A clinical and molecular study of 26 females with Xp deletions with special emphasis on inherited deletions

We have undertaken a clinical study of 26 females with deletions of Xp including five mother–daughter pairs. Cytogenetic and molecular analyses have mapped the breakpoints of the deletions. We determined the parental origin of each abnormality and studied the X-inactivation patterns. We describe the clinical features and compare them with the amount of Xp material lost. We discuss the putative loci for features of Turner syndrome and describe how our series contributes further to their delineation. We conclude that (1) fertility can be retained even with the loss of two-thirds of Xp, thus, if there are genes on Xp for ovarian development, they must be at Xp11–Xp11.2; (2) in our sample of patients there is no evidence to support the existence of a single lymphogenic gene on Xp; (3) there is no evidence for a second stature locus in proximal Xp; (4) there is no evidence to support the existence of a single gene for naevi; (5) we suggest that the interval in Xp21.1–Xp11.4 between DXS997 and DXS1368 may contain a gene conferring a predisposition to hypothyroidism.     

The role of the DIF motif of the DnaJ (Hsp40) co-chaperone in the regulation of the DnaK (Hsp70) chaperone cycle

To perform effectively as a molecular chaperone, DnaK (Hsp70) necessitates the assistance of its DnaJ (Hsp40) co-chaperone partner, which efficiently stimulates its intrinsically weak ATPase activity and facilitates its interaction with polypeptide substrates. In this study, we address the function of the conserved glycine- and phenylalanine-rich (G/F-rich) region of the Escherichia coli DnaJ in the DnaK chaperone cycle. We show that the G/F-rich region is critical for DnaJ co-chaperone functions in vivo and that despite a significant degree of sequence conservation among the G/F-rich regions of Hsp40 homologs from bacteria, yeast, or humans, functional complementation in the context of the E. coli DnaJ is limited. Furthermore, we found that the deletion of the whole G/F-rich region is mirrored by mutations in the conserved Asp-Ile/Val-Phe (DIF) motif contained in this region. Further genetic and biochemical analyses revealed that this amino acid triplet plays a critical role in regulation of the DnaK chaperone cycle, possibly by modulating a crucial step subsequent to DnaK-mediated ATP hydrolysis.     

Substrate specificity of human kallikrein 6: salt and glycosaminoglycan activation effects

Human kallikrein 6 (hK6) is abundantly expressed in the central nervous system and is implicated in demyelinating disease. This study provided biochemical data about the substrate specificity and activation of hK6 by glycosaminoglycans and by kosmotropic salts, which followed the Hofmeister series. The screening of fluorescence resonance energy transfer (FRET) peptide families derived from Abz-KLRSSKQ-EDDnp resulted in the finding that Abz-AFRFSQ-EDDnp (where Abz is ortho-aminobenzoic acid and EDDnp is N-[2,4-dinitrophenyl]ethylenediamine)) is the best synthetic substrate described so far for hK6 (kcat/Km 38,667 s(-1) mm(-1)). It is noteworthy that the AFRFS sequence was found as a motif in the amino-terminal domain of seven human ionotropic glutamate receptor subunits. We also examined the hK6 hydrolytic activity on FRET peptides derived from human myelin basic protein, precursor of the Abeta amyloid peptide, reactive center loop of alpha1-antichymotrypsin, plasminogen, and maturation and inactivation cleavage sites of hK6, which were described earlier as natural substrates for hK6. The best substrates were derived from myelin basic protein. The hK6 maturation cleavage site was poorly hydrolyzed, and no evidence was found to support a two-step self-activation process reported previously. Finally, we assayed FRET peptides derived from sequences that span the cleavage sites for activation of protease-activated receptors (PAR) 1-4, and only the substrate with the PAR 2 sequence was hydrolyzed. These results further supported the hypothesis that hK6 expressed in the central nervous system is involved in normal myelin turnover/demyelination processes, but it is unlikely to self-activate. This report also suggested the possible modulation of ionotropic glutamate receptors and activation of PAR 2 by hK6.     

"Conilon" coffee berries bored by Hypothenemus hampei (Ferrari) (Coleoptera: Scolytidae): what matters if they drop down during the fruiting phase?

