Heterogeneous responses of temperate-zone amphibian populations to climate change complicates conservation planning.

The pervasive and unabated nature of global amphibian declines suggests common demographic responses to a given driver, and quantification of major drivers and responses could inform broad-scale conservation actions. We explored the influence of climate on demographic parameters (i.e., changes in the probabilities of survival and recruitment) using 31 datasets from temperate zone amphibian populations (North America and Europe) with more than a decade of observations each. There was evidence for an influence of climate on population demographic rates, but the direction and magnitude of responses to climate drivers was highly variable among taxa and among populations within taxa. These results reveal that climate drivers interact with variation in life-history traits and population-specific attributes resulting in a diversity of responses. This heterogeneity complicates the identification of conservation 'rules of thumb' for these taxa, and supports the notion of local focus as the most effective approach to overcome global-scale conservation challenges.

Existence of tenascin-C isoforms in rat that contain the alternatively spliced AD1 domain are developmentally regulated during hippocampal development.

Tenascin-C (TN-C) is a multimodular glycoprotein of the extracellular matrix which is important for the development of the nervous system and has a range of different functions which are mediated by the different protein domains present. TN-C contains eight constitutive fibronectin type III (FNIII) domains and a region of alternatively spliced FNIII domains. In the mouse and chick, six of these domains have been described and characterized, whereas in human there are nine of them. In this report, we show that seven alternatively spliced FNIII domains exist in rat and describe the differential expression pattern of the additional domain AD1 during embryonic and postnatal rat brain development. The AD1 domain of rat is homologous to the ones described in human and chick proteins but does not exist in mouse. Its expression can be located to the developing rat hippocampus and the lining of the lateral ventricle, regions where the TN-C protein may affect the behavior of stem and progenitor cells. During hippocampal development AD1 and the other alternatively spliced domains are differentially expressed as shown by RT-PCRs, immunocytochemistry and in situ hybridizations.

Differential upregulation of extracellular matrix molecules associated with the appearance of granule cell dispersion and mossy fiber sprouting during epileptogenesis in a murine model of temporal lobe epilepsy.

We have investigated changes in the extracellular matrix of the hippocampus associated with the early progression of epileptogenesis in a murine model of temporal lobe epilepsy using immunohistochemistry. In the first week following intrahippocampal injection of the glutamate agonist, domoate, there is a latent period at the end of which begins a sequential upregulation of extracellular matrix (ECM) molecules in the granule cell layer of the dentate gyrus, beginning with neurocan and tenascin-C. This expression precedes the characteristic dispersion of the granule cell layer which is evident at 14 days post-injection when the first recurrent seizures can be recorded. At this stage, an upregulation of the chondroitin sulfate proteoglycan, phosphacan, the DSD-1 chondroitin sulfate motif, and the HNK-1 oligosaccharide are also observed. The expression of these molecules is localized differentially in the epileptogenic dentate gyrus, especially in the sprouting molecular layer, where a strong upregulation of phosphacan, tenascin-C, and HNK-1 is observed but there is no expression of the proteoglycan, neurocan, nor of the DSD-1 chondroitin sulfate motif. Hence, it appears that granule cell layer dispersion is accompanied by a general increase in the ECM, while mossy fiber sprouting in the molecular layer is associated with a more restricted repertoire. In contrast to these changes, the expression of the ECM glycoproteins, laminin and fibronectin, both of which are frequently implicated in tissue remodelling events, showed no changes associated with either granule cell dispersion or mossy fiber sprouting, indicating that the epileptogenic plasticity of the hippocampus is accompanied by ECM interactions that are characteristic of the CNS.

Should we give detailed advice and information booklets to patients with back pain? A randomized controlled factorial trial of a self-management booklet and doctor advice to take exercise for back pain.

