Molecular Biology and Clinical Occurrence of Emerging Human Polyomaviruses

Human polyomaviruses (HPyVs) are known to cause benign initial infection at an early age. They have a high prevalence in the population with frequent incidences of reactivation, and pathologic consequences in those who are elderly or immunosuppressed. Thus far 12 HPyV species have been known. The first two HPyVs, JC virus (JCPyV) and BK virus (BKPyV) were described in 1971. They are associated with specific diseases, progressive multifocal leukoencephalopathy (PML) and polyomavirus-associated nephropathy (PVAN), respectively. Since 2007, 10 additional HPyVs have been identified by molecular genetic techniques. Study of the role of these new viruses in human disease is a new challenge in the HPyV area. The Karolinska Institute (KIPyV) and Washington University (WUPyV) viruses were discovered in respiratory secretions of patients with unidentified causes of pneumonia. Other examples of newly found HPyVs are the Merkel cell polyomavirus (MCPyV) in Merkel cell carcinoma (MCC), and trichodysplasia spinulosa-associated polyomavirus (TSPyV) in Trichodysplasia spinulosa (TS), both skin diseases in immunocompromised patients. The potential pathogenicity of the remaining HPyVs awaits assessment. Seroprevalence studies indicate that HPyVs infect 30 to 90% of the general population and are transmitted apparently independently of one another. Thus far, although their modes of transmission have yet to be resolved, HPyVs are frequently detectable at different body sites and in bodily fluids of healthy immunocompetent individuals, including the skin, hair follicles, saliva, urine, feces, and respiratory secretions, and they can also be found in the environment. To investigate their tropism, persistence site, reactivation, transmission route, and contribution to disease, we have developed for KI, WU, MC, and TS polyomaviruses comprehensive diagnostic methods. We studied the occurrence of their DNAs and antibodies to these viruses from birth to death. In our study, using recombinant fusion protein antigens, IgG antibodies were detectable for KIPyV in 55% and for WUPyV in 69%. Rapidly increasing and high IgG seroprevalences showed that KIPyV and WUPyV are acquired early in childhood and supported the notion that these polyomaviruses are widespread. Our results not only suggested the significance of protein conformation in immunoreactivity of VP1, the major capsid protein, but also pointed to the antigenic importance of the minor proteins VP2 and VP3. Among aging individuals, by employment of recombinant virus-like particles (VLPs)as antigens in ELISA, MCPyV and TSPyV IgG seroprevalences were 59.6% and 67.3%. Among 462 pregnant women, MCPyV IgG seroprevalence was 46% and in constitutionally healthy individuals, TSPyV IgG seroprevalence among children was 39% and among adults 70%. In addition, our DNA PCR studies of respiratory specimens indicated exposure to KIPyV and WUPyV, as well as to MCPyV. We observed MCPyV and TSPyV DNAs particularly often in tonsillitis or hypertrophic tonsillar tissues, unlike for KIPyV or WUPyV. MCPyV and TSPyV DNA in the tonsillar biopsies suggested lifelong persistence in lymphoid tissue or mucosa. MCPyV DNA occurred in tonsils more frequently in adults than in children. By contrast, WUPyV DNA was found preferentially in children. MCPyV occurred also in nasal swabs and NPAs, at a frequency similar to that of KIPyV and WUPyV. The tonsil may be an initial site of WUPyV infection and a site of MCPyV persistence. On the other hand, TSPyV PCR positivity of tonsillar samples of individuals with long-term immunity provided evidence of TSPyV persistence in tonsils and suggests lymphoid tissue as a latency site also for this emerging human pathogen. Our results indicated that MCPyV DNA, unlike TSPyV DNA, occurs in low copy numbers in serum in a notable proportion of aging individuals. Whether the enhanced viral replication in our elderly participants is a reflection of waning immune surveillance and is correlated with increased MCC risk deserves further exploration. Furthermore, to investigate the frequency of fetal infections by these new viruses, we sought the KIPyV, WUPyV, and MCPyV DNAs by PCR, from 535 fetal