To penetrate host tissues, histotoxic clostridia secrete virulence factors including enzymes to hydrolyze extracellular matrix. Clostridium histolyticum, recently renamed as Hathewaya histolytica, produces two classes of collagenase (ColG and ColH). The high-speed AFM study showed that ColG collagenase moves unidirectionally to plane collagen fibril and rebundles fibril when stalled . The structural explanation of the roles for the tandem collagen-binding segment (CBDs) is illuminated by its calcium-bound crystal structure at 1.9 Å resolution (Rwork = 15.0%; Rfree = 19.6%). Activation may involve calcium-dependent domain rearrangement supported by both small-angle X-ray scattering and size exclusion chromatography. At pCa ≥ 5 (pCa = -log[Ca2+ ]), the tandem CBD adopts an extended conformation that may facilitate secretion from the bacterium. At pCa ≤ 4, the compact structure seen in the crystal structure is adopted. This arrangement positions the two binding surfaces ~ 55 Å apart, and possibly ushers ColG along tropocollagen molecules that allow for unidirectional movement. A sequential binding mode where tighter binding CBD2 binds first could aid in processivity as well. Switch from processive collagenolysis to fibril rearrangement could be concentration dependent. Collagen fibril formation is retarded at 1 : 1 molar ratio of tandem CBD to collagen. Tandem CBD may help isolate a tropocollagen molecule from a fibril at this ratio. At 0.1 : 1 to 0.5 : 1 molar ratios fibril self-assembly was accelerated. Gain of function as a result of gene duplication of CBD for the M9B enzymes is speculated. The binding and activation modes described here will aid in drug delivery design.

UNASSIGNED

The full atomic coordinates of the tandem CBD and its corresponding structure factor amplitudes have been deposited in the Protein Data Bank (PDB accession code 5IKU). Small-angle X-ray scattering data and corresponding ab initio models have been submitted to the Small Angle Scattering Biological Data Bank (SASBDB). Accession codes CL2, collagenase module 2, CN2, CP2 are assigned to envelopes for tandem CBD at -log[Ca2+ ] (pCa) 3, 4, 5, and 6, respectively. Accession code DC64 was assigned to the complex of polycystic kidney disease-CBD1-CBD2 with mini-collagen.

Purpose: This study aimed to determine the anatomical and functional outcomes of pars plana vitrectomy without encircling band for primary rhegmatogenous retinal detachments with inferior breaks utilizing 3D heads up viewing system.

Method: This prospective, single-center study included 22 consecutive eyes with primary rhegmatogenous retinal detachments with only inferior breaks with proliferative vitreoretinopathy (PVR) CP2 or less, who underwent pars plana vitrectomy without encircling band, with silicon oil as tamponade. All surgeries were performed by a single surgeon. The single operation success rate was recorded after silicon oil removal.

Results: The patient population consisted of 08 women (36%) and 14 men (64%) with a mean age of 56.6 +/- 14.7 years. The mean follow-up period was 8 months. A single break was present in 13 cases (59%), and 2-4 breaks were present in 9 cases (40.9%). The mean time for the surgical procedure was 35 min (range: 25-50). The macula was found to be detached in 19 cases (86.36%) and attached in 3 cases (13.6%). Single operation success rate (SOSR) of vitrectomy, after silicon oil removal without encircling band, for primary rhegmatogenous retinal detachment (RRD) with inferior breaks was 95.4%. One case redetached due to PVR changes and underwent re-surgery. Final reattachment was achieved in all 22 cases (100%). Mean best-corrected visual acuity (BCVA) significantly improved from 1.43 ± 0.59 logarithm of the minimum angle of resolution (logMAR) to postoperative BCVA was 0.48 ± 0.34 logMAR (P = 0.001).

Conclusion: Pars plana vitrectomy without encircling band, utilizing 3D heads up the system in RRDs with inferior breaks in eyes with PVR grade C2 or less, provides good outcome.

Keywords: 3D heads up viewing system; digitally assisted vitreoretinal surgery; encircling band; inferior retinal breaks; rhegmatogenous retinal detachment; silicone oil injection.

Background: Epidemiological studies have shown that dairy product consumption is beneficial for cognitive function in elderly individuals. β-lactolin is a lacto-tetrapeptide Gly-Thr-Trp-Tyr rich in fermented dairy products that improves memory retrieval, attention, and executive function in older adults with subjective cognitive decline and prevents the pathology of Alzheimer's disease in rodents. There has been no study on the effects of β-lactolin on neural activity in humans.

Objective: We investigated the effects of β-lactolin on neural activity and cognitive function in healthy adults.

Methods: In this randomized, double-blind, placebo-controlled study, 30 participants (45-64 years old) consumed β-lactolin or placebo for 6 weeks. Neural activity during auditory and language tasks was measured through 64-channel electroencephalography. Moreover, verbal fluency tests were performed at baseline and after 6 weeks.

