|5/16/2019||Patricia Zerfas||Division of Veterinary Resources||Article|
During infection, hepatocytes must undergo a reprioritization of metabolism, termed metabolic reprogramming. Hepatic metabolic
reprogramming in response to infection begins within hours of infection, suggesting a mechanism closely linked to
This work not only addresses a key component of end-organ physiology, but also raises questions about the side effects of biologics in the treatment of inflammatory diseases.
|Macrophage Derived TNFa Promotes Hepatic Reprogramming to Warburg-like Metabolism|
|3/20/2019||Christopher W. Belter||Division of Veterinary Resources||Journal|
For 50 years, the Fogarty International Center (FIC) has built research capacity particularly in low and middle-income countries responding to national and global public health priorities.
FIC provides a bridge between NIH and the greater global health community by facilitating exchanges among investigators, providing training opportunities and supporting promising research initiatives in developing countries.
|Fifty Years of Supporting Global Health Research at the NIH FIC|
|12/6/2018||Patricia Zerfas||Division of Library Services||Article|
Given the central role of the liver in MMA pathophysiology, we generated a viable mouse model to study the acute and chronic hepatic disease manifestations. To recapitulate the acute-on-chronic metabolic crises intermittently experienced by MMA patients, we subjected these mice to a fasting challenge and explored changes in the hepatic transcriptome between the baseline and fasting states.
Among the many pathways differentially expressed between MMA mice and control littermates, a key metabolic regulator, Fgf21, emerged as most significant.
|FGF21 Underlies a Hormetic Reponse to Metabolic Stress in Methylmalonic Acidemia|
|3/28/2018||NINDS, Dr. Alexander Ksendzovsky||Medical Arts Branch||Journal||Neurology Volume 88, Number 13 |
|12/5/2017||Lynn Young||Division of Library Services||Journal|
Piezo2 is a mechanically activated ion channel required for touch discrimination, vibration detection, and proprioception.
Here, we discovered that Piezo2 is extensively spliced, producing different Piezo2 isoforms with distinct properties. Together, our results describe, at the molecular level, a potential mechanism by which transduction is tuned, permitting the detection of a variety of mechanosensory stimuli.
|Cell-Type-Specific Splicing of Piezo2 Regulates Mechanotransduction|
|11/13/2017||NINDS, Dr. Antonina Roll-Mecak||Medical Arts Branch||Journal||Nature Chemical Biology: Flavors of RNA imaging |
|11/3/2017||Josh A. Duberman||Division of Library Services||Article|
The focus of this chapter is on information for a variety of clinical research tasks, including searching for adverse effects, evidence-based practices, and research protocol development.
This chapter [also] presents an overview of information resources for clinical research, their scope and capabilities, in an attempt to demystify the process and results of searching. The purpose of this chapter is to provide a background framework on which to build and learn more.
|Information Resources for the Clinical Researcher |
|10/3/2017||Derek A. Newcomer ||Division of Occupational Health and Safety||Article|
Known originally for their use in nuclear air cleaning systems, high efficiency particulate air (HEPA) filters containing specialized media are now commonplace in the biomedical, aerospace, pharmaceutical, and clinical care settings.
As an engineering control, HEPA filters are the crux of the biological safety cabinet’s (BSC) performance and are essential for achieving filtration standards in clean rooms.
|8/1/2017||NHLBI, Dr. Ryan McGlinchey||Medical Arts Branch||Journal||Biochemistry Volume 56 |
|7/18/2017||NEI, Dr. Anthony St Leger ||Medical Arts Branch||Journal||Immunity Volume 47|
|7/15/2017||Patricia Zerfas||Division of Veterinary Resources||Article|
Mucolipidosis type IV (MLIV) is a lysosomal storage disease characterized by neurologic and ophthalmologic abnormalities. There is currently no effective treatment. MLIV is caused by mutations in MCOLN1, a lysosomal cation channel from the transient receptor potential (TRP) family.
