Miracle-dz/UniFAR-FTUs huggingface dataset:
Expression of cathepsin K in periodontitis and in gingival fibroblasts.

OBJECTIVE To study non-osteoclastic sources of cathepsin K in periodontitis. MATERIALS AND METHODS Tissue samples were obtained from 10 otherwise healthy periodontitis pati-ents during routine periodontal flap operations and 10 systemically and periodontally healthy individuals who underwent extraction operations for retained third molars. Methods used were immunohistochemistry, image analysis, immunofluorescence double-staining, gingival fibroblast culture, tumour necrosis factor-α (TNF-α) stimulation and Western blotting. RESULTS Macrophage-like cells, fibroblast-like cells, vascular endothelial cells and gingival epithelial cells were more intensively stained for cathepsin K and also more frequent in periodontitis than in controls (665 ± 104 vs 258 ± 40 cells mm(-2) , P < 0.01). Some cathepsin K(+) cells in periodontal tissues were CD68(+) , but some were CD68(-) and probably fibroblasts. Indeed, in gingival fibroblast culture, resting fibroblasts released cathepsin K, more 43 kD procathepsin K than 29 kD active cathepsin K. TNF-α increased the release of the activated cathepsin K 4- to 5-fold. CONCLUSIONS Results suggest that GCF-cathepsin K is not only osteoclast-derived, but in periodontitis, also other cells contribute to it. GCF-cathepsin K, perhaps together with intracellular, lysosomal collagenolytically active cathepsin K in fibroblasts, macrophages and gingival epithelial cells, can contribute to the loss of attachment and destruction of the periodontal ligament.
Effects of management practices on the welfare of dairy donkeys and risk factors associated with signs of hoof neglect

This Research Paper aimed to investigate donkey welfare in dairy husbandry systems and to identify the potential factors affecting it at animal level. In 2015, twelve dairy donkey farms (19–170 donkeys per farm, mean = 55 ± 48), distributed throughout Italy, were visited. On each farm, the Animal Welfare Indicators (AWIN) welfare assessment protocol for donkeys was used by two trained assessors to evaluate the welfare of animals for a total of 257 donkeys assessed. The protocol includes animal-based indicators that were entered in a digitalised system. Prevalence of different scores at individual, farm and category level were calculated. Farmers were asked to fill out a questionnaire including information regarding the management of donkeys and their final destination. Answers to the questionnaire were then considered as effects in the risk factor analysis whereas the scores of the animal-based indicators were considered as response variables. Most of the donkeys (80·2%) enjoyed a good nutritional status (BCS = 3). 18·7% of donkeys showed signs of hoof neglect such as overgrowth and/or incorrect trimming (Min = 0% Max = 54·5%). Belonging to a given farm or production group influenced many of the welfare indicators. The absence of pasture affected the likelihood of having skin lesions, alopecia, low BCS scores and a less positive emotional state. Lack of routine veterinary visits (P < 0·001) and having neglected hooves (P < 0·001) affected the likelihood of being thin (BCS < 3). Belonging to specific production groups, lack of access to pasture and showing an avoidance reaction to an approaching human (AD) resulted in risk factors associated with a higher prevalence of signs of hoof neglect. Our results support the idea that lack of knowledge of proper donkey care among owners was behind many welfare issues found.
Activated wnt signaling in stroma contributes to development of pancreatic mucinous cystic neoplasms.

