Magnetic ordering in a vanadium-organic coordination polymer using a pyrrolo[2,3-d:5,4-d']bis(thiazole)-based ligand.

Here we present the synthesis and characterization of a hybrid vanadium-organic coordination polymer with robust magnetic order, a Curie temperature T C of ∼110 K, a coercive field of ∼5 Oe at 5 K, and a maximum mass magnetization of about half that of the benchmark ferrimagnetic vanadium(tetracyanoethylene)∼2 (V·(TCNE)∼2). This material was prepared using a new tetracyano-substituted quinoidal organic small molecule 7 based on a tricyclic heterocycle 4-hexyl-4H-pyrrolo[2,3-d:5,4-d']bis(thiazole) (C6-PBTz). Single crystal X-ray diffraction of the 2,6-diiodo derivative of the parent C6-PBTz, showed a disordered hexyl chain and a nearly linear arrangement of the substituents in positions 2 and 6 of the tricyclic core. Density functional theory (DFT) calculations indicate that C6-PBTz-based ligand 7 is a strong acceptor with an electron affinity larger than that of TCNE and several other ligands previously used in molecular magnets. This effect is due in part to the electron-deficient thiazole rings and extended delocalization of the frontier molecular orbitals. The ligand detailed in this study, a representative example of fused heterocycle aromatic cores with extended π conjugation, introduces new opportunities for structure-magnetic-property correlation studies where the chemistry of the tricyclic heterocycles can modulate the electronic properties and the substituent at the central N-position can vary the spatial characteristics of the magnetic polymer.

Functional ultrasound imaging for assessment of extracellular matrix scaffolds used for liver organoid formation.

A method of 3D functional ultrasound imaging has been developed to enable non-destructive assessment of extracellular matrix scaffolds that have been prepared by decellularization protocols and are intended for recellularization to create organoids. A major challenge in organ decellularization is retaining patent micro-vascular structures crucial for nutrient access and functionality of organoids. The imaging method described here provides statistical distributions of flow rates throughout the tissue volumes, 3D vessel network architecture visualization, characterization of microvessel volumes and sizes, and delineation of matrix from vascular circuits. The imaging protocol was tested on matrix scaffolds that are tissue-specific, but not species-specific, matrix extracts, prepared by a process that preserved >98% of the collagens, collagen-associated matrix components, and matrix-bound growth factors and cytokines. Image-derived data are discussed with respect to assessment of scaffolds followed by proof-of-concept studies in organoid establishment using Hep3B, a human hepatoblast-like cell line. Histology showed that the cells attached to scaffolds with patent vasculature within minutes, achieved engraftment at near 100%, expressed liver-specific functions within 24 h, and yielded evidence of proliferation and increasing differentiation of cells throughout the two weeks of culture studies. This imaging method should prove valuable in analyses of such matrix scaffolds.

Pericentric chromatin loops function as a nonlinear spring in mitotic force balance.

The mechanisms by which sister chromatids maintain biorientation on the metaphase spindle are critical to the fidelity of chromosome segregation. Active force interplay exists between predominantly extensional microtubule-based spindle forces and restoring forces from chromatin. These forces regulate tension at the kinetochore that silences the spindle assembly checkpoint to ensure faithful chromosome segregation. Depletion of pericentric cohesin or condensin has been shown to increase the mean and variance of spindle length, which have been attributed to a softening of the linear chromatin spring. Models of the spindle apparatus with linear chromatin springs that match spindle dynamics fail to predict the behavior of pericentromeric chromatin in wild-type and mutant spindles. We demonstrate that a nonlinear spring with a threshold extension to switch between spring states predicts asymmetric chromatin stretching observed in vivo. The addition of cross-links between adjacent springs recapitulates coordination between pericentromeres of neighboring chromosomes.

Root-soil friction: quantification provides evidence for measurable benefits for manipulation of root-tip traits.

