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The authors respond to the comments on their article about the use of the term social license in conservation. Topics include the authors' argument about the usefulness of social license as a distinct concept, their thoughts on the proposed definition of the term by the discussers, and the authors' view on the introduction of a new relationship between social and legal licenses. Also mentioned is the criticism of the use of social license in mining and forestry.

Abstract  Vicinity analysis (VA) is a new methodology developed to identify similarities between protein binding sites based on their three-dimensional structure and the chemical similarity of matching residues. The major objective is to enable searching of the Protein Data Bank (PDB) for similar sub-pockets, especially in proteins from different structural and biochemical series. Inspection of the ligands bound in these pockets should allow ligand functionality to be identified, thus suggesting novel monomers for use in library synthesis. VA has been developed initially using the ATP binding site in kinases, an important class of protein targets involved in cell signalling and growth regulation. This paper defines the VA procedure and describes matches to the phosphate binding sub-pocket of cyclin-dependent protein kinase 2 that were found by searching a small test database that has also been used to parameterise the methodology. [ABSTRACT FROM AUTHOR]

The secondary metabolite amygdalin is a cyanogenic diglucoside that at high concentrations is associated with intense bitterness in seeds of the Rosaceae, including kernels of almond (Prunus dulcis (Mill.), syn. Prunus amygdalus D. A. Webb Batsch). Amygdalin is a glucoside of prunasin, itself a glucoside of R-mandelonitrile (a cyanohydrin). Here we report the isolation of an almond enzyme (UGT85A19) that stereo-selectively glucosylates R-mandelonitrile to produce prunasin. In a survey of developing kernels from seven bitter and 11 non-bitter genotypes with polyclonal antibody raised to UGT85A19, the enzyme was found to accumulate to higher levels in the bitter types in later development. This differential accumulation of UGT85A19 is associated with more than three-fold greater mandelonitrile glucosyltransferase activity in bitter kernels compared with non-bitter types, and transcriptional regulation was demonstrated using quantitative-PCR analysis. UGT85A19 and its encoding transcript were most concentrated in the testa (seed coat) of the kernel compared with the embryo, and prunasin and amygdalin were differentially compartmentalised in these tissues. Prunasin was confined to the testa and amygdalin was confined to the embryo. These results are consistent with the seed coat being an important site of synthesis of prunasin as a precursor of amygdalin accumulation in the kernel. The presence of UGT85A19 in the kernel and other tissues of both bitter and non-bitter types indicates that its expression is unlikely to be a control point for amygdalin accumulation and suggests additional roles for the enzyme in almond metabolism. [ABSTRACT FROM AUTHOR]

BACKGROUND:: Allopregnanolone (ALLO) and structurally related endogenous neurosteroids are potent modulators of γ-aminobutyric acid A (GABAA) receptor function at physiologically relevant concentrations. Accumulating evidence implicates a modulatory role for ALLO in behavioral processes underlying ethanol self-administration, discrimination, and reinstatement. The purpose of this study was to evaluate the impact of exogenous neurosteroid challenges with the agonist ALLO and the partial agonist/antagonist epipregnanolone (EPI) on the microarchitecture of ethanol drinking patterns.METHODS:: Male C57BL/6J mice were initiated to consume an unsweetened 10% v/v ethanol solution (10E) by a saccharin fading procedure during daily 2-hr limited-access sessions beginning 1-hr after dark-phase onset. Cumulative lick responses were recorded for 10E and water by lickometer circuits. After establishing 10E intake baselines, mice were habituated to vehicle injection (VEH; 20% w/v β-cyclodextrin ip), and then were treated with either VEH or neurosteroid immediately before the drinking session. Each mouse received a series of ALLO doses (3.2, 10, 17, and 24 mg/kg) alone and EPI doses (0.15, 1, 3, and 10 mg/kg) alone in a counterbalanced within-group design.RESULTS:: The GABAA receptor-positive modulator ALLO dose-dependently modulated overall ethanol intake throughout the 2-hr session with the 3.2 mg/kg dose eliciting a significant increase, whereas the 24 mg/kg dose produced a significant suppression of ethanol intake versus VEH pretreatment. ALLO-evoked alterations in intake corresponded to significant, dose-dependent alterations in bout frequency and interbout interval. ALLO also elicited robust, dose-dependent elevations in 10E licks during the initial 5 min of access but subsequently produced in a dose-dependent suppression of 10E licks during session minutes 20–80. In contrast, the partial agonist/antagonist neurosteroid EPI exhibited no influence on any consumption parameter evaluated.CONCLUSIONS:: The present findings suggest that GABAA receptor-active neurosteroids may modulate the regulatory processes that govern the onset, maintenance, and termination of drinking episodes. The differential influence of ALLO and EPI on ethanol intake patterns may reflect an alteration in GABA-ergic inhibitory tone that is likely due to each neurosteroidʼs pharmacological profile at GABAA receptors. Manipulation of endogenous ALLO may prove a useful strategy for diminishing excessive intake and protecting against the loss of regulatory control over drinking. [ABSTRACT FROM AUTHOR]