BACKGROUND & AIMS Pancreatic mucinous cystic neoplasm (MCN), a cystic tumor of the pancreas that develops most frequently in women, is a potential precursor to pancreatic ductal adenocarcinoma. MCNs develop primarily in the body and tail of the pancreas and are characterized by the presence of a mucinous epithelium and ovarian-like subepithelial stroma. We investigated the involvement of Wnt signaling in KRAS-mediated pancreatic tumorigenesis and development of MCN in mice, and Wnt activation in human MCN samples. METHODS LSL-Kras(G12D), Ptf1a-cre mice were crossed with elastase-tva mice to allow for introduction of genes encoded by the replication-competent avian sarcoma-leukosis virus long-terminal repeat with splice acceptor viruses to pancreatic acinar cells and acinar cell progenitors, postnatally and sporadically. Repeat with splice acceptor viruses that expressed Wnt1 were delivered to the pancreatic epithelium of these mice; pancreatic lesions were analyzed by histopathology and immunohistochemical analyses. We analyzed levels of factors in Wnt signaling pathways in 19 MCN samples from patients. RESULTS Expression of Wnt1 in the pancreatic acinar cells and acinar cell progenitors of female mice led to development of unilocular or multilocular epithelial cysts in the pancreas body and tail, similar to MCN. The cystic lesions resembled the estrogen receptor- and progesterone receptor-positive ovarian-like stroma of MCN, but lacked the typical mucinous epithelium. Activated Wnt signaling, based on nuclear localization of β-catenin, was detected in the stroma but not cyst epithelium. Wnt signaling to β-catenin was found to be activated in MCN samples from patients, within the ovarian-like stroma, consistent with the findings in mice. CONCLUSIONS Based on studies of mice and pancreatic MCN samples from patients, the canonical Wnt signaling pathway becomes activated and promotes development of the ovarian-like stroma to contribute to formation of MCNs.
Parasites of Apollonia melanostoma (Pallas 1814) and Neogobius kessleri (Guenther 1861) (Osteichthyes, Gobiidae) from the Danube River in Austria.

Two invasive fish species, the round goby Apollonia melanostoma syn. Neogobius melanostomus (Pallas 1814) and the bighead goby Neogobius kessleri (Günther, 1861), have established a firm population in Austrian waters during the past 15 years. As there have been no records of the parasite fauna from these populations, a total of 79 specimens of A. melanostoma and 12 specimens of N. kessleri were examined for parasites between May and October 2007 from three different sampling sites from the Danube River in Austria. In total 12 parasite taxa were recovered. The protozoans Trichodina sp. and Ichthyophthirius multifiliis from the gills and skin; two crustacean species, Paraergasilus brevidigitus and Ergasilus sieboldi, from the gills; and the two monogeneans Gyrodactylus sp. and Dactylogyrus sp. , from the skin and gills respectively, all occurred at low prevalence and intensities. Furthermore, cystacanths of the acanthocephalan Acanthocephalus lucii were found in the body cavity. Metacercariae of the digeneans Diplostomum sp. and Tylodelphys clavata were found in the lens of the eye and the vitreous humour, respectively. Adults of two digeneans, Nicolla skrjabini and Bunodera nodulosa, were found in the intestine. In addition, during this survey metacercariae of the Holarctic digenean Bucephalus polymorphus, encysted in the skin and fins, with prevalence up to 78%, were recorded for the first time in Austria.
A length-dependent evolutionarily conserved pathway controls nuclear export of circular RNAs

Here, Huang et al. investigated how circRNA localization or nuclear export is controlled and, using RNAi screening, found that depletion of the Drosophila DExH/D-box helicase Hel25E results in nuclear accumulation of long (>800-nt), but not short, circRNAs. Their findings suggest that the lengths of mature circRNAs are measured to dictate the mode of nuclear export.
Neurobiologie und Altern

Mit dem zweiten Hauptsatz hat Clausius 1865 die Irreversibilitat in der Thermodynamik verankert. Die Zeit wurde damit gerichtet, Vergangenheit und Zukunft waren nicht mehr austauschbar wie in der klassischen Dynamik. Das Altern, der Verfall der Welt, schien damit vorprogrammiert. Ob das zutrifft, ist noch unentschieden, denn Prigogine's dissipative Strukturen zeigen, dal? Irreversibilität nicht nur mit zunehmender Desorganisation einhergeht. Fern vom Gleichgewicht können in chaotischen Systemen dynamische Ordnungsphãnomene auftreten, die selbstorganisierend und nicht voraussagbar sind. So oder so ist Altern aber em Phänomen der Interaktion der Materie und keine biologische Besonderheit. In den hochgeordneten Systemen der Biologie wird es lediglich besonders eindrucksvoll, da die Erhaltung der Ordnung und die an sie gebundene Funktion Energie erfordert, die zeitlich und räumlich kontrolliert verfugbar gemacht werden mu! Dies setzt einen differenzierten und damit fehleranfalligen Metabolismus voraus. In solchen Systemen ist eine rasche Fehlerakkumulation als Funktion der Zeit und damit schnelleres Altern zu erwarten.
Oxidative Damage to Proteins and Lipids During Ageing