Results: The β-lactolin group had a significantly higher P300 amplitude at the Cp2 site (a part of the parietal lobe near the center of brain, p = 0.008), and C4 site (the area between the frontal and parietal lobe, p = 0.021) during the auditory tasks after 6 weeks than the placebo group. Thus, β-lactolin supplementation promoted neural activity in the parietal area, which increases attention during auditory cognitive tasks. Compared with the placebo group, the β-lactolin group also showed significant changes in the scores of verbal fluency test after 6 weeks (p = 0.03).

Conclusion: Our findings provide insight into the mechanisms underlying the effects of β-lactolin on attention in healthy adults.

Keywords: Attention; EEG; P300; clinical trial; cognitive function; memory; whey; β-lactoglobulin; β-lactolin; β-lactopeptide.

The parent compound 1,3-dithiane (L1) was reacted with CuI providing the 1D coordination polymer [{Cu(μ₂-I)₂Cu}(μ₂-L1)₂] _n (CP1), an isostructural compound [{Cu(μ₂-Br)₂Cu}(μ₂-L1)₂] _n (CP2) was isolated upon treatment of CuBr with L1. In contrast, treatment of L1 with CuCl results in the formation of 2D polymeric [{Cu(μ₂-Cl)₂Cu}(μ₂-L1)] _n (CP3), in which each sulfur atom acts as a 4-electron donor. The 1D compounds [{Cu(μ₂-X)₂Cu}(μ₂-L2)₂] _n (CP7, X = Br, and CP8, X = Cl) resulting from treatment of 2-methyl-1,3 dithiane (L2) with CuBr and CuCl are isostructural with their CuI homologue [{Cu(μ₂-I)₂Cu}(μ₂-L2)₂] _n (CP5), reported previously. Using CuCN, a 2D CP of composition [{Cu(μ₂-CN)₂Cu}(μ₂-L2)₂] _n (CP9) has been isolated. Complexation of 2-isobutyl-1,3-dithiane (L3) on CuI generates a 2D material [{Cu₃(μ₃-I)(μ₂-I)₂(μ₂-L3)₂}] _n (CP10), incorporating the usual trinuclear μ₃-I-capped Cu clusters as SBUs, whereas 2D-polymeric compounds [{Cu(μ₂-Br)₂Cu}(μ₂-L3)₂] _n (CP11) and [{Cu(μ₂-Cl)₂Cu}(μ₂-L3)₂] _n (CP12) were obtained with CuBr and CuCl. Treatment of 2-Me₃Si-1,3-dithiane (L4) with CuX yields the series [{Cu₂(μ₄-X)(μ₂-X)}(μ₂-L4)] _n (CP13-CP15). With 2-phenyl-1,3-dithiane (L5), the outcome of the reaction with CuI depends on the reaction conditions. Reaction with CuI in MeCN provides a 1D ribbon [{Cu(μ₂-I)₂Cu}(MeCN)₂(μ₂-L5)₂] _n (CP16), whereas treatment of CuI with L5 in hot EtCN yields 2D-polymeric[{Cu₃(μ₃-I)(μ₂-I)₂(μ₂-L5)₂}] _n (CP17). A reversible phase transition from triclinic P1̅ to monoclinic P2₁/ m is observed when recording the structure of CP16 at five different temperatures in the 100-300 K range. Ligand L6 containing a ferrocenyl function at the 2-position was also probed as organometallic dithioether ligand. Reaction of L6 with 1 equiv of CuI produces the 0D dinuclear complex [{Cu(μ₂-I)₂Cu}(η¹-L6)₂(MeCN)₂] (D1), whereas treatment with 2 equiv of CuI affords the novel 1D CP [{Cu(μ₃-I)₂Cu}(μ-L6)] _n (CP18), in which both S atoms of one L6 molecule span two copper centers of the infinite (CuI) _n ribbon. Some selected results of thermal analyses and luminescence measurements are also presented.

A structurally unique and strongly luminescent nonporous 3D coordination polymer (CP) [Cu8I8(methyldithiane)4] n, CP3, has been prepared in a quasi-anticipated manner from 2-methyl-1,3-dithiane, L1, and CuI. This CP incorporates an unprecedented Cu8I8 cluster built upon two side-fused open cubanes. The crystal structure of CP3 has been determined at 100, 150, 200, 250, 300, 350, and 400 K to study the temperature dependence of the Cu···Cu distances. Two other topological 1D and 2D CPs isomers of formula [{Cu2I2}(L1)2] n featuring dinuclear {Cu2(μ2-I)2} rhomboids were also obtained independently by control of the reaction conditions. These two CPs convert into CP3 in hot PrCN, thus indicating that this latter material is the thermodynamic product. While CP1 and CP2 are not emissive, CP3 exhibits an intense luminescence due to the incorporation of the octanuclear Cu8I8 clusters as secondary building units within the network. The photophysical properties of CP3 have been investigated and rationalized by means of DFT and TDDFT computing. Furthermore, the thermal stability of these materials has been studied by ATG and DSC analyses. The Raman spectra of CP1-3 have been recorded in the solid state in the 50-500 cm-1 region.

