scholarly journals Substrate polyspecificity and conformational relevance in ABC transporters: new insights from structural studies

2018 ◽  
Vol 46 (6) ◽  
pp. 1475-1484 ◽  
Author(s):  
Jack Wright ◽  
Stephen P. Muench ◽  
Adrian Goldman ◽  
Alison Baker
Keyword(s):  
Atp Hydrolysis ◽  
Biological Membranes ◽  
General Mechanism ◽  
Structural Studies ◽  
Comprehensive Overview ◽  
New Information ◽  
Physiological Relevance ◽  
Evolutionarily Conserved ◽  
Multidrug Resistance Transporters ◽  
Made In

Transport of molecules and ions across biological membranes is an essential process in all organisms. It is carried out by a range of evolutionarily conserved primary and secondary transporters. A significant portion of the primary transporters belong to the ATP-binding cassette (ABC) superfamily, which utilise the free-energy from ATP hydrolysis to shuttle many different substrates across various biological membranes, and consequently, are involved in both normal and abnormal physiology. In humans, ABC transporter-associated pathologies are perhaps best exemplified by multidrug-resistance transporters that efflux many xenobiotic compounds due to their remarkable substrate polyspecificity. Accordingly, understanding the transport mechanism(s) is of great significance, and indeed, much progress has been made in recent years, particularly from structural studies on ABC exporters. Consequently, the general mechanism of ‘alternate access’ has been modified to describe individual transporter nuances, though some aspects of the transport process remain unclear. Moreover, as new information has emerged, the physiological relevance of the ‘open-apo’ conformation of MsbA (a bacterial exporter) has been questioned and, by extension, its contribution to mechanistic models. We present here a comprehensive overview of the most recently solved structures of ABC exporters, focusing on new insights regarding the nature of substrate polyspecificity and the physiological relevance of the ‘open-apo’ conformation. This review evaluates the claim that the latter may be an artefact of detergent solubilisation, and we hypothesise that the biophysical properties of the membrane play a key role in the function of ABC exporters allowing them to behave like a ‘spring-hinge’ during their transport cycle.

SOCIAL PROTECTION OF POPULATION IN THE SOUTHERN REGIONS OF UZBEKISTAN IN THE YEARS OF INDEPENDENCE

2019 ◽  
Vol 25 (2) ◽  
pp. 78-84
Author(s):  
Fakhriddin Yormatov ◽  
Keyword(s):  
Social Protection ◽  
Comprehensive Overview ◽  
Positive Work ◽  
Made In

This article provides a comprehensive overview on the positive work carried out in the southern provinces of Uzbekistan during the years of independence and the achievements made in this area

scholarly journals Narrative review of EHDI in South Africa

2015 ◽  
Vol 62 (1) ◽  
Author(s):  
Selvarani Moodley ◽  
Claudine Storbeck
Keyword(s):  
South Africa ◽  
Hearing Loss ◽  
Hearing Screening ◽  
Narrative Review ◽  
Current Status ◽  
Western Cape ◽  
Comprehensive Overview ◽  
National Priority ◽  
Newborn Hearing ◽  
Made In

Background: With 17 babies born with hearing loss every day in South Africa, there is a pressing need for systematic Early Hearing Detection and Intervention (EHDI) services. Progress is being made in offering newborn hearing screening and studies have been conducted to document these processes within South Africa. However, due to the lack of a national and holistic overview of EHDI services to date, an accurate picture of the current status of EHDI within the South African context is required. Objective: To document and profile what has been published within the field of EHDI in South Africa over the last two decades (Jan 1995–Sept 2014) in order to gain a comprehensive overview of the current status and practice of screening and diagnosis in the field of paediatric hearing loss. Method: A narrative review of peer-reviewed articles related to EHDI in South Africa was conducted by searching the EBSCOHOST, SCOPUS and JSTOR databases for the period January 1995 to September 2014. Results: Results indicate that over the last two decades research and publications in the field of EHDI have increased considerably. These publications have revealed extensive knowledge related to paediatric hearing screening and intervention services in South Africa; however, this knowledge seems to be limited primarily to the provinces of Gauteng and the Western Cape. Furthermore, studies pertaining to diagnosis have revealed that, although much has been written on the scientific aspects on tools for diagnosis of hearing loss, there is a lack of comprehensive information on diagnostic protocols and procedures. Conclusion: Despite the clear progress being made in South Africa in the field of early hearing detection and intervention, there is a need for comprehensive studies on protocols and procedures in diagnosing paediatric hearing loss. Finally, the narrative review revealed a clear need to ensure that development and growth in the field of EHDI is a national priority and extends beyond the two provinces currently showing growth.

