Pelvic Electrical Neuromodulation for the Treatment of Overactive Bladder Symptoms

Overactive bladder syndrome negatively affects the daily life of many people. First-line conservative treatments, such as antimuscarinics, do not always lead to sufficient improvement of the complaints and/or are often associated with disabling adverse effects leading to treatment failure. Electrical stimulation of the sacral nerves has emerged as an alternative and attractive treatment for refractory cases of bladder overactivity. Few theories attempted to explain its mechanism of action which remains elusive. It involves percutaneous posterior tibial nerve stimulation and more commonly sacral neuromodulation. For the latter, temporary sacral nerve stimulation is the first step. If the test stimulation is successful, a permanent device is implanted. The procedure is safe and reversible. It carries a durable success rate. The technique should be combined with careful followup and attentive adjustments of the stimulation parameters in order to optimize the clinical outcomes. This paper provides a review on the indications, possible mechanisms of action, surgical aspects and possible complications, and safety issues of this technique. The efficacy of the technique is also addressed

Improvement of Bioconversion of Vitamin D3 into Calcitriol by Actinomyces hyovaginalis through Protoplast Fusion and Enzyme Immobilization

Protoplast fusion and enzyme immobilization techniques were applied to increase calcitriol production from vitamin D3 using Actinomyces hyovaginalis, a local isolate recovered from Egyptian soil, that has a potential bioconversion activity of vitamin D3 into calcitriol. A total of sixteen protoplast hybrids, formed between Actinomyces hyovaginalis isolate and two Bacillus species (B. thuringiensis and B. weihenstephanensis) were screened for vitamin D3 bioconversion activity. Compared to wild type isolate, four hybrids (formed between Actinomyces hyovaginalis isolate and B. thuringiensis) were found to preserve the bioconversion activity; out of which, three hybrids coded V2B, V3B and V8A exhibited higher calcitriol production. The hybrids coded V2B and V8A produced, per 1 L culture medium, about 0.5 and 0.4 mg calcitriol corresponding to 350% and 280%, respectively, increase compared to the wild type isolate. Among different alginate concentrations applied, immobilization of cell lysate of Actinomyces hyovaginalis isolate using 2% alginate showed 140% increase in calcitriol production from vitamin D3 compared to the free cell lysate. Activity of the immobilized form was preserved for five repetitive uses over a period of 15 days but with a 50% decline in production occurring at the fifth use

An N-Terminal Extension to UBA5 Adenylation Domain Boosts UFM1 Activation: Isoform-Specific Differences in Ubiquitin-like Protein Activation

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.Modification of proteins by the ubiquitin-like protein, UFM1, requires activation of UFM1 by the E1-activating enzyme, UBA5. In humans, UBA5 possesses two isoforms, each comprising an adenylation domain, but only one containing an N-terminal extension. Currently, the role of the N-terminal extension in UFM1 activation is not clear. Here we provide structural and biochemical data on UBA5 N-terminal extension to understand its contribution to UFM1 activation. The crystal structures of the UBA5 long isoform bound to ATP with and without UFM1 show that the N-terminus not only is directly involved in ATP binding but also affects how the adenylation domain interacts with ATP. Surprisingly, in the presence of the N-terminus, UBA5 no longer retains the 1:2 ratio of ATP to UBA5, but rather this becomes a 1:1 ratio. Accordingly, the N-terminus significantly increases the affinity of ATP to UBA5. Finally, the N-terminus, although not directly involved in the E2 binding, stimulates transfer of UFM1 from UBA5 to the E2, UFC1.Marie Curie Career Integration GrantIsrael Science FoundationIsraeli Cancer Associatio

Efficacy of Mesenchymal Stem Cells in Suppression of Hepatocarcinorigenesis in Rats: Possible Role of Wnt Signaling

