enriched. Using splice-junction-specific probes, splicing of human beta-globin pre-mRNA occurred cotranscriptionally, whereas splicing of HIV-1 pre-mRNA did not. Taken together, our results indicate that the nucleolus and intranuclear speckles are not involved in Rev regulation, and provide further evidence that efficient splicing signals are critical for cotranscriptional splicing

Middle-Late Jurassic magmatism in the west central Lhasa subterrane, Tibet: Petrology, zircon chronology, elemental and Sr-Nd-Pb-Hf-Mg isotopic geochemistry

Mesozoic magmatic rocks are widespread in the Lhasa terrane, but most of them are of cretaceous age. Because Jurassic rocks are relatively rare and our knowledge on such earlier magmatism in the context of the tectonic setting and evolution is limited. In this study, we focus on the mid-late Jurassic granitoids that occur in the west central Lhasa subterrane. We present the results of a systematic study of these granitoid rocks of tonalite composition together with the hosted mafic magmatic enclaves. We dated 4 representative tonalite samples and 2 enclaves using zircon U-Pb method that gives the age range of 167–154 Ma. All these samples have Sr-Nd-Pb isotopic compositions (87Sr/86Sr = 0.713941–0.718417, εNd(t) = −14 to −9.8, 206Pb/204Pb = 18.806–18.936, 207Pb/204Pb = 15.739–15.764, 208Pb/204Pb = 39.257–39.798) similar to the composition of gneisses from the basement of the Lhasa terrane, suggesting that magmas parental to these mid-late Jurassic granitoids of tonalitic composition are of largely crustal origin, which is also supported by the petrographic observations. Both of the tonalite samples and the mafic enclaves have a wide span of zircon εHf(t) of −15.9 to −0.2 and − 13.8 to −7.4, respectively. These samples also show varying δ26Mg ranging from −0.40 to −0.18, with an average δ26Mg = −0.27 ± 0.06‰ (2SD) that is best understood as representing the Mg composition of the continental crust of the Lhasa terrane. All these observations allow us to conclude that basaltic melts derived from metasomatized mantle were involved in the petrogenesis of these granitoids. Specifically, southward subduction of the Bangong-Nujiang Ocean lithosphere and subsequent slab rollback metasomatized the mantle wedge and the lithospheric mantle above, whose melting produced basaltic magmas. Underplating and intrusion of these basaltic magmas caused crustal melting and generation of granitoid magmas parental to the tonalite and enclaves we study

PCB Design for EMC Testing

With technology speeding up, electronic circuits are widely used in different applications, such as communication, computation, automation. Circuitry is getting smaller in physical size which increases the chance of EMI problems. Devices maybe compromised polluting nearby equipment and environment. The goal of the thesis was to study and observe two versions of self-designed printed circuit board (PCB) by EMC testing. PCB No.1 was designed as the best by following EMC rules while PCB No.2 as the worst. Two similar schematics were given by the senior lecturer. The project was divided into three parts to be carried out. The first part was familiarizing with theoretical background. The second part was implementation. When implementing, design was mainly accomplished using PADS provided by Mentor Graphics. PCB were manufactured using milling machine LPKF ProtoMat S62. In the second part, procedure was repeat multiple times because of components issue. The final part was to test and analyze. When analyzing, comparison graphs were created and studied. The objective of the project was completed successfully. Two PCB were fully functional and tested. All relevant reports for PCB are attached into the thesis

Synthesis and preliminary structure-activity relationship study of 3-methylquinazolinone derivatives as EGFR inhibitors with enhanced antiproliferative activities against tumour cells

In this paper, a set of 3-methylquniazolinone derivatives were designed, synthesised, and studied the preliminary structure-activity relationship for antiproliferative activities. All target compounds performed significantly inhibitory effects against wild type epidermal growth factor receptor tyrosine kinase (EGFRwt-TK) and tumour cells (A431, A549, MCF-7, and NCI-H1975). In particular, compound 4d 3-fluoro-N-(4-((3-methyl-4-oxo-3,4-dihydroquinazolin-2-yl)methoxy)phenyl)benzamide showed higher antiproliferative activities against all tumour cells than Gefitinib (IC50 of 3.48, 2.55, 0.87 and 6.42 μM, respectively). Furthermore, compound 4d could induce apoptosis of MCF-7 cells and arrest in G2/M phase at the tested concentration. Molecular docking and ADMET studies showed that compound 4d could closely form many hydrogen bonds with EGFRwt-TK. Therefore, compound 4d is potential to develop as novel anti-cancer drug

Six-year removal of co-dominant grasses alleviated competitive pressure on subdominant grasses but dominant shrub removal had neutral effects in a subalpine ecosystem

The ‘stress-gradient hypothesis’ predicts increasing facilitative interactions with increasing environmental stress, but it remains unclear if the prevailing type of interaction (i.e. facilitative or competitive) between dominant and subordinate plant species occurring in harsh environments is dependent on the plant functional type. In addition, most plant-species removal experiments in grasslands are short-term (1–2 years), which may imprecisely reflect transient effects arising from methodological limitations. We conducted a dominant species removal experiment in a subalpine ecosystem, containing a mosaic of grass-dominated and shrub-dominated community patches, both of which are common in the subalpine zone of the Qinghai-Tibetan Plateau. We examined the direction and magnitude of the effects of three co-dominant grass and a dominant shrub species on subordinate species richness and biomass over a 6-year period. Removal of the dominant grass species alleviated their competitive pressure on subdominant grasses, which resulted in similar total and grass biomass detected in the final year of the study. By contrast, shrub removal showed no effects on its subordinate species biomass. Furthermore, neither the removal of the dominant shrubs nor the grasses altered their respective subordinate species richness. Thus, in subalpine ecosystems that experience harsh environmental conditions, our results showed that the direction of interactive effects of dominant plant species on subordinate species may be dependent on the plant functional type and are not necessarily facilitative. Furthermore, we showed that longer-term plant-removal experiment observations may be required to better determine the effects of species removal for this subalpine and other montane ecosystem(s).Published versio

Men and women differ in the neural basis of handwriting

There is an ongoing debate about whether, and to what extent, males differ from females in their language skills. In the case of handwriting, a composite language skill involving language and motor processes, behavioral observations consistently show robust sex differences but the mechanisms underlying the effect are unclear. Using functional magnetic resonance imaging (fMRI) in a copying task, the present study examined the neural basis of sex differences in handwriting in 53 healthy adults (ages 19-28, 27 males). Compared to females, males showed increased activation in the left posterior middle frontal gyrus (Exner's area), a region thought to support the conversion between orthographic and graphomotor codes. Functional connectivity between Exner's area and the right cerebellum was greater in males than in females. Furthermore, sex differences in brain activity related to handwriting were independent of language material. This study identifies a novel neural signature of sex differences in a hallmark of human behavior, and highlights the importance of considering sex as a factor in scientific research and clinical applications involving handwriting