Biot-Savart-like law in electrostatics

The Biot-Savart law is a well-known and powerful theoretical tool used to calculate magnetic fields due to currents in magnetostatics. We extend the range of applicability and the formal structure of the Biot-Savart law to electrostatics by deriving a Biot-Savart-like law suitable for calculating electric fields. We show that, under certain circumstances, the traditional Dirichlet problem can be mapped onto a much simpler Biot-Savart-like problem. We find an integral expression for the electric field due to an arbitrarily shaped, planar region kept at a fixed electric potential, in an otherwise grounded plane. As a by-product we present a very simple formula to compute the field produced in the plane defined by such a region. We illustrate the usefulness of our approach by calculating the electric field produced by planar regions of a few nontrivial shapes.Comment: 14 pages, 6 figures, RevTex, accepted for publication in the European Journal of Physic

Technology transfer. Multi-purpose cows for milk, meat and traction in smallholder farming systems. Proceedings of a consultation

The aim of this consultation is to explore the practicality of extending technologies that enable the use of dairy cows for multiple purposes, to help develop a regional project to transfer these technologies to relevant countries in east and Central Africa. The focus of the consultation is on new technologies developed by the International Livestock Research Institute (ILRI) and the Ethiopian Institute of Agricultural Research (IAR) to help introduce multi-purpose crossbred cows into smallholder production systems, focussing on traction in addition to milk and meat production. Topics of discussion include development of cow traction technologies, social and cultural altitudes towards adoption of cow traction, extension efforts to spread the technology, draft power use in smallholder farming systems, research on the nutrition of cows, and potential and extent of use of cows for draft work. Countries involved in the study include Kenya, Uganda, Tanzania, Malawi, Ethiopia, Mozambique, Indonesia, Philippines, Thailand, Vietnam, China and India

FGF23 is elevated in multiple myeloma and increases heparanase expression by tumor cells

Multiply myeloma (MM) grows in and destroys bone, where osteocytes secrete FGF23, a hormone which affects phosphate homeostasis and aging. We report that multiple myeloma (MM) cells express receptors for and respond to FGF23. FGF23 increased mRNA for EGR1 and its target heparanase, a pro-osteolytic factor in MM. FGF23 signals through a complex of klotho and a classical FGF receptor (FGFR); both were expressed by MM cell lines and patient samples. Bone marrow plasma cells from 42 MM patients stained positively for klotho, while plasma cells from 8 patients with monoclonal gammopathy of undetermined significance (MGUS) and 6 controls were negative. Intact, active FGF23 was increased 2.9X in sera of MM patients compared to controls. FGF23 was not expressed by human MM cells, but co-culture with mouse bone increased its mRNA. The FGFR inhibitor NVP-BGJ398 blocked the heparanase response to FGF23. NVP-BGJ398 did not inhibit 8226 growth in vitro but significantly suppressed growth in bone and induction of the osteoclast regulator RANK ligand, while decreasing heparanase mRNA. The bone microenvironment provides resistance to some anti-tumor drugs but increased the activity of NVP-BGJ398 against 8226 cells. The FGF23/klotho/heparanase signaling axis may offer targets for treatment of MM in bone

Spirotetramat resistance in Myzus persicae (Sulzer) (Hemiptera: Aphididae) and its association with the presence of the A2666V mutation

This is the final version. Available on open access from Wiley via the DOI in this recordData availability statement: The data that support the findings of this study are available from the corresponding author upon reasonable request.BACKGROUND: Chemicals are widely used to protect field crops against aphid pests and aphid-borne viral diseases. One such species is Myzus persicae (Sulzer), a global pest that attacks a broad array of agricultural crops and transmits many economically damaging plant viruses. This species has evolved resistance to a large number of insecticide compounds as a result of widespread and repeated chemical use in many parts of the world. In this study, we investigated the evolution of resistance to a new plant protection product, spirotetramat, following reported chemical control failures. RESULTS: Our study provides clear phenotypic and genotypic evidence of spirotetramat resistance in populations of M. persicae from Australia. We show there is cross-resistance to other insecticides within the same chemical group, namely spiromesifen and spirodiclofen. We also demonstrate that resistance is associated with the previously reported mutation, A2226V in the target site of spirotetramat, acetyl-CoA carboxylase. Our genetic analysis found all resistant M. persicae populations belong to the same multi-locus clonal type and carry the A2226V mutation, which appears to be inherited as a dominant trait in this species. CONCLUSION: Our findings provide new insight into the resistance conferred by A2226V and have implications for the control of M. persicae in Australia and worldwide. A diagnostic assay developed in this study should serve as a valuable tool for future resistance monitoring and to support the implementation of pest management strategies. © 2022 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.Grains Research and Development CorporationBayer CropScienceBiotechnology and Biological Sciences Research Council (BBSRC

