Analysis of RNAs and Proteins of Rotaviruses With Rearranged Genomes: A Study of Molecular Variability

Genome heterogeneity among cocirculating human rotaviruses (hrv) has been described in different parts of the world and in this project was exemplified by a small collection of 100 specimens collected from infected children in Britain between 1975 and 1983. Pedley et al. (1984) described protracted hrv infections and virus shedding in children who suffered from severe combined immunodeficiency (SCID). The viruses isolated from the children showed abnormal genomes carrying extra bands of dsRNA which were found to have arisen by rearrangement of normal RNA segments to covalently linked concatemers. Rotaviruses with similar genomes were obtained after serial passage in-vitro at high m.o.i.: Hundley et al. (1985) isolated mutants D, A4, B4 and B5 of bovine rotavirus (brv) whose genomes had lost RNA segment 5 and instead carried additional RNA bands A-H. The main part of the project was to further characterise these mutants. The additional RNA bands migrated between genomic segments 1 and 7, and were not integral multiples c segment 5 length. Further characterisation by RNase T1 oligonucleotide mapping (Follett and Desselberger, 1983b) showed that band A of brv mutant D (Hundley et al., 1985) and band E of brv mutant A4 (this thesis) consisted of segment 5-related sequences. The brv mutants D, A4, B4 and B5 were not replication-defective as they could be passaged through multiple rounds of plaque-to-plaque purification without requiring parent virus (standard brv). Reduction in the degree of genome transcription and replication, plaque formation, suppression of host cell protein synthesis and development of CPE was observed in cells infected with the brv mutants A4, B4 and B5 when compared to standard brv. However, brv mutant D was similar to standard brv in all these parameters. Standard brv and the brv mutants grew to different titres at 3

Cancer after solid organ transplantation : incidence, risk factors, and survival

Background: Solid organ transplant recipients (OTRs) are at increased risk of cancer compared with the general population, mainly due to post-transplant immunosuppressive treatment. Furthermore, once diagnosed with cancer, OTRs might experience worse cancerspecific and overall survival than non-transplanted cancer patients. Colorectal cancer (CRC), one of the most commonly occurring cancers in the general population, has often been associated with an even higher incidence after organ transplantation. Its relatively high posttransplantation frequency enables epidemiological research with comparatively high statistical power on e.g. differences in cancer characteristics and treatment associated with transplantation. The aims of the present thesis were to estimate relative and absolute (including excess) risks of a wide range of cancers among Nordic kidney transplant recipients (KTRs), compared with the general population (Study I); to investigate differences in cancerspecific survival among OTRs with cancer, compared with non-transplanted cancer patients, for different types of cancer (Study II); and to establish the influence of organ transplantation on various cancer characteristics, as well as on cancer treatment and outcomes, among Swedish CRC patients (Study III). Materials and methods: In Study I, Nordic national patient, cancer, cause of death, kidney, and transplantation registers were used to identify all recipients of a kidney transplant during 1995 through 2011, as well as corresponding patient and donor characteristics possibly associated with cancer risk. Standardized incidence ratios (SIR), cumulative incidence in the presence of competing events, and absolute excess risks of cancer were calculated. Risk factors for cancer were studied using Cox regression. In Study II, the Swedish national cancer register was used to identify all Swedish cancer patients with a first cancer diagnosis during 1992 through 2013. Data on patient, cancer, and cause of death characteristics were obtained through linkage with the national cancer and cause of death registers. Cox regression was used to estimate hazard ratios for cancer-specific and all-cause death, comparing cancer patients with a history of solid organ transplantation to those without. In Study III, the Swedish register linkage database CRCBaSe was used to identify all Swedish CRC patients with a history of solid organ transplantation prior to first CRC. Five non-transplanted CRC patients were matched to each OTR. Logistic and multinomial regression was used to evaluate the impact of transplantation on cancer characteristics and treatment, and Cox regression was used to estimate rates of cancer-specific and all-cause death depending on previous organ transplantation. Results: Among 12,984 Nordic KTRs included in Study I, increased incidence rates (compared with the general population) were found for a wide range of cancers, especially infection-related cancer types such as non-melanoma skin cancer (NMSC), lip, oral and nasal cancers, male and female external genital cancer, and non-Hodgkin lymphoma. However, excluding NMSC, absolute risks were generally higher for non-infection-related cancers (which were often associated with moderately increased rates), such as lung and kidney cancer. Accounting for the competing event of death, the five-year cumulative incidence of cancer was 8%. In Study II, the rate of cancer-specific death was 1.35-fold increased among 2,143 cancer patients with a history of organ transplantation, compared with 946,089 nontransplanted cancer patients. Specifically, lymphoma, malignant melanoma, and urothelial, breast, head/neck, and colorectal cancers were associated with increased cancer-specific death rates among OTRs, compared with non-OTRs. Study III included 99 OTRs and 491 matched non-OTR comparators with CRC. Transplantation history was associated with lower odds of receiving treatment with abdominal surgery, neoadjuvant radiation for rectal cancer, and adjuvant therapy for colon cancer. Cancer-specific and overall survival, as well as disease-free survival, was lower among the OTRs than among the non-OTRs. Conclusions: Nordic KTRs are at increased risk of developing a wide range of cancers posttransplant, both in relative and absolute terms. Once diagnosed with cancer, OTRs with cancer had worse cancer-specific prognosis, both overall and for several specific cancer types, than non-transplanted cancer patients. Among CRC patients, previous transplantation was associated with differences in both treatment and outcomes. These findings should be considered when evaluating Nordic post-transplant cancer screening protocols, and support holding multidisciplinary team conferences, including organ transplant specialists, for posttransplantation cancer care

