TLR4 signaling in the development of colitis-associated cancer and its possible interplay with microRNA-155

Ulcerative colitis (UC) has closely been associated with an increased risk of colorectal cancer. However, the exact mechanisms underlying colitis-associated cancer (CAC) development remain unclear. As a classic pattern-recognition receptor, Toll like receptor (TLR)4 is a canonical receptor for lipopolysaccharide of Gram-negative bacteria (including two CAC-associated pathogens Fusobacterium nucleatum and Salmonella), and functions as a key bridge molecule linking oncogenic infection to colonic inflammatory and malignant processes. Accumulating studies verified the overexpression of TLR4 in colitis and CAC, and the over-expressed TLR4 might promote colitis-associated tumorigenesis via facilitating cell proliferation, protecting malignant cells against apoptosis, accelerating invasion and metastasis, as well as contributing to the creation of tumor-favouring cellular microenvironment. In recent years, considerable attention has been focused on the regulation of TLR4 signaling in the context of colitis-associated tumorigenesis. MicroRNA (miR)-155 and TLR4 exhibited a similar dynamic expression change during CAC development and shared similar CAC-promoting properties. The available data demonstrated an interplay between TLR4 and miR-155 in the context of different disorders or cell lines. miR-155 could augment TLR4 signaling through targeting negative regulators SOCS1 and SHIP1; and TLR4 activation would induce miR-155 expression via transcriptional and post-transcriptional mechanisms. This possible TLR4-miR-155 positive feedback loop might result in the synergistic accelerating effect of TLR4 and miR-155 on CAC development.

Diabetic Nephropathy: Challenges in Pathogenesis, Diagnosis, and Treatment

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease worldwide. Chronic hyperglycemia and high blood pressure are the main risk factors for the development of DN. In general, screening for microalbuminuria should be performed annually, starting 5 years after diagnosis in type 1 diabetes and at diagnosis and annually thereafter in type 2 diabetes. Standard therapy is blood glucose and blood pressure control using the renin-angiotensin system blockade, targeting A 1 c < 7 % , and <130/80 mmHg. Regression of albuminuria remains an important therapeutic goal. However, there are problems in diagnosis and treatment of nonproteinuric DN (NP-DN), which does not follow the classic pattern of DN. In fact, the prevalence of DN continues to increase, and additional therapy is needed to prevent or ameliorate the condition. In addition to conventional therapies, vitamin D receptor activators, incretin-related drugs, and therapies that target inflammation may also be promising for the prevention of DN progression. This review focuses on the role of inflammation and oxidative stress in the pathogenesis of DN, approaches to diagnosis in classic and NP-DN, and current and emerging therapeutic interventions.

Bed Bugs (Hemiptera: Cimicidae) Population Diversity and First Record of Cimex hemipterus in Paris

Cimex lectularius and C. hemipterus are blood-sucking insects with a long history of presence in human communities. We investigated the molecular diversity of the bed bug population of Paris and its suburb cities using cytochrome oxidase 1 (CO1) sequencing. A total of 1211 specimens belonging to different life stages were collected from 62 infested human dwellings in Paris (13 out of 20 arrondissements) and the surrounding cities (18 cities). Morphological determination and COI sequencing of 132 specimens demonstrated C. lectularius as the predominant species and, surprisingly, the presence of C. hemipterus in four infested areas of Paris and its suburb cities. Neighbor-joining tree and network analyses depicted the presence of two C. lectularius populations. Most samples from Paris and its suburb cities clustered in a major clade. The second population encompasses specimens from Paris (arrondissements 11 and 19) and its suburb cities (e.g., Bobigny, Pantin, and Montreuil) that clustered with Hungary, Czechia, and Finland. This is the second evidence for C. hemipterus infestation in France and the third in Europe, which challenges the classic pattern of C. hemipterus dispersion and implies sympatric occurrence of C. lectularius and C. hemipterus. Since Paris is one of the most popular tourist destinations in the world, our observations shed light on bed bugs’ dispersal dynamic and may help future vector control strategies.

