Paramphistomosis, caused by the rumen fluke, Calicophoron daubneyi, is a parasitic infection of ruminant livestock which has seen a rapid rise in prevalence throughout Western Europe in recent years. Following ingestion of metacercariae (parasite cysts) by the mammalian host, newly-excysted juveniles (NEJs) emerge and invade the duodenal submucosa which causes significant pathology in heavy infections. The immature larvae then migrate upwards, along the gastrointestinal tract, and enter the rumen where they mature and begin to produce eggs. Despite their emergence, and sporadic outbreaks of acute disease, we know little about the molecular mechanisms used by C. daubneyi to establish infection, acquire nutrients and to avoid the host immune response. Here, transcriptome analysis of four intra-mammalian life-cycle stages, integrated with secretome analysis of the NEJ and adult parasites (responsible for acute and chronic disease respectively), revealed how the expression and secretion of selected families of vicommonly found as co-infections with rumen fluke.The choice for adjuvant chemotherapy in stage II colorectal cancer (CRC) is controversial as many patients are cured by surgery alone and it is difficult to identify patients with high-risk of recurrence of the disease. There is a need for better stratification of this group of patients. Mass spectrometry imaging could identify patients at risk. We report here the N-glycosylation signatures of the different cell populations in a group of stage II CRC tissue samples. The cancer cells, compared to normal epithelial cells, have increased levels of sialylation and high-mannose glycans, as well as decreased levels of fucosylation and highly branched N-glycans. When looking at the interface between cancer and its microenvironment, it seems that the cancer N-glycosylation signature spreads into the surrounding stroma at the invasive front of the tumor. This finding was more outspoken in patients with a worse outcome within this sample group.The insular cortex (IC) is notably implicated in emotional and cognitive processing; however, little is known regarding to what extent its two main subregions play functionally distinct roles on memory consolidation of conditioned fear tasks. Here we verified the effects of temporary functional inactivation of the anterior (aIC) and posterior IC (pIC) on contextual and tone fear memory. Rats received post-training bilateral infusions of the GABAA receptor agonist muscimol into either the aIC or pIC and were tested 48 and 72 h after the delay tone fear conditioning session to assess the background contextual (CFC) and tone (TFC) fear conditioning, respectively. Inactivation of the aIC during memory consolidation did not affect fear memory for CFC or TFC. On the other hand, post-training inactivation of the pIC impaired TFC but not CFC. Our findings indicate that the pIC is a necessary part of the neural circuitry related to the consolidation of cued-fear memories.As the incidence of anxiety disorders is more prevalent in females, comparing the neural underpinnings of anxiety in males and females is imperative. The bed nucleus of the stria terminalis (BNST) contributes to long-lasting, anxiety-like states including the expression of context fear conditioning. Currently, there is conflicting evidence as to which nuclei of the BNST contribute to these behaviors. The anterolateral portion of the BNST (BNST-AL) located dorsal to the anterior commissure and lateral to the stria terminalis sends robust projections to the central nucleus of the amygdala (CE). Here we asked whether the BNST-AL is active during the expression of context fear conditioning in both male and female rats. At the cellular level, the expression of context fear produced upregulation of the immediate-early gene ARC in the BNST-AL as well as an upregulation of ARC specifically in neurons projecting to the CE, as labeled by the retrograde tracer Fluorogold infused into the CE. However, this pattern of ARC expression was observed in male rats only. Excitotoxic lesions of the BNST reduced context fear expression in both sexes, suggesting that a different set of BNST subnuclei may be recruited by the expression of fear and anxiety-like behaviors in females. Overall, our data highlight the involvement of the BNST-AL in fear expression in males, and suggest that subnuclei of the BNST may be functionally different in male and female rats.Aging is a progressive degenerative process involving a chronic low-grade inflammation and the accumulation of senescent cells. One major issue is to reveal the mechanisms which promote the deposition of pro-inflammatory senescent cells within tissues. The accumulation involves mechanisms which increase cellular senescence as well as those inhibiting the clearance of senescent cells from tissues. It is known that a persistent inflammatory state evokes a compensatory immunosuppression which inhibits pro-inflammatory processes by impairing the functions of effector immune cells, e.g., macrophages, T cells and natural killer (NK) cells. Unfortunately, these cells are indispensable for immune surveillance and the subsequent clearance of senescent cells, i.e., the inflammation-induced counteracting immunosuppression prevents the cleansing of host tissues. Moreover, senescent cells can also repress their own clearance by expressing inhibitors of immune surveillance and releasing the ligands of NKG2D receptors which impair their surveillance by NK and cytotoxic CD8+ T cells. It seems that cellular senescence and immunosuppression establish a feed-forward process which promotes the aging process and age-related diseases. I will examine in detail the immunosuppressive mechanisms which impair the surveillance and clearance of pro-inflammatory senescent cells with aging. In addition, I will discuss several therapeutic strategies to halt the degenerative feed-forward circuit associated with the aging process and age-related diseases.Accurate signal transmission between neurons is accomplished by vesicle release with high spatiotemporal resolution in the central nervous system. LY3214996 The vesicle release occurs mainly in the active zone (AZ), a unique area on the presynaptic membrane. Many structural proteins expressed in the AZ connect with other proteins nearby. They can also regulate the precise release of vesicles through protein-protein interactions. RIM-binding proteins (RIM-BPs) are one of the essential proteins in the AZ. This review summarizes the structures and functions of three subtypes of RIM-BPs, including the interaction between RIM-BPs and other proteins such as Bassoon and voltage-gated calcium channel, their significance in stabilizing the AZ structure in the presynaptic region and collecting ion channels, and ultimately regulating the fusion and release of neuronal vesicles.