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Previous studies found that episodic long-term memory (eLTM) enhances working memory (WM) performance when both novel and previously learnt word pairs must be retained on a short-term basis. However, there is uncertainty regarding how and when WM draws on eLTM. Three possibilities are (a) that people draw on eLTM only if WM capacity is exceeded; (b) that there is always a contribution of eLTM to WM performance, irrespective of whether prior knowledge is helpful or not; or (c) benefits of prior knowledge are specific to comparisons between conditions which are similarly ambiguous concerning whether LTM may be useful. We built on the assumption that under conditions of a contribution from LTM, these LTM traces of memoranda could benefit or hamper performance in WM tasks depending on the match between the traces stored in LTM and the ones to-be stored in WM in the current trial, yielding proactive facilitation (PF) and proactive interference (PI), respectively. Across four experiments, we familiarized participants with some items before they completed a separate WM task. In accordance with possibility (a) we show that there are indeed conditions in which only WM contributes to performance. Performance deteriorated with the addition of stimuli from eLTM when WM load was low, but not when it was high; and an exchange of information between LTM and WM occurred only when WM capacity was exceeded, with PI and PF effects affecting immediate memory performance in verbal and visual tasks only at higher set sizes.

The authors find that the insulin receptor forms dynamic clusters during insulin signaling and that these clusters become dysfunctional in insulin resistance. This dysfunction is partially rescued by metformin, a drug used to treat type 2 diabetes.

Approaches to manage nonalcoholic fatty liver disease (NAFLD) are limited by an incomplete understanding of disease pathogenesis. The aim of this study was to identify hepatic gene‐expression patterns associated with different patterns of liver injury in a high‐risk cohort of adults with obesity. Using the NanoString Technologies (Seattle, WA) nCounter assay, we quantified expression of 795 genes, hypothesized to be involved in hepatic fibrosis, inflammation, and steatosis, in liver tissue from 318 adults with obesity. Liver specimens were categorized into four distinct NAFLD phenotypes: normal liver histology (NLH), steatosis only (steatosis), nonalcoholic steatohepatitis without fibrosis (NASH F0), and NASH with fibrosis stage 1‐4 (NASH F1‐F4). One hundred twenty‐five genes were significantly increasing or decreasing as NAFLD pathology progressed. Compared with NLH, NASH F0 was characterized by increased inflammatory gene expression, such as gamma‐interferon‐inducible lysosomal thiol reductase (IFI30) and chemokine (C‐X‐C motif) ligand 9 (CXCL9), while complement and coagulation related genes, such as C9 and complement component 4 binding protein beta (C4BPB), were reduced. In the presence of NASH F1‐F4, extracellular matrix degrading proteinases and profibrotic/scar deposition genes, such as collagens and transforming growth factor beta 1 (TGFB1), were simultaneously increased, suggesting a dynamic state of tissue remodeling. Conclusion: In adults with obesity, distinct states of NAFLD are associated with intrahepatic perturbations in genes related to inflammation, complement and coagulation pathways, and tissue remodeling. These data provide insights into the dynamic pathogenesis of NAFLD in high‐risk individuals.

Both the experimental and the psychometric investigation of the WM capacity limit depend critically on the assumption that performance in our tests of WM reflects that capacity limit to a good approximation. Most tasks to measure WM rely on testing memory after a short time during which participants are asked to maintain information in WM. In these tests, episodic long-term memory is likely to also lay down a trace of the memory set. Therefore, participants can draw on two sources of information when memory is tested, making it difficult to separate the contributions of WM and episodic LTM to the performance on immediate-memory tests. Here we use proactive interference to distinguish between these two sources of remembered information, building on the fact that episodic memory is vulnerable to proactive interference, whereas WM is protected against it. We use a release-from-PI paradigm to determine the extent to which commonly used WM tasks reflect contributions from episodic LTM. We focus on memory for serial order of verbal lists, but also include visual and spatial WM tasks. The results of five experiments demonstrate that although some tasks used to investigate WM are heavily contaminated by episodic LTM, other popular paradigms such as serial and probed recall, and the standard version of the continuous color-reproduction task, are not. Measuring proactive interference can help researchers determine the extent to which WM and episodic LTM contribute to performance in immediate-memory tasks.

Both acute and chronic hepatic inflammation likely result from an imbalance in the TH1/TH2 cell response and can lead to liver fibrosis and end-stage liver disease. More recently, a novel CD4+ T helper cell subset was described, characterized by the production of IL-17 and IL-22. These TH17 cells 50were predominantly implicated in host defense against infections and in autoimmune diseases. Interestingly, studies over the last 10 years revealed that the development of TH17 cells favors pro-inflammatory responses in almost all tissues and there is a reciprocal relationship between TH17 and TReg cells. The balance between TH17and TReg cells is critical for immune reactions, especially in injured liver tissue and the return to immune homeostasis. The pathogenic contribution of TH17 and TReg cells in autoimmunity, acute infection, and chronic liver injury is diverse and varies among disease etiologies. Understanding the mechanisms underlying TH17 cell development, recruitment, and maintenance, along with the suppression of TReg cells, will inform the development of new therapeutic strategies in liver diseases. Active manipulation of the balance between pathogenic and regulatory processes in the liver may assist in the restoration of homeostasis, especially in hepatic inflammation.

