I36T↑T mutation in South African subtype C (C-SA) HIV-1 protease significantly alters protease-drug interactions.

The efficacy of HIV-1 protease (PR) inhibition therapies is often compromised by the emergence of mutations in the PR molecule that reduces the binding affinity of inhibitors while maintaining viable catalytic activity and affinity for natural substrates. In the present study, we used a recombinant HIV-1 C-SA PR and a recently reported variant for inhibition (Ki, IC50) and thermodynamic studies against nine clinically used inhibitors. This is the first time that binding free energies for C-SA PR and the mutant are reported. This variant PR harbours a mutation and insertion (I36T↑T) at position 36 of the C-SA HIV-1 PR, and did not show a significant difference in the catalytic effect of the HIV-1 PR. However, the nine clinically approved HIV PR drugs used in this study demonstrated weaker inhibition and lower binding affinities toward the variant when compared to the wild type HIV-1 PR. All the protease inhibitors (PIs), except Amprenavir and Ritonavir exhibited a significant decrease in binding affinity (p<0.0001). Darunavir and Nelfinavir exhibited the weakest binding affinity, 155- and 95-fold decreases respectively, toward the variant. Vitality values for the variant PR, against the seven selected PIs, confirm the impact of the mutation and insertion on the South African HIV-1 subtype C PR. This information has important clinical implications for thousands of patients in Sub-Saharan Africa.

Experimental climate warming enforces seed dormancy in South African Proteaceae but seedling drought resilience exceeds summer drought periods.

Two hypotheses-that elevated night-time temperatures due to climate warming would enforce post-fire dormancy of Proteaceae seed due to low moisture, and that periods without rain during summer would exceed desiccation periods tolerated by Proteaceae seedlings-were tested empirically. Enforced dormancy, i.e., the inability to germinate due to an environmental restraint, was tested by measuring seed germination in 11 Proteaceae species in experimental mesocosms whose soils were artificially elevated by 1.4 and 3.5 °C above ambient by far-red wavelength filtered infrared lamps. Diminished totality of germination and velocities were observed in 91 and 64%, respectively, of the Proteaceae species tested. Drought resilience was tested in one-year-old seedlings of 16 Proteaceae species by withholding water from potted plants during summer in a greenhouse. The most drought-resilient Proteaceae species displayed the lowest initial transpiration rates at field capacity, the smallest declines in transpiration rate with decreasing soil water content, and the lowest water losses by transpiration. Projected drought periods leading to the complete cessation of transpiration in all Proteaceae species greatly exceeded the number of days without rain per month during summer in the current distribution ranges of those species. It was therefore concluded that enforced seed dormancy induced by elevated night-time temperatures is the post-fire recruitment stage of Proteaceae that is most sensitive to climate warming.

A TEST OF SHARKEY AND SINGELIS' (1995) MODEL OF SELF-CONSTRUAL AND EMBARRASSABILITY: SITUATIONAL VERSUS DISPOSITIONAL FACTORS.

Sharkey and Singelis (1995 ) tested a model of embarrassment focusing on strength of independent self-construal, sensitivity to evaluation, and strength of interdependent self-construal. Their findings indicated social anxiety and self-construal explained 28% of the variance in embarrassability. Separately, social anxiety contributed 5.8%, with independent and interdependent self-construal explaining 6.6 and 5.2%, respectively, thus supporting the model. Sharkey and Singelis used Modigiliani's ( 1968 ) Embarrassability Scale, which focuses on embarrassing situations. The current study repeated the analysis but measured embarrassability as a disposition on a sample of Black African (59.8%), Colored (6.1%), Asian/Indian (5.9%), and White (28.2%) first-year psychology students (139 men, 485 women) between 18 and 51 years old (M = 19.5, SD = 2.9). The three constructs together explained about 47% of dispositional embarrassability. Social anxiety explained 25% of the variance, when controlling for independent and interdependent self-construal. Sharkey and Singelis' model may be more applicable to the explanation of situational embarrassability than dispositional embarrassability.

A critical survey of average distances between catalytic carboxyl groups in glycoside hydrolases.

