1. No enzymes, no life

Author(s):  
Paul Engel

‘No enzymes, no life’ discusses the role of enzymes and how they orchestrate the whole of life. Almost every chemical step in every living thing is guided by its own dedicated enzyme. Out of all the multitude of reactions that might theoretically be possible, enzymes select and guide the orderly sequences of reactions which are called ‘metabolism’, breaking down foodstuffs stepwise to give useful building blocks and reassembling them to make new biological molecules. Ultimately, enzymes control every biological process. Can chemistry explain biology?

Author(s):  
S. T. Loseby

The Merovingians inherited an urban network from the Roman Empire that remained substantially intact. Although Gallic cities had long been declining in extent and sophistication, during late antiquity their landscapes were adapted to contemporary priorities through the provision of walls and churches, and their politics was transformed by the emergence of bishops as leaders of urban communities. When the upper tiers of imperial administration disappeared, this equipped the vast majority of cities to survive as the basic building blocks of Merovingian kingdoms that were initially conceived as aggregations of city–territories. In ruling through their cities, the Merovingians expanded upon existing mechanisms for the extraction of taxes and services, while relying on centrally appointed bishops and counts rather than city councils for the projection of their authority. This generated fierce competition between kings for control of cities and among local elites for positions of power within them. In the later Merovingian period, however, the significance of cities diminished as stable territorial kingdoms emerged, political practice was centralized around the royal courts, and the Roman administrative legacy finally disintegrated. But the cities remained preeminent religious centers, and, with the beginnings of economic revival, continued to perform a range of functions unmatched by other categories of settlement.


2021 ◽  
Vol 106 ◽  
pp. 152225
Author(s):  
Francesco Di Carlo ◽  
Mauro Pettorruso ◽  
Maria Chiara Alessi ◽  
Elena Picutti ◽  
Rebecca Collevecchio ◽  
...  

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 754
Author(s):  
Giulia Gaggi ◽  
Andrea Di Credico ◽  
Pascal Izzicupo ◽  
Giovanni Iannetti ◽  
Angela Di Baldassarre ◽  
...  

Parkinson’s disease (PD) is one of the most common neurodegenerative disease characterized by a specific and progressive loss of dopaminergic (DA) neurons and dopamine, causing motor dysfunctions and impaired movements. Unfortunately, available therapies can partially treat the motor symptoms, but they have no effect on non-motor features. In addition, the therapeutic effect reduces gradually, and the prolonged use of drugs leads to a significative increase in the number of adverse events. For these reasons, an alternative approach that allows the replacement or the improved survival of DA neurons is very appealing for the treatment of PD patients and recently the first human clinical trials for DA neurons replacement have been set up. Here, we review the role of chemical and biological molecules that are involved in the development, survival and differentiation of DA neurons. In particular, we review the chemical small molecules used to differentiate different type of stem cells into DA neurons with high efficiency; the role of microRNAs and long non-coding RNAs both in DA neurons development/survival as far as in the pathogenesis of PD; and, finally, we dissect the potential role of exosomes carrying biological molecules as treatment of PD.


Metabolites ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 479
Author(s):  
Elizabeth L. Lieu ◽  
Neil Kelekar ◽  
Pratibha Bhalla ◽  
Jiyeon Kim

History suggests that tasteful properties of sugar have been domesticated as far back as 8000 BCE. With origins in New Guinea, the cultivation of sugar quickly spread over centuries of conquest and trade. The product, which quickly integrated into common foods and onto kitchen tables, is sucrose, which is made up of glucose and fructose dimers. While sugar is commonly associated with flavor, there is a myriad of biochemical properties that explain how sugars as biological molecules function in physiological contexts. Substantial research and reviews have been done on the role of glucose in disease. This review aims to describe the role of its isomers, fructose and mannose, in the context of inborn errors of metabolism and other metabolic diseases, such as cancer. While structurally similar, fructose and mannose give rise to very differing biochemical properties and understanding these differences will guide the development of more effective therapies for metabolic disease. We will discuss pathophysiology linked to perturbations in fructose and mannose metabolism, diagnostic tools, and treatment options of the diseases.


