Green Mountain Power’s commitment to innovation delivered bigger savings to customers as New England recently hit a new yearly peak for power demand.

Trump's proposed budget severely cuts the EPA and DOE's efficiency and renewables offices, but allocates funding for R&D, clean coal and advanced nuclear.

Only time will tell whether this is right, but EV adoption is clearly rising both on the individual and fleet fronts. Utilities such as Southern California Edison and Ameren, among many others, are working to build EV charging infrastructure and align power distribution in a way to handle it.

Trump's proposed budget severely cuts the EPA and DOE's efficiency and renewables offices, but allocates funding for R&D, clean coal and advanced nuclear.

Steve Sawyer, 63, Senior Policy Advisor and former Secretary General of the Global Wind Energy Council, passed away on July 31, 2019 of a sudden and aggressive lung cancer.

Deepak Abbhi v Richard John Slade (trading as Richard Slade & Co) [2019] EWCA Civ 2175 The Court of Appeal recently unanimously held that an oral promise by a son-in-law to give money to his father-in-law to pay legal fees was an indemnity and n...

MARLBOROUGH (UNITED KINGDOM) - Leading English trainer Richard Hannon Junior is blessed with self-deprecatory humour, but that quality will be tested by how his horses run at Royal Ascot this week.

Hdac Technology AG(Hdac) together with Dream Global Partners (DREAMChain), held a business agreement ceremony on August 16th establishing the foundation of a comprehensive partnership to expand and incorporate blockchain-based real estate enterprises world-wide.The ceremony was held on the 3rd floor of Hdac office building, with Hdac Technology Korea CEO, Michael Yoon, Dream Global Partner’s President, Pietro A. Doran, and Dream Global Partner’s co-founder/Chief Crypto-Economics Officer, Samson ...

Pr�t� cette saison � l'AS Monaco apr�s...

Sur la base d'une mod�lisation, l'Oms estime que 190.000 personnes pourraient perdre la vie � cause du coronavirus qui infectera entre 29 � 44 millions d'Africains. ......

New Delhi: Union Home Minister Amit Shah on Saturday dismissed rumours about his ill-health, saying that he is healthy and has been working as the country fights coronavirus crisis. "I am completely healthy and am not suffering from any disease," Shah tweeted in Hindi. In his post, the Home Minister said that...

BELGRADE, Serbia (AP) — Serbia has protested to the European Union after one of its publications described inventor and electricity pioneer Nikola Tesla as a Croat. Foreign Minister Ivica Dacic said on Saturday he has sent the protest note to Brussels after the EU’s...

The world is at risk of widespread famines resulting from lockdowns to contain the spread of the coronavirus pandemic. The devastating economic impact of Covid-19 is seeing a huge rise in the number of hungry people. Hamida Begum, a domestic worker in Bangladesh who is now out of work, said: “We only have forty Taka […]

The post Amid Covid-19 Hunger Fear Mounts in Bangladesh appeared first on Inter Press Service.

Feminist responses to COVID-19 have been swift, insightful, and numerous. There have been webinars (so.many.webinars), twitter threads, illustrations, press releases and policy recommendations, and online house parties. Analysis pieces cover everything from the gendered impacts of COVID-19 to how to work remotely to the role of neoliberal capitalism. Most strikingly, feminists have mobilized on a […]

The post Autonomous Resourcing: the Engine Room of Feminist Work Amid a Global Pandemic appeared first on Inter Press Service.

Hotels in the southeastern province of Adıyaman are enjoying a 100 percent occupancy rate thanks to a flock of domestic visitors wanting to spend their upcoming nine-day Eid al-Fitr holiday, along with the increasing number of foreign visitors wanting to see the beautiful Mount Nemrut.

Visitors snap photos of massive stone heads that stare down on them from the summit of Mount Nemrut. (Source: The Associated Press)

Sixteen are from Unguja while 13 are from Pemba, all Tanzanians.

After two decades of dryness, enough rains have finally come to bring Hamoun wetland back to life in the southeastern Iranian province of Sistan-Baluchestan, reviving agriculture in the region as well. Hamoun is the third-largest lake of Iran after the Caspian Sea and Urmia Lake.