To penetrate soil, a root requires pressure both to expand the cavity it is to occupy, σn , and to overcome root-soil friction, σf . Difficulties in estimating these two pressures independently have limited our ability to estimate the coefficient of soil-root friction, µsr . We used a rotated penetrometer probe, of similar dimensions to a root, and for the first time entering the soil at a similar rate to a root tip, to estimate σn . Separately we measured root penetration resistance (PR) Qr . Root PR was between two to four times σn . We estimated that the coefficient of root-soil friction (µsr ) was 0.21-0.26, based on the geometry of the root tip. This is slightly larger than the 0.05-0.15 characteristic of boundary lubricants. Scanning electron microscopy showed that turgid border cells lined the root channel, supporting our hypothesis that the lubricant consisted of mucilage sandwiched between border cells and the surface of the root cap and epidermis. This cell-cell lubrication greatly decreased the friction that would otherwise be experienced had the surface of the root proper slid directly past unlubricated soil particles. Because root-soil friction can be a substantial component of root PR, successful manipulation of friction represents a promising opportunity for improving plant performance.

Out of control little-used clinical assets are draining healthcare budgets.

To improve utilization and reduce the cost of maintaining mobile clinical equipment, healthcare organization leaders should do the following: Select an initial asset group to target. Conduct a physical inventory. Evaluate the organization's asset "ecosystem." Optimize workflow processes. Phase in new processes, and phase out inventory. Devote time to change management. Develop a replacement strategy.

Synthesis and sulfur oxygenation of a (N3S)Ni complex related to nickel-containing superoxide dismutase.

A nickel(II) thiolate complex incorporating three N-donor types (amino, amido, and imidazole) has been synthesized and characterized. The (N(3)S)Ni complex, [N-{2-[(2-mercapto-2-methylpropyl)amino]ethyl}-1-methylimidazole-2-carboxamido]nickel(II) (1), is stable in the presence of O(2) but readily forms the sulfinato (RSO(2)(-)) derivative 2 upon the addition of H(2)O(2). Electrochemical investigations of 1 reveal an irreversible sulfur-based oxidation at +0.17 V vs Fc(+)/Fc (200 mV/s) that shifts to +0.81 V upon oxidation to 2. Density functional theory investigations of 1 reveal a highest occupied molecular orbital that is predominantly sulfur-based, consistent with the observed sulfur-based oxidation and O(2) stability.

The NIH Human Microbiome Project.

The Human Microbiome Project (HMP), funded as an initiative of the NIH Roadmap for Biomedical Research (http://nihroadmap.nih.gov), is a multi-component community resource. The goals of the HMP are: (1) to take advantage of new, high-throughput technologies to characterize the human microbiome more fully by studying samples from multiple body sites from each of at least 250 "normal" volunteers; (2) to determine whether there are associations between changes in the microbiome and health/disease by studying several different medical conditions; and (3) to provide both a standardized data resource and new technological approaches to enable such studies to be undertaken broadly in the scientific community. The ethical, legal, and social implications of such research are being systematically studied as well. The ultimate objective of the HMP is to demonstrate that there are opportunities to improve human health through monitoring or manipulation of the human microbiome. The history and implementation of this new program are described here.

Corroborative cobalt and zinc model compounds of alpha-amino-beta-carboxymuconic-epsilon-semialdehyde decarboxylase (ACMSD).

