Function (Oxford, England)最新文献

{"title":"How Do We Clean Up the Scientific Record?","authors":"Alexei Verkhratsky, Ole H Petersen","doi":"10.1093/function/zqad055","DOIUrl":"10.1093/function/zqad055","url":null,"abstract":"","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":"4 6","pages":"zqad055"},"PeriodicalIF":5.1,"publicationDate":"2023-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10568198/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41241711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Breathing and Oxygen Carrying Capacity in Ts65Dn and Down Syndrome.","authors":"Lara R DeRuisseau, Candace N Receno, Caitlin Cunningham, Melissa L Bates, Morgan Goodell, Chen Liang, Brianna Eassa, Jessica Pascolla, Keith C DeRuisseau","doi":"10.1093/function/zqad058","DOIUrl":"10.1093/function/zqad058","url":null,"abstract":"<p><p>Individuals with Down syndrome (Ds) are at increased risk of respiratory infection, aspiration pneumonia, and apnea. The Ts65Dn mouse is a commonly used model of Ds, but there have been no formal investigations of awake breathing and respiratory muscle function in these mice. We hypothesized that breathing would be impaired in Ts65Dn vs. wild-type (WT), and would be mediated by both neural and muscular inputs. Baseline minute ventilation was not different at 3, 6, or 12 mo of age. However, <i>V_T/T_i</i>, a marker of the neural drive to breathe, was lower in Ts65Dn vs. WT and central apneas were more prevalent. The response to breathing hypoxia was not different, but the response to hypercapnia was attenuated, revealing a difference in carbon dioxide sensing, and/or motor output in Ts65Dn. Oxygen desaturations were present in room air, demonstrating that ventilation may not be sufficient to maintain adequate oxygen saturation in Ts65Dn. We observed no differences in arterial <i>P</i>_O2 or <i>P</i>_CO2, but Ts65Dn had lower hemoglobin and hematocrit. A retrospective medical record review of 52,346 Ds and 52,346 controls confirmed an elevated relative risk of anemia in Ds. We also performed eupneic in-vivo electromyography and in-vitro muscle function and histological fiber typing of the diaphragm, and found no difference between strains. Overall, conscious respiration is impaired in Ts65Dn, is mediated by neural mechanisms, and results in reduced hemoglobin saturation. Oxygen carrying capacity is reduced in Ts65Dn vs. WT, and we demonstrate that individuals with Ds are also at increased risk of anemia.</p>","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":"4 6","pages":"zqad058"},"PeriodicalIF":0.0,"publicationDate":"2023-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10634617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89721633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Breast Milk Epidermal Growth Factor Confers Paracellular Calcium Absorption in the Infant Small Intestine.","authors":"Andreanna Burman, Izumi Kaji","doi":"10.1093/function/zqad057","DOIUrl":"10.1093/function/zqad057","url":null,"abstract":"","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":"4 6","pages":"zqad057"},"PeriodicalIF":0.0,"publicationDate":"2023-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1a/d5/zqad057.PMC10583193.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49685762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Striatal Dopamine Signals and Reward Learning.","authors":"Pol Bech,&nbsp;Sylvain Crochet,&nbsp;Robin Dard,&nbsp;Parviz Ghaderi,&nbsp;Yanqi Liu,&nbsp;Meriam Malekzadeh,&nbsp;Carl C H Petersen,&nbsp;Mauro Pulin,&nbsp;Anthony Renard,&nbsp;Christos Sourmpis","doi":"10.1093/function/zqad056","DOIUrl":"10.1093/function/zqad056","url":null,"abstract":"Abstract We are constantly bombarded by sensory information and constantly making decisions on how to act. In order to optimally adapt behavior, we must judge which sequences of sensory inputs and actions lead to successful outcomes in specific circumstances. Neuronal circuits of the basal ganglia have been strongly implicated in action selection, as well as the learning and execution of goal-directed behaviors, with accumulating evidence supporting the hypothesis that midbrain dopamine neurons might encode a reward signal useful for learning. Here, we review evidence suggesting that midbrain dopaminergic neurons signal reward prediction error, driving synaptic plasticity in the striatum underlying learning. We focus on phasic increases in action potential firing of midbrain dopamine neurons in response to unexpected rewards. These dopamine neurons prominently innervate the dorsal and ventral striatum. In the striatum, the released dopamine binds to dopamine receptors, where it regulates the plasticity of glutamatergic synapses. The increase of striatal dopamine accompanying an unexpected reward activates dopamine type 1 receptors (D1Rs) initiating a signaling cascade that promotes long-term potentiation of recently active glutamatergic input onto striatonigral neurons. Sensorimotor-evoked glutamatergic input, which is active immediately before reward delivery will thus be strengthened onto neurons in the striatum expressing D1Rs. In turn, these neurons cause disinhibition of brainstem motor centers and disinhibition of the motor thalamus, thus promoting motor output to reinforce rewarded stimulus-action outcomes. Although many details of the hypothesis need further investigation, altogether, it seems likely that dopamine signals in the striatum might underlie important aspects of goal-directed reward-based learning.","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":"4 6","pages":"zqad056"},"PeriodicalIF":0.0,"publicationDate":"2023-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10572094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41241713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elucidating a Complex Mechanism.","authors":"Victor Wray","doi":"10.1093/function/zqad051","DOIUrl":"10.1093/function/zqad051","url":null,"abstract":"ur understanding of the complex dynamic system dri v en by onformational change during adenosine triphosphate (ATP) ydr ol ysis by F 1 -ATPase is of fundamental biochemical imporance. 