"Quantum sensing" describes the use of a quantum system, quantum properties or quantum phenomena to perform a measurement of a physical quantity Historical examples of quantum sensors include magnetometers based on superconducting quantum interference devices and atomic vapors, or atomic clocks More recently, quantum sensing has become a distinct and rapidly growing branch of research within the area of quantum science and technology, with the most common platforms being spin qubits, trapped ions and flux qubits The field is expected to provide new opportunities - especially with regard to high sensitivity and precision - in applied physics and other areas of science In this review, we provide an introduction to the basic principles, methods and concepts of quantum sensing from the viewpoint of the interested experimentalist

Quantum sensing

Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control

The helix-loop-helix (HLH) family of transcriptional regulatory proteins are key players in a wide array of developmental processes. Over 240 HLH proteins have been identified to date in organisms ranging from the yeast Saccharomyces cerevisiae to humans (6). Studies in Xenopus laevis, Drosophila melanogaster, and mice have convincingly demonstrated that HLH proteins are intimately involved in developmental events such as cellular differentiation, lineage commitment, and sex determination. In yeast, HLH proteins regulate several important metabolic pathways, including phosphate uptake and phospholipid biosynthesis (19, 67, 112). In multicellular organisms, HLH factors are required for a multitude of important developmental processes, including neurogenesis, myogenesis, hematopoiesis, and pancreatic development (12, 86, 127, 179). The purpose of this review is to examine the structure and functional properties of HLH proteins.



E-box sites: elements mediating cell-type-specific gene transcription. 
Gene transcription of the immunoglobulin heavy-chain (IgH) gene has long been known to be regulated, in part, by a cis-acting DNA element known as the IgH intronic enhancer (109, 156). By in vivo methylation protection assays, a number of sites were identified in both the IgH and the kappa light-chain gene enhancers which were specifically protected in B cells but not in nonlymphoid cells (41). These elements shared a signature motif which consisted of the core hexanucleotide sequence, CANNTG, and were subsequently dubbed E boxes (41). A total of five E-box elements are present in the IgH gene enhancer: μE1, μE2, μE3, μE4, and μE5. The Ig kappa enhancer also contains three cannonical E boxes, designated κE1, κE2, and κE3. E-box sites have been subsequently found in B-cell-specific promoter and enhancer elements, including a subset of Ig light-chain gene promoters, the IgH and Ig light-chain 3′ enhancers, and, more recently, the λ5 promoter (110, 118, 156).

E-box elements have also been identified in promoter and enhancer elements that regulate muscle-, neuron-, and pancreas-specific gene expression. For example, in muscle, the muscle creatine kinase gene, acetylcholine receptor genes α and δ, and the myosin light-chain gene all require E-box elements for full activity (27, 51, 85). A number of genes whose expression is limited to the pancreas also require E-box sites for proper expression. The insulin and somatostatin genes, for example, contain E-box sites that, when multimerized, are sufficient to regulate pancreatic β-cell-specific gene expression (168). More recently, E-box regulatory sites have been identified in a number of neuron-specific genes, including the opsin, hippocalcin, beta 2 subunit of the neuronal nicotinic acetylcholine receptor, and muscarinic acetylcholine receptor genes (1, 21, 52, 125).




E-box sites: cognate recognition sequence for HLH proteins. 
Two proteins, termed E12 and E47, were originally identified as binding to the κE2/μE5 site (65, 102). They have a region of homology with the Drosophila Daughterless protein, the myogenic differentiation factor MyoD, members of the achaete-scute gene complex, and the Myc family of transcription factors (102). This stretch of conserved residues, known as the Myc homology region, appeared to be critical for the DNA binding properties of E12 and E47 (102). The E12 and E47 proteins, which differ only within this Myc homology region, arise by alternative splicing of the E2A gene (157). This conserved sequence, which was modeled as two amphipathic alpha helices separated by a flexible loop structure, was named the HLH motif and shown to function as a dimerization domain.




The HLH structure. 
The solution structure of the basic HLH (bHLH)-leucine zipper (LZ) factor Max first confirmed the existence of the HLH motif (44). Subsequently, the three-dimensional structure of the E47 bHLH polypeptide bound to its E-box recognition site, CACCTG, has been solved at 2.8-Å resolution (38). A number of interesting features were revealed from analysis of the E47 crystal structure. The E47 dimer forms a parallel, four-helix bundle which allows the basic region to contact the major groove (38). In addition to the basic region, residues in the loop and helix 2 also make contact with DNA (38). Stable interaction of the HLH domain is favored by van der Waals interactions between conserved hydrophobic residues (38). The E47 dimer is centered over the E box, with each monomer interacting with either a CAC or CAG half-site. A glutamate present in the basic region of each subunit makes contact with the cytosine and adenine bases in the E-box half-site. An adjacent arginine residue stabilizes the position of the glutamate by direct interaction with these nucleotides and additionally the phosphodiester backbone. Both the glutamate and the arginine residues are conserved in most bHLH proteins, consistent with a role in specific DNA binding (6, 38, 102).