Disease, also known as Botrytis cinerea, turns fruits partially black to brown near the stalk

They had visited more than 20 countries before coronavirus struck.

Abhishek Bachchan and Aishwarya Rai have stood strong through thick and thin

“His ultimate passion was for good governance and his advocacy was to help save the environment. He was a highly principled man who sought refuge in his faith.”

The post Dumaguete mourns death of broadcaster 2 days after World Press Freedom Day appeared first on Bulatlat.

A unanimous Supreme Court on Thursday threw out the convictions of two political insiders involved in the "Bridgegate" scandal that ultimately derailed the 2016 presidential bid of then-New Jersey Gov. Chris Christie. The justices found evidence of deception, corruption and abuse of power in the sch...

A unanimous Supreme Court on Thursday threw out the convictions of two political insiders involved in the “Bridgegate” scandal that ultimately derailed the 2016 presidential bid of then-New Jersey Gov. Chris Christie. The justices found evidence of deception, corruption and abuse of power in the scheme, but said “not every corrupt act by state or local officials is a federal crime.”

On Christmas Eve 1968, Apollo 8 became the first crewed spacecraft to circle the moon. Emerging from its dark side, one astronaut reached for his camera

Fossilised tree roots found in a New York quarry are 386 million years old, making them the remains of the oldest known forest yet

In a new report, KPMG ranks countries' autonomous vehicle (AV) readiness by analyzing how policymakers perform on four pillars: policy and legislation, technology and innovation, infrastructure, and consumer acceptance. The top rankings? The...

Title: Allergy-Linked Mouth Breathing Spells Trouble for Kids
Category: Health News
Created: 4/23/2010 12:10:00 PM
Last Editorial Review: 4/26/2010 12:00:00 AM

Title: TV Breakups: When a Show Ends, Fans May 'Mourn'
Category: Health News
Created: 4/23/2011 11:01:00 AM
Last Editorial Review: 4/25/2011 12:00:00 AM

Title: Health Tip: Use a Mouthguard
Category: Health News
Created: 4/27/2016 12:00:00 AM
Last Editorial Review: 4/27/2016 12:00:00 AM

Title: Health Tip: Prevent Hand, Foot and Mouth Disease
Category: Health News
Created: 4/30/2018 12:00:00 AM
Last Editorial Review: 4/30/2018 12:00:00 AM

Title: There May Be Antidote for Ocean's Most Venomous Creature
Category: Health News
Created: 5/1/2019 12:00:00 AM
Last Editorial Review: 5/2/2019 12:00:00 AM

Physical and chemical DNA-damaging agents are used widely in the treatment of cancer. Double-strand break (DSB) lesions in DNA are the most deleterious form of damage and, if left unrepaired, can effectively kill cancer cells. DNA-dependent protein kinase (DNA-PK) is a critical component of nonhomologous end joining (NHEJ), one of the two major pathways for DSB repair. Although DNA-PK has been considered an attractive target for cancer therapy, the development of pharmacologic DNA-PK inhibitors for clinical use has been lagging. Here, we report the discovery and characterization of a potent, selective, and orally bioavailable DNA-PK inhibitor, M3814 (peposertib), and provide in vivo proof of principle for DNA-PK inhibition as a novel approach to combination radiotherapy. M3814 potently inhibits DNA-PK catalytic activity and sensitizes multiple cancer cell lines to ionizing radiation (IR) and DSB-inducing agents. Inhibition of DNA-PK autophosphorylation in cancer cells or xenograft tumors led to an increased number of persistent DSBs. Oral administration of M3814 to two xenograft models of human cancer, using a clinically established 6-week fractionated radiation schedule, strongly potentiated the antitumor activity of IR and led to complete tumor regression at nontoxic doses. Our results strongly support DNA-PK inhibition as a novel approach for the combination radiotherapy of cancer. M3814 is currently under investigation in combination with radiotherapy in clinical trials.

