"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

The formation of cellular magnetic dipoles by chain assemblies of stable single-domain magnetite nanocrystals is a characteristic feature in magnetotactic bacteria (MTB). The dipole strength depends on the competition or cooperation between the various anisotropic energy contributions, mainly between the magnetocrystalline and the interaction-induced shape anisotropy. Ferromagnetic resonance spectroscopy and numerical simulations of intracellular magnetite assemblies in the MTB Desulfovibrio magneticus strain RS-1 show that the alignment of elongated nanocrystallites leads to a predominant uniaxial anisotropy, which is enhanced when the magnetocrystalline symmetry is collinear to the chain, i.e., the anisotropies are cooperative vs. being competitive. This direct insight into the anisotropy variations in chain assemblies provides a physical framework to tailor magnetic nanocomposites, where the collective magnetic properties result from the interactions between the individual nanocrystalline constituents.

Competitive and cooperative anisotropy in magnetic nanocrystal chains of magnetotactic bacteria

Cellular iron homeostasis is vital and maintained through tight regulation of iron import, efflux, storage, and detoxification. The most common modes of iron storage employ proteinaceous compartments that are composed of ferritin or related proteins. While lipid-bounded iron compartments have also been described, the basis for their formation and function remains unknown. Here, we focus on one such compartment, the ferrosome, which had been previously observed in the anaerobic bacterium Desulfovibrio magneticus. We identify three ferrosome-associated (Fez) proteins, encoded by a putative operon, that are associated with and responsible for forming ferrosomes in D. magneticus. Fez proteins include FezB, a P1B-6-ATPase found in phylogenetically and metabolically diverse species of bacteria and archaea with anaerobic lifestyles. In the majority of these species, two to ten genes define a cluster that encodes FezB. We show that two other species, Rhodopseudomonas palustris and Shewanella putrefaciens, make ferrosomes in anaerobic conditions through the action of their six-gene fez operon. Additionally, we find that the S. putrefaciens fez operon is sufficient for ferrosome formation in Escherichia coli. Using S. putrefaciens as a model, we find that ferrosomes likely play a role in the anaerobic adaptation to iron starvation. Overall, this work establishes ferrosomes as a new class of lipid-bounded iron storage organelles and sets the stage for studying ferrosome formation and structure in diverse microorganisms.

/pdf/ferrosomes-are-iron-storage-organelles-formed-by-broadly-2yqtczxzwz.pdf

Ferrosomes are iron storage organelles formed by broadly conserved gene clusters in bacteria and archaea

Abstract Magnetotactic bacteria are a diverse group of microorganisms that use intracellular chains of ferrimagnetic nanocrystals, produced within magnetosome organelles, to align and navigate along the geomagnetic field. Several conserved genes for magnetosome formation have been described, but the mechanisms leading to distinct species-specific magnetosome chain configurations remain unclear. Here, we show that the fragmented nature of magnetosome chains in Magnetospirillum magneticum AMB-1 is controlled by genes mcaA and mcaB . McaA recognizes the positive curvature of the inner cell membrane, while McaB localizes to magnetosomes. Along with the MamK actin-like cytoskeleton, McaA and McaB create space for addition of new magnetosomes in between pre-existing magnetosomes. Phylogenetic analyses suggest that McaA and McaB homologs are widespread among magnetotactic bacteria and may represent an ancient strategy for magnetosome positioning. 

