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Article: Response to comment on 'Protein crystal lattices are dynamic assemblies: the role of conformational entropy in the protein condensed phase'.

Dimova, Margarita / Devedjiev, Yancho D

2018 Volume 5, Issue Pt 4, Page(s) 520

Abstract: A response is given to Nespolo's comment [ ...

Abstract	A response is given to Nespolo's comment [
Language	English
Publishing date	2018-07-01
Publishing country	England
Document type	Journal Article ; Comment
ZDB-ID	2754953-7
ISSN	2052-2525
ISSN	2052-2525
DOI	10.1107/S2052252518006279
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Article: Protein crystal lattices are dynamic assemblies: the role of conformational entropy in the protein condensed phase.

Dimova, Margarita / Devedjiev, Yancho D

IUCrJ

2018 Volume 5, Issue Pt 2, Page(s) 130–140

Abstract: Until recently, the occurrence of conformational entropy in protein crystal contacts was considered to be a very unlikely event. A study based on the most accurately refined protein structures demonstrated that side-chain conformational entropy and ... ...

Abstract	Until recently, the occurrence of conformational entropy in protein crystal contacts was considered to be a very unlikely event. A study based on the most accurately refined protein structures demonstrated that side-chain conformational entropy and static disorder might be common in protein crystal lattices. The present investigation uses structures refined using ensemble refinement to show that although paradoxical, conformational entropy is likely to be the major factor in the emergence and integrity of the protein condensed phase. This study reveals that the role of shape entropy and local entropic forces expands beyond the onset of crystallization. For the first time, the complete pattern of intermolecular interactions by protein atoms in crystal lattices is presented, which shows that van der Waals interactions dominate in crystal formation.
Language	English
Publishing date	2018-01-10
Publishing country	England
Document type	Journal Article
ZDB-ID	2754953-7
ISSN	2052-2525
ISSN	2052-2525
DOI	10.1107/S2052252517017833
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Article ; Online: Response to comment on `Protein crystal lattices are dynamic assemblies

Margarita Dimova / Yancho D. Devedjiev

IUCrJ, Vol 5, Iss 4, Pp 520-

the role of conformational entropy in the protein condensed phase'

2018 Volume 520

Keywords	protein crystals ; crystal lattices ; Science ; Q
Language	English
Publishing date	2018-07-01T00:00:00Z
Publisher	International Union of Crystallography
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Protein crystal lattices are dynamic assemblies

Margarita Dimova / Yancho D. Devedjiev

IUCrJ, Vol 5, Iss 2, Pp 130-

the role of conformational entropy in the protein condensed phase

2018 Volume 140

Abstract	Until recently, the occurrence of conformational entropy in protein crystal contacts was considered to be a very unlikely event. A study based on the most accurately refined protein structures demonstrated that side-chain conformational entropy and static disorder might be common in protein crystal lattices. The present investigation uses structures refined using ensemble refinement to show that although paradoxical, conformational entropy is likely to be the major factor in the emergence and integrity of the protein condensed phase. This study reveals that the role of shape entropy and local entropic forces expands beyond the onset of crystallization. For the first time, the complete pattern of intermolecular interactions by protein atoms in crystal lattices is presented, which shows that van der Waals interactions dominate in crystal formation.
Keywords	protein crystals ; static disorder ; dynamic disorder ; conformational entropy ; elastic molecular shape ; oscillating crystal lattice ; local entropic force ; X-ray crystallography ; crystallization ; crystal growth ; Science ; Q
Subject code	612
Language	English
Publishing date	2018-03-01T00:00:00Z
Publisher	International Union of Crystallography
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A qualitative analysis of transitions to heroin injection in Kenya: implications for HIV prevention and harm reduction.

Guise, Andy / Dimova, Margarita / Ndimbii, James / Clark, Phil / Rhodes, Tim

Harm reduction journal

2015 Volume 12, Page(s) 27

Abstract: Background: Heroin injection is emerging as a significant dimension of the HIV epidemic in Kenya. Preventing transitions to injecting drug use from less harmful forms of use, such as smoking, is a potentially important focus for HIV prevention. There is, ...