With the objective to establish a correlation between the spacer distance and halide dependence on the structural features of coordination polymers (CPs) assembled by the reaction between CuX salts (X = Cl, Br, I) and dithioether ligands BzS(CH₂)_nSBz (<i>n</i> = 1-9; Bz = benzyl), a series of 26 compounds have been prepared and structurally investigated. A particular attention has been devoted to the design of networks with extremely long and flexible methylene spacer units between the SBz donor sites. Under identical conditions, CuI and CuBr react with BzSCH₂Bz (<b>L1</b>) affording respectively the one-dimensional (1D) CPs {Cu(μ₂-I)₂Cu}(μ-<b>L1</b>)₂]<i>n</i> (<b>CP1</b>) and {Cu(μ₂-Br)₂Cu}(μ-<b>L1</b>)₂] (<b><em>CP2</em></b>), which incorporate Cu(μ₂-X)₂Cu rhomboids as secondary building units (SBUs). The hitherto unknown architecture of two-dimensional (2D) layers obtained with CuCl (<b>CP3</b>) differs from that of <b>CP1</b> and <b><em>CP2</em></b>, which bear inorganic -Cl-Cu-Cl-Cu-Cl- chains interconnected through bridging <b>L1</b> ligands, thus forming a 2D architecture. The crystallographic characterization of a 1D CP obtained by reacting CuI with 1,3-bis(benzylthio)propane (<b>L2</b>) reveals that [{Cu(μ₂-I)₂Cu}(μ-<b>L2</b>)₂]<i>n</i> (<b>CP4</b>) contains conventional Cu₂I₂ rhomboids as SBUs. In contrast, unusual isostructural CPs [{Cu(μ₂-X)}(μ₂-<b>L2</b>)]<i>n</i> (<b>CP5</b>) and (<b>CP6</b>) are obtained with CuX when X = Br and Cl, respectively, in which the isolated Cu atoms are bridged by a single μ₂-Br or μ₂-Cl ion giving rise to infinite [Cu(μ₂-X)Cu]<i>n</i> ribbons. The crystal structure of the strongly luminescent three-dimensional (3D) polymer [{Cu₄(μ₃-I)₃(μ₄-I)(μ-<b>L3</b>)_1.5]<i>n</i> (<b>CP7</b>) issued from reacting 2 equiv of CuI with BzS(CH₂)₄SBz (<b>L3</b>) has been redetermined. <b>CP7</b> features unusual [(Cu₄I₃)(μ₄-I)]<i>n</i> arrays securing the 3D connectivity. In contrast, mixing CuI with an excess of <b>L3</b> provides the nonemissive material [{Cu(μ₂-I)₂Cu}(μ-<b>L3</b>)₂]<i>n</i> (<b>CP8</b>). Treatment of CuBr and CuCl with <b>L3</b> leads to [{Cu(μ₂-Br)₂Cu}(μ-<b>L3</b>)₂]<i>n</i> (<b>CP9</b>) and the 0D complex [{Cu(μ₂-Cl)₂Cu}(μ-<b>L3</b>)₂] (<b>D1</b>), respectively. The crystallographic particularity for <b>CP9</b> is the coexistence of two topological isomers within the unit cell. The first one, <b>CP9</b>-<b>1D</b>, consists of simple 1D ribbons running along the <i>a</i> axis of the unit cell. The second topological isomer, <b>CP9</b>-<b>2D</b>, also consists of [Cu(μ₂-Br)₂Cu] SBUs, but these are interconnected in a 2D manner forming 2D sheets placed perpendicular to the 1D ribbons. Four 2D CPs, namely, [{Cu₄(μ₃-I)₄}(μ-<b>L4</b>)₂]<i>n</i> (<b>CP10</b>), [{Cu(μ₂-I)₂Cu}(μ-<b>L4</b>)₂]<i>n</i> (<b>CP11</b>), [{Cu(μ₂-Br)₂Cu}(μ-<b>L4</b>)₂]<i>n</i> (<b>CP12</b>), and [{Cu(μ₂-Cl)₂Cu}(μ-<b>L4</b>)₂]<i>n</i> (<b>CP13</b>), stem from the self-assembly process of CuX with BzS(CH₂)₆SBz (<b>L4</b>). A similar series of 2D materials comprising [{Cu₄(μ₃-I)₄}(μ-<b>L5</b>)₂]<i>n</i> (<b>CP14</b>), [{Cu(μ₂-I)₂Cu}(μ-<b>L5</b>)₂]<i>n</i> (<b>CP15</b>), [{Cu(μ₂-Br)₂Cu}(μ-<b>L5</b>)₂]<i>n</i> (<b>CP16</b>), and [{Cu(μ₂-Cl)₂Cu}(μ-<b>L5</b>)₂]<i>n</i> (<b>CP17</b>) result from the coordination of BzS(CH₂)₇SBz (<b>L5</b>) on CuX. Ligation of CuX with the long-chain ligand BzS(CH₂)₈SBz (<b>L6</b>) allows for the X-ray characterization of the luminescent 2D [{Cu₄(μ₃-I)₄}(μ-<b>L6</b>)₂]<i>n</i> (<b>CP18</b>) and the isostructural 1D series [{Cu(μ₂-X)₂Cu}(μ-<b>L6</b>)₂]<i>n</i><b>CP19 (</b>X = I), <b><em>CP2</em>0</b> (X = Br) and <b><em>CP2</em>1</b>(X = Cl). Noteworthy, BzS(CH₂)₉SBz (<b>L7</b>) bearing a very flexible nine-atom chain generated the crystalline materials 2D [{Cu₄(μ₃-I)₄}(μ-<b>L7</b>)₂]<i>n</i> (<b><em>CP2</em>2</b>) and the isostructural 1D series [{Cu(μ₂-X)₂Cu}(μ-<b>L6</b>)₂]<i>n</i><b><em>CP2</em>3</b> (X = I), <b><em>CP2</em>4</b> (X = Br), and <b><em>CP2</em>5</b> (X = Cl), featuring nanometric separations between the cubane- or rhomboid-SBUs. This comparative study reveals that the outcome of the reaction of CuX with the shorter ligands BzS(CH₂)_nSBz (<i>n</i> = 1-4) is not predictable. However, with more flexible spacer chains BzS(CH₂)_nSBz (<i>n</i> = 6-9), a clear structural pattern can be established. Using a 1:1 CuX-to-ligand ratio, [{Cu(μ₂-X)₂Cu}(μ-<b>L4-7</b>)₂] CPs are always formed, irrespectively of <b>L4</b>-<b>L7</b>. Employing a 2:1 CuX-to-ligand ratio, only CuI is able to form networks incorporating Cu₄(μ₃-I)₄ clusters as SBUs. All attempts to construct polynuclear cluster using CuBr and CuCl failed. The materials have been furthermore analyzed by powder X-ray diffraction, Raman spectroscopy, and thermogravimetric analysis, and the photophysical properties of the emissive materials have been studied.

