Angular Forces Around Transition Metals in Biomolecules

Quantum-mechanical analysis based on an exact sum rule is used to extract an semiclassical angle-dependent energy function for transition metal ions in biomolecules. The angular dependence is simple but different from existing classical potentials. Comparison of predicted energies with a computer-generated database shows that the semiclassical energy function is remarkably accurate, and that its angular dependence is optimal.Comment: Tex file plus 4 postscript figure

Synthesis of octahydro-2H-chromen-4-ol from vanillin and isopulegol over acid modified montmorillonite clays: Effect of acidity on the Prins cyclization

Two calcium-rich natural layered aluminosilicates containing 90–95 wt.% montmorillonite were chemically activated using 0.125–3.0 M HCl solutions. Structural and textural properties were characterized by X-ray diffraction, elemental analysis and N2-adsorption/desorption analyses. According to infrared spectroscopy using pyridine as probe molecule, the amount of Brønsted acid sites increased when increasing HCl concentration. The catalytic performance of these materials was investigated in the Prins cyclization of (−)-isopulegol with vanillin to form octahydro-2H-chromen-4-ol, carried out in toluene at 35 °C. It was found that the amount of Brønsted acid sites and the microporosity of the catalysts are key factors for the control of the reaction rate and the selectivity towards octahydro-2H-chromen-4-o

Features of matrix metalloproteinases MMP2, MMP3, MMP9 genes regulatory region polymorphism in patients with uterine fbroids

Violation of the extracellular matrix components synthesis regulation contributes to the formation and growth of uterine fbroids (MM). Changes of collagen metabolism in connective tissue may be associated with polymorphism of matrix metalloproteinase (MMP) genes. Aim of the study was to analyze of the association of regulatory regions of matrix metalloproteinase genes MMP2 (rs243865), MMP3 (rs3025058), MMP9 (rs3918242) with the development of uterine myoma, its histological form, several concomitant gynecological diseases. Material and methods. The clinical study of 69 patients (23–54 years old) with uterine myoma was conducted. According to the anamnesis, 57.9 % of patients had childbirth, 46.4 % of women had an artifcial termination of pregnancy, and 15.9 % of women had endometriosis. In histological examination, in 48.14 % the nodes corresponded to the phenotype of simple fbroids with a large proportion of fbrous tissue, 51.6 % with the phenotype of proliferating fbroids. The comparison group is represented by a random population sample of women from Western Siberia. 183 women without pronounced gynecological pathologies were examined. MMP2-1306 C/T polymorphism was analyzed by TaqMan, MMP3-1171 5A/6A, MMP9-1562 C/T by restriction fragment length polymorphism method. Results. The genotype frequencies of the analyzed genes did not signifcantly differ between the groups. The complex genotype MMP2-1306CC:MMP3-11715A6A:MMP9-1562CT was decreased in women with uterine myoma relative to the persons of the comparison group. In endometriosis patients MMP9-1562CC genotype was reduced and heterozygosity was increased relative to patients without endometriosis. The frequency of MMP2-1306CC:MMP9-1562CT complex genotype is signifcantly higher in women who gave birth than in women who did not give birth. Complex genotypes differences between histological variants of uterine myoma were revealed. Conclusions. The results of the study show the signifcance of polymorphism effect of the regulatory regions of the MMP genes in the development and nature of the course of uterine myoma

Oral vitamin D supplementation induces transcriptomic changes in rectal mucosa that are linked to anti-tumour effects

Abstract Background The risk for several common cancers is influenced by the transcriptomic landscape of the respective tissue-of-origin. Vitamin D influences in vitro gene expression and cancer cell growth. We sought to determine whether oral vitamin D induces beneficial gene expression effects in human rectal epithelium and identify biomarkers of response. Methods Blood and rectal mucosa was sampled from 191 human subjects and mucosa gene expression (HT12) correlated with plasma vitamin D (25-OHD) to identify differentially expressed genes. Fifty subjects were then administered 3200IU/day oral vitamin D3 and matched blood/mucosa resampled after 12 weeks. Transcriptomic changes (HT12/RNAseq) after supplementation were tested against the prioritised genes for gene-set and GO-process enrichment. To identify blood biomarkers of mucosal response, we derived receiver-operator curves and C-statistic (AUC) and tested biomarker reproducibility in an independent Supplementation Trial (BEST-D). Results Six hundred twenty-nine genes were associated with 25-OHD level (P < 0.01), highlighting 453 GO-term processes (FDR<0.05). In the whole intervention cohort, vitamin D supplementation enriched the prioritised mucosal gene-set (upregulated gene-set P < 1.0E−07; downregulated gene-set P < 2.6E−05) and corresponding GO terms (P = 2.90E−02), highlighting gene expression patterns consistent with anti-tumour effects. However, only 9 individual participants (18%) showed a significant response (NM gene-set enrichment P < 0.001) to supplementation. Expression changes in HIPK2 and PPP1CC expression served as blood biomarkers of mucosal transcriptomic response (AUC=0.84 [95%CI 0.66–1.00]) and replicated in BEST-D trial subjects (HIPK2 AUC=0.83 [95%CI 0.77–0.89]; PPP1CC AUC=0.91 [95%CI 0.86–0.95]). Conclusions Higher plasma 25-OHD correlates with rectal mucosa gene expression patterns consistent with anti-tumour effects, and this beneficial signature is induced by short-term vitamin D supplementation. Heterogenous gene expression responses to vitamin D may limit the ability of randomised trials to identify beneficial effects of supplementation on CRC risk. However, in the current study blood expression changes in HIPK2 and PPP1CC identify those participants with significant anti-tumour transcriptomic responses to supplementation in the rectum. These data provide compelling rationale for a trial of vitamin D and CRC prevention using easily assayed blood gene expression signatures as intermediate biomarkers of response