autopsy samples (heart, liver, placenta) from intrauterine fetal deaths (IUFDs), miscarriages, or induced abortions. Examining by PCR 535 fetal autopsy samples and the corresponding pregnant women by serology, we obtained data to rule out vertical transmission of the new polyomaviruses KI, WU, and MC. Our data suggest that none of the three often cause miscarriages or IUFDs, nor are they transmitted to fetuses. By means of new molecular methods several emerging polyomaviruses have been discovered. Although it is still too early to reach a conclusion on this point, it seems apparent that these novel viruses follow the pattern established for the JC and BK polyomaviruses: a mild initial infection at an early age, high prevalence in the general population, lymphoid tissue as a latency site, and pathologic consequences among the immunosuppressed and/or the elderly.Uusien ihmispolyoomavirusten molekyylibiologia ja kliininen esiintyminen Polyoomavirukset ovat pieniä vaipattomia DNA-viruksia, joita tavataan ihmisillä yleisesti. Polyoomavirusten ensi-infektiot ovat usein oireettomia, mutta infektion jälkeen virukset jäävät elimistöön pysyvästi. Reaktivaatiot ja kliiniset ilmentymät ovat yleisiä erityisesti immuunipuutteisilla potilailla ja vanhuksilla. Tällä hetkellä tunnetaan 12 ihmisen polyoomavirusta. Ensimmäiset kaksi, BK ja JC, löydettin vuonna 1971 klassisella virusviljelymenetelmällä. JC-virus aiheuttaa aivosairaus PML:ää (progressiivinen multifokaalinen leukoenkefalopatia) ja BK-virus munuaistautia, polyomavirukseen liittyvä nefropatia. Kymmenen uutta ihmispolyoomavirusta löydettiin moderneilla sekvenointimenetelmillä. Niiden rooli taudinaiheuttajina on tutkimuksen tämän hetkinen haaste. Tässä väitöskirjassa tutkittiin neljää uutta polyoomavirusta: KI-, WU-, Merkelin solu- ja trichodysplasia spinulosa -virukset. KI-polyoomaviruksen (KIV, Karolinska Institutet) löysivät ruotsalaiset tutkijat 2007 nenänielunäytteistä, yhdistetyllä satunnais-PCR- ja massasekvenointimenetelmällä. WU-polyoomaviruksen (WUV, Washington University) löysi puolestaan yhdysvaltalais-australialainen tutkimusryhmä kolmivuotiaalta keuhkokuumepotilaalta. Merkelin solu -virus (MCV) löydettiin 2008, ja sen on osoitettu aiheuttavan syöpää. Virus-DNA:n havaittiin integroituneen useimpien Merkelin solu karsinooma (MCC) potilaiden kromosomistoon. MCC on harvinainen ja erittäin pahanlaatuinen ihon ja limakalvojen syöpätauti, jota esiintyy immuunipuutteisilla ja ikääntyvillä henkilöillä Suomessakin. Elokuussa 2010 julkaistu trichodysplasia spinulosa -polyoomavirus (TSV) löytyi vaikea-asteista ihosairautta sairastavan teini-ikäisen sydämensiirtopotilaan ihosta. Jatkotutkimusten sekä menestyksellisen viruslääkehoidon perusteella voitiin sanoa TSV:n aiheuttaneen kyseisen ihosairauden. Uusien polyoomavirusten mahdollinen taudinaiheuttamiskyky odottaa lisätutkimuksia. Levinneisyysselvitykset osoittavat näiden virusten vasta-aineita löytyvän 30 90%:lla väestöstä, ja virusten DNA:ta löydetään terveidenkin ihmisten kudoksista ja ruumiinnesteistä kuten ihosta, karvatupista, syljestä, virtsasta, ulosteesta, ja hengitystie-eritteistä. Eri polyoomavirustyypit tarttuvat ilmeisesti toisistaan riippumatta. Kaikki nämä uudet virukset näyttävät levinneen maailmanlaajuisesti ja niitä voi myös löytyä ympäristöstä. Olemme kehittäneet KI-, WU-, MC- ja TS-polyoomaviruksia varten kattavan diagnostisen menetelmästön, jolla voidaan tutkia virusten esiintymistä eri kudoksissa, säilymistä, reaktivaatioita, tartuntareittejä ja rooleja sairauksien synnyssä. Havaitsimme MC- ja TS-polyoomavirusten DNA:ta nielurisakudoksissa, toisin kuin KI- ja WU-polyoomavirusten DNA:ta. Osoitimme myös, että MC-polyoomaviruksen DNA:ta esiintyy yleisesti matalina kopiomäärinä ikääntyneiden henkilöiden seeruminäytteissä. Toisaalta, sikiönäytteistä emme löytäneet KI- WU- tai MC-polyoomavirusten DNA:ta, puhuen kohdunsisäistä tartuntaa vastaan. Serologiset tuloksemme tukevat käsitystä, että kaikki nämä polyoomavirukset ovat yleisiä väestössä. Lähitulevaisuus osoittaa missä määrin nämä uudet polyoomavirukset ovat samankaltaisia JC ja BK -virusten kanssa: oireeton ensitartunta nuorella iällä, korkea esiintyvyys väestössä ja vakavia sairauksia immuunipuutteisilla ja iäkkäillä

