Proton pump inhibitors as anti vacuolar-ATPases drugs: a novel anticancer strategy

The vacuolar ATPases are ATP-dependent proton pumps whose functions include the acidification of intracellular compartments and the extrusion of protons through the cell cytoplasmic membrane. These pumps play a pivotal role in the regulation of cell pH in normal cells and, to a much greater extent, in tumor cells. In fact, the glucose metabolism in hypoxic conditions by the neoplasms leads to an intercellular pH drift towards acidity. The acid microenvironment is modulated through the over-expression of H+ transporters that are also involved in tumor progression, invasiveness, distant spread and chemoresistance. Several strategies to block/downmodulate the efficiency of these transporters are currently being investigated. Among them, proton pump inhibitors have shown to successfully block the H+ transporters in vitro and in vivo, leading to apoptotic death. Furthermore, their action seems to synergize with conventional chemotherapy protocols, leading to chemosensitization and reversal of chemoresistance. Aim of this article is to critically revise the current knowledge of this cellular machinery and to summarize the therapeutic strategies developed to counter this mechanism

Metabolomics and lipid profile analysis of Coccomyxa melkonianii SCCA 048

With an unsupervised GC–MS metabolomics approach, polar metabolite changes of the microalgae Coccomyxa melkonianii SCCA 048 grown under standard conditions for seven weeks were studied. C. melkonianii was sampled at the Rio Irvi River, in the mining site of Montevecchio-Ingurtosu (Sardinia, Italy), which is severely contaminated by heavy metals and shows high concentrations of sulfates. The partial-least-square (PLS) analysis of the GC–MS data indicated that growth of C. melkonianii was characterized by an increase of the levels of threonic acid, myo-inositol, malic acid, and fumaric acid. Furthermore, at the sixth week of exponential phase the lipid fingerprint of C. melkonianii was studied by LC-QTOF-MS. C. melkonianii lipid extract characterized through an iterative MS/MS analysis showed the following percent levels: 61.34 ± 0.60% for triacylglycerols (TAG); 11.55 ± 0.09% for diacylglyceryltrimethyl homoserines (DGTS), 11.34 ± 0.10% for sulfoquinovosyldiacylglycerols (SQDG) and, 5.29 ± 0.04% for lysodiacylglyceryltrimethyl homoserines (LDGTS). Noteworthy, we were able to annotate different fatty acid ester of hydroxyl fatty acid, such as FAHFA (18:1_20:3), FAHFA (18:2_20:4), FAHFA (18:0_20:2), and FAHFA (18:1_18:0), with relevant biological activity. These approaches can be useful to study the biochemistry of this extremophile algae in the view of its potential exploitation in the phycoremediation of polluted mining areas

Is old stuff back? A fatal case of ethyl chloride sniffing

Background: Ethyl chloride (EC) or chloroethane is a colourless halogenated hydrocarbon gas regularly employed as a topical anaesthetic spray for pain-related injuries and muscle spasm in athletes. However, EC became also popular as a street drug in the 1980s. Brief inhalations of EC vapour can result in dizziness, euphoria, confusion, incoordination, hallucinosis, impairment of short-term memory and narcosis. Inhalation of higher doses, usually employed to \u201cget high\u201d, may be related to severe depression of the central nervous system. Indeed, toxicity and deaths have been reported so far. Case presentation: A 40-year-old man was found unresponsive after EC inhalation. EC determination was performed by dynamic headspace gas chromatography coupled to mass spectrometry. EC was detected in the peripheral blood (0.156 g/L), central blood concentration (0.203 g/L) and the lung and brain (19 and 25 mg/kg). EC in the vitreous humour showed a sensitively lower respect to blood (0.018 vs 0.203 g/L). Conclusions: Considering the results of toxicological analyses of investigations on the death scene besides the absence of any signs of trauma, death was attributed to inhalation of ethyl chloride

Sperm whale predator-prey interactions involve chasing and buzzing, but no acoustic stunning

Field work in Norway was funded by the Carlsberg Foundation and the National Danish Research Council to PTM. The NMFS study was funded by the U.S. Mineral Management Service. MJ is funded by the Marine Alliance for Science and Technology, Scotland, and by a Marie Curie Career Integration Grant. MW was funded by the Danish Council for Independent Research, Natural Science and NAS is currently funded by a EU Horizon 2020 MSC Fellowship.The sperm whale carries a hypertrophied nose that generates powerful clicks for long-range echolocation. However, it remains a conundrum how this bizarrely shaped apex predator catches its prey. Several hypotheses have been advanced to propose both active and passive means to acquire prey, including acoustic debilitation of prey with very powerful clicks. Here we test these hypotheses by using sound and movement recording tags in a fine-scale study of buzz sequences to relate the acoustic behaviour of sperm whales with changes in acceleration in their head region during prey capture attempts. We show that in the terminal buzz phase, sperm whales reduce inter-click intervals and estimated source levels by 1-2 orders of magnitude. As a result, received levels at the prey are more than an order of magnitude below levels required for debilitation, precluding acoustic stunning to facilitate prey capture. Rather, buzzing involves high-frequency, low amplitude clicks well suited to provide high-resolution biosonar updates during the last stages of capture. The high temporal resolution helps to guide motor patterns during occasionally prolonged chases in which prey are eventually subdued with the aid of fast jaw movements and/or buccal suction as indicated by acceleration transients (jerks) near the end of buzzes.Publisher PDFPeer reviewe

