Frequent coexistence of anti-topoisomerase I and anti-U1RNP autoantibodies in African American patients associated with mild skin involvement: a retrospective clinical study

Introduction  

The presence of anti-topoisomerase I (topo I) antibodies is a classic scleroderma (SSc) marker presumably associated with a unique clinical subset. Here the clinical association of anti-topo I was reevaluated in unselected patients seen in a rheumatology clinic setting.     

Characterization and distribution of bombesin binding sites in the goldfish hypothalamic feeding center and pituitary

Bombesin (BBS)/gastrin-releasing peptide (GRP) binding sites were characterized and their distribution examined in the goldfish brain and pituitary by radioligand binding and autoradiography. Binding of ¹²⁵I-[Tyr⁴]-BBS-14 to tissue sections was found to be saturable, reversible, time-dependent and displaceable by BBS/GRP-like peptides. Analysis of saturable equilibrium binding revealed a one-site model fit with a K_d of 0.665 ± 0.267 nM. This binding site displayed high affinity for members of the BBS subfamily of peptides, including GRP10 (K_i; 0.292 ± 0.038 nM) and GRP27 (K_i; 2.034 ± 1.597 nM), but showed no affinity for the BBS_8–14 fragment. While an approximate 100-fold lower binding affinity was displayed by the binding site for neuromedin B (K_i; 61.5 ± 28.2 nM), litorin was highly effective in displacing radiolabeled BBS binding (K_i; 1.469 ± 0.427 nM). The localization of saturable and high affinity BBS/GRP binding sites in specific areas of the goldfish brain and pituitary generally revealed a similar anatomical distribution to BBS/GRP-like immunoreactive material reported previously by our laboratory. Quantitative densitometric analysis of radiolabeled BBS binding to brain nuclei and the pituitary revealed a moderate concentration of BBS/GRP binding sites in the hypothalamic feeding area, including the nucleus diffusus lobi inferioris, nucleus recessus lateralis, nucleus lateral tuberis, and nucleus anterior tuberis. Other brain nuclei known to influence the brain feeding center which contained a high density of BBS/GRP binding sites included nuclei of the dorsal and ventro-medial telencephalon, the preoptic hypothalamus, and the optic tectum. High densities of BBS/GRP binding sites were also localized in the dorsal cerebellum, and nucleus habenularis. In the pituitary, BBS/GRP binding sites were present in high concentration in the neurointermediate lobe, with a relatively lower density localized in the pars distalis. The present study further supports a role for BBS/GRP-like peptides in the regulation of feeding behavior and anterior pituitary hormone secretion in teleosts.     

Species loss of stoneflies (Plecoptera) in the Czech Republic during the 20th century

1. Rapid expansion and intensification of anthropogenic activities in the 20th century has caused profound changes in freshwater assemblages. Unfortunately, knowledge of the extent and causes of species loss (SL) is limited due to the lack of reliable historical data. An unusual data set allows us to compare changes in the most sensitive of aquatic insect orders, the Plecoptera, at some 170 locations in the Czech Republic between two time periods, 1955–1960 and 2006–2010. Historical data (1890–1911) on assemblages of six lowland rivers allow us to infer even earlier changes. 2. Regional stonefly diversity decreased in the first half of the 20th century. Streams at lower altitudes lost a substantial number of species, which were never recovered. In the second half of the century, large‐scale anthropogenic pressure caused SL in all habitats, leading to a dissimilarity of contemporary and previous assemblages. The greatest changes were found at sites affected by organic pollution and a mixture of organic pollution and channelisation or impoundment. Colonisation of new habitats was observed in only three of the 80 species evaluated. 3. Species of moderate habitat specialisation and tolerance to organic pollution were most likely to be lost. Those with narrow specialisations in protected habitats were present in both historical and contemporary collections. 4. Contemporary assemblages are the consequence of more than a 100 years of anthropogenic impacts. In particular, streams at lower altitude and draining intensively exploited landscapes host a mere fragment of the original species complement. Most stonefly species are less frequently present than before, although their assemblages remain almost intact in near‐natural mountain streams. Our analyses demonstrate dramatic restriction of species ranges and, in some cases, apparent changes in altitudinal preference throughout the area.     

Hepatocyte growth factor is a regulator of monocyte-macrophage function

Hepatocyte growth factor (HGF) is a potent paracrine mediator of stromal/epithelial interactions, which is secreted as a matrix-associated inactive precursor (pro-HGF) and locally activated by tightly controlled urokinase cleavage. It induces proliferation and motility in epithelial and endothelial cells, and plays a role in physiological and pathological processes involving invasive cell growth, such as angiogenesis and parenchymal regeneration. We now report that HGF induces directional migration and cytokine secretion in human monocytes. Monocyte activation by endotoxin and IL-1beta results in the up-regulation of the HGF receptor expression and in the induction of cell-associated pro-HGF convertase activity, thus enhancing cell responsiveness to the factor. Furthermore, we provide evidence for the secretion of biologically active HGF by activated monocytes, implying an autocrine stimulation. Altogether, these data indicate that monocyte function is modulated by HGF in a paracrine/autocrine manner, and provide a new link between stromal environment and mononuclear phagocytes.     