2021 ◽  
pp. 1-9
Author(s):  
Etsuo Niki

Reactive oxygen and nitrogen species have been implicated in the onset and progression of various diseases and the role of antioxidants in the maintenance of health and prevention of diseases has received much attention. The action and effect of antioxidants have been studied extensively under different reaction conditions in multiple media. The antioxidant effects are determined by many factors. This review aims to discuss several important issues that should be considered for determination of experimental conditions and interpretation of experimental results in order to understand the beneficial effects and limit of antioxidants against detrimental oxidation of biological molecules. Emphasis was laid on cell culture experiments and effects of diversity of multiple oxidants on antioxidant efficacy.


2007 ◽  
Vol 64 (3) ◽  
pp. 695-710 ◽  
Author(s):  
H. de Vries ◽  
J. D. Opsteegh

Abstract Optimal perturbations are constructed for a two-layer β-plane extension of the Eady model. The surface and interior dynamics is interpreted using the concept of potential vorticity building blocks (PVBs), which are zonally wavelike, vertically confined sheets of quasigeostrophic potential vorticity. The results are compared with the Charney model and with the two-layer Eady model without β. The authors focus particularly on the role of the different growth mechanisms in the optimal perturbation evolution. The optimal perturbations are constructed allowing only one PVB, three PVBs, and finally a discrete equivalent of a continuum of PVBs to be present initially. On the f plane only the PVB at the surface and at the tropopause can be amplified. In the presence of β, however, PVBs influence each other’s growth and propagation at all levels. Compared to the two-layer f-plane model, the inclusion of β slightly reduces the surface growth and propagation speed of all optimal perturbations. Responsible for the reduction are the interior PVBs, which are excited by the initial PVB after initialization. Their joint effect is almost as strong as the effect from the excited tropopause PVB, which is also negative at the surface. If the optimal perturbation is composed of more than one PVB, the Orr mechanism dominates the initial amplification in the entire troposphere. At low levels, the interaction between the surface PVB and the interior tropospheric PVBs (in particular those near the critical level) takes over after about half a day, whereas the interaction between the tropopause PVB and the interior PVBs is responsible for the main amplification in the upper troposphere. In all cases in which more than one PVB is used, the growing normal mode configuration is not reached at optimization time.


Author(s):  
Francisco Prosdocimi ◽  
Savio Torres Farias ◽  
Marco V José

The origin of life was a cosmic event happened on primitive Earth. A critical problem to better understand the origins of life in Earth is to glimpse in which chemical scenarios the basic building blocks of biological molecules could be produced. Classic works in pre-biotic chemistry frequently considered early Earth as a homogeneous atmosphere constituted by chemical elements such as methane (CH4), ammonia (NH3), water (H2O), hydrogen (H2) and hydrogen sulfide (H2S). Under that scenario, Stanley Miller was capable to produce amino acids and solved the question about the origin of proteins. Conversely, the origin of nucleic acids has tricked scientists for decades as nucleotides are complex though necessary molecules to allow the existence of life. Here we review possible chemical scenarios that allowed not only the formation of nucleotides but also other significant biomolecules. We aim to provide a theoretical solution for the origin of biomolecules at specific sites named “Prebiotic Chemical Refugia”. A prebiotic chemical refugium should therefore be understood as a geographic site in prebiotic Earth on which certain chemical elements were accumulated in higher proportion than expected, facilitating the production of basic biomolecules. Plus, this higher proportion should not be understood as static, but dynamic; once the physicochemical conditions of our planet changed periodically. This different concentration of elements, together with geochemical and astronomical changes along days, synodic months and years provided somewhat periodic changes in temperature, pressure, electromagnetic fields, and conditions of humidity; among other features. Recent and classic works suggesting most likely prebiotic refugia on which the main building blocks of biological molecules might be accumulated are reviewed and discussed.


