This is a guest contribution by Carlos Manrique Clavijo. Carlos Manrique Clavijo is a Colombian/Australian sound editor/sound designer and animation producer based in South Australia. He’s worked on award winning fiction, documentary and predominantly, animation from 2002. With Ana María Méndez, he is the co-founder of animation company, KaruKaru. Carlos has taught film sound design, […]

Gustavo Quintero, secretario de Gobierno de Bogotá, compartió en 6AM las estrategias que adoptará el Distrito para garantizar los derechos de los menores de esta comunidad asentada en el parque desde octubre de 2023

Highlights from Keke Palmer's acting career.

Bermuda Hospitals Board [BHB] has shared a frequently-asked questions [FAQ] factsheet explaining “how patients are cared for and by whom at King Edward VII Memorial Hospital [KEMH].” A spokesperson said, “Bermuda Hospitals Board has posted a FAQ on its website that explains how patients are cared for and by whom at King Edward VII Memorial […]

read more

Welcome to an enlightening exploration into the world of macronutrients. These fundamental components of our diet — proteins, carbohydrates, and fats — play integral roles in our body’s physiological functions. While they’re clearly important to our health and well-being, they often remain shrouded in mystery for most of us. By learning more about macronutrients, you’ll understand how ... Read more

The post Macronutrients Unveiled: A Comprehensive Look at Their Roles in a Balanced Diet appeared first on Star Two.

Sebastian A. Wagner
Oct 1, 2011; 10:M111.013284-M111.013284
Research

IJ Goldberg
Apr 1, 1996; 37:693-707
Reviews

RNA-protein interfaces control key replication events during the HIV-1 life cycle. The viral trans-activator of transcription (Tat) protein uses an archetypal arginine-rich motif (ARM) to recruit the host positive transcription elongation factor b (pTEFb) complex onto the viral trans-activation response (TAR) RNA, leading to activation of HIV transcription. Efforts to block this interaction have stimulated production of biologics designed to disrupt this essential RNA-protein interface. Here, we present four co-crystal structures of lab-evolved TAR-binding proteins (TBPs) in complex with HIV-1 TAR. Our results reveal that high-affinity binding requires a distinct sequence and spacing of arginines within a specific β2-β3 hairpin loop that arose during selection. Although loops with as many as five arginines were analyzed, only three arginines could bind simultaneously with major-groove guanines. Amino acids that promote backbone interactions within the β2-β3 loop were also observed to be important for high-affinity interactions. Based on structural and affinity analyses, we designed two cyclic peptide mimics of the TAR-binding β2-β3 loop sequences present in two high-affinity TBPs (KD values of 4.2 ± 0.3 and 3.0 ± 0.3 nm). Our efforts yielded low-molecular weight compounds that bind TAR with low micromolar affinity (KD values ranging from 3.6 to 22 μm). Significantly, one cyclic compound within this series blocked binding of the Tat-ARM peptide to TAR in solution assays, whereas its linear counterpart did not. Overall, this work provides insight into protein-mediated TAR recognition and lays the ground for the development of cyclic peptide inhibitors of a vital HIV-1 RNA-protein interaction.

The field of phosphoinositide signaling has expanded significantly in recent years. Phosphoinositides (PIs) are universal signaling molecules that directly interact with membrane proteins or with cytosolic proteins containing domains that directly bind phosphoinositides and are recruited to cell membranes. Through the activities of PI kinases and PI phosphatases, seven distinct phosphoinositide lipid molecules are formed from the parent molecule phosphatidylinositol. PI signals regulate a wide range of cellular functions, including cytoskeletal assembly, membrane binding and fusion, ciliogenesis, vesicular transport, and signal transduction. Given the many excellent reviews on phosphoinositide kinases, phosphoinositide phosphatases, and PIs in general, in this review, we discuss recent studies and advances in PI lipid signaling in the retina. We specifically focus on PI lipids from vertebrate (e.g. bovine, rat, mice, toad, and zebrafish) and invertebrate (e.g. drosophila, horseshoe crab, and squid) retinas. We also discuss the importance of PIs revealed from animal models and human diseases, and methods to study PI levels both in vitro and in vivo. We propose that future studies should investigate the function and mechanism of activation of PI-modifying enzymes/phosphatases and further unravel PI regulation and function in the different cell types of the retina.

