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When the grandfather he never knew is released from prison suffering from dementia, eleven-year-old Nicholas, a mathematical and musical genius, tries to save the family's home by helping search for heirlooms Grandpa claims to have buried.
Book
Liquid biopsies: the future of cancer early detection
Cancer is a worldwide pandemic. The burden it imposes grows steadily on a global scale causing emotional, physical, and financial strains on individuals, families, and health care systems. Despite being the second leading cause of death worldwide, many cancers do not have screening programs and many people with a high risk of developing cancer fail to follow the advised medical screening regime due to the nature of the available screening tests and other challenges with compliance. Moreover, many liquid biopsy strategies being developed for early detection of cancer lack the sensitivity required to detect early-stage cancers. Early detection is key for improved quality of life, survival, and to reduce the financial burden of cancer treatments which are greater at later stage detection. This review examines the current liquid biopsy market, focusing in particular on the strengths and drawbacks of techniques in achieving early cancer detection. We explore the clinical utility of liquid biopsy technologies for the earlier detection of solid cancers, with a focus on how a combination of various spectroscopic and -omic methodologies may pave the way for more efficient cancer diagnostics.
Journal Article
1970s jazz fusion
\"From the earliest glimmers of America's music going electric, traditional fans accused such legends as Miles Davis and Donald Byrd of contaminating an art form so rich in history and complex in structure with the brazen commercialism and seeming simplicity of new genres like rock, soul, and funk. The accusations of selling out were only compounded by the fact that artists like Herbie Hancock and Chick Corea sold far more records and reached more non-jazz fans in the 1970s with their fusion records than with their straight-ahead jazz records. Find out more about the musical hybrid that has become one of the most influential genres of music in jazz, rock, soul, and hip-hop\"-- Provided by publisher.
BOOK
Contrast of warm and cold phases in the Bering Sea to understand spatial distributions of Arctic and sub-Arctic gadids
The influence of climate on the dynamics of Arctic gadids is of increasing interest, particularly as research and survey effort expands in the Pacific Arctic. Understanding species-specific thermal tolerance may inform models of species distribution and projections of available habitat and also clarify implications of warming for ecological communities. Analyzing shifts in species distribution in warm and cold periods, this study considers the effects of a warming climate on the distribution of two keystone Arctic gadids (polar cod, saffron cod) and two commercially important sub-Arctic gadids (walleye pollock, Pacific cod). Shifts in distribution were used to derive temperature tolerance thresholds and to project how these species might react to a warming Arctic. Significant shifts were noted in comparisons of warm (2002–2005, 2014–2016, 2017–2018) and cold (2006–2013) periods. Sub-Arctic species expanded and contracted their range as environmental conditions shifted. In contrast, Arctic species appeared constrained, such that population densities increased or decreased within the same core geographic area. Additionally, species with a demersal life history were able to tolerate a wider range of thermal conditions. These results provide important insights on relative thermal tolerance of each species, differential influence of temperature on pelagic versus demersal life histories, and depth as thermal refuge. This study demonstrates both the need to understand the spatial response of fish to changing ocean conditions in polar regions and the utility of distributional analyses to inform that effort.
Journal Article
Ion-Powered Rotary Motors: Where Did They Come from and Where They Are Going?
Molecular motors are found in many living organisms. One such molecular machine, the ion-powered rotary motor (IRM), requires the movement of ions across a membrane against a concentration gradient to drive rotational movement. The bacterial flagellar motor (BFM) is an example of an IRM which relies on ion movement through the stator proteins to generate the rotation of the flagella. There are many ions which can be used by the BFM stators to power motility and different ions can be used by a single bacterium expressing multiple stator variants. The use of ancestral sequence reconstruction (ASR) and functional analysis of reconstructed stators shows promise for understanding how these proteins evolved and when the divergence in ion use may have occurred. In this review, we discuss extant BFM stators and the ions that power them as well as recent examples of the use of ASR to study ion-channel selectivity and how this might be applied to further study of the BFM stator complex.
Journal Article
Spatial configuration and time of day impact the magnitude of urban tree canopy cooling
Tree cover is generally associated with cooler air temperatures in urban environments but the roles of canopy configuration, spatial context, and time of day are not well understood. The ability to examine spatiotemporal relationships between trees and urban climate has been hindered by lack of appropriate air temperature data and, perhaps, by overreliance on a single ‘tree canopy’ class, obscuring the mechanisms by which canopy cools. Here, we use >70 000 air temperature measurements collected by car throughout Washington, DC, USA in predawn (pd), afternoon (aft), and evening (eve) campaigns on a hot summer day. We subdivided tree canopy into ‘soft’ (over unpaved surfaces) and ‘hard’ (over paved surfaces) canopy classes and further partitioned soft canopy into distributed (narrow edges) and clumped patches (edges with interior cores). At each level of subdivision, we predicted air temperature anomalies using generalized additive models for each time of day. We found that the all-inclusive ‘tree canopy’ class cooled linearly at every time (pd = 0.5 °C ± 0.3 °C, aft = 1.8 °C ± 0.6 °C, eve = 1.7 °C ± 0.4 °C), but could be explained in the afternoon by aggregate effects of predominant hard and soft canopy cooling at low and high canopy cover, respectively. Soft canopy cooled nonlinearly in the afternoon with minimal effect until ∼40% cover but strongly (and linearly) across all cover fractions in the evening (pd = 0.7 °C ± 1.1 °C, aft = 2.0 °C ± 0.7 °C, eve = 2.9 °C ± 0.6 °C). Patches cooled at all times of day despite uneven allocation throughout the city, whereas more distributed canopy cooled in predawn and evening due to increased shading. This later finding is important for urban heat island mitigation planning since it is easier to find planting spaces for distributed trees rather than forest patches.