Falling of berries bored by Hypothenemus hampei (Ferrari) may be the major loosing factor during the fruiting period. However, only those bored berries which remain in the soil surface before a new yielding period have been recognized as responsible for the damage level Ho achieved by new developing berries. In this paper, we investigated in the plants and in the soil surface, the presence of Coffea canephora cv. Conilon berries bored by H. hampei during the yielding period in Ouro Preto d'Oeste, Rond?nia, Brazil. We took samples, weekly, from December 2000 to June 2001. The data were submitted to the Surviving Regression Analysis, based on a censored Weibull model. During the yielding period, berries fall down continuously and, in average, the proportion of H. hampei bored berries was 4 to 20 times higher in the soil (P < 2,3 x 10-18, n = 62,747) than in the plants. Thus, we argue that adding the "soil environment" to the integrated management strategies could point to new technologies for the control of this insect.     

C-nucleoside analogues of furanfurin as ligands to A1 adenosine receptors

Furanfurin (2-beta-D-ribofuranosylfuran-4-carboxamide) derivatives and analogues were synthesized and their affinity for adenosine receptors was determined. The agonistic behavior of furanfurin against A1 receptors is preserved only when the furan ring is substituted with isosteric pentatomic ring systems such as oxazole, thiazole or thiophene, and the carboxamide group is unsubstituted. Replacement of the hydrogen atoms of the carboxamide group with alkyl, cycloalkyl or arylalkyl groups generates compounds endowed with moderate antagonistic activity.     

The prognosis of acute and persistent low-back pain: a meta-analysis

Background:

Although low-back pain is a highly prevalent condition, its clinical course remains uncertain. Our main objective was to systematically review the literature on the clinical course of pain and disability in patients with acute and persistent low-back pain. Our secondary objective was to investigate whether pain and disability have similar courses.

Methods:

We performed a meta-analysis of inception cohort studies. We identified eligible studies by searching MEDLINE, Embase and CINAHL. We included prospective studies that enrolled an episode-inception cohort of patients with acute or persistent low-back pain and that measured pain, disability or recovery. Two independent reviewers extracted data and assessed methodologic quality. We used mixed models to determine pooled estimates of pain and disability over time.

Results:

Data from 33 discrete cohorts (11 166 participants) were included in the review. The variance-weighted mean pain score (out of a maximum score of 100) was 52 (95% CI 48–57) at baseline, 23 (95% CI 21–25) at 6 weeks, 12 (95% CI 9–15) at 26 weeks and 6 (95% CI 3–10) at 52 weeks after the onset of pain for cohorts with acute pain. Among cohorts with persistent pain, the variance-weighted mean pain score (out of 100) was 51 (95% CI 44–59) at baseline, 33 (95% CI 29–38) at 6 weeks, 26 (95% CI 20–33) at 26 weeks and 23 (95% CI 16–30) at 52 weeks after the onset of pain. The course of disability outcomes was similar to the time course of pain outcomes in the acute pain cohorts, but the pain outcomes were slightly worse than disability outcomes in the persistent pain cohorts.

Interpretation:

Patients who presented with acute or persistent low-back pain improved markedly in the first six weeks. After that time improvement slowed. Low to moderate levels of pain and disability were still present at one year, especially in the cohorts with persistent pain.Low-back pain is a highly prevalent condition associated with work absenteeism, disability and large health care costs; however, there is still disagreement about prognosis. For example, the European guidelines for the management of low-back pain states that 90% of patients with acute low-back pain recover in six weeks.¹ In contrast, some well-conducted cohort studies show a less optimistic picture, providing short-term estimates of recovery ranging from 39% to 76%.^2,3 This wide range of estimates of prognosis is likely explained by differences in cohorts and definitions used to define the onset or conclusion of an episode of low-back pain. Because very different definitions of recovery are often used, it is difficult to obtain pooled estimates of recovery rates. Instead, it might be more useful to describe the clinical course of low-back pain in terms of expected changes in pain or disability over time.A recent systematic review⁴ summarized the prognostic factors for persistent disabling low-back pain but did not describe the clinical course. The only meta-analysis to investigate the clinical course of acute low-back pain was published in 2003.⁵ This review concluded that both pain and disability improve rapidly within weeks (mean reduction of 58% of initial scores in the first month) and recurrences are common. A limitation of this review was that, although it retrieved 15 studies, only 5 were cohort studies; the remaining 10 were randomized controlled trials. Randomized trials often have narrow inclusion criteria and low rates of participation, which make them less suitable for inferring prognosis. The best design to describe the prognosis of a condition is a cohort study enrolling a representative sample of incident cases (i.e., by including patients at a similar early point in their condition).^6,7 Such studies are known as inception cohort studies. To the best of our knowledge, no review has yet investigated the clinical course of pain and disability among people with persistent low-back pain (subacute and chronic). Thus, the prognosis for people with persistent low-back pain is still uncertain.The aim of our study was to systematically review the clinical course of pain and disability in patients with acute and persistent low-back pain. We included only inception cohort studies. Our second aim was to investigate whether pain and disability have similar courses.     

