In Memoriam: Dan Tawfik

The biochemist Dan Tawfik passed away in May 2021 at age sixty-five and yet the height of his powers. Dan’s scientific research focused on proteins and, in particular, on enzyme evolution. Recently he had begun working on the most difficult challenge in biochemical evolution: reconstructing the metabolic pathways that may have led to the emergence of the first functional proteins.

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‘Sisters on Spring Outing’ (Paeonia suffruticosa ‘Zi Mei You Chun’) (Paeoniaceae): A Unique Chinese Tree Peony Cultivar Possessing Side Flowers and Bicolored Floral Discs

HortScience ◽

10.21273/hortsci.43.2.532 ◽

2008 ◽

Vol 43 (2) ◽

pp. 532-534 ◽

Cited By ~ 1

Author(s):

Zhi-li Suo ◽

Xiao-qing Zhao ◽

Jian-peng Zhao ◽

Xiao-chong Zhao ◽

Fu-fei Chen

Keyword(s):

Metabolic Pathways ◽

Scientific Research ◽

Developmental Genetics ◽

Paeonia Suffruticosa ◽

Tree Peony ◽

Central Plains ◽

Medicinal Uses ◽

The Past ◽

Cultivar Group

Large natural genetic diversifications have occurred among Chinese tree peony cultivars under the natural and artificial selections on the flower for ornamental and medicinal uses in the past over 1500 years in China. Paeonia suffruticosa ‘Zi Mei You Chun’ X.Q. Zhao & J.P. Zhao & X.Z. Zhao & X.C. Zhao & Q.X. Gao & Z.Q. Zhao & J.X. Zhao & Z.L. Suo (Paeoniaceae) is a unique cultivar possessing side flowers and bicolored floral disc belonging to the Central Plains tree peony cultivar group of China. This natural mutant is not only an outstanding ornamental, but also a valuable material for scientific research on evolution of tree peony cultivars, metabolic pathways of pigments in the floral disc, origin of floral disc in Paeoniaceae, and other issues in plant evolutionary and developmental genetics.

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6. Metabolic pathways and enzyme evolution

Enzymes: A Very Short Introduction ◽

10.1093/actrade/9780198824985.003.0006 ◽

2020 ◽

pp. 85-100

Author(s):

Paul Engel

Keyword(s):

Amino Acid ◽

Metabolic Pathway ◽

Metabolic Pathways ◽

Building Blocks ◽

Enzyme Evolution

‘Metabolic pathways and enzyme evolution’ focuses on metabolic pathways and enzyme evolution. Although a few enzymes catalyse a single isolated reaction, most are part of a team that catalyses a series of reactions in which each enzyme picks up its predecessor’s product, taking it a step further to create a metabolic pathway. This pathway may be to build up, say, an amino acid from simpler starting molecules, or conversely to break down food molecules to yield new chemical building blocks and sometimes also to trap useable energy. Life is the combined outcome of this seemingly logical enzyme teamwork.

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The Interactome between Metabolism and Gene Mutations in Myeloid Malignancies

International Journal of Molecular Sciences ◽

10.3390/ijms22063135 ◽

2021 ◽

Vol 22 (6) ◽

pp. 3135

Author(s):

Carmelo Gurnari ◽

Simona Pagliuca ◽

Valeria Visconte

Keyword(s):

Targeted Therapies ◽

Metabolic Pathways ◽

Gene Mutations ◽

High Sensitivity ◽

Leukemic Cells ◽

Altered Expression ◽

Myeloid Malignancies ◽

Cell Functions ◽

Energy Demands ◽

Difficult Challenge

The study of metabolic deregulation in myeloid malignancies has led to the investigation of metabolic-targeted therapies considering that cells undergoing leukemic transformation have excessive energy demands for growth and proliferation. However, the most difficult challenge in agents targeting metabolism is to determine a window of therapeutic opportunities between normal and neoplastic cells, considering that all or most of the metabolic pathways important for cancer ontogeny may also regulate physiological cell functions. Targeted therapies have used the properties of leukemic cells to produce altered metabolic products when mutated. This is the case of IDH1/2 mutations generating the abnormal conversion of α-ketoglutarate (KG) to 2-hydroxyglutarate, an oncometabolite inhibiting KG-dependent enzymes, such as the TET family of genes (pivotal in characterizing leukemia cells either by mutations, e.g., TET2, or by altered expression, e.g., TET1/2/3). Additional observations derive from the high sensitivity of leukemic cells to oxidative phosphorylation and its amelioration using BCL-2 inhibitors (Venetoclax) or by disrupting the mitochondrial respiration. More recently, nicotinamide metabolism has been described to mediate resistance to Venetoclax in patients with acute myeloid leukemia. Herein, we will provide an overview of the latest research on the link between metabolic pathways interactome and leukemogenesis with a comprehensive analysis of the metabolic consequences of driver genetic lesions and exemplificative druggable pathways.

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In Memoriam – Dr. Consolacion Y. Ragasa

KIMIKA ◽

10.26534/kimika.v32i1.58-69 ◽

2021 ◽

Vol 32 (1) ◽

pp. 58-69

Author(s):

Wyona Patalinghug ◽

Drexel Camacho ◽

Jaime Raul Janairo ◽

Lourdes Guidote ◽

Maria Carmen Tan ◽

...