In this study, we used genome editing to knockout the two mcoln1 genes present in Danio rerio (zebrafish). Our model successfully reproduced the retinal and neuromuscular defects observed in MLIV patients, indicating that this model is suitable for studying the disease pathogenesis.
|Novel Degenerative and Developmental Defects in a Zebrafish Model of Mucolipidosis Type IV|
|7/10/2017||NCI, Dr. Xin Wang ||Medical Arts Branch||Journal||Cancer Cell Volume 22 Number 1 |
|6/23/2017||NICHD, Dr. Garima Gupta||Medical Arts Branch||Journal||Endocrine Practice |
|6/6/2017||Patricia Zerfas||Division of Veterinary Resources||Article|
T cells undergo metabolic reprogramming with major changes in cellular energy metabolism during activation. In summary, the findings presented herein emphasize the role of COX particularly in T cells as a metabolic checkpoint for cell fate decisions following T cell activation, with heterogeneous effects in T cell subsets.
In addition, our studies highlight the utility of translational models that recapitulate human mitochondrial disease for understanding immunometabolism.
|Cytochrome c Oxidase Activity Is a Metabolic Checkpoint that Regulates Cell Fate Decisions During T Cell Activation and Differentiation.|
|5/23/2017||Josh Duberman||Division of Library Services||Article|
In this study, firstly, the length of time between patent application and approval of a new cancer drug is examined. For this purpose, the three most common cancer types - breast, prostate and lung cancer - were chosen. As part of this study it is clearly important to understand the pace of current basic biomedical research and to develop potential solutions to the obstacles and challenges that it faces.
With this in mind, in the second part of the study the reasons for this “time lag” in biomedical research are studied and defined in more detail.
|A Guide to Time Lag and Time Lag Shortening Strategies in Oncology-Based Drug Development|
|3/2/2017||Derek A. Newcomer ||Division of Occupational Health and Safety||Article|
Industrial hygiene practitioners are often consulted to recommend personal protective equipment (PPE) as a control strategy to minimize worker exposure to biological, chemical, and physical hazards.
When selecting laboratory coats, the industrial hygienist is concerned with limitations of dexterity, durability, employee comfort, and compatibility with the hazard of concern. These and other criteria provide the framework for an organization’s PPE program.
|The Last Line of Defense: Selecting the Right Laboratory Coat|
|1/4/2017||Verma Walker ||Division of Library Services||Journal|
The National Institutes of Health (NIH) Library ran a 3D-printing pilot to provide NIH staff with an opportunity to try out 3D-printing technology and to gauge their interest in a permanent 3D-printing service.
An additional goal of the pilot was to build partnerships among NIH scientists, fellows, students, engineers, and administrators who were interested in 3D printing, so that the library could serve as an information hub connecting individuals who have 3D printing needs to experts in 3D modeling and printing.
|Implementing a 3D Printing Service in a Biomedical Library |
|9/1/2016||NCI, Dr. Sam John ||Medical Arts Branch||Journal||Molecular Cell Volume 57 |
|7/15/2016||NCI, Dr. Christophe Marchand ||Medical Arts Branch||Journal||ACS Chemical Biology: The Community of Chemical Biologists |
|6/29/2016||NIAID, Dr. Daniel Green ||Medical Arts Branch||Journal||Cytokine & Growth Factor Reviews|
|6/2/2016||NCI, Dr. Ji Luo||Medical Arts Branch||Journal||Trends in Cancer |
|5/2/2016||Patricia Zerfas||Division of Veterinary Resources||Article|
In this paper we describe individuals with biallelic mutations in LAMA1, all of whom had the cerebellar dysplasia, myopia and retinal dystrophy, in addition to obsessive compulsive traits, tics and anxiety. Patient-derived fibroblasts have impaired adhesion, reduced migration, abnormal morphology and increased apoptosis due to impaired activation of Cdc42, a member of the Rho family of GTPases that is involved in cytoskeletal dynamics. LAMA1 knockdown in human neuronal cells also showed abnormal morphology and filopodia formation, supporting the importance of LAMA1 in neuronal migration, and marking these cells potentially useful tools for disease modelling and therapeutic target discovery.
