Podcasts about Transferrin

In the latest shortcast, Inez Bosnyak describes a case of ALG1-CDG presenting without an abnormal isoelectric focusing pattern. Normal transferrin glycosylation does not rule out severe ALG1 deficiency Inez Bosnyak, et al https://doi.org/10.1002/jmd2.12415

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.25.538145v1?rss=1 Authors: Barker, S. J., Thayer, M. B., Kim, C., Tatarakis, D., Simon, M., Dial, R. L., Nilewski, L., Wells, R. C., Zhou, Y., Afetian, M., Chappell, A., Chew, K. S., Chow, J., Clemens, A., Discenza, C. B., Dugas, J. C., Dwyer, C., Earr, T., Ha, C., Huynh, D., Jayaraman, S., Kwan, W., Mahon, C., Pizzo, M., Roche, E., Sanders, L., Stergioulis, A., Tong, R., Tran, H., Zuchero, J., Estrada, A. A., Gadkar, K., Koth, C. M., Sanchez, P. E., Thorne, R. G., Watts, R. J., Sandmann, T., Kane, L. A., Rigo, F., Dennis, M. S., Lewcock, J. W., DeVos, S. L. Abstract: Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.04.26.538462v1?rss=1 Authors: Esparza, T. J., Su, S., Francescutti, C. M., Rodionova, E., Kim, J., Brody, D. L. Abstract: Background: The blood brain barrier limits entry of macromolecular diagnostic and therapeutic cargos. Blood brain barrier transcytosis via receptor mediated transport systems, such as the transferrin receptor, can be used to carry macromolecular cargos with variable efficiency. Transcytosis involves trafficking through acidified intracellular vesicles, but it is not known whether pH-dependent unbinding of transport shuttles can be used to improve blood brain barrier transport efficiency. Methods: A mouse transferrin receptor binding nanobody, NIH-mTfR-M1, was engineered to confer greater unbinding at pH 5.5 vs 7.4 by introducing multiple histidine mutations. The histidine mutant nanobodies were coupled to neurotensin for in vivo functional blood brain barrier transcytosis testing via central neurotensin-mediated hypothermia in wild-type mice. Multi-nanobody constructs including the mutant M1R56H, P96H, Y102H and two copies of the P2X7 receptor-binding 13A7 nanobody were produced to test proof-of-concept macromolecular cargo transport in vivo using quantitatively verified capillary depleted brain lysates and in situ histology. Results: The most effective histidine mutant, M1R56H, P96H, Y102H -neurotensin, caused greater than 8 degrees C hypothermia after 25 nmol/kg intravenous injection. Levels of the heterotrimeric construct M1R56H, P96H, Y102H -13A7-13A7 in capillary depleted brain lysates peaked at 1 hour and were 60% retained at 8 hours. A control construct with no brain targets was only 15% retained at 8 hours. Addition of the albumin-binding Nb80 nanobody to make M1R56H, P96H, Y102H -13A7-13A7-Nb80 extended blood half-life from 21 minutes to 2.6 hours. At 30-60 minutes, biotinylated M1R56H, P96H, Y102H -13A7-13A7-Nb80 was visualized in capillaries using in situ histochemistry, whereas at 2-16 hours it was detected in diffuse hippocampal and cortical cellular structures. Levels of M1R56H, P96H, Y102H-13A7-13A7-Nb80 reached more than 3.5 percent injected dose/gram of brain tissue after 30 nmol/kg intravenous injection. However, higher injected concentrations did not result in higher brain levels, compatible with saturation and an apparent substrate inhibitory effect. Conclusion: The pH-sensitive mouse transferrin receptor binding nanobody M1R56H, P96H, Y102H may be a useful tool for rapid and efficient modular transport of diagnostic and therapeutic macromolecular cargos across the blood brain barrier in mouse models. Additional development will be required to determine whether this nanobody-based shuttle system will be useful for imaging and fast-acting therapeutic applications. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.03.28.534324v1?rss=1 Authors: Thorwald, M., Godoy-Lugo, J. A., Silva, J., Head, E., O'Day, P. A., Morgan, T. E., Forman, H. J., Finch, C. E. Abstract: The role of reactive iron in Alzheimers Disease (AD) has major gaps. Little is known of AD changes in iron transport, glutathione-mediated oxidative repair, and associations with ApoE alleles. Intravascular blood was minimized by washing minced postmortem brains. HNE from iron-associated lipid peroxidation was increased in AD prefrontal cortex by 50% for whole tissue and subcellular lipid rafts, where A{beta}-peptides are produced. Proteins mediating iron deposition and oxidative repair were extensively altered by AD. Protein oxidation was proportionate to the iron storage protein ferritin light chain (FTL); both higher in ApoE4. Loss of neurons and synapses in AD was proportionate to FTL. Iron transport was impaired with lower transferrin, transferrin receptor, and ferroportin. AD decreased Ferroptosis suppressor protein 1 and glutamate cysteine ligase modulator subunit (GCLM), which regulates glutathione synthesis. These findings provide a mechanistic framework for iron-associated neurodegeneration during AD through impairment of lipid peroxidation repair mechanisms involving glutathione. Graphical AbstractHypothesis: lipid peroxidation is driven by increased iron stores and decreased antioxidant defenses during AD. Schema shows proteins that mediate iron metabolism in relation to lipid peroxidation (HNE) and antioxidant defenses in prefrontal cortex. AD-associated increase (red), decrease (blue), or no change (grey) relative to cognitively normal elderly controls. A{beta}; amyloid beta, ALDH2; alcohol dehydrogenase, APP; amyloid precursor protein, DMT1; divalent metal transporter 1; FPN, ferroportin; FSP1, ferroptosis suppressor protein 1; FTH1, ferritin heavy chain; FTL; ferritin light chain; GCLC, glutathione cysteine ligase catalytic subunit; GCLM, glutathione cysteine ligase modulator; GPx4, glutathione peroxidase 4; GSH, glutathione; GSSG, glutathione disulfide; GSTA4, glutathione S-transferase A4; HMOX; heme oxygenase; IRP, iron regulatory protein; LAT1, large neutral amino acid transporter 1; LOOH, Lipid hydroperoxides; Nrf2, Nuclear factor erythroid 2-related factor 2; Prdx6, peroxiredoxin 6; TF, transferrin, TfR; Transferrin receptor; xCT, cysteine-glutamate antiporter. O_FIG O_LINKSMALLFIG WIDTH=174 HEIGHT=200 SRC="FIGDIR/small/534324v1_ufig1.gif" ALT="Figure 1" greater than View larger version (45K): org.highwire.dtl.DTLVardef@102dea1org.highwire.dtl.DTLVardef@1665a18org.highwire.dtl.DTLVardef@a4f3eaorg.highwire.dtl.DTLVardef@189aef5_HPS_FORMAT_FIGEXP M_FIG C_FIG Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.06.527405v1?rss=1 Authors: Rangaraj, N., Vaibhava, V., Sudhakar, C., Moharir, S. C., Swarup, G. Abstract: Transferrin and its receptor play an important role in iron homeostasis. Binding of transferrin to its receptor (TFRC, transferrin receptor protein 1) initiates endocytic trafficking and subsequent recycling of TFRC to the plasma membrane. RAB8-positive tubules emanating from the endocytic recycling compartment play an important role in receptor recycling. However, the signaling pathways or mechanisms that mediate formation of RAB8-positive tubules are not clear. Here, we have investigated the role of transferrin-induced signaling in the regulation of RAB8- and MICAL-L1-positive tubules. Addition of transferrin to the serum starved HeLa cells resulted in enhanced recruitment of RAB8 as well as MICAL-L1 to the tubules, which was mediated by TFRC. Dynasore, an inhibitor of dynamin and endocytosis, completely blocked transferrin-induced formation of RAB8/MICAL-L1-positive tubules. RAB8 showed strong colocalization with MICAL-L1 on the tubules. Blocking of SRC or AKT kinase activity by specific inhibitors abolished transferrin-induced recruitment of RAB8 and MICAL-L1 to the tubules. Recycling of transferrin receptor was inhibited by blocking of AKT activity. TBC1D17, a GTPase activating protein for RAB8, inhibited RAB8/MICAL-L1-positive tubule formation. A phospho-mimicking mutant S366D of TBC1D17 did not inhibit formation of RAB8-positive tubules. Overall, these results show that transferrin induces TFRC mediated signaling dependent on endocytosis that is essential for the formation of RAB8- and MICAL-L1-positive tubules involved in recycling of transferrin receptor. Our results also show that AKT regulates transferrin-induced formation of RAB8- and MICAL-L1-positive tubules, which might be mediated by phosphorylation of TBC1D17. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.10.522344v1?rss=1 Authors: Baringer, S. L., Palsa, K., Simpson, I. A., Connor, J. R. Abstract: Background: Apo- (iron free) and holo- (iron bound) transferrin (Tf) participate in precise regulation of brain iron uptake at endothelial cells of the blood-brain barrier. Apo-Tf indicates an iron deficient environment and stimulates iron release, while holo-Tf indicates an iron sufficient environment and suppresses additional iron release. Free iron is exported through ferroportin, with hephaestin as an aid to the process. Until now, the molecular mechanism of apo- and holo-Tfs influence on iron release was largely unknown. Methods: Here we use a variety of cell culture techniques, including co-immunoprecipitation and proximity ligation assay, in iPSC-derived endothelial cells and HEK 293 cells to investigate the mechanism of apo- and holo-Tfs influence over iron release. We placed our findings in physiological context by further deciphering how hepcidin played a role in this mechanism as well. Results: We demonstrate that holo-Tf induces the internalization of ferroportin through the established ferroportin degradation pathway. Furthermore, holo-Tf directly binds to ferroportin, whereas apo-Tf directly binds to hephaestin. Only pathological levels of hepcidin disrupt the interaction between holo-Tf and ferroportin, and no amount of hepcidin disrupts the interaction between apo-Tf and hephaestin. The disruption of the holo-Tf and ferroportin interaction by hepcidin is due to hepcidins ability to rapidly internalize ferroportin compared to holo-Tf. Conclusions: These novel findings provide a molecular mechanism for apo- and holo-Tf regulation of iron release from endothelial cells. They further demonstrate how hepcidin impacts these protein-protein interactions, and offer a model for how holo-Tf and hepcidin corporate to suppress iron release. We have established a more thorough understanding of the mechanisms behind iron release regulation with great clinical impact for a variety of neurological conditions in which iron release is dysregulated. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

