RK Tangirala
Nov 1, 1995; 36:2320-2328
Articles

AE Christian
Nov 1, 1997; 38:2264-2272
Articles

Stop codon read-through (SCR) is a process of continuation of translation beyond a stop codon. This phenomenon, which occurs only in certain mRNAs under specific conditions, leads to a longer isoform with properties different from that of the canonical isoform. MTCH2, which encodes a mitochondrial protein that regulates mitochondrial metabolism, was selected as a potential read-through candidate based on evolutionary conservation observed in the proximal region of its 3' UTR. Here, we demonstrate translational read-through across two evolutionarily conserved, in-frame stop codons of MTCH2 using luminescence- and fluorescence-based assays, and by analyzing ribosome-profiling and mass spectrometry (MS) data. This phenomenon generates two isoforms, MTCH2x and MTCH2xx (single- and double-SCR products, respectively), in addition to the canonical isoform MTCH2, from the same mRNA. Our experiments revealed that a cis-acting 12-nucleotide sequence in the proximal 3' UTR of MTCH2 is the necessary signal for SCR. Functional characterization showed that MTCH2 and MTCH2x were localized to mitochondria with a long t1/2 (>36 h). However, MTCH2xx was found predominantly in the cytoplasm. This mislocalization and its unique C terminus led to increased degradation, as shown by greatly reduced t1/2 (<1 h). MTCH2 read-through–deficient cells, generated using CRISPR-Cas9, showed increased MTCH2 expression and, consistent with this, decreased mitochondrial membrane potential. Thus, double-SCR of MTCH2 regulates its own expression levels contributing toward the maintenance of normal mitochondrial membrane potential.

Z. A. Kasumov and N. R. Akhmedzade
Trans. Moscow Math. Soc. 83 (), 67-74.
Abstract, references and article information

Realizing the Potential of Extractives for Industrial and Economic Development 18 October 2018 — 5:30PM TO 7:00PM Anonymous (not verified) 3 October 2018 Chatham House | 10 St James's Square | London | SW1Y 4LE

Over the past two decades, the extractives industries have risen in importance for many low- and middle- income countries their prospects for economic development and poverty reduction. During a period of rising commodities prices, the development of extractives became increasingly attractive to both governments and companies. There was - and remains - much discussion about their potential to support inclusive development.

However, there are also risks and uncertainties associated with the extractives industries and many things can, and do, go wrong. Fluctuations in commodity prices can be hard to manage and can lead to considerable fiscal pressures. In the longer-term, climate change and the various policy responses to this, will profoundly affect the extractives sector as renewables replace fossil fuels in the global energy mix.

Managing the extractives sectors will therefore remain highly challenging especially in low-income countries where institutions are often weak. This roundtable will bring together some of the foremost academics and practitioners working in the extractives industries and also in economic development to discuss a major new UNU-WIDER study Extractive Industries: The Management of Resources as a Driver of Sustainable Development.

Attendance at this event is by invitation only.

Gurmeet K. Bakshi, Jyoti Garg and Gabriela Olteanu
Math. Comp. 93 (), 3027-3058.
Abstract, references and article information

Ole Løseth Elvetun and Bjørn Fredrik Nielsen
Math. Comp. 93 (), 2811-2836.
Abstract, references and article information

The dimeric ectonucleotidase CD73 catalyzes the hydrolysis of AMP at the cell surface to form adenosine, a potent suppressor of the immune response. Blocking CD73 activity in the tumor microenvironment can have a beneficial effect on tumor eradication and is a promising approach for cancer therapy. Biparatopic antibodies binding different regions of CD73 may be a means to antagonize its enzymatic activity. A panel of biparatopic antibodies representing the pairwise combination of 11 parental monoclonal antibodies against CD73 was generated by Fab-arm exchange. Nine variants vastly exceeded the potency of their parental antibodies with ≥90% inhibition of activity and subnanomolar EC50 values. Pairing the Fabs of parents with nonoverlapping epitopes was both sufficient and necessary whereas monovalent antibodies were poor inhibitors. Some parental antibodies yielded potent biparatopics with multiple partners, one of which (TB19) producing the most potent. The structure of the TB19 Fab with CD73 reveals that it blocks alignment of the N- and C-terminal CD73 domains necessary for catalysis. A separate structure of CD73 with a Fab (TB38) which complements TB19 in a particularly potent biparatopic shows its binding to a nonoverlapping site on the CD73 N-terminal domain. Structural modeling demonstrates a TB19/TB38 biparatopic antibody would be unable to bind the CD73 dimer in a bivalent manner, implicating crosslinking of separate CD73 dimers in its mechanism of action. This ability of a biparatopic antibody to both crosslink CD73 dimers and fix them in an inactive conformation thus represents a highly effective mechanism for the inhibition of CD73 activity.

