The Drosophila Citrate Lyase Is Required for Cell Division during Spermatogenesis

The Drosophila melanogaster DmATPCL gene encodes for the human ATP Citrate Lyase (ACL) ortholog, a metabolic enzyme that from citrate generates glucose-derived Acetyl-CoA, which fuels central biochemical reactions such as the synthesis of fatty acids, cholesterol and acetylcholine, and the acetylation of proteins and histones. We had previously reported that, although loss of Drosophila ATPCL reduced levels of Acetyl-CoA, unlike its human counterpart, it does not affect global histone acetylation and gene expression, suggesting that its role in histone acetylation is either partially redundant in Drosophila or compensated by alternative pathways. Here, we describe that depletion of DmATPCL affects spindle organization, cytokinesis, and fusome assembly during male meiosis, revealing an unanticipated role for DmATPCL during spermatogenesis. We also show that DmATPCL mutant meiotic phenotype is in part caused by a reduction of fatty acids, but not of triglycerides or cholesterol, indicating that DmATPCL-derived Acetyl-CoA is predominantly devoted to the biosynthesis of fatty acids during spermatogenesis. Collectively, our results unveil for the first time an involvement for DmATPCL in the regulation of meiotic cell division, which is likely conserved in human cells

Clinical relevance of silent red blood cell autoantibodies.

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Radioresistance in rhabdomyosarcomas: much more than a question of dose

Management of rhabdomyosarcoma (RMS), the most common soft tissue sarcoma in children, frequently accounting the genitourinary tract is complex and requires a multimodal therapy. In particular, as a consequence of the advancement in dose conformity technology, radiation therapy (RT) has now become the standard therapeutic option for patients with RMS. In the clinical practice, dose and timing of RT are adjusted on the basis of patients' risk stratification to reduce late toxicity and side effects on normal tissues. However, despite the substantial improvement in cure rates, local failure and recurrence frequently occur. In this review, we summarize the general principles of the treatment of RMS, focusing on RT, and the main molecular pathways and specific proteins involved into radioresistance in RMS tumors. Specifically, we focused on DNA damage/repair, reactive oxygen species, cancer stem cells, and epigenetic modifications that have been reported in the context of RMS neoplasia in both in vitro and in vivo studies. The precise elucidation of the radioresistance-related molecular mechanisms is of pivotal importance to set up new more effective and tolerable combined therapeutic approaches that can radiosensitize cancer cells to finally ameliorate the overall survival of patients with RMS, especially for the most aggressive subtypes

Building Bridges to Enhance Degree and Career Opportunities

External pressures on higher education are challenging universities to focus on preparing graduates with more broadly designed curricula that contain translatable skills and include interdisciplinary knowledge. In this presentation, the process of identifying and creating new academic programs based on unique student goals and contemporary employment needs will be discussed

The botanical drug PBI-05204, a supercritical CO2 extract of Nerium oleander, sensitizes alveolar and embryonal rhabdomyosarcoma to radiotherapy in vitro and in vivo