STUDY DESIGN: Randomized controlled factorial trial. OBJECTIVE: To assess the effectiveness of a booklet and of physician advice to take regular exercise. SUMMARY OF BACKGROUND DATA: Educational booklets are one of the simplest interventions for back pain but have not been shown to alter pain and function. Although there is evidence that advice to mobilize is effective, doctors have also been advised to encourage regular exercise-but there is no evidence that such advice alone improves outcomes. METHOD: Eight doctors from six practices randomized 311 patients with a new episode of back pain using sealed numbered opaque envelopes to receive a detailed self-management booklet, advice to take regular exercise, both, or neither. All groups were advised to mobilize and to use simple analgesia. Patients were telephoned during the first week after entry into the study, and after 3 weeks to assess a validated numerical pain/function score (0 = no pain normal activities to 100 = extreme pain no normal activities). Patients also returned a postal questionnaire in the first week with the Aberdeen pain and function scale, a knowledge score, and a reliable satisfaction scale (mean score of 4 items: 0 = not satisfied to 100 = extremely satisfied). RESULTS: Pain/function scores were obtained in 239 (77%) patients. There were interactions between exercise and booklet groups for both pain/function scores and the Aberdeen scale, which are unlikely to have been chance findings (P = 0.009 and P = 0.012, respectively). In comparison with the control group, there were reductions in the pain/function score in the first week with a booklet (-8.7, 95% CI -17.4 to -0.03) or advice to exercise (-7.9; -16.7 to 0.8) but much less effect with both together (-0.08, -9.0 to 8.9). Similarly, the Aberdeen scale was lower in the booklet group (-3.8, -7.7 to 0.07) and in the exercise advice group (-5.3; -9.3 to -1.38) but much less with both combined (-1.9, -5.8 to 2.1). There was no significant difference between groups in pain/function scores by week 3, when 58% reported being back to normal. Satisfaction was increased in booklet (7.9, 1.3 to 14.4) and exercise groups (7.4, 0.8 to 13.9)), and a booklet also increased knowledge (Kruskal-Wallis chi2 27.2, P = 0.001). CONCLUSION: Doctors can increase satisfaction and moderately improve functional outcomes in the period immediately after the consultation when back pain is worst, by using very simple interventions: either by endorsing a self-management booklet or by giving advice to take exercise. Previous studies suggest that simple advice and the same written information provide reinforcement. This study supports evidence that it may not be helpful to provide a detailed information booklet and advice together, where the amounts or formats of information differ.

Glial tumor cell adhesion is mediated by binding of the FNIII domain of receptor protein tyrosine phosphatase beta (RPTPbeta) to tenascin C.

The extracellular domain of receptor protein tyrosine phosphatase beta (RPTPbeta) is composed of several domains which mediate its interactions with distinct ligands present on the surface of either neurons or glial cells. Here, we demonstrate that the fibronectin type III domain (FNIII) of RPTPbeta binds to glial tumor-derived cell lines and primary astrocytes. We used affinity purification to isolate several proteins that specifically bind to the FNIII domain of RPTPbeta. One of these, a 240 kDa protein that was purified from U118MG glioblastoma cell, was identified as tenascin C based on the amino acid sequence of several tryptic peptides. The interaction of RPTPbeta with tenascin C was found to mediate cell adhesion. Adhesion and spreading of SF763T astrocytoma cells expressing RPTPbeta on tenascin C was specifically abolished by the addition of a soluble fragment containing the FNIII domain of the receptor. RPTPbeta-dependent cell adhesion was mediated by binding to the alternatively spliced FNIII repeats A1,2,4 (TnfnA1,2,4) of tenascin C. Furthermore, COS cells expressing RPTPbeta adhere to TnfnA1,2,4, while the parental cells did not. These results demonstrate that the FNIII domain of RPTPbeta binds to tenascin C and suggest that RPTPbeta present on glial tumor cells is a primary adhesion receptor system to the extracellular matrix.

Tenascin glycoproteins and the complementary ligand DSD-1-PG/ phosphacan--structuring the neural extracellular matrix during development and repair.

The differentiation and morphogenesis of neural tissues involves a diversity of interactions between neural cells and their environment. Many potentially important interactions occur with the extracellular matrix (ECM), a complex association of extracellular molecules organised into aggregates and polymers. The large modular glycoprotein, Tenascin-C, and the chondroitin sulphate proteoglycan, DSD-1-PG/Phosphacan, have complex and frequently overlapping expression patterns in the developing CNS. Their presence in zones of cell proliferation, migration, and differentiation, as well as in boundary structures, suggest that they may be involved in the modulation of an extensive range of cellular processes. They are both strongly up-regulated in a range of CNS lesions and pathologies, being components of the glial scar, and expressed by gliomas. Functional roles in many cellular processes are possible through their extensive molecular interaction sites, both with each other, and with many of the same cell surface receptors, adhesion molecules, growth factors and other matrix proteins. These multiple interactions involve sites on both their protein domains and on the heterogeneous carbohydrate groups with which they are post-translationally modified. In vitro assays demonstrate cell-type specific effects on adhesion, migration and the formation and extension of cellular processes, including neurites and axons.

DSD-1-proteoglycan is the mouse homolog of phosphacan and displays opposing effects on neurite outgrowth dependent on neuronal lineage.