Review: Decolonization and its discontents The World Today mhiggins.drupal 1 August 2022

Jenna Marshall on a lively if flawed argument to find a way forward in a debate that has descended ‘into acrimony’.

Against Decolonization: Taking African Agency Seriously
Olufemi Taiwo, Hurst, £14.99

Decolonization was once heralded as a moment of potential and possibility for the formerly imperial world to chart a new way forward no longer tied to the apparatus of empire.

It marked a period of transition to nation states – and an expansion of a rights-based international community that would dispense with the morally bankrupt regime of racism, dispossession and subjugation that characterized colonialism.  
 

The descent of the decolonization debate

Half a century later, the debate surrounding decolonization has descended into acrimony. Some factions cast the issue of decolonization as a sustained attack on British and western culture writ large; other disparate voices coalesce around related social justice issues such as inequality, climate change and education. 

Decolonization has become ubiquitous in the public domain – and its ubiquity is the problem. In Against Decolonization, Olufemi Taiwo renounces a concept he conceives as having been emptied of serious study and analytical purchase; one incapable of addressing the complexities of modern global politics and more importantly, Africa’s place in it. 

Although the book attacks the inexhaustible ways in which the ‘trope of decolonization’ has been deployed, Taiwo is less bothered by the purported failures of scholars he deems ‘decolonizers’ and focuses his attention instead on the political landscape of African countries, past and present. 

Central to the book’s argument are two distinct scholarly strands on decolonization. The first, legal focus, centres on the political and economic forces of state-building. The second essays an ‘ideology’ of decolonization that rests on ‘forcing an ex-colony to forswear on pain of being forever under the yoke of colonization any and every cultural, political, intellectual, social and linguistic artefact, idea, process, institution and practice that retains even the slightest whiff of the colonial past’. 

Whether one should characterize the latter as simply a field of study or a potential set of policy arrangements remains unclear – yet what is certain is that it is too nebulous, too elastic, too open-ended to offer any substantive model or mechanism to understand postcolonial Africa. 
 

Correcting Eurocentric narcissism

 The decolonization research agenda in Africa came to prominence during the Cold War period of national liberation struggles.

The intellectual project that followed centred on dismantling Eurocentrism as colonial subjugation through its promotion of the West as the crucible of legitimate and scientific knowledge. Since then, scholars have argued that decolonization itself has become compromised by its enduringly Eurocentric gaze at the expense of the agency of African thinkers, creatives and statesmen and women. 

Taiwo seeks to correct this narcissism – and the omissions left in its wake – by introducing lesser-known Africans and pan-African scholars and cultural figures. These voices, he hopes, will illuminate issues often ignored by ‘decolonizers’ and spark a ‘renewed interest in an appreciation of the many different ways in which African thinkers have responded to the colonial experience’.
 

The decolonization of language

Taiwo challenges the decolonization of language as an oversold promise.

Romanticizing an imagined, pristine African pre-colonial past, he says, ultimately leads to nativism and atavism. As a case in point, Taiwo highlights bureaucratic instances of ‘language policy planning’ to deploy African languages in places such as Niger, Mali, Cameroon, Senegal and Nigeria that were hindered by multilingualism, education and high rates of illiteracy.

The author goes on to confront the abstract language of decolonization, which, he says, allows western scholars to unproblematically engage with the concept without any serious consideration of their own complicity in upholding systems of exclusion. It entrenches their own institutional power within the academy, amplifies their perspectives at the expense of others, and limits the possibilities for understanding the problems of world politics with deleterious effects on policy.

