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  • May 19, 2017
  • 05:13 AM
  • 66 views

Characterization of a FLCN mutation associated with RCC

by Joana Guedes in BHD Research Blog

Mutations in the FLCN gene are the cause of Birt-Hogg-Dubé (BHD) syndrome, a rare disease characterized by renal cell carcinoma (RCC), pneumothorax and fibrofolliculomas. In their new study, Bartram et al. (2017) identify a heterozygous mutation in the FLCN gene in a patient with RCC. DNA from tumour and a metastasis was analysed and the authors demonstrated skipping of exon 11 as the consequence of this mutation leading to a shift in the reading frame and the insertion of a premature sto........ Read more »

Bartram MP, Mishra T, Reintjes N, Fabretti F, Gharbi H, Adam AC, Göbel H, Franke M, Schermer B, Haneder S.... (2017) Characterization of a splice-site mutation in the tumor suppressor gene FLCN associated with renal cancer. BMC medical genetics, 18(1), 53. PMID: 28499369  

  • April 24, 2017
  • 04:22 AM
  • 204 views

Promising mouse model for Ngly1 deficiency

by adam phillips in It Ain't Magic

A recent study of Ngly1 deficient mice used a secondary knockout to create double knockouts with symptoms similar to human NGLY1 deficiency.... Read more »

  • April 20, 2017
  • 05:19 AM
  • 241 views

DHM attenuates obesity-induced slow-twitch-fiber decrease via FLCN/FNIP1/AMPK pathway

by Joana Guedes in BHD Research Blog

Obesity is often associated with decreases in the proportion of skeletal muscle slow-twitch fibers and insulin sensitivity. Slow-twitch fibers are rich in mitochondria and utilize fatty acid oxidative phosphorylation for energy production. In their new study, Zhou et al. (2017) explore the role of the FLCN/FNIP1/AMPK signalling pathway in obesity-induced reductions in slow-twitch fibers and insulin sensitivity in skeletal muscle using high-fat-diet-induced (HFD) obese mice, ob/ob mutant mice, an........ Read more »

  • April 14, 2017
  • 07:00 AM
  • 70 views

Friday Fellow: Crawling Spider Alga

by Piter Boll in Earthling Nature

by Piter Kehoma Boll The world of unicelular creatures includes fascinating species, some of which were already presented here. And today one more is coming, the marine phytoplanctonic amoeboid protist Chlorarachnion reptans, which again is a species without a common name, … Continue reading →... Read more »

  • March 24, 2017
  • 07:58 AM
  • 231 views

Ammonium regulates mTOR signalling

by Joana Guedes in BHD Research Blog

mTORC1 and mTORC2 are two distinct mammalian TOR (target of rapamycin) complexes that regulate cell growth and metabolism. In cancer, genetic alterations lead to activation of mTOR signalling impacting tumour metabolism. Upregulated glutaminolysis is part of the metabolic reaction occurring in cancer that liberates high levels of ammonium, a toxic waste product. Although the importance of glutamine as a tumour nutrient is recognized, little is known about the potential effects of ammonium produc........ Read more »

  • March 24, 2017
  • 07:00 AM
  • 223 views

Friday Fellow: Divergent Dinobryon

by Piter Boll in Earthling Nature

by Piter Kehoma Boll Let’s return once more to the troublesome and neglected protists. This time I’m bringing you another tiny but beautiful alga, more precisely a golden alga. Its name is Dinobryon divergens and as usual there is no common … Continue reading →... Read more »

  • January 27, 2017
  • 12:27 PM
  • 533 views

Impairment of neurogenesis in ZIKV infected neuronal cells: strain specific ? Asian/American v. African strains

by thelonevirologist in Virology Tidbits

uring the current Zika Virus (ZIKV) outbreaks in the Americas, an increased number of cognitive malformations including but not limited to microcephaly in foetuses and neonates of mothers who had been infected with ZIKV during pregnancy, lead to the conclusion that ZIKV might be neuroteratogenic, a hypothesis that has been supported by findings that various ZIKV strains –including isolates from Asia such ZIKV SZ 01, ZIKV FSS13025 and H/PF/2013 as well as isolates from the Americas such as........ Read more »