Forensic applications of micro-computed tomography: a systematic review

Purpose: The aim of this systematic review was to provide a comprehensive overview of micro-CT current applications in forensic pathology, anthropology, odontology, and neonatology. Methods: A bibliographic research on the electronic databases Pubmed and Scopus was conducted in the time frame 01/01/2001–31/12/2021 without any language restrictions and applying the following free-text search strategy: “(micro-computed tomography OR micro-CT) AND (forensic OR legal)”. The following inclusion criteria were used: (A) English language; (B) Application of micro-CT to biological and/or non-biological materials to address at least one forensic issue (e.g., age estimation, identification of post-mortem interval). The papers selected by three independent investigators have been then classified according to the investigated materials. Results: The bibliographic search provided 651 records, duplicates excluded. After screening for title and/or abstracts, according to criteria A and B, 157 full-text papers were evaluated for eligibility. Ninety-three papers, mostly (64) published between 2017 and 2021, were included; considering that two papers investigated several materials, an overall amount of 99 classifiable items was counted when referring to the materials investigated. It emerged that bones and cartilages (54.55%), followed by teeth (13.13%), were the most frequently analyzed materials. Moreover, micro-CT allowed the collection of structural, qualitative and/or quantitative information also for soft tissues, fetuses, insects, and foreign materials. Conclusion: Forensic applications of micro-CT progressively increased in the last 5 years with very promising results. According to this evidence, we might expect in the near future a shift of its use from research purposes to clinical forensic cases

Per- and polyfluoroalkyl substances (PFAS) presence in food: Comparison among fresh, frozen and ready-to-eat vegetables

There is a worldwide discussion to provide safety limits in food for per-and polyfluoroalkyl substances (PFAS), a group of persistent contaminants associated to human disease. Processed food is more at risk of containing increased amounts of PFAS as a consequence of intentionally or non-intentionally contamination during manipulation and packaging. Among food products, also vegetables can be submitted to industrial manipulation; therefore, a different PFAS content correlated to the level of vegetables processing is conceivable. This study assessed the amount and type of PFAS present in fresh, frozen and ready-to-eat vegetables. Differences have been observed between the three groups of samples in the average PFAS content; the difference between ready-to eat and frozen vegetables resulted statistically significative. Organic vegetables displayed a lower total amount of PFAS respect to the traditional counterpart. The impact of industrial manipulation remains to be cleared, but pesticides use during cultivation could be considered a source of PFAS contamination

PENGGUNAAN APLIKASI YOUTUBE SEBAGAI MEDIA DAKWAH DI ERA PANDEMI COVID-19

The existence of the Covid-19 pandemic is the background for holding this research, in which health protocols prohibit and limit activities that gather large numbers of people. This also has an impact on religious activities such as da'wah which require alternative solutions, because previously it was carried out face-to-face and gathered. The alternative offered in this study is through the social media platform Youtube. The purpose of this study is to analyze whether the Youtube platform is effectively used for preaching and to find out the methods applied in da'wah through the Youtube platform. This study uses a qualitative method, where data is collected from reliable sources such as explanations of the Qur'an and Hadith. The results of this study indicate that da'wah through the Youtube platform in the era of the Covid-19 pandemic has several advantages compared to conventional da'wah. Youtube has many advantages, such as being widely accessed by various groups in terms of sharing video content. Youtube and da'wah also have a relationship with segmentation that both target audiences. In this case, it is hoped that ustaz, scholars, and preachers can use Youtube media by using the available features. This also needs to be followed by good and correct da'wah methods in accordance with Islamic teachings

Perancangan dan Analisis Lengan Penggerak Roda Depan pada Mobil Minimalis Roda Tiga

Dewasa ini kemajuan teknologi sangat luar biasa termasuk dalam bidang transportasi,baik kendaraan roda dua, roda empat bahkan roda tiga berkembang kearah yang lebih baik.Di indonesia dengan wilayah yang sangat luas dan memiliki kontur yang berbeda-beda tentunya membutuhkan sebuah kendaraan yang baik dalam bermanuver serta irit dalam penggunaannya, para produsen dan ilmuan pun berlomba-lomba membuat kendaraan yang canggih, safety dan tentunya irit.Karena pertumbuhan penduduk yang semakin pesat jumlah mobil yang ada juga semakin banyak setiap harinya yang membuat semakin sempit jalan yang ada.Dengan bentuknya yang minimalis namun kompak diharapkan mobil roda 3 (three wheel car) ini menjadi salah satu yang diharapkan, dimana dengan body yang kecil diharapkan memiliki harga terjangkau,irit bahan bakar dan tentunya mudah dalam bermanuver.Dari permasalahan diatas diperlukan sebuah design mobil yang minimalis , kuat dan aman untuk digunakan,dalam penelitian kali ini diperlukan nilai sudut belok roda depan yang dapat di hitung dengan rumus ackerman serta untuk mengetahui apakah kontruksi lengan depan mobil aman,digunakan software catia untuk mengetahuinya.Dari hasil perhitungan dan perbandingan data dari mobil minimalis roda tiga dengan mobil suzuki karimun estilo yang memiliki spesifikasi hampir sama, sudut steer yang dihasilkan pada kemiringan roda 6 ͦ  dengan Radius Ackerman 16,25 m , 17,5 m dan 22,5 m mobil minimalis roda tiga memiliki sudut steer yang tidak jauh beda yakni 6,59  ͦ, 6,25 ͦ dan 6,10  ͦberbanding dengan sudut steer mobil karimun estilo sebesar 8,32 ͦ ,7,72 ͦ dan 6.01 ͦ  bisa dikatakan mobil minimalis roda tiga masih nyaman digunakan untuk berkendara karena memiliki nilai yang hampir sama dengan mobil yang telah diproduksi masal.&nbsp