Miracle-dz/UniFAR-FTUs huggingface dataset:
Expression of fibroblast activation protein in human pancreatic adenocarcinoma and its clinicopathological significance.

AIM To examine fibroblast activation protein (FAP) expression in pancreatic ductal adenocarcinoma (PDAC) and to analyze its relationship with the clinicopathology of PDAC. METHODS FAP expression was examined in 134 PDAC specimens by immunohistochemistry, and in four pancreatic cancer cell lines (SW1990, Miapaca-2, AsPC-1 and BxPC-3) by Western blotting assay. We also analyzed the association between FAP expression in PDAC cells and the clinicopathology of PDAC patients. RESULTS The results showed that the FAP was ex-pressed in both stromal fibroblast cells (98/134, 73.1%) and carcinoma cells (102/134, 76.1%). All 4 pancreatic cancer cell lines expressed FAP protein at different levels. Protein bands corresponding to the proteolytically active 170-kDa seprase dimer and its 88-kDa seprase subunit were identified. Higher FAP expression in carcinoma cells was associated with tumor size (P < 0.001), fibrotic focus (P = 0.003), perineural invasion (P = 0.009) and worse clinical outcome (P = 0.0085). CONCLUSION FAP is highly expressed in carcinoma cells and fibroblasts in PDAC tissues, and its expression is associated with desmoplasia and worse prognosis.
Identification of anthraquinone coloring matters in natural red dyes by electrospray mass spectrometry coupled to capillary electrophoresis.

Capillary electrophoresis with UV/visible diode-array detection (DAD) and electrospray mass spectrometric (ESI-MS) detection were used for the identification of anthraquinone color components of cochineal, lac-dye and madder, natural red dyestuffs often used by ancient painters. For the purpose of such analysis, ESI-MS was found to be a much more appropriate detection technique than DAD one owing to its higher sensitivity (detection limits in the range 0.1-0.5 micro g ml(-1)) and selectivity. The method developed made it possible to identify unequivocally carminic acid and laccaic acids A, B and E as coloring matters in the examined preparations of cochineal and lac-dye, respectively. In madder, European Rubia tinctorum, alizarin and purpurin were found. The method allows the rapid, direct and straightforward identification and quantification of components of natural products used in art and could be very helpful in restoration and conservation procedures.
Intended or unintended consequences? The likely implications of raising the bar for sexual dysfunction diagnosis in the proposed DSM-V revisions: 1. For women with incomplete loss of desire or sexual receptivity.

INTRODUCTION Combining female sexual desire and arousal disorders is proposed for the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). Brotto et al. challenged our findings that the proposed criteria could potentially exclude from diagnosis or treatment a large number of women with distressing loss of function or in sexual desire, because (i) our samples were insufficiently severe; (ii) we sought to retain the current diagnostic criteria, whereas they contend that "the bar should be raised"; and (iii) the current sexual function diagnostic criteria are unreliable. AIM Here we provide additional data to support our view suggesting that the proposed criteria would potentially exclude large numbers of women from diagnosis or treatment if they have moderate-to-marked (rather than severe) hypoactive sexual desire disorder (HSDD), or HSDD with incomplete loss of receptivity. METHODS In nontreatment validation studies of 481 women in North America and Europe, 231 women diagnosed with HSDD only were compared to women with no female sexual desire. MAIN OUTCOME MEASURES Clinicians experienced in sexual medicine determined the severity of HSDD using the standard Clinical Global Impression of Severity. Rating scale data were also used, including the clinician-rated Sexual Desire and Interest Inventory-Female and the self-rated Female Sexual Function Index, Changes in Sexual Functioning Questionnaire, Female Sexual Distress Scale, and an e-Diary about desire during sexual events. RESULTS The severity of the HSDD was rated by clinicians as generally moderate-to-marked, not mild. The women with HSDD scored as manifestly sexually dysfunctional and significantly sexually distressed, and reported markedly fewer satisfying sexual events compared to age-matched, non-dysfunctional controls, even for those with moderate or milder degrees of severity, providing compelling evidence that our sample of women with HSDD had clinically disordered sexual function. Yet the proposed criteria would apparently allow diagnosis (and therefore treatment) of only severe desire dysfunction. CONCLUSION It would be counterproductive to combine the two disorders, to make individual criteria for the disorders more stringent or to require more such criteria for a diagnosis because such disorders tend to be distinct in presentation, in treatability with currently available therapies, and in logical approaches to be tested to improve therapy.
The Microbiome of Seriola lalandi of Wild and Aquaculture Origin Reveals Differences in Composition and Potential Function

