Comparative and functional analysis of intron-mediated enhancement signals reveals conserved features among plants

Introns in a wide range of organisms including plants, animals and fungi are able to increase the expression of the gene that they are contained in. This process of intron-mediated enhancement (IME) is most thoroughly studied in Arabidopsis thaliana, where it has been shown that enhancing introns are typically located near the promoter and are compositionally distinct from downstream introns. In this study, we perform a comprehensive comparative analysis of several sequenced plant genomes. We find that enhancing sequences are conserved in the multi-cellular plants but are either absent or unrecognizable in algae. IME signals are preferentially located towards the 5′-end of first introns but also appear to be enriched in 5′-UTRs and coding regions near the transcription start site. Enhancing introns are found most prominently in genes that are highly expressed in a wide range of tissues. Through site-directed mutagenesis in A. thaliana, we show that IME signals can be inserted or removed from introns to increase or decrease gene expression. Although we do not yet know the specific mechanism of IME, the predicted signals appear to be both functional and highly conserved

Detection of defects using spatial variances of guided wave modes in testing of pipes

In the past decade, guided-wave testing has attracted the attention of the non-destructive testing industry for pipeline inspections. This technology enables the long-range assessment of pipelines’ integrity, which significantly reduces the expenditure of testing in terms of cost and time. Guided-wave testing collars consist of several linearly placed arrays of transducers around the circumference of the pipe, which are called rings, and can generate unidirectional axisymmetric elastic waves. The current propagation routine of the device generates a single time-domain signal by doing a phase-delayed summation of each array element. The segments where the energy of the signal is above the local noise region are reported as anomalies by the inspectors. Nonetheless, the main goal of guided-wave inspection is the detection of axisymmetric waves generated by the features within the pipes. In this paper, instead of processing a single signal obtained from the general propagation routine, we propose to process signals that are directly obtained from all of the array elements. We designed an axisymmetric wave detection algorithm, which is validated by laboratory trials on real-pipe data with two defects on different locations with varying cross-sectional area (CSA) sizes of 2% and 3% for the first defect, and 4% and 5% for the second defect. The results enabled the detection of defects with low signal-to-noise ratios (SNR), which were almost buried in the noise level. These results are reported with regard to the three different developed methods with varying excitation frequencies of 30 kHz, 34 kHz, and 37 kHz. The tests demonstrated the advantage of using the information received from all of the elements rather than a single signal.Brunel University London and National Structural Integrity Research Centre (NSIRC

Regulation of synaptic transmission by RAB-3 and RAB-27 in Caenorhabditis elegans

Rab small GTPases are involved in the transport of vesicles between different membranous organelles. RAB-3 is an exocytic Rab that plays a modulatory role in synaptic transmission. Unexpectedly, mutations in the Caenorhabditis elegans RAB-3 exchange factor homologue, aex-3, cause a more severe synaptic transmission defect as well as a defecation defect not seen in rab-3 mutants. We hypothesized that AEX-3 may regulate a second Rab that regulates these processes with RAB-3. We found that AEX-3 regulates another exocytic Rab, RAB-27. Here, we show that C. elegans RAB-27 is localized to synapse-rich regions pan-neuronally and is also expressed in intestinal cells. We identify aex-6 alleles as containing mutations in rab-27. Interestingly, aex-6 mutants exhibit the same defecation defect as aex-3 mutants. aex-6; rab-3 double mutants have behavioral and pharmacological defects similar to aex-3 mutants. In addition, we demonstrate that RBF-1 (rabphilin) is an effector of RAB-27. Therefore, our work demonstrates that AEX-3 regulates both RAB-3 and RAB-27, that both RAB-3 and RAB-27 regulate synaptic transmission, and that RAB-27 potentially acts through its effector RBF-1 to promote soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) function

Journey mapping long COVID: agency and social support for long-hauling

Long COVID, also known as Post COVID-19 condition, is defined by the WHO as the continuation or development of new symptoms three months after the initial SARS-CoV-2 infection, with these symptoms lasting for at least two months with no other explanation. Despite many studies examining the causes and mechanisms of this disease, fewer studies have sought to understand the experience of those suffering from long COVID, or “long-haulers,” This study contributes to the understanding of long-haulers (N = 14) by examining the role of agency and social support in shaping their journeys with long COVID. Drawing on a combination of interviews, questionnaires, and video diaries over a three-month period, journey mapping was used to document the participants’experiences, including symptoms, coping strategies, and lifestyle changes. Analysis of these journey maps resulted in a framework with four clusters demonstrating the importance of social support and patient agency shaping participants’ Long COVID trajectory; the study contributes valuable insights into the daily lives and challenges individuals face with long COVID, informing the development of targeted support programs

5D gravity and the discrepant G measurements

It is shown that 5D Kaluza-Klein theory stabilized by an external bulk scalar field may solve the discrepant laboratory G measurements. This is achieved by an effective coupling between gravitation and the geomagnetic field. Experimental considerations are also addressed.Comment: 13 pages, to be published in: Proceedings of the 18th Course of the School on Cosmology and Gravitation: The gravitational Constant. Generalized gravitational theories and experiments (30 April-10 May 2003, Erice). Ed. by G. T. Gillies, V. N. Melnikov and V. de Sabbata, (Kluwer), 13pp. (in print) (2003

