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Mutations in ataxia telangiectasia mutated (ATM) kinase lead to cerebellar neurodegeneration. In this issue of Molecular Cell, Lee et al. (2021) revealed how transcription-induced reactive oxygen species and DNA-RNA hybrids activate PARP enzymes, generating the nucleic acid poly-ADP-ribose, which promotes the accumulation of protein aggregates in A-T-like disorders.Cieśla et al. (2021) uncover intricate circuits of post-transcriptional regulation induced by the Myc oncogene, including alternative splicing and translational control, which are relevant for breast cancer prognosis and contribute to metabolic reprogramming and stem cell-like features of cancer cells.In this issue of Molecular Cell, Kaiho-Soma et al. (2021) demonstrate that the HECT-type E3 ubiquitin ligase TRIP12 cooperates with CRL complexes to promote PROTAC-induced degradation of neo-substrates by generating K29/K48-branched ubiquitin chains.We talk to the authors of "Structural basis for conformational equilibrium of the catalytic spliceosome" about their paper, advances in cryo-EM that made it possible, and the influence of their late mentor Kiyoshi Nagai, to whom the paper is dedicated.As part of our commitment to amplifying the voices of underrepresented scientists, we are publishing the insights and experiences of a panel of underrepresented scientists. In this piece, they discuss ways to make science more inclusive-from key points they wish their colleagues understood to actions those in the scientific community can take. These are the personal opinions of the authors and may not reflect the views of their institutions.Protein modifications modulate nearly every aspect of cell biology in organisms, ranging from Archaea to Eukaryotes. The earliest evidence of covalent protein modifications was found in the early 20th century by studying the amino acid composition of proteins by chemical hydrolysis. These discoveries challenged what defined a canonical amino acid. The advent and rapid adoption of mass-spectrometry-based proteomics in the latter part of the 20th century enabled a veritable explosion in the number of known protein modifications, with more than 500 discrete modifications counted today. Now, new computational tools in data science, machine learning, and artificial intelligence are poised to allow researchers to make significant progress in discovering new protein modifications and determining their function. In this review, we take an opportunity to revisit the historical discovery of key post-translational modifications, quantify the current landscape of covalent protein adducts, and assess the role that new computational tools will play in the future of this field.The retina dissects the visual scene into parallel information channels, which extract specific visual features through nonlinear processing. The first nonlinear stage is typically considered to occur at the output of bipolar cells, resulting from nonlinear transmitter release from synaptic terminals. In contrast, we show here that bipolar cells themselves can act as nonlinear processing elements at the level of their somatic membrane potential. Intracellular recordings from bipolar cells in the salamander retina revealed frequent nonlinear integration of visual signals within bipolar cell receptive field centers, affecting the encoding of artificial and natural stimuli. These nonlinearities provide sensitivity to spatial structure below the scale of bipolar cell receptive fields in both bipolar and downstream ganglion cells and appear to arise at the excitatory input into bipolar cells. Thus, our data suggest that nonlinear signal pooling starts earlier than previously thought that is, at the input stage of bipolar cells.Over the past 20 years, the use of telemedicine has increased exponentially. Its fundamental aim is to improve access to care. In this review, we assess the extent to which telemedicine has fulfilled this promise across medical domains. Additionally, we assess whether telemedicine has improved related health outcomes. Finally, we determine who has benefited from this novel form of health care delivery. A review of the literature indicates that (a) telemedicine has improved access to care for a wide range of clinical conditions ranging from stroke to pregnancy; (b) telemedicine in select circumstances has demonstrated improved health outcomes; and (c) telemedicine has addressed geographical, but less so social, barriers to care. For telemedicine to fulfill its promise, additional evidence needs to be gathered on health outcomes and cost savings, the digital divide needs to be bridged, and policy changes that support telemedicine reimbursement need to be enacted.The human microbiome contributes metabolic functions, protects against pathogens, educates the immune system, and through these basic functions, directly or indirectly, affects most of our physiologic functions. Here, we consider the human microbiome and its relationship to several major noncommunicable human conditions, including orodigestive tract cancers, neurologic diseases, diabetes, and obesity. We also highlight the scope of contextual macroenvironmental factors (toxicological and chemical environment, built environment, and socioeconomic environment) and individual microenvironmental factors (smoking, alcohol, and diet) that may push the microbiota toward less healthy or more healthy conditions, influencing the development of these diseases. Last, we highlight current uncertainties and challenges in the study of environmental influences on the human microbiome and implications for understanding noncommunicable disease, suggesting