Biology

Reconciling Pasteur and Darwin to control infectious diseases

PLOS Biology (new articles) - 9 hours 36 min ago

by Samuel Alizon, Pierre-Olivier Méthot

The continual emergence of new pathogens and the increased spread of antibiotic resistance in bacterial populations remind us that microbes are living entities that evolve at rates that impact public health interventions. Following the historical thread of the works of Pasteur and Darwin shows how reconciling clinical microbiology, ecology, and evolution can be instrumental to understanding pathology, developing new therapies, and prolonging the efficiency of existing ones.
Categories: Biology, Journals

Control of recollection by slow gamma dominating mid-frequency gamma in hippocampus CA1

PLOS Biology (new articles) - 9 hours 36 min ago

by Dino Dvorak, Basma Radwan, Fraser T. Sparks, Zoe Nicole Talbot, André A. Fenton

Behavior is used to assess memory and cognitive deficits in animals like Fmr1-null mice that model Fragile X Syndrome, but behavior is a proxy for unknown neural events that define cognitive variables like recollection. We identified an electrophysiological signature of recollection in mouse dorsal Cornu Ammonis 1 (CA1) hippocampus. During a shocked-place avoidance task, slow gamma (SG) (30–50 Hz) dominates mid-frequency gamma (MG) (70–90 Hz) oscillations 2–3 s before successful avoidance, but not failures. Wild-type (WT) but not Fmr1-null mice rapidly adapt to relocating the shock; concurrently, SG/MG maxima (SGdom) decrease in WT but not in cognitively inflexible Fmr1-null mice. During SGdom, putative pyramidal cell ensembles represent distant locations; during place avoidance, these are avoided places. During shock relocation, WT ensembles represent distant locations near the currently correct shock zone, but Fmr1-null ensembles represent the formerly correct zone. These findings indicate that recollection occurs when CA1 SG dominates MG and that accurate recollection of inappropriate memories explains Fmr1-null cognitive inflexibility.
Categories: Biology, Journals

Structure, function, and control of the human musculoskeletal network

PLOS Biology (new articles) - 9 hours 36 min ago

by Andrew C. Murphy, Sarah F. Muldoon, David Baker, Adam Lastowka, Brittany Bennett, Muzhi Yang, Danielle S. Bassett

The human body is a complex organism, the gross mechanical properties of which are enabled by an interconnected musculoskeletal network controlled by the nervous system. The nature of musculoskeletal interconnection facilitates stability, voluntary movement, and robustness to injury. However, a fundamental understanding of this network and its control by neural systems has remained elusive. Here we address this gap in knowledge by utilizing medical databases and mathematical modeling to reveal the organizational structure, predicted function, and neural control of the musculoskeletal system. We constructed a highly simplified whole-body musculoskeletal network in which single muscles connect to multiple bones via both origin and insertion points. We demonstrated that, using this simplified model, a muscle’s role in this network could offer a theoretical prediction of the susceptibility of surrounding components to secondary injury. Finally, we illustrated that sets of muscles cluster into network communities that mimic the organization of control modules in primary motor cortex. This novel formalism for describing interactions between the muscular and skeletal systems serves as a foundation to develop and test therapeutic responses to injury, inspiring future advances in clinical treatments.
Categories: Biology, Journals

The gram-negative bacterial periplasm: Size matters

PLOS Biology (new articles) - Thu, 2018-01-18 00:00

by Samuel I. Miller, Nina R. Salama

Gram-negative bacteria are surrounded by two membrane bilayers separated by a space termed the periplasm. The periplasm is a multipurpose compartment separate from the cytoplasm whose distinct reducing environment allows more efficient and diverse mechanisms of protein oxidation, folding, and quality control. The periplasm also contains structural elements and important environmental sensing modules, and it allows complex nanomachines to span the cell envelope. Recent work indicates that the size or intermembrane distance of the periplasm is controlled by periplasmic lipoproteins that anchor the outer membrane to the periplasmic peptidoglycan polymer. This periplasm intermembrane distance is critical for sensing outer membrane damage and dictates length of the flagellar periplasmic rotor, which controls motility. These exciting results resolve longstanding debates about whether the periplasmic distance has a biological function and raise the possibility that the mechanisms for maintenance of periplasmic size could be exploited for antibiotic development.
Categories: Biology, Journals