Purpose: To determine the relative contributions of patient, disease and therapy specific factors on neurocognitive outcome of brain tumor patients.Patients and methods: Seventy-nine patients (mean age = 41.1 years; range: 17–75 years; 54% male, 46% female) with glioblastoma multiforme (37%), anaplastic astrocytoma (17%), low grade astrocytoma (13%), and oligodendroglioma (10%) predominantly in the frontal regions (45%) were evaluated in an outpatient neuro-oncology clinic. A neuropsychological test battery emphasized elements of attention/concentration. Multiple regression analyses determined relationships between functional outcomes and demographic and clinical predictors.Results: Key predictors of neurocognitive functioning included age of the patient (36–59 years, p < 0.01; ≥60 years, p < 0.05) and frontal region tumor location (p < 0.01). As expected, older patients did not perform as well as younger patients in absolute terms on neuropsychological tests; decrements persisted when comparisons were based on age-standardized versions of neurocognitive outcomes. Major depressive disorder was marginally associated with outcomes, while surgical interventions and radiotherapy did not show strong associations with test performances.Conclusions: Primary malignant brain disease was found to be less negative on neurocognitive outcomes for younger than for either middle-aged or older patients. Treatments were not as predictive of neurocognitive outcomes as age. No single test outcome measure was as sensitive to neurocognitive status as the empirically derived index of attention and concentration. [ABSTRACT FROM AUTHOR]

SUMMARY: BACKGROUND Estradiol (E2) potentiates the self-administration of numerous psychoactive drugs in female rodents. An analogous modulatory role of E2 on ethanol consumption remains unresolved because of examination of limited doses. The purpose of this study was to delineate a dose-response relationship for E2 on ethanol intake with an extended range and number of E2 doses.METHODS Female Long-Evans rats had continuous access (22 hr/day) to both 10% ethanol (10E) solution and water. After the establishment of stable 10E intake baselines, rats were assigned to one of seven dose groups balanced for 10E intake [sham-operated (Shm) or ovariectomized (Ovx) plus E2 (μg/kg)]: Shm + 0, Ovx + 0, Ovx + 0.05, Ovx + 0.15, Ovx + 0.5, Ovx + 1.5, and Ovx + 5. Ethanol preference drinking was evaluated during 25 consecutive days of E2 replacement treatment, and trunk blood was collected for the determination of plasma E2 and progesterone concentrations.RESULTS Chronic E2 replacement regimens (0.05-1.5 μg/kg) dose-dependently augmented 10E intakes and ethanol preference ratios without concomitantly altering water consumption. Despite the maintenance of 2- to 3-fold greater plasma E2 levels, a supraphysiologic E2 dose (5 μg/kg) failed to precipitate ethanol intakes in excess of levels observed after treatment with a high physiologic E2 dose (1.5 μg/kg). Plasma progesterone concentrations were significantly increased in treatment groups (1.5 and 5 μg/kg E2) that exhibited corresponding significant increases in ethanol consumption.CONCLUSIONS A positive dose-response relationship between E2 and ethanol intake (incremental increases in E2 dose corresponded to incremental increases in intake) was apparently limited to a physiologic concentration range, because a supraphysiologic dose failed to elicit an additional stepwise increase in ethanol intake. These findings stipulate a modulatory role for E2 in the regulation of moderate ethanol intake and suggest that endogenous fluctuations of E2 may alter the propensity toward consumption in women and in female animal models of ethanol self-administration. [ABSTRACT FROM AUTHOR]

Alt?s three-dimensional cell balance equation characterizing the chemotactic bacteria was analyzed under the presence of one-dimensional spatial chemoattractant gradients. Our work differs from that of others who have developed rather general models for chemotaxis in the use of a non-smooth anisotropic tumbling frequency function that responds biphasically to the combined temporal and spatial chemoattractant gradients. General three-dimensional expressions for the bacterial transport parameters were derived for chemotactic bacteria, followed by a perturbation analysis under the planar geometry. The bacterial random motility and chemotaxis were summarized by a motility tensor and a chemotactic velocity vector, respectively. The consequence of invoking the diffusion-approximation assumption and using intrinsic one-dimensional models with modified cellular swimming speeds was investigated by numerical simulations. Characterizing the bacterial random orientation after tumbles by a turn angle probability distribution function, we found that only the first-order angular moment of this turn angle probability distribution is important in influencing the bacterial long-term transport. [ABSTRACT FROM AUTHOR]