scholarly journals Evolutionary Conservation of Reactions in Translation

2002 ◽  
Vol 66 (3) ◽  
pp. 460-485 ◽  
Author(s):  
M. Clelia Ganoza ◽  
Michael C. Kiel ◽  
Hiroyuki Aoki
Keyword(s):  
Molecular Mechanisms ◽  
Tertiary Structure ◽  
Evolutionary Conservation ◽  
Initiation Factor ◽  
Structural Studies ◽  
X Ray Diffraction ◽  
X Ray ◽  
Common Features ◽  
New Information ◽  
And Function

SUMMARY Current X-ray diffraction and cryoelectron microscopic data of ribosomes of eubacteria have shed considerable light on the molecular mechanisms of translation. Structural studies of the protein factors that activate ribosomes also point to many common features in the primary sequence and tertiary structure of these proteins. The reconstitution of the complex apparatus of translation has also revealed new information important to the mechanisms. Surprisingly, the latter approach has uncovered a number of proteins whose sequence and/or structure and function are conserved in all cells, indicating that the mechanisms are indeed conserved. The possible mechanisms of a new initiation factor and two elongation factors are discussed in this context.

scholarly journals Rediscovery of the Yellow-bellied Sea Snake, Hydrophis platurus (Linnaeus, 1766) in Máncora, northern Perú

Check List ◽  
2014 ◽  
Vol 10 (6) ◽  
pp. 1563
Author(s):  
Javier Quiñones ◽  
Karla García Burneo ◽  
Claudio Barragan
Keyword(s):  
Surface Temperature ◽  
Sea Surface Temperature ◽  
Sea Surface ◽  
Sea Snake ◽  
Warm Event ◽  
New Information ◽  
Southeast Pacific ◽  
Northern Peru ◽  
Sst Anomalies ◽  
Made In

The presence of the Yellow-bellied Sea Snake (Hydrophis platurus) in the Southeast Pacific is rarely reported, with only one confirmed observation from northern Perú made in the early 1950s. We present new information based on a live-stranded specimen recently found in Peruvian waters, having washed ashore at Máncora (04.1255° S, 81.0958° W) in northern Perú on 12 July 2012. This stranding was associated with a Modoki El Niño warm event, since positive sea surface temperature (SST) anomalies up to 2.5°C were registered at this time.

scholarly journals Reward and aversion encoding in the lateral habenula for innate and learned behaviours

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Sarah Mondoloni ◽  
Manuel Mameli ◽  
Mauro Congiu
Keyword(s):  
Animal Species ◽  
Brain Structures ◽  
Individual Member ◽  
Negative Events ◽  
Lateral Habenula ◽  
Sensory Stimuli ◽  
Aversive Events ◽  
Evolutionarily Conserved ◽  
The Brain ◽  
Made In

AbstractThroughout life, individuals experience a vast array of positive and aversive events that trigger adaptive behavioural responses. These events are often unpredicted and engage actions that are likely anchored on innate behavioural programs expressed by each individual member of virtually all animal species. In a second step, environmental cues, that are initially neutral, acquire value through the association with external sensory stimuli, and become instrumental to predict upcoming positive or negative events. This process ultimately prompts learned goal-directed actions allowing the pursuit of rewarding experience or the avoidance of a danger. Both innate and learned behavioural programs are evolutionarily conserved and fundamental for survival. Among the brain structures participating in the encoding of positive/negative stimuli and contributing to innate and learned behaviours is the epithalamic lateral habenula (LHb). The LHb provides top-down control of monoaminergic systems, responds to unexpected appetitive/aversive stimuli as well as external cues that predict the upcoming rewards or punishments. Accordingly, the LHb controls a number of behaviours that are innate (originating from unpredicted stimuli), and learned (stemming from predictive cues). In this review, we will discuss the progresses that rodent’s experimental work made in identifying how LHb activity governs these vital processes, and we will provide a view on how these findings integrate within a complex circuit connectivity.