Effects of Phosphorus on Different Genotypes of Wheat and Canola Differing in P-Efficiency in Acidic Soils of Western Australia

We hypothesized that phosphorus addition would result in plant morphological changes and changes in rhizosphere carboxylates among wheat and canola cultivars in different acidic soils. Concentration of carboxylates in the rhizosphere extracted with 0.2 mM CaCl2, expressed per unit root dry mass. Dry weight of root and shoot were measures after harvest; total root length, and average root diameter were determined using a scanner. Also, the concentration of phosphorus (Colwell P) in rhizosphere and bulk soil was measured using UV-VIS Spectrophotometer. Shoot and root dry mass of wheat and canola increased significantly with increasing P supply. There was significant difference in total root length and average root diameter between treatments and genotypes in both acidic soils. Citrate was the dominant carboxylate in the rhizosphere of wheat genotypes, and malate was the second one. In canola genotypes, concentration of carboxylates in the rhizosphere were at least 10 times higher than rhizosphere of wheat genotypes. Surprisingly, malonate which there was not in the rhizosphere of wheat genotypes, was the most important carboxylate in the rhizosphere of canola genotypes followed by malate and citrate. This study showed there were significant differences between plant P-efficient and non-efficient in acidic soils when we used different level of P

C3: Cross-instance guided Contrastive Clustering

Clustering is the task of gathering similar data samples into clusters without using any predefined labels. It has been widely studied in machine learning literature, and recent advancements in deep learning have revived interest in this field. Contrastive clustering (CC) models are a staple of deep clustering in which positive and negative pairs of each data instance are generated through data augmentation. CC models aim to learn a feature space where instance-level and cluster-level representations of positive pairs are grouped together. Despite improving the SOTA, these algorithms ignore the cross-instance patterns, which carry essential information for improving clustering performance. This increases the false-negative-pair rate of the model while decreasing its true-positive-pair rate. In this paper, we propose a novel contrastive clustering method, Cross-instance guided Contrastive Clustering (C3), that considers the cross-sample relationships to increase the number of positive pairs and mitigate the impact of false negative, noise, and anomaly sample on the learned representation of data. In particular, we define a new loss function that identifies similar instances using the instance-level representation and encourages them to aggregate together. Moreover, we propose a novel weighting method to select negative samples in a more efficient way. Extensive experimental evaluations show that our proposed method can outperform state-of-the-art algorithms on benchmark computer vision datasets: we improve the clustering accuracy by 6.6%, 3.3%, 5.0%, 1.3% and 0.3% on CIFAR-10, CIFAR-100, ImageNet-10, ImageNet-Dogs, and Tiny-ImageNet.Comment: 10 pages, 8 Figures, 1 Table

RNA Viruses in Aquatic Unicellular Eukaryotes

Increasing sequence information indicates that RNA viruses constitute a major fraction of marine virus assemblages. However, only 12 RNA virus species have been described, infecting known host species of marine single-celled eukaryotes. Eight of these use diatoms as hosts, while four are resident in dinoflagellate, raphidophyte, thraustochytrid, or prasinophyte species. Most of these belong to the order Picornavirales, while two are divergent and fall into the families Alvernaviridae and Reoviridae. However, a very recent study has suggested that there is extraordinary diversity in aquatic RNA viromes, describing thousands of viruses, many of which likely use protist hosts. Thus, RNA viruses are expected to play a major ecological role for marine unicellular eukaryotic hosts. In this review, we describe in detail what has to date been discovered concerning viruses with RNA genomes that infect aquatic unicellular eukaryotes

Comparison of two educational methods (slide presentation & using microscope monitoring) in teaching experimental histology