Keyword(s):

Scientific Research ◽

Research Community ◽

Huge Impact ◽

In Memoriam ◽

Chemistry Community

On April 14, 2021, the Philippine chemistry community lost one of its most prolific researchers due to the COVID19 virus. Herein we reflect on the extraordinary life and work of Dr. Consolacion Y. Ragasa. We highlight her story, her scientific contributions, and the huge impact she left, not only on her students and colleagues but also on the scientific research community.

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Metabolite–Enzyme Coevolution: From Single Enzymes to Metabolic Pathways and Networks

Annual Review of Biochemistry ◽

10.1146/annurev-biochem-062917-012023 ◽

2018 ◽

Vol 87 (1) ◽

pp. 187-216 ◽

Cited By ~ 36

Author(s):

Lianet Noda-Garcia ◽

Wolfram Liebermeister ◽

Dan S. Tawfik

Keyword(s):

Metabolic Pathways ◽

Current Knowledge ◽

Network Evolution ◽

Enzyme Evolution ◽

Pathway Evolution ◽

Current State ◽

Open Questions ◽

Open Question ◽

Survival Of The Fittest ◽

New Metabolites

How individual enzymes evolved is relatively well understood. However, individual enzymes rarely confer a physiological advantage on their own. Judging by its current state, the emergence of metabolism seemingly demanded the simultaneous emergence of many enzymes. Indeed, how multicomponent interlocked systems, like metabolic pathways, evolved is largely an open question. This complexity can be unlocked if we assume that survival of the fittest applies not only to genes and enzymes but also to the metabolites they produce. This review develops our current knowledge of enzyme evolution into a wider hypothesis of pathway and network evolution. We describe the current models for pathway evolution and offer an integrative metabolite–enzyme coevolution hypothesis. Our hypothesis addresses the origins of new metabolites and of new enzymes and the order of their recruitment. We aim to not only survey established knowledge but also present open questions and potential ways of addressing them.

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In memoriam: John Dunn, Scientist Extraordinaire (May 29, 1944–July 13, 2012): Reminiscences of John’s 40 years of exhilarating scientific research at BNL

Protein Expression and Purification ◽

10.1016/j.pep.2012.09.005 ◽

2013 ◽

Vol 87 (1) ◽

pp. 1-2

Keyword(s):

Scientific Research ◽

In Memoriam

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Statistical analysis of classification

Symposium - International Astronomical Union ◽

10.1017/s0074180900053420 ◽

1966 ◽

Vol 24 ◽

pp. 188-189

Author(s):

T. J. Deeming

Keyword(s):

Multivariate Analysis ◽

Statistical Analysis ◽

Classification Scheme ◽

Analytical Procedure ◽

Narrow Band ◽

Scientific Research ◽

Maximum Amount ◽

Amount Of Information

If we make a set of measurements, such as narrow-band or multicolour photo-electric measurements, which are designed to improve a scheme of classification, and in particular if they are designed to extend the number of dimensions of classification, i.e. the number of classification parameters, then some important problems of analytical procedure arise. First, it is important not to reproduce the errors of the classification scheme which we are trying to improve. Second, when trying to extend the number of dimensions of classification we have little or nothing with which to test the validity of the new parameters.Problems similar to these have occurred in other areas of scientific research (notably psychology and education) and the branch of Statistics called Multivariate Analysis has been developed to deal with them. The techniques of this subject are largely unknown to astronomers, but, if carefully applied, they should at the very least ensure that the astronomer gets the maximum amount of information out of his data and does not waste his time looking for information which is not there. More optimistically, these techniques are potentially capable of indicating the number of classification parameters necessary and giving specific formulas for computing them, as well as pinpointing those particular measurements which are most crucial for determining the classification parameters.

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Immunoprobe localization in mammalian embryos

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100157693 ◽

1990 ◽

Vol 48 (3) ◽

pp. 32-33

Author(s):

Patricia G. Calarco ◽

Margaret C. Siebert

Keyword(s):

Electron Microscopy ◽

Endoplasmic Reticulum ◽

Thin Sections ◽

Relative Lack ◽

Large Size ◽

Mammalian Embryos ◽

Antigen Localization ◽

Difficult Challenge ◽

Lowicryl K4m ◽

Fertilized Egg

Visualization of preimplantation mammalian embryos by electron microscopy is difficult due to the large size of the ircells, their relative lack of internal structure, and their highly hydrated cytoplasm. For example, the fertilized egg of the mouse is a single cell of approximately 75μ in diameter with little organized cytoskelet on and apaucity ofor ganelles such as endoplasmic reticulum (ER) and Golgi material. Thus, techniques that work well on tissues or cell lines are often not adaptable to embryos at either the LM or EM level.Over several years we have perfected techniques for visualization of mammalian embryos by LM and TEM, SEM and for the pre-embedding localization of antigens. Post-embedding antigenlocalization in thin sections of mouse oocytes and embryos has presented a more difficult challenge and has been explored in LR White, LR Gold, soft EPON (after etching of sections), and Lowicryl K4M. To date, antigen localization has only been achieved in Lowicryl-embedded material, although even with polymerization at-40°C, the small ER vesicles characteristic of embryos are unrecognizable.

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