We have synthesised and characterised a series of new Co(II) complexes (1-4, 6, 7) and one new Zn(II) complex (5) employing N(3)- and N(3)O-donor ligands [biap: N,N-bis(2-ethyl-5-methyl-imidazol-4-ylmethyl)amino-propane, KBPZG: potassium N,N-bis(3,5-dimethylpyrazolylmethyl) glycinate, KBPZA: potassium N,N-bis(3,5-dimethylpyrazolylmethyl) alaninate, KB(i)PrPZG: potassium N,N-bis(3,5-di-iso-propylpyrazolylmethyl) glycinate, and KB((t)BuM)PZG: potassium N,N-bis(3-methyl-5-tert-butyl-pyrazolylmethyl)glycinate] as structural models of the metalloenzyme alpha-amino-beta-carboxymuconic-epsilon-semialdehyde decarboxylase (ACMSD). These complexes were characterised by several techniques including X-ray crystallographic analysis, X-band EPR, and mass spectrometry (ESI-MS). The crystal structures of 1, 2, 6,7 revealed that they exist as mononuclear Co(II) complexes with trigonal-bipyramidal geometry in the solid state. Compounds 3 and 5 form infinite polymeric chains of Co(II) or Zn(II) complexes, respectively, linked by the pendant carboxylate arms of the BPZG(-) ligand. By comparing the degree of distortion in the penta-coordinate complexes, defined by the Addison-parameter tau, with the value determined for the five-coordinate centres found in the active site of ACMSD, it could be seen that complexes 5 and 7 are very good matches for the geometry of the zinc(II) centre in monomer A of the native enzyme. All complexes could be seen as model compounds for the active site of the enzyme ACMSD, where the Co(II) complexes reflected the structural flexibility found in case of two histidine (His177 and His228) residues found in the active site of the enzyme.

Reflections on Small Molecule Manganese Models that Seek to Mimic Photosynthetic Water Oxidation Chemistry.

Recent advances in the study of the Oxygen Evolving Complex (OEC) of Photosystem II (PSII) include structural information attained from several X-ray crystallographic (XRD) and spectroscopic (XANES and EXAFS) investigations. The possible structural features gleaned from these studies have enabled synthetic chemists to design more accurate model complexes, which in turn, offer better insight into the possible pathways used by PSII to drive photosynthetic water oxidation catalysis. Mononuclear model compounds have been used to advance the knowledge base regarding the physical properties and reactivity of high-valent (Mn(IV) or Mn(V)) complexes. Such investigations have been especially important in regard to the manganyl (Mn(IV)=O or Mn(V)≡O) species, as there are no reports, to date, of any structural characterized multinuclear model compounds that incorporate such a functionality. Dinuclear and trinuclear model compounds have also been thoroughly studied in attempts to draw further comparison to the physical properties observed in the natural system and to design systems of catalytic relevance. As the reactive center of the OEC has been shown to contain an oxo-Mn(4)Ca cluster, exact structural models necessitate a tetranuclear Mn core. The number of models that make use of Mn(4) clusters has risen substantially in recent years, and these models have provided evidence to support and refute certain mechanistic proposals. Further work is needed to adequately address the rationale for Ca (and Cl) in the OEC and to determine the sequence of events that lead to O(2) evolution.

Germination responses to water potential in neotropical pioneers suggest large-seeded species take more risks.

BACKGROUND AND AIMS: In neotropical forests, very small-seeded pioneer species (<0.1 mg seed mass) recruit preferentially in small tree fall gaps and at gap edges, but large-seeded pioneers do not. Since water availability is related to gap size, these differences in microsite preference may reflect in part species-specific differences in germination at reduced water potentials. METHODS: For 14 neotropical pioneer species, the hypothesis is tested that small-seeded species, with shallow initial rooting depths, reduce the risks associated with desiccation by germinating more slowly and at higher water potentials than large-seeded species. KEY RESULTS: Germination occurred both more quickly and at lower water potentials with increasing seed mass. For example, Ochroma pyramidale (seed mass 5.5 mg) had a time to 50 % germination (T50) of 2.8 d and a median base potential for germination (psi(b50)) of -1.8 MPa while Clidemia quinquenervia (seed mass 0.017 mg) had a T50 of 17.6 d and psi(b50) of -1.1 MPa. CONCLUSIONS: These data suggest that small-seeded species germinate only in comparatively moist microsites, such as small canopy gaps, which may reduce the risk of drought-induced mortality. Conversely, large-seeded species are able to germinate in the drier environment of large gaps, where they benefit by enhanced seedling growth in a high irradiance environment. The positive association of seed size and canopy gap size for optimal seedling establishment is maintained by differential germination responses to soil water availability coupled with the scaling of radicle growth rate and seed size, which collectively confer greater drought tolerance on large-seeded species.

Psychosocial variables affect the quality of life of men diagnosed with chronic prostatitis/chronic pelvic pain syndrome.

