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"Kim, Peter"
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How trust works : the science of how relationships are built, broken, and repaired
\"From the world's leading expert on trust repair, a guide to understanding the most essential foundation of our relationships and communities. When our trust is broken, and when our own trustworthiness is called into question, many of us are left wondering what to do. We barely know how trust works. How could we possibly repair it? Dr. Peter H. Kim, the world's leading expert in the rapidly growing field of trust repair, has conducted over two decades of groundbreaking research to answer that question. In How Trust Works, he draws on this research and the work of other social scientists to reveal the surprising truths about how relationships are built, how they are broken, and how they are repaired. Dr. Kim's work shows how we are often more trusting than we think and how easily our trust in others can be distorted. He illustrates these insights with accounts of some of the most striking and well-known trust violations that have occurred in modern times and unveils the crucial secrets behind when and why our attempts to repair trust are effective, and which breaches of confidence are just too deep. How Trust Works transforms our understanding of our deepest bonds, giving us the tools to build strong and supportive relationships on every level. With our families, coworkers, and friends. With the groups, organizations, and institutions that touch our lives. And even with societies and nations\"-- Provided by publisher.
Book
ORP1L mediated PI(4)P signaling at ER-lysosome-mitochondrion three-way contact contributes to mitochondrial division
Mitochondrial division is not an autonomous event but involves multiple organelles, including the endoplasmic reticulum (ER) and lysosomes. Whereas the ER drives the constriction of mitochondrial membranes, the role of lysosomes in mitochondrial division is not known. Here, using super-resolution live-cell imaging, we investigate the recruitment of lysosomes to the site of mitochondrial division. We find that the ER recruits lysosomes to the site of division through the interaction of VAMP-associated proteins (VAPs) with the lysosomal lipid transfer protein ORP1L to induce a three-way contact between the ER, lysosome, and the mitochondrion. We also show that ORP1L might transport phosphatidylinositol-4-phosphate (PI(4)P) from lysosomes to mitochondria, as inhibiting its transfer or depleting PI(4)P at the mitochondrial division site impairs fission, demonstrating a direct role for PI(4)P in the division process. Our findings support a model where the ER recruits lysosomes to act in concert at the fission site for the efficient division of mitochondria.
Membrane contact sites between organelles have specialized functions that are only beginning to be understood. Here, the authors show that ORP1L mediates lysosome recruitment and PI(4)P signaling at endoplasmic reticulum-lysosome-mitochondria three-way contact sites involved in mitochondrial division.
Journal Article
Efficient evolution of human antibodies from general protein language models
Natural evolution must explore a vast landscape of possible sequences for desirable yet rare mutations, suggesting that learning from natural evolutionary strategies could guide artificial evolution. Here we report that general protein language models can efficiently evolve human antibodies by suggesting mutations that are evolutionarily plausible, despite providing the model with no information about the target antigen, binding specificity or protein structure. We performed language-model-guided affinity maturation of seven antibodies, screening 20 or fewer variants of each antibody across only two rounds of laboratory evolution, and improved the binding affinities of four clinically relevant, highly mature antibodies up to sevenfold and three unmatured antibodies up to 160-fold, with many designs also demonstrating favorable thermostability and viral neutralization activity against Ebola and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pseudoviruses. The same models that improve antibody binding also guide efficient evolution across diverse protein families and selection pressures, including antibiotic resistance and enzyme activity, suggesting that these results generalize to many settings.
A general protein language model guides protein evolution with 20 or fewer variants needed for testing.
Journal Article
Pexophagy: A Model for Selective Autophagy
The removal of damaged or superfluous organelles from the cytosol by selective autophagy is required to maintain organelle function, quality control and overall cellular homeostasis. Precisely how substrate selectivity is achieved, and how individual substrates are degraded during selective autophagy in response to both extracellular and intracellular cues is not well understood. The aim of this review is to highlight pexophagy, the autophagic degradation of peroxisomes, as a model for selective autophagy. Peroxisomes are dynamic organelles whose abundance is rapidly modulated in response to metabolic demands. Peroxisomes are routinely turned over by pexophagy for organelle quality control yet can also be degraded by pexophagy in response to external stimuli such as amino acid starvation or hypoxia. This review discusses the molecular machinery and regulatory mechanisms governing substrate selectivity during both quality-control pexophagy and pexophagy in response to external stimuli, in yeast and mammalian systems. We draw lessons from pexophagy to infer how the cell may coordinate the degradation of individual substrates by selective autophagy across different cellular cues.