The vertebrate limb serves as an experimental paradigm to study mechanisms that regulate development of the stereotypical skeletal elements. In this study, we simultaneously inactivated Sall4 using Hoxb6Cre and Plzf in mouse embryos, and found that their combined function regulates development of the proximal-anterior skeletal elements in hindlimbs. The Sall4; Plzf double knockout exhibits severe defects in the femur, tibia, and anterior digits, distinct defects compared to other allelic series of Sall4; Plzf. We found that Sall4 regulates Plzf expression prior to hindlimb outgrowth. Further expression analysis indicated that Hox10 genes and GLI3 are severely downregulated in the Sall4; Plzf double knockout hindlimb bud. In contrast, PLZF expression is reduced but detectable in Sall4; Gli3 double knockout limb buds, and SALL4 is expressed in the Plzf; Gli3 double knockout limb buds. These results indicate that Plzf, Gli3, and Hox10 genes downstream of Sall4, regulate femur and tibia development. In the autopod, we show that Sall4 negatively regulates Hedgehog signaling, which allows for development of the most anterior digit. Collectively, our study illustrates genetic systems that regulate development of the proximal-anterior skeletal elements in hindlimbs.

Key Points

Epstein-Barr virus (EBV) causes B cell lymphomas and transforms B cells in vitro. The EBV protein EBNA3A collaborates with EBNA3C to repress p16 expression and is required for efficient transformation in vitro. An EBNA3A deletion mutant EBV strain was recently reported to establish latency in humanized mice but not cause tumors. Here, we compare the phenotypes of an EBNA3A mutant EBV (3A) and wild-type (WT) EBV in a cord blood-humanized (CBH) mouse model. The hypomorphic 3A mutant, in which a stop codon is inserted downstream from the first ATG and the open reading frame is disrupted by a 1-bp insertion, expresses very small amounts of EBNA3A using an alternative ATG at residue 15. 3A caused B cell lymphomas at rates similar to their induction by WT EBV but with delayed onset. 3A and WT tumors expressed equivalent levels of EBNA2 and p16, but 3A tumors in some cases had reduced LMP1. Like the WT EBV tumors, 3A lymphomas were oligoclonal/monoclonal, with typically one dominant IGHV gene being expressed. Transcriptome sequencing (RNA-seq) analysis revealed small but consistent gene expression differences involving multiple cellular genes in the WT EBV- versus 3A-infected tumors and increased expression of genes associated with T cells, suggesting increased T cell infiltration of tumors. Consistent with an impact of EBNA3A on immune function, we found that the expression of CLEC2D, a receptor that has previously been shown to influence responses of T and NK cells, was markedly diminished in cells infected with EBNA3A mutant virus. Together, these studies suggest that EBNA3A contributes to efficient EBV-induced lymphomagenesis in CBH mice.

IMPORTANCE The EBV protein EBNA3A is expressed in latently infected B cells and is important for efficient EBV-induced transformation of B cells in vitro. In this study, we used a cord blood-humanized mouse model to compare the phenotypes of an EBNA3A hypomorph mutant virus (3A) and wild-type EBV. The 3A virus caused lymphomas with delayed onset compared to the onset of those caused by WT EBV, although the tumors occurred at a similar rate. The WT EBV and EBNA3A mutant tumors expressed similar levels of the EBV protein EBNA2 and cellular protein p16, but in some cases, 3A tumors had less LMP1. Our analysis suggested that 3A-infected tumors have elevated T cell infiltrates and decreased expression of the CLEC2D receptor, which may point to potential novel roles of EBNA3A in T cell and NK cell responses to EBV-infected tumors.

Upon infection, the highly structured 5' untranslated region (5' UTR) of picornavirus is involved in viral protein translation and RNA synthesis. As a critical element in the 5' UTR, the internal ribosome entry site (IRES) binds to various cellular proteins to function in the processes of picornavirus replication. Foot-and-mouth disease virus (FMDV) is an important member in the family Picornaviridae, and its 5' UTR contains a functional IRES element. In this study, the cellular heterogeneous nuclear ribonucleoprotein L (hnRNP L) was identified as an IRES-binding protein for FMDV by biotinylated RNA pulldown assays, mass spectrometry (MS) analysis, and determination of hnRNP L-IRES interaction regions. Further, we found that hnRNP L inhibited the growth of FMDV through binding to the viral IRES and that the inhibitory effect of hnRNP L on FMDV growth was not due to FMDV IRES-mediated translation, but to influence on viral RNA synthesis. Finally, hnRNP L was demonstrated to coimmunoprecipitate with RNA-dependent RNA polymerase (3D^pol) in an FMDV RNA-dependent manner in the infected cells. Thus, our results suggest that hnRNP L, as a critical IRES-binding protein, negatively regulates FMDV replication by inhibiting viral RNA synthesis, possibly by remaining in the replication complex.