It is a serious claim, but there are issues to be addressed: Taiwo assumes there is coherence among scholars of decolonization, which is not the case. 

When Taiwo approaches how to foster political systems that cater to the needs of their citizens he dismantles the binary of ‘West as modern’ v ‘Africa as traditional’. Chieftaincies as traditional African governance, he points out, were the product of colonial anthropology, not Africans themselves. From the Fanti Confederation of 1871 to the Egba United Government in what is now Nigeria, Taiwo demonstrates that there has been a sustained tradition towards demands for democratic values. 

As he concedes an intellectual neglect of African philosophers that underlies the design and operations of Africa’s political institutions, Taiwo’s initial dismissal of the significance of cultural decolonization deserves another look. How should political and economic drives toward self-determination be advanced in the absence of knowledge shaped and mediated through African lived experiences?

In this respect, the tale of two decolonizations – the legal alongside the ideological – suggest an unhelpful, if not false, binary.
 

The problem of reconciling modernity and colonialism

What resonates throughout the book is the idea that Europe cannot profess to hold an exclusive intellectual claim to modernity. Its universal aspirations are open to all of humanity, allowing those who have historically been marginalized to be worldmakers. 

The idea that modernity and colonialism are irreconcilable is problematic. For instance, Taiwo argues that the curtailment of capitalism in Africa by restricting the growth of the middle classes while limiting competition between African capitalists and the metropole is the consequence of colonialism.

Yet the celebrated cultural anthropologist Sidney Mintz established an understanding that the matter for debate is not whether non-westerners were part of the modern system, but how and to what degree they were included and able to actualise its ideals. 

The emerging capitalist world economy needed non-western lands and labour, and so they were conscripted to this end. Recent abolitionist and black radical scholarship has built on this argument to maintain that capitalism not only requires inequality for it to function but that race – as a mechanism for producing ‘difference’ – enshrines it.

Acknowledging the unacknowledged

In the end, Taiwo communicates a palpable frustration at the state of academic discourses on contemporary Africa under the guise of emancipatory and radical scholarship. He offers an alternative approach whereby African students might rid themselves of a faddism that is ‘at best unsatisfactory’ and at worst produces ‘confusion, obscurantism, if not outright distortion and falsification’.

Yet out of this irritation, Taiwo’s greatest contribution in Against Decolonization might be to urge an acknowledgement of how and to what degree decolonization has become subdued and its political possibilities curtailed. He ultimately urges us to reconsider the purpose of the decolonization academic movement as an ethics to abide by rather than a social theory of the postcolonial world. 

This requires those ‘decolonizers’ on whose careers the term is built to adopt greater intellectual humility – to resist the posture of the anarchist radical scholar armed for the ‘good fight’. Instead, they should apply a scholarly curiosity to genuinely engage with those already on the battlefield, so to speak; those ‘doing the work’ in practice, but who have been unacknowledged until now.

Toma Keser
Dec 29, 2020; 0:RA120.002433v1-mcp.RA120.002433
Research

Alba Simats
Dec 1, 2020; 19:1921-1935
Research

Xinting Zhang
Dec 8, 2020; 0:RA120.002306v1-mcp.RA120.002306
Research

AMP-activated protein kinase (AMPK) is a key regulator of energy metabolism that phosphorylates a wide range of proteins to maintain cellular homeostasis. AMPK consists of three subunits: α, β, and γ. AMPKα and β are encoded by two genes, the γ subunit by three genes, all of which are expressed in a tissue-specific manner. It is not fully understood, whether individual isoforms have different functions. Using RNA-Seq technology, we provide evidence that the loss of AMPKβ1 and AMPKβ2 lead to different gene expression profiles in human induced pluripotent stem cells (hiPSCs), indicating isoform-specific function. The knockout of AMPKβ2 was associated with a higher number of differentially regulated genes than the deletion of AMPKβ1, suggesting that AMPKβ2 has a more comprehensive impact on the transcriptome. Bioinformatics analysis identified cell differentiation as one biological function being specifically associated with AMPKβ2. Correspondingly, the two isoforms differentially affected lineage decision toward a cardiac cell fate. Although the lack of PRKAB1 impacted differentiation into cardiomyocytes only at late stages of cardiac maturation, the availability of PRKAB2 was indispensable for mesoderm specification as shown by gene expression analysis and histochemical staining for cardiac lineage markers such as cTnT, GATA4, and NKX2.5. Ultimately, the lack of AMPKβ1 impairs, whereas deficiency of AMPKβ2 abrogates differentiation into cardiomyocytes. Finally, we demonstrate that AMPK affects cellular physiology by engaging in the regulation of hiPSC transcription in an isoform-specific manner, providing the basis for further investigations elucidating the role of dedicated AMPK subunits in the modulation of gene expression.