1 , 2 Cr yo-electr on micr oscopy (Cr yo-EM) studies 3 −5 have ontributed v alua b le structural information on how the F 1 TPase functions, although, in themselves, these have not led o a definiti v e mechanism. The F 1 -ATPase is a multi-subunit sysem containing 3 β-catalytic sites that have been studied by biohysical single-molecule experiments based on direct visualizaion of the rotation of its central γ -subunit. 6 However, it is difcult to esta b lish which interconverting site or sites contribute nergy for the observ ed r otation, gi v en that a site can perform he elementary chemical steps of ATP binding, ATP hydr ol ytic ond cleav a ge, and pr oduct (Pi and adenosine diphosphate, ADP) elease. 7 Originally, the molecular mechanism of ATP syntheis/hydr ol ysis w as studied using classical biochemical pproaches that provided a wealth of fundamental data. A i-site Boyer’s binding change mechanism of ATP syntheis/hydr ol ysis (Nobel Prize for Chemistry, 1997) was postulated etween 1973 and 1993 based on biochemical unisite/multisite atalysis and oxygen exchange experiments. 8 An alternati v e ri-site Nath’s torsional mechanism of energy transduction nd ATP synthesis/hydr ol ysis w as first pr oposed in 1999 and ev eloped ov er the next 25 yr using a nov el m ultidisciplinar y pproac h, 9 whic h inte gr ated physics, c hemistry, bioc hemistry, nd engineering. The dir ect measur ements by Senior and oworkers of the fluorescence quenching of tryptophan probes","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":"4 6","pages":"zqad051"},"PeriodicalIF":0.0,"publicationDate":"2023-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10548849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41164820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Do Endogenously Produced and Dietary ω-3 Fatty Acids Act Differently?","authors":"","doi":"10.1093/function/zqad052","DOIUrl":"10.1093/function/zqad052","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1093/function/zqad009.].</p>","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":"4 6","pages":"zqad052"},"PeriodicalIF":0.0,"publicationDate":"2023-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10532101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41172212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inactivation of TRPM7 Kinase Targets AKT Signaling and Cyclooxygenase-2 Expression in Human CML Cells.","authors":"Birgit Hoeger,&nbsp;Wiebke Nadolni,&nbsp;Sarah Hampe,&nbsp;Kilian Hoelting,&nbsp;Marco Fraticelli,&nbsp;Nadja Zaborsky,&nbsp;Anna Madlmayr,&nbsp;Viktoria Sperrer,&nbsp;Laura Fraticelli,&nbsp;Lynda Addington,&nbsp;Dirk Steinritz,&nbsp;Vladimir Chubanov,&nbsp;Roland Geisberger,&nbsp;Richard Greil,&nbsp;Andreas Breit,&nbsp;Ingrid Boekhoff,&nbsp;Thomas Gudermann,&nbsp;Susanna Zierler","doi":"10.1093/function/zqad053","DOIUrl":"10.1093/function/zqad053","url":null,"abstract":"<p><p>Cyclooxygenase-2 (COX-2) is a key regulator of inflammation. High constitutive <i>COX-2</i> expression enhances survival and proliferation of cancer cells, and adversely impacts antitumor immunity. The expression of <i>COX-2</i> is modulated by various signaling pathways. Recently, we identified the melastatin-like transient-receptor-potential-7 (TRPM7) channel-kinase as modulator of immune homeostasis. TRPM7 protein is essential for leukocyte proliferation and differentiation, and upregulated in several cancers. It comprises of a cation channel and an atypical α-kinase, linked to inflammatory cell signals and associated with hallmarks of tumor progression. A role in leukemia has not been established, and signaling pathways are yet to be deciphered. We show that inhibiting TRPM7 channel-kinase in chronic myeloid leukemia (CML) cells results in reduced constitutive <i>COX-2</i> expression. By utilizing a CML-derived cell line, HAP1, harboring CRISPR/Cas9-mediated TRPM7 knockout, or a point mutation inactivating TRPM7 kinase, we could link this to reduced activation of AKT serine/threonine kinase and mothers against decapentaplegic homolog 2 (SMAD2). We identified AKT as a direct in vitro substrate of TRPM7 kinase. Pharmacologic blockade of TRPM7 in wildtype HAP1 cells confirmed the effect on <i>COX-2</i> via altered AKT signaling. Addition of an AKT activator on TRPM7 kinase-dead cells reconstituted the wildtype phenotype. Inhibition of TRPM7 resulted in reduced phosphorylation of AKT and diminished <i>COX-2</i> expression in peripheral blood mononuclear cells derived from CML patients, and reduced proliferation in patient-derived CD34⁺ cells. These results highlight a role of TRPM7 kinase in AKT-driven <i>COX-2</i> expression and suggest a beneficial potential of TRPM7 blockade in COX-2-related inflammation and malignancy.