Attempts to Image the Early Inflammatory Response during Infection with the Lymphatic Filarial Nematode Brugia pahangi in a Mouse Model

Helminth parasites remain a major constraint upon human health and well-being in many parts of the world. Treatment of these infections relies upon a very small number of therapeutics, most of which were originally developed for use in animal health. A lack of high throughput screening systems, together with limitations of available animal models, has restricted the development of novel chemotherapeutics. This is particularly so for filarial nematodes, which are long-lived parasites with a complex cycle of development. In this paper, we describe attempts to visualise the immune response elicited by filarial parasites in infected mice using a non-invasive bioluminescence imaging reagent, luminol, our aim being to determine whether such a model could be developed to discriminate between live and dead worms for in vivo compound screening. We show that while imaging can detect the immune response elicited by early stages of infection with L3, it was unable to detect the presence of adult worms or, indeed, later stages of infection with L3, despite the presence of worms within the lymphatic system of infected animals. In the future, more specific reagents that detect secreted products of adult worms may be required for developing screens based upon live imaging of infected animals

Cloning and characterization of a novel alternatively spliced transcript of the human CHD7 putative helicase

<p>Abstract</p> <p>Background</p> <p>The <it>CHD7 </it>(Chromodomain Helicase DNA binding protein 7) gene encodes a member of the chromodomain family of ATP-dependent chromatin remodeling enzymes. Mutations in the <it>CHD7 </it>gene are found in individuals with CHARGE, a syndrome characterized by multiple birth malformations in several tissues. CHD7 was identified as a binding partner of PBAF complex (Polybromo and BRG Associated Factor containing complex) playing a central role in the transcriptional reprogramming process associated to the formation of multipotent migratory neural crest, a transient cell population associated with the genesis of various tissues. <it>CHD7 </it>is a large gene containing 38 annotated exons and spanning 200 kb of genomic sequence. Although genes containing such number of exons are expected to have several alternative transcripts, there are very few evidences of alternative transcripts associated to <it>CHD7 </it>to date indicating that alternative splicing associated to this gene is poorly characterized.</p> <p>Findings</p> <p>Here, we report the cloning and characterization by experimental and computational studies of a novel alternative transcript of the human <it>CHD7 </it>(named CHD7 CRA_e), which lacks most of its coding exons. We confirmed by overexpression of CHD7 CRA_e alternative transcript that it is translated into a protein isoform lacking most of the domains displayed by the canonical isoform. Expression of the CHD7 CRA_e transcript was detected in normal liver, in addition to the DU145 human prostate carcinoma cell line from which it was originally isolated.</p> <p>Conclusions</p> <p>Our findings indicate that the splicing event associated to the CHD7 CRA_e alternative transcript is functional. The characterization of the CHD7 CRA_e novel isoform presented here not only sets the basis for more detailed functional studies of this isoform, but, also, contributes to the alternative splicing annotation of the <it>CHD7 </it>gene and the design of future functional studies aimed at the elucidation of the molecular functions of its gene products.</p

The farnesoid X receptor regulates transcription of 3 beta-hydroxysteroid dehydrogenase type 2 in human adrenal cells

Recent studies have shown that the adrenal cortex expresses high levels of farnesoid X receptor (FXR), but its function remains not known. Herein, using microarray technology, we tried to identify candidate FXR targeting genes in the adrenal glands, and showed that FXR regulates 3β-hydroxysteroid dehydrogenase type 2 (HSD3B2) expression in human adrenocortical cells. We further demonstrated that FXR stimulated HSD3B2 promoter activity and have defined the cis-element responsible for FXR regulation of HSD3B2 transcription. Transfection of H295R adrenocortical cells with FXR expression vector effectively increased FXR expression levels and additional treatment with chenodeoxycholic acid (CDCA) caused a 25-fold increase in the mRNA for organic solute transporter alpha (OSTα), a known FXR target gene. HSD3B2 mRNA levels also increased following CDCA treatment in a concentration-dependent manner. Cells transfected with a HSD3B2 promoter construct and FXR expression vector responded to CDCA with a 20-fold increase in reporter activity compared to control. Analysis of constructs containing sequential deletions of the HSD3B2 promoter suggested a putative regulatory element between -166 and -101. Mutation of an inverted repeat between -137 and -124 completely blocked CDCA/FXR induced reporter activity. Chromatin immunoprecipitation assays further confirmed the presence of a FXR response element in the HSD3B2 promoter. In view of the emerging role of FXR agonists as therapeutic treatment of diabetes and certain liver diseases, the effects of such agonists on other FXR expressing tissues should be considered. Our findings suggest that in human adrenal cells, FXR increases transcription and expression of HSD3B2. Alterations in this enzyme would influence the capacity of the adrenal gland to produce corticosteroids

Pfmrk, a MO15-related protein kinase from Plasmodium falciparum. Gene cloning, sequence, stage-specific expression and chromosome localization.