When viewing a SAS Visual Analytics report, you might intermittently see an error that includes content similar to the following:

When you log on to the SAS Risk Governance Framework and choose a solution, the web application might fail to load the solution content. When the problem occurs, you continue to see "Loading..." on the screen, an

The adipocyte-derived hormone leptin increases trafficking of KATP and Kv2.1 channels to the pancreatic β-cell surface, resulting in membrane hyperpolarization and suppression of insulin secretion. We have previously shown that this effect of leptin is mediated by the NMDA subtype of glutamate receptors (NMDARs). It does so by potentiating NMDAR activity, thus enhancing Ca2+ influx and the ensuing downstream signaling events that drive channel trafficking to the cell surface. However, the molecular mechanism by which leptin potentiates NMDARs in β-cells remains unknown. Here, we report that leptin augments NMDAR function via Src kinase–mediated phosphorylation of the GluN2A subunit. Leptin-induced membrane hyperpolarization diminished upon pharmacological inhibition of GluN2A but not GluN2B, indicating involvement of GluN2A-containing NMDARs. GluN2A harbors tyrosine residues that, when phosphorylated by Src family kinases, potentiate NMDAR activity. We found that leptin increases phosphorylation of Tyr-418 in Src, an indicator of kinase activation. Pharmacological inhibition of Src or overexpression of a kinase-dead Src mutant prevented the effect of leptin, whereas a Src kinase activator peptide mimicked it. Using mutant GluN2A overexpression, we show that Tyr-1292 and Tyr-1387 but not Tyr-1325 are responsible for the effect of leptin. Importantly, β-cells from db/db mice, a type 2 diabetes mouse model lacking functional leptin receptors, or from obese diabetic human donors failed to respond to leptin but hyperpolarized in response to NMDA. Our study reveals a signaling pathway wherein leptin modulates NMDARs via Src to regulate β-cell excitability and suggests NMDARs as a potential target to overcome leptin resistance.

Renal Cell Carcinoma (RCC) is one of the most commonly diagnosed cancers worldwide with research efforts dramatically improving understanding of the biology of the disease. To investigate the role of the immune system in treatment-naïve clear cell Renal Cell Carcinoma (ccRCC), we interrogated the immune infiltrate in patient-matched ccRCC tumor samples, benign normal adjacent tissue (NAT) and peripheral blood mononuclear cells (PBMCs isolated from whole blood, focusing our attention on the myeloid cell infiltrate. Using flow cytometric, MS, and ExCYT analysis, we discovered unique myeloid populations in PBMCs across patient samples. Furthermore, normal adjacent tissues and ccRCC tissues contained numerous myeloid populations with a unique signature for both tissues. Enrichment of the immune cell (CD45⁺) fraction and subsequent gene expression analysis revealed a number of myeloid-related genes that were differentially expressed. These data provide evidence, for the first time, of an immunosuppressive and pro-tumorigenic role of myeloid cells in early, clinically localized ccRCC. The identification of a number of immune proteins for therapeutic targeting provides a rationale for investigation into the potential efficacy of earlier intervention with single-agent or combination immunotherapy for ccRCC.