Since the publication of the Age-Related Eye Disease Study (AREDS2) in 2013, the macular pigment carotenoids lutein and zeaxanthin have become well known to both the eye care community and the public. It is a fascinating aspect of evolution that primates have repurposed photoprotective pigments and binding proteins from plants and insects to protect and enhance visual acuity. Moreover, utilization of these plant-derived nutrients has been widely embraced for preventing vision loss from age-related macular degeneration (AMD). More recently, there has been growing awareness that these nutrients can also play a role in improving visual performance in adults. On the other hand, the potential benefits of lutein and zeaxanthin supplementation at very young ages have been underappreciated. In this review, we examine the biochemical mechanisms and supportive data for lutein and zeaxanthin supplementation throughout the lifespan, with particular emphasis on prenatal supplementation. We propose that prenatal nutritional recommendations may aim at improving maternal and infant carotenoid status. Prenatal supplementation with lutein and zeaxanthin might enhance infant visual development and performance and may even prevent retinopathy of prematurity, possibilities that should be examined in future clinical studies.

Wendi McLendon-Covey, David Alan Grier and Allison Tolman discuss the comedy in their harried medical characters on "St. Denis Medical," premiering Tuesday on NBC.

While President Donald Trump signed executive orders this week that could have widespread impact on immigrant communities, many in K-12 education await word on his decision on Deferred Action for Childhood Arrivals.

US President-elect Donald Trump announced that Elon Musk will lead the 'Department of Government Efficiency'.

New findings reveal that mitochondria in nutrient-deprived cells adopt specialised roles to prioritise either energy generation or amino acid synthesis. Led by Dr. Craig Thompson of Memorial Sloan Kettering Cancer Center, the study identified specific mitochondrial subpopulations, allowing cells to maintain critical functions even under stress. These discoveries have implications for understanding how cancer cells survive low-nutrient conditions and how cells repair after injury.

Jennifer Lopez and Ben Affleck filed for divorce in August 2024

US President-elect Donald Trump announced that Elon Musk will lead the 'Department of Government Efficiency'.

Timothée Chalamet was told to gain weight to get more roles.Timothée Chalamet doesn’t struggle to land big roles for movies anymore.However, there was a time when the Wonka star was rejected from two movie roles at the initial stages of his career.On Monday, November 11th,...

Neural reflexes occupy a central role in physiological homeostasis. The vagus nerve is a major conduit for transmitting afferent and efferent signals in homeostatic reflex arcs between the body and the brain. Recent advances in neuroscience, immunology, and physiology have revealed important vagus nerve mechanisms in suppressing inflammation and treating rheumatoid arthritis and other autoimmune conditions. Numerous clinical trials indicate that there is significant benefit to vagus nerve stimulation therapy. Although many questions are still unanswered, it will be important, even necessary, to pursue answers that will be useful in guiding interventions to modulate immunological and physiological homeostasis.

ATP-binding cassette transporter subfamily G member 2 (ABCG2) is a membrane-bound transporter responsible for the efflux of various xenobiotics and endobiotics, including protoporphyrin IX (PPIX), an intermediate in the heme biosynthesis pathway. Certain genetic mutations and chemicals impair the conversion of PPIX to heme and/or increase PPIX production, leading to PPIX accumulation and toxicity. In mice, deficiency of ABCG2 protects against PPIX-mediated phototoxicity and hepatotoxicity by modulating PPIX distribution. In addition, in vitro studies revealed that ABCG2 inhibition increases the efficacy of PPIX-based photodynamic therapy by retaining PPIX inside target cells. In this review, we discuss the roles of ABCG2 in modulating the tissue distribution of PPIX, PPIX-mediated toxicity, and PPIX-based photodynamic therapy.