Breathing in a nanoparticle spray could prevent heart damage

Genetics - Wed, 2018-01-17 21:00
An inhalable drug is designed to move straight from the lungs to the heart, where it is hoped it will prevent the organ from deteriorating after heart attacks
Categories: Biology

How ‘stem cell’ clinics became a Wild West for dodgy treatments

Genetics - Wed, 2018-01-17 20:00
Hundreds of clinics offering unregulated stem cell therapies have sprung up across the US and Australia thanks to lax oversight
Categories: Biology

Algorithms that change lives should be trialled like new drugs

Genetics - Wed, 2018-01-17 20:00
An algorithm used by US courts to predict reoffenders turns out to be no more accurate than random people on the internet. Why wasn’t it properly tested before now?
Categories: Biology

Blindness treatment will insert algae gene into people’s eyes

Genetics - Wed, 2018-01-17 19:50
Optogenetic techniques that use light to control nerve cells are being tried in people at last – and could lead to treatments for several types of blindness
Categories: Biology

Swollen eye is setback for blindness treatment using stem cells

Genetics - Wed, 2018-01-17 19:08
A man in a flagship stem cell trial for age-related macular degeneration has swelling in his eye, but the cause is probably surgery – not stem cells
Categories: Biology

Bitcoin’s utopia has failed as big players hold all the power

Genetics - Wed, 2018-01-17 18:42
Cryptocurrencies are built on the idea that no one institution holds the power. But for bitcoin and ethereum, that’s no longer true
Categories: Biology

DNA of man who died in 1827 recreated from his living relatives

Genetics - Wed, 2018-01-17 18:40
The DNA of Hans Jonaton, an ex-slave who fled to Iceland in 1802, has been reconstructed using only the genes of his descendants
Categories: Biology

Trump, this ‘shithole’ continent pioneered heart swaps and more

Genetics - Wed, 2018-01-17 18:15
Seeking to understand other people is better than dismissing them with insults. Trump needs lessons in African history, culture and science, says Curtis Abraham
Categories: Biology

No sweat: Should my muscles be hurting days after a workout?

Genetics - Wed, 2018-01-17 18:00
Tiny tears in your muscles cause the aching that sets in a day or so after a heavy exercise session. But what sounds bad can help them to rebuild stronger
Categories: Biology

Chit-chat makes humans and robots work together better

Genetics - Wed, 2018-01-17 17:43
Introducing some chatter between humans and artificial intelligence improved the amount of collaboration – and results – across hundreds of games
Categories: Biology

Source of world’s biggest listeria outbreak still unknown

Genetics - Wed, 2018-01-17 15:00
There have been almost 750 cases of listeriosis in South Africa so far, and the source of the food poisoning infection remains unknown
Categories: Biology

End of days: Is Western civilisation on the brink of collapse?

Genetics - Wed, 2018-01-17 14:00
History tells us all cultures have their sell-by date. Do political strife, crippling inequality and climate change mean the West’s time is now up
Categories: Biology

All other primates live their lives according to a simple rule

Genetics - Wed, 2018-01-17 02:01
Hundreds of species of primate all form groups of the same five sizes, suggesting that the ecosystems in which they live strongly shape their lifestyles
Categories: Biology

Identification of a noncanonical function for ribose-5-phosphate isomerase A promotes colorectal cancer formation by stabilizing and activating β-catenin via a novel C-terminal domain

PLOS Biology (new articles) - Wed, 2018-01-17 00:00

by Yu-Ting Chou, Jeng-Kai Jiang, Muh-Hwa Yang, Jeng-Wei Lu, Hua-Kuo Lin, Horng-Dar Wang, Chiou-Hwa Yuh

