RESUMO
In this article, the history and taxonomy of Placoneis gastrum, the type species of the genus Placoneis, was discussed. We investigated the structure of pore occlusions in Placoneis and related genera. As a result, we propose a new classification for tectulum-like types of pore occlusions. The new classification is congruent with previously-published and newly-constructed phylogenies based on molecular data. Based on the different structures of the pore occlusions, species of Placoneis are transferred to Witkowskia gen. nov. Hence, 168 new combinations are introduced. A new diatom species, with a similar morphology to Placoneis flabellata, was discovered in Bac Kan Province, Vietnam. It is described in this article as Chudaevia densistriata sp. nov. Placoneis flabellata is transferred to Chudaevia gen. nov. We also illustrate Placoneis flabellata herein and compare it to Chudaevia densistriata sp. nov. An unknown diatom, similar to Placoneis coloradensis, was discovered in Chukotka, Russia. It is introduced as Placoneis elinae sp. nov. below. Additionally, we discuss the distribution of some species of Witkowskia gen. nov. and Chudaevia gen. nov.
Assuntos
Diatomáceas , Filogenia , Diatomáceas/classificação , Vietnã , Federação Russa , Especificidade da EspécieRESUMO
A van der Waals telluride, NbFeTe2, has been synthesized using chemical vapor transport reactions. The optimized synthetic conditions yield high-quality single crystals with a novel monoclinic crystal structure. Monoclinic NbFeTe2 demonstrates a (100) cleavage plane, bulk ferromagnetism below 87 K, and a metallic ground state-the necessary prerequisites for needed spintronics technologies.
RESUMO
Single crystals of two new intermetallic phases Sm2Mn1-xGa6-yGey (x = 0.1-0.3, y = 0.6-1.0) and Sm4MnGa12-yGey (y = 3.0-3.5) were grown using a self-flux technique. According to single crystal X-ray diffraction data, Sm4MnGa12-yGey is characterised by the Y4PdGa12 structure type (a â¼ 8.65 Å; Im3Ìm), while Sm2Mn1-xGa6-yGey formally adopts the K2PtCl6 structure type (a â¼ 8.71 Å; Fm3Ìm). The general features of both compounds with rather similar crystal structures are represented by the alternation of empty and Mn-filled p-element octahedra, the order of which is determined by the Mn concentration. The diffraction data for Sm2Mn1-xGa6-yGey reveal a large concentration of Mn vacancies (x â¼ 0.3), which affects adjacent Ga/Ge atoms leading to their shift towards the vacancy. Both compounds demonstrate two ferromagnetic-like transitions and the presence of two interacting Mn and Sm magnetic sublattices. The Mn sublattice orders at TC1 of 143 K and 318 K, while the Sm one orders at lower temperatures at TC2 of 50 K and 280 K for Sm4MnGa8.6Ge3.4 and Sm2Mn0.74Ga5.1Ge0.9, respectively. The increase in Mn content not only increases the ordering temperatures, but also dramatically decreases the coercivity µ0HC from 230 mT to just 6.5 mT at 2 K. Despite the presence of two magnetically active sublattices in Sm2Mn0.74Ga5.1Ge0.9, the magnetic entropy change is quite low and only reaches 0.3 J kg-1 K-1 at T = 300 K and µ0H = 5 T, while the estimated relative cooling power (RCP) is about 36 J kg-1 at 5 T.
RESUMO
Single crystals of RMnxGa3 and their new quaternary derivatives R4Mn1-xGa12-yGey (R = Tb, Dy, x ≤ 0.25, y ≈ 1.0-3.3) were grown from a Ga flux. The compounds are derivatives of cubic RGa3 phases, with Mn atoms filling the Ga6 voids. RMnxGa3 formally adopts a cubic ABO3 perovskite structure, in which the presence of Mn atoms results in a shift of the neighboring Ga atoms from their ideal position. A partial substitution of Ga by Ge leads to a higher Mn content, resulting in structural ordering of the latter and the formation of the superstructure phases R4Mn1-xGa12-yGey, which can be formally described in the Y4PdGa12 structure type. The presence of Mn vacancies, which was observed for R = Tb, and Ga/Ge mixing lead to a noticeable deviation from the idealized structure. The compounds contain two magnetic sublattices: the R sublattice, which orders antiferromagnetically near 20 K, and the Mn sublattice, which orders ferromagnetically at TC = 125-225 K with the Ge doping resulting in higher TC. The two sublattices are not independent, as the Mn sublattice induces partial ferromagnetic ordering of the rare earth atoms below TC, at least for the Ge-doped phases. Near TN, both magnetic susceptibility and heat capacity reveal complex behavior, indicating changes in magnetic structures below TN.
