scholarly journals The thymic way to transplantation tolerance.

1995 ◽  
Vol 5 (9) ◽  
pp. 1639-1646
Author(s):  
G Remuzzi ◽  
N Perico ◽  
C B Carpenter ◽  
M H Sayegh
Keyword(s):  
Islet Cell ◽  
Critical Role ◽  
Donor Strain ◽  
Major Goal ◽  
Isolated Pancreatic Islets ◽  
The Past ◽  
Self Tolerance ◽  
Initial Work ◽  
Intrathymic Injection ◽  
Privileged Site

Within the past three decades, extensive research has been carried out with the aim to prevent graft rejection by minimizing the side effects related to the use of immunosuppressants. The major goal in transplantation research remains the development of strategies that would allow one to achieve a state of donor-specific unresponsiveness in order to promote a condition of true tolerance without the need of immunosuppressants. Recent evidence has been provided that this is a pursuing goal, at least in experimental animals. The thymus plays the major role in the development of self-tolerance, and initial work in the late 1960s indicated that the thymus also plays a critical role in the induction of acquired tolerance to exogenous antigens. Recently, the interest in acquired thymic tolerance has been renewed by the observation that, in the rat, the thymus is an immunologically privileged site in which isolated pancreatic islets can be engrafted and survive indefinitely. Moreover, intrathymic injection of the islets induced donor-specific unresponsiveness, which allowed survival of a second donor-strain islet cell allograft transplanted into an extrathymic site. These findings on cellular allografts have been extended to vascularized organ allografts.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Small Molecule Inhibitors of Influenza Virus Entry

2021 ◽  
Vol 14 (6) ◽  
pp. 587
Author(s):  
Zhaoyu Chen ◽  
Qinghua Cui ◽  
Michael Caffrey ◽  
Lijun Rong ◽  
Ruikun Du
Keyword(s):  
Influenza Virus ◽  
Membrane Fusion ◽  
Small Molecule ◽  
Drug Target ◽  
Small Molecule Inhibitors ◽  
Virus Entry ◽  
Critical Role ◽  
Structural Basis ◽  
Future Directions ◽  
The Past

Hemagglutinin (HA) plays a critical role during influenza virus receptor binding and subsequent membrane fusion process, thus HA has become a promising drug target. For the past several decades, we and other researchers have discovered a series of HA inhibitors mainly targeting its fusion machinery. In this review, we summarize the advances in HA-targeted development of small molecule inhibitors. Moreover, we discuss the structural basis and mode of action of these inhibitors, and speculate upon future directions toward more potent inhibitors of membrane fusion and potential anti-influenza drugs.

Recent Developments in Heck-Type Reaction of Unactivated Alkenes and Alkyl Electrophiles

Synthesis ◽  
2020 ◽  
Author(s):  
Lili Shi ◽  
Junkai Fu ◽  
Shuangqiu Gao ◽  
Le Chang ◽  
Binglin Wang
Keyword(s):  
Heck Reaction ◽  
Alkyl Radicals ◽  
Type Reaction ◽  
The Past ◽  
Alkyl Electrophiles ◽  
Recent Developments ◽  
Palladium Catalyzed ◽  
Initial Work ◽  
Activated Olefins ◽  
Pseudo Halides

