Biology

The UK is spending billions on overseas fossil fuel projects

Genetics - 19 hours 39 min ago
The UK plans to be carbon neutral by 2050, but it gave more than £4.5bn in aid money to fossil fuel projects overseas between 2010 and 2017
Categories: Biology

N-terminal β-strand underpins biochemical specialization of an ATG8 isoform

PLOS Biology (new articles) - 21 hours 40 min ago

by Erin K. Zess, Cassandra Jensen, Neftaly Cruz-Mireles, Juan Carlos De la Concepcion, Jan Sklenar, Madlen Stephani, Richard Imre, Elisabeth Roitinger, Richard Hughes, Khaoula Belhaj, Karl Mechtler, Frank L. H. Menke, Tolga Bozkurt, Mark J. Banfield, Sophien Kamoun, Abbas Maqbool, Yasin F. Dagdas

Autophagy-related protein 8 (ATG8) is a highly conserved ubiquitin-like protein that modulates autophagy pathways by binding autophagic membranes and a number of proteins, including cargo receptors and core autophagy components. Throughout plant evolution, ATG8 has expanded from a single protein in algae to multiple isoforms in higher plants. However, the degree to which ATG8 isoforms have functionally specialized to bind distinct proteins remains unclear. Here, we describe a comprehensive protein–protein interaction resource, obtained using in planta immunoprecipitation (IP) followed by mass spectrometry (MS), to define the potato ATG8 interactome. We discovered that ATG8 isoforms bind distinct sets of plant proteins with varying degrees of overlap. This prompted us to define the biochemical basis of ATG8 specialization by comparing two potato ATG8 isoforms using both in vivo protein interaction assays and in vitro quantitative binding affinity analyses. These experiments revealed that the N-terminal β-strand—and, in particular, a single amino acid polymorphism—underpins binding specificity to the substrate PexRD54 by shaping the hydrophobic pocket that accommodates this protein’s ATG8-interacting motif (AIM). Additional proteomics experiments indicated that the N-terminal β-strand shapes the broader ATG8 interactor profiles, defining interaction specificity with about 80 plant proteins. Our findings are consistent with the view that ATG8 isoforms comprise a layer of specificity in the regulation of selective autophagy pathways in plants.
Categories: Biology, Journals

Early life on Earth may have existed as miniature droplets of jelly

Genetics - Mon, 2019-07-22 21:00
Microscopic jelly blobs that form when simple carbon-based chemicals dry out could have been the precursors to the first biological cells on Earth
Categories: Biology

Our ancestors may have begun barbecuing 1.5 million years ago

Genetics - Mon, 2019-07-22 18:53
Our ancestors may have learned to control fire 1.5 million years ago, which could explain how we came to be human
Categories: Biology

Deforestation in Brazil has rocketed since Bolsonaro became president

Genetics - Mon, 2019-07-22 17:46
More than 3700 square kilometres of Brazilian rainforest has been cleared since Jair Bolsonaro became president, but he has dismissed the data as "lies"
Categories: Biology

US groundwater shortage is forcing us to dig extremely deep wells

Genetics - Mon, 2019-07-22 17:00
Groundwater provides drinking water for 120 million Americans and irrigates farmland - but demand in some places, including in California, is drying up wells
Categories: Biology

The Milky Way devoured another galaxy and we've spotted the remains

Genetics - Mon, 2019-07-22 17:00
We’ve identified the original stars that were in the Milky Way before it devoured another smaller galaxy called Gaia-Enceladus about 10 billion years ago
Categories: Biology

Strange stars that go supernova may be dimming because of dark matter

Genetics - Mon, 2019-07-22 16:02
Some stars that go supernova are dimmer than we expect, so something must be filching their energy - it may be a possible dark matter particle called the axion
Categories: Biology

India has launched its Chandrayaan 2 mission to the moon

Genetics - Mon, 2019-07-22 15:59
India launched its second moon mission on 22 July. The mission will place a lander and rover near the moon’s south pole, a promising site for human exploration
Categories: Biology

Strange illusion makes people forget where their teeth are

Genetics - Sat, 2019-07-20 09:00
An illusion can trick people into thinking their teeth are closer to their neck than in reality, showing that our bodily perceptions are easily influenced
Categories: Biology

Diversification of the type IV filament superfamily into machines for adhesion, protein secretion, DNA uptake, and motility