Li H, Saucedo-Cuevas L, Shresta S, & Gleeson JG. (2016) The Neurobiology of Zika Virus. Neuron, 92(5), 949-958. PMID: 27930910  

van den Pol AN, Mao G, Yang Y, Ornaghi S, & Davis JN. (2017) Zika virus targeting in the developing brain. The Journal of neuroscience : the official journal of the Society for Neuroscience. PMID: 28123079  

Li H, Saucedo-Cuevas L, Regla-Nava JA, Chai G, Sheets N, Tang W, Terskikh AV, Shresta S, & Gleeson JG. (2016) Zika Virus Infects Neural Progenitors in the Adult Mouse Brain and Alters Proliferation. Cell stem cell, 19(5), 593-598. PMID: 27545505  

Tang H, Hammack C, Ogden SC, Wen Z, Qian X, Li Y, Yao B, Shin J, Zhang F, Lee EM.... (2016) Zika Virus Infects Human Cortical Neural Progenitors and Attenuates Their Growth. Cell stem cell, 18(5), 587-90. PMID: 26952870  

Garcez PP, Nascimento JM, de Vasconcelos JM, Madeiro da Costa R, Delvecchio R, Trindade P, Loiola EC, Higa LM, Cassoli JS, Vitória G.... (2017) Zika virus disrupts molecular fingerprinting of human neurospheres. Scientific reports, 40780. PMID: 28112162  

Gabriel, E., Ramani, A., Karow, U., Gottardo, M., Natarajan, K., Gooi, L., Goranci-Buzhala, G., Krut, O., Peters, F., Nikolic, M.... (2017) Recent Zika Virus Isolates Induce Premature Differentiation of Neural Progenitors in Human Brain Organoids. Cell Stem Cell. DOI: 10.1016/j.stem.2016.12.005  

Gromley A, Jurczyk A, Sillibourne J, Halilovic E, Mogensen M, Groisman I, Blomberg M, & Doxsey S. (2003) A novel human protein of the maternal centriole is required for the final stages of cytokinesis and entry into S phase. The Journal of cell biology, 161(3), 535-45. PMID: 12732615  

Meitinger F, Anzola JV, Kaulich M, Richardson A, Stender JD, Benner C, Glass CK, Dowdy SF, Desai A, Shiau AK.... (2016) 53BP1 and USP28 mediate p53 activation and G1 arrest after centrosome loss or extended mitotic duration. The Journal of cell biology, 214(2), 155-66. PMID: 27432897  

Souza BS, Sampaio GL, Pereira CS, Campos GS, Sardi SI, Freitas LA, Figueira CP, Paredes BD, Nonaka CK, Azevedo CM.... (2016) Zika virus infection induces mitosis abnormalities and apoptotic cell death of human neural progenitor cells. Scientific reports, 39775. PMID: 28008958  

  • January 24, 2017
  • 11:52 AM
  • 434 views

Crowdfunding and Tribefunding in Science

by Jalees Rehman in The Next Regeneration

Competition for government research grants to fund scientific research remains fierce in the United States. The budget of the National Institutes of Health (NIH), which constitute the major source of funding for US biological and medical research, has been increased only modestly during the past decade but it is not even keeping up with inflation. This problem is compounded by the fact that more scientists are applying for grants now than one or two decades ago, forcing the NIH to enforce strict........ Read more »

Vachelard J, Gambarra-Soares T, Augustini G, Riul P, & Maracaja-Coutinho V. (2016) A Guide to Scientific Crowdfunding. PLoS Biology, 14(2). PMID: 26886064  

