Resonant Young's Slit Interferometer for Sensitive Detection of Low-Molecular-Weight Biomarkers.

The detection of low-molecular-weight biomarkers is essential for diagnosing and managing various diseases, including neurodegenerative conditions such as Alzheimer's disease. A biomarker's low molecular weight is a challenge for label-free optical modalities, as the phase change they detect is directly proportional to the mass bound on the sensor's surface. To address this challenge, we used a resonant Young's slit interferometer geometry and implemented several innovations, such as phase noise matching and optimisation of the fringe spacing, to maximise the signal-to-noise ratio.

Identification of robust RT-qPCR reference genes for studying changes in gene expression in response to hypoxia in breast cancer cell lines.

Hypoxia is common in breast tumours and is linked to therapy resistance and advanced disease. To understand hypoxia-driven breast cancer progression, RT-qPCR is a widely used technique to quantify transcriptional changes that occur during malignant transformation. Reference genes (RGs) are endogenous RT-qPCR controls used to normalise mRNA levels, allowing accurate assessment of transcriptional changes.

Tubulin detyrosination shapes cytoskeletal architecture and virulence.

Tubulin detyrosination has been implicated in various human disorders and is important for regulating microtubule dynamics. While in most organisms this modification is restricted to α-tubulin, in trypanosomatid parasites, it occurs on both α- and β-tubulin. Here, we show that in , a single vasohibin (LmVASH) enzyme is responsible for differential kinetics of α- and β-tubulin detyrosination.

Unsupervised self-organising map classification of Raman spectra from prostate cell lines uncovers substratified prostate cancer disease states.

Prostate cancer is a disease which poses an interesting clinical question: Should it be treated? Only a small subset of prostate cancers are aggressive and require removal and treatment to prevent metastatic spread. However, conventional diagnostics remain challenged to risk-stratify such patients; hence, new methods of approach to biomolecularly sub-classify the disease are needed. Here we use an unsupervised self-organising map approach to analyse live-cell Raman spectroscopy data obtained from prostate cell-lines; our aim is to exemplify this method to sub-stratify, at the single-cell-level, the cancer disease state using high-dimensional datasets with minimal preprocessing.

TransLeish: Identification of membrane transporters essential for survival of intracellular Leishmania parasites in a systematic gene deletion screen.

For the protozoan parasite Leishmania, completion of its life cycle requires sequential adaptation of cellular physiology and nutrient scavenging mechanisms to the different environments of a sand fly alimentary tract and the acidic mammalian host cell phagolysosome. Transmembrane transporters are the gatekeepers of intracellular environments, controlling the flux of solutes and ions across membranes. To discover which transporters are vital for survival as intracellular amastigote forms, we carried out a systematic loss-of-function screen of the L.

Memory control deficits in the sleep-deprived human brain.

Sleep disturbances are associated with intrusive memories, but the neurocognitive mechanisms underpinning this relationship are poorly understood. Here, we show that sleep deprivation disrupts prefrontal inhibition of memory retrieval, and that the overnight restoration of this inhibitory mechanism is associated with time spent in rapid eye movement (REM) sleep. The functional impairments arising from sleep deprivation are linked to a behavioral deficit in the ability to downregulate unwanted memories, and coincide with a deterioration of deliberate patterns of self-generated thought.

Worldwide Sodium Channel Conference, January 31st-February 2nd, 2024, Grindelwald, Switzerland.

The following is a brief report of the inaugural Worldwide Sodium Channels Conference, held in Grindelwald, Switzerland, in January 2024. This excellent in-person conference followed the highly successful online Worldwide Sodium Channel Seminars series which started following the COVID-19 pandemic, in 2021. We present here our highlights of the 45 presentations delivered over the two-and-a-half-day conference, focusing on key outputs from each of the eight sessions.

Emotional inertia is independently associated with cognitive emotion regulation strategies and sleep quality.

Emotional inertia (i.e. the tendency for emotions to persist over time) is robustly associated with lower wellbeing.

Immunoinformatic predictions and characterization of Schistosoma mansoni peptides as candidates for immunodiagnostic.

Schistosoma mansoni represents a significant etiological agent of schistosomiasis, a neglected tropical disease with a global distribution. Although the Kato-Katz technique is an effective diagnostic tool in areas with a high prevalence of the disease, it lacks sensitivity in regions with lower prevalence. The objective of this study was to identify and validate novel immunogenic peptide targets derived from the S.

Mechanisms of life cycle simplification in African trypanosomes.