|Cystic cerebellar dysplasia and biallelic LAMA1 mutations|
|2/1/2016||Patricia Zerfas||Division of Veterinary Resources||Journal|
Mutations in TRPML1 cause the lysosomal storage disease mucolipidosis type IV (MLIV). Most studies focus on the role of TRPML1 in constitutive membrane trafficking to and from the lysosomes. However, this cannot explain impaired neuromuscular and secretory cells’ functions that mediate regulated exocytosis.
Here, we analyzed several forms of regulated exocytosis in a mouse model of MLIV and, opposite to expectations, we found enhanced exocytosis in secretory glands due to enlargement of secretory granules in part due to fusion with lysosomes.
|Fusion of lysosomes with secretory organelles leads to uncontrolled exocytosis in the lysosomal storage disease mucolipidosis type IV.|
|1/12/2016||NCI, Dr. Nicholas Restifo||Medical Arts Branch||Journal||Cell Metabolism Volume 23 |
|11/1/2015||CC, Dr. Steven Solomon ||Medical Arts Branch||Journal||Transfusion |
|9/9/2015||Patricia Zerfas||Division of Veterinary Resources||Article|
Bone sialoprotein (BSP) is a multifunctional extracellular matrix protein found in mineralized tissues, including bone, cartilage, tooth root cementum (both acellular and cellular types), and dentin. These analyses confirm a critical role for BSP in processes of cementogenesis and intramembranous ossification of craniofacial bone, whereas endochondral ossification in the cranial base was minimally affected and dentinogenesis was normal in Bsp(-/-) molar teeth.
|Mineralization defects in cementum and craniofacial bone from loss of bone sialoprotein|
|9/1/2015||Casey Skvorc, PhD, JD||Division of Occupational Health and Safety||Article|
Until recently, academic institutions and Principal Investigators (PIs) maintained a de-facto immunity from criminal prosecution for worker injuries and deaths attributed to unsafe laboratory practices. This status quo changed in 2011 when a state prosecutor filed felony charges for statutory and regulatory safety violations against the Regents of a state university system and a tenured professor.
This article presents sentinel factors associated with the prosecution and settlement of the prosecution, with a discussion of resulting implications for academic institutions/institutes and PIs.
|Criminal Prosecution—A Jumpstart for Laboratory Safety Accountability? |
|7/30/2015||NHLBI, Dr. Robert Balaban ||Medical Arts Branch||Journal||Nature: Cellular Power Grid |
|7/2/2015||Patricia Zerfas||Division of Veterinary Resources||Article|
Ablepharon macrostomia syndrome (AMS) and Barber-Say syndrome (BSS) are rare congenital ectodermal dysplasias characterized by similar clinical features. To establish the genetic basis of AMS and BSS, we performed extensive clinical phenotyping, whole exome and candidate gene sequencing, and functional validations.
Our results suggest that autosomal-dominant TWIST2 mutations cause AMS or BSS by inducing protean effects on the transcription factor’s DNA binding.
|Recurrent Mutations in the Basic Domain of TWIST2 Cause Ablepharon Macrostomia and Barber-Say Syndromes|
|5/29/2015||Patricia Zerfas||Division of Veterinary Resources||Article|
By employing an immunomodulation strategy to deplete Kupffer cells, we were able to improve the expression of multiple genes involved in β-oxidation.
Based on these findings, we are the first to suggest that the role of the liver as an immunologic organ is central in the pathophysiology of hepatic metabolic decompensation in inborn errors of metabolism due to respiratory viral infection.
|BBA Molecular Basis of Disease|