Ultrasound-guided hook-wire localization for surgical excision of non-palpable superficial inguinal lymph nodes in dogs: A pilot study

The evaluation of loco-regional lymph nodes (LN) plays an important prognostic role and assists the clinical decision making in canine cancer patients. Excision of non-palpable LN can be challenging. The aim of the study was to evaluate surgical time, successful excision rate and surgical complications associated with the use of an ultrasound-guided hook-wire (UGHW) LN localization method for non-palpable superficial inguinal LN (SILN) in dogs. Dogs that presented for excision of non-palpable SILN, performed with the aid of an UGHW placement, were enrolled. Information including signalment, SILN width, UGHW placement and surgical procedure time, hook-wire position, successful excision and intra-and post-operative complications were reviewed. Seventeen dogs were enrolled. Median LN width was 3 mm (range 2–11). Median time of preoperative UGHW placement and surgical LN excision was 8 min and 15 min, respectively. Successful SILN excision was achieved in all cases. Two minor intra-operative (hook migration and wire fragmentation) and one minor post-operative complications (seroma) were observed. No major intraoperative or post-operative complications occurred. The UGHW LN localization method is safe and effective and may allow a high rate of successful SILN excisions in dogs. This method has the potential to facilitate LN excision for other superficial LN locations

Vaccines and Senior Travellers

Background: International tourist travel has been increasingly steadily in recent years, and looks set to reach unprecedented levels in the coming decades. Among these travellers, an increasing proportion is aged over 60 years, and is healthy and wealthy enough to be able to travel. However, senior travellers have specific risks linked to their age, health and travel patterns, as compared to their younger counterparts. Methods: We review here the risk of major vaccine-preventable travel-associated infectious diseases, and forms and efficacy of vaccination for these diseases. Results: Routine vaccinations are recommended for older persons, regardless of whether they travel or not (e.g., influenza, pneumococcal vaccines). Older individuals should be advised about the vaccines that are recommended for their age group in the framework of the national vaccination schedule. Travel-specific vaccines must be discussed in detail on a case-by-case basis, and the risk associated with the vaccine should be carefully weighed against the risk of contracting the disease during travel. Travel-specific vaccines reviewed here include yellow fever, hepatitis, meningococcal meningitis, typhoid fever, cholera, poliomyelitis, rabies, Japanese encephalitis, tick-borne encephalitis and dengue. Conclusion: The number of older people who have the good health and financial resources to travel is rising dramatically. Older travellers should be advised appropriately about routine and travel-specific vaccines, taking into account the destination, duration and purpose of the trip, the activities planned, the type of accommodation, as well as patient-specific characteristics, such as health status and current medications

A Role for Actin, Cdc1p, and Myo2p in the Inheritance of Late Golgi Elements in \u3cem\u3eSaccharomyces cerevisiae\u3c/em\u3e

In Saccharomyces cerevisiae, Golgi elements are present in the bud very early in the cell cycle. We have analyzed this Golgi inheritance process using fluorescence microscopy and genetics. In rapidly growing cells, late Golgi elements show an actin-dependent concentration at sites of polarized growth. Late Golgi elements are apparently transported into the bud along actin cables and are also retained in the bud by a mechanism that may involve actin. A visual screen for mutants defective in the inheritance of late Golgi elements yielded multiple alleles of CDC1. Mutations in CDC1 severely depolarize the actin cytoskeleton, and these mutations prevent late Golgi elements from being retained in the bud. The efficient localization of late Golgi elements to the bud requires the type V myosin Myo2p, further suggesting that actin plays a role in Golgi inheritance. Surprisingly, early and late Golgi elements are inherited by different pathways, with early Golgi elements localizing to the bud in a Cdc1p- and Myo2p-independent manner. We propose that early Golgi elements arise from ER membranes that are present in the bud. These two pathways of Golgi inheritance in S. cerevisiae resemble Golgi inheritance pathways in vertebrate cells

RIS-enabled smart wireless environments: deployment scenarios, network architecture, bandwidth and area of influence

Reconfigurable intelligent surfaces (RISs) constitute the key enabler for programmable electromagnetic propagation environments and are lately being considered as a candidate physical-layer technology for the demanding connectivity, reliability, localisation, and sustainability requirements of next-generation wireless networks. In this paper, we first present the deployment scenarios for RIS-enabled smart wireless environments that have been recently designed within the ongoing European Union Horizon 2020 RISE-6G project, as well as a network architecture integrating RISs with existing standardised interfaces. We identify various RIS deployment strategies and sketch the core architectural requirements in terms of RIS control and signalling, depending on the RIS hardware architectures and respective capabilities. Furthermore, we introduce and discuss, with the aid of simulations and reflect array measurements, two novel metrics that emerge in the context of RIS-empowered wireless systems: the RIS bandwidth of influence and the RIS area of influence. Their extensive investigation corroborates the need for careful deployment and planning of the RIS technology in future wireless networks

Achieving In Vivo Target Depletion through the Discovery and Optimization of Benzimidazolone BCL6 Degraders.