زمینه و هدف: در سال های اخیر استفاده از فناوری های جدید در آموزش بسیار مورد تاکید است. اما تاثیر تغییر روش های آموزشی بر روی فراگیری دانشجویان از دیر باز مورد سوال بوده است. این مطالعه با هدف بررسی تاثیر شیوه آموزشی قدیمی نمایش اسلاید های پروژکتوری و روش نوین استفاده از میکروسکوپ مونیتورینگ بر روی نمره آزمون نهایی درس بافت شناسی عملی دانشجویان رشته پزشکی انجام شده است. روش بررسی: در این مطالعه تجربی تعداد 36 نفر از دانشجویان رشته پزشکی که در کلاس بافت شناسی عملی ثبت نام کرده بودند بطور تصادفی به دو گروه تقسیم شدند. گروه اول با روش سنتی نمایش اسلاید و گروه دوم با استفاده از میکروسکوپ مونیتورینگ مورد آموزش قرار گرفتند. در پایان نیمسال تحصیلی دانشجویان هر دو گروه در آزمون عملی ایستگاهی و یکسان شرکت کردند. سپس نمرات دانشجویان هر دو گروه جمع آوری و با استفاده از آزمون t مستقل آنالیز و مقایسه شدند. یافته ها: میانگین نمره دانشجویان گروه میکروسکوپ مونیتورینگ 39/2±32/14 و نمره گروه نمایش اسلاید 18/2±18/13 بود (05/0P>). نتیجه گیری: داده های حاصل دلالت بر آن دارند که روش های آموزشی پیشرفته تر ممکن است تاثیر زیادی در نمره آزمون نهایی فراگیران نداشته باشد

Prevention of occupational traumas by developing an ergonomic design and modifying farmers’ postures in walnut gardens of Tuyserkan, Iran

Background and Objectives: Occupational traumas are known as work-related disorders, associating with some sorts of factors such as repetitive tasks, body postures, workstations, and hand tools. These traumas cause various problems for both workers and employers. Due to occupational hygiene considerations, problems such as cumulative trauma disorders, occupational trauma, low back pain (LBP), and work-related musculoskeletal disorders should be controlled. In this regard, ergonomic interventions can have efficient outcomes toward controlling occupational traumas. In this study, the focus was on working at some walnut gardens in the city of Tuyserkan in Iran, to reach an ergonomic analysis base, in which hand tools were assessed. The main objective was to develop a new ergonomic design for workers using hand tools. Subjects and Methods: In this cross-sectional study, 19 workers participated and filled out the Nordic Musculoskeletal Questionnaire (NMQ). Their body postures during harvesting walnuts were evaluated by the Ovako Working Posture Analysis System method. Hand tool analysis was also performed by ergonomic risk assessments. Results: The results showed that 15% of the farmers experienced some sorts of trauma during the harvest while using traditional hand tools. The results also emphasized that 61.5% of the workers' body postures should be modified. In addition, according to the NMQ, the most common problems among workers were wrist disorders, LBP, and knees' and shoulders' disorders. Conclusions: Considering experimental data, a new device was developed in which the weight, adjustability, and form of hand tools were modified under ergonomic considerations. The benefits of the new design were confirmed by SOLIDWORKS software. Since this new device helps farmers to decrease extra force exertion in awkward postures, it is expected to improve farmers' condition while using it

A review on using ultrasound for evaluation of pediatric blunt abdominal trauma

This study reviewed the former studies conducted on the usefulness of accuracy of focused assessment withsonography for trauma (FAST) or any plain ultrasonography (US) scan in pediatric blunt abdominal trauma(BAT), to assess its accuracy, sensitivity, specificity, and positive and negative predictive values (PPV and NPV).Searches were conducted using the predefined keywords and Medical Subject Headings (MeSH) terms acrossMEDLINE (PubMed), Scopus, Web of Science, Cochrane Collaboration Library, Embase, ClinicalTrials.gov, Magiran and SID.ir databases. Duplicate publications were excluded; then the titles and abstracts of eligible studies were reviewed for how they report blunt trauma, pediatric patients, and ultrasound modality in their text. Cochrane RevMan version 5.3 was used for the results analysis and assessing the risk of bias in the studies.Out of 923 studies, 902 were excluded, and only 19 articles were included in this review, out of which one wasa randomized clinical trial (RCT), three were cohort studies, two were contrast-enhanced US (CEUS) studies,and 13 were prospective or retrospective descriptive studies. The total population studied in the articles was3454 patients. The results showed that the specificity of US in pediatric BAT was 93%, the sensitivity was 54%,and the PPV in comparison to clinical examination was 73% versus 37%. CEUS protocol achieved 100% in bothsensitivity and specificity analysis. The only RCT study which included about 28% of the studies population alsoreached a sensitivity and specificity of 97% and 98%, respectively using a combinational protocol of clinical examination, laboratory investigation, and US assessment. Ultrasonography does not provide more results than clinical examination, though better PPV results. A combination of follow-up, US examination, and laboratory requests may also have more accurate results. Moreover, a CEUS protocol may reach that goal with an acceptable time-saving outcome, but it needs more studies to be confirmed