T cells play an important role to build up an effective immune response and are essential in the eradication of pathogens. To establish a long-lasting protection even after a re-challenge with the same pathogen, some T cells differentiate into memory T cells. Recently, a certain subpopulation of memory T cells at different tissue-sites of infection was detected—tissue-resident memory T cells (TRM cells). These cells can patrol in the tissue in order to encounter their cognate antigen to establish an effective protection against secondary infection. The liver as an immunogenic organ is exposed to a variety of pathogens entering the liver through the systemic blood circulation or via the portal vein from the gut. It could be shown that intrahepatic TRM cells can reside within the liver tissue for several years. Interestingly, hepatic TRM cell differentiation requires a distinct cytokine milieu. In addition, TRM cells express specific surface markers and transcription factors, which allow their identification delimited from their circulating counterparts. It could be demonstrated that liver TRM cells play a particular role in many liver diseases such as hepatitis B and C infection, non-alcoholic fatty liver disease and even play a role in the development of hepatocellular carcinoma and in building long-lasting immune responses after vaccination. A better understanding of intrahepatic TRM cells is critical to understand the pathophysiology of many liver diseases and to identify new potential drug targets for the development of novel treatment strategies.

A fundamental question in memory research has long been the interplay between briefly maintaining information in working memory (WM) and its enduring retention in long-term memory (LTM). Much of the research has explored how WM processes influence the formation of LTM and, in turn, how stored LTM can either support or disrupt WM performance. This Special Issue of Memory & Cognition brings together cutting-edge research that delves into this relationship, showcasing studies that reveal the latest advances in the field. Additionally, it includes articles offering conceptual and theoretical insights to better understand the dynamic interaction between WM and LTM. The 25 articles presented here emphasize the ways in which information is transferred from WM to more durable representations in LTM, as well as how WM flexibly draws on LTM to overcome its limited capacity. In many ways, the quality and quantity of contributions to this Special Issue highlight the importance of jointly studying WM and LTM, inspiring future work to challenge pre-existing conceptions and stimulate new directions in the field of memory. [ABSTRACT FROM AUTHOR]

Priority-based allocation of attentional resources has shown robust effects in working memory (WM) with both cue-based and reward-based prioritization. However, direct comparisons between these effects in WM are needed. Additionally, the consequences of WM prioritization for remembering in the long term remain unclear for both prioritization procedures. Here, we tested and compared the immediate and long-term memory (LTM) effects of cue-based versus reward-based retrospective prioritization of WM content. Participants encoded four memory items and were then indicated to prioritize one of the items through the presentation of either a retro-cue or a reward pattern. We then tested their immediate and delayed memory. The results of the first experiment showed better memory for prioritized than for unprioritized information in WM and LTM, but the WM effect was driven solely by the retro-cue, making it difficult to interpret any reward-based effects in LTM. In the second experiment, using a more explicit and meaningful reward-based manipulation, the results showed a prioritization benefit in WM for both prioritization procedures. In LTM, however, the prioritization effect was predominantly driven by the retro-cue manipulation. Taken together, we found that (1) the way in which attention is directed in WM impacts the size of the prioritization benefit in WM, (2) WM prioritization generally results in a prioritization effect in LTM, and (3) that the effect in LTM is more robust for cue-based prioritization. Exploratory analyses indicated that the LTM effect of cue-based prioritization reflected a cost in performance for noncued items rather than a benefit for cued items. [ABSTRACT FROM AUTHOR]

Individuals can use information stored in episodic long-term memory (LTM) to optimize performance in a working memory (WM) task, and the WM system negotiates the exchange of information between WM and LTM depending on the current memory load. In this study, we assessed the ability of different accounts of interactions between LTM and WM to explain these findings, by investigating whether the position of pre-learnt information within a memory list encoded into WM affects the benefit it provides to immediate memory. In two experiments we varied the input position of previously learned word-word pairs within a set of four to-be-remembered pairs. We replicated previous findings of superior performance when these LTM pairs were included in the WM task and show that the position in the list in which these LTM pairs were included not seem to matter. These results are most consistent with the idea that having access to information in LTM reduces or removes the need to rely on WM for its storage, implying that people "offload" information in conditions containing LTM pairs. [ABSTRACT FROM AUTHOR]