PLOS Biology (new articles) - Fri, 2019-07-19 23:00

by Rémi Denise, Sophie S. Abby, Eduardo P. C. Rocha

Processes of molecular innovation require tinkering and shifting in the function of existing genes. How this occurs in terms of molecular evolution at long evolutionary scales remains poorly understood. Here, we analyse the natural history of a vast group of membrane-associated molecular systems in Bacteria and Archaea—the type IV filament (TFF) superfamily—that diversified in systems involved in flagellar or twitching motility, adhesion, protein secretion, and DNA uptake. The phylogeny of the thousands of detected systems suggests they may have been present in the last universal common ancestor. From there, two lineages—a bacterial and an archaeal—diversified by multiple gene duplications, gene fissions and deletions, and accretion of novel components. Surprisingly, we find that the ‘tight adherence’ (Tad) systems originated from the interkingdom transfer from Archaea to Bacteria of a system resembling the ‘EppA-dependent’ (Epd) pilus and were associated with the acquisition of a secretin. The phylogeny and content of ancestral systems suggest that initial bacterial pili were engaged in cell motility and/or DNA uptake. In contrast, specialised protein secretion systems arose several times independently and much later in natural history. The functional diversification of the TFF superfamily was accompanied by genetic rearrangements with implications for genetic regulation and horizontal gene transfer: systems encoded in fewer loci were more frequently exchanged between taxa. This may have contributed to their rapid evolution and spread across Bacteria and Archaea. Hence, the evolutionary history of the superfamily reveals an impressive catalogue of molecular evolution mechanisms that resulted in remarkable functional innovation and specialisation from a relatively small set of components.
Categories: Biology, Journals

LATS1/2 suppress NFκB and aberrant EMT initiation to permit pancreatic progenitor differentiation

PLOS Biology (new articles) - Fri, 2019-07-19 23:00

by Caitlin M. Braitsch, D. Berfin Azizoglu, Yadanar Htike, Haley R. Barlow, Ulrike Schnell, Christopher P. Chaney, Thomas J. Carroll, Ben Z. Stanger, Ondine Cleaver

The Hippo pathway directs cell differentiation during organogenesis, in part by restricting proliferation. How Hippo signaling maintains a proliferation-differentiation balance in developing tissues via distinct molecular targets is only beginning to be understood. Our study makes the unexpected finding that Hippo suppresses nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) signaling in pancreatic progenitors to permit cell differentiation and epithelial morphogenesis. We find that pancreas-specific deletion of the large tumor suppressor kinases 1 and 2 (Lats1/2PanKO) from mouse progenitor epithelia results in failure to differentiate key pancreatic lineages: acinar, ductal, and endocrine. We carried out an unbiased transcriptome analysis to query differentiation defects in Lats1/2PanKO. This analysis revealed increased expression of NFκB activators, including the pantetheinase vanin1 (Vnn1). Using in vivo and ex vivo studies, we show that VNN1 activates a detrimental cascade of processes in Lats1/2PanKO epithelium, including (1) NFκB activation and (2) aberrant initiation of epithelial-mesenchymal transition (EMT), which together disrupt normal differentiation. We show that exogenous stimulation of VNN1 or NFκB can trigger this cascade in wild-type (WT) pancreatic progenitors. These findings reveal an unexpected requirement for active suppression of NFκB by LATS1/2 during pancreas development, which restrains a cell-autonomous deleterious transcriptional program and thereby allows epithelial differentiation.
Categories: Biology, Journals

Structural basis for recognition of the tumor suppressor protein PTPN14 by the oncoprotein E7 of human papillomavirus

PLOS Biology (new articles) - Fri, 2019-07-19 23:00

by Hye-Yeoung Yun, Min Wook Kim, Hye Seon Lee, Wantae Kim, Ji Hye Shin, Hyunmin Kim, Ho-Chul Shin, Hwangseo Park, Byung-Ha Oh, Won Kon Kim, Kwang-Hee Bae, Sang Chul Lee, Eun-Woo Lee, Bonsu Ku, Seung Jun Kim

Human papillomaviruses (HPVs) are causative agents of various diseases associated with cellular hyperproliferation, including cervical cancer, one of the most prevalent tumors in women. E7 is one of the two HPV-encoded oncoproteins and directs recruitment and subsequent degradation of tumor-suppressive proteins such as retinoblastoma protein (pRb) via its LxCxE motif. E7 also triggers tumorigenesis in a pRb-independent pathway through its C-terminal domain, which has yet been largely undetermined, with a lack of structural information in a complex form with a host protein. Herein, we present the crystal structure of the E7 C-terminal domain of HPV18 belonging to the high-risk HPV genotypes bound to the catalytic domain of human nonreceptor-type protein tyrosine phosphatase 14 (PTPN14). They interact directly and potently with each other, with a dissociation constant of 18.2 nM. Ensuing structural analysis revealed the molecular basis of the PTPN14-binding specificity of E7 over other protein tyrosine phosphatases and also led to the identification of PTPN21 as a direct interacting partner of E7. Disruption of HPV18 E7 binding to PTPN14 by structure-based mutagenesis impaired E7’s ability to promote keratinocyte proliferation and migration. Likewise, E7 binding-defective PTPN14 was resistant for degradation via proteasome, and it was much more effective than wild-type PTPN14 in attenuating the activity of downstream effectors of Hippo signaling and negatively regulating cell proliferation, migration, and invasion when examined in HPV18-positive HeLa cells. These results therefore demonstrated the significance and therapeutic potential of the intermolecular interaction between HPV E7 and host PTPN14 in HPV-mediated cell transformation and tumorigenesis.
Categories: Biology, Journals

