410 research outputs found
Towards a Conceptualization of Sociomaterial Entanglement
In knowledge representation, socio-technical systems can be modeled
as multiagent systems in which the local knowledge of each individual agent can
be seen as a context. In this paper we propose formal ontologies as a means to
describe the assumptions driving the construction of contexts as local theories and
to enable interoperability among them. In particular, we present two alternative
conceptualizations of the notion of sociomateriality (and entanglement), which
is central in the recent debates on socio-technical systems in the social sciences,
namely critical and agential realism.
We thus start by providing a model of entanglement according to the critical realist
view, representing it as a property of objects that are essentially dependent on
different modules of an already given ontology. We refine then our treatment by
proposing a taxonomy of sociomaterial entanglements that distinguishes between
ontological and epistemological entanglement. In the final section, we discuss the
second perspective, which is more challenging form the point of view of knowledge
representation, and we show that the very distinction of information into
modules can be at least in principle built out of the assumption of an entangled
reality
Relationships and events: towards a general theory of reification and truthmaking.
We propose a novel ontological analysis of relations and relationships based on a re-visitation of a classic problem in the practice of knowledge repre- sentation and conceptual modeling, namely relationship reification. Our idea is that a relation holds in virtue of a relationship's existence. Relationships are therefore truthmakers of relations. In this paper we present a general theory or reification and truthmaking, and discuss the interplay between events and rela- tionships, suggesting that relationships are the focus of events, which emerge from the context (the scene) they occur in
Towards an Ontological Modelling of Preference Relations
Preference relations are intensively studied in Economics,
but they are also approached in AI, Knowledge Representation, and
Conceptual Modelling, as they provide a key concept in a variety of
domains of application. In this paper, we propose an ontological foundation
of preference relations to formalise their essential aspects across
domains. Firstly, we shall discuss what is the ontological status of the
relata of a preference relation. Secondly, we investigate the place of preference
relations within a rich taxonomy of relations (e.g. we ask whether
they are internal or external, essential or contingent, descriptive or nondescriptive
relations). Finally, we provide an ontological modelling of
preference relation as a module of a foundational (or upper) ontology
(viz. OntoUML).
The aim of this paper is to provide a sharable foundational theory of
preference relation that foster interoperability across the heterogeneous
domains of application of preference relations
Molecular Biomarkers of Neovascular Age-Related Macular Degeneration With Incomplete Response to Anti-Vascular Endothelial Growth Factor Treatment.
The standard treatment for neovascular age-related macular degeneration (nAMD) consists of intravitreal anti-vascular endothelial growth factors (VEGF). However, for some patients, even maximal anti-VEGF treatment does not entirely suppress exudative activity. The goal of this study was to identify molecular biomarkers in nAMD with incomplete response to anti-VEGF treatment. Aqueous humor (AH) samples were collected from three groups of patients: 17 patients with nAMD responding incompletely to anti-VEGF (18 eyes), 17 patients affected by nAMD with normal treatment response (21 eyes), and 16 control patients without any retinopathy (16 eyes). Proteomic and multiplex analyses were performed on these samples. Proteomic analyses showed that nAMD patients with incomplete anti-VEGF response displayed an increased inflammatory response, complement activation, cytolysis, protein-lipid complex, and vasculature development pathways. Multiplex analyses revealed a significant increase of soluble vascular cell adhesion molecule-1 (sVCAM-1) [ p = 0.001], interleukin-6 (IL-6) [ p = 0.009], bioactive interleukin-12 (IL-12p40) [ p = 0.03], plasminogen activator inhibitor type 1 (PAI-1) [ p = 0.004], and hepatocyte growth factor (HGF) [ p = 0.004] levels in incomplete responders in comparison to normal responders. Interestingly, the same biomarkers showed a high intercorrelation with r2 values between 0.58 and 0.94. In addition, we confirmed by AlphaLISA the increase of sVCAM-1 [ p < 0.0001] and IL-6 [ p = 0.043] in the incomplete responder group. Incomplete responders in nAMD are associated with activated angiogenic and inflammatory pathways. The residual exudative activity of nAMD despite maximal anti-VEGF treatment may be related to both angiogenic and inflammatory responses requiring specific adjuvant therapy. Data are available via ProteomeXchange with identifier PXD02247
Antenatal Microbial Colonization of Mammalian Gut