AbstractThe Mizoroki–Heck reaction is considered as one of the most ingenious and widely used methods for constructing C–C bonds. This reaction mainly focuses on activated olefins (styrenes, acrylates, or vinyl ethers) and aryl/vinyl (pseudo) halides. In comparison, the studies on unactivated alkenes and alkyl electrophiles are far less due to the low reactivity, poor selectivity, as well as competitive β-H elimination. In the past years, a growing interest has thus been devoted and significant breakthroughs have been achieved in the employment of unactivated alkenes and alkyl electrophiles as the reaction components, and this type of coupling is called as Heck-type or Heck-like reaction, which distinguishes from the traditional Heck reaction. Herein, we give a brief summary on Heck-type reaction between unactivated alkenes and alkyl electrophlies, covering its initial work, recent advancements, and mechanistic discussions.1 Introduction2 Intramolecular Heck-Type Reaction of Unactivated Alkenes and Alkyl Electrophiles2.1 Cobalt-Catalyzed Intramolecular Heck-Type Reaction2.2 Palladium-Catalyzed Intramolecular Heck-Type Reaction2.3 Nickel-Catalyzed Intramolecular Heck-Type Reaction2.4 Photocatalysis and Multimetallic Protocol for Intramolecular Heck-Type Reaction3 Intermolecular Heck-Type Reaction of Unactivated Alkenes and Alkyl Electrophiles3.1 Electrophilic Trifluoromethylating Reagent as Reaction Partners3.2 Alkyl Electrophiles as Reaction Partners4 Oxidative Heck-Type Reaction of Unactivated Alkenes and Alkyl Radicals5 Conclusions and Outlook

Disorders of Musical Cognition

2012 ◽  
Author(s):  
Lauren Stewart ◽  
Katharina von Kriegstein ◽  
Simone Dalla Bella ◽  
Jason D. Warren ◽  
Timothy D. Griffiths
Keyword(s):  
Case Studies ◽  
Cognitive Neuroscience ◽  
Cognitive Architecture ◽  
Critical Role ◽  
Theoretical Models ◽  
Systematic Evaluation ◽  
Neural Basis ◽  
The Past ◽  
Musical Cognition ◽  
Musical Listening

This article presents an overview of case studies of acquired disorders of musical listening. Like any cognitive faculty, music is multifaceted, and the identification of the neural basis of any complex faculty must proceed, hand in hand, with an elucidation of its cognitive architecture. The past decade has seen an evolution in the theoretical models of musical processing, allowing the development of theoretically motivated instruments for the systematic evaluation of musical disorders. Such developments have allowed reports of musical disorders to evolve from historical anecdotes to systematic, verifiable accounts that can play a critical role in contributing to our understanding of the cognitive neuroscience of music.

scholarly journals Comparison of Juvenile Feed Protocols on Growth and Spawning in Zebrafish

2021 ◽  
Author(s):  
Stephen C Frederickson ◽  
Mark D Steinmiller ◽  
Tiffany Rae Blaylock ◽  
Mike E Wisnieski II ◽  
James D Malley ◽  
...  
Keyword(s):  
Reproductive Performance ◽  
Critical Role ◽  
Fertilization Rate ◽  
Long Term Effects ◽  
The Past ◽  
Adult Feeding ◽  
Freeze Dried ◽  
Feeding Protocol ◽  
Spawning Success

Over the past 2 decades, zebrafish, Danio rerio, have become a mainstream laboratory animal model, yet zebrafish husbandrypractices remain far from standardized. Feeding protocols play a critical role in the health, wellbeing, and productivity ofzebrafish laboratories, yet they vary significantly between facilities. In this study, we compared our current feeding protocol for juvenile zebrafish (30 dpf to 75 dpf), a 3:1mixture of fish flake and freeze-dried krill fed twice per day with live artemia twice per day (FKA), to a diet of Gemma Micro 300 fed once per day with live artemia once per day (GMA). Our results showed that juvenile EK wild-type zebrafish fed GMA were longer and heavier than juveniles fed FKA. As compared with FKA-fed juveniles, fish fed GMA as juveniles showed better reproductive performance as measured by spawning success, fertilization rate, and clutch size. As adults, fish from both feeding protocols were acclimated to our standard adult feeding protocol, and the long-term effects of juvenile diet were assessed. At 2 y of age, the groups showed no difference in mortality or fecundity. Reproductive performance is a crucial aspect of zebrafish research, as much of the research focuses on the developing embryo. Here we show that switching juvenile zebrafish from a mixture of flake and krill to Gemma Micro 300 improves reproductive performance, even with fewer feedings of live artemia, thus simplifying husbandry practices.

