We have investigated the role of TGIF, a TALE-class homeodomain transcription factor, in Drosophila development. In vertebrates, TGIF has been implicated, by in vitro analysis, in several pathways, most notably as a repressor modulating the response to TGFß signalling. Human TGIF has been associated with the developmental disorder holoprosencephaly. Drosophila TGIF is represented by the products of two tandemly repeated highly similar genes, achintya and vismay. We have generated mutations that delete both genes. Homozygous mutant flies are viable and appear morphologically normal, but the males are completely sterile. The defect lies at the primary spermatocyte stage and differentiation is blocked prior to the onset of the meiotic divisions. We show that mutants lacking TGIF function fail to activate transcription of many genes required for sperm manufacture and of some genes required for entry into the meiotic divisions. This groups TGIF together with two other genes producing similar phenotypes, always early and cookie monster, as components of the machinery required for the activation of the spermatogenic programme of transcription. TGIF is the first sequence-specific transcription factor identified in this pathway. By immunolabelling in mouse testes we show that TGIF is expressed in the early stages of spermatogenesis consistent with a conserved role in the activation of the spermatogenesis transcription programme.

BackgroundAn increasing number of publications demonstrate conservation of function of cis-regulatory elements without sequence similarity. In invertebrates such functional conservation has only been shown for closely related species. Here we demonstrate the existence of an ancient arthropod regulatory element that functions during the selection of neural precursors. The activity of genes of the achaete-scute (ac-sc) family endows cells with neural potential. An essential, conserved characteristic of proneural genes is their ability to restrict their own activity to single or a small number of progenitor cells from their initially broad domains of expression. This is achieved through a process called lateral inhibition. A regulatory element, the sensory organ precursor enhancer (SOPE), is required for this process. First identified in Drosophila, the SOPE contains discrete binding sites for four regulatory factors. The SOPE of the Drosophila asense gene is situated in the 5' UTR.ResultsThrough a manual comparison of consensus binding site sequences we have been able to identify a SOPE in UTR sequences of asense-like genes in species belonging to all four arthropod groups (Crustacea, Myriapoda, Chelicerata and Insecta). The SOPEs of the spider Cupiennius salei and the insect Tribolium castaneum are shown to be functional in transgenic Drosophila. This would place the origin of this regulatory sequence as far back as the last common ancestor of the Arthropoda, that is, in the Cambrian, 550 million years ago.ConclusionsThe SOPE is not detectable by inter-specific sequence comparison, raising the possibility that other ancient regulatory modules in invertebrates might have escaped detection.

Two distinct roles are described for Dorsal, Dif and Relish, the three NF-κB/Rel proteins of Drosophila, in the development of the peripheral nervous system. First, these factors regulate transcription of scute during the singling out of sensory organ precursors from clusters of cells expressing the proneural genes achaete and scute. This effect is possibly mediated through binding sites for NF-κB/Rel proteins in a regulatory module of the scute gene required for maintenance of scute expression in precursors as well as repression in cells surrounding precursors. Second, genetic evidence suggests that the receptor Toll-8, Relish, Dif and Dorsal, and the caspase Dredd pathway are active over the entire imaginal disc epithelium, but Toll-8 expression is excluded from sensory organ precursors. Relish promotes rapid turnover of transcripts of the target genes scute and asense through an indirect, post-transcriptional mechanism. We propose that this buffering of gene expression levels serves to keep the neuro-epithelium constantly poised for neurogenesis.