  • January 17, 2017
  • 05:05 PM
  • 374 views

Axl and GAS6: apoptotic mimicry and NLRP-3 inhibition during Zika Virus infection

by thelonevirologist in Virology Tidbits

Zika Virus (ZIKV) is a positive sense RNA virus that belongs to the Flavivirus genus of the Flaviviridae family that includes other human pathogens including Hepatitis C Virus (HCV), Yellow Fever Virus (YFV), West Nile Virus, Dengue Virus (DENV), Tick Borne Encephalitis Virus (TBEV), and Japanese Encephalitis Virus (JEV).
Although being first isolated in 1947, until recently ZIKV was not associated with severe disease; following the introduction of ZIKV in the Americas however, foetal ZIKV inf........ Read more »

Retallack H, Di Lullo E, Arias C, Knopp KA, Laurie MT, Sandoval-Espinosa C, Mancia Leon WR, Krencik R, Ullian EM, Spatazza J.... (2016) Zika virus cell tropism in the developing human brain and inhibition by azithromycin. Proceedings of the National Academy of Sciences of the United States of America, 113(50), 14408-14413. PMID: 27911847  

El Costa H, Gouilly J, Mansuy JM, Chen Q, Levy C, Cartron G, Veas F, Al-Daccak R, Izopet J, & Jabrane-Ferrat N. (2016) ZIKA virus reveals broad tissue and cell tropism during the first trimester of pregnancy. Scientific reports, 35296. PMID: 27759009  

Quicke KM, Bowen JR, Johnson EL, McDonald CE, Ma H, O'Neal JT, Rajakumar A, Wrammert J, Rimawi BH, Pulendran B.... (2016) Zika Virus Infects Human Placental Macrophages. Cell host , 20(1), 83-90. PMID: 27247001  

Savidis, G., Perreira, J., Portmann, J., Meraner, P., Guo, Z., Green, S., & Brass, A. (2016) The IFITMs Inhibit Zika Virus Replication. Cell Reports, 15(11), 2323-2330. DOI: 10.1016/j.celrep.2016.05.074  

Brass AL, Huang IC, Benita Y, John SP, Krishnan MN, Feeley EM, Ryan BJ, Weyer JL, van der Weyden L, Fikrig E.... (2009) The IFITM proteins mediate cellular resistance to influenza A H1N1 virus, West Nile virus, and dengue virus. Cell, 139(7), 1243-54. PMID: 20064371  

Bailey CC, Zhong G, Huang IC, & Farzan M. (2014) IFITM-Family Proteins: The Cell's First Line of Antiviral Defense. Annual review of virology, 261-283. PMID: 25599080  

Meertens L, Carnec X, Lecoin MP, Ramdasi R, Guivel-Benhassine F, Lew E, Lemke G, Schwartz O, & Amara A. (2012) The TIM and TAM families of phosphatidylserine receptors mediate dengue virus entry. Cell host , 12(4), 544-57. PMID: 23084921  

Bhattacharyya S, Zagórska A, Lew ED, Shrestha B, Rothlin CV, Naughton J, Diamond MS, Lemke G, & Young JA. (2013) Enveloped viruses disable innate immune responses in dendritic cells by direct activation of TAM receptors. Cell host , 14(2), 136-47. PMID: 23954153  

  • January 13, 2017
  • 05:11 AM
  • 376 views

Nutrient-dependent FNIP degradation regulates FLCN localization and promotes renal cancer progression

by Joana Guedes in BHD Research Blog

Birt-Hogg-Dubé (BHD) syndrome is a rare disorder caused by mutations in FLCN and associated with increased risk of kidney cancer. It has been shown that FLCN-interacting protein 1 and 2 (FNIP1 and FNIP2) double knockout mice, like the FLCN knockout mice, develop renal carcinoma (Hasumi et al., 2015). However, the molecular mechanisms linking FNIP and FLCN remain unknown. In their new study, Nagashima et al. (2016) show that FNIP2 undergoes proteasome-dependent degradation via β-TRCP ........ Read more »