BACKGROUND

Postgraduate year 2 ambulatory care pharmacy residents (PGY2 residents) may be able to improve healthcare quality by providing clinical pharmacy services provided to self-insured employer health plan patients. The objectives of this study are to describe this care delivery in a family medicine clinic, and to identify patients most likely to benefit from the service.

METHODS

From October 1, 2014 till June 30, 2015, comprehensive medication review was completed by PGY2 residents for patients insured by CU Anthem at the University of Colorado Westminster Family Medicine. For patients with medication-related problems (MRPs), a note was sent to the provider before the patient visit. Patient characteristics were compared in those who received a clinical pharmacy note with those who did not.

RESULTS

Sixty-eight MRPs were identified in 39 notes; 40 (58.8%) recommendations were implemented. The following Clinical Pharmacy Priority (CP2) score criteria were identified more frequently in patients with MRPs: age ≥65 years, diagnosis of diabetes, hypertension, chronic obstructive pulmonary disease, cardiovascular disease, blood pressure ≥140/90, hemoglobin A1c >7.9%, and ≥6 items on the medication list.

CONCLUSIONS

PGY2 residents identified and resolved numerous clinically relevant MRPs. Patient-specific criteria can be utilized to target self-insured employer health plan patients who are likely to have clinically relevant MRPs.

In this work, three mono- and bidimensional coordination polymers (CPs) based on Cu(II) and Cu(I) ([Cu₂(TAcO)₂(C₂O₄)(4,4'-bpy)]·4H₂O (CP1), [Cu₂(UAcO)₂(C₂O₄)(4,4'-bpy)]·2H₂O (CP2) and [Cu₂(TAcO)₂(4,4'-bpy)] (CP3)), decorated with thymine and uracil-1-acetate (TAcO and UAcO), 4,4'-bipyridine (4,4'-bpy) and oxalate are synthetized. The supramolecular structures of the CPs are based on the formation of non-canonical hydrogen bonds established between the free moieties of nucleobases. Interestingly, the presence of Cu(II) centers provide for compound CP1, magnetism and semiconducting properties. Additionally, CP1 has been doped with iodine, increasing its electrical conductivity up to two orders of magnitude. Moreover, the size of the materials can be modulated from millimeters to the nanoscale, depending on the crystallization conditions and/or using ultrasound.