Deregulation of the transcriptional repressor BCL6 enables tumorigenesis of germinal center B-cells, and hence BCL6 has been proposed as a therapeutic target for the treatment of diffuse large B-cell lymphoma (DLBCL). Herein we report the discovery of a series of benzimidazolone inhibitors of the protein-protein interaction between BCL6 and its co-repressors. A subset of these inhibitors were found to cause rapid degradation of BCL6, and optimization of pharmacokinetic properties led to the discovery of 5-((5-chloro-2-((3R,5S)-4,4-difluoro-3,5-dimethylpiperidin-1-yl)pyrimidin-4-yl)amino)-3-(3-hydroxy-3-methylbutyl)-1-methyl-1,3-dihydro-2H-benzo[d]imidazol-2-one (CCT369260), which reduces BCL6 levels in a lymphoma xenograft mouse model following oral dosing

Myosin-driven peroxisome partitioning in S. cerevisiae

In Saccharomyces cerevisiae, the class V myosin motor Myo2p propels the movement of most organelles. We recently identified Inp2p as the peroxisome-specific receptor for Myo2p. In this study, we delineate the region of Myo2p devoted to binding peroxisomes. Using mutants of Myo2p specifically impaired in peroxisome binding, we dissect cell cycle–dependent and peroxisome partitioning–dependent mechanisms of Inp2p regulation. We find that although total Inp2p levels oscillate with the cell cycle, Inp2p levels on individual peroxisomes are controlled by peroxisome inheritance, as Inp2p aberrantly accumulates and decorates all peroxisomes in mother cells when peroxisome partitioning is abolished. We also find that Inp2p is a phosphoprotein whose level of phosphorylation is coupled to the cell cycle irrespective of peroxisome positioning in the cell. Our findings demonstrate that both organelle positioning and cell cycle progression control the levels of organelle-specific receptors for molecular motors to ultimately achieve an equidistribution of compartments between mother and daughter cells

Sec12 Binds to Sec16 at Transitional ER Sites

COPII vesicles bud from an ER domain known as the transitional ER (tER). Assembly of the COPII coat is initiated by the transmembrane guanine nucleotide exchange factor Sec12. In the budding yeast Pichia pastoris, Sec12 is concentrated at tER sites. Previously, we found that the tER localization of P. pastoris Sec12 requires a saturable binding partner. We now show that this binding partner is Sec16, a peripheral membrane protein that functions in ER export and tER organization. One line of evidence is that overexpression of Sec12 delocalizes Sec12 to the general ER, but simultaneous overexpression of Sec16 retains overexpressed Sec12 at tER sites. Additionally, when P. pastoris Sec12 is expressed in S. cerevisiae, the exogenous Sec12 localizes to the general ER, but when P. pastoris Sec16 is expressed in the same cells, the exogenous Sec12 is recruited to tER sites. In both of these experimental systems, the ability of Sec16 to recruit Sec12 to tER sites is abolished by deleting a C-terminal fragment of Sec16. Biochemical experiments confirm that this C-terminal fragment of Sec16 binds to the cytosolic domain of Sec12. Similarly, we demonstrate that human Sec12 is concentrated at tER sites, likely due to association with a C-terminal fragment of Sec16A. These results suggest that a Sec12–Sec16 interaction has a conserved role in ER export

Who Needs Microtubules? Myogenic Reorganization of MTOC, Golgi Complex and ER Exit Sites Persists Despite Lack of Normal Microtubule Tracks

A wave of structural reorganization involving centrosomes, microtubules, Golgi complex and ER exit sites takes place early during skeletal muscle differentiation and completely remodels the secretory pathway. The mechanism of these changes and their functional implications are still poorly understood, in large part because all changes occur seemingly simultaneously. In an effort to uncouple the reorganizations, we have used taxol, nocodazole, and the specific GSK3-β inhibitor DW12, to disrupt the dynamic microtubule network of differentiating cultures of the mouse skeletal muscle cell line C2. Despite strong effects on microtubules, cell shape and cell fusion, none of the treatments prevented early differentiation. Redistribution of centrosomal proteins, conditional on differentiation, was in fact increased by taxol and nocodazole and normal in DW12. Redistributions of Golgi complex and ER exit sites were incomplete but remained tightly linked under all circumstances, and conditional on centrosomal reorganization. We were therefore able to uncouple microtubule reorganization from the other events and to determine that centrosomal proteins lead the reorganization hierarchy. In addition, we have gained new insight into structural and functional aspects of the reorganization of microtubule nucleation during myogenesis