Publications by authors named "Simm M"

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with poor survival. Novel biomarkers are urgently needed to improve the outcome through early detection. Here, we aimed to discover novel biomarkers for early PDAC detection using multi-omics profiling in pre-diagnostic plasma samples biobanked after routine health examinations.

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Background: Pancreatic ductal adenocarcinoma (pancreatic cancer) is often detected at late stages resulting in poor overall survival. To improve survival, more patients need to be diagnosed early when curative surgery is feasible. We aimed to identify circulating metabolites that could be used as early pancreatic cancer biomarkers.

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  • The thymic involution process starts shortly after birth and continues throughout life, with notable acceleration after puberty, but its timeline in humans is not well-defined.
  • A 96-year-old male’s thymus showed distinct differences between the right and left lobes, with the right lobe remaining well-preserved and the left lobe significantly replaced by fat tissue.
  • Advanced testing revealed T-cell populations in the preserved right lobe, suggesting it may continue to contribute to immune responses even in old age, highlighting different regression rates in the thymic lobes.
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Exogenous anomalies induced by contemporary climate change may severely impact dynamics of early life stages of fish. Here, we modelled how growth rate and abundance of postflexion larvae, and recruitment of Baltic spring-spawning herring (Clupea harengus membras) in the Pärnu Bay, Gulf of Riga (GoR) may respond to shifting climate variables. Higher larval growth rates were aligned with later seasonal emergence of yolk-sac larvae, while lower abundance of postflexion larvae occurred in years of earlier seasonal seawater warming.

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  • DING proteins exhibit phosphatase activity which impacts HIV-1 gene transcription by dephosphorylating key factors, specifically RNA polymerase II and NF-κB subunits.
  • Experimental methods such as ELISA, northern-blot, and western-blot assays were used to show that DING proteins significantly inhibit HIV-1 infection and reduce the phosphorylation of the p65 NF-κB subunit.
  • The presence of DING leads to an accumulation of hypo-phosphorylated p65 NF-κB in cells, suggesting that DING disrupts the activation and nuclear import of NF-κB, ultimately suppressing its ability to promote HIV-1 transcription.
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Aim: To determine the performance of plasma calprotectin as a marker of sepsis on intensive care unit (ICU) admission and as a marker of mortality day 30 post-ICU admission.

Materials & Methods: Consecutive ICU patients were allocated to: sepsis (n = 15), postoperative inflammation (n = 23) and intoxication without inflammation (n = 7) groups.

Results: Calprotectin was 4.

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X-DING-CD4 is a novel phosphatase mediating antiviral responses to HIV-1 infection. This protein is constitutively expressed and secreted by HIV-1 resistant CD4(+) T cells and its mRNA transcription is up-regulated in peripheral blood mononuclear cells from HIV-1 elite controllers. The secreted/soluble X-DING-CD4 protein form is of particular importance because it blocks virus transcription when added to HIV-1 susceptible cells.

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Because of the high management relevance, commercial fish related aspects have often been central in marine ecosystem investigations. The iterative shiftogram method was applied to detect occurrence, type and timing of shifts in the single and multivariate time series linked to the spring spawning herring larvae in the Gulf of Riga (Baltic Sea). Altogether nineteen larval herring and related environmental variables were utilized during the period of 1957-2010.

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Independent research groups reported that DING protein homologues isolated from bacterial, plant and human cells demonstrate the anti-HIV-1 activity. This might indicate that diverse organisms utilize a DING-mediated broad-range protective innate immunity response to pathogen invasion, and that this mechanism is effective also against HIV-1. We performed structural analyses and evaluated the anti-HIV-1 activity for four DING protein homologues isolated from different species.

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X-DING-CD4 blocks HIV-1 long terminal repeat (LTR) and pathogen induced pro-inflammatory response. Increased activity of the X-DING-CD4 gene is associated with cellular resistance to virus; therefore, HIV-1 elite controllers (ECs) should have higher X-DING-CD4 and reduced pro-inflammatory mRNA activity than viremic or uninfected individuals. Also, depending on the cell stimulating factor, expression of X-DING-CD4 mRNA in ECs might be autonomous or contingent on IFN signaling.

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Clinical reports indicate that some infected individuals control HIV-1 replication through undefined mechanisms. Our group reported that a human protein named X-DING-CD4 holds a potent antiviral activity, blocking transcription of HIV-1 LTR through the inhibition of NF-κB/DNA binding. Based on observations that transformed HIV-1 resistant CD4(+) T cells produce higher levels of soluble X-DING-CD4 protein upon their exposure to virus, we hypothesized that resistance to HIV-1 in these cells may be regulated through function of the X-DING-CD4 gene.

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Onsets of bacterial infections devastate the compromised immune system in AIDS patients. Damaged gut mucosa permits dissemination of bacterial toxins into deeper layers and hyper-activation of the immune system. We previously reported that the unfractionated supernatants of HIV-resistant CD4(+) T cells impeded the NF-κB/DNA binding in macrophages induced by either HIV-1 or LPS.