Patent cooperative patterns and development trends of Chinese construction enterprises: A network analysis

Despite the rapid development of Chinese construction industry, there has been little research effort directed towards exploring patent cooperative patterns and evolution trends of construction enterprises, especially from the perspective of the patent development network. This paper extracts implicit collaborative information and introduces Social Network Analysis (SNA) method to conduct the patentometric analysis based on patent data from the “Top 500 Chinese Construction Enterprises” sourced from PatSnap database. The enterprise-enterprise networks and enterprise-university networks are analyzed quantitatively. The results reveal that: 1) there is a rising trend in the number of patents and patentees; 2) state-owned enterprises play a dominant role in patent development; 3) most of patents are classified as International Patent Classification E04G21; 4) the cooperative relationships are mainly within enterprises and their subsidiaries; 5) when enterprises choose to cooperate with universities, in addition to professional qualification, geographical factors should also be considered. Finally, the development and patent evolution trends are discussed. Some useful suggestions are proposed. The contribution lies in: (a) providing a visualization of the implicit collaboration information of patents in Chinese construction enterprises; (b) revealing cooperative patterns of construction enterprises on patents; and (c) providing enterprises some useful suggestions for patent cooperation

RNA-Seq identifies SPGs as a ventral skeletal patterning cue in sea urchins

The sea urchin larval skeleton offers a simple model for formation of developmental patterns. The calcium carbonate skeleton is secreted by primary mesenchyme cells (PMCs) in response to largely unknown patterning cues expressed by the ectoderm. To discover novel ectodermal cues, we performed an unbiased RNA-Seq-based screen and functionally tested candidates; we thereby identified several novel skeletal patterning cues. Among these, we show that SLC26a2/7 is a ventrally expressed sulfate transporter that promotes a ventral accumulation of sulfated proteoglycans, which is required for ventral PMC positioning and skeletal patterning. We show that the effects of SLC perturbation are mimicked by manipulation of either external sulfate levels or proteoglycan sulfation. These results identify novel skeletal patterning genes and demonstrate that ventral proteoglycan sulfation serves as a positional cue for sea urchin skeletal patterning

A subcellular tug of war involving three MYB-like proteins underlies a molecular antagonism in Antirrhinum flower asymmetry

The establishment of meristematic domains with different transcriptional activity is essential for many developmental processes. The asymmetry of the Antirrhinum majus flower is established by transcription factors with an asymmetric pattern of activity. To understand how this asymmetrical pattern is established, we studied the molecular mechanism through which the dorsal MYB protein RADIALIS (RAD) restricts the activity of the MYB transcription factor DIVARICATA (DIV) to the ventral region of the flower meristem. We show that RAD competes with DIV for binding with other MYB-like proteins, termed DRIF1 and DRIF2 (DIV- and-RAD-interacting-factors). DRIF1 and DIV interact to form a protein complex that binds to the DIV-DNA consensus region, suggesting that the DRIFs act as co-regulators of DIV transcriptional activity. In the presence of RAD, the interaction between DRIF1 and DIV bound to DNA is disrupted. Moreover, the DRIFs are sequestered in the cytoplasm by RAD, thus, preventing or reducing the formation of DRIF-DIV heterodimers in the nuclei. Our results suggest that in the dorsal region of the Antirrhinum flower meristem the dorsal protein RAD antagonises the activity of the ventral identity protein DIV in a subcellular competition for a DRIF protein promoting the establishment of the asymmetric pattern of gene activity in the Antirrhinum flower.- We are grateful to Roger Tsien for providing the plasmids with red fluorescent protein, Barry Causier and Brendan Davies for help in the screening of the Antirrhinum yeast-two hybrid library and Ulises Rosas for providing part of the cDNA sequence for DRIF2. We also thank Nicolas Arnaud and Alejandro Ferrando for providing BiFC plasmids, Desmond Bradley and Alexandra Rebocho for helpful comments on the manuscript and Lucilia Goreti Pinto and Grant Calder for helping with the confocal microscopy. This work was funded by FCT/COMPETE/FEDER with a project grant (ref. FCOMP-01-0124-FEDER-008818) and with a Royal Society International Joint Project grant (2008/R2). JR was supported by funding from FCT with a PhD grant (ref. SFRH/BD/75050/2010). The authors have no conflict of interest to declare

Rigidity and flexibility of biological networks

The network approach became a widely used tool to understand the behaviour of complex systems in the last decade. We start from a short description of structural rigidity theory. A detailed account on the combinatorial rigidity analysis of protein structures, as well as local flexibility measures of proteins and their applications in explaining allostery and thermostability is given. We also briefly discuss the network aspects of cytoskeletal tensegrity. Finally, we show the importance of the balance between functional flexibility and rigidity in protein-protein interaction, metabolic, gene regulatory and neuronal networks. Our summary raises the possibility that the concepts of flexibility and rigidity can be generalized to all networks.Comment: 21 pages, 4 figures, 1 tabl