Oxidative Damage to Proteins and Lipids During Ageing The present work is a theoretical study in the field of monitoring oxidative damage to proteins and lipids during ageing. The basic terminology and interactions are discussed as well as the sources of oxidants and their elimination through antioxidant protection. We focus on the effects of oxidative stress on the biomolecules (proteins, lipids and DNA), the role of mitochondria, antioxidants, physical activity and caloric restriction in relation to ageing. Previous research indicates the crucial role of mitochondria in the ageing process by their formation of oxidants, the accumulation of oxidative damage to mtDNA and other biomolecules leading to impairment of mitochondrial function, energy failure, apoptosis and necrosis. Although the role of oxidative stress in the ageing process is evident and well documented, the precise mechanisms of its relationships remain largely unknown. Further research is needed to clarify them and to show ways to slow down the ageing process.
Patient-reported outcome measures in recurrent aphthous stomatitis: A critical assessment of quality properties.

OBJECTIVES To analyse the range of existing patient-reported outcome measures (PROMs) used in studies of recurrent aphthous stomatitis (RAS) and to evaluate their quality properties via the assessment of psychometric properties and interpretability. MATERIALS AND METHODS Electronic databases were searched to identify relevant publications related to PROMs used in RAS. Publications were selected based on predefined criteria. All identified PROMs were then classified by measuring concepts and assessed for instrument characteristics and evidence for quality properties for RAS patients. RESULTS Twenty-eight PROMs were used in studies of RAS patients. Instruments focused upon oral symptoms (n = 4), psychosocial status (n = 15) and quality of life (n = 9). Five PROMs (Oral Health-related Quality of Life-UK, Chronic Oral Mucosal Disease Questionnaire, Oral Health Impact Profile-14, Medical Outcome Study Short Form-36 and Mumcu's composite index) were found to have some evidence of psychometric performance. No PROMs showed evidence for interpretability of their scores in RAS patients. CONCLUSION There was a wide range of PROMs used in clinical studies of RAS. The majority of these PROMs lack evidence of measurement properties and interpretability for RAS patients. Further studies are required to confirm whether these instruments are suitable and useful for this patient group.
Morphometric characteristics of the metacestode Echinococcus vogeli Rausch & Bernstein, 1972 in human infections from the northern region of Brazil

Abstract Polycystic echinococcosis, caused by the larval stage (metacestode) of the small-sized tapeworm, Echinococcus vogeli, is an emerging parasitic zoonosis of great public health concern in the humid tropical rainforests of South and Central America. Because morphological and morphometric characteristics of the metacestode are not well known, hydatid cysts from the liver and the mesentery were examined from patients following surgical procedures. Whole mounts of protoscoleces with rostellar hooks were examined under light and confocal laser scanning microscopy. Measurements were made of both large and small hooks, including the total area, total length, total width, blade area, blade length, blade width, handle area, handle length and handle width. The results confirmed the 1:1 arrangement of hooks in the rostellar pad and indicated, for the first time, that the morphometry of large and small rostellar hooks varies depending upon the site of infection. Light and confocal microscopy images displayed clusters of calcareous corpuscles in the protoscoleces. In conclusion, morphological features of large and small rostellar hooks of E. vogeli are adapted to a varied environment within the vertebrate host and such morphological changes in calcareous corpuscles occur at different stages in the maturation of metacestodes.
The Man Who Shocked the World: The Life and Legacy of Stanley Milgram

T he late Stanley Milgram fairly lays claim to be one of the greatest behavioural scientists of the 20th century. He derives his renown from of a series of experiments on obedience to authority, which he conducted at Yale University in 1961-2. Milgram found, surprisingly, that 65% of his subjects, ordinary residents of New Haven, were willing to give apparently harmful electric shocks—up to 450 volts—to a pitifully protesting victim, simply because a scientific, lab coated authority commanded them to, and despite the fact that the victim did nothing to deserve such punishment. The victim was, in reality, a good actor who did not actually receive shocks, a fact that was revealed to the subjects at the end of the experiment. [][1] Thomas Blass Basic Books, £15.50/$26/$C40, pp 360 ISBN 0 7382 0399 8 Due for publication in paperback next month Rating: ! [Graphic][2] ! [Graphic][3] ! [Graphic][4] Milgram's interest in the study of obedience partly emerged out of a deep concern with the suffering of fellow Jews at the hands of the Nazis and an attempt to fathom how the Holocaust … [1]: /embed/graphic-1.gif [2]: /embed/inline-graphic-1.gif [3]: /embed/inline-graphic-2.gif [4]: /embed/inline-graphic-3.gif
Superficial tumors of the gastrointestinal mucosa: the problem of the histological diagnosis of intravascular infiltration in tissues from endoscopic submucosal dissection