OBJECTIVE: To examine interactions between demographic, pain, urinary, psychological and environmental predictors of quality of life (QOL) in men with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). PATIENTS AND METHODS: In all, 253 men previously enrolled in the National Institutes of Health Chronic Prostatitis Cohort study in North American tertiary-care clinical centres (six in the USA and one in Canada) self-reported with validated instruments, including the QOL subscales of the Short Form-12 (physical, SF12-PCS; and mental, SF12-MCS), demographics, urinary symptoms, depression, current pain, pain coping, 'catastrophizing' (catastrophic thinking about pain), pain control, social support and solicitous responses from a partner. Data were collected through a one-time survey. Covariates determined to be significant were entered into a multivariable regression model predicting SF12-PCS and SF12-MCS. RESULTS: Adjusting for covariates, regression models showed that poorer SF12-PCS scores were predicted by worse urinary function (P < 0.001) and increased use of pain-contingent resting as a coping strategy (P = 0.026). Further, poorer SF12-MCS scores were predicted by greater pain catastrophizing (P = 0.002) and lower perceptions of social support (P< 0.001). In separate follow-up analyses, helplessness was the significant catastrophizing subscale (P < 0.001), while support from family and friends were the significant social support subscales (P = 0.002 and <0.001). CONCLUSIONS: These data suggest that specific coping and environmental factors (i.e. catastrophizing, pain-contingent resting, social support) are significant in understanding how patients with CP/CPPS adjust. These data can be used to develop specific cognitive-behavioural programmes for men with CP/CPPS who are refractory to standard medical therapy.

Characterization of HIV type 1 reverse transcriptase mutations in infants infected by mothers who received peripartum nevirapine prophylaxis in Jos, Nigeria.

This study was carried out to characterize HIV-1 reverse transcriptase (RT) mutations in vertically infected infants in Jos, Nigeria. DNA was extracted from peripheral blood mononuclear cells of 102 infants, aged 0 to 6 months, born to HIV-1-infected mothers who had received peripartum single-dose nevirapine prophylaxis. PCR-based diagnosis revealed that 14 infants (13.7%) were infected with HIV-1. Phylogenetic analyses of RT revealed wide viral diversity, with CRF02_AG, subtype G, subsubtype A3, CRF06_cpx, and a subtype D recombinant present in the population. Four of 13 (31%) infants had NNRTI resistance mutations--V179I (2 infants), Y181C, and V179E. Intriguingly, subtype G sequences did not have NNRTI mutations but rather carried a Q207N mutation, which may undergo negative selection under drug pressure. Our data suggest wide diversity for vertically transmitted HIV-1 viruses in Nigeria and highlight the potential significance of transmitting rare mutations in subtype G.

Twenty years of prospective molecular epidemiology in Senegal: changes in HIV diversity.

Over a 20-year period we have observed the dynamics of HIV-1 subtypes and HIV-2 infection in a prospective cohort of registered female sex workers (FSW) in Dakar, Senegal. Prevalence and incidence rates for HIV-1 and HIV-2 are described from 290 seroprevalent and 193 seroincident subjects who were among the 3,910 women enrolled between 1985 and 2004. We report a significant decrease of HIV-2 prevalence in the cohort, parallel to the introduction and rise of HIV-1 infection. In 328 HIV-1-infected women, a 385-bp C2-V3 fragment of the envelope gene was sequenced and classified into the following subtypes or recombinant forms: 239 (72%) were subtype A [of which 180 (55%) were CRF02_AG and 53 (16%) were A3], 10 (3%) were B, 12 (4%) were C, 11 (4%) were D, 18 (6%) were G, 24 (7%) were CRF06_cpx, and 7 (2%) were CRF09_cpx. We found an increasing proportion of CRF02_AG over many years, but recently subsubtype A3 has over-taken CRF02_AG, with the largest proportion of new infections. The predominance of existing HIV-1 subtypes did not preclude the emergence and increase of other closely related subtypes or recombinant forms. This 20-year prospective serological and sequence analysis of HIV viruses reveals a complex and changing HIV epidemic in Senegal.