Objective: We have conducted a series of experiments to show that the bacteriocin piscicolin 126 (P126) retains antilisterial activity after injection into a mouse. Methods: Groups of mice were challenged intravenously with Listeria monocytogenes and treated with purified P126 at varying times before and after challenge to determine whether administration of this peptide reduced numbers of colonizing L. monocytogenes and the symptoms of listeriosis. Results: The bacteriocin P126 retained antilisterial activity after injection into the mouse. During the early time-points of listerial infection, the purified P126 was found to significantly reduce the listerial load in the liver and spleen and, further, that this reduction translated to reduced clinical signs of disease. Conclusions: This is the first report of a Class IIA bacteriocin displaying in vivo antimicrobial activity. Such a result provides preliminary evidence that this class of molecules may be useful in controlling systemic bacterial infections. [ABSTRACT FROM AUTHOR]

This paper, the second part of a series, extends the capabilities of the LADERA FORTRAN code for massively parallel dual control volume grand canonical molecular dynamics (DCVGCMD). DCV-GCMD is a hybrid of two more common molecular simulation techniques (grand canonical Monte Carlo and molecular dynamics) which allows the direct molecularlevel modelling of diffusion under a chemical potential gradient. The present version of the code, LADERA-B has the capability of modelling systems with explicit intramolecular interactions such as bonds, angles, and dihedral rotations. The utility of the new code for studying gradient-driven diffusion of small molecules through polymers is demonstrated by applying it to two model systems. LADERA-B includes another new feature, which is the use of neighbour lists in force calculations. This feature increases the speed of the code but presents several challenges in the parallel hybrid algorithm. There is discussion on how these problems were addressed and how our implementation results in a significant increase in speed over the original LADERA. Scaling results are presented for LADERA-B on two massively parallel message-passing machines. [ABSTRACT FROM AUTHOR]

Organizational learning is depicted most frequently as an intra-organizational information processing activity, but the role that experience plays in the development of organizational knowledge has recently become a more central focus of learning t heories. The two primary perspectives on organizational learning present strikingly different depictions of the relationship between action and learning: systems-structural models based on positivist epistemological assumptions emphasize internally-direc ted information collection and distribution activities aimed at reducing uncertainty; interpretive models utilize an interpretivist epistemology that emphasizes the necessity of taking action in ambiguous circumstances as a means of creating knowledge. P roposes that neither of these alternative views of organizational learning describe how learning outcomes vary as a consequence of different types of action and that, specifically, previous models of organizational learning have not emphasized the critic al role that creative actions play in the development of organizational knowledge. Delineates assumptions which serve to legitimize creative action taking within organizational contexts, and describes the learning outcomes which result from creative and routine actions. Extends previous models of organizational learning which emphasize cognition and communication processes by distinguishing the varied influences that different actions have on the production of knowledge. [ABSTRACT FROM AUTHOR]

The article explores whether the relatively costly geriatric day hospitals and their skilled staffs play a very different role from community day care centers for old people in Great Britain. The study involved the St. Clement's Hospital, a psychiatric day hospital for patients over the age of 65 with reversible psychiatric illness, opened with the support from the King Edward Fund. It was found that almost 88 percent of patients referred to the day hospital needed skilled care and 62 percent of discharged patients had received specialized psychiatric treatment.

Background and Aims l-Ascorbate (vitamin C) has well-documented roles in many aspects of redox control and anti-oxidant activity in plant cells. This Botanical Briefing highlights recent developments in another aspect of l-ascorbate metabolism: its function as a precursor for specific processes in the biosynthesis of organic acids. Scope The Briefing provides a summary of recent advances in our understanding of l-ascorbate metabolism, covering biosynthesis, translocation and functional aspects. The role of l-ascorbate as a biosynthetic precursor in the formation of oxalic acid, l-threonic acid and l-tartaric acid is described, and progress in elaborating the mechanisms of the formation of these acids is reviewed. The potential conflict between the two roles of l-ascorbate in plant cells, functional and biosynthetic, is highlighted. Conclusions Recent advances in the understanding of l-ascorbate catabolism and the formation of oxalic and l-tartaric acids provide compelling evidence for a major role of l-ascorbate in plant metabolism. Combined experimental approaches, using classic biochemical and emerging ‘omics’ technologies, have provided recent insight to previously under-investigated areas. [ABSTRACT FROM AUTHOR]

This contribution summarizes investigations of organic–inorganic hybrid materials wherein the inorganic phase is ordered mesoporous silica such as MCM-41 and SBA-15. The review, which covers work performed in the last three years, emphasizes studies of: (1) covalently attached functional groups, (2) new approaches to functionalization, (3) approaches for achieving high densities of uniform functional groups, (4) periodic mesoporous organosilicas (PMOs) with hierarchical ordering, (5) new functional chemistries, and (6) the application of new materials to enantioselective catalysis and emerging areas. The review concludes with the authors outlining some outstanding problems in the field. [ABSTRACT FROM AUTHOR]