In this week's episode, we'll learn more about the impact of dietary methionine restriction on the progression of AML, discuss transferrin upregulation as a cause of high-altitude-induced hypercoagulability, and learn more about the protective effects of leukemia inhibitory factor against graft-versus-host disease.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.04.515170v1?rss=1 Authors: Datta, S., Sugatha, J., Priya, A., Raj, P., Jaimon, E., Jose, A. Abstract: Sorting nexins (SNX) are a family of proteins containing the Phox homology domain, which shows a preferential endo-membrane association and regulates cargo sorting processes. Even with the vast amount of information unveiled systematically, the underlying mechanism of sorting remains elusive. Here, we established that SNX32, a SNX-BAR (Bin/Amphiphysin/Rvs) sub-family member, is associated with SNX4 via its BAR domain. We identified A226, Q259, E256, R366 of SNX32, and Y258, S448 of SNX4 at the interface of these two SNX proteins that are important for maintaining the association. Via its PX domain, SNX32 interacts with the Transferrin receptor (TfR) and Cation Independent Mannose-6-Phosphate Receptor (CIMPR). We showed that the conserved F131 in its PX domain is important in stabilising the above interactions. Silencing of SNX32 led to a defect in intracellular trafficking of TfR and CIMPR, which could be rescued by overexpressing shRNA-resistant snx32. We also showed that both individual domains play an essential role in trafficking. Our results indicate that SNX4, SNX32 and Rab11 may participate in a common pathway regulating transferrin trafficking; however, the existence of an independent pathway for Rab11 and SNX32 could not be completely ruled out. Further, we established that the PX domain of SNX32 could bind to PI(3)P and PI(4)P, suggesting a possible explanation for its sub-cellular localization. Taken together, our study showed that SNX32 mediate the trafficking of specific cargo molecules along distinct pathway via its PX domain-directed binding to phosphoinositides and its BAR domain-mediated association with other SNX family members. Further, using SILAC-based differential proteomics of the wild type and the mutant SNX32, impaired in cargo binding, we identified Basigin (BSG), an immunoglobulin super family member, as a potential interactor of SNX32 in SH-SY-5Y cells. We then demonstrated that SNX32 binds to BSG through its PX domain and facilitates its trafficking to the cell surface. In Neuro-Glial cell lines, the silencing of SNX32 led to defects in neuronal differentiation. Moreover, abrogation in lactate transport in the SNX32 depleted cells led us to propose that the SNX may contribute to maintaining the neuro-glial coordination via its role in BSG trafficking and the associated Monocarboxylate transporter activity. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Good morning and welcome to your Thursday dose of Your Daily Meds.Bonus Review: How is iron carried (or transferred) in the blood? Answer: Fe2+ is converted into Fe3+ Which is then carried on transferrin. Transferrin is a plasma protein, of the B-1 globulin class and is produced in the liver.Quick Question:In approximately what proportion of pregnancies does a single loop of umbilical cord around the foetal neck occur?0.5%2%12%15%25%Have a think.Have a guess.Scroll for the chat.Psyche:When considering schizoid personality disorder, which of the following correctly describes the expected thought form, thought content and relationships that patients may express?(I shall be trying to confuse you between schizoid and schizotypal personality disorders; and schizophrenia with these answer options…)Thought form organised; thought content without psychosis; no desire for social relationshipsThought form vague and circumstantial; thoughts of odd beliefs and magical thinking; socially ineptThought form disorganised; psychotic thought content; socially marginalised, not by choiceThought form disorganised; thought content without psychosis; socially marginalised, not by choiceThought form organised; psychotic thought content; socially ineptHave a think.More scroll for more chat.Looping Back:One loop of umbilical cord around the foetal neck occurs in approximately 25% of pregnancies. The rates for second and third loops are much lower, at 2.5% and 0.5% respectively. Furthermore, a loop of umbilical cord around the foetal body occurs in 4% of pregnancies.It is important to note that true knots of the umbilical cord occur in 1% of pregnancies but are overrepresented in stillbirths, where they occur at an incidence of 4%.On the Clusters:Schizoid personality disorder is a Cluster A personality disorder, characterised by a lack of desire or enjoyment in close relationships and lifelong pattern of social withdrawal. They often have a detached or flat affect and may be described as emotionally cold. They rarely have close friends and take pleasure in few, if any, activities.In contrast to schizotypal personality disorder, another Cluster A disorder, and schizophrenia (not a personality disorder, a distinct disorder of reality testing), people with schizoid personality disorder have organised thoughts, no psychosis and have no desire for close relationships.Check out my hastily created reference table:Bonus: What are the major blood groups? How are they determined and why are they important?Answer in tomorrow’s dose.Closing:Thank you for taking your Meds and we will see you tomorrow for your MANE dose. As always, please contact us with any questions, concerns, tips or suggestions. Have a great day!Luke.Remember, you are free to rip these questions and answers and use them for your own flashcards, study and question banks. Just credit us where credit is due. This is a public episode. If you would like to discuss this with other subscribers or get access to bonus episodes, visit yourdailymeds.substack.com