Planning for floods after fires: Lessons from the 2018 Montecito Debris Flow (California)

&lt;p&gt;On January 9, 2018 a series of debris flows killed 23 people and caused over a $1 billion in economic losses in Montecito, Santa Barbara County. The debris flows followed a classic pattern in mountainous areas of southern California: A large wildfire (the 2017 Thomas Fire) burned the headwaters of streams draining the Transverse Ranges southward to the Pacific, creating hydrophobic soil conditions that prevented infiltration of water, resulting in larger runoff during rains. A cell of intense precipitation over Montecito triggered debris flows, affecting areas along the stream channels.&amp;#160;&lt;/p&gt;&lt;p&gt;The 2018 Montecito debris flows raise compelling questions about the role of scientific information in decision making generally, and specifically how hazardous areas along rivers and streams are mapped, how land use is regulated in these zones, and how best to respond in emergency situations.&amp;#160;&lt;/p&gt;&lt;p&gt;This presentation analyzes the evacuation planning process during the emergency management (making emphasis on the maps used by public officials), the recovery planning strategies that the local government adopted after the event, and the evolution of houses in flood hazard areas since the beginning of the 20&lt;sup&gt;th&lt;/sup&gt; century, to highlight the importance of exposure as a key element to reduce risk.&lt;/p&gt;

Phenotypic plasticity, population structure and adaptation in a young weed species with a worldwide distribution

SummaryThe colonization success of a species depends on phenotypic plasticity, adaptive potential and population structure. Assessing their relative contributions during a colonization process is challenging, and a large-scale experiment had yet to be done. In this study, we attempted to tease apart their effects on the fitness of one of the most common plant on Earth, the shepherd’s purse (Capsella bursa-pastoris), a self-fertilizing and allopolyploid weed, with a worldwide distribution. The overarching goal is to eventually understand how the shepherd’s purse extensive distribution range was established so rapidly. To do so, we carried out three common gardens, located in Europe, Asia and North America, and measured several life-history traits on field-collected accessions belonging to three distinct genetic clusters (Middle East, Europe, and Asia). Our experiment showed that (i) the success of C. bursa-pastoris is mainly due to its high degree of phenotypic plasticity; and (ii), genetic cluster effect reflected a classic pattern observed in core vs marginal populations, with the Middle Eastern cluster (putative core population) outperforming the European and Asian clusters. This study therefore revealed, in a model species, different relative contributions of plasticity and adaptation to fitness, depending on the population and the time since colonization occurred.

