A dynamic interface between ubiquitylation and cAMP signaling

Phosphorylation waves drive the propagation of signals generated in response to hormones and growth factors in target cells. cAMP is an ancient second messenger implicated in key biological functions. In mammals, most of the effects elicited by cAMP are mediated by protein kinase A (PKA). Activation of the kinase by cAMP results in the phosphorylation of a variety of cellular substrates, leading to differentiation, proliferation, survival, metabolism. The identification of scaffold proteins, namely A-Kinase Anchor proteins (AKAPs), that localize PKA in specific cellular districts, provided critical cues for our understanding of the role played by cAMP in cell biology. Multivalent complexes are assembled by AKAPs and include signaling enzymes, mRNAs, adapter molecules, receptors and ion channels. A novel development derived from the molecular analysis of these complexes nucleated by AKAPs is represented by the presence of components of the ubiquitin-proteasome system (UPS). More to it, the AKAP complex can be regulated by the UPS, eliciting relevant effects on downstream cAMP signals. This represents a novel, yet previously unpredicted interface between compartmentalized signaling and the UPS. We anticipate that impairment of these regulatory mechanisms could promote cell dysfunction and disease. Here, we will focus on the reciprocal regulation between cAMP signaling and UPS, and its relevance to human degenerative and proliferative disorders

HoVer-UNet: Accelerating HoVerNet with UNet-based multi-class nuclei segmentation via knowledge distillation

We present HoVer-UNet, an approach to distill the knowledge of the multi-branch HoVerNet framework for nuclei instance segmentation and classification in histopathology. We propose a compact, streamlined single UNet network with a Mix Vision Transformer backbone, and equip it with a custom loss function to optimally encode the distilled knowledge of HoVerNet, reducing computational requirements without compromising performances. We show that our model achieved results comparable to HoVerNet on the public PanNuke and Consep datasets with a three-fold reduction in inference time. We make the code of our model publicly available at https://github.com/DIAGNijmegen/HoVer-UNet.Comment: 4 pages, 2 figures, submitted to ISBI 202

Evoluzione della ricerca scientifica nell'ambito della biologia umana: abbiamo raggiunto il momento in cui dobbiamo fermarci e riflettere?

n/

The comparison of FLOTAC, FECPAK and McMaster techniques for nematode egg counts in cattle

AbstractThree methods, FLOTAC, FECPAK and McMaster were compared for accuracy and sensitivity for counting numbers of nematode eggs in faeces of naturally infected cattle with high or low nematode egg counts. Only FLOTAC gave positive results for 12 replicates from pooled samples with low egg counts making it more sensitive than FECPAK (67%) and McMaster (41.7%). FLOTAC resulted in generally higher egg counts and lower coefficients of variation than the other two methods used. The reliability of FECPAK and McMaster is depended on the area under the slide counted. All three methods can be used for making decisions whether to treat but FLOTAC or Mini-FLOTAC should be used for faecal egg count reduction tests when lower egg counts are present

Increased circulating levels of vitamin D binding protein in MS patients

Vitamin D (vitD) low status is currently considered a main environmental factor in multiple sclerosis (MS) etiology and pathogenesis. VitD and its metabolites are highly hydrophobic and circulate mostly bound to the vitamin D binding protein (DBP) and with lower affinity to albumin, while less than 1\% are in a free form. The aim of this study was to investigate whether the circulating levels of either of the two vitD plasma carriers and/or their relationship are altered in MS. We measured DBP and albumin plasma levels in 28 MS patients and 24 healthy controls. MS patients were found to have higher DBP levels than healthy subjects. Concomitant interferon beta therapy did not influence DBP concentration, and the difference with the control group was significant in both females and males. No significant correlation between DBP and albumin levels was observed either in healthy controls or in patients. These observations suggest the involvement of DBP in the patho-physiology of MS

Mapping, cluster detection and evaluation of risk factors of ovine toxoplasmosis in Southern Italy