Allometric relationships between seed mass and seedling characteristics reveal trade-offs for neotropical gap-dependent species.

A seed size-seed number trade-off exists because smaller seeds are produced in greater number but have a lower probability of establishment. This reduced establishment success of smaller-seeded species may be determined by biophysical constraints imposed by scaling rules. Root and shoot diameter, root growth extension rate (RGER) and shoot length at death for dark-grown seedlings are predicted to scale with the cube root of seed embryo and endosperm mass (m). We confirmed this expectation for ten neotropical gap-dependent tree species with an embryo and endosperm dry mass>1 mg. However, for nine smaller seeded species (m<1 mg) with photoblastic germination, root and shoot diameters were larger than expected, and consequently, RGER was slower than expected. The maximum shoot thrust of seedlings from seeds with masses>or=1 mg was comparable to the estimated force required to displace overlying litter, supporting the hypothesis that photoblastic behaviour only occurs in seeds with insufficient shoot thrust to displace overlying leaves. Using the model soil water, energy and transpiration to predict soil drying in small and large gaps, we showed that: (1) gaps that receive a significant amount of direct sunlight will dry more quickly than small gaps that do not, (2) compared to the wet-season, soil that is already dry at depth (i.e. the dry-season) will dry faster after rainfall (this drying would most likely kill seedlings from small seeds) and (3) even during the wet-season, dry periods of a few days in large gaps can kill shallow-rooted seedlings. We conclude that the smaller the seed, the more vulnerable its seedling would be to both covering by litter and soil drying because it can only emerge from shallow depths and has a slow RGER. Consequently, we suggest that these allometrically related factors contribute to the reduced establishment success of smaller-seeded species that underpins the seed size-seed number trade-off.

Variable desiccation tolerance in Acer pseudoplatanus seeds in relation to developmental conditions: a case of phenotypic recalcitrance?

Nine seedlots of the widely planted southern and central European native tree species Acer pseudoplatanus L. were collected along a north-south gradient spanning 21° of latitude in Europe. We investigated how the heat sum during seed development influences seed maturity as assessed by physical, physiological and biochemical traits. Using principal component analysis we found predictable and consistent patterns in all traits, which correlated with heat sum. For example, compared with fruits from their native range (Italy and France, heat sum >3000°C d), fruits from the coldest location (Scotland; heat sum of 1873°C d) were shorter (c. 30 v. 42 mm), germinated over a narrower temperature range (5-20 v. 5-35°C) and had smaller embryos (28 v. > 70 mg) with a higher water content (c. 63 v. 48%), less negative solute potentials (c. -2.4 v. -4.1 MPa) and were more desiccation sensitive (critical water potential of -20.2 v. -55.4 to -60.7 MPa). The observed level of desiccation-tolerance for the French and Italian seedlots is more consistent with the intermediate category than the previous classification of A. pseudoplatanus as recalcitrant. Our results demonstrate that a lower heat sum causes fruits from northern Europe to be dispersed before maximum potential seed quality is achieved.

Viral dynamics of primary HIV-1 infection in Senegal, West Africa.

BACKGROUND: Few studies have addressed primary human immunodeficiency virus (HIV) type 1 infection in sub-Saharan Africa, where the epidemic is of a predominantly heterosexual character and is caused by different subtypes. The present study examines the dynamics of viral replication in subjects infected with various HIV-1 subtypes. METHODS: Seven hundred fifty-two HIV-negative Senegalese women at high risk for infection were monitored every 3 months for acute/early HIV infection; 26 infections were identified (23 HIV-1 and 3 HIV-2), with an HIV-1 incidence rate of 3.23 cases/person-years observation. Multiple viral-load measurements were taken for all seroconverters. RESULTS: The mean+/-standard deviation viral load for all subjects during the early stage of infection was 4.13+/-0.66 log10 copies/mL, with an overall decrease of 0.22 log10 copies/mL after the early stage; the viral set point was reached after 12 months of infection. Most subjects had relatively low viral loads during the early stage of infection. HIV-1 CRF02_AG-infected women had a significantly higher mean viral load during the early stage of infection (mean +/- SD, 4.45+/-0.60 log(10) copies/mL) than did non-HIV-1 CRF02_AG-infected women (mean+/-SD, 3.78+/-0.46 log(10) copies/mL) (P=.008). None of the subjects reported symptoms consistent with primary HIV-1 infection. CONCLUSION: Our findings in Senegalese women differ from what have been described for primary HIV-1 infection. Further investigations of primary infections with non-B subtypes are warranted, to better characterize their differences with primary infections with subtype B.