Stroke remains a leading cause of death and disability worldwide. Despite continuous advances, the identification of key molecular signatures in the hyper-acute phase of ischemic stroke is still a primary interest for translational research on stroke diagnosis, prognosis, and treatment. Data integration from high-throughput -omics techniques has become crucial to unraveling key interactions among different molecular elements in complex biological contexts, such as ischemic stroke. Thus, we used advanced data integration methods for a multi-level joint analysis of transcriptomics and proteomics data sets obtained from mouse brains at 2 h after cerebral ischemia. By modeling net-like correlation structures, we identified an integrated network of genes and proteins that are differentially expressed at a very early stage after stroke. We validated 10 of these deregulated elements in acute stroke, and changes in their expression pattern over time after cerebral ischemia were described. Of these, CLDN20, GADD45G, RGS2, BAG5, and CTNND2 were next evaluated as blood biomarkers of cerebral ischemia in mice and human blood samples, which were obtained from stroke patients and patients presenting stroke-mimicking conditions. Our findings indicate that CTNND2 levels in blood might potentially be useful for distinguishing ischemic strokes from stroke-mimicking conditions in the hyper-acute phase of the disease. Furthermore, circulating GADD45G content within the first 6 h after stroke could also play a key role in predicting poor outcomes in stroke patients. For the first time, we have used an integrative biostatistical approach to elucidate key molecules in the initial stages of stroke pathophysiology and highlight new notable molecules that might be further considered as blood biomarkers of ischemic stroke.

Gonadal soma-derived factor (gsdf) has been demonstrated to be essential for testicular differentiation in medaka (Oryzias latipes). To understand the protein dynamics of Gsdf in spermatogenesis regulation, we used a His-tag "pull-down" assay coupled with shotgun LC-MS/MS to identify a group of potential interacting partners for Gsdf, which included cytoplasmic dynein light chain 2, eukaryotic polypeptide elongation factor 1 alpha (eEF1α), and actin filaments in mature medaka testis. As for the interaction with TGFβ-dynein being critical for spermatogonial division in Drosophila melanogaster, the physical interactions of Gsdf-dynein and Gsdf-eEF1α were identified through a yeast 2-hybrid (Y2H) screening of an adult testis cDNA library using Gsdf as bait, which were verified by a paired Y2H assay. Co-immunoprecipitation of Gsdf and eEF1α was defined in adult testes as supporting the requirement of a Gsdf and eEF1α interaction in testis development. Proteomics analysis (data are available via ProteomeXchange with identifier PXD022153) and ultrastrutural observations showed that Gsdf deficiency activated eEF1α-mediated protein synthesis and ribosomal biogenesis, which in turn led to the differentiation of undifferentiated germ cells. Thus, our results provide a framework and new insight into the coordination of a Gsdf (TGFβ and eEF1α complex in the basic processes of germ cell proliferation, transcriptional and translational control of sexual RNA which may be fundamentally conserved across phyla during sexual differentiation.

Alpha-1-acid glycoprotein (AGP) is an acute phase glycoprotein in blood, which is primarily synthetized in the liver and whose biological role is not completely understood. It consists of 45% carbohydrates that are present in the form of five N-linked complex glycans. AGP N-glycosylation was shown to be changed in many different diseases and some changes appear to be disease-specific, thus it has a great diagnostic and prognostic potential. However, AGP glycosylation was mainly analyzed in small cohorts and without detailed site-specific glycan information. Here, we developed a cost-effective method for a high-throughput and site-specific N-glycosylation LC-MS analysis of AGP which can be applied on large cohorts, aid in search for novel disease biomarkers and enable better understanding of AGP’s role and function in health and disease. The method does not require isolation of AGP with antibodies and affinity chromatography, but AGP is enriched by acid precipitation from 5 μl of bloodplasma in a 96 well format. After trypsinization, AGP glycopeptides are purified using a hydrophilic interaction chromatography based solid-phase extraction and analyzed by RP-LC-ESI-MS. We used our method to show for the first time that AGP N-glycan profile is stable in healthy individuals (14 individuals in 3 time points), which is a requirement for evaluation of its diagnostic potential. Furthermore, we tested our method on a population including individuals with registered hyperglycemia in critical illness (59 cases and 49 controls), which represents a significantly increased risk of developing type 2 diabetes. Individuals at higher risk of diabetes presented increased N-glycan branching on AGP’s second glycosylation site and lower sialylation of N-glycans on AGP’s third and AGP1’s fourth glycosylation site. Although this should be confirmed on a larger prospective cohort, it indicates that site-specific AGP N-glycan profile could help distinguish individuals who are at risk of type 2 diabetes.