The widely accepted dogma of intrauterine sterility and initial colonization of the newborn during birth has been blurred by recent observations of microbial presence in meconium, placenta, and amniotic fluid. Given the importance of a maternal-derived in utero infant seeding, it is crucial to exclude potential environmental or procedural contaminations and to assess fetal colonization before parturition. To this end, we analyzed sterilely collected intestinal tissues, placenta, and amniotic fluid from rodent fetuses and tissues from autoptic human fetuses. Total bacterial DNA was extracted from collected samples and analyzed by Next Generation Sequencing (NGS) techniques using hypervariable 16S ribosomal RNA (rRNA) regions (V3-V4). Colonizing microbes were visualized in situ, using labeled probes targeting 16S ribosomal DNA by fluorescent in situ hybridization. The NGS analysis showed the presence of pioneer microbes in both rat and human intestines as well as in rodent placentas and amniotic fluids. Microbial communities showed fetus- and dam-dependent clustering, confirming the high interindividual variability of commensal microbiota even in the antenatal period. Fluorescent in situ hybridization analysis confirmed the microbes' presence in the lumen of the developing gut. These findings suggest a possible antenatal colonization of the developing mammalian gut
Genome sequences of two Lactococcus garvieae strains isolated from meat
Lactococcus garvieae is an important fish pathogen and an emerging opportunistic human pathogen, as well as a component of natural microbiota in dairy and meat products. We present the first report of genome sequences of L. garvieae I113 and Tac2 strains isolated from a meat source
GUT microbiota change and time of restore in intensive care therapy : a case report
Exposure of gut microbiota to antibiotics can promote antibiotic resistance and development of diseases caused by multi-drug-resistant organisms. Here we present a case of a 54-year-old male patient with a diagnosis of acute cholecystitis with significant biliary duct leakage, admitted to Intensive Care Unit (ICU) due to a septic syndrome after surgery. Fecal microbial population was analyzed by DGGE and Real Time PCR during and after a combined antibiotic therapy and enteral nutritional feeding. Gut microbiota dysbiosis was demonstrated during ICU recovery. After antibiotic therapy discontinuation and the switch to normal diet, microbial gut population gradually increased up to values comparable with those of a healthy subject. Bifidobacterium spp. took longer to re-stabilize, reaching normal value after two weeks. Our case report corroborates the resilient nature of gut microbiota, but points out the long time needed to recover after antibiotic treatment, paving the way to supplementation with key probiotic species
Evaluation of BAFF, APRIL and CD40L in ocrelizumab-treated pwMS and infectious risk
Simple Summary Since B cells have been linked to multiple sclerosis (MS) and its progression as well as T cells, the second-generation anti-CD20 recombinant humanized monoclonal antibody ocrelizumab has been approved for MS treatment. Although ocrelizumab efficiently depletes B cells in peripheral blood, some B cells and CD20 negative plasma cells persist in lymphatic organs, and their survival is regulated by the B-cell-activating factor (BAFF)/a proliferation-inducing ligand (APRIL) system. Moreover, ocrelizumab may result in higher infectious risk. Herein, we investigated plasma BAFF, APRIL and CD40L levels and their relationship with infectious risk in ocrelizumab-treated people with (pw) MS at baseline, at 6 months and at 12 months after starting the treatment, comparing the above-mentioned findings with a control group. At baseline, plasma levels of all three cytokines were higher compared to the control group. In pwMS, the longitudinal assessment showed a significant increase in plasma BAFF levels and a significant reduction in plasma APRIL and CD40L. Moreover, when stratifying pwMS according to the onset of an infectious event during the 12-month follow-up period, significantly higher plasma BAFF levels were found at all time-points in the group with an infectious event than in the group without an infectious event. Hence, BAFF may have a role as a marker of immune dysfunction and infectious risk. Background: The anti-CD20 monoclonal antibody ocrelizumab has been widely employed in the treatment of people with multiple sclerosis (pwMS). However, its B-cell-depleting effect may induce a higher risk of infectious events and alterations in the secretion of B-cell-activating factors, such as BAFF, APRIL and CD40L. Methods: The aim of this study was to investigate plasma BAFF, APRIL and CD40L levels and their relationship with infectious risk in ocrelizumab-treated pwMS at baseline (T0), at 6 months (T6) and at 12 months (T12) after starting the treatment. As a control group, healthy donors (HD) were enrolled too. Results: A total of 38 pwMS and 26 HD were enrolled. At baseline, pwMS showed higher plasma BAFF (p < 0.0001), APRIL (p = 0.0223) and CD40L (p < 0.0001) levels compared to HD. Compared to T0, plasma BAFF levels were significantly increased at both T6 and T12 (p < 0.0001 and p < 0.0001, respectively). Whereas plasma APRIL and CD40L levels were decreased at T12 (p = 0.0003 and p < 0.0001, respectively). When stratifying pwMS according to the development of an infectious event during the 12-month follow-up period in two groups-with (14) and without an infectious event (24)-higher plasma BAFF levels were observed at all time-points; significantly, in the group with an infectious event compared to the group without an infectious event (T0: p < 0.0001, T6: p = 0.0056 and T12: p = 0.0400). Conclusions: BAFF may have a role as a marker of immune dysfunction and of infectious risk
The effect of timing and composition of gestational weight gain in obese pregnant women on infant birth weight: A prospective cohort study.