RESUMO
Transition metal-based layered compounds with van der Waals gaps between the structural layers are a rich source of magnetic materials for spintronic applications. Bulk crystals can be cleaved, providing high-quality two-dimensional nanomaterials, which are promising for the manipulation of spins in spintronic devices and low power quantum logic interfaces. The layered van der Waals telluride Fe5AsTe2 can be synthesized by the high-temperature reaction of elements. In the crystal structure, Fe-rich structural layers with the composition of Fe4.58(4)AsTe2 are separated by the van der Waals gaps with no atoms in the interstitial region. Crystal growth employing chemical vapor transport reactions yields bulk cleavable crystals, which exhibit weak inherent ferromagnetism below the Curie temperature of TC = 48 K. In the ordered state, the magnetization shows a dual-slope behavior in low magnetic fields, indicating the compensated or canted nature of magnetism. Magnetic susceptibility and magnetization measurements reveal perpendicular magnetic anisotropy. The large Rhodes-Wohlfarth ratio of 4.6 indicates the itinerant nature of ferromagnetism in Fe5AsTe2.
RESUMO
Despite remarkable progress in photoconversion efficiency, the toxicity of lead-based hybrid perovskites remains an important issue hindering their applications in consumer optoelectronic devices, such as solar cells, LED displays, and photodetectors. For that reason, lead-free metal halide complexes have attracted great attention as alternative optoelectronic materials. In this work, we demonstrate that reactions of two aromatic diamines with iodine in hydroiodic acid produced phenylenediammonium (PDA) and N,N-dimethyl-phenylenediammonium (DMPDA) triiodides, PDA(I3)2â 2H2O and DMPDA(I3)I, respectively. If the source of bismuth was added, they were converted into previously reported PDA(BiI4)2â I2 and new (DMPDA)2(BiI6)(I3)â 2H2O, having band gaps of 1.45 and 1.7 eV, respectively, which are in the optimal range for efficient solar light absorbers. All four compounds presented organic-inorganic hybrids, whose supramolecular structures were based on a variety of intermolecular forces, including (N)Hâ â â I and (N)Hâ â â O hydrogen bonds as well as Iâ â â I secondary and weak interactions. Details of their molecular and supramolecular structures are discussed based on single-crystal X-ray diffraction data, thermal analysis, and Raman and optical spectroscopy.
RESUMO
The influenza vaccine Grippol® Quadrivalent (GQ) is a new vaccine, containing the adjuvant Polyoxidonium® and recombinant hemagglutinins from 4 strains of the influenza virus in amount of 5-6 µg of each hemagglutinin per human dose. These doses of antigens are about 3 times less than the standard dose recommended by WHO. We sought to characterize the immune response to the GQ vaccine and to determine the contribution of the adjuvant in this response. BALB/c mice were vaccinated with GQ or with adjuvant-free antigen mixtures (AGs). Then, the antibody response, the number of memory T cells in the spleen, and the functional properties of splenocytes were determined. The vaccine GQ has been shown to induce antibodies to all 4 influenza hemagglutinins. The vaccination with GQ caused a strong increase in the AG-induced proliferation and production of Th2 cytokines ex vivo. These effects were equal to effect achieved by standard dose of antigens. Vaccination also caused the accumulation of CD4+ large lymphocytes with the phenotype of central and effector memory T cells in the spleen. The GQ vaccine enhanced the cytolytic activity of natural killer (NK) cells, whereas the adjuvant-free mixture of AGs in lowered and standard doses did not affect NK activity. We did not find a noticeable response of Th1 and CD8+ T cells to vaccination. In vitro, the GQ vaccine stimulated the maturation of human monocyte-derived dendritic cells (DCs) enhancing the expression of HLA-DR, CD80, CD83, CD86 and ICOSL molecules. Polyoxidonium without AGs also induced expression of ICOSL, which plays an important role in T-dependent humoral immune response. In summary, the low-dose influenza vaccine GQ with Polyoxidonium adjuvant is immunogenic, induces a Th2-polarized T-cell response and CD4+ memory T cells maturation, activates the production of antibodies to influenza hemagglutinins, and increases the activity of NK cells.