Abstract	Background: Heroin injection is emerging as a significant dimension of the HIV epidemic in Kenya. Preventing transitions to injecting drug use from less harmful forms of use, such as smoking, is a potentially important focus for HIV prevention. There is, however, little evidence to support comprehensive programming in this area, linked to a shortage of analysis of the social and structural context for transitions, particularly in low-income settings. We explore accounts of transitions from smoking to injecting in Kenya to understand the role of individual, social and structural processes. Methods: We combine data from two separate studies conducted in Kenya: an in-depth qualitative study of HIV care access for people who inject drugs (study 1) and an ethnographic study of the political economy of the heroin trade in Kenya (study 2). In-depth interviews with PWID and community observation from study 1 are triangulated with accounts from stakeholders involved in the heroin trade and documentary data from study 2. Results: People who inject drugs link transitions to injecting from smoking to a range of social and behavioural factors, as well as particular aspects of the local drug supply and economy. We present these results in the form of two narratives that account for factors shaping transitions. A dominant narrative of 'managing markets and maintaining a high' results from a process of trying to manage poverty and a shifting heroin supply, in the context of deepening addiction to heroin. A secondary narrative focuses on people's curiosity for the 'feeling' of injecting, and the potential pleasure from it, with less emphasis on structural circumstances. Conclusions: The narratives we describe represent pathways through which structural and social factors interact with individual experiences of addiction to increase the risk of transitions to injecting. In response, HIV and harm reduction programmes need combinations of different strategies to respond to varied experiences of transitions. These strategies should include, alongside behaviour-oriented interventions, structural interventions to address economic vulnerability and the policing of the drug supply.
MeSH term(s)	Adult ; Comorbidity ; Drug Users/statistics & numerical data ; Female ; HIV Infections/epidemiology ; HIV Infections/prevention & control ; Harm Reduction ; Heroin/administration & dosage ; Heroin Dependence/epidemiology ; Humans ; Interviews as Topic ; Kenya/epidemiology ; Male ; Middle Aged ; Qualitative Research ; Substance Abuse, Intravenous/epidemiology ; Substance Abuse, Intravenous/prevention & control ; Young Adult
Chemical Substances	Heroin (70D95007SX)
Language	English
Publishing date	2015-09-04
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1477-7517
ISSN (online)	1477-7517
DOI	10.1186/s12954-015-0061-2
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Article ; Online: An ethnographic exploration of drug markets in Kisumu, Kenya.

Syvertsen, Jennifer L / Ohaga, Spala / Agot, Kawango / Dimova, Margarita / Guise, Andy / Rhodes, Tim / Wagner, Karla D

The International journal on drug policy

2016 Volume 30, Page(s) 82–90

Abstract: Background: Illegal drug markets are shaped by multiple forces, including local actors and broader economic, political, social, and criminal justice systems that intertwine to impact health and social wellbeing. Ethnographic analyses that interrogate ... ...

Abstract	Background: Illegal drug markets are shaped by multiple forces, including local actors and broader economic, political, social, and criminal justice systems that intertwine to impact health and social wellbeing. Ethnographic analyses that interrogate multiple dimensions of drug markets may offer both applied and theoretical insights into drug use, particularly in developing nations where new markets and local patterns of use traditionally have not been well understood. This paper explores the emergent drug market in Kisumu, western Kenya, where our research team recently documented evidence of injection drug use. Methods: Our exploratory study of injection drug use was conducted in Kisumu from 2013 to 2014. We draw on 151 surveys, 29 in-depth interviews, and 8 months of ethnographic fieldwork to describe the drug market from the perspective of injectors, focusing on their perceptions of the market and reports of drug use therein. Results: Injectors described a dynamic market in which the availability of drugs and proliferation of injection drug use have taken on growing importance in Kisumu. In addition to reports of white and brown forms of heroin and concerns about drug adulteration in the market, we unexpectedly documented widespread perceptions of cocaine availability and injection in Kisumu. Examining price data and socio-pharmacological experiences of cocaine injection left us with unconfirmed evidence of its existence, but opened further possibilities about how the chaos of new drug markets and diffusion of injection-related beliefs and practices may lend insight into the sociopolitical context of western Kenya. Conclusions: We suggest a need for expanded drug surveillance, education and programming responsive to local conditions, and further ethnographic inquiry into the social meanings of emergent drug markets in Kenya and across sub-Saharan Africa.
MeSH term(s)	Adult ; Anthropology, Cultural ; Cocaine/economics ; Cocaine/supply & distribution ; Commerce/economics ; Data Collection ; Drug Contamination ; Drug Trafficking/economics ; Drug Trafficking/statistics & numerical data ; Female ; Heroin/economics ; Heroin/supply & distribution ; Humans ; Interviews as Topic ; Kenya/epidemiology ; Male ; Street Drugs/economics ; Street Drugs/supply & distribution ; Substance Abuse, Intravenous/epidemiology ; Young Adult
Chemical Substances	Street Drugs ; Heroin (70D95007SX) ; Cocaine (I5Y540LHVR)
Language	English
Publishing date	2016-04
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2010000-0
ISSN	1873-4758 ; 0955-3959
ISSN (online)	1873-4758
ISSN	0955-3959
DOI	10.1016/j.drugpo.2016.01.001
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Article ; Online: Membrane flow patterns in multicomponent giant vesicles induced by alternating electric fields†Electronic supplementary information (ESI) available: Vesicle preparation procedure, numerical calculations and confocal microscopy movies of domain motion. See DOI: 10.1039/b811876kClick here for additional data file.Click here for additional data file.Click here for additional data file.Click here for additional data file.Click here for additional data file.