Renal cell carcinoma (RCC) is a major healthcare burden globally. Tumor‑derived extracellular vesicles (EVs) contribute to the formation of a pro‑metastatic microenvironment. In the present study, we explored the role and mechanism of RCC cell 786‑O‑derived EVs (786‑O‑EVs) in RCC. First, 786‑O‑EVs were extracted and identified, and EV internalization of RCC cells was observed. RCC cell malignant behaviors and long noncoding RNA (lncRNA) metastasis‑associated lung adenocarcinoma transcript 1 (MALAT1) expression patterns were detected before and after 786‑O‑EV treatment. MALAT1 was intervened to evaluate RCC cell behaviors. The downstream mechanism involving MALAT1 was predicted. In addition, the relationship among MALAT1, transcription factor CP2 like 1 (TFCP2L1) and ETS proto‑oncogene 1, transcription factor (ETS1) was analyzed. TFCP2L1 expression patterns were measured after 786‑O‑EV exposure. Tumor xenograft formation assay and lung metastasis model were adopted to verify the role of 786‑O‑EVs in vivo in RCC. It was found that 786‑O‑EVs could be internalized by RCC cells. 786‑O‑EVs promoted RCC cell malignant behaviors, accompanied by elevated MALAT1 expression levels. The 786‑O‑EVs with MALAT1 knockdown attenuated the promotive effect of sole 786‑O‑EVs on RCC cells. MALAT1 located ETS1 in the TFCP2L1 promoter and negatively regulated TFCP2L1, and ETS1 protein could specifically bind to MALAT1. 786‑O‑EVs enhanced the binding of ETS1 and the TFCP2L1 promoter and decreased TFCP2L1 expression. In vivo, 786‑O‑EVs promoted tumor growth and RCC lung metastasis, which was suppressed following inhibition of MALAT1. Our findings indicated that 786‑O‑EVs promoted RCC invasion and metastasis by transporting MALAT1 to promote the binding of transcription factor ETS1 and TFCP2L1 promoter.

Keywords: ETS1; TFCP2L1; extracellular vesicles; invasion; lncRNA MALAT1; migration; renal cell carcinoma.

SPRY domain- and SOCS box-containing proteins SPSB1, SPSB2, and SPSB4 interact with inducible nitric oxide synthase (iNOS), causing the iNOS to be polyubiquitinated and targeted for degradation. Inhibition of this interaction increases iNOS levels, and consequently cellular nitric oxide (NO) concentrations, and has been proposed as a potential strategy for killing intracellular pathogens. We previously described two DINNN-containing cyclic peptides (CP1 and CP2) as potent inhibitors of the murine SPSB-iNOS interaction. In this study, we report the crystal structures of human SPSB4 bound to CP1 and CP2 and human SPSB2 bound to CP2. We then used these structures to design a new inhibitor in which an intramolecular hydrogen bond was replaced with a hydrocarbon linkage to form a smaller macrocycle while maintaining the bound geometry of CP2 observed in the crystal structures. This resulting pentapeptide SPSB-iNOS inhibitor (CP3) has a reduced macrocycle ring size, fewer nonbinding residues, and includes additional conformational constraints. CP3 has a greater affinity for SBSB2 ( KD = 7 nM as determined by surface plasmon resonance) and strongly inhibits the SPSB2-iNOS interaction in macrophage cell lysates. We have also determined the crystal structure of CP3 in complex with human SPSB2, which reveals the structural basis for the increased potency of CP3 and validates the original design.

To compare three different protocols to assess the velocity associated with the maximal oxygen uptake (V_max) in soccer players. Sixteen semi-professional soccer players performed three maximum incremental tests on treadmill: two continuous protocols [1 km·h^-1·min^-1 (CP1); and 1 km·h^-1 every 2 min (CP2)], and one discontinuous (DP) protocol to determine V_max, maximum oxygen uptake (VO_2max) and oxygen cost of running (i.e., the slope of the VO₂ vs velocity relationship at submaximal exercise). V_max was higher in CP1> CP2> DP (19.4 ± 1.7, 17.4 ± 1.2, 16.1 ± 1.1 km·h^-1 for CP1, CP2, and DP, respectively; P < 0.05 ES: 0.09 to 3.36). No difference in VO_2max was found between CP1, CP2 and DP (P > 0.05). Oxygen cost of running showed between-protocol differences (CP1> CP2> DP; P < 0.05; ES: 0.28 to 3.30). V_max was higher when determined using continuous vs discontinuous protocols due to the greater overestimation in oxygen cost of running. Such differences in V_max should be considered to optimize acute physiological responses during high-intensity running activities.

Keywords: Sports; aerobic power; football; running economy; training.

Background: Molecular analysis has shown that breast carcinomas can be classified into several intrinsic subtypes, with implications for management and prognosis. In the majority of pathology laboratories molecular analysis of each case is not possible and immunohistochemistry is used for subtyping. This includes analysis of hormone receptors as well as HER2-neu and Ki67. The methodology for the interpretation of the proliferation index using Ki67 remains an area of uncertainty. We investigated the degree of agreement between different methods of Ki67 interpretation.