Seriola lalandi is an economically important species that is globally distributed in temperate and subtropical marine waters. Aquaculture production of this species has had problems associated with intensive fish farming, such as disease outbreaks or nutritional deficiencies causing high mortalities. Intestinal microbiota has been involved in many processes that benefit the host, such as disease control, stimulation of the immune response, and the promotion of nutrient metabolism, among others. However, little is known about the potential functionality of the microbiota and the differences in the composition between wild and aquacultured fish. Here, we assayed the V4-region of the 16S rRNA gene using high-throughput sequencing. Our results showed that there are significant differences between S. lalandi of wild and aquaculture origin (ANOSIM and PERMANOVA, P < 0.05). At the genus level, a total of 13 genera were differentially represented between the two groups, all of which have been described as beneficial microorganisms that have an antagonistic effect against pathogenic bacteria, improve immunological parameters and growth performance, and contribute to nutrition. Additionally, the changes in the presumptive functions of the intestinal microbiota of yellowtail were examined by predicting the metagenomes using PICRUSt. The most abundant functional categories were those corresponding to the metabolism of cofactors and vitamins, amino acid metabolism and carbohydrate metabolism, revealing differences in the contribution of the microbiota depending on the origin of the animals. To our knowledge, this is the first study to characterize and compare the intestinal microbiota of S. lalandi of wild and aquaculture origin using high-throughput sequencing.
Tandem Arrangement of the Clathrin and AP-2 Binding Domains in Amphiphysin 1 and Disruption of Clathrin Coat Function by Amphiphysin Fragments Comprising These Sites*

Amphiphysin 1 and 2 are proteins implicated in the recycling of synaptic vesicles in nerve terminals. They interact with dynamin and synaptojanin via their COOH-terminal SH3 domain, whereas their central regions contain binding sites for clathrin and for the clathrin adaptor AP-2. We have defined here amino acids of amphiphysin 1 crucial for binding to AP-2 and clathrin. Overexpression in Chinese hamster ovary cells of an amphiphysin 1 fragment that binds both AP-2 and clathrin resulted in a segregation of clathrin, which acquired a diffuse distribution, from AP-2, which accumulated at patches also positive for Eps15. These effects correlated with a block in clathrin-mediated endocytosis. A fragment selectively interacting with clathrin produced a similar effect. These results can be explained by the binding of amphiphysin to the NH2-terminal domain of clathrin and by a competition with the binding of this domain to the β-subunit of AP-2 and AP180. The interaction of amphiphysin 1 with either clathrin or AP-2 did not prevent its interaction with dynamin, supporting the existence of tertiary complexes between these proteins. Together with previous evidence indicating a direct interaction between amphiphysin and membrane lipids, these findings support a model in which amphiphysin acts as a multifunctional adaptor linking the membrane to coat proteins and coat proteins to dynamin and synaptojanin.
Cerebral vasomotor paralysis produced by intracranial hypertension