Published X-ray crystallographic structures for glycoside hydrolases (GHs) from 39 different families are surveyed according to some rigorous selection criteria, and the distances separating 208 pairs of catalytic carboxyl groups (20 α-retaining, 87 ß-retaining, 38 α-inverting, and 63 ß-inverting) are analyzed. First, the average of all four inter-carboxyl O…O distances for each pair is determined; second, the mean of all the pair-averages within each GH family is determined; third, means are determined for groups of GH families. No significant differences are found for free structures compared with those complexed with a ligand in the active site of the enzyme, nor for α-GHs as compared with ß-GHs. The mean and standard deviation (1σ) of the unimodal distribution of average O…O distances for all families of inverting GHs is 8 ± 2Å, with a very wide range from 5Å (GH82) to nearly 13Å (GH46). The distribution of average O…O distances for all families of retaining GHs appears to be bimodal: the means and standard deviations of the two groups are 4.8 ± 0.3Å and 6.4 ± 0.6Å. These average values are more representative, and more likely to be meaningful, than the often-quoted literature values, which are based on a very small sample of structures. The newly-updated average values proposed here may alter perceptions about what separations between catalytic residues are "normal" or "abnormal" for GHs.

A neuropsychological rehabilitation service delivery model for South African adults with acquired brain injury (RSDM-SA).

In low- and- middle- income countries (LMICs) such as South Africa, a high number of Acquired Brain Injuries (ABIs) and a lack of accessibility to healthcare lead to many survivors of brain injury not receiving the level of healthcare and rehabilitation required. Further, in LMICs life-saving or acute care is prioritized with an inadequate focus on the lifelong effects of ABI. This study used Program Theory to develop a Rehabilitation Service Delivery Model for South African Adults with Acquired Brain Injury (RSDM-SA) that caters for the unique nuances of a resource-constrained and culturally diverse context. The RSDM-SA has four interdependent levels, namely (i) Integration of Relevant Aspects of Explanatory Frameworks (ii) South African Contextual Influences on the Model (iii) Systemic Role players Necessary for the Model and (iv) Evidence-Based Guidelines in a Holistic Rehabilitation Process. The Model is a valuable resource in guiding future research endeavors and its contribution lies in the Model's focus on quality, accessibility, relevance, and efficiency, all of which are needed in healthcare internationally.

Butane-1,4-diammonium bis(perchlorate).

The butane-1,4-diammonium cation of the title compound, C(4)H(14)N(2) (2+)·2ClO(4) (-), lies on a special position of site symmetry 2/m, whereas the perchlorate anion is located on a crystallographic mirror plane. An intricate three-dimensional hydrogen-bonding network exists in the crystal structure with each H atom of the ammonium group exhibiting bifurcated inter-actions to the perchlorate anion. Complex hydrogen-bonded ring and chain motifs are also evident, in particular a 50-membered ring with graph-set notation R(10) (10)(50) is identified.

Executive functioning and positive psychological characteristics: a replication and extension.

Positive psychological characteristics and executive function are correlated with gratitude, satisfaction with life, and forgiveness. The goal of this study was to replicate these findings while examining two additional constructs, namely, hope and optimism. 113 students (25 men, 88 women) between the ages of 17 to 24 years (M = 19.4, SD = 1.5) volunteered to participate. Positive correlations between executive function and gratitude were found but mixed results were obtained for forgiveness and satisfaction with life. Hope and optimism correlated positively with executive function and hierarchical multiple regression analysis indicated that they contributed significantly to the explanation of executive functioning. Further investigation into relationships between executive functioning, its neurobiological substrates, and positive psychological attributes is recommended.

Ethane-1,2-diammonium dibromide: a redetermination at 100†K.

In the redetermined [for the previous study, see Søtofte (1976 ▶). Acta Chem. Scand. Ser. A, 30, 309-311] crystal structure of the title compound, C(2)H(10)N(2) (2+)·2Br(-), the H atoms have been located and the hydrogen-bonding scheme is described. The ethane-1,2-diammonium cation lies over a crystallographic inversion centre and straddles a crystallographic mirror plane with the C and N atoms in special positions. In the crystal, the cations and anions are linked by N-H⋯Br and N-H⋯(Br,Br) hydrogen bonds, which generate various ring and chain motifs including an R(10) (5)(32) loop.

Hexane-1,6-diammonium dinitrate.