Chemical composition of 90 F and G disk dwarfs

High resolution, high S/N spectra have been obtained for a sample of 90 F and G main-sequence disk stars covering the metallicity range -1.0 < [Fe/H] < +0.1, and have been analysed in a parallel way to the work of Edvardsson et al. (1993). Effective temperatures are based on the Alonso et al. (1996) calibration of color indices and surface gravities are calculated from Hipparcos parallaxes, which also allow more accurate ages to be calculated. In addition, more reliable kinematical parameters are derived from Hipparcos distances and proper motions. Finally, a larger spectral coverage, 5600 - 8800 A, makes it possible to improve the abundance accuracy by studying more lines and to discuss several elements not included in the work of Edvardsson et al. The present paper provides the data and discusses some general results of the abundance survey. A group of stars in the metallicity range of -1.0 < [Fe/H] < -0.6 having a small mean Galactocentric distance in the stellar orbits, Rm < 7 kpc, are shown to be older than the other disk stars and probably belong to the thick disk. Excluding these stars, a slight decreasing trend of [Fe/H] with increasing Rm and age is found, but a large scatter in [Fe/H] (up to 0.5 dex) is present at a given age and Rm. The derived trends of O, Mg, Si, Ca, Ti, Ni and Ba as a function of [Fe/H] agree rather well with those of Edvardsson et al., but the overabundance of Na and Al for metal-poor stars found in their work is not confirmed. Furthermore, the Galactic evolution of elements not included in Edvardsson et al., K, V and Cr, is studied.Comment: 16 pages with 10 figures. Accepted for publication in A&A

In-Hand Object Stabilization by Independent Finger Control

Grip control during robotic in-hand manipulation is usually modeled as part of a monolithic task, relying on complex controllers specialized for specific situations. Such approaches do not generalize well and are difficult to apply to novel manipulation tasks. Here, we propose a modular object stabilization method based on a proposition that explains how humans achieve grasp stability. In this bio-mimetic approach, independent tactile grip stabilization controllers ensure that slip does not occur locally at the engaged robot fingers. Such local slip is predicted from the tactile signals of each fingertip sensor i.e., BioTac and BioTac SP by Syntouch. We show that stable grasps emerge without any form of central communication when such independent controllers are engaged in the control of multi-digit robotic hands. These grasps are resistant to external perturbations while being capable of stabilizing a large variety of objects.Comment: Submitted to IEEE Transactions on Robotics Journal. arXiv admin note: text overlap with arXiv:1612.0820

Neurohypophyseal hormones and skeletal muscle: a tale of two faces

The neurohypophyseal hormones vasopressin and oxytocin were invested, in recent years, with novel functions upon striated muscle, regulating its differentiation, trophism, and homeostasis. Recent studies highlight that these hormones not only target skeletal muscle but represent novel myokines. We discuss the possibility of exploiting the muscle hypertrophying activity of oxytocin to revert muscle atrophy, including cancer cachexia muscle wasting. Furthermore, the role of oxytocin in cardiac homeostasis and the possible role of cardiac atrophy as a concause of death in cachectic patients is discussed

The mechanical stimulation of myotubes counteracts the effects of tumor-derived factors through the modulation of the activin/follistatin ratio

