Spatial variability in species' potential distributions during the Last Glacial Maximum under different Global Circulation Models: Relevance in evolutionary biology

Ecological niche models (ENM) have been used to reconstruct potential distributions during the Last Glacial Maximum (LGM)—or other time periods—and this use is increasingly common in zoological studies. For this reason, we urgently need understanding factors affecting these predictions. Here, we examine how the use of different Global Circulation Models (GCMs) affects the variability in species' potential distributions during the LGM and how the degree of model extrapolation and its associated uncertainty depends on the GCM used. We develop these issues using two North American shrews, Notiosorex crawfordi and Cryptotis alticola, inhabiting two environmentally different regions. First, we compared paleoclimates in these two regions simulated by three GCMs: Community Climate System Model (CCSM), Model for Interdisciplinary Research on Climate (MIROC), and the Max‐Planck‐Institute für Meteorologie model (MPI). Then, we used maxent to estimate the LGM potential distribution of these two mammals under the three GCMs to assess the spatial variability and extrapolation uncertainty associated with idiosyncrasies of GCM. MIROC estimated noticeably more different climatic conditions than CCSM and MPI in the study areas during the LGM, and its pattern of environmental conditions was distributed differently. The MIROC scenario suggested a remarkable different prediction of potential distribution for both species, being more dramatic for the high mountain shrew, C. alticola. In particular, climatic differences among GCMs resulted in differences in the factors that limit and drive the potential distribution of the species during the LGM. Equally dramatic was the disagreement of extrapolation areas among GCMs. MIROC showed a greater number of pixels where extrapolation is required in both regions. Our findings should be taken into consideration when identifying areas of endemism, dynamic geographic barriers, and glacial refugia. When projecting into alternative scenarios of LGM climate, the idiosyncrasies of each GCM should be explicitly taken into account.     

Novel functions for `nuclear factors' in the cytoplasm: theSex-lethalparadigm

In recent years, novel functions for a number of nuclear factors have been uncovered in the cytoplasm, mainly at the level of translation. These factors behave as multifunctional regulators of gene expression and many play key roles in cell differentiation and development. One of the best characterized examples is that of Sex-lethal (SXL), an RNA-binding protein that is expressed in female Drosophila flies and controls sex determination and dosage compensation. Recent findings indicate that SXL, a paradigmatic regulator of splicing, also controls translation of target mRNAs. This review attempts to summarize this evidence and provide an overview of `nuclear factors' with roles in translation.     

Mowat-Wilson syndrome

Hypereosinophilic syndromes (HES) constitute a rare and heterogeneous group of disorders, defined as persistent and marked blood eosinophilia (> 1.5 × 10⁹/L for more than six consecutive months) associated with evidence of eosinophil-induced organ damage, where other causes of hypereosinophilia such as allergic, parasitic, and malignant disorders have been excluded. Prevalence is unknown. HES occur most frequently in young to middle-aged patients, but may concern any age group. Male predominance (4–9:1 ratio) has been reported in historic series but this is likely to reflect the quasi-exclusive male distribution of a sporadic hematopoietic stem cell mutation found in a recently characterized disease variant. Target-organ damage mediated by eosinophils is highly variable among patients, with involvement of skin, heart, lungs, and central and peripheral nervous systems in more than 50% of cases. Other frequently observed complications include hepato- and/or splenomegaly, eosinophilic gastroenteritis, and coagulation disorders. Recent advances in underlying pathogenesis have established that hypereosinophilia may be due either to primitive involvement of myeloid cells, essentially due to occurrence of an interstitial chromosomal deletion on 4q12 leading to creation of the FIP1L1-PDGFRA fusion gene (F/P⁺ variant), or to increased interleukin (IL)-5 production by a clonally expanded T cell population (lymphocytic variant), most frequently characterized by a CD3^-CD4⁺ phenotype. Diagnosis of HES relies on observation of persistent and marked hypereosinophilia responsible for target-organ damage, and exclusion of underlying causes of hypereosinophilia, including allergic and parasitic disorders, solid and hematological malignancies, Churg-Strauss disease, and HTLV infection. Once these criteria are fulfilled, further testing for eventual pathogenic classification is warranted using appropriate cytogenetic and functional approaches. Therapeutic management should be adjusted to disease severity and eventual detection of pathogenic variants. For F/P⁺ patients, imatinib has undisputedly become first line therapy. For others, corticosteroids are generally administered initially, followed by agents such as hydroxycarbamide, interferon-alpha, and imatinib, for corticosteroid-resistant cases, as well as for corticosteroid-sparing purposes. Recent data suggest that mepolizumab, an anti-IL-5 antibody, is an effective corticosteroid-sparing agent for F/P-negative patients. Prognosis has improved significantly since definition of HES, and currently depends on development of irreversible heart failure, as well as eventual malignant transformation of myeloid or lymphoid cells.     