Materials and methods: We analyzed 204 breast core biopsies diagnostic of breast carcinoma using visual estimation/eyeballing (EB), ImmunoRatio, and counting by 2 pathologists (CP1 and CP2). The correlation between the different methods and the interobserver agreement between the 2 pathologists was assessed. Specific analysis was also done with respect to classification of cases into low Ki67 groups (using Ki67 values<14% and <20%) since this is critical in classifying tumors into luminal A and luminal B subtypes.

Results: Correlation between the different methods was best achieved comparing ImmunoRatio and CP1, and worst comparing CP1 and EB. Correlation was better when considering interobserver variability (CP1 vs. CP2). Comparing the number of cases classified as low Ki67 (<14% and <20%) the Cohen κ statistic varied from κ=0.267 to 0.814 with different methods. When limiting the analysis to cases with a Ki67 of 10% to 25% according to any method, there was greater disagreement.

Conclusions: At the higher and lower Ki67 levels, the correlation between the methods of assessment was acceptable, however, at levels close to the cut-off values for lumial A versus luminal B, several patients would be differently classified by the different methods and therefore potentially receive suboptimal management.

Purpose: The transcription factors YY1 and CP2 have been associated with tumor promotion and suppression in various cancers. Recently, simultaneous expression of both markers was correlated with negative prognosis in cancer. The aim of this study was to explore the expression of YY1 and CP2 in head and neck squamous cell carcinoma (HNSCC) patients and their association with survival.

Methods: First, we analyzed mRNA expression and copy number variations (CNVs) of YY1 and CP2 using "The Cancer Genome Atlas" (TCGA) with 510 HNSCC patients. Secondly, protein expression was investigated via immunohistochemistry in 102 patients, who were treated in the Vienna General Hospital, utilizing a tissue microarray.

Results: The median follow-up was 2.9 years (1.8-4.6) for the TCGA cohort and 10.3 years (6.5-12.8) for the inhouse tissue micro-array (TMA) cohort. The median overall survival of the TCGA cohort was decreased for patients with a high YY1 mRNA expression (4.0 vs. 5.7 years, p = 0.030, corr. p = 0.180) and high YY1-CNV (3.53 vs. 5.4 years, p = 0.0355, corr. p = 0.213). Furthermore, patients with a combined high expression of YY1 and CP2 mRNA showed a worse survival (3.5 vs. 5.4 years, p = 0.003, corr. p = 0.018). The mortality rate of patients with co-expression of YY1 and CP2 mRNA was twice as high compared to patients with low expression of one or both (HR 1.99, 95% CI 1.11-3.58, p = 0.021). Protein expression of nuclear YY1 and CP2 showed no association with disease outcome in our inhouse cohort.

Conclusion: Our data indicate that simultaneous expression of YY1 and CP2 mRNA is associated with shorter overall survival. Thus, combined high mRNA expression might be a suitable prognostic marker for risk stratification in HNSCC patients. However, since we could not validate this finding at genomic or protein level, we hypothesize that unknown underlying mechanisms which regulate mRNA transcription of YY1 and CP2 are the actual culprits leading to a worse survival.

Keywords: CP2; Head and neck squamous cell carcinoma; Prognosis; Survival; Transcription factor; YY1.

Three new coordination polymers (CPs) named [Cu(6mna)]n (CP1), [CuCl(H6mna)(H2O)0.33]n (CP2), and {[(CuI)2H2dtdn].MeCN}n (CP3), (H6mna = 6-mercaptonicotinic acid, and H2dtdn = 6,6'-dithiodinicotinic acid) have been synthesized and their structures determined by single-crystal X-ray diffraction. Complexes 1 and 3 are 2D-CPs while complex 2 is a 1D-CP. The optical properties of these complexes have been evaluated in the solid state, at room temperature and at 77 K, and compared with those of the starting ligands. The electrical conductivity of CPs 1-3 has been evaluated and their thermal stabilities have been studied. CP2 shows an interesting crystal arrangement, where the connection between the ligand and the copper forms a channel-like structure characterized by an intrinsic disorder. Crystal data collected at low temperatures for this complex revealed minor structural changes in the CuCu distances and Cu-S-Cu angles along the chain, excluding phase transition. In CP1, the N and S atoms are involved in metal coordination bonds giving rise to a 2D coordination polymer. In CP3, the Cu-I bonds compose double ladder-like structures, bridged by H2dtdn ligands. The electrical conductivities of CPs 1-3 suggest their semiconductive behavior.