G protein–coupled receptors (GPCRs) couple to heterotrimeric G proteins, comprised of α and β subunits, to convert extracellular signals into activation of intracellular signaling pathways. Canonically, GPCR-mediated activation results in the exchange of GDP for GTP on G protein α subunits (Gα) and the dissociation of Gα-GTP and G protein β subunits (Gβ), both of which can regulate a variety of signaling pathways. Hydrolysis of bound GTP by Gα returns the protein to Gα-GDP and allows reassociation with Gβ to reform the inactive heterotrimer. Naturally occurring mutations in Gα have been found at conserved glutamine and arginine amino acids that disrupt the canonical G protein cycle by inhibiting GTP hydrolysis, rendering these mutants constitutively active. Interestingly, these dysregulated Gα mutants are found in many different cancers due to their ability to sustain aberrant signaling without a need for activation by GPCRs. This review will highlight an increased recognition of the prevalence of such constitutively activating Gα mutations in cancers and the signaling pathways activated. In addition, we will discuss new knowledge regarding how these constitutively active Gα are regulated, how different mutations are biochemically distinct, and how mutationally activated Gα are unique compared with GPCR-activated Gα. Lastly, we will discuss recent progress in developing inhibitors directly targeting constitutively active Gα mutants.

Our knowledge of the roles of individual cytochrome P450 (P450) enzymes in drug metabolism has developed considerably in the past 30 years, and this base has been of considerable use in avoiding serious issues with drug interactions and issues due to variations. Some newer approaches are being considered for "phenotyping" metabolism reactions with new drug candidates. Endogenous biomarkers are being used for noninvasive estimation of levels of individual P450 enzymes. There is also the matter of some remaining "orphan" P450s, which have yet to be assigned reactions. Practical problems that continue in drug development include predicting drug-drug interactions, predicting the effects of polymorphic and other P450 variations, and evaluating interspecies differences in drug metabolism, particularly in the context of "metabolism in safety testing" regulatory issues ["disproportionate (human) metabolites"].

Redox reactions control fundamental biochemical processes, including energy production, metabolism, respiration, detoxification, and signal transduction. Cancer cells, due to their generally active metabolism for sustained proliferation, produce high levels of reactive oxygen species (ROS) compared to normal cells and are equipped with antioxidant defense systems to counteract the detrimental effects of ROS to maintain redox homeostasis. The KEAP1-NRF2 system plays a major role in sensing and regulating endogenous antioxidant defenses in both normal and cancer cells, creating a bivalent contribution of NRF2 to cancer prevention and therapy. Cancer cells hijack the NRF2-dependent antioxidant program and exploit a very unique metabolism as a trade-off for enhanced antioxidant capacity. This work provides an overview of redox metabolism in cancer cells, highlighting the role of the KEAP1-NRF2 system, selenoproteins, sulfur metabolism, heme/iron metabolism, and antioxidants. Finally, we describe therapeutic approaches that can be leveraged to target redox metabolism in cancer.

1. Top Roles For Elon Musk, Vivek Ramaswamy In Donald Trump's Cabinet  NDTV
2. Trump’s 'Manhattan Project' of government reform: Musk and Ramaswamy to lead efficiency crusade  The Times of India
3. Donald Trump Picks Elon Musk, Vivek Ramaswamy For Cabinet: Internet Has This To Say  News18
4. A dope for DOGE (and Dogecoin): Trump taps Musk in efficiency team, crypto fans rejoice  The Economic Times
5. Video | Elon Musk In Trump's New Cabinet, UK Church Abuse Scandal, Saudi Megacity in Trouble  NDTV

The announcement was made in a video unveiled at Disney’s D23 event in Brazil, featuring the returning stars in a reveal

Jason, 84, said senior actors had a ‘tremendous amount to offer’

La vedette colombienne du reggaeton Karol G s’est excusée pour des paroles de son nouveau single «+57» jugées offensantes.

Michael Jones - #NMClientStory

The school is pivotal for identity evolution in young minds and given the space to explore it can shape inclusiveness among students

Arshad Warsi and Meher Vij came together to promote their new film, Bandaa Singh Chaudhary, based on the events of 1971 War, a movie that is being produced by Arbaaz Khan.

US Perspectives on Sino-Russian Cooperation in the Arctic and Roles for Partners US Perspectives on Sino-Russian Cooperation in the Arctic and Roles for Partners

Coimbatore’s policewomen maintain weapons at the Armoury, handle sniffer dogs, drive heavy duty vehicles, and are a part of the police commissioner’s striking force

National Bureau of Economic Research

The author, citing his own experiences, delves into the qualities required to become a good leader

'I was tense the night before the shoot; I developed cold feet. However, when I got up in the morning, I was confident and looking forward to playing Sandhya.' Niharika Konidela gets candid about her first film, Ok Manasu.