Activation of hypothalamic RIP‐Cre neurons promotes beiging of WAT via sympathetic nervous system

Activation of brown adipose tissue (BAT) and beige fat by cold increases energy expenditure. Although their activation is known to be differentially regulated in part by hypothalamus, the underlying neural pathways and populations remain poorly characterized. Here, we show that activation of rat‐insulin‐promoter‐Cre (RIP‐Cre) neurons in ventromedial hypothalamus (VMH) preferentially promotes recruitment of beige fat via a selective control of sympathetic nervous system (SNS) outflow to subcutaneous white adipose tissue (sWAT), but has no effect on BAT. Genetic ablation of APPL2 in RIP‐Cre neurons diminishes beiging in sWAT without affecting BAT, leading to cold intolerance and obesity in mice. Such defects are reversed by activation of RIP‐Cre neurons, inactivation of VMH AMPK, or treatment with a β3‐adrenergic receptor agonist. Hypothalamic APPL2 enhances neuronal activation in VMH RIP‐Cre neurons and raphe pallidus, thereby eliciting SNS outflow to sWAT and subsequent beiging. These data suggest that beige fat can be selectively activated by VMH RIP‐Cre neurons, in which the APPL2–AMPK signaling axis is crucial for this defending mechanism to cold and obesity.     

Muscle fiber type-specific response of Hsp70 expression in human quadriceps following acute isometric exercise.

To investigate the time course of fiber type-specific heat shock protein 70 (Hsp70) expression in human skeletal muscle after acute exercise, 10 untrained male volunteers performed single-legged isometric knee extensor exercise at 60% of their maximal voluntary contraction (MVC) with a 50% duty cycle (5-s contraction and 5-s relaxation) for 30 min. Muscle biopsies were collected from the vastus lateralis before (Pre) exercise in the rested control leg (C) and immediately after exercise (Post) in the exercised leg (E) only and on recovery days 1 (R1), 2 (R2), 3 (R3), and 6 (R6) from both legs. As demonstrated by Western blot analysis, whole muscle Hsp70 content was unchanged (P > 0.05) immediately after exercise (Pre vs. Post), was increased (P < 0.05) by approximately 43% at R1, and remained elevated throughout the entire recovery period in E only. Hsp70 expression was also assessed in individual muscle fiber types I, IIA, and IIAX/IIX by immunohistochemistry. There were no fiber type differences (P > 0.05) in basal Hsp70 expression. Immediately after exercise, Hsp70 expression was increased (P < 0.05) in type I fibers by approximately 87% but was unchanged (P > 0.05) in type II fibers (Pre vs. Post). At R1 and throughout recovery, Hsp70 content in E was increased above basal levels (P < 0.05) in all fiber types, but Hsp70 expression was always highest (P < 0.05) in type I fibers. Hsp70 content in C was not different from Pre at any time throughout recovery. Glycogen depletion was observed at Post in all type II, but not type I, fibers, suggesting that the fiber type differences in exercise-induced Hsp70 expression were not related to glycogen availability. These results demonstrate that the time course of exercise-induced Hsp70 expression in human skeletal muscle is fiber type specific.     

Identification of nonsulfated cholecystokinin-58 in canine intestinal extracts and its biological properties

Nonsulfated CCK(58) [CCK(58)(ns)] has not been considered to be of biological importance because CCK(58)(ns) binds poorly to the CCK(A) receptor and has only been identified once in intestinal extracts. In this work, a radioimmunoassay specific for the COOH-terminal region of gastrin and CCK (antibody 5135) was used to monitor the purification of CCK molecular forms from canine intestinal extracts. A minor immunoreactive peak was associated with a major absorbance peak during an ion-exchange, HPLC step. Characterization of this minor immunoreactive peak demonstrated that it was CCK(58)(ns). CCK(58)(ns) is 14% as immunoreactive as sulfated CCK(8) [CCK(8)(s)]. Amino acid analysis demonstrated that CCK(58)(ns) was present at 50% the amount of CCK(58)(s). In addition, we found that CCK(58)(ns) does not potently displace an (125)I-labeled CCK(10) analog from the CCK(A) receptor in mouse pancreatic membranes and does not stimulate amylase release from isolated pancreatic acini, or stimulate pancreatic secretion in an anesthetized rat model. By contrast, CCK(58)(ns) does bind to CCK(B) receptors and stimulates gastric acid secretion via this receptor. The presence of CCK(58)(ns) and its ability to selectively stimulate the CCK(B) receptor without stimulation of the CCK(A) receptor suggest that CCK(58)(ns) may have unique physiological properties, especially tissues where the nonsulfated peptide can act as a paracrine or neurocrine agent.     

Interactions of Cultures and Top People of Wikipedia from Ranking of 24 Language Editions

Wikipedia is a huge global repository of human knowledge that can be leveraged to investigate interwinements between cultures. With this aim, we apply methods of Markov chains and Google matrix for the analysis of the hyperlink networks of 24 Wikipedia language editions, and rank all their articles by PageRank, 2DRank and CheiRank algorithms. Using automatic extraction of people names, we obtain the top 100 historical figures, for each edition and for each algorithm. We investigate their spatial, temporal, and gender distributions in dependence of their cultural origins. Our study demonstrates not only the existence of skewness with local figures, mainly recognized only in their own cultures, but also the existence of global historical figures appearing in a large number of editions. By determining the birth time and place of these persons, we perform an analysis of the evolution of such figures through 35 centuries of human history for each language, thus recovering interactions and entanglement of cultures over time. We also obtain the distributions of historical figures over world countries, highlighting geographical aspects of cross-cultural links. Considering historical figures who appear in multiple editions as interactions between cultures, we construct a network of cultures and identify the most influential cultures according to this network.