Mutations in the genome of avian influenza viruses of the H1 and H5 subtypes responsible for adaptation to mammals

Avian influenza viruses of the H1 and H5 subtypes were involved in the formation of highly pathogenic viruses that caused pandemics and panzootics in the 20th–21st centuries. In order to assess the zoonotic potential of viruses of these subtypes, two viruses of the H1N1 and H5N3 subtypes have been isolated from wild ducks in Moscow and adapted for growth in mouse lungs. Their phenotypic properties were studied, and the genetic changes that occurred during adaptation were identified. The original A/duck/Moscow/4970/2013 (H1N1) and A/duck/Moscow/4182-C/2010 (H5N3) viruses were apathogenic for mice but became pathogenic after 7–10 passages in mouse lungs. Complete genome sequencing revealed 2 amino acid substitutions in the proteins of the H1N1 mouse-adapted variant (Glu627Lys in PB2 and Asp35Asn in hemagglutinin (HA) – numbering according to H3) and 6 mutations in the proteins of H5N3 virus (Glu627lys in PB2, Val113Ala in PB1, Ser82Pro in PB1-F2, Lys52Arg in HA2, Arg65Lys in NP, and Ser-59Ile in NA). The increase in virulence is most likely due to a Glu627Lys substitution in the protein PB2 found in both viruses. The replacement Asp35Asn in HA of the mouse-adapted H1N1 virus is associated with an increase in the pH value of the HA transition to 5.5 versus 5.0 for that of the wild virus. The mutations found in the HA, NA, and PB1-F2 proteins of the adapted H5N3 variant are unique. The mutations Glu627Lys in PB2, Arg65Lys in NP, and Val113Ala in PB1 are most likely host adaptive

Combination approach to diagnosis and treatment of an elderly patient with chronic Ph-negative myeloproliferative neoplasm and concomitant surgical pathology. Clinical observation

Chronic myeloproliferative neoplasms (CMPN), Ph-negative, are of clonal nature, develop on the level of hematopoietic stem cell and are characterized by proliferation of one or more hematopoietic pathways. Currently, the group of Ph-negative CMPN includes essential thrombocythemia, primary myelofibrosis, polycythemia vera, myeloproliferative neoplasm unclassifiable.Identification of mutations in the Jak2 (V617F), CALR, and MPL genes extended understanding of biological features of Ph-negative CMPN and improved differential diagnosis of myeloid neoplasms. Nonetheless, clinical practice still encounters difficulties in clear separation between such disorders as primary myelofibrosis, early-stage and transformation of essential thrombocythemia into myelofibrosis with high thrombocytosis. Thrombocytosis is one of the main risk factors for thromboembolic complications, especially in elderly people.A clinical case of an elderly patient with fracture of the left femur developed in the context of Ph-negative CMPN (myelofibrosis) with high level of thrombocytosis is presented which in combination with enforced long-term immobilization and presence of additional risk created danger of thrombosis and hemorrhage during surgery and in the postoperative period