The hexane-1,6-diammonium cation of the title compound, C(6)H(18)N(2) (2+)·2NO(3) (-), lies across a crystallographic inversion centre and shows significant deviation from planarity in the hydro-carbon chain. This is evident from the torsion angle of -64.0°(2) along the N-C-C-C bond and thse torsion angle of -67.1°(2) along the C-C-C-C bonds. An intricate three-dimensional hydrogen-bonding network exists in the crystal structure, with each H atom on the ammonium group exhibiting bifurcated inter-actions to the nitrate anion. Complex hydrogen-bonded ring and chain motifs are also evident, in particular a 26-membered ring with graph-set notation R(4) (4)(26) is observed.

Penta-carbonyl-2κC-chlorido-1κCl-bis-[1(η)-cyclo-penta-dien-yl](µ-1-oxido-ethyl-ene-1:2κO:C)chromium(0)zirconium(IV).

The title compound, [CrZr(C(5)H(5))(2)(C(2)H(3)O)Cl(CO)(5)], consists of two metal centres, with a (penta-carbonyl-chromium)oxymethyl-carbene group coordinating as a monodentate ligand to the zirconocene chloride. π-Delocalization through the Zr-O-C=Cr unit is indicated by a short Zr-O distance [2.041 (3) Å] and a nearly linear Zr-O-C angle [170.5 (3)°]. Mol-ecules are aligned with their mol-ecular planes (through Zr, Cl, carbene and Cr) parallel to the ab plane. C-H⋯Cl inter-actions result in zigzag chains of mol-ecules propagating parallel to the b axis.

Hydrogen-bonding motifs and thermotropic polymorphism in redetermined halide salts of hexamethylenediamine.

The redetermined crystal structures of hexane-1,6-diammonium dichloride, C(6)H(18)N(2)(2+) x 2 Cl(-), (I), hexane-1,6-diammonium dibromide, C(6)H(18)N(2)(2+) x 2 Br(-), (II), and hexane-1,6-diammonium diiodide, C(6)H(18)N(2)(2+) x 2 I(-), (III), are described, focusing on their hydrogen-bonding motifs. The chloride and bromide salts are isomorphous, with both demonstrating a small deviation from planarity [173.89 (10) and 173.0 (2) degrees, respectively] in the central C-C-C-C torsion angle of the hydrocarbon backbone. The chloride and bromide salts also show marked similarities in their hydrogen-bonding interactions, with subtle differences evident in the hydrogen-bond lengths reported. Bifurcated interactions are exhibited between the N-donor atoms and the halide acceptors in the chloride and bromide salts. The iodide salt is very different in molecular structure, packing and intermolecular interactions. The hydrocarbon chain of the iodide straddles an inversion centre and the ammonium groups on the diammonium cation of the iodide salt are offset from the planar hydrocarbon backbone by a torsion angle of 69.6 (4) degrees. All three salts exhibit thermotropic polymorphism, as is evident from differential scanning calorimetry analysis and variable-temperature powder X-ray diffraction studies.

Penta-carbonyl-2κC-chlorido-1κCl-bis-[1(η)-cyclo-penta-dien-yl][µ(2)-oxido(meth-yl)methyl-ene-1:2κO:C]tungsten(0)zirconium(IV).

The title compound, [ZrW(C(5)H(5))(2)(C(2)H(3)O)Cl(CO)(5)] or [W(CO)(5)C(CH(3))OZr(C(5)H(5))(2)Cl], consists of two metal centres, with a (tungsten penta-carbon-yl)oxymethyl-carbene group coordinating as a monodentate ligand to the chloridozirconocene. The two halves of the mol-ecule are related by a crystallographic mirror plane. Delocalization through the Zr-O-C=W unit is indicated by a short Zr-O distance and a nearly linear Zr-O-C angle.

The role of low soil temperature in the inhibition of growth and PSII function during dark chilling in soybean genotypes of contrasting tolerance.