Journal Article
بحيرة البجع
تتناول الرواية (بحيرة البجع) وهي إحدى روائع الموسيقي الروسي تشايكوفسكي، أن حفلا أقيم في الذكرى 21 لميلاد الأمير سيجفرايد، حيث يحتفل بهذه المناسبة في حديقة قصره الذي ورثه عن عائلته ويشاركه في هذه المناسبة عدد من شباب المناطق المجاورة، الذين جاءوا لتحيته وتهنئته. وبينما يستمتع الجميع بالاحتفال، تدخل الأميرة الأم وبصحبتها وصيفاتها الأربع مما يعكر صفو الحفل ويتوقف المرح. تشير إلى ابنها موضحة أن المرحلة المقبلة من حياته يجب أن تختلف عن هذا العبث، وأن عليه أن يختار عروسا له في الحفل الراقص الذي سيتم في الغد ببلاط القصر الملكي، ويتعين عليه أن يختار زوجة المستقبل من بين أجمل الفتيات الموجودات الراقيات. يخيم الليل، ويدرك بينو (صديق الأمير) بأنه يجب إبعاد الأمير سيجفرايد من هذه الأمسية التي تعدها الأميرة الأم، ويسمع صوت أجنحة ترفرف فوق رأسه، فيرفع ناظريه ليرى سربا كاملا من البجع البري الجميل في السماء، وعندما هم الجميع باصطياد هذه البجعات، يرى الأمير شيئا عن بعد يجعله يتوقف على مقربة من جانب البحيرة، وهناك لمح أجمل فتاة لم يراها من قبل، ولا يستطيع أن يصدق عينيه، فالفتاة تبدو وكأنها بجعة وفتاة في نفس الوقت، ويعرف أنها أوديت ملكة البجع. وأنها ستظل بجعة إلى الأبد ما عدا الفترة الواقعة ما بين منتصف الليل وطلوع الفجر، حتى يحبها رجل ويتزوجها، ولا يحب غيرها على الإطلاق، عندئذ يتحمس الأمير العاشق لإنقاذها ويؤكد لها أنها لن تصبح بجعة بعد ذلك، فهل سيفي الأمير بوعده للملكة أوديت ؟.
Book
A systematic review of empirical studies of pro-environmental behavior in hospitality and tourism contexts
Purpose
The purpose of this study was to gain a holistic view of pro-environmental behavior (PEB) among hospitality and tourism consumers through a systematic review of empirical studies. Based on this comprehensive review, this study demonstrates how the literature has been created and has evolved over time, thereby providing proposals for future research agendas.
Design/methodology/approach
The preferred reporting items for systematic reviews and meta-analyses method was used as a rigorous searching method to provide an updated picture of the research on the PEBs of consumers in hospitality and tourism contexts. A total of 234 empirical studies from both hospitality and nonhospitality publications were selected for the review.
Findings
The results reveal a growing interest in PEB in the hospitality and tourism context. Focal points, theories and research designs used to explain PEB among hospitality and tourism consumers were identified. In addition, the findings from the cross-tabulation analyses have provided valuable insights for tourism and hospitality research in this area.
Research limitations/implications
Based on the research findings, this study makes significant contributions to the literature by providing theoretical and practical implications with detailed directions for future researchers and practitioners.
Originality/value
This study offers one of the first reviews to comprehensively and systematically analyze the empirical research into PEBs among hospitality and tourism consumers. PEB has received significant attention from researchers, practitioners and those policymakers concerned with the sustainability of environments. The findings of this research provide a comprehensive overview of the literature relating to hospitality and tourism through the identification of gaps that require further investigation. Future suggestions to assist practitioners and policymakers in eliciting PEBs are also discussed.
Journal Article
A high-affinity human PD-1/PD-L2 complex informs avenues for small-molecule immune checkpoint drug discovery
Immune checkpoint blockade of programmed death-1 (PD-1) by monoclonal antibody drugs has delivered breakthroughs in the treatment of cancer. Nonetheless, small-molecule PD-1 inhibitors could lead to increases in treatment efficacy, safety, and global access. While the ligand-binding surface of apo-PD-1 is relatively flat, it harbors a striking pocket in the murine PD-1/PD-L2 structure. An analogous pocket in human PD-1 may serve as a small-molecule drug target, but the structure of the human complex is unknown. Because the CC′ and FG loops in murine PD-1 adopt new conformations upon binding PD-L2, we hypothesized that mutations in these two loops could be coupled to pocket formation and alter PD-1’s affinity for PD-L2. Here, we conducted deep mutational scanning in these loops and used yeast surface display to select for enhanced PD-L2 binding. A PD-1 variant with three substitutions binds PD-L2 with an affinity two orders of magnitude higher than that of the wild-type protein, permitting crystallization of the complex. We determined the X-ray crystal structures of the human triple-mutant PD-1/PD-L2 complex and the apo triple-mutant PD-1 variant at 2.0 Å and 1.2 Å resolution, respectively. Binding of PD-L2 is accompanied by formation of a prominent pocket in human PD-1, as well as substantial conformational changes in the CC′ and FG loops. The structure of the apo triple-mutant PD-1 shows that the CC′ loop adopts the ligand-bound conformation, providing support for allostery between the loop and pocket. This human PD-1/PD-L2 structure provide critical insights for the design and discovery of small-molecule PD-1 inhibitors.
Journal Article