scholarly journals Inherited podocytopathies

2008 ◽  
Vol 136 (Suppl. 4) ◽  
pp. 327-339
Author(s):  
Radovan Bogdanovic
Keyword(s):  
Congenital Nephrotic Syndrome ◽  
Structural Studies ◽  
Glomerular Filtration Barrier ◽  
Filtration Barrier ◽  
Glomerular Epithelial Cells ◽  
Causes Of Disease ◽  
Stage Renal Disease ◽  
End Stage ◽  
Made In

Podocytes, the visceral glomerular epithelial cells, are the postmythotic cells that line the outer aspects of the glomerular basement membrane. A number of advances have been made in recent years, linked to the discovery of singlegene defects in hereditary glomerular disease, which highlight the role of these cells in preventing proteinuria. Despite the rarity of hereditary proteinuric syndromes, genetic, biochemical, and structural studies of these diseases have made important contributions to our knowledge of how the normal glomerular filter works and the mechanism of proteinuria. The course of these diseases can vary; some patients present with severe proteinuria and congenital nephrotic syndrome, whereas others have only moderate proteinuria and focal segmental glomerulosclerosis. Regardless of its cause, the disease often progresses to end-stage renal disease. There can be overlap between the diseases: mutations in the same gene can lead to different renal phenotypes. It is important to know that some hereditary podocytopathies respond to therapy, whereas majority does not. For this reason, genetic testing, which is available for some hereditary podocytopathies should be performed whenever possible. This review summarizes recent progress in the eludication of genetic causes of disease and discusses their implication for the understanding of the pathogenic mechanisms which can lead to disruption of the glomerular filtration barrier.

scholarly journals Genome-wide Identification and Expression Analysis of Autophagy-related Genes (ATGs) in Medicago Truncatula

2020 ◽  
Author(s):  
Mingkang Yang ◽  
Liping Wang ◽  
Xu Guo ◽  
Chuanglie Lin ◽  
Wei Huang ◽  
...  
Keyword(s):  
Medicago Truncatula ◽  
Expression Analysis ◽  
Interaction Network ◽  
Degradation Process ◽  
Abiotic Stress Response ◽  
Biotic And Abiotic Stress ◽  
Comprehensive Overview ◽  
Genome Wide ◽  
Evolutionarily Conserved ◽  
Gene Structures

Abstract Background: Autophagy is a highly conserved degradation process of cytoplasmic constituents in eukaryotes. Autophagy is known to be involved in the regulation of plant growth and development, as well as biotic and abiotic stress response. Although autophagy-related genes (ATGs) have been identified and characterized in many plant species, little is known about the autophagy process in Medicago truncatula. Results: In this study, 39 ATGs were identified in M. truncatula (MtATGs), and the gene structures and conserved domains of MtATGs were systematically characterized. In addition, many cis-elements which are related to hormone and stress responsiveness were identified in the promoters of MtATGs. Furthermore, phylogenetic analysis and interaction network analysis suggested that the function of MtATGs is evolutionarily conserved in Arabidopsis and M. truncatula. Gene expression analysis showed that most MtATGs were largely induced during seed development, but repressed by nodulation. Moreover, MtATGs were up-regulated in response to salt and drought stresses.Conclusion: These results provide a comprehensive overview of the MtATGs, which provided important clues for further functional analysis of autophagy in M. truncatula.

scholarly journals An Empirical Investigation of the Option Value of College Enrollment

2012 ◽  
Vol 4 (1) ◽  
pp. 49-84 ◽  
Author(s):  
Kevin M Stange
Keyword(s):  
Educational Outcomes ◽  
Empirical Investigation ◽  
College Attendance ◽  
Academic Ability ◽  
Option Value ◽  
School Graduate ◽  
Schooling Decisions ◽  
New Information ◽  
Average High School ◽  
Made In

