Publications by authors named "Baechler S"

Article Synopsis
  • High-fat diets contribute significantly to metabolic dysfunctions like metabolic dysfunction-associated steatotic liver disease (MASLD) and steatohepatitis (MASH), with mitochondria implicated in their development.
  • The study investigates the role of mitochondrial topoisomerase I (Top1MT) by using mice that lack this enzyme, revealing that these mice are more susceptible to severe MASH after being fed a high-fat diet for 16 weeks.
  • Findings show that Top1MT deficiency leads to severe liver issues, mitochondrial dysfunction, increased reactive oxygen species production, and enhanced hepatic inflammation, underscoring its critical role in maintaining liver cell health and preventing MASH.
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From the beginnings of Silk Road in 2011, anonymous online marketplaces have continued to grow despite the best efforts of law enforcement. While these ever-present marketplaces remain flooded with illicit drugs and related paraphernalia, the sale and distribution of fraudulent identity documents remains a persistent problem, with these items consistently appearing for sale on both the open and dark web. While fraudulent Australian documents are some of the most popular products for sale, there is still much that is unknown about the Australian criminal market and its place within anonymous online marketplaces.

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The serial character of document fraud and its connection to organised crime groups who produce, sell and/or use fraudulent documents is a challenge for security and crime fighting. As a response, the added value of forensic intelligence is increasingly recognised. Using a forensic profiling method and a dedicated system deployed in Switzerland, document examiners can detect series (i.

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Colorectal cancers (CRCs) are prevalent worldwide, yet current treatments remain inadequate. Using chemical genetic screens, we identify that co-inhibition of topoisomerase I (TOP1) and NEDD8 is synergistically cytotoxic in human CRC cells. Combination of the TOP1 inhibitor irinotecan or its bioactive metabolite SN38 with the NEDD8-activating enzyme inhibitor pevonedistat exhibits synergy in CRC patient-derived organoids and xenografts.

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Over the years, forensic science has primarily positioned itself as a service provider for the criminal justice system, following the dominant and traditional reactive law enforcement model. Unfortunately, this focus has limited its capacity to provide knowledge about crime systems and to support other forms of policing styles through forensic intelligence. Although forensic intelligence research has steadily developed over the last few years, it is rarely covered in the core of academic teaching and research programs.

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Document fraud is a transnational form of crime, and its serial character has already been highlighted. To combat this phenomenon, the Interstate Database of Fraudulent Identity Documents (BIDIF) has been created and implemented in Switzerland. It supports the comparison of documents and the detection of series, i.

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The present study demonstrates how TOP3B is involved in resolving R-loops. We observed elevated R-loops in TOP3B knockout cells (TOP3BKO), which are suppressed by TOP3B transfection. R-loop-inducing agents, the topoisomerase I inhibitor camptothecin, and the splicing inhibitor pladienolide-B also induce higher R-loops in TOP3BKO cells.

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Cancer/Testis Antigens (CTAs) represent a group of proteins whose expression under physiological conditions is restricted to testis but activated in many human cancers. Also, it was observed that co-expression of multiple CTAs worsens the patient prognosis. Five CTAs were reported acting in mitochondria and we recently reported 147 transcripts encoded by 67 CTAs encoding for proteins potentially targeted to mitochondria.

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Criminal offenders missing from police files limit the capacity to reconstruct criminal networks for criminological research and operational purposes. Recent studies show that forensic DNA databanks offer potential to address this problem, through large-scale analysis of DNA matches, many of which involve unidentified offenders. Applying social network analysis (SNA) to 18 years of DNA match data from Québec, Canada, we found that 1400 unknowns do not occupy more marginal positions in the network than 13,000 known offenders, and explain up to 18% of SNA values (e.

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Within the framework of the Swiss Radium Action Plan 2015-22, which aims to investigate and remediate sites contaminated by the radium used in the Swiss watch industry, a reference level of 1 mSv per y has been defined for the exposure of residents. An additional protection objective has been set for soil contamination, which should not exceed the value of 1000 Bq per kg 226Ra. Based on measurements on the study sites, the doses received by residents were calculated accordingly to the methodology, in both indoor and outdoor areas, taking into account external exposure and ingestion.

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In the area of illicit drugs, forensic case data have proven effective at detecting links between seizures and providing greater insights into illicit drug markets. This research explored the application of mathematical and statistical techniques to several chemical profiles of Australian methylamphetamine seizures. The main aim was to create and deliver a method that would expand the use of illicit drug profiling for strategic intelligence purposes, contributing to the fight against illicit drug trafficking.

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Pancreatic ductal adenocarcinoma (PDAC) is a lethal aggressive cancer, in part due to elements of the microenvironment (hypoxia, hypoglycemia) that cause metabolic network alterations. The FDA-approved antihelminthic pyrvinium pamoate (PP) has previously been shown to cause PDAC cell death, although the mechanism has not been fully determined. We demonstrated that PP effectively inhibited PDAC cell viability with nanomolar IC50 values (9-93 nmol/L) against a panel of PDAC, patient-derived, and murine organoid cell lines.

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The present study demonstrates that topoisomerase 3B (TOP3B) forms both RNA and DNA cleavage complexes (TOP3Bccs) in vivo and reveals a pathway for repairing TOP3Bccs. For inducing and detecting cellular TOP3Bccs, we engineer a "self-trapping" mutant of TOP3B (R338W-TOP3B). Transfection with R338W-TOP3B induces R-loops, genomic damage, and growth defect, which highlights the importance of TOP3Bcc repair mechanisms.

