Carbohydrate based meningococcal vaccines: past and present overview

Glycoconjugate Journal - Neisseria meningitidis is a major cause of bacterial meningitidis worldwide. Children less than five years and adolescents are particularly affected. Nearly all invasive...     

Integration of life cycle assessment into a decision support system for selecting sustainable road asphalt pavement mixtures prepared with waste

The International Journal of Life Cycle Assessment - A challenge that the road paving sector is facing concerns the achievement of highly performing bituminous asphalt mixture solutions that do not...     

Cosolute modulation of protein oligomerization reactions in the homeostatic timescale

Protein oligomerization processes are widespread and of crucial importance to understand degenerative diseases and healthy regulatory pathways. One particular case is the homo-oligomerization of folded domains involving domain swapping, often found as a part of the protein homeostasis in the crowded cytosol, composed of a complex mixture of cosolutes. Here, we have investigated the effect of a plethora of cosolutes of very diverse nature on the kinetics of a protein dimerization by domain swapping. In the absence of cosolutes, our system exhibits slow interconversion rates, with the reaction reaching the equilibrium within the average protein homeostasis timescale (24–48 h). In the presence of crowders, though, the oligomerization reaction in the same time frame will, depending on the protein's initial oligomeric state, either reach a pure equilibrium state or get kinetically trapped into an apparent equilibrium. Specifically, when the reaction is initiated from a large excess of dimer, it becomes unsensitive to the effect of cosolutes and reaches the same equilibrium populations as in the absence of cosolute. Conversely, when the reaction starts from a large excess of monomer, the reaction during the homeostatic timescale occurs under kinetic control, and it is exquisitely sensitive to the presence and nature of the cosolute. In this scenario (the most habitual case in intracellular oligomerization processes), the effect of cosolutes on the intermediate conformation and diffusion-mediated encounters will dictate how the cellular milieu affects the domain-swapping reaction.     

General descriptions of the dermis structure of a juvenile whale shark Rhincodon typus from the Gulf of California

The aim of this study is to provide preliminary observations on the microanatomy of Rhincodon typus skin using histology and electron microscopy analyses. Skin biopsies were obtained from a deceased juvenile male shark (548 cm total length) stranded in La Paz, Mexico, during February 2018. The results of this study evidenced the basic structure of the dermal denticles in the epidermis of the trunk of the shark, as well as the composition of the connective tissue in the hypodermis. Histological images of the hypodermis showed a high concentration of collagen fibres, formed by a large number of fine and wavy fibres of compact shape and little intercellular substance.     

Invading parasites: spillover of an alien nematode reduces survival in a native species

Biological Invasions - It is widely assumed that spillover of alien parasites to native host species severely impacts naïve populations, ultimately conferring a competitive advantage to...     

Total neoadjuvant treatment in locally advanced rectal cancer

Locally advanced rectal cancer requires a multidisciplinary management, traditionally based on neo-adjuvant (chemo) radiotherapy, conservative surgery with total mesorectal excision and adjuvant chemotherapy. Despite effective in term of local control, this strategy is linked to a high risk of distant metastasis (up to 30%). In this context, recent published randomized phase III clinical trials have tested the potential benefits with a different sequencing and/or intensification of the standard components of the trimodal therapy.Here, we briefly assess the efficacy and discuss the clinical relevance of total neoadjuvant treatment with a focus on indications and results in the short-course radiotherapy followed by chemotherapy use for this setting of patients. Long term results and additional prospective studies are necessary to more accurately estimate the clinical benefit and further establish the role of total neoadjuvant therapy in locally advanced rectal cancer disease.     

Hepatocellular cancer therapy in patients with HIV infection: Disparities in cancer care,trials enrolment,and cancer-related research

In the highly active antiretroviral therapy (HAART) era, hepatocellular carcinoma (HCC) is arising as a common late complication of human immunodeficiency virus (HIV) infection, with a great impact on morbidity and mortality. Though HIV infection alone may not be sufficient to promote hepatocarcinogenesis, the complex interaction of HIV with hepatitis is a main aspect influencing HCC morbidity and mortality.Data about sorafenib effectiveness and safety in HIV-infected patients are limited, particularly for patients who are on HAART. However, in properly selected subgroups, outcomes may be comparable to those of HIV-uninfected patients. Scarce data are available for those other systemic treatments, either tyrosine kinase inhibitors, as well as immune checkpoint inhibitors (ICIs), which have been added to our therapeutic armamentarium. This review examines the influence of HIV infection on HCC development and natural history, summarizes main data on systemic therapies, offers some insight into possible mechanisms of T cell exhaustion and reversal of HIV latency with ICIs and issues about clinical trials enrollment. Nowadays, routine exclusion of HIV-infected patients from clinical trial participation is totally inappropriate, since it leaves a number of patients deprived of life-prolonging therapies.     