THE SIGNS and symptoms of increased intracranial pressure and cerebral compression have occupied the interest of numerous investigators since earliest times. Although changes in vital signs in response to alterations in intracranial dynamics have long been recognized, the importance of these changes in the diagnosis and management of patients with expanding intracranial lesions has been questioned. In particular, the arterial hypertension which is readily produced experimentally by increased intracranial pressure has been considered to be of limited clinical significance because it has been assumed that blood pressure does not increase until the intracranial pressure approaches the diastolic pressure and that this rarely occurs. This conclusion was based primarily on periodic recording of the lumbar subarachnoid pressnre and thus requires the additional assumption that the spinal fluid pressure at all times approximates the intracranial pressure. In a previous report we presented experimental evidence that obstruction at the tentorial incisura during expansion of a supratentorial mass prevents communication of pressure to the posterior fossa and spinal cana1.l Also, as the pressure gradient across the incisura increases, the vasopressor threshold decreases, and arterial hypertension may then occur, with absolute intracranial pressures far below the diastolic pressure. The first purpose of the present experiments was to extend these observations in an attempt to determine the sequence of events which ultimately lead to neurological deterioration and death during gradual expansion of an intracranial mass lesion. The history of the investigation of cerebral compression before 1900 was reviewed by
Biochemical and Structural Studies of a HECT-like Ubiquitin Ligase from Escherichia coli O157:H7*

Many microbial pathogens deliver effector proteins via the type III secretion system into infected host cells. Elucidating the function of these effectors is essential for our understanding of pathogenesis. Here, we describe biochemical and structural characterization of an effector protein (NleL) from Escherichia coli O157:H7, a widespread pathogen causing severe foodborne diseases. We show that NleL functionally and structurally mimics eukaryotic HECT E3 ligases and catalyzes formation of unanchored polyubiquitin chains using Lys6 and Lys48 linkage. The catalytic cysteine residue forms a thioester intermediate with ubiquitin. The structure of NleL contains two domains, a β-helix domain formed by pentapeptide repeats and a bilobed catalytic domain reminiscent of the N- and C-lobe architecture of HECT E3s. Six structures of NleL observed in two crystal forms revealed a large range of different positions of the C-lobe relative to the N-lobe, indicating that the helix linking the two lobes is extremely flexible. Comparing the structure of NleL with that of the Salmonella homolog SopA showed that the orientation of the C-lobes differ by as much as 108°, suggesting that large movements of the C-lobe may be required to facilitate the transfer of ubiquitin from E2 to the substrate. These results provide critical knowledge toward understanding the molecular mechanism by which pathogens utilize the host ubiquitination system during infection.
Neurocognitive impairment in euthymic young adults with bipolar spectrum disorder and recurrent major depressive disorder.

OBJECTIVE Patients with remitted major depressive disorder (MDD) and bipolar disorder have persistent impairments in executive function and verbal memory that may represent endophenotypic abnormalities. In this study, we examine neurocognitive function in a sample of euthymic young adults with bipolar spectrum disorder (BSD) (Can J Psychiatry 2002; 47: 125-134) and compare this to well-matched samples of young adults with recurrent MDD and controls. METHOD Twenty-one euthymic young adult patients with BSD were compared with 42 young adult patients with MDD and 33 controls on a neuropsychological battery assessing attention, executive function and verbal memory. RESULTS Patients with BSD were significantly more impaired than MDD patients and controls on tests of executive function and verbal memory. MDD patients did not differ significantly from controls on verbal memory function but performed less well on a test of executive function. CONCLUSION Euthymic young adults with BSD had greater impairment on neurocognitive measures associated with prefrontal and hippocampal function than MDD patients and controls. This is a reflection of a strong bipolar diathesis in the BSD group rather than being a consequence of a more severe unipolar illness.
Comparative expressed sequence hybridization reveals differential gene expression in morphological breast cancer subtypes