Assuntos
Vacinas contra Influenza , Adjuvantes Imunológicos , Animais , Anticorpos Antivirais , Linfócitos T CD8-Positivos , Imunidade Humoral , Células Matadoras Naturais , Camundongos , Camundongos Endogâmicos BALB C , Piperazinas , PolímerosRESUMO
Exploiting a template effect of 1,4-diazacycloheptane (also known as homopiperazine, Hpipe), four new hybrid iodides, (HpipeH2)2Bi2I10·2H2O, (HpipeH2)I(I3), (HpipeH2)3I6·H2O, and (HpipeH2)3(H3O)I7, were prepared and their crystal structures were solved using single crystal X-ray diffraction data. All four solid-state crystal structures feature the HpipeH22+ cation alternating with Bi2I104-, I3-, or I- anions and solvent water or H3O+ cation. HpipeH22+ assembles anionic and neutral building blocks into polymer structures by forming four strong (N)H···I and (N)H···O hydrogen bonds per cation, with the H···I distances ranging from 2.44 to 2.93 Å and H···O distances of 1.88-1.89 Å. These hydrogen bonds strongly affect the properties of compounds; in particular, in the case of (HpipeH2)2Bi2I10·2H2O, they ensure narrowing of the band gap down to 1.8 eV and provide high thermal stability up to 240 °C, remarkable for a hydrated molecular solid.
Assuntos
Bismuto/química , Iodetos/química , Piperazina/química , Cátions/química , Complexos de Coordenação/química , Cristalografia por Raios X/métodos , Compostos Heterocíclicos/química , Ligação de Hidrogênio , Estrutura Molecular , Polímeros/química , Água/químicaRESUMO
Three new and complementary approaches to S-arylation of 2-thiohydantoins have been developed: copper-catalyzed cross coupling with either arylboronic acids or aryl iodides under mild conditions, or direct nucleophilic substitution in activated aryl halides. For 38 diverse compounds, reaction yields for all three methods have been determined. Selected by molecular docking, they have been tested on androgen receptor activation, and p53-Mdm2 regulation, and A549, MCF7, VA13, HEK293T, PC3, LnCAP cell lines for cytotoxicity, Two of them turned out to be promising as androgen receptor activators (likely by allosteric regulation), and another one is shown to activate the p53 cascade. It is hoped that 2-thiohydantoin S-arylidenes are worth further studies as biologically active compounds.
Assuntos
Androgênios/química , Androgênios/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Tioidantoínas/química , Tioidantoínas/farmacologia , Regulação Alostérica/efeitos dos fármacos , Androgênios/síntese química , Antineoplásicos/síntese química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Técnicas de Química Sintética , Células HEK293 , Humanos , Simulação de Acoplamento Molecular , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Mapas de Interação de Proteínas/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Receptores Androgênicos/metabolismo , Tioidantoínas/síntese química , Proteína Supressora de Tumor p53/metabolismoRESUMO
The modification of Chan-Lam-Evans cross-coupling reaction for the selective Se-arylation of 2-selenohydantoins under base-free mild conditions via aryl boronic acids is described herein. This approach was used to synthesize novel 5-arylidene-3-substituted-2-(arylselanyl)-imidazoline-4-ones with high yields. The anticancer activity of the final compounds was evaluated in vitro against different cancer cells, and thus, the possibility of 5-arylidene-3-substituted-2-(arylselanyl)-imidazoline-4-ones successful application as cytotoxic agents was demonstrated.