  • January 10, 2017
  • 01:49 AM
  • 366 views

Blocking obesity with a protein-sugar combination

by adam phillips in It Ain't Magic

Discovery of an enzyme that prevents obesity in mice through glycosylation of a protein involved fat-cell differentiation.... Read more »

Kaburagi T, Kizuka Y, Kitazume S, & Taniguchi N. (2016) Inhibitory role of α2,6-sialylation in adipogenesis. The Journal of biological chemistry. PMID: 28031460  

  • January 9, 2017
  • 04:48 AM
  • 354 views

H255Y and K508R missense mutations in FLCN promote kidney neoplasia

by Joana Guedes in BHD Research Blog

The germline FLCN missense mutations H255Y (Hasumi et al., 2009) and K508R (Toro et al., 2008) have been identified in patients with bilateral multifocal (BMF) kidney tumours and other clinical symptoms of Birt-Hogg-Dube (BHD) syndrome, or with BMF kidney tumours as the only manifestation. Building on their previous work identifying the H255Y mutation in human BHD kidney tumour, Hasumi et al. (2016) investigated whether these mutations have an impact on FLCN function. The authors evaluated the F........ Read more »

  • January 6, 2017
  • 05:00 AM
  • 423 views

Friday Fellow: Conan the Bacterium

by Piter Boll in Earthling Nature

by Piter Kehoma Boll Most people would agree that 2016 was a hard year. So let’s try to make 2017 better by starting this year with a tough Friday Fellow, actually the toughest of them all: Conan the bacterium, or Deinococcus … Continue reading →... Read more »

  • December 23, 2016
  • 06:43 AM
  • 458 views

Establishment of a new BHD Syndrome cell line

by Joana Guedes in BHD Research Blog

Birt-Hogg-Dubé syndrome is caused by mutations in the FLCN gene. The FLCN protein acts as a tumour suppressor and BHD patients have a high risk of developing renal cell carcinoma (RCC). The mechanisms of tumour formation in BHD have been investigated using mouse models and human RCC tissues. However, in vitro signalling studies of human renal cells with mutant FLCN are still scarce. In a recent study, Furuya et al. (2016) established a new cell line from a BHD patient’s chromophobe ........ Read more »

  • December 20, 2016
  • 08:19 AM
  • 477 views

Poking holes into membranes to label proteins for live imaging

by Gal Haimovich in Green Fluorescent Blog

There are two major way to label inner proteins, structures or organnelles for live cell imaging. The most common method is fusing the studied protein to a fluorescent protein. A second approach is the addition of labeling agents from outside the … Continue reading →... Read more »

  • December 14, 2016
  • 08:40 PM
  • 385 views

ZIKV replication and the induction of p53: a tale of three places ?

by thelonevirologist in Virology Tidbits

Zika Virus (ZIKV) is a mosquitoe-borne Flavivirus (MBFV), related to other Flavivirus’ that are transmitted by mosquitoes such as Dengue Virus (DENV), Yellow Fever Virus (YFV) or Tick Borne Encephalitis Virus (TBEV) and as such the viral genome is released into the cytoplasm following viral entry and translated into a single polyprotein that is cleaved by both viral and cellular proteases into the 3 structural and 7 non-structural proteins.
Here the induction of p53 dependent apoptosis an........ Read more »

Li H, Saucedo-Cuevas L, Shresta S, & Gleeson JG. (2016) The Neurobiology of Zika Virus. Neuron, 92(5), 949-958. PMID: 27930910  

Vasilakis N, & Weaver SC. (2016) Flavivirus transmission focusing on Zika. Current opinion in virology, 30-35. PMID: 27936448  

Barreto-Vieira DF, Barth OM, Silva MA, Santos CC, Santos Ada S, F JB Filho, & Filippis AM. (2016) Ultrastructure of Zika virus particles in cell cultures. Memorias do Instituto Oswaldo Cruz, 111(8), 532-4. PMID: 27581122  