Celebrating her 100th episode of Update in Under 30 and welcomed back to the Metagenics Institute Podcast by popular demand – it's quite the month for Rachel Arthur! In this episode, the Naturopath and diagnostics aficionado shares her exceptional understanding of iron studies. Rachel covers when to test and why, how to assess each marker, confounders, and important considerations for certain populations, including pregnant women and those who are inflamed or obese. If you're a clinician eager to improve your understanding of iron studies, you will not be disappointed. *Highlights * An evolutionary perspective on iron (10:50) Important considerations pre-iron testing (17:00) Which markers do not reliably reflect of iron status (22:20) Transferrin (27:00) Transferrin saturation (38:00) Ferritin (51:00) What you might not know about iron supplementation (1:00:00) Useful Links Rachel Arthur's webpage - https://rachelarthur.com.au/ Update in Under 30 - https://rachelarthur.com.au/product-category/update-in-under-30/

Aedes Aegypti Gelecekte 2020'li yıllar, yaşanan COVID-19 Pandemisi, depremler, ekonomik krizler, siyasal ve politik skandallar derken herhalde kriz yılları olarak hatırlanacak. Ancak tüm bunların yanında küçük ama rahatsız edici bir felaket daha vardı. Yaz kış demeden amansız sivrisinek saldırıları. Üstelik alışageldiğimiz kahverengi Culex'lerin yanında nispeten yeni bir tür olan siyah ve benekli Aedes saldırıları sanırım hepimizi canımızdan bezdirdi. Skeeter Sendromu Nedir? Özellikle kıyı kesimleri başta olmak üzere evlerde, balkon ve bahçelerde açık havayı zehreden nispeten yeni bir tür olan Aedes sivrisineklerin saldırısına maruz kaldık. Bir türlü görülmeyen ama vızıldayan açgözlü saldırgan sivrisinekler hortumunu (proboskis) uzatıp derileri deldi ve kanları hunharca emdi; ardında bıraktığı sıra dışı büyüklükteki papular ürtikeryel lezyonlar kaşınmaya başlayınca farkına vardık. Eğer sivrisinek sokması sonrası ciltte anormal büyüklükte şişlikler oluşuyor bazen ateş buna eşlik ediyor ama kaşıntı-kızarıklık dışında başka bulgu yoksa işte buna Skeeter Sendromu deniyor.​1​ Normalde sivrisineklerin salgılarındaki bazı proteinlere karşı çoğu insanın derisinde basit bir alerjik reaksiyon gelişir; genelde bu durum lokal küçük bir şişlik ve kızarıklık ile sınırlı kalırken bazı insanlarda biraz abartılı bir reaksiyon olabilir. Bu kaşıntılı lezyonlar tek büyük bir kabartı olabileceği gibi birçok küçük kabartı olarak da görülebilir. Skeeter Sendromu sivrisinek sokmasına bağlı abartılı alerjik reaksiyondur​1​ Skeeter Sendromunun bilinen hayati riski ve klinik bir önemi olmadığı gibi spesifik bir tedavisi de yoktur. Çok rahatsızlık verirse topikal ya da oral antihistaminik ilaçlar kullanılabilir. Skeeter Sendromuna karşı tek çare sivrisinek sokmalarından korunmaktır. Sivrisinek yaşam döngüsü Sivrisinek sokmasından korunmak için de sivrisineğin yaşam döngüsünü, neden ve nasıl soktuğunu bilmek gerekiyor:   Sivrisineğin yaşamında yaklaşık iki hafta kadar süren dört evre vardır: durgun suda geçen (i) yumurta, (ii) larva ve (iii) pupa evresi ve karada geçen (iv) erişkin evresi. Suda geçen evreler en kritik süreçtir; sivrisinek bu süreçleri yaşam alanımızın 50-100 metre yarıçapı bir alanda eski saksılar, lastikler teneke kutular, çukurlar vb toplanan her türlü durgun su birikintisinde geçirir. Sonrasında erişkin hale gelen dişi sivrisinek yumurtalarını olgunlaştırabilmek için demire ihtiyaç duyar ve bu demir ihtiyacını memeli kanındaki Hemoglobin ve Transferrin proteinlerinden elde eder.​​2​ Dişi sivrisinek proboskis denen evrimleşmiş ağız ve burun ortak hortumunun yapısında gelişmiş koku reseptörlerini kullanarak avlarının kokusunu karanlıkta bile bulabilir. Özellikle parfüm, ter asiti ve nefesteki karbondioksit kokuları sivrisineği çeker; bu şekilde sivrisinek cilde yaklaşır ve konar. Sivrisinek proboskisi ile cildi delip kılcal kan damarlara ulaşır. Bu delme ve emme işlemi olağanüstü gelişmiş bir doğal biyomikroelektromekanik sistemdir.​3​ Acil serviste damar yolu açarken kullandığımız kateter mantığı ile sivrisinek proboskisin sivri ucu ile cildi deler, sert kısmı geri çekerken burna benzer esnek kısım kılcal damarın içine yerleştirir. Bu da gösteriyorki sivrisinekler doğanın minik muazzam damaryolu açıcıları, canlı kateterlerdir ve damar bulmada hiç başarısız olmazlar. Delme ve emme işleminde ağız ve burun parçalarının ortak çalışması kan emeceği kişiyi seçmesinde o kişinin yaydığı kokunun önemli olduğunu göstermektedir. Sivrisinekler koklar, görür ve işitir; yaklaşık 50 metre öteden havadaki karbondioksit kokusunu alır, kokuyu takip eder 5-10 metre uzaktan insanı görebilir ve yaklaşır ve son 20-30 cm de ciltten yükselen termal ısı buharını ve kokuyu algılar. Artık geriye sadece cildi delip kanı emmek kalır. Sonuçta artık sivrisinek soktuğunda “Bakın ne kadar kabardım!” demektense “Sanırım ben Skeeter Sendromu oldum” demek belki kaşıntınızı azaltmasa da havanızı artırabilir.