Mine Action in Angola: Clearing the Legacies of Conflict to Harness the Potential of Peace Other resource sysadmin 14 June 2019

This publication draws on and updates the briefing note published following a meeting of the All- Party Parliamentary Group (APPG) on Angola on 26 April 2017. It also incorporates insights from a Chatham House Africa Programme conference session on the legacies of the Angolan Civil War, held on 23 March 2018; and draws on the Africa Programme’s research into conservation-driven development models in Southern Africa.

Almost two decades after the end of its civil war, Angola remains one of the most heavily landmine-contaminated countries in the world. The Angolan government has committed to clearing its landmines by 2025, and there is constructive collaboration between the government and mine clearing agencies in this endeavour, but the target will be achievable only if a decline in funding from international donors is reversed. International funding for mine clearance in Angola fell by more than 80 per cent between 2005 and 2017, and this sharp drop in external support has compounded the impact on domestic funding for national clearance efforts as a result of the downturn in prices for Angola’s main export commodities.

The national mine action agency, the Comissão Nacional Intersectorial de Desminagem e Assistência Humanitária (CNIDAH), is supported by the Mines Advisory Group (MAG), Norwegian People’s Aid (NPA) and the HALO Trust. By 2017, 15 years after the end of the civil war, these organizations had collectively helped clear 56 per cent of known landmine-contaminated land. State-led demining has focused principally on clearing areas designated for infrastructure projects. Now, it is critical that humanitarian demining in largely agricultural and conservation areas is prioritized to bring to an end the daily threat to Angola’s rural poor – as well as to the country’s livestock and wildlife – of injury or death as a result of landmine accidents.

Angola has some of the world’s most important remaining wilderness, including the tributary system for the unique Okavango Delta, and the country has the potential to host one of the most diverse wildlife populations on the continent. However, the presence of landmines and other remnants of the civil war render large areas of the country unsafe both for wildlife and for the local people, whose ability to derive a sustainable livelihood from their natural environment is fundamental to its protection.

Wildlife and tourism provide important economic opportunities for diversification beyond an oil-dominated economy. Critically, Angola’s economic diversification and development objectives can only be achieved if the landmines that prohibit access to land for agriculture, mining, tourism and wildlife are cleared.

There are economic opportunities for released land in the most heavily mined provinces of Cuando Cubango and Moxico. Already, some new funding for mine action in Angola, if upscaled or matched by international donors, could be transformative for its people, and for the conservation of the region’s vital biodiversity.

Prognosticators anticipate the Federal Reserve on Thursday will announce a second rate cut after lowering the federal lending rate by 0.5% in September.

SANTA CLARA, Calif., Oct. 22, 2024 — Celestial AI today announced the acquisition of silicon photonics intellectual property from Rockley Photonics, including worldwide issued and pending patents. The combination of Celestial […]

The post Celestial AI Acquires Rockley Photonics Patent Portfolio, Strengthening Photonic Fabric IP appeared first on HPCwire.

As U.S. and Slovenian troops wrapped up a joint exercise, military officials from both countries met to discuss their response to potential threats, the Air Force said Wednesday.

The allergy and asthma drug montelukast, also known as Singulair, can cause psychiatric side effects—and researchers aren’t sure why

Discover why more content isn’t solving your boredom but making it worse.

Schools must make the critical decision whether to reinforce the learning that students have already done this year or introduce new content.

School boards play a critical role in steering the progress of the nation’s schools, but the relationship between school boards and school district leaders could be better.

Cursive writing is experiencing a resurgence of sorts in North Carolina elementary schools thanks to a state law that was passed in 2013.

The U.S. Supreme Court ruled that a large swath of land in Oklahoma is still an American Indian reservation, a decision that may have ramifications for education.

Acellus Learning Accelerator, used by 6,000 schools nationwide, is under fire for lessons that parents and educators have decried as racist, sexist, and age-inappropriate.

South Carolina's public universities only produce enough teachers each year to fill half of the state's vacant teacher positions.