Altered metabolism is one of the hallmarks of cancers. Deregulation of ribose-5-phosphate isomerase A (RPIA) in the pentose phosphate pathway (PPP) is known to promote tumorigenesis in liver, lung, and breast tissues. Yet, the molecular mechanism of RPIA-mediated colorectal cancer (CRC) is unknown. Our study demonstrates a noncanonical function of RPIA in CRC. Data from the mRNAs of 80 patients’ CRC tissues and paired nontumor tissues and protein levels, as well as a CRC tissue array, indicate RPIA is significantly elevated in CRC. RPIA modulates cell proliferation and oncogenicity via activation of β-catenin in colon cancer cell lines. Unlike its role in PPP in which RPIA functions within the cytosol, RPIA enters the nucleus to form a complex with the adenomatous polyposis coli (APC) and β-catenin. This association protects β-catenin by preventing its phosphorylation, ubiquitination, and subsequent degradation. The C-terminus of RPIA (amino acid 290 to 311), a region distinct from its enzymatic domain, is necessary for RPIA-mediated tumorigenesis. Consistent with results in vitro, RPIA increases the expression of β-catenin and its target genes, and induces tumorigenesis in gut-specific, promotor-carrying RPIA transgenic (Tg) zebrafish. Together, we demonstrate a novel function of RPIA in CRC formation in which RPIA enters the nucleus and stabilizes β-catenin activity and suggests that RPIA might be a biomarker for targeted therapy and prognosis.
Categories: Biology, Journals

Anteroposterior axis patterning by early canonical Wnt signaling during hemichordate development

PLOS Biology (new articles) - Wed, 2018-01-17 00:00

by Sébastien Darras, Jens H. Fritzenwanker, Kevin R. Uhlinger, Ellyn Farrelly, Ariel M. Pani, Imogen A. Hurley, Rachael P. Norris, Michelle Osovitz, Mark Terasaki, Mike Wu, Jochanan Aronowicz, Marc Kirschner, John C. Gerhart, Christopher J. Lowe

The Wnt family of secreted proteins has been proposed to play a conserved role in early specification of the bilaterian anteroposterior (A/P) axis. This hypothesis is based predominantly on data from vertebrate embryogenesis as well as planarian regeneration and homeostasis, indicating that canonical Wnt (cWnt) signaling endows cells with positional information along the A/P axis. Outside of these phyla, there is strong support for a conserved role of cWnt signaling in the repression of anterior fates, but little comparative support for a conserved role in promotion of posterior fates. We further test the hypothesis by investigating the role of cWnt signaling during early patterning along the A/P axis of the hemichordate Saccoglossus kowalevskii. We have cloned and investigated the expression of the complete Wnt ligand and Frizzled receptor complement of S. kowalevskii during early development along with many secreted Wnt modifiers. Eleven of the 13 Wnt ligands are ectodermally expressed in overlapping domains, predominantly in the posterior, and Wnt antagonists are localized predominantly to the anterior ectoderm in a pattern reminiscent of their distribution in vertebrate embryos. Overexpression and knockdown experiments, in combination with embryological manipulations, establish the importance of cWnt signaling for repression of anterior fates and activation of mid-axial ectodermal fates during the early development of S. kowalevskii. However, surprisingly, terminal posterior fates, defined by posterior Hox genes, are unresponsive to manipulation of cWnt levels during the early establishment of the A/P axis at late blastula and early gastrula. We establish experimental support for a conserved role of Wnt signaling in the early specification of the A/P axis during deuterostome body plan diversification, and further build support for an ancestral role of this pathway in early evolution of the bilaterian A/P axis. We find strong support for a role of cWnt in suppression of anterior fates and promotion of mid-axial fates, but we find no evidence that cWnt signaling plays a role in the early specification of the most posterior axial fates in S. kowalevskii. This posterior autonomy may be a conserved feature of early deuterostome axis specification.
Categories: Biology, Journals

Bowel cancer test may be a much better way to screen for polyps

Genetics - Wed, 2018-01-17 00:00
A new blood test seems to be more than twice as good at detecting bowel cancer than the method currently used to screen for polyps and early bowel cancer
Categories: Biology