Thousands of pornography sites leak data to Google and Facebook

Genetics - Fri, 2019-07-19 16:17
More than 90 per cent of pornography sites leak data on people browsing them to third party companies including Google and Facebook
Categories: Biology

Man on the moon? Why we said Apollo 11 was an empty, obsessional quest

Genetics - Fri, 2019-07-19 13:31
New Scientist was opposed to the Apollo missions from the start, and complained for decades that the money to send people into space was being wasted. Why were we so grumpy and pessimistic about putting a man on the moon?
Categories: Biology

Does the drop in US drug deaths mean the opioid crisis is ending?

Genetics - Fri, 2019-07-19 12:40
Overdose deaths in the US have dropped for the first time in two decades, but many people are still dependent on painkillers and struggling to get them legally
Categories: Biology

Hawaii declares state of emergency amid protests over huge telescope

Genetics - Fri, 2019-07-19 11:47
The planned construction of an enormous telescope atop Mauna Kea is being blocked by Hawaiian protesters for whom the mountain is sacred land
Categories: Biology

AI passes theory of mind test by imagining itself in another's shoes

Genetics - Fri, 2019-07-19 09:00
AI has passed a test used to assess theory of mind in dominant and subordinate chimpanzees, paving the way towards machines that are more effective at communicating with humans
Categories: Biology

Delayed death in the malaria parasite <i>Plasmodium falciparum</i> is caused by disruption of prenylation-dependent intracellular trafficking

PLOS Biology (new articles) - Thu, 2019-07-18 23:00

by Kit Kennedy, Simon A. Cobbold, Eric Hanssen, Jakob Birnbaum, Natalie J. Spillman, Emma McHugh, Hannah Brown, Leann Tilley, Tobias Spielmann, Malcolm J. McConville, Stuart A. Ralph

Apicomplexan parasites possess a plastid organelle called the apicoplast. Inhibitors that selectively target apicoplast housekeeping functions, including DNA replication and protein translation, are lethal for the parasite, and several (doxycycline, clindamycin, and azithromycin) are in clinical use as antimalarials. A major limitation of such drugs is that treated parasites only arrest one intraerythrocytic development cycle (approximately 48 hours) after treatment commences, a phenotype known as the ‘delayed death’ effect. The molecular basis of delayed death is a long-standing mystery in parasitology, and establishing the mechanism would aid rational clinical implementation of apicoplast-targeted drugs. Parasites undergoing delayed death transmit defective apicoplasts to their daughter cells and cannot produce the sole, blood-stage essential metabolic product of the apicoplast: the isoprenoid precursor isopentenyl-pyrophosphate. How the isoprenoid precursor depletion kills the parasite remains unknown. We investigated the requirements for the range of isoprenoids in the human malaria parasite Plasmodium falciparum and characterised the molecular and morphological phenotype of parasites experiencing delayed death. Metabolomic profiling reveals disruption of digestive vacuole function in the absence of apicoplast derived isoprenoids. Three-dimensional electron microscopy reveals digestive vacuole fragmentation and the accumulation of cytostomal invaginations, characteristics common in digestive vacuole disruption. We show that digestive vacuole disruption results from a defect in the trafficking of vesicles to the digestive vacuole. The loss of prenylation of vesicular trafficking proteins abrogates their membrane attachment and function and prevents the parasite from feeding. Our data show that the proximate cause of delayed death is an interruption of protein prenylation and consequent cellular trafficking defects.
Categories: Biology, Journals

The biology of extracellular vesicles: The known unknowns

PLOS Biology (new articles) - Thu, 2019-07-18 23:00

by Leonid Margolis, Yoel Sadovsky

For many years, double-layer phospholipid membrane vesicles, released by most cells, were not considered to be of biological significance. This stance has dramatically changed with the recognition of extracellular vesicles (EVs) as carriers of biologically active molecules that can traffic to local or distant targets and execute defined biological functions. The dimensionality of the field has expanded with the appreciation of diverse types of EVs and the complexity of vesicle biogenesis, cargo loading, release pathways, targeting mechanisms, and vesicle processing. With the expanded interest in the field and the accelerated rate of publications on EV structure and function in diverse biomedical fields, it has become difficult to distinguish between well-established biological features of EV and the untested hypotheses or speculative assumptions that await experimental proof. With the growing interest despite the limited evidence, we sought in this essay to formulate a set of unsolved mysteries in the field, sort out established data from fascinating hypotheses, and formulate several challenging questions that must be answered for the field to advance.
Categories: Biology, Journals