</p>","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":"4 6","pages":"zqad053"},"PeriodicalIF":0.0,"publicationDate":"2023-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6d/e8/zqad053.PMC10541797.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41160752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extravasation of Blood and Blood Toxicity Drives Tubular Injury from RBC Trapping in Ischemic AKI.","authors":"Sarah R McLarnon, Chloe Johnson, Jingping Sun, Qingqing Wei, Gabor Csanyi, Phillip O'Herron, Brendan Marshall, Priya Giddens, Jennifer C Sullivan, Amanda Barrett, Paul M O'Connor","doi":"10.1093/function/zqad050","DOIUrl":"10.1093/function/zqad050","url":null,"abstract":"<p><p>Red blood cell (RBC) trapping is common in ischemic acute kidney injury (AKI) and presents as densely packed RBCs that accumulate within and engorge the kidney medullary circulation. In this study, we tested the hypothesis that \"RBC trapping directly promotes tubular injury independent of extending ischemia time.\" Studies were performed on rats. Red blood cell congestion and tubular injury were compared between renal arterial clamping, venous clamping, and venous clamping of blood-free kidneys. Vessels were occluded for either 15 or 45 min with and without reperfusion. We found that RBC trapping in the medullary capillaries occurred rapidly following reperfusion from renal arterial clamping and that this was associated with extravasation of blood from congested vessels, uptake of blood proteins by the tubules, and marked tubular injury. To determine if this injury was due to blood toxicity or an extension of ischemia time, we compared renal venous and arterial clamping without reperfusion. Venous clamping resulted in RBC trapping and marked tubular injury within 45 min of ischemia. Conversely, despite the same ischemia time, RBC trapping and tubular injury were minimal following arterial clamping without reperfusion. Confirming the role of blood toward tubular injury, injury was markedly reduced in blood-free kidneys with venous clamping. Our data demonstrate that RBC trapping results in the rapid extravasation and uptake of blood components by tubular cells, causing toxic tubular injury. Tubular toxicity from extravasation of blood following RBC trapping appears to be a major component of tubular injury in ischemic AKI, which has not previously been recognized.</p>","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":"4 6","pages":"zqad050"},"PeriodicalIF":5.1,"publicationDate":"2023-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10519276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41161519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intermittent Hypoxia and Respiratory Plasticity: The Good, the Bad, and the Unknown.","authors":"Andrew William Sheel","doi":"10.1093/function/zqad045","DOIUrl":"10.1093/function/zqad045","url":null,"abstract":"","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":"4 6","pages":"zqad045"},"PeriodicalIF":0.0,"publicationDate":"2023-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10519271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41160793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beliefs Made It into Science: Believe It or Not.","authors":"Rüdiger J Seitz,&nbsp;Raymond F Paloutzian","doi":"10.1093/function/zqad049","DOIUrl":"10.1093/function/zqad049","url":null,"abstract":"© t n c long-standing discourse in philosophy dating back to antiqity concerns the nature of beliefs and believing. Until today, he notion “belief” has been of importance in philosophy, as evient from the definition of knowledge as justified true belief. In act, the notion “belief” was understood as a topic of resear c h ocused on people’s attitudes or opinions about what was or was ot true in the w orld. 1 Resear c h questions were summarized by he formula “ S A that P ,” where S denotes the mental state, A he attitude of a putati v el y rational a gent, and P the v erball y xpr essed pr oposition r eflecting the belief. 1 By contrast, the tudy of beliefs was generally assumed to be incompatible with he natural sciences. Ver y r ecentl y, howev er, the term “belief” as been described as to be used widespread in the cogniti v e cience literature to explain human reasoning and behavior. 2 pecifically, it has been described that beliefs act as fundamenal hypotheses about the world that result from any amount of ogniti v e pr ocessing and ar e held with any degr ee of certainty. 3 hus, beliefs are apparently not propositions expressed by conciousl y aw ar e , so-called r ational agents, but, on the contrary, eterminants of people’s spontaneous and intuiti v e behavior in complex world, as highlighted in a recent interdisciplinary esear c h topic. 4 Here , w e put the implications of the recent dvancements in this rapidly evolving field in perspective for the ciences and beyond.","PeriodicalId":73119,"journal":{"name":"Function (Oxford, England)","volume":"4 6","pages":"zqad049"},"PeriodicalIF":0.0,"publicationDate":"2023-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6f/e5/zqad049.PMC10519273.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41171008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}