Question: Why would ferritin be extremely high when transferrin saturation is low? Ferritin as a potential indicator of iron overload should not be anywhere near the level that was set to try to rule in biopsy provable hemochromatosis that is just a profoundly negligent approach to setting the range for ferritin. Now, I think part of what has stopped, you know— This mostly is a problem of the binary diagnostic mindset of conventional medicine. So, I'm not saying that this mindset is not useful. It is tremendously useful, but too many people confuse it for a reality when in fact it is a reality distortion filter meant to more efficiently triage people through various treatments or nontreatments. It may be inflammation as you very well tried to feather out. And if it's not that, it's probably oxidative stress. So, I’m not gonna say that’s the only other thing it could be. And for the record, you cannot rule out hemochromatosis genetics with 23andMe or any other genetic test by anyone because there are a small percentage of hemochromatosis genetics that are not in the HFE genes and no one has a panel for them. And so, it’s improbable that it’s hemochromatosis based on 23andMe. You can’t rule it out, but I would say it’s probably not hemochromatosis because his iron is low. And so, you know, I'm highly suspicious of oxidative stress, which also upregulates ferritin. If you have Testing Nutritional Status: The Ultimate Cheat Sheet, I would measure everything in the oxidative stress section. If you would like to be part of the next live Ask Me Anything About Nutrition, sign up for the CMJ Masterpass, which includes access to these live Zoom sessions, a private discussion group, premium features on all my content, and hundreds of dollars of exclusive discounts. You can sign up at https://chrismasterjohnphd.com/masterpass/ and use the code QANDA to get 10% off the membership for life. For the remainder of 2020, I will be working full-time on finishing my Vitamins and Minerals 101 book, while reserving a portion of my time for consulting clients. You can pre-order my book at https://chrismasterjohnphd.com/book. You can sign up for a consultation at https://chrismasterjohnphd.com/consultations  DISCLAIMER: I have a PhD in Nutritional Sciences and my expertise is in performing and evaluating nutritional research. I am not a medical doctor and nothing herein is medical advice.

Hier erfahrt ihr die wichtigsten Nachrichten rund um die Goethe Uni: Wissenschaftler*innen vermuten, dass Transferrin ein Indikator für schwere Krankheitsverläufe

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.05.133819v1?rss=1 Authors: Kucharz, K., Kristensen, K., Johnsen, K. B., Lund, M. A., Lønstrup, M., Moos, T., Andresen, T. L., Lauritzen, M. J. Abstract: Treatments of neurodegenerative diseases require biologic drugs to be actively transported across the blood-brain barrier (BBB). To answer outstanding questions regarding transport mechanisms, we determined how and where transcytosis occurs at the BBB. Using two-photon microscopy, we characterized the transport of therapeutic nanoparticles at all steps of delivery to the brain at the nanoscale resolution in vivo. Transferrin receptor-targeted nanoparticles were taken up by endothelium at capillaries and venules, but not at arterioles. The nanoparticles moved unobstructed within endothelial cells, but transcytosis across the BBB occurred only at post-capillary venules, where endothelial and glial basement membranes form a perivascular space that can accommodate biologics. In comparison, transcytosis was absent in capillaries with closely apposed basement membranes. Thus, post-capillary venules, not capillaries, provide an entry point for the transport of large molecules across the BBB, and targeting therapeutic agents to this locus may be an effective way for treating brain disorders. Copy rights belong to original authors. Visit the link for more info

Question: In hemochromatosis, why would ferritin be low but transferrin saturation high? Ferritin is your long-term iron storage. Transferrin is your short-term iron storage. The problem with hemochromatosis is that usually in a normal functioning system, there is a hormonal regulatory system that prevents you from absorbing iron from food when you have enough iron that when you have too much iron, shuttle the iron into ferritin which is protective both against pathogens eating the iron to grow and against oxidative stress, which free iron causes, which if you don't know the details about can be thought of as wear and tear on your tissues over time. In hemochromatosis, normally the way you judge how much iron you have is in the circulating transferrin pool, which is your short-term storage. How full is it? The defect in hemochromatosis is that when the short-term storage, transferrin, starts getting fuller than usual, you don't notice it, so you don't stop absorbing iron from food that makes the transferrin saturation go up even further. But you don't shuttle the iron into ferritin. That makes ferritin lower. What people get confused by is that historically, we have only paid attention to hemochromatosis when it's too late, when the person has been suffering for it from 30 or 40 years and they need organ transplants. What happens at that point is that the ferritin is very, very high. Why is the ferritin high? Not because you had too much iron. The person without hemochromatosis has the ferritin go up when they have too much iron. The defect in hemochromatosis is that you do not stop absorbing from food when you have enough, and you do not put the iron into ferritin when you have too much. The reason that ferritin is high in someone who's had hemochromatosis for 30 or 40 years is not because they have too much iron. It is because they have oxidative stress and damage caused by that iron. Oxidative stress and damage cause ferritin to go up no matter how much iron you have. So does infection, no matter how much iron you have. Essentially, what you have is ferritin is not the fireman that he should be to put out the fire as it starts, and the smoke detectors go off. Ferritin hemochromatosis is the cleanup crew who got to the fire after the house burned down. This Q&A can also be found as part of a much longer episode, here: https://chrismasterjohnphd.com/podcast/2019/03/30/ask-anything-nutrition-march-4-2019 If you would like to be part of the next live Ask Me Anything About Nutrition, sign up for the CMJ Masterpass, which includes access to these live Zoom sessions, premium features on all my content, and hundreds of dollars of exclusive discounts. You can sign up with a 10% lifetime discount here: https://chrismasterjohnphd.com/q&a