Staykova, Margarita / Lipowsky, Reinhard / Dimova, Rumiana

Soft matter

2008 Volume 4, Issue 11, Page(s) 2168–2171

Abstract: Alternating electric (AC) fields induce circular patterns of lipid transport in membranes of giant vesicles. The flow is visualized by fluorescently labelled lipid domains. ...

Abstract	Alternating electric (AC) fields induce circular patterns of lipid transport in membranes of giant vesicles. The flow is visualized by fluorescently labelled lipid domains.
Language	English
Publishing date	2008-09-10
Publishing country	England
Document type	Journal Article
ZDB-ID	2191476-X
ISSN	1744-6848 ; 1744-683X
ISSN (online)	1744-6848
ISSN	1744-683X
DOI	10.1039/b811876k
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Article ; Online: SCN1A mutation spectrum in a cohort of Bulgarian patients with GEFS+ phenotype.

The Turkish journal of pediatrics

2020 Volume 62, Issue 5, Page(s) 711–725

Abstract: Background: Dravet syndrome (DS) is the most severe form of Generalized Epilepsy with Febrile Seizures plus (GEFS+) syndrome with a clear genetic component in 85% of the cases. It is characterized by fever-provoked seizure onset around six months of age ...

Abstract	Background: Dravet syndrome (DS) is the most severe form of Generalized Epilepsy with Febrile Seizures plus (GEFS+) syndrome with a clear genetic component in 85% of the cases. It is characterized by fever-provoked seizure onset around six months of age and subsequent developmental deterioration later in life. Methods: In the current study, 60 patients with fever-provoked seizures and suspicion either of GEFS+ (50 patients) or of DS (10 patients) were referred for SCN1A gene sequence analysis. Results: SCN1A gene sequencing revealed clinically significant variants in 11 patients (18.3%); seven pathogenic (11.7%) and four likely pathogenic (6.7%). Five of these variants have not been reported previously. Among the preselected group of ten DS patients, five had pathogenic SCN1A variants which confirmed diagnosis of DS. In four patients with preliminary diagnosis GEFS+, the detected SCN1A variant enabled us to specify the diagnosis of DS in these patients. Thus, SCN1A sequencing led to confirmation of the genetic diagnosis in 50% (5/10) of DS patients, as well as clarification of the diagnosis of DS in 8% of GEFS+ patients (4/50). In this study, four patients with truncating mutations had refractory seizures and additional psychomotor abnormalities. Additionally, pathogenic missense mutations were detected in three children with comparable phenotypes, which support the observations that missense mutations in critical channel function regions can cause a devastating epileptic condition. Conclusions: This is the first systematic screening of SCN1A gene in our country, which expands the spectrum of SCN1A variants with five novel variants from Bulgaria and demonstrates the clinical utility of confirmatory SCN1A testing, which helps clinicians make early and precise diagnoses. It is important for a better followup, choice of proper treatment, avoidance of development of refractory seizures and neuropsychological complications. Identification of pathogenic variants in SCN1A in the milder GEFS+ and severe DS cases, will help to offer adequate prenatal diagnosis and improve the genetic counselling provided to affected families.
MeSH term(s)	Bulgaria ; Epilepsies, Myoclonic ; Female ; Humans ; Infant ; Mutation ; Mutation, Missense ; NAV1.1 Voltage-Gated Sodium Channel/genetics ; Phenotype ; Spasms, Infantile
Chemical Substances	NAV1.1 Voltage-Gated Sodium Channel ; SCN1A protein, human
Language	English
Publishing date	2020-11-11
Publishing country	Turkey
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	123487-0
ISSN	2791-6421 ; 0041-4301
ISSN (online)	2791-6421
ISSN	0041-4301
DOI	10.24953/turkjped.2020.05.002
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Article ; Online: Metabolic characteristics of transmembrane prolyl 4-hydroxylase (P4H-TM) deficient mice.