Both the experimental and the psychometric investigation of the WM capacity limit depend critically on the assumption that performance in our tests of WM reflects that capacity limit to a good approximation. Most tasks to measure WM rely on testing memory after a short time during which participants are asked to maintain information in WM. In these tests, episodic long-term memory is likely to also lay down a trace of the memory set. Therefore, participants can draw on two sources of information when memory is tested, making it difficult to separate the contributions of WM and episodic LTM to the performance on immediate-memory tests. Here we use proactive interference to distinguish between these two sources of remembered information, building on the fact that episodic memory is vulnerable to proactive interference, whereas WM is protected against it. We use a release-from-PI paradigm to determine the extent to which commonly used WM tasks reflect contributions from episodic LTM. We focus on memory for serial order of verbal lists, but also include visual and spatial WM tasks. The results of five experiments demonstrate that although some tasks used to investigate WM are heavily contaminated by episodic LTM, other popular paradigms such as serial and probed recall, and the standard version of the continuous colorreproduction task, are not. Measuring proactive interference can help researchers determine the extent to which WM and episodic LTM contribute to performance in immediate-memory tasks. [ABSTRACT FROM AUTHOR]

Insulin receptor (IR) signaling is central to normal metabolic control and is dysregulated in metabolic diseases such as type 2 diabetes. We report here that IR is incorporated into dynamic clusters at the plasma membrane, in the cytoplasm and in the nucleus of human hepatocytes and adipocytes. Insulin stimulation promotes further incorporation of IR into these dynamic clusters in insulin-sensitive cells but not in insulin-resistant cells, where both IR accumulation and dynamic behavior are reduced. Treatment of insulin-resistant cells with metformin, a first-line drug used to treat type 2 diabetes, can rescue IR accumulation and the dynamic behavior of these clusters. This rescue is associated with metformin's role in reducing reactive oxygen species that interfere with normal dynamics. These results indicate that changes in the physico-mechanical features of IR clusters contribute to insulin resistance and have implications for improved therapeutic approaches. The authors find that the insulin receptor forms dynamic clusters during insulin signaling and that these clusters become dysfunctional in insulin resistance. This dysfunction is partially rescued by metformin, a drug used to treat type 2 diabetes. [ABSTRACT FROM AUTHOR]

Both acute and chronic hepatic inflammation likely result from an imbalance in the TH1/TH2 cell response and can lead to liver fibrosis and end-stage liver disease. More recently, a novel CD4+ T helper cell subset was described, characterized by the production of IL-17 and IL-22. These TH17 cells 50were predominantly implicated in host defense against infections and in autoimmune diseases. Interestingly, studies over the last 10 years revealed that the development of TH17 cells favors pro-inflammatory responses in almost all tissues and there is a reciprocal relationship between TH17 and TReg cells. The balance between TH17and TReg cells is critical for immune reactions, especially in injured liver tissue and the return to immune homeostasis. The pathogenic contribution of TH17 and TReg cells in autoimmunity, acute infection, and chronic liver injury is diverse and varies among disease etiologies. Understanding the mechanisms underlying TH17 cell development, recruitment, and maintenance, along with the suppression of TReg cells, will inform the development of new therapeutic strategies in liver diseases. Active manipulation of the balance between pathogenic and regulatory processes in the liver may assist in the restoration of homeostasis, especially in hepatic inflammation. [ABSTRACT FROM AUTHOR]

Refreshing and elaboration are cognitive processes assumed to underlie verbal working-memory maintenance and assumed to support long-term memory formation. Whereas refreshing refers to the attentional focussing on representations, elaboration refers to linking representations in working memory into existing semantic networks. We measured the impact of instructed refreshing and elaboration on working and long-term memory separately, and investigated to what extent both processes are distinct in their contributions to working as well as long-term memory. Compared with a no-processing baseline, immediate memory was improved by repeating the items, but not by refreshing them. There was no credible effect of elaboration on working memory, except when items were repeated at the same time. Long-term memory benefited from elaboration, but not from refreshing the words. The results replicate the long-term memory benefit for elaboration, but do not support its beneficial role for working memory. Further, refreshing preserves immediate memory, but does not improve it beyond the level achieved without any processing. [ABSTRACT FROM AUTHOR]

T cells play an important role to build up an effective immune response and are essential in the eradication of pathogens. To establish a long-lasting protection even after a re-challenge with the same pathogen, some T cells differentiate into memory T cells. Recently, a certain subpopulation of memory T cells at different tissue-sites of infection was detected—tissue-resident memory T cells (TRM cells). These cells can patrol in the tissue in order to encounter their cognate antigen to establish an effective protection against secondary infection. The liver as an immunogenic organ is exposed to a variety of pathogens entering the liver through the systemic blood circulation or via the portal vein from the gut. It could be shown that intrahepatic TRM cells can reside within the liver tissue for several years. Interestingly, hepatic TRM cell differentiation requires a distinct cytokine milieu. In addition, TRM cells express specific surface markers and transcription factors, which allow their identification delimited from their circulating counterparts. It could be demonstrated that liver TRM cells play a particular role in many liver diseases such as hepatitis B and C infection, non-alcoholic fatty liver disease and even play a role in the development of hepatocellular carcinoma and in building long-lasting immune responses after vaccination. A better understanding of intrahepatic TRM cells is critical to understand the pathophysiology of many liver diseases and to identify new potential drug targets for the development of novel treatment strategies. [ABSTRACT FROM AUTHOR]