a research agenda to strengthen the scientific evidence base.An often-stated public health comment is that "vaccination is a victim of its own success." While the scientific and medical consensus on the benefits of vaccination is clear and unambiguous, an increasing number of people are perceiving vaccines as unsafe and unnecessary. The World Health Organization identified "the reluctance or refusal to vaccinate despite availability of vaccines" as one of the 10 threats to global health in 2019. The negative influence of anti-vaccination movements is often named as a cause of increasing vaccine resistance in the public. In this review, we give an overview of the current literature on the topic, beginning by agreeing on terminology and concepts before looking at potential causes, consequences, and impacts of resistance to vaccination.Introduction The goal for pediatric short bowel syndrome (SBS) patients is intestinal adaptation. Until recently, the medical management of pediatric SBS has centered on the prevention and treatment of complications in order to allow time for adaptation. Teduglutide, glucagon-like peptide 2 (GLP-2) analog, has recently been approved for use in pediatric SBS patients greater than 1 year of age as a novel agent to augment intestinal adaptation. Areas covered This article reviews the pharmacology, safety, efficacy, and tolerability of GLP-2 analog teduglutide in pediatric patients greater than 1 year of age. selleck chemical We review all current studies and discuss teduglutide's place in pediatric SBS therapy. Expert opinion Teduglutide marks the first successful pharmacological intervention that augments the natural process of adaptation safely and effectively in SBS pediatric patients. More studies and further development are needed to optimize its potential in other pediatric patients.Introduction Bronchoscopy and related procedures have unambiguously been affected during the Corona Virus Disease 2019 (COVID-19) pandemic caused by Severe Acute Respiratory Syndrome-Corona Virus-2 (SARS COV-2). Ordinary bronchoscopy practices and lung cancer services might have changed over this pandemic and for the years to come.Areas covered This manuscript summarizes the utility of bronchoscopy in COVID-19 patients, and the impact of the pandemic in lung cancer diagnostic services, in view of possible viral spread during these We conducted a literature review of articles published in PubMed/Medline from inception to November 5th, 2020 using relevant terms.Expert opinion Without doubt this pandemic has changed the way bronchoscopy and related procedures are being performed. Mandatory universal personal protective equipment, pre-bronchoscopy PCR tests, dedicated protective barriers and disposable bronchoscopes might be the safest and simpler way to perform even the most complicated procedures.Background Postoperative infections after rhinoplasties are rare, yet devastating on patient outcomes. The literature reports an overall incidence of less then 2% with higher numbers seen in those requiring revision procedures. Materials and Methods A retrospective chart review of rhinoplasty patients from 2002 to 2019 of the primary author (D.M.T.) was performed. The objective of this study is to demonstrate the use of postoperative antibiotic soaks and irrigations in rhinoplasty, as well as evaluate the postoperative infection rates. Results Of the 3084 rhinoplasty procedures evaluated, there were 19 postoperative infections (infection rate [IR] = 0.62%). Patients without antibiotic soaks or irrigations had 17 infections (IR = 1.01%). The IR of antibiotic soaks was 0.08% with a significant reduction compared with no soaks/irrigations (p = 0.0053). With antibiotic soaks and irrigations, there was 1 infection (IR = 0.49%) with no significant difference between no soaks/irrigations or soaks alone. Conclusions The use of antibiotic soaks and irrigations resulted in an IR of 0.62%. Antibiotic soaks reduced the rate of postoperative infection, particularly in secondary rhinoplasty. Antibiotic soaks and irrigations are safe, effective, and well-tolerated by patients. As a result, these techniques may be considered in patients undergoing rhinoplasty, particularly those with an extensive revision history, trauma, filler, prior infection, or underlying disease processes.Objective The aim of this study is to investigate the effect of complex decongestive physiotherapy (CDP) plus intermittent pneumatic compression (IPC) applications on upper extremity circumference and volume in patients with lipedema. Methods and Results All participants included in the study were included in a treatment protocol consisting of CDP and IPC. The Perometer 400 NT was used in the measurement of upper extremity volume and circumference before and after treatment. The measurements were performed in four reference points. According to the Perometer results before and after CDP, statistically significant reduction was found in the circumference of 3 of the 4 points of measurements performed in each of the left and right upper extremities. When the volume assessments were compared, it was seen that statistically significant reduction was found in the volume of both limbs. Conclusion A treatment program consisting of CDP and IPC can be effective in reducing the circumference and volume of the arm in patients with upper extremity lipedema. So, CDP applications can help prevent the development of complications such as lipolymphedema, hypertension, and heart failure. Clinical Trial Registration number NCT04643392 https//register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S000AF9B&selectaction=Edit&uid=U00055NT&ts=2&cx=-3oevdw.