<p>Abstract</p> <p>Background</p> <p>The present study was conducted to evaluate the tumor suppressive effects of bone marrow derived mesenchymal stem cells (MSCs) in an experimental hepatocellular carcinoma (HCC) model in rats and to investigate the possible role of Wnt signaling in hepato-carcinogenesis.</p> <p>Methods</p> <p>Ninety rats were included in the study and were divided equally into: Control group, rats which received MSCs only, rats which received MSCs vehicle only, HCC group induced by diethylnitroseamine (DENA) and CCl_<b>4</b>, rats which received MSCs after HCC induction, rats which received MSCs before HCC induction. Histopathological examination and gene expression of Wnt signaling target genes by real time, reverse transcription-polymerase chain reaction (RT-PCR) in rat liver tissue, in addition to serum levels of ALT, AST and alpha fetoprotein were performed in all groups.</p> <p>Results</p> <p>Histopathological examination of liver tissue from animals which received DENA-CCl₄only, revealed the presence of anaplastic carcinoma cells and macro-regenerative nodules type II with foci of large and small cell dysplasia. Administration of MSCs into rats after induction of experimental HCC improved the histopathological picture which showed minimal liver cell damage, reversible changes, areas of cell drop out filled with stem cells. Gene expression in rat liver tissue demonstrated that MSCs downregulated <it>β-catenin</it>, proliferating cell nuclear antigen (<it>PCNA</it>), <it>cyclin D </it>and <it>survivin </it>genes expression in liver tissues after HCC induction. Amelioration of the liver status after administration of MSCs has been inferred by the significant decrease of ALT, AST and Alpha fetoprotein serum levels. Administration of MSCs before HCC induction did not show any tumor suppressive or protective effect.</p> <p>Conclusions</p> <p>Administration of MSCs in chemically induced HCC has tumor suppressive effects as evidenced by down regulation of Wnt signaling target genes concerned with antiapoptosis, mitogenesis, cell proliferation and cell cycle regulation, with subsequent amelioration of liver histopathological picture and liver function.</p

DATAMAN: A global database of methane, nitrous oxide, and ammonia emission factors for livestock housing and outdoor storage of manure

Livestock manure management systems can be significant sources of nitrous oxide (N2O), methane (CH4), and ammonia (NH3) emissions. Many studies have been conducted to improve our understanding of the emission processes and to identify influential variables in order to develop mitigation techniques adapted to each manure management step (animal housing, outdoor storage, and manure spreading to land). The international project DATAMAN (http://www.dataman.co.nz) aims to develop a global database on greenhouse gases (N2O, CH4) and NH3 emissions from the manure management chain to refine emission factors (EFs) for national greenhouse gas and NH3 inventories. This paper describes the housing and outdoor storage components of this database. Relevant information for different animal categories, manure types, livestock buildings, outdoor storage, and climatic conditions was collated from published peer reviewed research, conference papers, and existing databases published between 1995 and 2021. In the housing database, 2024 EFs were collated (63% for NH3, 19.5% for CH4, and 17.5% for N2O). The storage database contains 654 NH3 EFs from 16 countries, 243 CH4 EFs from 13 countries, and 421 N2O EFs from 17 countries. Across all gases, dairy cattle and swine production in temperate climate zones are the most represented animal and climate categories. As for the housing database, the number of EFs for the tropical climate zone is under-represented. The DATAMAN database can be used for the refinement of national inventories and better assessment of the cost-effectiveness of a range of mitigation strategies

Model generation of coronary artery bifurcations from CTA and single plane angiography

International audiencePurpose: To generate accurate and realistic models of coronary artery bifurcations before and after percutaneous coronary intervention (PCI), using information from two image modalities. Because bifurcations are regions where atherosclerotic plaque appears frequently and intervention is more challenging, generation of such realistic models could be of high value to predict the risk of restenosis or thrombosis after stent implantation, and to study geometrical and hemodynamical changes. Methods: Two image modalities have been employed to generate the bifurcation models: computer tomography angiography (CTA) to obtain the 3D trajectory of vessels, and 2D conventional coronary angiography (CCA) to obtain radius information of the vessel lumen, due to its better contrast and image resolution. In addition, CCA can be acquired right before and after the intervention in the operation room; therefore, the combination of CTA and CCA allows the generation of realistic prepro-cedure and postprocedure models of coronary bifurcations. The method proposed is semiautomatic, based on landmarks manually placed on both image modalities. Results: A comparative study of the models obtained with the proposed method with models manually obtained using only CTA, shows more reliable results when both modalities are used together. The authors show that using preprocedure CTA and postprocedure CCA, realistic postprocedure models can be obtained. Analysis carried out of the Murray's law in all patient bifurcations shows the geometric improvement of PCI in our models, better than using manual models from CTA alone. An experiment using a cardiac phantom also shows the feasibility of the proposed method. Conclusions: The authors have shown that fusion of CTA and CCA is feasible for realistic generation of coronary bifurcation models before and after PCI. The method proposed is efficient, and relies on minimal user interaction, and therefore is of high value to study geometric and hemo-dynamic changes of treated patients

The Palestinian Terrestrial Vertebrate Fauna Preserved at the Biology Exhibitions of the Universities of the Gaza Strip