Assuntos
Antineoplásicos/química , Ácidos Borônicos/química , Cobre/química , Hidantoínas/química , Imidazolinas/química , Compostos de Selênio/química , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Imidazolinas/síntese química , Imidazolinas/farmacologiaRESUMO
In this study, we modify the flux-growth method for the purpose of exploratory synthesis of ternary intermetallic compounds. Our concept is based on the assumption that valence electron count plays a crucial role in the stability of polar intermetallic compounds of different structure types. Control of the valence electron count parameter is made possible through the use of an excess of two metals having a different number of valence electrons. By gradually changing the ratio between these metals in the joint flux, we scan the gross number of valence electrons and explore the crystallization of new compounds. In the ternary system Re-Ga-Zn, we detect compounds belonging to three structure types, ReGa5, PtHg4, and V8Ga41, while gradually increasing the content of Zn metal in the flux. Two new compounds, ReGa3Zn and Re8Ga41- xZn x with x = 21.2(5), are obtained in the form of high-quality single crystals, and the former compound shows the narrow-gap semiconducting behavior favorable for high thermoelectric performance.
RESUMO
The structure of synthetic tennantite Cu12As4S13 was investigated at various temperatures in the 90-293â K range. It crystallizes in space group I{\overline 4}3m. No structural transformation was observed in this temperature range. The structures were refined in anharmonic approximation for atomic displacements and electron density maps were refined using the maximum entropy method. Both approaches indicate a noticeable static disorder of the copper atoms in the triangular sulfur coordination and neighbouring site at high temperatures, whereas these split copper sites are well defined at lower temperatures. One particle potential is used to describe the behaviour of atoms at these copper sites. Such behaviour may be the structural reason for changes in magnetic properties.
RESUMO
We report the synthesis, crystal structures, and optical properties of two new compounds, K18Bi8I42(I2)0.5·14H2O (1) and (NH4)7Bi3I16(I2)0.5·4.5H2O (2), as well as the electronic structure of the latter. They crystallize in tetragonal space group P4/ mmm with the unit cell parameters a = 12.974(1) and c = 20.821(3) Å for 1 and a = 13.061(3) and c = 15.162(7) Å for 2. Though 1 and 2 are not isomorphous, their crystal structures display the same structural organization; namely, the BiI6 octahedra are linked by I2 units to form disordered layers in 1 and perfectly ordered chains in 2. The I-I bond distances in the thus formed I-I-I-I linear links are not uniform; the central bond is only slightly longer than in a standalone I2 molecule, whereas the peripheral bonds are significantly shorter than longer bonds typical for various polyiodides, which is confirmed by Raman spectroscopy. The analysis of the electronic structure shows that the atoms forming the I-I-I-I subunits transfer electron density from their occupied 5p orbitals onto their vacant states as well as onto 6s orbitals of bismuth atoms that center the BiI6 octahedra. This leads to low direct band gaps that were found to be 1.57 and 1.27 eV for 1 and 2, respectively, by optical absorption spectroscopy. Luminescent radiative relaxation was observed in the near-IR region with emission maxima of 1.39 and 1.24 eV for 1 and 2, respectively, in good agreement with the band structure, despite the strong quenching propensity of I2 moieties.
RESUMO
A new phase Fe32+δGe33As2 (δ ≤ 0.136) was obtained by two-step synthesis from the elements. Fe32+δGe33As2 crystallizes in its own structure type (space group P6/mmm, Z = 1, a = 11.919(3) Å, c = 7.558(4) Å) that can be described as a recurrent two-dimensional intergrowth of two intermetallic structure types, MgFe6Ge6 and Co2Al5. Their blocks are represented by infinite columns in the structure. No visible structural changes were observed in the temperature range from 10 to 300 K. At 125 K, Fe32+δGe33As2 undergoes an antiferromagnetic-like transition, while above 150 K it shows a typical Curie-Weiss paramagnetic behavior. Below the transition temperature, a peculiar field-dependent magnetic susceptibility, that shows a significant increase of the susceptibility upon increasing the magnetic field, and a change in transport properties have been observed. Above 140 K, Fe32+δGe33As2 reveals a metallic behavior, in agreement with electronic structure calculation, while below this point the resistivity nonmonotonically increases upon cooling. The Seebeck coefficient is positive, indicating that holes are the major charge carriers, and shows a broad maximum around 57 K.