scholarly journals CUL4A ubiquitin ligase: a promising drug target for cancer and other human diseases

Open Biology ◽  
2014 ◽  
Vol 4 (2) ◽  
pp. 130217 ◽  
Author(s):  
Puneet Sharma ◽  
Alo Nag
Keyword(s):  
Ubiquitin Ligase ◽  
Drug Target ◽  
Critical Role ◽  
Cellular Transformation ◽  
Biological Processes ◽  
Molecular Architecture ◽  
The Past ◽  
Cullin 4A ◽  
Broad Overview

The ability of cullin 4A (CUL4A), a scaffold protein, to recruit a repertoire of substrate adaptors allows it to assemble into distinct E3 ligase complexes to mediate turnover of key regulatory proteins. In the past decade, a considerable wealth of information has been generated regarding its biology, regulation, assembly, molecular architecture and novel functions. Importantly, unravelling of its association with multiple tumours and modulation by viral proteins establishes it as one of the key proteins that may play an important role in cellular transformation. Considering the role of its substrate in regulating the cell cycle and maintenance of genomic stability, understanding the detailed aspects of these processes will have significant consequences for the treatment of cancer and related diseases. This review is an effort to provide a broad overview of this multifaceted ubiquitin ligase and addresses its critical role in regulation of important biological processes. More importantly, its tremendous potential to be exploited for therapeutic purposes has been discussed.

2007 Laennec Clinician/Educator Lecture—Unraveling the Mysteries of Diastology

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Rick Nishimura
Keyword(s):  
Heart Failure ◽  
Diastolic Dysfunction ◽  
Patient Care ◽  
Hospital Admissions ◽  
Critical Role ◽  
Rapid Assessment ◽  
Radionuclide Angiography ◽  
Signs And Symptoms ◽  
Diastolic Filling ◽  
The Past

Diastolic dysfunction plays a critical role in the pathophysiology of producing signs and symptoms of heart failure. Heart failure with a normal ejection fraction (HFnlEF) is one of the leading causes of hospital admissions today and is associated with significant morbidity and mortality. It is thus important to understand the pathophysiology of diastolic dysfunction, which itself is a complex series of multiple interrelated events, including relaxation, suction, ventricular interaction, ventricular arterial coupling, pericardial restraint, and myocardial viscoelastic forces. It was difficult for the clinician to understand “diastology” in the past. Initial studies were limited to complex equations derived from animal models and were difficult to apply to patient care. The development of radionuclide angiography and Doppler echocardiography allowed noninvasive rapid assessment of volumetric filling and flow velocity curves, which began to provide insight into the complex process of diastolic filling for the clinician. As our understanding of diastology evolved over the past 2 decades, it has become clear that we now need to pursue new areas to understand this fascinating subject and apply it to patient care. These areas include the underlying mechanism HFnlEF (ventricular-vascular coupling versus true myocardial stiffness), relationship of rest versus exercise hemodynamics, and the complex ventricular fiber “twisting and shortening” of both contraction and relaxation.

Recent advances on the pre-oxidation process in electrocatalytic urea oxidation reaction

2022 ◽  
Author(s):  
Wenbin Sun ◽  
Jiechen Li ◽  
Wen Gao ◽  
Luyao Kang ◽  
Fengcai Lei ◽  
...  
Keyword(s):  
Energy Conversion ◽  
Oxidation Reaction ◽  
Oxidation Process ◽  
Critical Role ◽  
Electrochemical Systems ◽  
The Past ◽  
Recent Advances

The electrocatalytic urea oxidation reaction (UOR) has attracted substantial research interests during the past few years owing to its critical role in coupled electrochemical systems for energy conversion, for example,...