In this study, comparative expressed sequence hybridization (CESH) has been used to compare gene expression patterns in three morphologically different breast cancer subtypes: classic‐type invasive lobular carcinoma (ILC), poorly differentiated ERBB2‐negative invasive ductal carcinoma‐not otherwise specified (IDC‐NOS), and poorly differentiated ERBB2‐positive IDC‐NOS. CESH allows global detection of chromosomal regions with differential gene expression in a way similar to that of comparative genomic hybridization (CGH). Eight cases of each breast cancer subtype were included in the study. For each subtype, two pools of four cases each were constructed. CESH was used to compare both pools within the same morphological subtype, followed by a comparison of pools belonging to different subtypes. This revealed three chromosomal regions that were differentially expressed in ductal and lobular carcinomas, including relative overexpression at 8q13–q23 and 16q22, and relative underexpression at 8p21–p22. In addition, an expression signature characterized by relative overexpression at 3q24–q26.3, 14q23–31, 17q12, and 20q12–13 was identified for ERBB2‐positive IDC‐NOS. In summary, CESH analysis highlights chromosomal regions of differential gene expression that are associated with morphologically defined breast cancer subtypes and suggests that regions on chromosome 8 are of interest in the discrimination between ductal and lobular carcinomas. In addition, using CESH, it was possible to identify an ERBB2 expression signature, comprising four chromosomal regions with potential significance in the aggressive behaviour of ERBB2‐positive IDC‐NOS. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
When the treatment goal is not cure: are cancer patients equipped to make informed decisions?

PURPOSE Informed decision making now is considered the underpinning of ethical medical practice. We aimed to determine the extent to which patients with incurable cancer are adequately informed of their prognosis and treatment options and encouraged to participate in treatment decisions. PATIENTS AND METHODS One hundred eighteen cancer patients with incurable disease presenting for an initial consultation with one of nine oncologists at two Sydney tertiary referral hospitals participated in the study. Consultations were recorded on audiotape to permit a content analysis of doctor-patient interactions. We devised a coding system to assess disclosure of information and to evaluate doctor encouragement of patient participation in treatment decision making. Patient recall, satisfaction, anxiety, and perceptions of the decision-making process were assessed to determine the effects of informed decision making on patient outcomes. RESULTS Most patients were informed about the aim of anticancer treatment (84.7%), that their disease was incurable (74.6%), and about life expectancy (57.6%). An alternative to anticancer treatments was presented to 44.1%, 36.4% were informed about how anticancer treatment would affect quality of life, and 29.7% were offered a management choice. Oncologists checked patient understanding in only 10.2% of consultations. Although greater information disclosure did not seem to elevate anxiety levels, greater patient participation in the decision-making process was associated with increased anxiety levels (P =.0005), which persisted over a 2-week time span. CONCLUSION Most patients were well informed, but important gaps remain, especially concerning information about prognosis and alternatives to anticancer treatment. These gaps invite the question concerning whether patients are led toward anticancer treatment.
γ‐Aminobutyric acid is present in a spatially discrete subpopulation of hair cells in the crista ampullaris of the toadfish Opsanus tau

Although γ‐aminobutyric acid (GABA) and glutamate are known to be present in the vestibular sensory epithelia of a variety of species, the functional relationship between these two transmitters is not clear. The present study addresses the three‐dimensional spatial distribution of GABA and glutamate immunoreactivity in the vestibular labyrinth of the oyster toadfish by using whole end organs labeled by immunofluorescence with monoclonal anti‐GABA and/or antiglutamate antibodies and visualized as whole mounts by multiphoton confocal microscopy. We find glutamate‐immunoreactive hair cells present throughout the sensory epithelium. In contrast, prominent GABA immunoreactivity is restricted to a small population of hair cells located in the central region of the crista. Double immunofluorescence reveals two distinct staining patterns in GABA‐labeled hair cells. Most (∼80%) GABA‐labeled cells show trace levels of glutamate, appropriate for the metabolic/synthetic role of cytoplasmic glutamate. The remainder of the GABA‐stained cells contain substantial levels of both GABA and glutamate, suggesting transmitter colocalization. In the toadfish utricle, glutamatergic hair cells are present throughout the macula. GABA‐immunoreactive hair cells follow the arc of the striola, and most GABA‐labeled receptor cells coexpress glutamate. The localization of GABA was explored in other species as well. In the pigeon, GABAergic hair cells are present throughout the crista ampullaris. Our findings demonstrate that multiple, neurochemically distinct types of hair cells are present in vestibular sensory epithelia. These observations, together with the excitatory activity generally associated with 8th nerve afferent fibers, strongly suggest that GABA serves an important, specific, and complex role in determining primary afferent response dynamics. J. Comp. Neurol. 471:1–10, 2004. © 2004 Wiley‐Liss, Inc.
Long-term Follow-up of Open Reduction Surgery for Developmental Dislocation of the Hip