Cyclin-dependent kinases (Cdks) play a central role in the regulation of the eukaryotic cell cycle. A novel gene encoding a Cdk-like protein, Pfmrk, has been isolated from the human malaria parasite Plasmodium falciparum. The gene has no introns and comprises an open reading frame encoding a protein of 324 amino acids with a predicted molecular mass of 38 kDa. Database searches revealed a striking similarity to the Cdk subfamily with the highest similarity to human MO15 (Cdk7). The overall sequence of Pfmrk shares 62% similarity and 46% identity with human MO15, in comparison to the 49-58% similarity and 34-43% identity with other human Cdks. Pfmrk contains two unique inserts: one consisting of 5 amino acids just before the cyclin-binding motif and the other composed of 13 amino acids within the T-loop equivalent region. Southern blots of genomic DNA digests and chromosomal separations showed that Pfmrk is a single-copy gene conserved between several parasite strains and is located on chromosome 10. A 2500-nucleotide transcript of this gene is expressed predominantly in the sexual blood stages (gametocytes), suggesting that Pfmrk may be involved in sexual stage development

Clinical management of gastric cancer: results of a multicentre survey

<p>Abstract</p> <p>Background</p> <p>The National Comprehensive Cancer Network clinical practice guidelines in oncology-gastric cancer guidelines have been widely used to provide appropriate recommendations for the treatment of patients with gastric cancer. The aim of this study was to examine the adherence of surgical oncologists, medical oncologists, and radiation oncologists' to the recommended guidelines.</p> <p>Methods</p> <p>A questionnaire asking the treatment options for gastric cancer cases was sent to 394 Chinese oncology specialists, including surgical oncologists, medical oncologists, and radiation oncologists working in hospitals joined in The Western Cooperative Gastrointestinal Oncology Group of China. The questionnaire involved a series of clinical scenarios regarding the interpretation of surgery, neoadjuvant, adjuvant, and advanced treatment planning of gastric cancer.</p> <p>Results</p> <p>Analysis of 358 respondents (91%) showed variations between each specialization and from the recommended guidelines in the management approaches to specific clinical scenarios. The majority of specialists admitted that less than 50% of patients received multidisciplinary evaluation before treatment. The participants gave different responses to questions involving adjuvant, neoadjuvant, and advanced settings, compared to the recommended guidelines.</p> <p>Conclusions</p> <p>These results highlight the heterogeneity of the treatment of gastric cancer. Surgical oncologists, medical oncologists, and radiation oncologists are not adhering to the recommended guidelines.</p

DNA methylation in the promoter region of the p16 (CDKN2/MTS-1/INK4A) gene in human breast tumours

The p16 (CDKN2/MTS-1/INK4A) gene is one of several tumour-suppressor genes that have been shown to be inactivated by DNA methylation in various human cancers including breast tumours. We have used bisulphite genomic sequencing to examine the detailed sequence specificity of DNA methylation in the CpG island promoter/exon 1 region in the p16 gene in DNA from a series of human breast cancer specimens and normal human breast tissue (from reductive mammaplasty). The p16 region examined was unmethylated in the four normal human breast specimens and in four out of nine breast tumours. In the other five independent breast tumour specimens, a uniform pattern of DNA methylation was observed. Of the nine major sites of DNA methylation in the amplified region from these tumour DNAs, four were in non-CG sequences. This unusual concentration of non-CG methylation sites was not a general phenomenon present throughout the genome of these tumour cells because the methylated CpG island regions of interspersed L1 repeats had a pattern of (almost exclusively) CG methylation similar to that found in normal breast tissue DNA and in DNA from tumours with unmethylated p16 genes. These data suggest that DNA methylation of the p16 gene in some breast tumours could be the result of an active process that generates a discrete methylation pattern and, hence, could ultimately be amenable to theraputic manipulation. © 1999 Cancer Research Campaig