The genus Saccharum is composed of species with high polyploidy and highly varied chromosome numbers, laying a challenge for uncovering its genomic structure and evolution. We developed a chromosome 2 painting (CP2) probe by designing oligonucleotides covering chromosome 2 of Saccharum spontaneum (2n = 8x = 64). Fluorescence in situ hybridization (FISH) using this CP2 probe revealed six types of ploidies from twenty S. spontaneum clones, including 6x, 8x, 10x, 11x, 12x, and 13x clones. The finding of S. spontaneum clones with uneven of ploid suggested that certain S. spontaneum clones come from hybridization. It renews our knowledge that S. spontaneum is derived from autopolyploidization. Combined with a S. spontaneum-specific probe, chromosome 2-derived chromosome or fragments from either S. spontaneum or Saccharum officinarum can be identified in sugarcane modern cultivars. We revealed unexpected high level of interspecific recombination from introgressive S. spontaneum chromosomes (>50.0%) in cultivars ROC22 and ZZ1, indicating frequent chromosome exchange in cultivars. Intriguingly, we observed interspecific recombination recurring among either homoeologous or non-homoeologous chromosomes in sugarcane cultivars. These results demonstrated that chromosome painting FISH is a powerful tool in the genome dissection of sugarcane and provide new insights into the genome structure and evolution of the complex genus Saccharum.

Keywords: FISH; Saccharum; chromosome painting; interspecies recombination; ploidy.

The reaction of Mo2(SCH2CH2S)2Cp2 (1; Cp=eta-C5H5) with an excess of an alkyne in refluxing dichloromethane affords the bis(dithiolene) complexes Mo2(micro-SCR1=CR2S)2Cp2 (2a, R1=R2=CO2Me; 2b, R1=R2=Ph; 2c, R1=H, R2=CO2Me) whereas with 1 equiv of alkyne at room temperature the mixed dithiolene-dithiolate species Mo2(micro-SCR1=CR2S)(micro-SCH2CH2S)Cp2 (3a, R1=R2=CO2Me; 3b, R1=R2=Ph) are formed. The remaining dithiolate ligand in 3 can then be converted into a different dithiolene by reaction with a second alkyne. Applying this methodology, we have used bis(diphenylphosphino)acetylene to prepare the first examples of complexes containing phosphine-substituted dithiolene ligands: Mo2{micro-SC(CO2Me)=C(CO2Me)S}{micro-SC(PPh2)=C(PPh2)S}Cp2 (2g) and Mo2{micro-SC(PPh2)=C(PPh2)S}2Cp2 (2h). Tri- and tetrametallic complexes can then be assembled by coordination of these diphosphines to CpRuCl units by reaction with CpRu(PPh3)2Cl. Electrochemical studies of the Ru(II)/Ru(III) couple in Mo2{micro-SC(PPh2)=C(PPh2)S}2Cp2(RuClCp)2 (4b) reveals that the two separate ruthenium centers are oxidized electrochemically at different potentials, demonstrating communication between them through the dimolybdenum bis(dithiolene) core. Density functional theory calculations were carried out to explore the electronic structures of these species and to predict and assign their electronic spectra.

Adaptation to visual or auditory motion affects within-modality motion processing as reflected by visual or auditory free-field motion-onset evoked potentials (VEPs, AEPs). Here, a visual-auditory motion adaptation paradigm was used to investigate the effect of visual motion adaptation on VEPs and AEPs to leftward motion-onset test stimuli. Effects of visual adaptation to (i) scattered light flashes, and motion in the (ii) same or in the (iii) opposite direction of the test stimulus were compared. For the motion-onset VEPs, i.e. the intra-modal adaptation conditions, direction-specific adaptation was observed--the change-N2 (cN2) and change-P2 (cP2) amplitudes were significantly smaller after motion adaptation in the same than in the opposite direction. For the motion-onset AEPs, i.e. the cross-modal adaptation condition, there was an effect of motion history only in the change-P1 (cP1), and this effect was not direction-specific--cP1 was smaller after scatter than after motion adaptation to either direction. No effects were found for later components of motion-onset AEPs. While the VEP results provided clear evidence for the existence of a direction-specific effect of motion adaptation within the visual modality, the AEP findings suggested merely a motion-related, but not a direction-specific effect. In conclusion, the adaptation of veridical auditory motion detectors by visual motion is not reflected by the AEPs of the present study.

Ultraviolet-quenching substances (UVQS), recently identified pollutants in landfill leachate, can interfere with ultraviolet disinfection when landfill leachate is co-treated with municipal sewage. This study investigated the elimination of UVQS in mature landfill leachates through a membrane bioreactor (MBR) and a semi-aerobic aged refuse biofilter (SAARB). Humus (i.e., fulvic and humic acids) was the main component of organic matter in both MBR- and SAARB-treated landfill leachates, while there was a more stable chemical structure of humus in the MBR-treated leachate. The concentration of UVQS in MBR-treated mature landfill leachate was higher than that of SAARB-treated leachate. Ozonation can degrade UVQS effectively, especially for landfill leachate containing a high concentration UVQS (i.e., MBR-treated landfill leachate). However, a large accumulation of small molecule acid might be caused by ozonation for highly concentrated UVQS in landfill leachate, leading to the delayed degradation of total organic carbon. Moreover, ozonation degraded both fulvic acid and humic acid; and degraded humic acid more effectively. For instance, 88.0% removal (MBR-CP2) and 96.0% removal (SAARB-CP2) of humic acid was higher than those (83.3% for MBR-CP1 and 92.3% for SAARB-CP1) of fulvic acid. The destruction of UV-quenching functional groups of organics (such as CC) by ozone was the main UVQS degradation mechanism of ozonation applied to MBR- and SAARB-treated landfill leachates. Therefore, the ozonation process can efficiently decrease UV absorption intensity in both MBR- and SAARB-treated landfill leachates.