/pdf/mcaa-and-mcab-control-the-dynamic-positioning-of-a-bacterial-1596bl10.pdf

McaA and McaB control the dynamic positioning of a bacterial magnetic organelle

Magnetotactic bacteria (MTB) are a phylogenetically diverse group of bacteria remarkable for their ability to biomineralize magnetite (Fe3O4) or greigite (Fe3S4) in organelles called magnetosomes. The majority of genes required for magnetosome formation are encoded by a magnetosome gene island (MAI). Most previous genetic studies in MTB have focused on the MAI, using screens to identify key MAI genes or targeted genetics to isolate specific genes and their function in one specific growth condition. Here, we conducted random barcoded transposon mutagenesis (RB-TnSeq) in Magnetospirillum magneticum AMB-1 to identify the global genetic requirements for magnetosome formation under different growth conditions. We generated a library of 184,710 unique strains in a wild-type background, generating ~34 mutant strains for each gene. RB-TnSeq also allowed us to determine the essential gene set of AMB-1 under standard laboratory growth conditions. To pinpoint novel genes that are important for magnetosome formation, we subjected the library to magnetic selection screens in varied growth conditions. We compared biomineralization in standard growth conditions to biomineralization in high iron and anaerobic conditions, respectively. Strains with transposon insertions in the MAI gene mamT had an exacerbated biomineralization defect under both high iron and anerobic conditions compared to standard conditions, adding to our knowledge of the role of MamT in magnetosome formation. Mutants in amb4151, a gene outside of the MAI, are more magnetic than wild-type cells under anaerobic conditions. All three of these phenotypes were validated by creating a markerless deletion strain of the gene and evaluating with TEM imaging. Overall, our results indicate that growth conditions affect which genes are required for biomineralization and that some MAI genes may have more nuanced functions than was previously understood.

https://biorxiv.org/content/10.1101/2021.08.13.456315v1.full.pdf

Mapping the genetic landscape of biomineralization in Magnetospirillum magneticum AMB-1 with RB-Tnseq

Magnetotactic bacteria (MTB) are a group of bacteria that can form nano-sized crystals of magnetic minerals. MTB are likely an important part of their ecosystems, because they can account for up to a third of the microbial biomass in an aquatic habitat and consume large amounts of iron, potentially impacting the iron cycle. ABSTRACT Magnetotactic bacteria (MTB) are a phylogenetically diverse group of bacteria remarkable for their ability to biomineralize magnetite (Fe3O4) or greigite (Fe3S4) in organelles called magnetosomes. The majority of genes required for magnetosome formation are encoded by a magnetosome gene island (MAI). Most previous genetic studies of MTB have focused on the MAI, using screens to identify key MAI genes or targeted genetics to isolate specific genes and their function in one specific growth condition. This is the first study that has taken an unbiased approach to look at many different growth conditions to reveal key genes both inside and outside the MAI. Here, we conducted random barcoded transposon mutagenesis (RB-TnSeq) in Magnetospirillum magneticum AMB-1. We generated a library of 184,710 unique strains in a wild-type background, generating ∼34 mutant strains for each gene. RB-TnSeq also allowed us to determine the essential gene set of AMB-1 under standard laboratory growth conditions. To pinpoint novel genes that are important for magnetosome formation, we subjected the library to magnetic selection screens under varied growth conditions. We compared biomineralization under standard growth conditions to biomineralization under high-iron and anaerobic conditions, respectively. Strains with transposon insertions in the MAI gene mamT had an exacerbated biomineralization defect under both high-iron and anaerobic conditions compared to standard conditions, adding to our knowledge of the role of MamT in magnetosome formation. Mutants in an ex-MAI gene, amb4151, are more magnetic than wild-type cells under anaerobic conditions. All three of these phenotypes were validated by creating a markerless deletion strain of the gene and evaluating with TEM imaging. Overall, our results indicate that growth conditions affect which genes are required for biomineralization and that some MAI genes may have more nuanced functions than was previously understood. IMPORTANCE Magnetotactic bacteria (MTB) are a group of bacteria that can form nano-sized crystals of magnetic minerals. MTB are likely an important part of their ecosystems, because they can account for up to a third of the microbial biomass in an aquatic habitat and consume large amounts of iron, potentially impacting the iron cycle. The ecology of MTB is relatively understudied; however, the cell biology and genetics of MTB have been studied for decades. Here, we leverage genetic studies of MTB to inform environmental studies. We expand the genetic toolset for studying MTB in the lab and identify novel genes, or functions of genes, that have an impact on biomineralization.

/pdf/global-analysis-of-biomineralization-genes-in-11wu7qnx.pdf

Arash Komeili

Papers

Competitive and cooperative anisotropy in magnetic nanocrystal chains of magnetotactic bacteria

Ferrosomes are iron storage organelles formed by broadly conserved gene clusters in bacteria and archaea

McaA and McaB control the dynamic positioning of a bacterial magnetic organelle

Mapping the genetic landscape of biomineralization in Magnetospirillum magneticum AMB-1 with RB-Tnseq

Global Analysis of Biomineralization Genes in Magnetospirillum magneticum AMB-1