The Gaza Strip (365 km2 ) of Palestine (27,000 km2 ) is home to a wealth of terrestrial vertebrate fauna. Some of these faunistic species find their ways to preservation at the local universities. Hence, the current study comes to document the Palestinian terrestrial vertebrate fauna acquired by the biology exhibitions (BEs) of Al-Azhar University, Islamic University of Gaza and Al-Aqsa University that are located at the Gaza City of the Gaza Strip. The amphibians, reptiles, birds and mammals preserved at BEs of the universities in question were surveyed and scientifically classified during a three-month period extending from January to March, 2012. The study showed that all BEs of local universities are underdeveloped, lacking attention and suffer from specimen scarcity and good preservation. The BE at Al-Azhar University is the best in the arrangement and preservation of bird specimens. A total number of 200 specimens belonging to 54 terrestrial vertebrate fauna species, 39 families and 17 orders was recorded at BEs. Reptiles constituted 40.7% of the total species recorded, followed by birds (38.9%), mammals (14.8%) and amphibians (5.6%). The Islamic University of Gaza was considered the best in terms of the number of preserved species (39.8%), followed by Al-Azhar University (36.3%) and Al-Aqsa University (23.9%). The Common Toad (Bufo viridis) was the most preserved among the amphibian species recorded. Squamata was the biggest reptilian order, comprising 20 species (8 lizards and 12 snakes), with the Syrian Black Snake (Coluber jugularis asianus) was the commonest. The Palestine Viper (Vipera palaestinae) is endemic to Palestine and most venomous and dangerous to human health. The Great White Pelican (Pelecanus onocrotalus) was the largest Palestinian bird preserved at BE of Al-Azhar University. The Egyptian Mongoose (Herpestes ichneumon) and the Common Badger (Meles meles) were the biggest mammalian specimens preserved, while the Palestine Mole-rat (Spalax leucodon ehrenbergi) was the only Palestine endemic species encountered among the preserved mammals. Finally, the improvement of BEs of local universities and the construction of a Central Museum of Natural History is highly recommended in order to change the Palestinians’ attitudes toward a sustainable ecological conservation in the Gaza Strip

Ketogenic diet uncovers differential metabolic plasticity of brain cells

To maintain homeostasis, the body, including the brain, reprograms its metabolism in response to altered nutrition or disease. However, the consequences of these challenges for the energy metabolism of the different brain cell types remain unknown. Here, we generated a proteome atlas of the major central nervous system (CNS) cell types from young and adult mice, after feeding the therapeutically relevant low-carbohydrate, high-fat ketogenic diet (KD) and during neuroinflammation. Under steady-state conditions, CNS cell types prefer distinct modes of energy metabolism. Unexpectedly, the comparison with KD revealed distinct cell type–specific strategies to manage the altered availability of energy metabolites. Astrocytes and neurons but not oligodendrocytes demonstrated metabolic plasticity. Moreover, inflammatory demyelinating disease changed the neuronal metabolic signature in a similar direction as KD. Together, these findings highlight the importance of the metabolic cross-talk between CNS cells and between the periphery and the brain to manage altered nutrition and neurological disease

Structural basis for UFM1 transfer from UBA5 to UFC1

This is the final version. Available on open access from Nature Research via the DOI in this recordData availability: Atomic coordinates and structure factors were deposited in the RCSB PDB (https://www.rcsb.org/) with the accession codes 7NW1, 7NVK, and 7NVJ for UFC1-UBA5 (389–404), UBA5(347-404)-UFC1, and UFC1(Y110A and F121A), respectively. NMR assignments for UFC1 were taken from the BMRB entry 6546. Previously published crystal structures used in this study are available from the RCSB PDB under the accession codes: 3TGD; 1J7D; 1U9A; 1×23; 1Y6L; 4Q5E; 4YII; 1Y8X; 1WZW; 6CYO; 1FZY; 1YLA; 2YBF; 2C4P; 5LBN; 3FN1; 2CYX; 2Z5D; 2F4W; 5BNB; 1YH2; 1YRV; 2Z6P; 2Z6O; 1JBB; 4Q5H; 1WZV; 3RZ3; 2DYT; 6H77. The coordinates of the structural models generated by in silico docking are provided as Supplementary Data 1–3. Source data are provided with this paper.Ufmylation is a post-translational modification essential for regulating key cellular processes. A three-enzyme cascade involving E1, E2 and E3 is required for UFM1 attachment to target proteins. How UBA5 (E1) and UFC1 (E2) cooperatively activate and transfer UFM1 is still unclear. Here, we present the crystal structure of UFC1 bound to the C-terminus of UBA5, revealing how UBA5 interacts with UFC1 via a short linear sequence, not observed in other E1-E2 complexes. We find that UBA5 has a region outside the adenylation domain that is dispensable for UFC1 binding but critical for UFM1 transfer. This region moves next to UFC1’s active site Cys and compensates for a missing loop in UFC1, which exists in other E2s and is needed for the transfer. Overall, our findings advance the understanding of UFM1’s conjugation machinery and may serve as a basis for the development of ufmylation inhibitors.Israel Science FoundationIsrael Cancer Research FundUS-Israel Binational Science Foundatio