RESUMO
The incommensurate modulated crystal structure of Bi2.27Sr1.73CuO6â +â δ (2201) phase [a = 5.3874â (5), b = 5.3869â (4), c = 24.579â (3)â Å; ß = 90.01â (1)°, q = 0.2105â (3)a(*)â +â 0.538â (4)c(*), Z = 4, the (3â +â 1)-dimensional monoclinic A2/a(α0γ) group] has been refined with R = 0.041, wR = 0.052 from X-ray single-crystal data including up to third-order satellite reflections. The same structure has also been considered as incommensurate composite with a2 = 2.437, b2 = 5.387, c2 = 24.614, ß2 = 93.06, q2 = 0.4524a2(*)-0.243c2(*) and the (3â +â 1)-dimensional A2/m(α0γ)0s group for the second component. Both approaches give quite similar results. The structure possesses oxygen disorder in the oxygen-rich region of the BiO layer. An extra O atom is determined in the bridging position shifted â¼â 0.6â Å from BiO towards the SrO layer. Its presence is the cause of the tremendous increase of the bismuth U(11) atomic displacement parameter in â¼â 20% of the unit cells (t = -0.05-0.15). Vacancies are determined in the oxygen site of the SrO layer, which may result in the oxygen content variation with annealing at different oxygen pressures. The total refined oxygen content 6.18â (1) corresponds to the results of chemical analysis.
RESUMO
Four iodobismuthates, LiBiI4·5H2O (1), MgBi2I8·8H2O (2), MnBi2I8·8H2O (3), and KBiI4·H2O (4), were prepared by a facile solution route and revealed thermal stability in air up to 120 °C. Crystal structures of compounds 1-4 were solved by a single crystal X-ray diffraction method. 1: space group C2/c, a = 12.535(2), b = 16.0294(18), c = 7.6214(9) Å, ß = 107.189(11)°, Z = 4, R = 0.029. 2: space group P21/c, a = 7.559(2), b = 13.1225(15), c = 13.927(4) Å, ß = 97.14(3)°, Z = 2, R = 0.031. 3: space group P21/c, a = 7.606(3), b = 13.137(3), c = 14.026(5) Å, ß = 97.14(3)°, Z = 2, R = 0.056. 4: space group P21/n, a = 7.9050(16), b = 7.7718(16), c = 18.233(4) Å, ß = 97.45(3)°, Z = 4, R = 0.043. All solid state structures feature one-dimensional (BiI4)(-) anionic chains built of [BiI6] octahedra that share two opposite edges in such a fashion that two iodine atoms in cis-positions remain terminal. The calculated electronic structures and observed optical properties confirmed that compounds 1-4 are semiconductors with direct band gaps of 1.70-1.76 eV, which correspond to their intense red color. It was shown that the cations do not affect the optical properties, and the optical absorption is primarily associated with the charge transfer from the I 5p orbitals at the top of the valence band to the Bi 6p orbitals at the bottom of the conduction band. Based on their properties and facile synthesis, the title compounds are proposed as promising light-harvesting materials for all-solid solar cells.
RESUMO
We have synthesized and characterized a panel of new binuclear mixed valence Cu(I,II) complexes containing substituted 2-alkylthio-5-arylmethylene-4H-imidazolin-4-ones with unusual structure. These complexes are shown to be cytotoxic for various cell lines. We have found that these compounds did not intercalate DNA, inhibited number of polymerases (telomerase predominantly), accumulated in the cell nucleus, and caused DNA degradation. Preliminary studies revealed that lead compound inhibited human breast adenocarcinoma growth in mice model.