Ala-Nisula, Tuulia / Halmetoja, Riikka / Leinonen, Henri / Kurkela, Margareta / Lipponen, Henna-Riikka / Sakko, Samuli / Karpale, Mikko / Salo, Antti M / Sissala, Niina / Röning, Tapio / Raza, Ghulam S / Mäkelä, Kari A / Thevenot, Jérôme / Herzig, Karl-Heinz / Serpi, Raisa / Myllyharju, Johanna / Tanila, Heikki / Koivunen, Peppi / Dimova, Elitsa Y

Pflugers Archiv : European journal of physiology

2024

Abstract: Transmembrane prolyl 4-hydroxylase (P4H-TM) is an enigmatic enzyme whose cellular function and primary substrate remain to be identified. Its loss-of-function mutations cause a severe neurological HIDEA syndrome with hypotonia, intellectual disability, ... ...

Abstract	Transmembrane prolyl 4-hydroxylase (P4H-TM) is an enigmatic enzyme whose cellular function and primary substrate remain to be identified. Its loss-of-function mutations cause a severe neurological HIDEA syndrome with hypotonia, intellectual disability, dysautonomia and hypoventilation. Previously, P4H-TM deficiency in mice was associated with reduced atherogenesis and lower serum triglyceride levels. Here, we characterized the glucose and lipid metabolism of P4h-tm
Language	English
Publishing date	2024-02-24
Publishing country	Germany
Document type	Journal Article
ZDB-ID	6380-0
ISSN	1432-2013 ; 0031-6768
ISSN (online)	1432-2013
ISSN	0031-6768
DOI	10.1007/s00424-024-02920-5
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Article ; Online: Effector Vγ9Vδ2 T cells dominate the human fetal γδ T-cell repertoire.

Dimova, Tanya / Brouwer, Margreet / Gosselin, Françoise / Tassignon, Joël / Leo, Oberdan / Donner, Catherine / Marchant, Arnaud / Vermijlen, David

Proceedings of the National Academy of Sciences of the United States of America

2015 Volume 112, Issue 6, Page(s) E556–65

Abstract: γδ T cells are unconventional T cells recognizing antigens via their γδ T-cell receptor (TCR) in a way that is fundamentally different from conventional αβ T cells. γδ T cells usually are divided into subsets according the type of Vγ and/or Vδ chain they ...

Abstract	γδ T cells are unconventional T cells recognizing antigens via their γδ T-cell receptor (TCR) in a way that is fundamentally different from conventional αβ T cells. γδ T cells usually are divided into subsets according the type of Vγ and/or Vδ chain they express in their TCR. T cells expressing the TCR containing the γ-chain variable region 9 and the δ-chain variable region 2 (Vγ9Vδ2 T cells) are the predominant γδ T-cell subset in human adult peripheral blood. The current thought is that this predominance is the result of the postnatal expansion of cells expressing particular complementary-determining region 3 (CDR3) in response to encounters with microbes, especially those generating phosphoantigens derived from the 2-C-methyl-d-erythritol 4-phosphate pathway of isoprenoid synthesis. However, here we show that, rather than requiring postnatal microbial exposure, Vγ9Vδ2 T cells are the predominant blood subset in the second-trimester fetus, whereas Vδ1(+) and Vδ3(+) γδ T cells are present only at low frequencies at this gestational time. Fetal blood Vγ9Vδ2 T cells are phosphoantigen responsive and display very limited diversity in the CDR3 of the Vγ9 chain gene, where a germline-encoded sequence accounts for >50% of all sequences, in association with a prototypic CDR3δ2. Furthermore, these fetal blood Vγ9Vδ2 T cells are functionally preprogrammed (e.g., IFN-γ and granzymes-A/K), with properties of rapidly activatable innatelike T cells. Thus, enrichment for phosphoantigen-responsive effector T cells has occurred within the fetus before postnatal microbial exposure. These various characteristics have been linked in the mouse to the action of selecting elements and would establish a much stronger parallel between human and murine γδ T cells than is usually articulated.
MeSH term(s)	Animals ; DNA Primers/genetics ; Fetus/immunology ; Flow Cytometry ; Gene Expression Profiling ; Humans ; Immune System/growth & development ; Mice ; Microarray Analysis ; Receptors, Antigen, T-Cell, gamma-delta/immunology ; Sequence Analysis, DNA ; Statistics, Nonparametric ; T-Lymphocyte Subsets/immunology ; T-Lymphocyte Subsets/metabolism
Chemical Substances	DNA Primers ; Receptors, Antigen, T-Cell, gamma-delta
Language	English
Publishing date	2015-02-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.1412058112
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