DSD-1-PG is a chondroitin sulfate proteoglycan (CSPG) expressed by glial cells that can promote neurite outgrowth from rat embryonic mesencephalic (E14) and hippocampal (E18) neurons, an activity that is associated with the CS glycosaminoglycans (GAGs). Further characterization of DSD-1-PG has included sequencing of peptides from the core protein and the cloning of the corresponding cDNA using polyclonal antisera against DSD-1-PG to screen phage expression libraries. On the basis of these studies we have identified DSD-1-PG as the mouse homolog of phosphacan, a neural rat CSPG. Monoclonal antibodies 3H1 and 3F8 against carbohydrate residues on rat phosphacan recognize these epitopes on DSD-1-PG. The epitopes of the antibodies, L2/HNK-1 and L5/Lewis-X, which have been implicated in functional interactions, are also found on DSD-1-PG. Although DSD-1-PG has previously been shown to promote neurite outgrowth, its upregulation after stab wounding of the CNS and its localization in regions that are considered boundaries to axonal extension suggested that it may also have inhibitory functions. Neonatal dorsal root ganglion (DRG) explants grown on a rich supportive substrate (laminin) with and without DSD-1-PG were strikingly inhibited by the proteoglycan. The inhibitory effects of DSD-1-PG on the DRG explants were not relieved by removal of the CS GAGs, indicating that this activity is associated with the core glycoprotein. The neurite outgrowth from embryonic hippocampal neurons on laminin was not affected by the addition of DSD-1-PG. This indicates that DSD-1-PG/mouse phosphacan can have opposing effects on the process of neurite outgrowth dependent on neuronal lineage.

Co-ordination between membrane oriC sequestration factors and a chromosome partitioning protein, TolC (MukA).

oriC DNA in the hemimethylated (but not in the fully methylated) state reacts with an Escherichia coli K-12 outer membrane preparation. This reaction is drastically reduced when the membrane preparation of a seqA null mutant is used. An in vitro reconstitution of the activity was undertaken by adding a partially purified SeqA protein to a seqA mutant membrane without success. A possible reason for this failure might be a profound modification of the outer membrane of the seqA mutant (as revealed by the fact that membrane from the mutant sediments more slowly than that from the wild type during ultracentrifugation). There is also a reduction in the content of OmpF protein. Moreover, one of the minor outer membrane proteins involved in partitioning of newly synthesized chromosomes, the ToiC (MukA) protein, was also found to be downregulated in the seqA mutant. This is also true of the hobH mutant grown in a high-osmolarity medium. Mutants of both seqA and hobH stop dividing after hyperosmotic shock, forming filaments (as observed in dam mutants).

A novel cytoplasmic hemimethylated oriC binding activity.

Using hemimethylated, fully methylated, and unmethylated oligonucleotide probes corresponding to part of the origin of Escherichia coli DNA replication, oriC (+81-136), we have characterized a novel hemimethylated DNA-specific protein binding activity. This activity appears to be located in the cytoplasm rather than in membrane fractions. It has been partially purified and, in DNase footprinting analysis, found to preferentially protect only a subset of the hemimethylated GATC sites present in the minimal oriC. These sites are found adjacent to the DnaA binding box, R1, and overlap the integration host factor binding site. The activity does not correspond to known hemimethylated binding proteins, although in the seqA deletion mutant, there is a 3-fold reduction of the activity. The stage of the cell cycle in synchronized PC2 cultures does not seem to significantly affect thte relative levels of this binding activity. A possible role in sequestration of the newly replicated hemimethylated origin is discussed.

The Drosophila melanogaster homolog of ribosomal protein S18.

The sequence of the cDNA encoding the Drosophila melanogaster homolog of the human and rat small-subunit ribosomal protein, S18 (rpS18), is presented. The deduced 152-amino-acid (aa) sequence exhibits 76% identity to that of the human and rat rpS18 (152 aa), and is, like them, a member of the larger rpS13 family which includes archaebacterial, eubacterial and plant mitochondrial (mt) rpS13. The D. melanogaster rpS18 gene is single copy and maps at 56F, a chromosome region encompassing a previously characterised Minute locus, M(2)56F. The rpS18 gene gives rise to a single 700-nucleotide transcript present throughout development. A comparison of the rpS13 family members suggests that conservation is greatest at the N- and C-termini, whilst additional insertions are present in the Drosophila, mammalian and archaebacterial proteins relative to the eubacterial and plant mt proteins.

The Drosophila melanogaster homolog of ribosomal protein L27a.

The amino acid sequence of the Drosophila melanogaster 60S ribosomal sub-unit protein, L27a, was deduced from the sequence of nucleotides in a recombinant cDNA. Ribosomal protein L27a has 149 amino acids with a molecular weight of 17,123 Daltons. Hybridisation of the cDNA to polytene chromosomes indicates the presence of a single gene on chromosome 3R at 87F/88A. There is a single mRNA for the protein of around 650 nucleotides in length. Drosophila ribosomal protein L27a is homologous to the rat and yeast L27a and to the other members of the L15 ribosomal protein family. There is also significant homology with an invertebrate motor protein and a Drosophila photoreceptor morphogenesis protein.