Assuntos
Antineoplásicos/farmacologia , Cobre/química , Neoplasias Experimentais/tratamento farmacológico , Compostos Organometálicos/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cristalografia por Raios X , Dano ao DNA , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células HEK293 , Células Hep G2 , Humanos , Células MCF-7 , Camundongos , Camundongos Endogâmicos C57BL , Modelos Moleculares , Estrutura Molecular , Neoplasias Experimentais/patologia , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Relação Estrutura-AtividadeRESUMO
Sanger sequencing is a common method of reading DNA sequences. It is less expensive than high-throughput methods, and it is appropriate for numerous applications including molecular diagnostics. However, sequencing mixtures of similar DNA of pathogens with this method is challenging. This is important because most clinical samples contain such mixtures, rather than pure single strains. The traditional solution is to sequence selected clones of PCR products, a complicated, time-consuming, and expensive procedure. Here, we propose the base-calling with vocabulary (BCV) method that computationally deciphers Sanger chromatograms obtained from mixed DNA samples. The inputs to the BCV algorithm are a chromatogram and a dictionary of sequences that are similar to those we expect to obtain. We apply the base-calling function on a test dataset of chromatograms without ambiguous positions, as well as one with 3-14% sequence degeneracy. Furthermore, we use BCV to assemble a consensus sequence for an HIV genome fragment in a sample containing a mixture of viral DNA variants and to determine the positions of the indels. Finally, we detect drug-resistant Mycobacterium tuberculosis strains carrying frameshift mutations mixed with wild-type bacteria in the pncA gene, and roughly characterize bacterial communities in clinical samples by direct 16S rRNA sequencing.
Assuntos
Algoritmos , Biologia Computacional/métodos , Análise de Sequência de DNA , Genótipo , HIV-1/genética , Vírus de Hepatite/classificação , Vírus de Hepatite/genética , Humanos , Mutação INDEL , Mycobacterium tuberculosis/classificação , Mycobacterium tuberculosis/genética , Filogenia , RNA Ribossômico 16SRESUMO
It is generally accepted that functionally important RNA structure is more conserved than sequence due to compensatory mutations that may alter the sequence without disrupting the structure. For small RNA molecules sequence-structure relationships are relatively well understood. However, structural bioinformatics of mRNAs is still in its infancy due to a virtual absence of experimental data. This report presents the first quantitative assessment of sequence-structure divergence in the coding regions of mRNA molecules based on recently published transcriptome-wide experimental determination of their base paring patterns. Structural resemblance in paralogous mRNA pairs quickly drops as sequence identity decreases from 100% to 85-90%. Structures of mRNAs sharing sequence identity below roughly 85% are essentially uncorrelated. This outcome is in dramatic contrast to small functional non-coding RNAs where sequence and structure divergence are correlated at very low levels of sequence similarity. The fact that very similar mRNA sequences can have vastly different secondary structures may imply that the particular global shape of base paired elements in coding regions does not play a major role in modulating gene expression and translation efficiency. Apparently, the need to maintain stable three-dimensional structures of encoded proteins places a much higher evolutionary pressure on mRNA sequences than on their RNA structures.
Assuntos
RNA Fúngico/química , RNA Mensageiro/química , Candida glabrata/genética , Conformação de Ácido Nucleico , Saccharomyces cerevisiae/genética , Alinhamento de Sequência , Análise de Sequência de RNARESUMO
Pre-mRNA structure impacts many cellular processes, including splicing in genes associated with disease. The contemporary paradigm of RNA structure prediction is biased toward secondary structures that occur within short ranges of pre-mRNA, although long-range base-pairings are known to be at least as important. Recently, we developed an efficient method for detecting conserved RNA structures on the genome-wide scale, one that does not require multiple sequence alignments and works equally well for the detection of local and long-range base-pairings. Using an enhanced method that detects base-pairings at all possible combinations of splice sites within each gene, we now report RNA structures that could be involved in the regulation of splicing in mammals. Statistically, we demonstrate strong association between the occurrence of conserved RNA structures and alternative splicing, where local RNA structures are generally more frequent at alternative donor splice sites, while long-range structures are more associated with weak alternative acceptor splice sites. As an example, we validated the RNA structure in the human SF1 gene using minigenes in the HEK293 cell line. Point mutations that disrupted the base-pairing of two complementary boxes between exons 9 and 10 of this gene altered the splicing pattern, while the compensatory mutations that reestablished the base-pairing reverted splicing to that of the wild-type. There is statistical evidence for a Dscam-like class of mammalian genes, in which mutually exclusive RNA structures control mutually exclusive alternative splicing. In sum, we propose that long-range base-pairings carry an important, yet unconsidered part of the splicing code, and that, even by modest estimates, there must be thousands of such potentially regulatory structures conserved throughout the evolutionary history of mammals.