This paper quantifies the option value arising from sequential schooling decisions made in the presence of uncertainty and learning about academic ability. College attendance has option value since enrolled students have the option, but not obligation, to continue in school after learning their aptitude and tastes. I estimate that option value accounts for 14 percent of the total value of the opportunity to attend college for the average high school graduate and is greatest for moderate-aptitude students. Students' ability to make decisions sequentially in response to new information increases welfare and also makes educational outcomes less polarized by background. (JEL D83, I23)

Initiation by RNA polymerase II and formation of runoff transcripts containing unblocked and unmethylated 5' termini

1983 ◽  
Vol 3 (12) ◽  
pp. 2172-2179
Author(s):  
H Ernst ◽  
W Filipowicz ◽  
A J Shatkin
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Atp Hydrolysis ◽  
Beta Globin ◽  
Whole Cell ◽  
Whole Cell Lysate ◽  
Cell Lysate ◽  
Promoter Dna ◽  
Gamma S ◽  
Made In

Transcription of cloned adenovirus, beta-globin, and retrovirus long terminal repeat DNAs in HeLa whole-cell lysate was inhibited by S-adenosylhomocysteine. However, full-length 1.7-kilobase transcripts made on adenovirus 2 late promoter DNA contained 5'-terminal GpppA, consistent with specific initiation and runoff synthesis in the absence of product methylation. Formation of runoff transcripts including retrovirus RNAs that normally contain 5'-m7GpppGmpC was not decreased by replacing GTP with non-hydrolyzable analogs, and Rous-associated virus-2 runoff products made in the presence of GTP-gamma-S contained 5'-terminal gamma-S-pppGpC. The results indicate that capping and specific transcript synthesis by RNA polymerase II are not obligatorily linked in HeLa whole-cell lysate. Accurate initiation is dependent on ATP hydrolysis, and in contrast to GTP, replacement of ATP by 5'-adenylyl-imidodiphosphate blocked specific initiation of transcripts that start with either GTP (Rous-associated virus-2, Rous-associated virus-0) or ATP (beta-globin, adenovirus).

scholarly journals Function of the p97–Ufd1–Npl4 complex in retrotranslocation from the ER to the cytosol

2003 ◽  
Vol 162 (1) ◽  
pp. 71-84 ◽  
Author(s):  
Yihong Ye ◽  
Hemmo H. Meyer ◽  
Tom A. Rapoport
Keyword(s):  
Atp Hydrolysis ◽  
Bound State ◽  
Polyubiquitin Chain ◽  
Polyubiquitin Chains ◽  
Evolutionarily Conserved ◽  
The Family ◽  
Complex Functions ◽  
Ubiquitin Binding ◽  
Subsequent Degradation ◽  
Er Membrane

Amember of the family of ATPases associated with diverse cellular activities, called p97 in mammals and Cdc48 in yeast, associates with the cofactor Ufd1–Npl4 to move polyubiquitinated polypeptides from the endoplasmic reticulum (ER) membrane into the cytosol for their subsequent degradation by the proteasome. Here, we have studied the mechanism by which the p97–Ufd1–Npl4 complex functions in this retrotranslocation pathway. Substrate binding occurs when the first ATPase domain of p97 (D1 domain) is in its nucleotide-bound state, an interaction that also requires an association of p97 with the membrane through its NH2-terminal domain. The two ATPase domains (D1 and D2) of p97 appear to alternate in ATP hydrolysis, which is essential for the movement of polypeptides from the ER membrane into the cytosol. The ATPase itself can interact with nonmodified polypeptide substrates as they emerge from the ER membrane. Polyubiquitin chains linked by lysine 48 are recognized in a synergistic manner by both p97 and an evolutionarily conserved ubiquitin-binding site at the NH2 terminus of Ufd1. We propose a dual recognition model in which the ATPase complex binds both a nonmodified segment of the substrate and the attached polyubiquitin chain; polyubiquitin binding may activate the ATPase p97 to pull the polypeptide substrate out of the membrane.

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