Question: For someone who is homozygous for the H63D allele of the iron- and hemochromatosis-related HFE gene, if ferritin is low but transferrin saturation is high, should they still donate blood?   H63D is one of the genes that predisposes to hemochromatosis, a condition of iron overload. Most clinicians who work in this area do not consider the H63D allele to be a concern because it's less severe. With that said, most people who are progressive on the iron research front do believe it's a concern. There is literature showing that people can get clinical hemochromatosis from it and you don't have to get clinically hemochromatosis to be worried about iron overload.     My opinion on this is going to be different than someone who is an expert clinician, but is not immersing themselves deeply in the physiological literature about how this works.   I don't have the skills that they have in triaging and filtering who’s ideal for what treatment and looking at large numbers of people that do one or another treatment and knowing intuitively what happens in those — but what I do have is I have immersed myself very deeply in the physiology.    So the way that I look at this is as follows: iron saturation is an estimate of your transferrin saturation. It's a cheaper way to estimate it than to actually measure transferrin saturation, so it's much more common to get iron saturation.   But let's assume that we're talking about actual transferrin saturation or that iron saturation is a good metric of it. That's your short-term iron storage. Ferritin is your long-term iron storage. The defect in the H63D allele, same for the C282Y allele of the HFE gene, the two moderate and severe hemochromatosis alleles. Allele is a variant of the gene.   In normal physiology what happens is transferrin acts as a gauge of your iron status. The normal physiological levels are between 30 and 40 percent. Now being 41 percent doesn't mean you have a disease, we're not talking about diagnosis here, we're talking about understanding the physiology.   Mechanistically this is designed so that as you go from 30 to 40 percent and especially as you go over 40 percent that communicates the signal to a hormonal system that says you have more iron than you need. So you ramp down iron absorption and you ramp up ferritin. Why do you ramp up ferritin? Because you have more than you need in your short-term storage, so that's when you put it into your long-term storage. Also, because ferritin is a protective response that prevents you from having free iron.   Free iron is bad because it feeds pathogens and it makes infections worse. Free iron is bad because it causes oxidative stress and causes wear and damage on your tissues. And so to avoid free iron you ramp up ferritin while you take down your absorption from food at the same time.   And now is that a problem at all?  You could debate that, but if you're just talking, if you're not talking about diagnosis and you're talking about wellness, and you're talking about health management then… What I would want to do myself in that situation is I would first of all not let the ferritin go under 20, and if it's going near there I would be getting a CBC to make sure I'm not making myself anemic.    And so I would not stop donating blood just because the ferritin is going down 60, 50, 40, I would consider it a gray area, it would be my preference to focus on the transferrin saturation and get it consistently under 40%. You get the pinprick to look at your serum iron levels, they're not going to let you donate blood if you're actually in the danger zone of anemia.   So I would get the CBC to be proactive about it.   This Q&A can also be found as part of a much longer episode, here: https://chrismasterjohnphd.com/podcast/2019/02/24/ask-anything-nutrition-feb-17-2019/   If you would like to be part of the next live Ask Me Anything About Nutrition, sign up for the CMJ Masterpass, which includes access to these live Zoom sessions, premium features on all my content, and hundreds of dollars of exclusive discounts. You can sign up with a 10% lifetime discount here: https://chrismasterjohnphd.com/q&a

Podcaster:Caitlyn VlasschaertMedical Discipline/Topic:Hematology, Internal MedicineIntended AudienceYear 1, Year 2, Year 3, Year 4Brief Synopsis/Key Takeaways:1. Think of the 4 major AOLI causes (alcohol, overload, liver, inflammation), keeping in mind that several are likely contributing in one patient.2. Transferrin saturation >45% is highly suggestive of iron overload as a contributing factor, including hemochromatosis, and would warrant referral to hematology. Other key tests to order include: CBC, ESR, CRP, Cr and lytes, LFTs and hepatitis serology (B and C), abdominal U/S, glucose, A1C, lipids, and HFE gene testing if you’re suspicious of hemochromatosis.3. Good rule of thumb: High ferritin is anything >300, but for those in the 300-1000 range, lifestyle modification targeting the non-iron overload causes is appropriate, with hematology referral for ferritin above 1000 as this plus high transferrin saturation is specific for hemochromatosis and phlebotomy may be necessary. Alcohol cessation is also recommended in hemochromatosis.

Do you want to know why you may be feeling so tired all the time? In this episode, I share 3 common reasons that are, at times, overlooked and the lab work you need to ask for at your next doctor's appointment. 3 Possible Reasons for Your Fatigue: Thyroid: Full thyroid panel including: thyroid peroxidase, anti-thyroglobulin, TSH, Free T3, Total T3, Free T4, Total T4, Reverse T3, Adrenals: Saliva testing or A.M. cortisol, fasting and no coffee or tea Iron Deficiency: Iron panel including, total iron binding capacity, Ferritin, Transferrin, and % Saturation. Show notes: http://www.margaretromero.com/episode86  

The TWIPniks solve the case of the Man With Diarrhea and 100 Micron Objects In Stool, and discuss the reticulocyte receptor for Plasmodium vivax. Hosts: Vincent Racaniello, Dickson Despommier, and Daniel Griffin Become a patron of TWiP. Links for this episode: Reticulocyte receptor for Plasmodium vivax (Science) Image credit: Parasitic Diseases, 6th Ed. Parasite Heroine: Marietta Voge Letters read on TWiP 146 Case Study for TWiP 146 27 yo male lawyer comes NY area to be seen, has 4 cm ulcer on right foot. Painless, has raised borders, minimal surrounding erythema. Going on for quite a while. Initially was papule, enlarged, ulcerated, this enlarged and has been more than 4 weeks. No past med probs, allergic to penicillin but just upset his stomach. No meds. Social habits: drinking. Own apt in NYC. Travel: 1 month before papule was whitewater rafting in Costa Rica, noticed when he got back. Wore sandals, got lots of insect bites. Afebrile, normal BP, fit athletic young man. Non tender lesion, base is red, white fibrous coating. Border raised but not undermined. No surrounding swelling, no eschar over wound, open non healing. Send your case diagnosis, questions and comments to twip@microbe.tv Music by Ronald Jenkees