Dark chilling affects growth and yield of warm-climate crops such as soybean [Glycine max (L.) Merr.]. Several studies have investigated chilling-stress effects on photosynthesis and other aspects of metabolism, but none have compared effects of whole-plant chilling (WPC; shoots and roots) with that of aboveground chilling in legumes. This is important because low root temperatures might induce additional constraints, such as inhibition of N(2) fixation, thereby aggravating chilling-stress symptoms. Effects of dark chilling on PSII, shoot growth, leaf ureide content and photosynthetic capacity were studied in two soybean genotypes, Highveld Top (chilling tolerant) and PAN809 (chilling sensitive), in experiments comparing effects of WPC with that of shoot chilling (SC). Both treatments inhibited shoot growth in PAN809 but not Highveld Top. Also, WPC in PAN809 caused a decrease in leaf ureide content followed by severe chlorosis and alterations in O-J-I-P fluorescence-rise kinetics, distinct from SC. A noteworthy difference was the appearance of a Delta K peak in the O-J-I-P fluorescence rise in response to WPC. These genotypic and treatment differences also reflected in the degree of inhibition of CO(2) assimilation rates. The appearance of a Delta K peak, coupled with growth inhibition, reduced ureide content, chlorosis and lower CO(2) assimilation rates, provides mechanistic information about how WPC might have aggravated chilling-stress symptoms in PAN809. We introduce a model explaining how chilling soil temperatures might trigger N-limitation in sensitive genotypes and how characteristic changes in O-J-I-P fluorescence-rise kinetics are linked to changes in carbon and nitrogen metabolism.

Dichlorido(3,5-dimethyl-1H-pyrazole)[(3,5-dimethyl-1H-pyrazol-1-yl)(o-tol-yl)methanone]palladium(II).

In the title compound, [PdCl(2)(C(5)H(8)N(2))(C(12)H(12)N(2)O)], the Pd atom adopts a slightly distorted trans-PdCl(2)N(2) square-planar arrangement. The different Pd-N bond lengths can be related to the the electron-withdrawing effect of the o-toluoyl group on the substituted pyrazole ligand. The complex crystallizes as centrosymmetric hydrogen-bonded dimers through N-H⋯Cl linkages.

Small molecule distribution in rat lung: a comparison of various cryoprotectants as inflation media and their applicability to MSI.

Given the recent explosion of mass spectrometric imaging (MSI), it has become easier to assess drug tissue localisation without the use of radiolabeling and other more complex methods (such as PET and MRI). For MSI tissue preparation is of utmost importance, however, the lung in particular does pose some difficulties with imaging since it is made up of a number of air-filled alveoli. These organs are known to collapse when the thoracic cavity is pierced, losing its structural integrity and giving poor histological representation for drug distribution analysis. The use of cryoprotectants as a tissue inflation media will aid in the preservation of the lung's structural integrity during MSI experiments involving small molecule distribution. Various established cryoprotectants (DMSO, PvP, ethylene glycol, sucrose, DMEM, control serum, OCT) were selected as lung inflation media for MSI analysis of gatifloxacin (GAT). Female Sprague-Dawley rats were treated with GAT (10 mg/kg b.w) via i.p. injection. After 15 min the animals were terminated by halothane overdose, and each set of tissue inflated with a specific agent. Cryosections were made and MSI conducted to determine drug tissue distribution. During the early stages of the experimental procedure some crypreservatives were eliminated due to difficulties with sample preparation. While others displayed excellent preservation of the tissue structure and integrity. Following MSI analysis, some agents showed homogenous drug distribution while some displayed heterogeneous distribution favoring the basal periphery. Taking into account the physiology of the lung and previous MRI investigations of its perfusion, it is expected that a systemically administered drug would localize in the basal areas. DMSO and DMEM proved to display this distribution pattern while keeping structural integrity intact. However, the later was ruled out since it showed complete suppression of GAT in solution. From the cryoprotectants selected for this study, DMSO is the most promising lung inflation media focusing on small molecule distribution via MSI.

Neuroprotective potential of Linezolid: a quantitative and distribution study via mass spectrometry.

A study was undertaken to determine the neuroprotective potential of Linezolid (LIN) in an animal model. Female Sprague-Dawley rats were either given a single (100 mg/kg) dose or treated daily for 4 weeks. A validated LC-MS/MS method was used to measure LIN levels in plasma and brain, this was paired with mass spectrometry imaging to determine the tissue spatial distribution of the drug. The results showed that after a single dose there was poor penetration of the drug into the brain. With multiple doses there were high tissue levels, with the drug reaching steady state in subsequent weeks. LIN displayed a promising distribution pattern with localisation in the brainstem. Systemic circulation is fed into the brain by the carotid and vertebral arteries which enter through the brain stem, therefore high drug concentrations is this area may protect against infectious agents entering via this route.