Classification of the HLH proteins. 
Owing to the large number of HLH proteins that have been described, a classification scheme that was based upon tissue distribution, dimerization capabilities, and DNA-binding specificities was devised (Fig. ​(Fig.1)1) (101). Class I HLH proteins, also known as the E proteins, include E12, E47, HEB, E2-2, and Daughterless. These proteins are expressed in many tissues and capable of forming either homo- or heterodimers (103). The DNA-binding specificity of class I proteins is limited to the E-box site. Class II HLH proteins, which include members such as MyoD, myogenin, Atonal, NeuroD/BETA2, and the achaete-scute complex, show a tissue-restricted pattern of expression. With few exceptions, they are incapable of forming homodimers and preferentially heterodimerize with the E proteins. Class I-class II heterodimers can bind both canonical and noncanonical E-box sites (103). Class III HLH proteins include the Myc family of transcription factors, TFE3, SREBP-1, and the microphthalmia-associated transcription factor, Mi. Proteins of this class contain an LZ adjacent to the HLH motif (66, 177). Class IV HLH proteins define a family of molecules, including Mad, Max, and Mxi, that are capable of dimerizing with the Myc proteins or with one another (7, 22, 174). A group of HLH proteins that lack a basic region, including Id and emc, define the class V HLH proteins (18, 39, 47). Class V members are negative regulators of class I and class II HLH proteins (18, 39, 47). Class VI HLH proteins have as their defining feature a proline in their basic region. This group includes the Drosophila proteins Hairy and Enhancer of split (76, 141). Finally, the class VII HLH proteins are categorized by the presence of the bHLH-PAS domain and include members such as the aromatic hydrocarbon receptor (AHR), the AHR nuclear-translocator (Arnt), hypoxia-inducible factor 1α, and the Drosophila Single-minded and Period proteins (34). 



FIG. 1

Multiple sequence alignment and classification of some representative members of the HLH family of transcription factors. Shown is a dendrogram created by aligning the sequences of the indicated HLH proteins by the Clustal W algorithm (160).



Recently, another classification method of HLH proteins has been described (6). Based on the amino acid sequences of 242 HLH proteins, a phylogenetic tree was created to group family members according to evolutionary relationships (6). Four major groups, A through D, which comprise more than 24 protein families were identified (6). The groupings were based upon DNA-binding specificity as well as conservation of amino acids at certain positions (6). As the number of HLH proteins continues to grow, this evolutionary or “natural” classification may provide a more accurate and convenient means of categorization.

Helix-loop-helix proteins: regulators of transcription in eucaryotic organisms.

THE JOURNAL OF BIOLOGICAL CHEMISTRY: The Biochemical Behavior of LeadL I. Influence of Calcium, Phosphorus, and Vitamin D on Lead in Blood and Bone

Crystal defects in diamond have emerged as unique objects for a variety of applications, both because they are very stable and because they have interesting optical properties. Embedded in nanocrystals, they can serve, for example, as robust single-photon sources or as fluorescent biomarkers of unlimited photostability and low cytotoxicity. The most fascinating aspect, however, is the ability of some crystal defects, most prominently the nitrogen-vacancy (NV) center, to locally detect and measure a number of physical quantities, such as magnetic and electric fields. This metrology capacity is based on the quantum mechanical interactions of the defect's spin state. In this review, we introduce the new and rapidly evolving field of nanoscale sensing based on single NV centers in diamond. We give a concise overview of the basic properties of diamond, from synthesis to electronic and magnetic properties of embedded NV centers. We describe in detail how single NV centers can be harnessed for nanoscale sensing,...

Nitrogen-Vacancy Centers in Diamond: Nanoscale Sensors for Physics and Biology

Magnetic imaging is a powerful tool for probing biological and physical systems. However, existing techniques either have poor spatial resolution compared to optical microscopy and are hence not generally applicable to imaging of sub-cellular structure (e.g., magnetic resonance imaging [MRI] 1 ), or entail operating conditions that preclude application to living biological samples while providing sub-micron resolution (e.g., scanning superconducting quantum interference device [SQUID] microscopy 2 , electron holography 3 , and magnetic resonance force microscopy [MRFM] 4 ). Here we demonstrate magnetic imaging of living cells (magnetotactic bacteria) under ambient laboratory conditions and with sub-cellular spatial resolution (400 nm), using an optically-detected magnetic field imaging array consisting of a nanoscale layer of nitrogen-vacancy (NV) colour centres implanted at the surface of a diamond chip. With the bacteria placed on the diamond surface, we optically probe the NV quantum spin states and rapidly reconstruct images of the vector components of the magnetic field created by chains of magnetic nanoparticles (magnetosomes) produced in the bacteria, and spatially correlate these magnetic field maps with optical images acquired in the same apparatus. Wide-field sCMOS acquisition allows parallel optical and magnetic imaging of multiple cells in a population with sub-micron resolution and >100 micron field-of-view. Scanning electron microscope (SEM) images of the bacteria confirm that the correlated optical and magnetic images can be used to locate and characterize the magnetosomes in each bacterium. The results provide a new capability

