Sanfordbreen4612

The signal-transducing innate receptors represent classes of pattern recognition receptors (PRRs) that play crucial roles in the first line of the host defense against infections by the recognition of pathogen-derived molecules. Because of their poorly discriminative nature compared with antigen receptors of the adaptive immune system, they also recognize endogenous molecules and evoke immune responses without infection, resulting in the regulation of tumor immunity. Therefore, PRRs may be promising targets for effective cancer immunotherapy, either by activating or inhibiting them. Here, we summarize our current knowledge of signal-transducing PRRs in the regulation of tumor immunity.

Retinol binding protein 1 (Rbp1) acts as an intracellular regulator of vitamin A metabolism and retinoid transport. In mice, Rbp1 deficiency decreases the capacity of hepatic stellate cells to take up all-trans retinol and sustain retinyl ester stores. Furthermore, Rbp1 is crucial for visual capacity. Although the function of Rbp1 has been studied in the mature eye, its role during early anterior neural development has not yet been investigated in detail.

We showed that rbp1 is expressed in the eye, anterior neural crest cells (NCCs) and prosencephalon of the South African clawed frog Xenopus laevis. Rbp1 knockdown led to defects in eye formation, including microphthalmia and disorganized retinal lamination, and to disturbed induction and differentiation of the eye field, as shown by decreased rax and pax6 expression. Furthermore, it resulted in reduced rax expression in the prosencephalon and affected cranial cartilage. Rbp1 inhibition also interfered with neural crest induction and migration, as shown by twist and slug. Moreover, it led to a significant reduction of the all-trans retinoic acid target gene pitx2 in NCC-derived periocular mesenchyme. The Rbp1 knockdown phenotypes were rescued by pitx2 RNA co-injection.

Rbp1 is crucial for the development of the anterior neural tissue.

Rbp1 is crucial for the development of the anterior neural tissue.

Previous studies have demonstrated the acrylamide-removing properties of probiotic monocultures; however, potential advantages of consortia over monocultures in reducing the dietary exposure to acrylamide have not been proven. Hence this work aims to assess the acrylamide (AA)-binding properties of bacterial consortia, consisting of either probiotic strains and / or representative bacteria of duodenal microbiota, exposed to simulated gastrointestinal conditions (SGC). read more The AA binding capacity of ten probiotic strains (PS) and six duodenal strains (NDS) was evaluated under different conditions; then, three different consortia (PS, NDS, and PS + NDS) were assessed under SGC.

Among individual PS, Bacillus coagulans GBI-30, Lactobacillus fermentum J23, L. pentosus J37 and J24, and L. casei Shirota, exhibited the highest AA-binding capacity (80-87%), while Bifidobacterium catenulatun ATCC27676, Streptococcus salivarius subsp. thermophilus ATCC19258, and S. gallolyticus ATCC9809 were the best (ca. 68%) NDS monocultures. Probiotic strain consortia showed higher (P < 0.05) AA binding capacity (> 90%) than monoculture bacteria. Conversely, individual NDS cultures displayed higher (P < 0.05) binding capacity than NDS consortia (60%). A significant reduction (P < 0.05) in AA removal capacity was observed when consortia were exposed to SGC, PS consortia being the most effective (> 60% removal).

These results suggest that consortia of specific PS could play an important role in reducing the intestinal availability of acrylamide. © 2021 Society of Chemical Industry.