Chargeâ Transport Properties of F6TNAPâ Based Chargeâ Transfer Cocrystals

The crystal structures of the chargeâ transfer (CT) cocrystals formed by the Ï â electron acceptor 1,3,4,5,7,8â hexafluoroâ 11,11,12,12â tetracyanonaphthoâ 2,6â quinodimethane (F6TNAP) with the planar Ï â electronâ donor molecules triphenylene (TP), benzo[b]benzo[4,5]thieno[2,3â d]thiophene (BTBT), benzo[1,2â b:4,5â bâ ²]dithiophene (BDT), pyrene (PY), anthracene (ANT), and carbazole (CBZ) have been determined using singleâ crystal Xâ ray diffraction (SCXRD), along with those of two polymorphs of F6TNAP. All six cocrystals exhibit 1:1 donor/acceptor stoichiometry and adopt mixedâ stacking motifs. Cocrystals based on BTBT and CBZ Ï â electron donor molecules exhibit brickwork packing, while the other four CT cocrystals show herringboneâ type crystal packing. Infrared spectroscopy, molecular geometries determined by SCXRD, and electronic structure calculations indicate that the extent of groundâ state CT in each cocrystal is small. Density functional theory calculations predict large conduction bandwidths and, consequently, low effective masses for electrons for all six CT cocrystals, while the TPâ , BDTâ , and PYâ based cocrystals are also predicted to have large valence bandwidths and low effective masses for holes. Chargeâ carrier mobility values are obtained from spaceâ charge limited current (SCLC) measurements and fieldâ effect transistor measurements, with values exceeding 1 cm2 Vâ 1 s1 being estimated from SCLC measurements for BTBT:F6TNAP and CBZ:F6TNAP cocrystals.Structural, electronic band structure, and electrical properties of a series of chargeâ transfer cocrystals based on F6TNAP and six planar donors are presented. Density functional theory calculations afford large conduction bandwidths and low effective masses for all six cocrystals. A few cocrystals exhibit chargeâ carrier mobilities in excess of 1 cm2 Vâ 1 sâ 1, as estimated from spaceâ charge limited current measurements.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153248/1/adfm201904858-sup-0001-S1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153248/2/adfm201904858.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153248/3/adfm201904858_am.pd

Мутации в геноме вирусов гриппа птиц подтипов Н1 и Н5, ответственные за адаптацию к млекопитающим

Avian influenza viruses of H1 and H5 subtypes were involved in the formation of highly pathogenic viruses that caused pandemics and panzootics in the 20th–21st centuries. In order to assess the zoonotic potential of viruses of these subtypes, two viruses of H1N1 and H5N3 have been isolated from wild ducks in Moscow and adapted to growth in mouse lungs. Their phenotypic properties were studied, and the genetic changes that occurred during adaptation were identified. The original A/duck/Moscow/4970/2013 (H1N1) and A/duck/Moscow/4182-C/2010 (H5N3) viruses were apathogenic for mice but became pathogenic after 7–10 passages in mouse lungs. Complete genome sequencing revealed 2 amino acid substitutions in the proteins of the H1N1 mouse-adapted variant (Glu627Lys in PB2 and Asp35Asn in hemagglutinin (HA) – numbering according to H3) and 6 mutations in the proteins of H5N3 virus (Glu627lys in PB2, Val113Ala in PB1, Ser82Pro in PB1-F2, Lys52Arg in HA2, Arg65Lys in NP, and Ser59Ile in NA). The increase in virulence is most likely due to a common substitution in the protein PB2 Glu627Lys as revealed in both viruses. The replacement of Asp35Asn in HA of the mouse-adapted H1N1 virus is associated with an increase in the pH value of the HA transition from 5.0 for 5.5 in comparison to the HA of parent virus. The found mutations in HA, NA, and PB1-F2 proteins of the adapted H5N3 variant are unique. The mutations Glu627Lys in PB2, Arg65Lys in NP, and Val113Ala in PB1 are most likely host adaptive.Вирусы гриппа птиц подтипов Н1 и Н5 участвовали в формировании высокопатогенных вариантов вирусов, вызвавших пандемии и  панзоотии в  XX–XXI  веках. С  целью оценки зоонозного потенциала вирусов этих подтипов, выделенных от диких уток в черте Москвы, была проведена адаптация вирусов к размножению в легких мышей, изучены их фенотипические свойства и идентифицированы генетические изменения, возникшие при адаптации. Изначально апатогенные для мышей вирусы A/duck/Moscow/4970/2013 (H1N1) и A/duck/Moscow/4182‑C/2010 (H5N3) после 7–10 пассажей через легкие мышей изменили фенотип на патогенный. Полногеномное секвенирование выявило в адаптированных к мышам вирусах 2 аминокислотные замены в вирусе гриппа H1N1 (Glu627Lys в белке PB2 и Asp35Asn в гемагглютинине (HA) — нумерация по H3) и 6 мутаций в белках вируса H5N3 (Glu627Lys в PB2, Val113Ala в PB1, Ser82Pro в PB1‑F2, Lys52Arg в HA2, Arg65Lys в NP и Ser59Ile в NA). Возрастание вирулентности для мышей, скорее всего, обусловлено общей для обоих вирусов заменой – Glu627Lys в  белке PB2. Замена Asp35Asn в  HA адаптированного к  мышам вируса гриппа H1N1  ассоциирована с возрастанием значения рН конформационного перехода HA с 5.0 до 5.5 относительно HA дикого вируса. Обнаруженные в адаптированном варианте H5N3 мутации в белках НА, NA и PB1‑F2 — уникальные. Мутации Glu627Lys в PB2, Arg65Lys в NP и Val113Ala в PB1, скорее всего, носят адаптационный характер