Reduction of dark chilling stress in N-fixing soybean by nitrate as indicated by chlorophyll a fluorescence kinetics.

Sub-optimal night temperatures below 15 degrees C (dark chilling) frequently reduce soybean [Glycine max (L.) Merrill] production. Nitrate application is known to alleviate some of the negative effects of low root zone temperatures, probably by counteracting the inhibition caused by decreased symbiotic nitrogen fixation (SNF). Under field conditions, however, dark chilling is frequently not accompanied by low root zone temperatures. The possibility that nitrate might increase dark-chilling tolerance under these conditions is still largely unexplored. In addition to quantifying vegetative development by means of the plastochron index, O-J-I-P (O-I(1)-I(2)-P) chlorophyll a fluorescence transients were recorded in soybean genotypes of contrasting chilling tolerance during and following exposure to dark chilling in the absence of low root zone temperatures. Plants, inoculated with the N(2)-fixing bacteria, Bradyrhizobium japonicum, were grown with and without nitrate supplementation. The recorded O-J-I-P chlorophyll a fluorescence transients were analysed by the so-called JIP-test which translates stress-induced alterations in these transients to changes in biophysical parameters that quantifies the energy flow through photosystem II (PSII). One of these parameters, the performance index (PI(ABS)), combines the three main functional steps (light energy absorption, excitation energy trapping, and conversion of excitation energy to electron transport) of photosynthetic activity by a PSII reaction centre complex into a single multiparametric expression. By using the PI(ABS) we could convincingly show that nitrate supplementation considerably enhances dark-chilling tolerance and recovery capacity of plants in the absence of low root zone temperatures. This was especially true for the chilling-sensitive genotype ('Java 29'), suggesting that the response of SNF to dark chilling might be an important factor contributing towards genotypic differences in chilling tolerance. Our results corroborated previous reports about the superior chilling tolerance of 'Maple Arrow', a chilling-tolerant genotype. The results obtained indicated that the PI(ABS) is a far more sensitive indicator of dark-chilling stress than the maximum quantum yield of primary photochemistry (F(V)/F(M)).

Dark chilling effects on soybean genotypes during vegetative development: parallel studies of CO2 assimilation, chlorophyll a fluorescence kinetics O-J-I-P and nitrogen fixation.

The effects of dark chilling on CO2 assimilation, chlorophyll a fluorescence kinetics and nitrogen fixation were compared in two Glycine max (L.) Merr. genotypes. The aim was to elucidate the mechanisms by which photosynthesis was inhibited as well as identification of selection criteria for dark chilling tolerance. Seedlings were dark chilled (8 degrees C) for 9 consecutive nights but kept at normal day temperatures (28 degrees C). CO2 gas exchange analysis indicated that photosynthesis in Maple Arrow was inhibited largely as a result of stomatal limitation, while in Fiskeby V, it indicated inhibition of the mesophyll reactions. Increased intercellular CO2 concentration and decreased carboxylation efficiency suggested loss of Rubisco activity in Fiskeby V, although no effect on the KM (CO2) of Rubisco was observed. Quantification and deconvolution of the Chl a fluorescence transients into several phenomenological and biophysical parameters (JIP-test) revealed large genotypic differences in the response of PSII to dark chilling. These parameters differentially changed in the two genotypes during the progression of the chilling treatment. Among them, the performance index, reflecting several responses of the photochemical apparatus, provided the best preliminary overall assessment of the genotypes. In contrast, the quantum yield of primary photochemistry varphiPo (FV/FM) was quite insensitive. The recovery of most of the JIP-test parameters in Maple Arrow after 6 and 9 nights of dark chilling was a major genotypic difference. Genotypic differences were also observed with regard to the ureide response and N2 fixation appeared to be more sensitive to dark chilling than CO2 assimilation. The JIP-test provided information consistent with results derived from CO2 assimilation and N2 fixation studies suggesting that it can substitute the much more time-consuming methods for the detection of chilling stress and can well satisfy the requirements of a rapid and accurate screening method.