These results suggest that consortia of specific PS could play an important role in reducing the intestinal availability of acrylamide. © 2021 Society of Chemical Industry.Forty years have passed since the first pluripotent stem cells (PSCs), mouse embryonic stem cells (ESCs), were established. Since then, several PSCs have been reported, including human ESCs in 1998, mouse epiblast stem cells (EpiSCs) in 2007, induced PSCs (iPSCs) in 2006 and 2007, and naïve human PSCs in 2014. Naïve PSCs are thought to correspond to pre-implantation epiblast cells, whereas conventional (or primed) human PSCs correspond to post-implantation epiblast cells. Thus, naïve and primed PSCs are classified by their developmental stages and have stage-specific characteristics, despite sharing the common feature of pluripotency. In this review, we discuss the current status of PSCs and their use to model human peri-implantation development.Ecological studies are observational studies commonly used in public health research. The main characteristic of this study design is that the statistical analysis is based on pooled (i.e., aggregated) rather than on individual data. Thus, patient-level information such as age, gender, income and disease condition are not considered as individual characteristics but as mean values or frequencies, calculated at country or community level. Ecological studies can be used to compare the aggregated prevalence and incidence data of a given condition across different geographical areas, to assess time-related trends of the frequency of a pre-defined disease/condition, to identify factors explaining changes in health indicators over time in specific populations, to discriminate genetic from environmental causes of geographical variation in disease, or to investigate the relationship between a population-level exposure and a specific disease or condition. The major pitfall in ecological studies is the ecological fallacy, a bias which occurs when conclusions about individuals are erroneously deduced from results about the group to which those individuals belong. In this paper, by using a series of examples, we provide a general explanation of the ecological studies and provide some useful elements to recognize or suspect ecological fallacy in this type of studies.The gut microbiota and the immune system have co-evolved to interact and cooperate in many ways. A recent study characterizing the immunomodulatory effects of over 60 different human-derived gut microbes across phyla showed that bacteria-induced immunomodulations are not dictated by the bacterial phylogeny. Yet, it remains unclear whether strains from the same species induce the same immunomodulatory effects on the host. We analyzed the strain-level data from this recent study and found that strains from the same species can induce distinct and sometimes even opposing immunophenotypes. Hence, we suggest that the immunomodulatory capabilities of gut bacteria can be strain-specific.Previous work suggests that auditory-vestibular interactions, which emerge during bodily movement to music, can influence the perception of musical rhythm. In a seminal study on the ontogeny of musical rhythm, Phillips-Silver and Trainor (2005) found that bouncing infants to an unaccented rhythm influenced infants' perceptual preferences for accented rhythms that matched the rate of bouncing. In the current study, we ask whether nascent, diffuse coupling between auditory and motor systems is sufficient to bootstrap short-term Hebbian plasticity in the auditory system and explain infants' preferences for accented rhythms thought to arise from auditory-vestibular interactions. First, we specify a nonlinear, dynamical system in which two oscillatory neural networks, representing developmentally nascent auditory and motor systems, interact through weak, non-specific coupling. The auditory network was equipped with short-term Hebbian plasticity, allowing the auditory network to tune its intrinsic resonant properties. Next, we simulate the effect of vestibular input (e.g., infant bouncing) on infants' perceptual preferences for accented rhythms. We found that simultaneous auditory-vestibular training shaped the model's response to musical rhythm, enhancing vestibular-related frequencies in auditory-network activity. Moreover, simultaneous auditory-vestibular training, relative to auditory- or vestibular-only training, facilitated short-term auditory plasticity in the model, producing stronger oscillator connections in the auditory network. Finally, when tested on a musical rhythm, models which received simultaneous auditory-vestibular training, but not models that received auditory- or vestibular-only training, resonated strongly at frequencies related to their "bouncing," a finding qualitatively similar to infants' preferences for accented rhythms that matched the rate of infant bouncing.A concurrent human papilloma virus (HPV) infection potentiates the efficacy of ionizing radiation for treatment of head and neck cancer by promoting apoptosis. Studies in cell culture indicated an opposite effect for photodynamic therapy (PDT) when this leads to mitochondrial and ER photodamage. The explanation for this difference in PDT efficacy remains to be established. While apoptosis was impaired in HPV(-) cells, such cells can be killed via photodamage directed at the ER this leads to a nonapoptotic death pathway termed paraptosis. No differences in photosensitizer uptake or reactive oxygen species (ROS) production were observed in HPV(+) vs. HPV(-) tumors. We now provide evidence that death pathways initiated by ER/mitochondrial photodamage leading to either paraptosis or apoptosis are impaired in an HPV(+) head and neck cell line. These results illustrate the complex determinants of PDT efficacy, a topic that has yet to be fully explored.

Manual histologic assessment is currently the accepted standard for diagnosing and monitoring disease progression in nonalcoholic steatohepatitis (NASH), but is limited by variability in interpretation and insensitivity to change. Thus, there is a critical need for improved tools to assess liver pathology in order to risk stratify NASH patients and monitor treatment response.

Here, we describe a machine learning (ML)-based approach to liver histology assessment, which accurately characterizes disease severity and heterogeneity, and sensitively quantifies treatment response in NASH. We utilize samples from three randomized controlled trials to build and then validate deep convolutional neural networks to measure key histologic features in NASH including steatosis, inflammation, hepatocellular ballooning, and fibrosis. The ML-based predictions showed strong correlations with expert pathologists and were prognostic of progression to cirrhosis and liver-related clinical events. We developed a new heterogeneity-sensitive metric of fibrosis response, the Deep Learning Treatment Assessment (DELTA) Liver Fibrosis score, which measured anti-fibrotic treatment effects that went undetected by manual pathological staging and was concordant with histologic disease progression.

Our ML method has shown reproducibility, sensitivity, and was prognostic for disease progression demonstrating the power of ML to advance our understanding of disease heterogeneity in NASH, risk stratify affected patients, and facilitate the development of novel therapies.

Our ML method has shown reproducibility, sensitivity, and was prognostic for disease progression demonstrating the power of ML to advance our understanding of disease heterogeneity in NASH, risk stratify affected patients, and facilitate the development of novel therapies.