In episode 32, I tell the story of my personal story with iron overload, and weigh in on the proper use of blood tests and strategies to manage anemia, hemochromatosis, and everything in between. It's important to realize that these are the extremes, and there is a large middle space where we need to not only manage how much iron we accumulate, but how we direct it away from its disease-promoting roles and into its health-promoting roles. This is a great primer on iron as well as a source of insights you may not have encountered elsewhere, such as the importance of oxidative stress as an independent regulator of ferritin, and the potential dangers of supplements designed to protect against oxidative stress like milk thistle, Protandim, sulforaphane, and green tea extract, for people at risk of anemia. You can find the show notes to this episode at chrismasterjohnphd.com/32. This episode is also brought to you by US Wellness Meats. Head to grasslandbeef.com and enter "Chris" at checkout to get 15% off your order as long as the final price is over $75 and you order fewer than 40 pounds of meat. You can use "Chris" to get the same discount twice. This episode is brought to you by Kettle and Fire Bone Broth. Use the link kettleandfire.com/chris to get $10 off your first order. In this episode, you will find all of the following and more: 0:33 Cliff Notes; 10:30 Introduction; 13:12 My personal story with iron overload; 30:12 The physiological roles of iron: hemoglobin, myoglobin, nitric oxide synthase, iron-sulfur clusters in the cytochromes of the electron transport chain, guanylyl cyclase, thyroid peroxidase (TPO), myeloperoxidase (MPO), oxygen transport, energy and ATP production, cellular regulation, thyroid hormone production, immunity; 38:20 Iron as a source of oxidative stress: free iron, hydrogen peroxide, and the hydroxyl radical, oxidative stress as an independent regulator of ferritin; 41:10 Regulation of iron status; Ferritin, long-term storage, protector against pathogens, protector against oxidative stress; Transferrin, short-term iron storage; Hepcidin, master coordinator of iron metabolism; HFE, communicator between transferrin and hepcidin; 49:10 Regulation of dietary absorption of plant and animal iron; 51:00 Measuring and assessing iron status: complete blood count (MCH, MCV, RDW, CHr), full iron panel, sensitivity and specificity of transferrin saturation versus ferritin, differential interpretation of ferritin as a marker of iron overload, inflammation, or oxidative stress; 1:11:43 What to do for anemia: differentiate potential causes, iron in foods (heme, nonheme, vitamin C, polyphenols, phytate, calcium), iron in supplements (iron-saturated lactoferrin, heme iron, liposomal iron), avoid Nrf2-stimulating supplements (like Protandim, sulforaphane, milk thistle, green tea extract), importance of followup measurements of ferritin 01:21:03 What to do for iron overload: blood donation, dietary management, phlebotomy, chelation, importance of followup  

An iron hand controls endosome-mitochondria contacts In erythroid cells, endocytosed iron is directly transferred into mitochondria at dynamic endosome-mitochondria contacts. Das et al. reveal that this process also occurs in epithelial cells, and that the motility of endosomes, and the duration of their interactions with mitochondria, is modulated by intra-endosomal iron release from transferrin. This biosights episode presents the paper by Das et al. from the September 26th, 2016, issue of The Journal of Cell Biology and includes an interview with the paper's senior author, Margarida Barroso (Albany Medical College, Albany, NY). Produced by Caitlin Sedwick and Ben Short. See the associated paper in JCB for details on the funding provided to support this original research. Subscribe to biosights via iTunes or RSS View biosights archive The Rockefeller University Press biosights@rockefeller.edu

Hosts: Vincent Racaniello, Alan Dove, Rich Condit, and Kathy Spindler In their final episode of the year, the TWiV team reviews ten compelling virology stories from 2013. Links for this episode Antiviral RNAi (TWiV 255, 256, 263) MERS-CoV (TWiV 215, 223, 224, 233, 239, 247, 251, 258) Placental trophoblasts confer viral resistance (TWiV 241) Origin of REV (TWiV 248) Phage T7 gets a cat scan (TWiV 220) It's a cGAS! (TWiV 222) Dual virus-host arms race (TWiV 242) Pandoraviruses (TWiV 246, 261) CMV based SIV vaccine (TWiV 254) Threading the NEIDL Letters read on TWiV 265 Video of this episode - view at YouTube Weekly Science Picks Kathy - Women in ScienceAlan - ContagiumRich - RC helicopter (demo)Vincent - The athletic power of quadcopters Listener Pick of the Week Lindsay - Alcohol consumption and vaccines (Vaccine)Johnye - The Singing Microbiologist Send your virology questions and comments (email or mp3 file) to twiv@twiv.tv

Hosts: Vincent Racaniello, Dickson Despommier, Alan Dove, Rich Condit, and Kathy Spindler The complete TWiV team talks about how two different viruses shape the evolution of an essential housekeeping protein. Links for this episode: Dual virus-host arms race (PLoS Biology) Dual virus-receptor duel (see comments - virology blog) Ferritin and transferrin (Protein Data Bank) Money for nothing (YouTube) Letters read on TWiV 242 Weekly Science Picks Dickson - Mantid imagesKathy - No email? (phd comics)Alan - The turbid plaqueVincent - AAM Faq: West Nile VirusRich - Science is awesome Listener Pick of the Week Luis - Public Health Image LibraryStephen - Hopkins closes graduate science-writing program Send your virology questions and comments (email or mp3 file) to twiv@twiv.tv

Thu, 8 May 2008 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/8507/ https://edoc.ub.uni-muenchen.de/8507/4/Mueller_Rahel.pdf.pdf Müller, Rahel

Aims: During pregnancy, the placenta produces a variety of steroid hormones and proteins. Several of these substances have been shown to exert immunomodulatory effects. Progesterone is thought to mediate some of these effects by regulating uterine responsiveness. The aim of this study was to clarify the effect of amniotic fluid transferrin and its N-glycans on the release of progesterone by first trimester trophoblast cells in vitro. Methods: Cytotrophoblast cells were prepared from human first trimester placentae by trypsin-DNAse dispersion of villous tissue followed by a percoll gradient centrifugation and depletion of CD45 positive cells by magnetic cell sorting. Trophoblasts were incubated with varying concentrations (50-300 mug/ml) of transferrin from human amniotic fluid and serum as well as with N-glycans obtained from amniotic fluid transferrin. Culture supernatants were assayed for progesterone by enzyme-immunometric methods. Results: The release of progesterone increased in amniotic fluid transferrin- and N-glycan-treated trophoblast cell cultures compared to untreated trophoblast cells. There was no stimulating effect of serum transferrin on the progesterone production of trophoblast cells. Conclusions: The results suggest that amnion-transferrin and especially its N-glycans modulate the endocrine function of trophoblasts in culture by up regulating progesterone secretion.