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A nearly universal practice among forensic DNA scientists includes mentioning an unrelated person as the possible alternative source of a DNA stain, when one in fact refers to an person. Hence, experts typically express their conclusions with statements like: "The probability of the DNA evidence is times higher if the suspect is the source of the trace than if another person to the suspect is the source of the trace." Published forensic guidelines encourage such allusions to the unrelated person.

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Forensic science has been evolving towards a separation of more and more specialised tasks, with forensic practitioners increasingly identifying themselves with only one sub-discipline or task of forensic science. Such divisions are viewed as a threat to the advancement of science because they tend to polarise researchers and tear apart scientific communities. The objective of this article is to highlight that a piece of information is not either intelligence or evidence, and that a forensic scientist is not either an investigator or an evaluator, but that these notions must all be applied in conjunction to successfully understand a criminal problem or solve a case.

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A collaborative study conducted by three police forensic units, a DNA laboratory, and a forensic academic institute was undertaken in order to compare the performance of four different swabs in controlled and quasi-operational conditions. For this purpose, a reference swab (Prionics cardboard evidence collection kit) currently used within the police forensic units and 3 challenger swabs (COPAN 4N6FLOQSwabs™ (Genetics variety), Puritan FAB-MINI-AP and Sarstedt Forensic Swab) were used for collecting DNA traces from previously used items (referred as "touch DNA" in this article) including on 60 collars, 60 screwdrivers and 60 steering wheels obtained from volunteers. For each comparison, the surface considered was divided into two equal components; one was sampled with the reference swab and the other with one of the three challenger swabs.

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What do policing leaders think and know of forensic science? Beyond crime scene investigators or detectives, how do police senior managers perceive the role, utility and limitations of forensic science? Very few empirical studies have addressed the issue. Forensic scientsts should be concerned about the perception that law enforcement senior managers have of their discipline for two reasons. First, strategic and financial decision-makers are obviously key players in the overall administration and provision of forensic science, either as a supervisor, money provider or as a customer.

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Mitochondria contain their own genome (mtDNA), encoding 13 proteins of the enzyme complexes of the oxidative phosphorylation. Synthesis of these 13 mitochondrial proteins requires a specific translation machinery, the mitoribosomes whose RNA components are encoded by the mtDNA, whereas more than 80 proteins are encoded by nuclear genes. It has been well established that mitochondrial topoisomerase I (TOP1MT) is important for mtDNA integrity and mitochondrial transcription as it prevents excessive mtDNA negative supercoiling and releases topological stress during mtDNA replication and transcription.

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Mitochondrial topoisomerase IB (TOP1MT) is a nuclear-encoded topoisomerase, exclusively localized to mitochondria, which resolves topological stress generated during mtDNA replication and transcription. Here, we report that TOP1MT is overexpressed in cancer tissues and demonstrate that TOP1MT deficiency attenuates tumor growth in human and mouse models of colon and liver cancer. Due to their mitochondrial dysfunction, TOP1MT-KO cells become addicted to glycolysis, which limits synthetic building blocks and energy supply required for the proliferation of cancer cells in a nutrient-deprived tumor microenvironment.

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Background: Gastrin-releasing peptide receptor antagonists have promise in theranostics of several highly incident tumours, including prostate and breast. This study presents the first human dosimetry of Ga-NODAGA-MJ9 in the first five consecutive patients with recurrent prostate cancer included in a dual-tracer positron emission tomography (PET) protocol. Five male patients with biochemical relapse of prostate adenocarcinoma underwent four whole-body time-of-flight PET/CT scans within 2 h after tracer injection.

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Ra is a natural radioelement emitting α and γ radiations. It can be highly concentrated in TENORM materials from the petroleum or fertilizer industries. In Switzerland, Ra is currently a radioactive inheritance problem from the watch industry.

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Industrial activities involving radium sources, such as watchmaking, were still common up until the 1960s. They produced contaminations in building materials and the soil in a large variety of geometries. The potential remediation of such places requires instruments that are properly calibrated as well as adequate procedures.

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Tyrosyl-DNA phosphodiesterase 2 (TDP2) repairs abortive topoisomerase II cleavage complexes. Here, we identify a novel short isoform of TDP2 (TDP2) expressed from an alternative transcription start site. TDP2 contains a mitochondrial targeting sequence, contributing to its enrichment in the mitochondria and cytosol, while full-length TDP2 contains a nuclear localization signal and the ubiquitin-associated domain in the N-terminus.

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SLFN11 sensitizes cancer cells to a broad range of DNA-targeted therapies. Here we show that, in response to replication stress induced by camptothecin, SLFN11 tightly binds chromatin at stressed replication foci via RPA1 together with the replication helicase subunit MCM3. Unlike ATR, SLFN11 neither interferes with the loading of CDC45 and PCNA nor inhibits the initiation of DNA replication but selectively blocks fork progression while inducing chromatin opening across replication initiation sites.

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Aim: The aim of this work was to assess the doses received by a diver exposed to a radiation source during maintenance work in the fuel transfer pool at a Swiss nuclear power plant, and to define whether the statutory limit was breached or not.

Method: Onsite measurements were carried out and different scenarios were simulated using the MicroShield Software and the MCNPX Monte Carlo radiation transport code to estimate the activity of the irradiating object as well as the doses to the limbs and the effective dose delivered to the operator.

Results: The activity of the object was estimated to 1.

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