A VALLÁSOS ATTITŰDÖK KLASSZIFIKÁCIÓJA AZ ÉRTELEMMEGÉLÉS ÉS AZ ASPIRÁCIÓK TÜKRÉBEN

Háttér és célkitűzésekA wulffi elméletet alapul vevő Kritika Utáni Vallásosság skála két dimenzión alapuló kiértékelése (Martos, Kézdy, Robu, Urbán és Horváth-Szabó, 2009) lehetőséget nyújt egy újfajta vallásosságtipológia létrehozására. Kutatásunk célja az volt, hogy a vallás iránti attitűdöket személyorientált statisztikai eljárások segítségével vizsgáljuk annak érdekében, hogy a valláshoz való személyes viszonyulás differenciáltabb típusait tárjuk fel.MódszerHierarchikus agglomeratív és k-központú klaszteranalízist végeztünk el egy 1417 fős és egy 506 fős mintán, majd megbízhatóságát centroid módszerrel és egy újfajta validálási eljárással ellenőriztük (vö. Vargha, Bergman és Takács, 2016), majd a létrejövő klaszterstruktúrákat vizsgáltuk az értelemmegélés és értelemkeresés, valamint az aspirációk tükrében.EredményekAz eredmények szerint azonosítható egy megbízható 7 klaszteres struktúra. A feltárt klasz- terek között megjelent a szakirodalom által sugallt klasszikus négy attitűddel közel azonos mintázat (Ortodoxia, Külső Kritika, Relativizmus, Második Naivitás). Három további típus kimutatása hozzájárult ahhoz, hogy a vallás iránti egyéni viszonyulásokról árnyaltabb képet tárjunk fel.KövetkeztetésekAz Ortodoxia és a Második Naivitás csoportba tartozók kedvezőbb, a Külső Kritika csoportjába tartozók kedvezőtlenebb pontszámot érnek el az értelemmegélés és -keresés, illetve az aspirációk tekintetében. A transzcendencia befogadása az értelmesség megélésének pozitív előrejezője.Based on Wulffs theorem the two dimensional evaluation of the Post Critical belief scale presents a valuable opportunity to create a typology of religious attitudes. The main goal of the research was to explore different types of attitudes towards religiosity in a person-oriented framework. We performed a hierarchical agglomerative and k-means cluster analysis in two distinct samples (one with 1417 and one with 506 participants), and verified the results with centroid-method and a new validation process (Vargha, Bergman & Takács, 2016). Furthermore we examined the relationship between the given cluster structures and the presence of/ searching for meaning in life, and the intrinsic/extrinsic aspirations. The results show that there is a reliable underlying 7-cluster solution in both samples. The explored cluster structures include the classic pattern of religious attitudes (Orthodoxy, External Critique, Relativism, Second Naivité), moreover it expands the model with three additional types. The members of the Orthodoxy and Second Naivité clusters had higher scores, while the External Critique group had lower scores in the given external variables. The inclusion of transcendence is in a positive relationship with presence of meaning in life.

Was facial width-to-height ratio subject to sexual selection pressures? A life course approach

Sexual selection researchers have traditionally focused on adult sex differences; however, the schedule and pattern of sex-specific ontogeny can provide insights unobtainable from an exclusive focus on adults. Recently, it has been debated whether facial width-to-height ratio (fWHR; bi-zygomatic breadth divided by midface height) is a human secondary sexual characteristic (SSC). Here, we review current evidence, then address this debate using ontogenetic evidence, which has been under-explored in fWHR research. Facial measurements collected from males and females aged 3 to 40 (Study 1; US, n=2449), and 7 to 21 (Study 2; Bolivia, n=179) were used to calculate three fWHR variants (which we call fWHRnasion, fWHRstomion, and fWHRbrow) and two other common facial masculinity ratios (facial width-to-lower-face-height ratio, fWHRlower, and cheekbone prominence). We test whether the observed pattern of facial development exhibits patterns indicative of SSCs, i.e. differential adolescent growth in either male or female facial morphology leading to an adult sex difference. Results showed that only fWHRlower exhibited both adult sex differences as well as the classic pattern of ontogeny for SSCs—greater lower-face growth in male adolescents relative to females. fWHRbrow was significantly wider among both pre- and post-pubertal males in the 2D sample; post-hoc analyses revealed that the effect was driven by large sex differences in brow height, with females having higher placed brows than males across ages. In both samples, all fWHR measures were inversely associated with age; that is, human facial growth is characterized by greater relative growth in the mid-face and lower face relative to facial width. This trend continues even into middle adulthood. BMI was also a positive predictor of most of the ratios across ages, with greater BMI associated with wider faces. Researchers collecting data on fWHR should target fWHRlower and fWHRbrow and should control for both age and BMI.