Adenosine Deaminase Activity in Serum and Lymphocytes of Rats Infected with Sporothrix schenckii

Sporotrichosis is a fungal infection of subcutaneous or chronic evolution, inflammatory lesions characterized by their pyogranulomatous aspect, caused by the dimorphic fungus Sporothrix schenckii. Adenosine deaminase (ADA) is a "key" enzyme in the purine metabolism, promoting the deamination of adenosine, an important anti-inflammatory molecule. The increase in ADA activity has been demonstrated in several inflammatory conditions; however, there are no data in the literature associated with this fungal infection. The objective of this study was to evaluate the activity of serum ADA (S-ADA) and lymphocytes (L-ADA) of rats infected with S. schenckii. We used seventy-eight rats divided into two groups. In the first experiment, rats were infected subcutaneously and in the second experiment, infected intraperitoneally. Blood samples for hematologic evaluation and activities of S-ADA and L-ADA were performed at days 15, 30, and 40 post-infection (PI) to assess disease progression. In the second experiment, it was observed an acute decrease in activity of S-ADA and L-ADA (P?相似文献   

Floristics and environmental factors determining the geographic distribution of epiphytic bromeliads in the Brazilian Atlantic Rain Forest

We investigated how epiphytic species and subfamilies of Bromeliaceae change along the extent of the Atlantic Rain Forest, to answer the questions: (i) How do the epiphytic genera and subfamilies of Bromeliaceae change along the domain? (ii) How similar are the different regions of the Atlantic Rain Forest in relation to the epiphytic species of bromeliads? (iii) Which environmental variables are the most important factors in determining species composition along the domain? We found 114 species of Bromelioideae and 73 of Tillandsioideae. The predominance of Bromelioideae was unexpected, because they are not wind-dispersed as would be expected for most epiphytes. The smaller number of species of Tillandsioideae, and the high frequency of species of Vriesea with limited geographic distributions indicated that epiphytes with rather limited geographic distributions predominate in this domain. Species similarity was divided into one block of south–southeastern localities, and a second block of northeastern–southeastern localities. These results suggest that the distribution of epiphytic bromeliad species resembles that of the phorophyte trees, more than a previous pattern suggested for all epiphytes in the domain. Latitude, temperature and altitude were important factors affecting the species composition along the domain. In general, our results differ from those of other studies in Latin America, and we suggest that historical and evolutionary events generated these differences.     

STK25 Protein Mediates TrkA and CCM2 Protein-dependent Death in Pediatric Tumor Cells of Neural Origin

The TrkA receptor tyrosine kinase induces death in medulloblastoma cells via an interaction with the cerebral cavernous malformation 2 (CCM2) protein. We used affinity proteomics to identify the germinal center kinase class III (GCKIII) kinases STK24 and STK25 as novel CCM2 interactors. Down-modulation of STK25, but not STK24, rescued medulloblastoma cells from NGF-induced TrkA-dependent cell death, suggesting that STK25 is part of the death-signaling pathway initiated by TrkA and CCM2. CCM2 can be phosphorylated by STK25, and the kinase activity of STK25 is required for death signaling. Finally, STK25 expression in tumors is correlated with positive prognosis in neuroblastoma patients. These findings delineate a death-signaling pathway downstream of neurotrophic receptor tyrosine kinases that may provide targets for therapeutic intervention in pediatric tumors of neural origin.