Toxoplasmosis, an important cause of reproductive failure in sheep, is responsible for significant economic losses to the ovine industry worldwide. Moreover, ovine meat contaminated by the parasite Toxoplasma gondii is considered as a common source of infection for humans. The aim of this study was to develop point and risk profiling maps of T. gondii seroprevalence in sheep bred in Campania Region (Southern Italy) and analyse risk factors associated at the flock-level. We used serological data from a previous survey of 117 sheep flocks, while environmental and farm management information were obtained from an analysis based on geographical information systems and a questionnaire purveyance, respectively. An univariate Poisson regression model revealed that the type of farm production (milk and meat vs only meat) was the only independent variable associated with T. gondii positivity (P<0.02); the higher within-flock seroprevalence in milking herds suggests that milking practices might influence the spread of the infection on the farm. Neither environmental nor other management variables were significant. Since a majority of flocks were seasonally or permanently on pasture, the animals have a high exposure to infectious T. gondii oocysts, so the high within-flock seroprevalence might derive from this management factor. However, further studies are needed to better assess the actual epidemiological situation of toxoplasmosis in sheep and to clarify the factors that influence its presence and distribution

The Presence of Toxocara Eggs on Dog’s Fur as Potential Zoonotic Risk in Animal-Assisted Interventions: A Systematic Review

Animal-assisted interventions (AAIs) usually contribute to the well-being and health of users/patients, but it is essential that the animals involved in these activities do not represent a source of zoonoses. This systematic review focused on the evaluation of the potential risk of the transmission of Toxocara by dogs’ fur, considering their involvement as the main animal species in AAIs. Three databases were considered: MEDLINE/PubMed, Scopus, and Web of Science, and the PRISMA guidelines were used. Out of 162 articles found, 14 papers were identified as eligible for inclusion in the review. Although the findings were very heterogeneous, they showed that regular parasitological surveillance to plan effective control programs is strongly needed to guarantee the health of pets and consequently the public health, according to the concept of One Health. Since AAIs involve patients and/or users potentially susceptible, it is very important to appropriately treat dogs enrolled in these interventions after an accurate diagnosis of parasitic zoonoses

Parasitic infections in dogs involved in animal-assisted interventions

Animal Assisted Interventions (AAIs) programmes have been considered useful in different settings, such as hospital, therapeutic, educational and assisted living environments. In these contexts, all animals, and particularly dogs, should be subjected to appropriate health controls to prevent a potential risk of transmission of zoonotic agents. Domestic dogs are reservoirs of many zoonotic pathogens including several gastrointestinal parasites (protozoa and helminths). Therefore, the aim of the present study was to investigate the presence of the protozoan Giardia duodenalis and zoonotic gastrointestinal nematodes (geohelminths) in dogs hosted in a dog educational centre in the city of Naples (southern Italy) where the animals were trained to AAI. Between April and June 2016, 74 dog faecal samples were analysed using the FLOTAC dual technique to detect G. duodenalis cysts and other parasitic elements. Out of the 74 faecal samples examined, 18 (24.3%; 95% CI = 15.4–35.9) were positive for parasitic elements. Specifically, 8 were positive for G. duodenalis (44.4%; 95% CI = 22.4–68.7). In addition, some co-infections were also found: one sample (5.6%; 95% CI = 0.3–29.4) resulted positive to both Toxocara canis and Trichuris vulpis and two samples (11.1%; 95% CI = 1.9–36.1) were positive to both G. duodenalis and Ancylostomidae. Given that children, young adults and immunocompromised individuals are among the main users of the AAIs, specific guidelines targeting G. duodenalis and other gastrointestinal zoonotic parasites should be formulated in order to develop effective control and prevention strategies and reduce the zoonotic risk favoured by the human-dog interaction

Investigation on the Reflection Coefficient for Seawalls Protected by a Rubble Mound Structure

Sea wave reflection from coastal protection structures is one of the main issues in the coastal design process. Several empirical formulas have been proposed so far to predict reflection coefficient from rubble mound breakwaters and smooth slopes. The aim of this study is to investigate wave reflection from a rubble mound structure placed in front of a vertical concrete seawall. Several experimental tests were performed on a two-dimensional wave flume by reproducing on a rubble mound structure with a steep single primary layer armored with a novel artificial unit. A new approach for the prediction of the reflection coefficient based on dimensional analysis is also proposed, and a new empirical equation is derived. The performance of the proposed equation was compared with widespread existing formulas, and a good accuracy was found