Introduction: CK2 is a protein kinase implicated in several essential cellular
processes, over-expressed in cancer and described to regulate insulin
signaling cascade. Recently CK2 has been described to negatively regulate
thermogenesis (Shinoda K et al, 2015, Cell Metabolism) and to inhibit
insulin release (Rossi M et al, 2015, PNAS). Nevertheless, the role of CK2
in adipose tissue (AT) and its involvement in human obesity development
and therapy has been poorly investigated.
Methods: Our multi-disciplinary team performed biochemical analysis of
signaling pathways by WB and in vitro kinase activity assays, and glucose
handling studies using glucose uptake assay and IF in adipocyte cultures
and glucose and insulin tolerance test in mice. Moreover we quantify CK2
expression/activity in human AT specimens of 27 obese patients, clinically
characterized, in 12 obese patients underwent relevant weight loss and 11
normal-weight controls.
Results: We proved that CK2 amount and activity were not influenced
by insulin stimulation and that CK2 activity was efficiently inhibited by
specific inhibitors, structurally unrelated. We worked with CX-4945, a
CK2 inhibitor currently used in cancer clinical trials, using the minimal
concentration (2.5 \u192
dM) and pre-treatment time (1hr) able to efficiently
inhibit CK2 activity, avoiding any cytotoxic effect. Pharmacological
inhibition of CK2 did not significantly affect in vitro adipogenic differentiation
or expression profiling of mature adipocytes. Conversely, we
showed that in human and murine adipocytes CK2-inhibition decreases
the insulin-induced glucose uptake by counteracting Akt-signaling and
GLUT4-translocation to the plasma membrane. We compared CK2 expression
and activity in different mouse tissues highlighted that white
skeletal muscle fibres and liver contained the highest quantity of this kinase.
CK2 was expressed more in brown AT than in white AT depots. We
show that CK2 promotes insulin-signaling in mouse AT, liver and skeletal
muscle and that in vivo acute treatment with CX-4945 impairs glucose-
tolerance in mice. Studies in tissues of ob/ob and db/db mice highlights
an up-regulation of CK2 expression and activity only in WAT. CK2
hyper-activation is strongly evident also in SAT and VAT of obese patients
and weight loss obtained by bariatric surgery or hypocaloric diet reverts
CK2 up-regulation to normal level.
Conclusion: We show that CK2 is involved in insulin sensitivity, glucose
handling and remodeling of WAT. Moreover we identify CK2 hyper-activation
as a hallmark of human obesity, suggesting a new potential therapeutic
target for metabolic diseases
Methicillin-Resistant Staphylococcus aureus in Raw Milk : Prevalence, SCCmec Typing, Enterotoxin Characterization, and Antimicrobial Resistance Patterns
Staphylococcus aureus is a known major cause of foodborne illnesses, and raw milk and dairy products are often contaminated by enterotoxigenic and antimicrobial-resistant S. aureus strains. In the present study, 35 S. aureus strains were isolated from 383 raw milk samples collected from various dairy herds in the province of Milan (northern Italy). The isolates were characterized based on their antimicrobial susceptibility patterns and the presence of genes encoding staphylococcal enterotoxins
(sea, seb, sec, sed, and see). About half (45.7%) of the strains were enterotoxigenic, and 37.1% were resistant to at least one of the antimicrobial drugs tested. Seven (20%) of 35 isolates were identified as methicillin-resistant S. aureus (MRSA), and
SCCmec typing performed with a multiplex PCR assay revealed the presence of gene cassettes IV and V, typical of community acquired MRSA, and I and II, characteristic of health care\u2013associated MRSA. The MRSA strains were evaluated for the presence
of the Panton-Valentine leukocidin gene, but this gene was not found. The results of the present study revealed the presence of toxin-producing S. aureus and MRSA strains in raw milk. MRSA and enterotoxigenic S. aureus in dairy farms are an important risk factor for the spread of staphylococcal infections; therefore, further studies are needed to find strategies for monitoring and controlling the presence of S. aureus, especially MRSA, in dairy products
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