Highly active antiretroviral therapy and viral response in HIV type 2 infection.

Human immunodeficiency virus type 2 (HIV-2), the second human retrovirus known to cause AIDS, is endemic to West Africa but is infrequently found outside this region. We present a case series of 10 HIV-2--infected individuals treated in the United States. Physicians applied the principles of highly active antiretroviral therapy (HAART), normally used in treating HIV type 1, with modifications considered appropriate for treating HIV-2. CD4+ cell count, HIV-2 virus load, and clinical status were found to correlate well, providing evidence that HIV-2 virus load is useful in managing treatment of patients with HIV-2 who are receiving therapy. However, HAART regimens with predicted efficacy for treatment of HIV type 1 infection are not as efficacious for treatment of HIV-2. Controlled clinical trials of HIV-2-infected patients receiving various HAART regimens are needed to provide therapeutic guidance to the medical community.

Synthesis and oxygenation of a nickel(II) and zinc(II) dithiolate: an experimental and theoretical comparison.

The diamino-dithiolato N2S2 ligand N,N'-bis-2-methyl-mercaptopropyl-N,N'-dimethylethylenediamine, H2bmmp-dmed), and its nickel (1) and zinc (2) complexes have been prepared and their reactivities with hydrogen peroxide investigated. Complex 1 yields a mixture of sulfenato (RSO-), 4, sulfinato (RSO2-), 3, and sulfonato (RSO3-), 5, products upon addition of H2O2. Products are separable by column chromatography. Stoichiometric addition of H2O2 to 2 yields an inseparable mixture. Excess peroxide addition results in oxygenation of the ligand to the disulfonate, 6, and decomplexation of zinc. Complexes 1, 2, and 3 and compound 6 have been investigated by X-ray crystallography, and their structures are reported. Density functional theory (DFT) calculations of 1 and 2 reveal significant sulfur p character in the HOMO of each complex. However, 1 also shows significant metal d character that is pi-antibonding with respect to the sulfur p orbitals. Complex 2 shows little metal character in the HOMO. Implications of the HOMO with respect to S-centered reactivity and metal ligand distances in S-oxygenated products are provided.

Comparison of HIV-1 and HIV-2 infectivity from a prospective cohort study in Senegal.

From a prospective cohort study of 1948 initially human immunodeficiency virus (HIV) uninfected female commercial sex workers followed between 1985 and 1999 in Dakar, Senegal, the authors compared the male to female per infectious sexual exposure transmission probability of HIV types one (HIV-1) and two (HIV-2). New non-parametric competing risks failure time methods were used, which minimized modelling assumptions and controlled for risk factors for HIV infection. The HIV-1 versus HIV-2 infectivity ratio over time was estimated by the ratio of smoothed non-parametric kernel estimates of the HIV-1 and HIV-2 infection hazard functions in sex workers, adjusted by an estimate of the relative HIV-1 versus HIV-2 prevalence in the partner population. HIV-1 was found to be significantly more infectious than HIV-2 throughout the follow-up period (P < 0.001). The HIV-1/HIV-2 infectivity ratio was inferred to be approximately constant over time, with estimated common value 3.55. The finding of greater HIV-1 infectivity persisted in sensitivity analyses and in covariate-adjusted analyses, with adjusted infectivity ratio estimates ranging between 3.40 and 3.86. Understanding the mechanisms by which HIV-1 infects more efficiently than HIV-2 may be useful in the development of HIV-1 vaccines. Additionally, the methodology developed here may be useful for analysing other data sets.