No abstract

No abstract

A 50-year-old man with intractable anal pain attributed to proctalgia fugax underwent insertion of a sacral nerve stimulator via the right S3 vertebral foramen for pain control with good symptomatic relief. Thirteen months later, he presented with signs of sepsis. Computed tomography (CT) and magnetic resonance imaging (MRI) showed a large presacral abscess. MRI demonstrated increased enhancement along the pathway of the stimulator electrode, indicating that the abscess was caused by infection introduced at the time of sacral nerve stimulator placement.The patient was treated with broad spectrum antibiotics, and the sacral nerve stimulator and electrode were removed. Attempts were made to drain the abscess transrectally using minimally invasive techniques but these were unsuccessful and CT guided transperineal drainage was then performed. Despite this, the presacral abscess progressed, developing enlarging gas locules and extending to the pelvic brim to involve the aortic bifurcation, causing hydronephrosis and radiological signs of impending sacral osteomyelitis. MRI showed communication between the rectum and abscess resulting from transrectal drainage. In view of the progressive presacral sepsis, a laparotomy was performed with drainage of the abscess, closure of the upper rectum and formation of a defunctioning end sigmoid colostomy. Following this, the presacral infection resolved.Presacral abscess formation secondary to an infected sacral nerve stimulator electrode has not been reported previously. Our experience suggests that in a similar situation, the optimal management is to perform laparotomy with drainage of the presacral abscess together with simultaneous removal of the sacral nerve stimulator and electrode. Sacral nerve stimulation is the implantation of a permanent pulse generator that delivers controlled electrical impulses via an electrode placed in contact with the sacral nerve roots, the S3 nerve root being the most common. It is of proven value in the treatment of urinary and faecal incontinence, urinary non-obstructive retention, and chronic pelvic and anal pain including proctalgia fugax. 1 We report the case of a 50-year-old man having severe anal pain attributed to proctalgia fugax for 7 years. Treatments with caudal epidural injection and ganglion impar block had been unsuccessful. He was referred to a tertiary centre for chronic pain management, where a temporary trial of S3 nerve stimulation was successful in controlling his anal pain. A permanent nerve stimulator was then implanted with the electrode being sited adjacent to the right S3 nerve root with good symptomatic relief. The patient presented 13 months later with symptoms and signs of sepsis including poor appetite, weight loss, night sweats, pyrexia, leucocytosis and elevated C-reactive protein. Computed tomography (CT) showed a chronic presacral abscess and magnetic resonance imaging (MRI) demonstrated enhancement along the pathway of the implanted electrode, indicating that the presacral abscess was caused by infectio...

Research and innovation are growing in India with significant investments being made towards institutions, researchers and research infrastructure. Although still under 1% of GDP, funding for science and technology in India has increased each year for over two decades. There is also increasing realization that public funding for research should be supplemented with that from industry and philanthropy. Like their counterparts worldwide, Indian researchers require access to professional research management support at their institutions to fully leverage emerging scientific opportunities and collaborations. However, there are currently significant  gaps in the research management support available to these researchers and this has implications for research in India. The India Research Management Initiative (IRMI) was launched by the Wellcome Trust/DBT (Department of Biotechnology, Government of India) India Alliance (hereafter India Alliance) in February 2018 to narrow these gaps. A 12-month pilot phase has enabled conversations across multiple stakeholders. In this Open Letter, we share some insights from the IRMI pilot phase, which could aid systemic development and scaling up of research management as a professional support service across India. We anticipate these will stimulate dialogue and guide future policy and interventions towards building robust research and innovation ecosystems in India.

Research and innovation are growing in India with significant investments being made towards institutions, researchers and research infrastructure. Although still under 1% of GDP, funding for science and technology in India has increased each year for over two decades. There is also increasing realization that public funding for research should be supplemented with that from industry and philanthropy. Like their counterparts worldwide, Indian researchers require access to professional research management support at their institutions to fully leverage emerging scientific opportunities and collaborations. However, there are currently significant  gaps in the research management support available to these researchers and this has implications for research in India. The India Research Management Initiative (IRMI) was launched by the Wellcome Trust/DBT (Department of Biotechnology, Government of India) India Alliance (hereafter India Alliance) in February 2018 to narrow these gaps. A 12-month pilot phase has enabled conversations across multiple stakeholders. In this Open Letter, we share some insights from the IRMI pilot phase, which could aid systemic development and scaling up of research management as a professional support service across India. We anticipate these will stimulate dialogue and guide future policy and interventions towards building robust research and innovation ecosystems in India.