PREX is a positive regulatory element for xenobiotic responsive element (XRE)-mediated gene expression that is located upstream of the XRE in the CYP2A8 gene. Using gel mobility shift assays, we demonstrated that NF2d9 (LBP-1a), a transcription factor related to CP2 (LBP-1c/LSF), bound directly to PREX and also interacts indirectly with XRE. Luciferase-reporter gene assays showed that the overexpression of NF2d9 enhanced PREX and XRE-driven CYP2A8 gene transcriptional induction. These findings suggest that the interaction of NF2d9 with PREX and XRE enhances XRE-driven CYP2A8 gene transcriptional induction.

We study the information metric on instanton moduli spaces in two-dimensional nonlinear sigma models. In the CP1 model, the information metric on the moduli space of one instanton with the topological charge Q=k(k>> or =1) is a three-dimensional hyperbolic metric, which corresponds to Euclidean anti-de Sitter space-time metric in three dimensions, and the overall scale factor of the information metric is 4k(2)/3; this means that the sectional curvature is -3/4k(2). We also calculate the information metric in the CP2 model.

Stimulus-responsive polymeric nanocapsules usable as cell mimics can be engineered to precisely control cargo release. This work reports the release behavior of post-loaded nanoparticles through permeable membranes of stable pH and temperature dual-responsive polymeric nanocapsules (CP1, CP2, and CP3) with the same membrane thickness but different membrane composition, prepared by layer-by-layer assembly and surface-initiated single electron transfer living radical polymerization, respectively. These nanocapsules differ in their tunable membrane permeability for post-loaded nanoparticles as protein mimics, tailored by pH and temperature stimuli. Release mechanisms are dominated by membrane composition, such as polyelectrolyte multilayer membrane for CP1, pure cationic membrane for CP2, and valve-like functions for CP3. Thus, one can postulate the main locations of post-loaded protein mimics in the different nanocapsules. Understanding the post-loading and diffusion mechanism of nanoparticles through permeable membranes in cell mimics paves the way for the construction of new "smart" synthetic protocells with control over the exchange of bioactive nanoparticles between different compartments.

Vinylsilanes and/or allylsilanes are formed upon silylation of terminal alkenes with R3' SiCl in the presence of a Grignard reagent and a catalytic amount of [Cp2 ZrCl2 ] [Eq. (a)]. The reaction also proceeds under mild conditions when silylsulfides (X=SPh), silylselenides (X=SePh), and silyltellurides (X=TePh) are used in place of chlorosilanes (X=Cl). R″=alkyl, aryl, alkylsilyl; R'=Me, Et, nPr; R=CH2 R″, aryl, H.

Expression of the genes of the human beta-globin cluster is subject to stringent developmental regulation. An integral component of this control is competition between the gamma- and beta-promoters for the upstream regulatory sequences of the Locus Control Region (LCR). We have defined two stage selector elements (SSE and SSE-2), located in the proximal gamma-promoter and gamma-genes 5'UTR which mediate the preferential interaction of the gamma-gene with the LCR in the foetal developmental stage. The activity of both elements is dependent upon the binding of foetal and erythroid-specific proteins. We have purified the protein binding the proximal SSE and characterised it as a complex between the ubiquitous transcription factor CP2 and a 40 hD partner protein. Comparative studies between human CP2 and the chicken stage selector protein, NF-E4, demonstrate homology between the protein complexes. These findings demonstrate that competitive silencing of globin genes mediated by developmentally-specific protein complexes is conserved in evolution.

The reaction of [Cp2*Rh2Cl4] (Cp* = C5Me5) with a slight excess of K(3)SbS(3) in boiling THF gave the neutral clusters [Cp*4Rh4S5] (1), [Cp*3Rh3Sb2S5] (2), and after salt metathesis [Cp*3Rh3SbSn]PF6 (3; n = 5 and 6). The structures of 1-3 are heterocubane clusters with CpRh, S, and Sb vertices but with sulfur inserted into one (1 and 2) or two (3) edges. X-ray diffraction analysis of 2 additionally reveals a very short Sb-S distance of 2.297(1) A within the novel mu3-Sb2S4 ligand. Density functional theory calculation of the model compounds [SSbS]3-, [HSSbS]2-, and [HSSbH2S]0 provided strong evidence for the existence of a stable terminal Sb=S double bond in 2.