In den vergangenen Jahren wurden einige angeborene Stoffwechselerkrankungen entdeckt, deren Ursache in einer defekten Synthese von N-gebundenen Glykoproteinen liegt, so genannte „Congenital Disorders of Glycosylation“ (CDG). Die klassische Galaktosämie und der Fruktosemangel führen auf ähnliche Weise zu sekundären Glykosylierungsstörungen. Um Patienten mit CDG-Syndrom und anderen Stoffwechselerkrankungen auf eine Glykosylierungsstörung hin zu untersuchen, haben wir im ersten Teil der Arbeit eine Methode zur Isoelektrofokussierung von Transferrin entwickelt. Die IEF im Mini-PhastSystem ist hier besonders schnell und zuverlässig. Die charakteristischen Bandenmuster des mit einer verminderten Anzahl an Sialinsäureresten glykosylierten Transferrins liefern erste differentialdiagnostische Erkenntnisse. Zwei unserer Patienten zeigten in der Mini-PhastSystem-IEF ein Muster, wie es normalerweise bei Patienten mit CDG Ia gefunden wird. Entgegen der Erwartung erwiesen sich aber die Enzyme Phosphomannomutase sowie auch die Phosphomannoisomerase als normal hoch im Vergleich zu gesunden Kontrollpersonen. Die Ergebnisse deuten darauf hin, dass es sich bei den genannten Patienten um eine Gruppe handelt, die an einer seltenen Form des CDG-Syndroms leidet, „CDG-X“ genannt. Die Patienten zeigen in der Isoelektrofokussierung ein klassisches Bandenmuster, wobei der zugrundeliegende pathophysiologische Defekt im Stoffwechselweg bislang nicht aufgeklärt werden konnte. Neben typischen Mini-IEFT-Mustern von Patienten mit CDG Ia haben wir auch Patienten mit folgender interessanter Befundkonstellation gefunden: Einige Neugeborene mit Epimerase- Mangel zeigten überraschenderweise CDG Banden mit 0-3 SR. Diese Banden korrelierten nicht mit der Höhe der Galaktose-Metaboliten und verschwanden auch nicht nach einer diätetischen Behandlung. Diese Befunde unterscheiden sich von den Befunden der klassischen Galaktosämie, da hier die pathologischen IEFT Muster nach diätetischen Maßnahmen verschwunden sind. Das Screening der Serum IEFT Banden mittels dieser schnellen Mini-IEFT Technik kann als sinnvolle Methode für die Überwachung und Nachbetreuung des Epimerase Mangels verwendet werden. Im zweiten Teil der Arbeit erfolgte die biochemische Charakterisierung der Enzyme Phosphomannomutase und Phosphomannoisomerase in Leukozyten, Fibroblasten und Chorionzotten. Diese beiden Enzyme sind für die häufigsten Formen des CDG-Syndroms, Typ Ia und Ib, verantwortlich, welche bei ca. 80% der gesamten CDG-Patienten vorliegen. Während die Enzymdiagnostik in Fibroblasten und Leukozyten auf einer bereits etablierten Methode beruht und eine zuverlässige und effektive Quelle für die postnatale Diagnostik darstellt, untersuchten wir erstmals Chorionzotten, um zusätzlich die Möglichkeit einer pränatalen Kontrolle beurteilen zu können. Die Km-Werte und andere kinetische Eigenschaften der Enzyme waren in Leukozyten, Fibroblasten und Chorionzotten ähnlich und ermöglichen somit eine gute post- sowie eine pränatale Diagnostik der Enzymdefekte. Zusammenfassend stellt die Mini- IEF von Transferrin eine einfache und schnelle Screeningmethode zum Nachweis von Glykosylierungsstörungen, klassischer Galaktosämie und Epimerase-Mangel dar. Die Enzymmessung der PMM und PMI in Leukozyten und Fibroblasten nach der Geburt kann in der weiterführenden iagnostik durch die pränatale Untersuchung von Chorionzotten sinnvoll ergänzt werden. Die Tatsache, dass wir Patienten mit ausgeprägten Typ I IEFT-Banden bei normalen Enzymwerten gefunden haben, lässt vermuten, dass es CDG-Varianten mit noch stärkeren Glykosylierungsdefekten gibt.

Transferrin, an iron-transporting serum glycoprotein, is efficiently taken up into cells by the process of receptor-mediated endocytosis. Transferrin receptors are found on the surface of most proliferating cells, in elevated numbers on erythroblasts and on many kinds of tumors. The efficient cellular mechanism for uptake of transferrin has been subverted for the delivery of low-molecular-weight drugs, protein toxins, and liposomes by linkage of these agents to transferrin or to anti-transferrin receptor antibodies. Linkage may be via chemical conjugation procedures or by the generation of chimeric fusion proteins. Transferrin conjugated to DNA-binding compounds (e.g. polycations or intercalating agents) has been successfully used for the import of DNA molecules into cells. High-level gene expression is obtained only if endosome-disruptive agents such as influenza hemagglutinin peptides or adenovirus particles are included which release the DNA complex from intracellular vesicles into the cytoplasm.

Complexes containing plasmid DNA, transferrin-polylysine conjugates, and polylysine-conjugated peptides derived from the N-terminal sequence of the influenza virus hemagglutinin subunit HA-2 have been used for the transfer of luciferase or beta-galactosidase marker genes to K562 cells, HeLa cells, and BNL CL.2 hepatocytes. These DNA complexes mimic the entry of viruses into cells, as they contain functions for (i) the packaging of the nucleic acid with polylysine, (ii) the attachment to the cell and receptor-mediated endocytosis with transferrin as a ligand, and (iii) the release from endosomes by using membrane-disrupting influenza peptides. The presence of these influenza peptide conjugates in the DNA complexes renders the complexes active in membrane disruption in a liposome leakage assay and results in a substantial augmentation of the transferrin-polylysine-mediated gene transfer.

We are developing efficient methods for gene transfer into tissue culture cells. We have previously shown that coupling of a chimeric adenovirus with polylysine allowed the construction of an adenovirus-polylysine-reporter-gene complex that transferred the transporter gene with great efficiency into HeLa cells. We have now explored simpler, biochemical means for coupling adenovirus to DNA/polylysine complexes and show that such complexes yield virtually 100% transfection in tissue culture cell lines. In these methods adenovirus is coupled to polylysine, either enzymatically through the action of transglutaminase or biochemically by biotinylating adenovirus and streptavidinylating the polylysine moiety. Combination complexes containing DNA, adenovirus-polylysine, and transferrin-polylysine have the capacity to transfer the reporter gene into adenovirus-receptor- and/or transferrin-receptor-rich cells.