Activin negatively affects muscle fibers and progenitor cells in aging (sarcopenia) and in chronic diseases characterized by severe muscle wasting (cachexia). High circulating activin levels predict poor survival in cancer patients. However, the relative impact of activin in mediating muscle atrophy and hampered homeostasis is still unknown. To directly assess the involvement of activin, and its physiological inhibitor follistatin, in cancer-induced muscle atrophy, we cultured C2C12 myotubes in the absence or in the presence of a mechanical stretching stimulus and in the absence or presence of C26 tumor-derived factors (CM), so as to mimic the mechanical stimulation of exercise and cancer cachexia, respectively. We found that CM induces activin release by myotubes, further exacerbating the negative effects of tumor-derived factors. In addition, mechanical stimulation is sufficient to counteract the adverse tumor-induced effects on muscle cells, in association with an increased follistatin/activin ratio in the cell culture medium, indicating that myotubes actively release follistatin upon stretching. Recombinant follistatin counteracts tumor effects on myotubes exclusively by rescuing fusion index, suggesting that it is only partially responsible for the stretch-mediated rescue. Therefore, besides activin, other tumor-derived factors may play a significant role in mediating muscle atrophy. In addition to increasing follistatin secretion mechanical stimulation induces additional beneficial responses in myotubes. We propose that in animal models of cancer cachexia and in cancer patients purely mechanical stimuli play an important role in mediating the rescue of the muscle homeostasis reported upon exercise

Are collagenous and lymphocytic colitis different aspects of the same disease?

Objective. Collagenous colitis (CC) and lymphocytic colitis (LC) are two subtypes of microscopic colitis (MC). Even though they most often are described as different entities they share many clinical and histological features. The aim of this study was to investigate the occurrence of conversion between CC and LC in a larger cohort of patients. Materials and methods. All 664 patients in our Pathology register with a diagnosis of CC and LC were scrutinized and those where additional endoscopies had been carried out were included, and their biopsies were re-examined. Results. Sixty-five patients (55 women, 10 men, median age 58 years; range 29-86) fulfilled our criteria for inclusion. The primary diagnosis was CC in 47 patients (39 women, 8 men, median age 58 years; range 29-86) and LC in 18 patients (16 women, 2 men, median age 58 years; range 33-74). Conversion occurred in nine of the 65 patients (14%, all women, median age 59 years; range 41-72), three from CC to LC and six from LC to CC. Conclusion. This study has found that patients can show histological features consistent with both CC and LC over time. These patients could represent a subgroup with a true conversion between two separate entities. Alternatively, MC could be a spectral disease where the varying histological features are manifestations of the natural fluctuation. A third possibility could be that the histological changes reflect different manifestations during the disease course and consequently, the diagnostic criteria could be too vague

Vilken sträng var det som brast? En språklig och medicinsk diskussion med utgångspunkt från episoden med Teukros i Iliaden 8.321-334

During the Trojan War, the Greek archer Teucer was hit by a stone on the collar-bone. His arm went numb, indicating a nerve injury. Through a linguistic and medical analysis, Homer’s anatomical knowledge is examined. The conclusion is that Homer’s concept of anatomy was mainly founded on an empirical and functional knowledge, to a lesser degree on systematic knowledge. The paper offers an explanation to Homer’s consistent use of the word τένων (tendon) in either dualis or plural, never in singular. Furthermore, different translations of this episode into English and Swedish are discussed. Some translators state that the bow-string broke, others that a tendon in Teucer’s shoulder was crushed. One finding is that the translation of the words νευρή, ἡ, νεῦρον, τό and τένων, ὁ are in some instances imprecise and contradictory in Greek-English dictionaries. The analysis suggests that the correct tenor of the word νευρήν (string) in the Teucer episode is similar to the Egyptian word "met" meaning string-formed structures such as tendons, vessels, possibly nerves.I Iliaden 8.321-334 beskrivs hur den grekiske bågskytten Teukros träffas av en sten på nyckelbenet. Armen domnar, vilket tyder på en nervskada. I uppsatsen görs en språklig och medicinsk analys av Homeros anatomiska kunskaper. Mycket talar för att Homeros anatomiuppfattning framförallt är av empiriskt–funktionell art, den är i mindre grad grundad på systematiska kunskaper. I uppsatsen presenteras en förklaring till varför Homeros genomgående använder ordet τένων (sena) i dualis eller pluralis, aldrig singularis. Dessutom diskuteras hur olika engelska och svenska översättare har tolkat episoden. Vissa översättare anger att bågsträngen brister, andra att en sena i Teukros axel krossas. Ett fynd är att översättningen av orden νευρή, ἡ, νεῦρον, τό och τένων, ὁ i vissa avseenden är ofullständiga och motsägelsefulla i grekisk-engelska lexika. I Iliadens text framkommer flera orientaliska influenser, inte minst egyptiska. I uppsatsen framförs hypotesen att ordet νευρήν (sträng) i denna episod har samma betydelse som det egyptiska ordet "met", dvs. strängformade anatomiska strukturer; senor, blodkärl, möjligen nerver