Neuropsychological studies of auditory-visual fusion illusions. Four case studies and their implications.

A heard speech sound which is not the same as the synchronized speech sound can sometimes give rise to an illusory phonological percept. Typically, a heard /ba/ combines with a seen /ga/ to give the impression that /da/ has been heard (McGurk, H. and MacDonald, J. Nature Lond. 264, 746-748, 1976). We report the susceptibility to this illusion of four individuals with localized brain lesions affecting perceptual function. We compare their performance to that of ten control subjects and relate these findings to the efficiency of processing seen and heard speech in separate and combined modalities. The pattern of performance strongly suggests LH specialization for the phonological integration of seen and heard speech. The putative site of such integration can be effectively isolated from unilateral and from bilateral inputs and may be driven by either modality.

Carbon dioxide laser treatment of the conjunctiva and the cornea.

Carbon dioxide (CO2) laser treatment was applied to the cornea and conjunctiva of 16 eyes from eight young pigs at power levels of 2.5 to 20.0 W, an exposure time of 0.1 seconds and different numbers of overlapping burns. Four animals were euthanatized at 30 minutes, one at 36 hours and three from 18 to 21 days after the treatment. Nitrous oxide (N2O) cryotherapy also was applied in a double freeze-thaw fashion to three of the eyes to compare the effects of the CO2 laser and cryotherapy at each of the time intervals. Epithelial destruction was achieved with CO2 laser power levels of 5.0 W and one or more superimposed burns. At 5.0 W, Bowman's membrane was destroyed while the conjunctival substantia propria protected the underlying sclera. The anterior chamber reaction was minimal and appeared to be less intense than with cryotherapy after 36 hours. At high energy levels (20.0 W), corneal and scleral perforation occurred. Furthermore, we have treated five human patients with the CO2 laser for bulbar conjunctival epithelial proliferative disorders. Minimal scarring occurred and local control of the disease was obtained in four patients. The CO2 laser may offer advantages over other modalities of treatment for bulbar conjunctival epithelial disorders. Its use is not recommended for lesions of the cornea and forniceal or palpebral conjunctiva.

Bone loss during oestriol therapy in postmenopausal women.

In contrast to all other oestrogens examined thus far oestriol hemisuccinate (12 mg/day) did not prevent bone loss in 28 postmenopausal women. The average bone loss, however, was somewhat less than expected from placebo studies, while the bone loss achieved by a group taking 4-6 mg/day was equal to that achieved by previous placebo groups. To be an effective agent for prevention of post-menopausal osteoporosis oestriol would have to be prescribed in daily doses considerably in excess of 12 mg.

PIP: Studies have shown that estrogen therapy is useful in preventing bone loss, osteoporosis, in postmenopausal women. Long-term estrogen therapy, however, may be associated with an increased incidence of endometrial carcinoma. To be effective against bone loss, the therapy would have to be continued for a long time. A double-blind study was conducted to determine whether estriol, which has weaker effects on the endometrium, at relatively low doses could be used to retard osteoporosis in postmenopausal women. The estriol, at 4mg daily, was ineffective in controlling postmenopausal symptoms; 35% of the patients required a 14 mg-dose, and 5 patients were dissatisfied even with that doage. In addition, the 12 mg-dose did not prevent bone loss, which continued at a rate only slightly lower than for patients on placebo therapy. It is likely that a higher dosage would be more effective, but would cause the potential endometrial effects. Laboratory procedures involved in the study are outlined and results are graphed.

Bone response to termination of oestrogen treatment.

Forty-three oophorectomised patients were reviewed 8 years after their initial attendance at a research clinic investigating the aetiology and prevention of postmenopausal osteoporosis. Fifteen patients who had been treated with an oestrogen did not lose a significant amount of bone during the 8 years of therapy. Patients in the placebo-treated control group initially had bone loss of 2.6% per annum, which later fell to an average of 0.75% per annum. Fourteen patients who had been treated with oestrogen for the first 4 years lost no bone, but on withdrawal of oestrogen their bone mineral content fell over the next 4 years at an average rate of 2.5% per annum. 8 years after their initial attendance there was no significant difference between this group and patients who had received placebo for the full 8 years. The result of this study indicates that long-term prevention of bone loss by oestrogens has important medical, social, economic implications.

Keratosis pilaris.

This benign skin disorder is recognized by a characteristic appearance and a positive family history. Safe, effective treatment with urea creams and lotions is available.