Evidence for the presence of β-subunit of hexosaminidase in a case of Sandhoff disease using a blotting technique

Hexosaminidases, lysosomal enzymes whose deficiency is responsible for several genetic disorders, exist as two major forms: form A, containing two types of subunits alpha and beta; and form B, containing only beta subunits. We have used a technique involving successively electrophoresis of denatured proteins, transfer (blotting) onto nitrocellulose, and labelling by appropriate antibodies raised against the dissociated forms of hexosaminidases A and B. This technique allows the detection of alpha and beta subunits in crude extracts of normal tissues. The presence of beta chains was demonstrated in the liver of a fetus affected with Sandhoff's disease, deficient in functional hexosaminidases A and B.     

Global phosphorylation at Ser16 of the 32-residue cytoplasmic domain of phospholamban: Comparison of di-t-butyl- and dibenzyl-N,N-diisopropylphosphoramidites

Summary Phospholamban (PLB), a 52-residue integral membrane protein of the cardiac sarcoplasmic reticulum, is known as the regulator of the Ca²⁺-ATPase pump via its phosphorylation-dephosphorylation at Ser¹⁶. In order to investigate the structural effects of the phosphorylation on the cytoplasmic domain of PLB, we synthesized PLB 2–33 in its nonphosphorylated and phosphorylated forms using Fmoc chemistry. PLB 2–33 was phosphorylated using the global phosphorylation method. Phosphorylation with di-t-butyl-N,N-diisopropylphosphoramidite led to an incomplete reaction (nonphosphorylated peptide was recovered) and to the formation of an H-phosphonate. In contrast, the use of dibenzyl-N,N-diisopropylphosphoramidite yielded the desired phosphorylated peptide quantitatively and did not give rise to the H-phosphonate. Our results show the effectiveness of the dibenzyl-protected phosphoramidite when the site to be phosphorylated is particularly hindered.     

Short Communication: Urinary excretion of glutamine transaminase K as an early index of mercuric chloride-induced nephrotoxicity

The possibili that urinary glutamine transaminase K activity might be a marker of a proximal tubule segment-specific response to mercuric chloride was investigated in male rats after a single i.p. injection in time-course and dose-response experiments. Urinary total proteins and angiotensin converting enzyme activity were determined simultaneously. Urinary indices showed an early increase (within 5 h of treatment) of total proteins and angiotensin converting enzyme, whereas glubmine transaminase K increased 10 h after treatment. The peak of all these indices was observed 24 h after mercuric chloride injection. The lowest dose that induced a significant increase in proteins and enzymes was 0.25 mg kg^-1; in addition, a dose-response effect was observed. Glutamine transaminase K appeared to be an early and sensitive index of response of mercuric chloride effects, similar to total proteins and angiotensin converting enzyme. It is suggested that this enzyme is mainly localized in the 'pars recta' of the proximal tubule. Therefore glutamine transaminase K might be a segment-specific marker for the detection of damage localized in this portion of the proximal tubule.     

Evidence for a phosphorylation-induced conformational change in phospholamban cytoplasmic domain by CD analysis.

Phospholamban (PLB), an integral membrane protein of cardiac sarcoplasmic reticulum (SR), is described as the regulator of the Ca(2+)-ATPase pump, via its phosphorylation-dephosphorylation of Ser-16. Recently it has been shown that a direct interaction between the N-terminal hydrophilic domain of PLB and Ca(2+)-ATPase may be one of the mechanisms of regulation. In order to show that this interaction could be modulated by a phosphorylation-induced conformational change in PLB, we ran CD studies on the synthetic peptide PLB(2-33) in its phosphorylated and non-phosphorylated forms, at various pHs, concentrations and in the absence or presence of trifluoroethanol. The results show a clear difference in structure of the phosphorylated and non-phosphorylated peptide.     

Fluorescence-assisted mismatch analysis (FAMA) for exhaustive screening of the α-galactosidase A gene and detection of carriers in Fabry disease

We used the fluorescence-assisted mismatch analysis (FAMA) method to screen rapidly the α-galactosidase A gene in patients with Fabry disease in order to identify unknown mutations and help define genotype-phenotype correlations in this X-linked lysosomal storage disorder. Chemical cleavage at mismatches on heteroduplex DNA end-labeled with strand-specific fluorescent dyes, reliably detects sequence changes in DNA fragments of up to 1.5 kb and locates them precisely. Exhaustive scanning of the α-galactosidase gene was accomplished on four polymerase chain reaction-generated amplicons, covering all seven exons, the exon-intron boundaries, and 700 bp of 5′-flanking sequence. Mutations were identified in each of the 15 patients studied from nine unrelated kindreds. Among the seven previously undescribed sequence changes, three are obviously pathogenic because they lead to premature protein termination. The other four, a splice-site mutation and three missense mutations, were the only changes found upon complete scanning of the gene and its promoter. In addition, FAMA also detects female heterozygous carriers more dependably than direct sequencing, and thus provides a valuable diagnostic test. In Fabry disease, this molecular criterion is especially important for genetic counseling since heterozygotes can be asymptomatic and their enzymatic values within the normal range. Received: 9 April 1996 / Revised: 8 July 1996