/pdf/optical-magnetic-imaging-of-living-cells-2z9u5d2jsq.pdf

Optical magnetic imaging of living cells

Magnetosomes are membranous bacterial organelles sharing many features of eukaryotic organelles. Using electron cryotomography, we found that magnetosomes are invaginations of the cell membrane flanked by a network of cytoskeletal filaments. The filaments appeared to be composed of MamK, a homolog of the bacterial actin-like protein MreB, which formed filaments in vivo. In a mamK deletion strain, the magnetosome-associated cytoskeleton was absent and individual magnetosomes were no longer organized into chains. Thus, it seems that prokaryotes can use cytoskeletal filaments to position organelles within the cell.

https://science.sciencemag.org/content/sci/311/5758/242.full.pdf

Magnetosomes Are Cell Membrane Invaginations Organized by the Actin-Like Protein MamK

Transcription factors are often phosphorylated at multiple sites. Here it is shown that multiple phosphorylation sites on the budding yeast transcription factor Pho4 play distinct and separable roles in regulating the factor's activity. Phosphorylation of Pho4 at two sites promotes the factor's nuclear export and phosphorylation at a third site inhibits its nuclear import. Phosphorylation of a fourth site blocks the interaction of Pho4 with the transcription factor Pho2. Multiple phosphorylation sites provide overlapping and partially redundant layers of regulation that function to efficiently control the activity of Pho4.

https://science.sciencemag.org/content/sci/284/5416/977.full.pdf

Roles of phosphorylation sites in regulating activity of the transcription factor Pho4.

Bacterial magnetosomes are intracellular compartments that house highly ordered magnetite crystals. By using Magnetospirillum sp. AMB-1 as a model system, we show that magnetosome vesicles exist in the absence of magnetite, biomineralization of magnetite proceeds simultaneously in multiple vesicles, and biomineralization proceeds from the same location in each vesicle. The magnetosome-associated protein, MamA, is required for the formation of functional magnetosome vesicles and displays a dynamic subcellular localization throughout the growth cycle of magnetotactic bacteria. Together, these results suggest that the magnetosome precisely coordinates magnetite biomineralization and can serve as a model system for the study of organelle biogenesis in noneukaryotic cells.

https://www.pnas.org/content/pnas/101/11/3839.full.pdf

Magnetosome vesicles are present before magnetite formation, and MamA is required for their activation.

Although membrane-bounded compartments are commonly considered a unique eukaryotic characteristic, many species of bacteria have organelles. Compartmentalization is well studied in eukaryotes; however, the molecular factors and processes leading to organelle formation in bacteria are poorly understood. We use the magnetosome compartments of magnetotactic bacteria as a model system to investigate organelle biogenesis in a prokaryotic system. The magnetosome is an invagination of the cell membrane that contains a specific set of proteins able to direct the synthesis of a nanometer-sized magnetite crystal. A well-conserved region called the magnetosome island (MAI) is known to be essential for magnetosome formation and contains most of the genes previously implicated in magnetosome formation. Here, we present a comprehensive functional analysis of the MAI genes in a magnetotactic bacterium, Magnetospirillum magneticum AMB-1. By characterizing MAI deletion mutants, we show that parts of its conserved core are not essential for magnetosome biogenesis and that nonconserved genes are important for crystal formation. Most importantly, we show that the mamAB gene cluster encodes for factors important for magnetosome membrane biogenesis, for targeting of proteins to this compartment and for several steps during magnetite production. Altogether, this genetic analysis defines the function of more than a dozen factors participating in magnetosome formation and shows that magnetosomes are assembled in a step-wise manner in which membrane biogenesis, magnetosome protein localization, and biomineralization are placed under discrete genetic control.

https://www.pnas.org/content/pnas/107/12/5593.full.pdf

Arash Komeili

Papers

Optical magnetic imaging of living cells

Magnetosomes Are Cell Membrane Invaginations Organized by the Actin-Like Protein MamK

Roles of phosphorylation sites in regulating activity of the transcription factor Pho4.

Magnetosome vesicles are present before magnetite formation, and MamA is required for their activation.

Comprehensive genetic dissection of the magnetosome gene island reveals the step-wise assembly of a prokaryotic organelle