Background: We posed 2 questions: what is the long-term result of open reduction surgery in developmental dysplasia of the hip, and is there an age at surgery above which the outcome was too poor to recommend the operation? Methods: Between 1955 and 1995, 148 patients with 179 dislocated hips had open reduction surgery for developmental dysplasia of the hip (141 anterior and 38 Ludloff medial approaches). We attempted to locate all 148 patients for the follow-up evaluation. Results: Fifty-three patients (36%) with 66 hips (37%) were located and participated in the study. These 66 hips represented 34% of the anterior open reductions and 47% of the Ludloff medial reductions. Twenty-two of the 66 hips had Severin IV or worse outcomes and included 7 with total hip arthroplasties and 2 with hip fusions. Age at surgery was significantly lower for Severin I, II, and III, compared with Severin IV and above (P=0.003, 0.001, 0.003) with outcomes deteriorating substantially after age 3. Approximately half of the hips required further surgery for dysplasia. All hips that sustained osseous necrosis had Severin IV or worse outcomes, and hips that redislocated and required revision surgery only achieved Severin I or II ratings 18% of the time. Nine “normal” hips became dysplastic and 3 had pelvic osteotomies as teenagers. Two other normal hips developed osseous necrosis during treatment of the contralateral hip. Conclusions: Results deteriorate as the age at surgery increases. Osseous necrosis and redislocation predict a poor functional and radiographic result. The “normal” hip may develop insidious dysplasia and also may be injured during treatment of the involved hip. Above age 3, some patients may not have sufficient acetabular growth to remodel a surgically reduced hip. Level of Evidence: Level IV—case series.
Specific cognitive deficits in tests sensitive to frontal lobe dysfunction in obsessive–compulsive disorder

Synopsis Forty patients with obsessive–compulsive disorder (OCD) were compared to matched healthy controls on neuropsychological tests which are sensitive to frontal lobe dysfunction. On a computerized version of the Tower of London test of planning, the patients were no different from healthy controls in the accuracy of their solutions. However, when they made a mistake, they spent more time than the controls in generating alternative solutions or checking that the next move would be correct. The results suggest that OCD patients have a selective deficit in generating alternative strategies when they make a mistake. In a separate attentional set-shifting task, OCD patients were impaired in a simple discrimination learning task and showed a continuous cumulative increase in the number who failed at each stage of the task, including the crucial extra-dimensional set shifting stage. This suggests that OCD patients show deficits in both acquiring and maintaining cognitive sets. The cognitive deficits in OCD may be summarized as: (i) being easily distracted by other competing stimuli; (ii) excessive monitoring and checking of the response to ensure a mistake does not occur; and (iii) when a mistake does occur, being more rigid at setting aside the main goal and planning the necessary subgoals. Both studies support the evidence of fronto-striatal dysfunction in OCD and the results are discussed in terms of an impaired Supervisory Attentional System.
Optical probes based on G protein‐coupled receptors – added work or added value?

In 2003, the first report was published that presented proof of principle for a novel class of FRET biosensors for use in living cells. This novel sensor class was built on the base of GPCRs, which represent an integral transmembrane receptor family passing the membrane seven times and are thus also called the 7TM receptor family. As an estimated number of 30% of all marketed drugs exert their effects by modulating GPCR function, these initial reports promised the gain of novel insights into receptor function. Such FRET sensors have slowly, but progressively, made their way into the standard toolbox for GPCR research as several groups are now reporting on the generation and use of these sensors. By now, FRET sensors have been reported for 18 different GPCRs, and more are expected to be added. These particular receptor sensors have been used to investigate receptor dynamics in living cells to evaluate ligand binding and ligand efficacy in real time, to study voltage and mechanosensitivity of GPCRs or to study the influence of receptor polymorphisms on receptor function in real‐time. In this review we will describe the different design principles of these GPCR‐based sensors and will summarize their current biological applications in living cells.