Holly Oakley
Oct 4, 2006; 26:10129-10140
Neurobiology of Disease

Holly Oakley
Oct 4, 2006; 26:10129-10140
Neurobiology of Disease

Matthew F. Glasser
Aug 10, 2011; 31:11597-11616
BehavioralSystemsCognitive

Sleep is known to drive the consolidation of motor memories. During nonrapid eye movement (NREM) sleep, the close temporal proximity between slow oscillations (SOs) and spindles ("nesting" of SO-spindles) is known to be essential for consolidation, likely because it is closely associated with the reactivation of awake task activity. Interestingly, recent work has found that spindles can occur in temporal clusters or "trains." However, it remains unclear how spindle trains are related to the nesting phenomenon. Here, we hypothesized that spindle trains are more likely when SOs co-occur in the prefrontal and motor cortex. We conducted simultaneous neural recordings in the medial prefrontal cortex (mPFC) and primary motor cortex (M1) of male rats training on the reach-to-grasp motor task. We found that intracortically recorded M1 spindles are organized into distinct temporal clusters. Notably, the occurrence of temporally precise SOs between mPFC and M1 was a strong predictor of spindle trains. Moreover, reactivation of awake task patterns is much more persistent during spindle trains in comparison with that during isolated spindles. Together, our work suggests that the precise coupling of SOs across mPFC and M1 may be a potential driver of spindle trains and persistent reactivation of motor memory during NREM sleep.

It is well established that holding information in working memory (WM) elicits sustained stimulus-specific patterns of neural activity. Nevertheless, here we provide evidence for a distinct class of neural activity that tracks the number of individuated items in working memory, independent of the type of visual features stored. We present two EEG studies of young adults of both sexes that provide robust evidence for a signal tracking the number of individuated representations in working memory, regardless of the specific feature values stored. In Study 1, subjects maintained either colors or orientations across separate blocks in a single session. We found near-perfect generalization of the load signal between these two conditions, despite being able to simultaneously decode which feature had been voluntarily stored. In Study 2, participants attended to two features with very distinct cortical representations: color and motion coherence. We again found evidence for a neural load signal that robustly generalized across these distinct visual features, even though cortically disparate regions process color and motion coherence. Moreover, representational similarity analysis provided converging evidence for a content-independent load signal, while simultaneously showing that unique variance in EEG activity tracked the specific features that were stored. We posit that this load signal reflects a content-independent "pointer" operation that binds objects to the current context while parallel but distinct neural signals represent the features that are stored for each item in memory.

Marc Edwards and Leeanne Walters | Smithsonian Magazine’s 2016 American Ingenuity Award Winners for Social Progress The duo joined forces to protect tens of thousands of people during the disastrous water crisis in Flint, Michigan. Walters, a Flint resident, grew suspicious when her tap water changed color and her family suffered odd maladies. Officials insisted that the problems were limited to her household, but she refused to accept that answer and sought out Edwards, a Virginia Tech civil engineering professor and a veteran of municipal water wars. Combining political action and scientific credibility, the testing initiative undertaken by Walters and Edwards showed that the city’s water supply was contaminated with toxic chemicals—an explosive finding that finally forced state and local officials to address the dangers. Read more about their work: http://smithmag.co/D4dIHy | #IngenuityAwards And more about the American Ingenuity Awards: http://smithmag.co/77xPqy

The artist's cityscapes, once dismissed as too masculine, would later influence the floral artworks that became central to her iconic style

U.S. president-elect Donald Trump has promised sweeping global tariffs in his next term, but the Canadian Steel Producers Association remains confident that the industry can come out unscathed.

There is a sign of progress in the effort toward four-laning the final section of Highway 69 that links northern Ontario to the southern part of the province, and improving the safety of the heavily-travelled route.

Faster. Higher. Stronger. Together — and just don't test positive. That's the rallying cry for thousands of athletes as they prepare for the Olympics.

A young Toronto Maple Leafs fan has caught the attention of the NHL with his Halloween costume this year. With the help of his dad, Grayson Haire, of Trenton, Ont., will wear a 3D version of an Upper Deck MVP Auston Matthews hockey card.

After Canada Post workers gave a 72-hour notice to strike early Tuesday, some Calgary business owners are worried about what this means for holiday season sales. 

Eliminates the Cost and Complexity of Maintaining Online Parts Catalogs; Improves Search, Navigation, and Communication for Engineers Seeking 3D Part Models

Expanded 3D CAD curriculum gives instructors more time for individual instruction and special projects

U.K.