We have previously demonstrated that transferrin-polycation conjugates are efficient carrier molecules for the introduction of genes into eucariotic cells. We describe here a more specific method for conjugation of transferrin with DNA-binding compounds involving attachment at the transferrin carbohydrate moiety. We used the polycation poly(L-lysine) or the DNA intercalator, ethidium homodimer as DNAbinding domains. Successful transferrin-receptor-mediatedd elivery and expression of the Photinus pyralis luciferase gene in K562 cells has been shown with these new transferrin conjugates. The activity of the transferrin-ethidium homodimer (TfEtD) conjugates is low relative to transferrin-polylysine conjugates; probably because of incomplete condensation of the DNA. However, DNA delivery with TfEtD is drastically improved when ternary complexes of the DNA with TfEtD and the DNA condensing agent polylysine are prepared. The gene delivery with the carbohydrate-linked transferrin-polylysine conjugates is equal or superior to described conjugates containing disulfide linkage. The new ligation method facilitates the synthesis of large quantities (>lo0 mg) of conjugates. INTRODUCTION Transferrin-polycation conjugates are efficient carriers for the uptake of DNA into eucariotic cells (I). This gene transfer technique, termed tramferrinfection, is based on receptor-mediated endocytosis of DNA complexed with polycation-transferrin conjugates (2,3). Our initial conjugate synthesis (1) involved the modification of one to two amino groups on the transferrin molecule with the bifunctional reagent succinimidyl34 2-pyridy1dithio)propionate (SPDP), followed by ligation to similarly modified polycations (polylysine or protamine) through the formation of disulfide bonds. Because there are more than 50 lysines on the large (about 80 kDa) transferrin protein, the actual site (or sites) of ligation to the polycation is unknown with this method. In this paper we describe the synthesis of new transferrin conjugates that are ligated with DNA-binding compounds in a specific manner through modification of the transferrin carbohydrate moiety. The conjugates thus obtained are free of any groups derived from chemical linking agents, since the connecting atoms are already present within the starting compounds. The carbohydrate group acts as anatural spacer that puts a 32-atom distance between the transferrin and the DNA binding moiety. This spacer effect may be important for appropriate presentation of the ligand to its receptor. As a DNA-binding compound, the polycation polylysine was used, similar to the use described in ref 1 or to the asialo-orosomucoid conjugates prepared by Wu and Wu (4). We have also prepared a novel type of transferrin conjugate that contains the DNA intercalator ethidium homodimer (5) as the DNAbinding group and demonstrate successful receptormediated gene delivery with these conjugates. EXPERIMENTAL PROCEDURES Human transferrin (iron-free), conalbumin (iron-free), and poly(L-lysine) were obtained from Sigma. Liquid chro- Abbreviations used: FITC, fluorescein ieothiocyenate; TfEtD, traneferrin-ethidium homodimer conjugate; TfpL, traneferrinpolytL- lysine) conjugate; HEPES, 4-(2-hydroxyethyl)-l-piperazineethanesulfonic acid.

Tue, 1 Jan 1991 12:00:00 +0100 http://epub.ub.uni-muenchen.de/4032/ http://epub.ub.uni-muenchen.de/4032/1/012.pdf Curiel, David T.; Agarwal, Santosh; Wagner, Ernst; Cotten, Matt Curiel, David T.; Agarwal, Santosh; Wagner, Ernst und Cotten, Matt (1991): Adenovirus enhancement of transferrin-polylysine-mediated gene delivery. In: Proceedings of the National Academy of Science of the U S A, Vol. 88, Nr. 19: pp. 8850-8854. Chemie und Pharmazi

Tue, 1 Jan 1991 12:00:00 +0100 http://epub.ub.uni-muenchen.de/4031/ http://epub.ub.uni-muenchen.de/4031/1/011.pdf Wagner, Ernst; Cotten, Matt; Foisner, Roland; Birnstiel, Max L. Wagner, Ernst; Cotten, Matt; Foisner, Roland und Birnstiel, Max L. (1991): Transferrin-polycation-DNA complexes. The effect of polycations on the structure of the complex and DNA delivery to cells. In: Proceedings of the National Academy of Science of the U S A, Vol. 88, Nr. 10: pp. 4255-4259.

Mon, 1 Jan 1990 12:00:00 +0100 http://epub.ub.uni-muenchen.de/4030/ http://epub.ub.uni-muenchen.de/4030/1/009.pdf Cotten, Matt; Längle-Rouault, Francoise; Kirlappos, Helen; Wagner, Ernst; Mechtler, Karl; Zenke, Martin; Beug, Hartmut; Birnstiel, Max L. Cotten, Matt; Längle-Rouault, Francoise; Kirlappos, Helen; Wagner, Ernst; Mechtler, Karl; Zenke, Martin; Beug, Hartmut und Birnstiel, Max L. (1990): Transferrin-polycation-mediated introduction of DNA into human leukemic cells. Stimulation by agents that affect the survival of transfected DNA or modulate transferrin receptor levels. In: Proceedings of the National Academy of S

Mon, 1 Jan 1990 12:00:00 +0100 http://epub.ub.uni-muenchen.de/4029/ http://epub.ub.uni-muenchen.de/4029/1/008.pdf Zenke, Martin; Steinlein, Peter; Wagner, Ernst; Cotten, Matt; Beug, Hartmut; Birnstiel, Max L. Zenke, Martin; Steinlein, Peter; Wagner, Ernst; Cotten, Matt; Beug, Hartmut und Birnstiel, Max L. (1990): Receptor-mediated endocytosis of transferrin-polycation conjugates. An efficient way to introduce DNA into hematopoietic cells. In: Proceedings of the National Academy of Science of the U S A, Vol. 87, Nr. 10: pp. 3655-3659.

We have developed a high-efficiency nucleic acid delivery system that uses receptor-mediated endocytosis to carry DNA macromolecules into cells. We accomplished this by conjugating the iron-transport protein transferrin to polycations that bind nucleic acids. Human transferrin, as well as the chicken homologue conalbumin, has been covalently linked to the small DNA-binding protein protamine or to polylysines of various sizes through a disulfide linkage. These modified transferrin molecules maintain their ability to bind their cognate receptor and to mediate efficient iron transport into the cell. The transferrin-polycation molecules form electrophoretically stable complexes with double-stranded DNA, single-stranded DNA, and modified RNA molecules independent of nucleic acid size (from short oligonucleotides to DNA of 21 kilobase pairs). When complexes of transferrin-polycation and a bacterial plasmid DNA containing the gene for Photinus pyralis luciferase are supplied to eukaryotic cells, high-level expression of the luciferase gene occurs, demonstrating transferrin receptor-mediated endocytosis and expression of the imported DNA. We refer to this delivery system as "transferrinfection."

Mon, 1 Jan 1979 12:00:00 +0100 https://epub.ub.uni-muenchen.de/8823/1/8823.pdf