Author(s):  
Tatyana Bodrug ◽  
Kaeli A. Welsh ◽  
Megan Hinkle ◽  
Michael J. Emanuele ◽  
Nicholas G. Brown

The ubiquitin (Ub)-proteasome system is vital to nearly every biological process in eukaryotes. Specifically, the conjugation of Ub to target proteins by Ub ligases, such as the Anaphase-Promoting Complex/Cyclosome (APC/C), is paramount for cell cycle transitions as it leads to the irreversible destruction of cell cycle regulators by the proteasome. Through this activity, the RING Ub ligase APC/C governs mitosis, G1, and numerous aspects of neurobiology. Pioneering cryo-EM, biochemical reconstitution, and cell-based studies have illuminated many aspects of the conformational dynamics of this large, multi-subunit complex and the sophisticated regulation of APC/C function. More recent studies have revealed new mechanisms that selectively dictate APC/C activity and explore additional pathways that are controlled by APC/C-mediated ubiquitination, including an intimate relationship with chromatin regulation. These tasks go beyond the traditional cell cycle role historically ascribed to the APC/C. Here, we review these novel findings, examine the mechanistic implications of APC/C regulation, and discuss the role of the APC/C in previously unappreciated signaling pathways.


2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Zarni Htun ◽  
Yingxi Zhao ◽  
Hannah Gilbert ◽  
Chunling Lu

Abstract Background The Global Fund has been a major funding source for HIV/AIDS programs in Myanmar. In this qualitative study, we aim to understand the impact of Global Fund on national HIV/AIDS response in Myanmar during the era of Millennium Development Goals (MDGs). Methods We conducted individual in-depth interviews by recruiting key informants through purposive snowball sampling. The respondents were engaged in the national/subnational response to HIV/AIDS in Myanmar and worked for the United Nations agencies, non-governmental organizations (NGOs), and civil society. Interview questions were organized around the role of Global Fund in strengthening national response to HIV/AIDS in the six building blocks of the Myanmar’s health system. Transcripts from the key informants were synthesized into specific themes through a deductive approach. Results We found that the Global Fund has provided substantial support to (1) finance the national HIV/AIDS response in Myanmar, and (2) strengthen leadership and governance at the central level through improving coordination and collaboration, including more stakeholders (e.g. civil society, NGOs) in decision making process, and catalyzing policy changes on scaling-up key interventions. Yet, its role remains limited in addressing new demands at the township level in terms of capacity building, staffing, and medical supply resulting from rapid scale-up of HIV interventions and decentralization of service delivery in the public sector. Conclusion There was a missed opportunity for Myanmar to capitalize on the use of the Global Fund’s funding to strengthen the health system. Deliberate planning is required to optimize the use of those scarce resources to provide universal coverage for HIV/AIDS.


2021 ◽  
Vol 22 (16) ◽  
pp. 8540
Author(s):  
Ioanna E. Stergiou ◽  
Efstathia K. Kapsogeorgou

The hematopoietic system relies on regulation of both metabolism and autophagy to maintain its homeostasis, ensuring the self-renewal and multipotent differentiation potential of hematopoietic stem cells (HSCs). HSCs display a distinct metabolic profile from that of their differentiated progeny, while metabolic rewiring from glycolysis to oxidative phosphorylation (OXPHOS) has been shown to be crucial for effective hematopoietic differentiation. Autophagy-mediated regulation of metabolism modulates the distinct characteristics of quiescent and differentiating hematopoietic cells. In particular, mitophagy determines the cellular mitochondrial content, thus modifying the level of OXPHOS at the different differentiation stages of hematopoietic cells, while, at the same time, it ensures the building blocks and energy for differentiation. Aberrations in both the metabolic status and regulation of the autophagic machinery are implicated in the development of hematologic malignancies, especially in leukemogenesis. In this review, we aim to investigate the role of metabolism and autophagy, as well as their interconnections, in normal and malignant hematopoiesis.


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