Seroprevalence of anti-SARS-CoV-2 antibodies in COVID-19 patients and healthy volunteers

SARS-CoV-2 has emerged as a novel human pathogen, causing clinical signs, from fever to pneumonia - COVID-19 - but may remain mild or even asymptomatic. To understand the continuing spread of the virus, to detect those who are and were infected, and to follow the immune response longitudinally, reliable and robust assays for SARS-CoV-2 detection and immunological monitoring are needed and have been setup around the world. We quantified immunoglobulin M (IgM), IgG and IgA antibodies recognizing the SARS-CoV-2 receptor-binding domain (RBD) or the Spike (S) protein over a period of five months following COVID-19 disease onset or in previously SARS-CoV-2 PCR-positive volunteers. We report the detailed setup to monitor the humoral immune response from over 300 COVID-19 hospital patients and healthcare workers, 2500 University staff and 187 post-COVID19 volunteers, and assessing titres for IgM, IgG and IgA. Anti-SARS-CoV-2 antibody responses followed a classic pattern with a rapid increase within the first three weeks after symptoms. Although titres reduce from approximately four weeks, the ability to detect SARS-CoV-2 antibodies remained robust for five months in a large proportion of previously virus-positive screened subjects. Our work provides detailed information for the assays used, facilitating further and longitudinal analysis of protective immunity to SARS-CoV-2. Moreover, it highlights a continued level of circulating neutralising antibodies in most people with confirmed SARS-CoV-2, at least up to five months after infection.

Physiological and pathogenic role of scavenger receptors in humans

The scavenger receptors (SRs)) include > 30 different molecules structurally classified into 11 classes (A to L). They are expressed mostly on stromal macrophages, and their expression may be augmented in direct dependence with concentrations of their ligands. The SRs are heterogenous by their structure, however, being common in their functional potential. E.g., different SR classes may participate in absorption of modified low-density lipoproteins and glycated proteins, apoptotic and ageing cells, altered erythrocytes and platelets, like as a big variety of other endogenous ligands from metabolic and cellular “trash”. A common property of SRs is their participation in removal of small pathogen amounts from blood circulation, regulation of cell and tissue stress responses, ability to form complicated receptor complexes with other receptor types including integrins and toll-like receptors. Opposite to classic pattern-recognizing receptors, the SR involvement does not always elicit a pronounced cellular activation and development of pro-inflammatory cellular stress. The SR functional effects provide interactions between different physiological events and immune system, including the processes of neuroendocrine and metabolic regulation. These mechanisms provide both homeostatic stability and, likewise, act at the border of normal and pathological conditions, i.e., participating in pathogenesis of transitional processes, e.g., physiological ageing. Moreover, the SR-associated processes represent a key pathogenetic factor in different somatic diseases, e.g., those associated with low-intensity chronic inflammation, including obesity, type 2 diabetes, atherosclerosis, arterial hypertension, various neurodegenerative disorders. Similarly, the SRs are involved into the processes of cancer transformation and antitumor response, different processes of classical inflammation, from antigen presentation to the morphofunctional T cell and macrophage polarization in the inflammation foci and immunocompetent organs. SR are playing a controversial role in development of acute systemic inflammation, the main reason for lethal outcomes in the intensive care wards. Targeted effects upon the SRs represent a promising approach when treating a broad variety of diseases, whereas detection of membrane-bound and soluble SR forms could be performed by means of diagnostic and monitoring techniques in many human disorders.

‘Van koper blijf je proper, van ijzer wordt je niets wijzer’: klooster Yesse, metaalvondsten uit 2017 en 2018

The Yesse monastery: Metal finds from 2017 and 2018. The female Cistercian monastery at Yesse (1215–1594), situated on what is today the southern edge of city of Groningen (province of Groningen), has recently experienced increased archaeological interest in its history and inhabitants. In addition to ceramic, botanical and zooarchaeological finds, metal objects reflect economic activities as well as activities of daily life which, at first glance, may not present the sobriety of monastic life. On the contrary, they tell of (supra-)regional trade, craftsmanship, metalworking, administrative duties, and the presence of books, that allowed the convent to flourish and become an important economic actor. While the reconstruction of the cloister lay-out on the basis of metal finds is not conclusive, the find locations of specific objects seem to indicate that Yesse followed the classic pattern of Cistercian cloisters, with a secular western side and a religious eastern side.