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Purpose: Our laboratory receives many routine requests for plasma zinc analysis from intensive care units (ICUs) throughout Scotland. However, such requests are inappropriate because plasma zinc concentrations fall independently of nutritional deficiency during the systemic inflammatory response and, therefore, in critically ill patients. This survey was performed to investigate how widespread this practice was and if low plasma zinc concentrations were interpreted as zinc deficiency so triggering inappropriate initiation of zinc supplementation.

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The feeding ecology of four pelagic fish species was studied in relation to their prey availability in the Gulf of Riga (Baltic Sea) during the summer 1999-2006. The zooplankton community was dominated by the cladoceran Bosmina longispina, rotifers Keratella cochlearis and K. quadrata and the copepod Eurytemora affinis, with the highest interannual variability in abundance recorded for B.

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Article Synopsis
  • Researchers identified a new anti-viral factor called X-DING-CD4 from HIV-1 resistant cells known as HRF(+) cells, which shares similarities with DING proteins.
  • The factor was confirmed to be present in the extracellular space of HRF(+) cells using a specific antibody, differentiating it from HRF(-) control cells.
  • X-DING-CD4 was shown to block HIV-1 replication and expression in certain assays, with its activity being neutralized by targeted antibodies.
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Intranasal transmission of hepatitis C virus (HCV) via contaminated drug-sniffing implements is a potential but unconfirmed source of viral infection. We demonstrate the virological plausibility of intranasal transmission by confirming that blood and HCV RNA are present in the nasal secretions and drug-sniffing implements of HCV-infected intranasal drug users recruited from a community health clinic in New York City.

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  • Researchers used a CD4(+) T cell model called HRF(+) to investigate how certain soluble molecules create anti-HIV-1 responses.
  • They discovered that these soluble products activated the CTCF gene in CD4(+) T cells, leading to temporary resistance against HIV-1.
  • CTCF protein binds to the HIV-1 promoter, blocking key interactions that normally help the virus thrive, indicating that CTCF plays a crucial role in the cells' resistance to HIV-1.
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Concentrations of polychlorinated dibenzo-p-dioxins (PCDD), polychlorinated dibenzofurans (PCDF) and polychlorinated biphenyls (PCB) in Baltic Sea fish like herring (Clupea harengus membras), sprat (Sprattus sprattus balticus), perch (Perca fluviatilis), pikeperch (Sander lucioperca) and flounder (Platichthys flesus trachurus) collected from four areas of the Estonian coastal waters are reported. All samples are studied for their relationship between the length (cm) and wet weight (g); length (cm) and age (years); lipid content and dry matter. The level of PCDD/F and PCB concentrations in younger 1-5 years old Baltic herring and sprat collected in 2002-2005 from the eastern and central parts of the Gulf of Finland, Gulf of Riga and Open Baltic Sea (Central Baltic) is related to the fish age and compared with those found in the 1990s.

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  • Recent research explored the anti-viral effects of the HIV-1 resistance factor (HRF) on CD4 T cells, demonstrating its role in blocking the NF-kappaB/DNA complex crucial for HIV gene expression.
  • HRF was tested on primary macrophages and shown to inhibit HIV-1 replication while also promoting HRF-like activity in these immune cells.
  • The study concluded that HRF disrupts NF-kappaB binding in macrophages triggered by HIV-1 and bacterial components, leading to reduced inflammatory responses against these pathogens.
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  • Human cells can produce proteins that block HIV replication, but these proteins aren't specifically designed to target the virus.
  • Interferons and certain proteins regulated by them are known to effectively inhibit HIV, showcasing the body's natural defense mechanisms.
  • Ongoing research aims to discover new antiviral factors secreted by immune cells, which could lead to understanding how to better fight HIV.
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The concentrations and congeners pattern of the polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) were determined in sprat collected by the commercial catches in the Gulf of Finland, Baltic Sea. Based on the toxic equivalent concentrations 2,3,4,7,8-PeCDF prevailed among the congeners of PCDD/Fs. The significance of age- and season-specific relationship between the concentration of lipids and dioxins was demonstrated.

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  • Research has identified anti-HIV factors secreted by CD8 and CD4 T cells, with one notable factor, HIV-1 resistance factor (HRF), found in a newly established HIV-1-resistant CD4 T cell line.
  • HRF inhibits HIV-1 transcription by interfering with the NF-kappaB pathway, a key process in virus activation.
  • The study reveals that HRF binds to the p50 protein after it enters the nucleus, preventing its ability to form a complex with DNA, which is essential for activating HIV-1 transcription.
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  • Linker histone H1B was identified as a coeluting protein with antiviral activity during the purification of the HIV-1 resistance factor (HRF) from cell supernatants.
  • Analysis showed that the presence of H1B correlated with HIV-1 resistance, as silencing H1B significantly reduced the antiviral activity of HRF(+) cell supernatants.
  • The study suggests that ubiquitinated H1B may act as a cofactor for HRF, influencing its expression and secretion from CD4(+) T cells, which becomes crucial in resisting HIV-1 infection.
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