Effects of 90 min of manual repetitive work on skin temperature and median and ulnar nerve conduction parameters: A pilot study in normal subjects

To test whether the influence of manual activity should be considered when interpreting the results of nerve conduction study (NCS) of the upper limbs performed during work shifts, we evaluated the short-term effect of 90-min repetitive manual work on NCS parameters. Twenty-eight healthy volunteers underwent NCS of the dominant limb at the end of an interview (T₀), after a 30-min rest in sitting position (T₁) and after performing a standardized 90-min manual task (T₂). The task was designed to simulate typical assembly and packing activities. No significant differences were observed for skin temperature (Ts) and NCS parameters between T₀ and T₁. Significantly (p < 0.001) higher Ts mean values were found at T₂ as compared to the previous tests for both females and males. The regression analysis showed an association between temperature variation and nerve conduction velocity values for the median and ulnar nerve at T₂ as compared to T₁. In females, a reduction of the mean sensory nerve action potential (SNAP) amplitude at T₂ was recorded, whereas an opposite trend was observed among males. Manual work is able to influence hand Ts and to modify NCS parameters. SNAP amplitudes changes suggest gender differences in peripheral nerve characteristics that deserve further investigation.     

Next Generation Semiconductor Based-Sequencing of a Nutrigenetics Target Gene (GPR120) and Association with Growth Rate in Italian Large White Pigs

The GPR120 gene (also known as FFAR4 or O3FAR1) encodes for a functional omega-3 fatty acid receptor/sensor that mediates potent insulin sensitizing effects by repressing macrophage-induced tissue inflammation. For its functional role, GPR120 could be considered a potential target gene in animal nutrigenetics. In this work we resequenced the porcine GPR120 gene by high throughput Ion Torrent semiconductor sequencing of amplified fragments obtained from 8 DNA pools derived, on the whole, from 153 pigs of different breeds/populations (two Italian Large White pools, Italian Duroc, Italian Landrace, Casertana, Pietrain, Meishan, and wild boars). Three single nucleotide polymorphisms (SNPs), two synonymous substitutions and one in the putative 3′-untranslated region (g.114765469C > T), were identified and their allele frequencies were estimated by sequencing reads count. The g.114765469C > T SNP was also genotyped by PCR-RFLP confirming estimated frequency in Italian Large White pools. Then, this SNP was analyzed in two Italian Large White cohorts using a selective genotyping approach based on extreme and divergent pigs for back fat thickness (BFT) estimated breeding value (EBV) and average daily gain (ADG) EBV. Significant differences of allele and genotype frequencies distribution was observed between the extreme ADG-EBV groups (P < 0.001) whereas this marker was not associated with BFT-EBV.     

Interactive effects of elevated temperature and CO2 levels on metabolism and oxidative stress in two common marine bivalves (Crassostrea virginica and Mercenaria mercenaria)

Marine bivalves such as the hard shell clams Mercenaria mercenaria and eastern oysters Crassostrea virginica are affected by multiple stressors, including fluctuations in temperature and CO₂ levels in estuaries, and these stresses are expected to be exacerbated by ongoing global climate change. Hypercapnia (elevated CO₂ levels) and temperature stress can affect survival, growth and development of marine bivalves, but the cellular mechanisms of these effects are not yet fully understood. In this study, we investigated whether oxidative stress is implicated in cellular responses to elevated temperature and CO₂ levels in marine bivalves. We measured the whole-organism standard metabolic rate (SMR), total antioxidant capacity (TAOC), and levels of oxidative stress biomarkers in the muscle tissues of clams and oysters exposed to different temperatures (22 and 27 °C) and CO₂ levels (the present day conditions of ~ 400 ppm CO₂ and 800 ppm CO₂ predicted by a consensus business-as-usual IPCC emission scenario for the year 2100). SMR was significantly higher and the antioxidant capacity was lower in oysters than in clams. Aerobic metabolism was largely temperature-independent in these two species in the studied temperature range (22–27 °C). However, the combined exposure to elevated temperature and hypercapnia led to elevated SMR in clams indicating elevated costs of basal maintenance. No persistent oxidative stress signal (measured by the levels of protein carbonyls, and protein conjugates with malondialdehyde and 4-hydroxynonenal) was observed during the long-term exposure to moderate warming (+ 5 °C) and hypercapnia (~ 800 ppm CO₂). This indicates that long-term exposure to moderately elevated CO₂ and temperature minimally affects the cellular redox status in these bivalve species and that the earlier observed negative physiological effects of elevated CO₂ and temperature must be explained by other cellular mechanisms.