Journal Article
Development of high-throughput ATR-FTIR technology for rapid triage of brain cancer
Non-specific symptoms, as well as the lack of a cost-effective test to triage patients in primary care, has resulted in increased time-to-diagnosis and a poor prognosis for brain cancer patients. A rapid, cost-effective, triage test could significantly improve this patient pathway. A blood test using attenuated total reflection (ATR)-Fourier transform infrared (FTIR) spectroscopy for the detection of brain cancer, alongside machine learning technology, is advancing towards clinical translation. However, whilst the methodology is simple and does not require extensive sample preparation, the throughput of such an approach is limited. Here we describe the development of instrumentation for the analysis of serum that is able to differentiate cancer and control patients at a sensitivity and specificity of 93.2% and 92.8%. Furthermore, preliminary data from the first prospective clinical validation study of its kind are presented, demonstrating how this innovative technology can triage patients and allow rapid access to imaging.
Diagnosing brain cancer is frequently difficult and requires specialist equipment. Here, the authors develop their previous attenuated total reflectance-Fourier transform infrared spectroscopy method and incoporate the use of disposable silicon wafers for diagnosing brain cancer using serum samples.
Journal Article
Gating machinery of InsP3R channels revealed by electron cryomicroscopy
Inositol-1,4,5-trisphosphate receptors (InsP
3
Rs) are ubiquitous ion channels responsible for cytosolic Ca
2+
signalling and essential for a broad array of cellular processes ranging from contraction to secretion, and from proliferation to cell death. Despite decades of research on InsP
3
Rs, a mechanistic understanding of their structure–function relationship is lacking. Here we present the first, to our knowledge, near-atomic (4.7 Å) resolution electron cryomicroscopy structure of the tetrameric mammalian type 1 InsP
3
R channel in its apo-state. At this resolution, we are able to trace unambiguously ∼85% of the protein backbone, allowing us to identify the structural elements involved in gating and modulation of this 1.3-megadalton channel. Although the central Ca
2+
-conduction pathway is similar to other ion channels, including the closely related ryanodine receptor, the cytosolic carboxy termini are uniquely arranged in a left-handed α-helical bundle, directly interacting with the amino-terminal domains of adjacent subunits. This configuration suggests a molecular mechanism for allosteric regulation of channel gating by intracellular signals.
This study has determined the electron cryomicroscopy structure of the mammalian type 1 InsP
3
receptor in a ligand-free state at 4.7 Å resolution; although the central Ca
2+
-conduction pathway is similar to other ion channels, the unique architecture of the C-terminal domains of the tetrameric channel suggests that a distinctive allosteric mechanism underlies the activation of InsP
3
gating.
InsP
3
receptor structure
Irina Serysheva and colleagues have determined the electron cryomicroscopy structure of the mammalian type 1 inositol-1,4,5-trisphosphate receptor (InsP
3
R) in a ligand-free state at 4.7 Å resolution. InsP
3
Rs are responsible for cytosolic Ca
2+
signalling and are involved in a wide range of physiological functions. The structure reveals a central Ca
2+
-conduction pathway similar to that found in other ion channels, including the closely related ryanodine receptor, but the unique architecture of the C-terminal domain of the tetrameric channel points to a distinctive allosteric mechanism for the activation of InsP
3
R gating.
Journal Article
Light Control in Microbial Systems
Light is a key environmental component influencing many biological processes, particularly in prokaryotes such as archaea and bacteria. Light control techniques have revolutionized precise manipulation at molecular and cellular levels in recent years. Bacteria, with adaptability and genetic tractability, are promising candidates for light control studies. This review investigates the mechanisms underlying light activation in bacteria and discusses recent advancements focusing on light control methods and techniques for controlling bacteria. We delve into the mechanisms by which bacteria sense and transduce light signals, including engineered photoreceptors and light-sensitive actuators, and various strategies employed to modulate gene expression, protein function, and bacterial motility. Furthermore, we highlight recent developments in light-integrated methods of controlling microbial responses, such as upconversion nanoparticles and optical tweezers, which can enhance the spatial and temporal control of bacteria and open new horizons for biomedical applications.
Journal Article
The parasitic lifestyle of an archaeal symbiont
DPANN archaea are a diverse group of microorganisms characterised by small cells and reduced genomes. To date, all cultivated DPANN archaea are ectosymbionts that require direct cell contact with an archaeal host species for growth and survival. However, these interactions and their impact on the host species are poorly understood. Here, we show that a DPANN archaeon (
Candidatus
Nanohaloarchaeum antarcticus) engages in parasitic interactions with its host (
Halorubrum lacusprofundi
) that result in host cell lysis. During these interactions, the nanohaloarchaeon appears to enter, or be engulfed by, the host cell. Our results provide experimental evidence for a predatory-like lifestyle of an archaeon, suggesting that at least some DPANN archaea may have roles in controlling host populations and their ecology.
DPANN archaea are a group of microorganisms that require direct cell contact with other archaeal host species for growth. Here, Hamm et al. show that a DPANN archaeon engages in parasitic interactions with its host leading to host cell lysis, thus providing experimental evidence of a predatory-like lifestyle for an archaeon.
Journal Article