Li H, Saucedo-Cuevas L, Regla-Nava JA, Chai G, Sheets N, Tang W, Terskikh AV, Shresta S, & Gleeson JG. (2016) Zika Virus Infects Neural Progenitors in the Adult Mouse Brain and Alters Proliferation. Cell stem cell, 19(5), 593-598. PMID: 27545505  

Pingen M, Bryden SR, Pondeville E, Schnettler E, Kohl A, Merits A, Fazakerley JK, Graham GJ, & McKimmie CS. (2016) Host Inflammatory Response to Mosquito Bites Enhances the Severity of Arbovirus Infection. Immunity, 44(6), 1455-69. PMID: 27332734  

Agarwal A, Joshi G, Nagar DP, Sharma AK, Sukumaran D, Pant SC, Parida MM, & Dash PK. (2016) Mosquito saliva induced cutaneous events augment Chikungunya virus replication and disease progression. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases, 126-35. PMID: 26925703  

Hewitt G, Carroll B, Sarallah R, Correia-Melo C, Ogrodnik M, Nelson G, Otten EG, Manni D, Antrobus R, Morgan BA.... (2016) SQSTM1/p62 mediates crosstalk between autophagy and the UPS in DNA repair. Autophagy, 12(10), 1917-1930. PMID: 27391408  

Danthi P. (2016) Viruses and the Diversity of Cell Death. Annual review of virology, 3(1), 533-553. PMID: 27501259  

Parquet MC, Kumatori A, Hasebe F, Morita K, & Igarashi A. (2001) West Nile virus-induced bax-dependent apoptosis. FEBS letters, 500(1-2), 17-24. PMID: 11434919  

Zhao P, Han T, Guo JJ, Zhu SL, Wang J, Ao F, Jing MZ, She YL, Wu ZH, & Ye LB. (2012) HCV NS4B induces apoptosis through the mitochondrial death pathway. Virus research, 169(1), 1-7. PMID: 22542667  

Netsawang J, Noisakran S, Puttikhunt C, Kasinrerk W, Wongwiwat W, Malasit P, Yenchitsomanus PT, & Limjindaporn T. (2010) Nuclear localization of dengue virus capsid protein is required for DAXX interaction and apoptosis. Virus research, 147(2), 275-83. PMID: 19944121  

Licon Luna RM, Lee E, Müllbacher A, Blanden RV, Langman R, & Lobigs M. (2002) Lack of both Fas ligand and perforin protects from flavivirus-mediated encephalitis in mice. Journal of virology, 76(7), 3202-11. PMID: 11884544  

Tudzarova S, Mulholland P, Dey A, Stoeber K, Okorokov AL, & Williams GH. (2016) p53 controls CDC7 levels to reinforce G1 cell cycle arrest upon genotoxic stress. Cell cycle (Georgetown, Tex.), 15(21), 2958-2972. PMID: 27611229  

Abraham AG, & O'Neill E. (2014) PI3K/Akt-mediated regulation of p53 in cancer. Biochemical Society transactions, 42(4), 798-803. PMID: 25109960  

  • December 11, 2016
  • 02:07 PM
  • 480 views

MS2 mRNA imaging in yeast: more evidence for artefacts

by Gal Haimovich in Green Fluorescent Blog

Previously, on the story of MS2 in yeast: Last year, Roy Parker published a short article, in which he claimed that using the MS2 system in yeast causes the accumulation of 3′ RNA fragments, probably due to inhibition of mRNA … Continue reading →... Read more »

  • December 2, 2016
  • 07:48 AM
  • 443 views

Case studies: BHD syndrome associated with pulmonary malformation and with lung neoplasm

by Joana Guedes in BHD Research Blog

Matsutani et al. (2016) reported for the first time BHD syndrome accompanied by pulmonary arteriovenous malformation. The patient, a young male with no significant medical history, presented with chest pain. Chest X-ray and CT revealed emphysematous changes in both lungs and a tumour with pleural fluid. A thoracoscopy revealed dark red pleural fluid and multiple cysts in the lung. The tumour lesion was resected and identified as a non-malignant intrapulmonary hematoma caused by a significant hae........ Read more »