Professor of Pathology at Universidade Federal de Minas Gerais-Medical School (UFMG-MS); associate editor of the Brazilian Journal of Pathology and Laboratory Medicine ( Jornal Brasileiro de Patologia e Medicina Laboratorial [JBPML]). Superficial tumors of the gastrointestinal mucosa: the problem of the histological diagnosis of intravascular infiltration in tissues from endoscopic submucosal dissection
Spatial variability of helminth parasites and evidence for stock discrimination in the round sardinella, Sardinella aurita (Valenciennes, 1847), off the coast of Tunisia

Abstract Three digeneans – Parahemiurus merus (Linton, 1910), Aphanurus stossichii (Monticelli, 1891) and Lecithochirium sp. – and one tetraphyllidean cestode larva were used as biological tags to discriminate the stock of Sardinella aurita (Valenciennes, 1847). In total, 579 fish were examined in five zones off the Tunisian coast, including Bizerte and Kelibia in the north, Mahdia in the east, Gabes and Zarzis in the south. Discriminant analyses used for the separation of S. aurita allowed for the identification of two discrete stocks. Sardinella aurita from Bizerte, Kelibia and Zarzis clumped together as a single stock. Parahemiurus merus and A. stossichii were the most important species in determining the location of sampled fish from these regions. Specimens from Mahdia and Gabes were grouped as one stock characterized by the presence of Lecithochirium sp. and larvae of the Tetraphyllidea. These results were corroborated by comparing the parameters of prevalence and mean abundance of parasites among zones. The separation of S. aurita between localities after pooling specimens from Bizerte, Kelibia and Zarzis and separately pooling those from Mahdia and Gabes also allowed the identification of two discrete stocks, one in offshore waters from Bizerte, Kelibia and Zarzis characterized by the digeneans P. merus and A. stossichii and one in inshore waters from Mahdia and Gabes characterized by Lechithochirium sp. and tetraphyllidean larvae.
Absence of capsule reveals glycan-mediated binding and recognition of salivary mucin MUC7 by Streptococcus pneumoniae.

Salivary proteins modulate bacterial colonization in the oral cavity and interact with systemic pathogens that pass through the oropharynx. An interesting example is the opportunistic respiratory pathogen Streptococcus pneumoniae that normally resides in the nasopharynx, but belongs to the greater Mitis group of streptococci, most of which colonize the oral cavity. Streptococcus pneumoniae also expresses a serine-rich repeat (SRR) adhesin, PsrP, which is a homologue to oral Mitis group SRR adhesins, such as Hsa of Streptococcus gordonii and SrpA of Streptococcus sanguinis. As the latter bind to salivary glycoproteins through recognition of terminal sialic acids, we wanted to determine whether S. pneumoniae also binds to salivary proteins through possibly the same mechanism. We found that only a capsule-free mutant of S. pneumoniae TIGR4 binds to salivary proteins, most prominently to mucin MUC7, but that this binding was not mediated through PsrP or recognition of sialic acid. We also found, however, that PsrP is involved in agglutination of human red blood cells (RBCs). After removal of PsrP, an additional previously masked lectin-like adhesin activity mediating agglutination of sialidase-treated RBCs becomes revealed. Using a custom-spotted glycoprotein and neoglycoprotein dot blot array, we identify candidate glycan motifs recognized by PsrP and by the putative S. pneumoniae adhesin that could perhaps be responsible for pneumococcal binding to salivary MUC7 and glycoproteins on RBCs.
Epilepsy in autism spectrum disorders

Epilepsy occurs frequently in individuals with autism spectrum disorders (ASDs). However, the mechanisms responsible for increased seizure susceptibility in ASDs are largely unknown. Clues to neural hyperexcitability in the autistic brain might be derived from disorders in which single gene mutations cause both epilepsy and an autistic phenotype, such as fragile X syndrome. For an expanded treatment of this topic see Jasper’s Basic Mechanisms of the Epilepsies, Fourth Edition (Noebels JL, Avoli M, Rogawski MA, Olsen RW, Delgado‐Escueta AV, eds) published by Oxford University Press (available on the National Library of Medicine Bookshelf [NCBI] at http://www.ncbi.nlm.nih.gov/books).
Analysis of gene expression from the Wolbachia genome of a filarial nematode supports both metabolic and defensive roles within the symbiosis