Patient Fall Risk Caused by Unintended Diphenhydramine Use

2020 ◽  
Vol 35 (3) ◽  
pp. 113-119 ◽  
Author(s):  
Kimberly C. McKeirnan ◽  
Kyle R. Frazier ◽  
Andrew A. Yabusaki
Keyword(s):  
Back Pain ◽  
Rural Community ◽  
Fall Risk ◽  
Critical Role ◽  
Community Pharmacists ◽  
Past Medical History ◽  
The Past ◽  
Patient Reported ◽  
Medication Complexity

A 62-year-old patient living in a rural community was referred to participate in a pharmacist-led home visit program because of concerns with the patient's increasing falls and medication complexity. The patient reported experiencing an increasing number of falls over the past few months, resulting in a recent hospitalization and mild head trauma. The patient's past medical history included diabetes mellitus type 2, hypertension, hyperlipidemia, gastroesophageal reflux disease, paroxysmal atrial fibrillation, unspecified back pain, and benign prostatic hyperplasia. During the comprehensive medication review, pharmacists determined the patient had inadvertently purchased an acetaminophen/ diphenhydramine combination medication, rather than his usual acetaminophen. According to the 2019 Beers criteria, use of acetaminophen/diphenhydramine for back pain without insomnia is not the best option and may contribute to falls. With an estimated four to eight tablets per day, the patient was taking 200-400 mg of diphenhydramine daily. Pharmacist recommendations included contacting the prescribing physician to obtain a prescription for acetaminophen. By asking the local pharmacy to dispense acetaminophen as a prescription, the risk of the patient inadvertently purchasing an inappropriate product is reduced. After removing the diphenhydramine from the patient's regimen, the falls ceased. This case demonstrates the effects of inappropriate diphenhydramine use in an especially vulnerable population. It also highlights the critical role that rural community pharmacists can play in improving their patients' health care.

An Aerobic Walking Program to Promote Physical Fitness in Older Blind Adults

1985 ◽  
Vol 79 (3) ◽  
pp. 97-99 ◽  
Author(s):  
Donald Mark Weitzman
Keyword(s):  
Physical Fitness ◽  
Critical Role ◽  
Indirect Evidence ◽  
Well Being ◽  
Fitness Program ◽  
Fast Walking ◽  
The Past ◽  
Walking Program ◽  
Group Fitness

Both direct and indirect evidence gathered over the past 40 years strongly suggest that personal exercise can play a critical role in one's emotional and physical well-being. This article describes a unique group fitness program that combines Fast walking with safe calisthenics. The program is especially suitable for older blind adults who get very little healthful exercise and experience considerable depression.

scholarly journals Divergent Response of Leaf Coloring Seasons to Temperature Change in Northern China over the Past 50 Years

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Zexing Tao ◽  
Yunjia Xu ◽  
Junhu Dai ◽  
Huanjiong Wang
Keyword(s):  
Temperature Difference ◽  
Climatic Factors ◽  
Critical Role ◽  
Terrestrial Ecosystem ◽  
Northern China ◽  
Night Temperature ◽  
Start Date ◽  
The Past ◽  
Mean Temperature ◽  
Divergent Response

Autumn phenology plays a critical role in terrestrial ecosystem circulations. However, the changes in autumn phenology and their correlation with temperature remain uncertain because mean temperature alone was not able to determine the changes in autumn phenology at various sites. Here, the leaf coloring season (LCS) was defined as the period when the leaves of more than half of the species had recognized changes in color. We systematically studied the changes in peak, start, end, and duration of LCS and their correlations with five temperature parameters (mean temperature, accumulated cold temperature, day temperature, night temperature, and temperature difference between day and night) in four periods. Similarly to previous findings, the start date of LCS advanced and the end of LCS delayed over the past 50 years, which consequently led to a lengthened duration of LCS in Xi’an, Harbin, Minqin, and Shenyang. In general, the rise in mean temperature, day temperature, and night temperature would delay the peak, start, and end of LCS and lengthen the duration of LCS in most cases. We also proved that the changes in LCS metrics not only could completely be explained by mean temperature but also were influenced by day temperature, night temperature, temperature difference, and even other climatic factors such as precipitation, at different sites.

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