IMPORTANCE Picornaviruses, as a large family of human and animal pathogens, cause a bewildering array of disease syndromes. Many host factors are implicated in the pathogenesis of these viruses, and some proteins interact with the viral IRES elements to affect function. Here, we report for the first time that cellular hnRNP L specifically interacts with the IRES of the picornavirus FMDV and negatively regulates FMDV replication through inhibiting viral RNA synthesis. Further, our results showed that hnRNP L coimmunoprecipitates with FMDV 3D^pol in a viral RNA-dependent manner, suggesting that it may remain in the replication complex to function. The data presented here would facilitate further understanding of virus-host interactions and the pathogenesis of picornavirus infections.

Transcription factors (TFs) enact precise regulation of gene expression through site-specific, genome-wide binding. Common methods for TF-occupancy profiling, such as chromatin immunoprecipitation, are limited by requirement of TF-specific antibodies and provide only end-point snapshots of TF binding. Alternatively, TF-tagging techniques, in which a TF is fused to a DNA-modifying enzyme...

ABSTRACT

The effect of the rapid accumulation of nonsynonymous mutations on the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is not yet known. The 3a protein is unique to SARS-CoV and is essential for disease pathogenesis. Our study aimed at determining the nonsynonymous mutations in the 3a protein in SARS-CoV-2 and determining and characterizing the protein’s structure and spatial orientation in comparison to those of 3a in SARS-CoV. A total of 51 different nonsynonymous amino acid substitutions were detected in the 3a proteins among 2,782 SARS-CoV-2 strains. We observed microclonality within the ORF3a gene tree defined by nonsynonymous mutations separating the isolates into distinct subpopulations. We detected and identified six functional domains (I to VI) in the SARS-CoV-2 3a protein. The functional domains were linked to virulence, infectivity, ion channel formation, and virus release. Our study showed the importance of conserved functional domains across the species barrier and revealed the possible role of the 3a protein in the viral life cycle. Observations reported in this study merit experimental confirmation.

IMPORTANCE At the surge of the coronavirus disease 2019 (COVID-19) pandemic, we detected and identified six functional domains (I to VI) in the SARS-CoV-2 3a protein. Our analysis showed that the functional domains were linked to virulence, infectivity, ion channel formation, and virus release in SARS-CoV-2 3a. Our study also revealed the functional importance of conserved domains across the species barrier. Observations reported in this study merit experimental confirmation.

Nadia Vicenzi, Alejandro Laspiur, Paola L. Sassi, Ruben Massarelli, John Krenz, and Nora R. Ibargüengoytia

In ectotherms, temperature exerts a strong influence on the performance of physiological and ecological traits. One approach to understand the impact of rising temperatures on animals and their ability to cope with climate change is to quantify variation in thermal-sensitive traits. Here, we examined the thermal biology, the temperature dependence and the thermal plasticity of bite force (endurance and magnitude) in Diplolaemus leopardinus, an aggressive and territorial lizard, endemic to Mendoza province, Argentina. Our results indicated that this lizard behaves like a moderate thermoregulator which uses the rocks of its environment as the main heat source. Bite endurance was not influenced by head morphometry and body temperature, whereas bite force was influenced by head length and jaw length, and exhibited thermal dependence. Before thermal acclimation treatments, the maximum bite force for D. leopardinus occured at the lowest body temperature and fell sharply with increasing body temperature. After acclimation treatments, lizards acclimated at higher temperatures exhibited greater bite force. Bite force showed phenotypic plasticity, which reveals that leopard iguanas are able to maintain (and even improve) their bite force under a rising-temperature scenario.