African trypanosomes are important parasites in sub-Saharan Africa that undergo a quorum-sensing dependent development to morphologically 'stumpy forms' in mammalian hosts to favour transmission by tsetse flies. However, some trypanosome clades have simplified their lifecycle by escaping dependence on tsetse allowing an expanded geographic range, with direct transmission between hosts achieved via blood-feeding biting flies and vampire bats (Trypanosoma brucei evansi, causing 'surra') or through sexual transmission (Trypanosoma brucei equiperdum, causing 'dourine'). Concomitantly, stumpy formation is reduced and the isolates are described as monomorphic, with infections spread widely in Africa, Asia, South America and parts of Europe.

The holistic forgetting of events and the (sometimes) fragmented forgetting of objects.

Episodic events are typically retrieved and forgotten holistically. If you recall one element (e.g.

Photonic and electrochemical biosensors for near-patient tests-a critical comparison.

Research into diagnostic biosensors is a vibrant field that combines scientific challenge with translational opportunities; innovation in healthcare is of great societal interest and is an essential element of future healthcare provision. Photonic and electrochemical biosensors are the dominant modalities, both scientifically and commercially, yet the two scientific communities largely remain separated and siloed. It seems astute to better understand what the two fields can learn from one another so as to progress the key scientific, translational, and commercial challenges.

Isolobal Cationic Iridium Dihydride and Dizinc Complexes: A Dual Role for the ZnR Ligand Enhances H Activation.

The reaction of [Ir(IPr)H][BAr] (; IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene; BAr = B{CH(3,5-CF)}) with ZnMe proceeds with CH elimination to give [Ir(IPr)(IPr')(ZnMe)H][BAr] (, where (IPr') is a cyclometalated IPr ligand). reacts with H to form tetrahydride [Ir(IPr)(ZnMe)H][BAr], , that loses H under forcing conditions to form [Ir(IPr)(ZnMe)H][BAr], . Crystallization of also results in the formation of its noncyclometalated isomer, [Ir(IPr)(ZnMe)][BAr], , in the solid state.

Co-expression gene module analysis in response to attenuated cercaria vaccine reveals a critical role for NK cells in protection against Schistosoma mansoni.

Background: Despite decades of research, an effective schistosomiasis vaccine remains elusive. The radiation-attenuated (RA) cercarial vaccine remains the best model for eliciting high levels of protection. We have recently explored this model in mice to identify potentially protective pathways by examining gene expression patterns in peripheral blood mononuclear cells (PBMC).

Structure and selectivity of a glutamate-specific TAXI TRAP binding protein from Vibrio cholerae.

Tripartite ATP-independent periplasmic (TRAP) transporters are widespread in prokaryotes and are responsible for the transport of a variety of different ligands, primarily organic acids. TRAP transporters can be divided into two subclasses; DctP-type and TAXI type, which share the same overall architecture and substrate-binding protein requirement. DctP-type transporters are very well studied and have been shown to transport a range of compounds including dicarboxylates, keto acids, and sugar acids.

Exploring the Impact of Variability in Cell Segmentation and Tracking Approaches.

Segmentation and tracking are essential preliminary steps in the analysis of almost all live cell imaging applications. Although the number of open-source software systems that facilitate automated segmentation and tracking continue to evolve, many researchers continue to opt for manual alternatives for samples that are not easily auto-segmented, tracing cell boundaries by hand and reidentifying cells on consecutive frames by eye. Such methods are subject to inter-user variability, introducing idiosyncrasies into the results of downstream analysis that are a result of subjectivity and individual expertise.

PU.1 eviction at lymphocyte-specific chromatin domains mediates glucocorticoid response in acute lymphoblastic leukemia.

The epigenetic landscape plays a critical role in cancer progression, yet its therapeutic potential remains underexplored. Glucocorticoids are essential components of treatments for lymphoid cancers, but resistance, driven in part by epigenetic changes at glucocorticoid-response elements, poses a major challenge to effective therapies. Here we show that glucocorticoid treatment induces distinct patterns of chromosomal organization in glucocorticoid-sensitive and resistant acute lymphoblastic leukemia xenograft models.

Clinical anemia predicts dermal parasitism and reservoir infectiousness during progressive visceral leishmaniosis.

Dogs represent the primary reservoir for Leishmania infantum human visceral leishmaniasis (VL) transmitted through phlebotomine sand flies. Public health initiatives targeting zoonotic VL commonly focus on dogs with severe clinical disease, often in renal failure, as they have previously been considered the most infectious to sand flies. However, more recent studies suggest that dogs with mild to moderate clinical disease may be more infectious than dogs with severe disease.

Toscana virus - an emerging Mediterranean arbovirus transmitted by sand flies.

Toscana virus (TOSV) is an emerging arthropod-borne virus (arbovirus) of medical importance that is increasing its range across much of the Mediterranean Basin, Europe and the Middle East. Transmitted by spp. sand flies, it is the most clinically relevant sand fly-borne phlebovirus.