Matsutani, N., Dejima, H., Takahashi, Y., Uehara, H., Iinuma, H., Tanaka, F., & Kawamura, M. (2016) Birt-Hogg-Dube syndrome accompanied by pulmonary arteriovenous malformation. Journal of Thoracic Disease, 8(10). DOI: 10.21037/jtd.2016.09.68  

Gunji-Niitsu, Y., Kumasaka, T., Kitamura, S., Hoshika, Y., Hayashi, T., Tokuda, H., Morita, R., Kobayashi, E., Mitani, K., Kikkawa, M.... (2016) Benign clear cell “sugar” tumor of the lung in a patient with Birt-Hogg-Dubé syndrome: a case report. BMC Medical Genetics, 17(1). DOI: 10.1186/s12881-016-0350-y  

  • November 25, 2016
  • 06:40 AM
  • 452 views

FLCN haploinsufficiency leads to lung fibroblast dysfunction in patients with BHD syndrome

by Joana Guedes in BHD Research Blog

Birt–Hogg–Dubé syndrome (BHD) is caused by germline mutations in the FLCN gene and characterized by fibrofolliculomas, lung cysts, spontaneous pneumothorax and renal tumours. The stretch hypothesis for pulmonary cyst formation proposes that cysts in BHD arise from defects in cell–cell adhesion, leading to repeated respiration-induced physical stretch-induced stress and, over time, expansion of alveolar spaces particularly in vulnerable regions of lung (Kennedy et al., 20........ Read more »

Hoshika, Y., Takahashi, F., Togo, S., Hashimoto, M., Nara, T., Kobayashi, T., Nurwidya, F., Kataoka, H., Kurihara, M., Kobayashi, E.... (2016) Haploinsufficiency of the gene leads to impaired functions of lung fibroblasts in patients with Birt–Hogg–Dubé syndrome . Physiological Reports, 4(21). DOI: 10.14814/phy2.13025  

  • November 12, 2016
  • 05:53 PM
  • 428 views

Neutralizing and non-neutralizing antibodies: Zika Virus and antibody dependent enhancement of infection

by thelonevirologist in Virology Tidbits

the infection of both mice and non-human primates with various ZIKV strains including the original ZIKV MR766 strain as well as strains from Asia (ZIKV FSS13025), Oceania (ZIKV H/PF/2013) and the Americas (ZIKV Paraiba 2015) as well as the infection of human placenta explants (ZIKV MR766 and ZIKV Nica-1/-2 2016) suggest that ZIKV can cross the placenta probably by infecting maternal cytotrophoblast cells (CTB) and maternal decidual fibroblast cells combined with placental injury due to the relea........ Read more »

Panyasrivanit M, Greenwood MP, Murphy D, Isidoro C, Auewarakul P, & Smith DR. (2011) Induced autophagy reduces virus output in dengue infected monocytic cells. Virology, 418(1), 74-84. PMID: 21813150  

Dejnirattisai W, Supasa P, Wongwiwat W, Rouvinski A, Barba-Spaeth G, Duangchinda T, Sakuntabhai A, Cao-Lormeau VM, Malasit P, Rey FA.... (2016) Dengue virus sero-cross-reactivity drives antibody-dependent enhancement of infection with zika virus. Nature immunology, 17(9), 1102-8. PMID: 27339099  

Sapparapu G, Fernandez E, Kose N, Cao B, Fox JM, Bombardi RG, Zhao H, Nelson CA, Bryan AL, Barnes T.... (2016) Neutralizing human antibodies prevent Zika virus replication and fetal disease in mice. Nature. PMID: 27819683  

Savidis G, Perreira JM, Portmann JM, Meraner P, Guo Z, Green S, & Brass AL. (2016) The IFITMs Inhibit Zika Virus Replication. Cell reports, 15(11), 2323-30. PMID: 27268505  

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