Treatment of rhabdomyosarcoma (RMS), the most common a soft tissue sarcoma in childhood, provides intensive multimodal therapy, with radiotherapy (RT) playing a critical role for local tumor control. However, since RMS efficiently activates mechanisms of resistance to therapies, despite improvements, the prognosis remains still largely unsatisfactory, mainly in RMS expressing chimeric oncoproteins PAX3/PAX7-FOXO1, and fusion-positive (FP)-RMS. Cardiac glycosides (CGs), plant-derived steroid-like compounds with a selective inhibitory activity of the Na+/K+-ATPase pump (NKA), have shown antitumor and radio-sensitizing properties. Herein, the therapeutic properties of PBI-05204, an extract from Nerium oleander containing the CG oleandrin already studied in phase I and II clinical trials for cancer patients, were investigated, in vitro and in vivo, against FN- and FP-RMS cancer models. PBI-05204 induced growth arrest in a concentration dependent manner, with FP-RMS being more sensitive than FN-RMS, by differently regulating cell cycle regulators and commonly upregulating cell cycle inhibitors p21Waf1/Cip1 and p27Cip1/Kip1. Furthermore, PBI-05204 concomitantly induced cell death on both RMS types and senescence in FN-RMS. Notably, PBI-05204 counteracted in vitro migration and invasion abilities and suppressed the formation of spheroids enriched in CD133+ cancer stem cells (CSCs). PBI-05204 sensitized both cell types to RT by improving the ability of RT to induce G2 growth arrest and counteracting the RT-induced activation of both Non‐Homologous End‐Joining and homologous recombination DSBs repair pathways. Finally, the antitumor and radio-sensitizing proprieties of PBI-05204 were confirmed in vivo. Notably, both in vitro and in vivo evidence confirmed the higher sensitivity to PBI-05204 of FP-RMS. Thus, PBI-05204 represents a valid radio-sensitizing agent for the treatment of RMS, including the intrinsically radio-resistant FP-RMS

A power-optimal design methodology for high-resolution low-bandwidth SC ΔΣ Modulators

In this paper, a methodology for the power-optimal design of high-resolution low-bandwidth switched-capacitor $DeltaSigma$ modulators ($DeltaSigmahbox{Ms}$) is presented. The most power-efficient $DeltaSigma$ architecture is identified among single-loop feedback and feedforward topologies with different loop orders $N$, oversampling ratios $OSR$, and quantizer resolutions $B$. Based on this study, an experimental prototype has been implemented in a 0.18- $muhbox{m}$ CMOS process. It achieves a signal-to-noise ratio of 95 dB over a signal bandwidth $f_{rm BW}$ of 10 kHz. The prototype operates with a 1.28-MHz sampling rate and consumes 210 $muhbox{W}$ from a 1.8-V supply

A power-optimal design methodology for high-resolution low-bandwidth SC ΔΣ Modulators

In this paper, a methodology for the power-optimal design of high-resolution low-bandwidth switched-capacitor $DeltaSigma$ modulators ($DeltaSigmahbox{Ms}$) is presented. The most power-efficient $DeltaSigma$ architecture is identified among single-loop feedback and feedforward topologies with different loop orders $N$, oversampling ratios $OSR$, and quantizer resolutions $B$. Based on this study, an experimental prototype has been implemented in a 0.18- $muhbox{m}$ CMOS process. It achieves a signal-to-noise ratio of 95 dB over a signal bandwidth $f_{rm BW}$ of 10 kHz. The prototype operates with a 1.28-MHz sampling rate and consumes 210 $muhbox{W}$ from a 1.8-V supply

Power optimization of high-resolution low-bandwidth SC ΔΣ modulators

This paper presents a procedure for the power-optimal design of high-resolution low-bandwidth switched-capacitor (SC) ¿S modulators (¿SMs). The most power efficient ¿S architecture is identified among single-loop switched-capacitor (SC) feedback (FB) and feed-forward (FF) topologies with different loop order N, oversampling ratio OSR, and quantizer resolution B. Based on the results obtained, an experimental prototype is implemented in a 0.18µm CMOS process, achieving a signal-to-noise ratio (SNR) of 95 dB over a signal bandwidth fBW of 10 kHz. The prototype operates with a 1.28MHz sampling rate and dissipates a total power of 210uW from a 1.8V supply

Field-effect and capacitive properties of water-gated transistors based on polythiophene derivatives

Recently, water-gated organic field-effect transistors (WGOFET) have been intensively studied for their application in the biological field. Surprisingly, a very limited number of conjugated polymers have been reported so far. Here, we systematically explore a series of polythiophene derivatives, presenting different alkyl side chains lengths and orientation, and characterized by various morphologies: comparative evaluation of their performances allows highlighting the critical role played by alkyl side chains, which significantly affects the polymer/water interface capacitance. Reported results provide useful guidelines towards further development of WGOFETs and represent a step forward in the understanding of the polymer/water interface phenomena