The α-proteobacterium Wolbachia is probably the most prevalent, vertically transmitted symbiont on Earth. In contrast with its wide distribution in arthropods, Wolbachia is restricted to one family of animal-parasitic nematodes, the Onchocercidae. This includes filarial pathogens such as Onchocerca volvulus, the cause of human onchocerciasis, or river blindness. The symbiosis between filariae and Wolbachia is obligate, although the basis of this dependency is not fully understood. Previous studies suggested that Wolbachia may provision metabolites (e.g., haem, riboflavin, and nucleotides) and/or contribute to immune defense. Importantly, Wolbachia is restricted to somatic tissues in adult male worms, whereas females also harbor bacteria in the germline. We sought to characterize the nature of the symbiosis between Wolbachia and O. ochengi, a bovine parasite representing the closest relative of O. volvulus. First, we sequenced the complete genome of Wolbachia strain wOo, which revealed an inability to synthesize riboflavin de novo. Using RNA-seq, we also generated endobacterial transcriptomes from male soma and female germline. In the soma, transcripts for membrane transport and respiration were up-regulated, while the gonad exhibited enrichment for DNA replication and translation. The most abundant Wolbachia proteins, as determined by geLC-MS, included ligands for mammalian Toll-like receptors. Enzymes involved in nucleotide synthesis were dominant among metabolism-related proteins, whereas the haem biosynthetic pathway was poorly represented. We conclude that Wolbachia may have a mitochondrion-like function in the soma, generating ATP for its host. Moreover, the abundance of immunogenic proteins in wOo suggests a role in diverting the immune system toward an ineffective antibacterial response.
A novel strategy to inhibit FAK and IGF‐1R decreases growth of pancreatic cancer xenografts

Deregulation of insulin‐like growth factor‐1 receptor (IGF‐1R) and focal adhesion kinase (FAK) signaling pathways plays an important role in cancer cell proliferation and metastasis. In pancreatic cancer cells, the crosstalk and compensatory mechanisms between these two pathways reduce the efficacy of the treatments that target only one of the pathways. Ablation of IGF‐1R signaling by siRNA showed minimal effects on the survival and growth of pancreatic cancer cells. An increased activity of FAK pathway was seen in these cells after IGF‐1R knockdown. Further inhibition of FAK pathway using Y15 significantly decreased cell survival, adhesion, and promoted apoptosis. The combination of Y15 treatment and IGF‐1R knockdown also showed significant antitumor effect in vivo. The current study demonstrates the importance of dual inhibition of both these signaling pathways as a novel strategy to decrease both in vitro and in vivo growth of human pancreatic cancer. © 2009 Wiley‐Liss, Inc.
Differences in DNA methylation signatures reveal multiple pathways of progression from adenoma to colorectal cancer.

BACKGROUND & AIMS Genetic and epigenetic alterations contribute to the pathogenesis of colorectal cancer (CRC). There is considerable molecular heterogeneity among colorectal tumors, which appears to arise as polyps progress to cancer. This heterogeneity results in different pathways to tumorigenesis. Although epigenetic and genetic alterations have been detected in conventional tubular adenomas, little is known about how these affect progression to CRC. We compared methylomes of normal colon mucosa, tubular adenomas, and colorectal cancers to determine how epigenetic alterations might contribute to cancer formation. METHODS We conducted genome-wide array-based studies and comprehensive data analyses of aberrantly methylated loci in 41 normal colon tissue, 42 colon adenomas, and 64 cancers using HumanMethylation450 arrays. RESULTS We found genome-wide alterations in DNA methylation in the nontumor colon mucosa and cancers. Three classes of cancers and 2 classes of adenomas were identified based on their DNA methylation patterns. The adenomas separated into classes of high-frequency methylation and low-frequency methylation. Within the high-frequency methylation adenoma class a subset of adenomas had mutant KRAS. Additionally, the high-frequency methylation adenoma class had DNA methylation signatures similar to those of cancers with low or intermediate levels of methylation, and the low-frequency methylation adenoma class had methylation signatures similar to that of nontumor colon tissue. The CpG sites that were differentially methylated in these signatures are located in intragenic and intergenic regions. CONCLUSIONS Genome-wide alterations in DNA methylation occur during early stages of progression of tubular adenomas to cancer. These findings reveal heterogeneity in the pathogenesis of colorectal cancer, even at the adenoma step of the process.