scholarly journals The evolutionary history of topological variations in the CPA/AT transporters

2021 ◽  
Vol 17 (8) ◽  
pp. e1009278
Author(s):  
Govindarajan Sudha ◽  
Claudio Bassot ◽  
John Lamb ◽  
Nanjiang Shu ◽  
Yan Huang ◽  
...  
Keyword(s):  
Core Domain ◽  
Structure Topology ◽  
Fold Type ◽  
History Of ◽  
Topology Information ◽  
Transport Of Ions ◽  
And Function ◽  
Type 3 ◽  
Shed Light

CPA/AT transporters are made up of scaffold and a core domain. The core domain contains two non-canonical helices (broken or reentrant) that mediate the transport of ions, amino acids or other charged compounds. During evolution, these transporters have undergone substantial changes in structure, topology and function. To shed light on these structural transitions, we create models for all families using an integrated topology annotation method. We find that the CPA/AT transporters can be classified into four fold-types based on their structure; (1) the CPA-broken fold-type, (2) the CPA-reentrant fold-type, (3) the BART fold-type, and (4) a previously not described fold-type, the Reentrant-Helix-Reentrant fold-type. Several topological transitions are identified, including the transition between a broken and reentrant helix, one transition between a loop and a reentrant helix, complete changes of orientation, and changes in the number of scaffold helices. These transitions are mainly caused by gene duplication and shuffling events. Structural models, topology information and other details are presented in a searchable database, CPAfold (cpafold.bioinfo.se).

scholarly journals Heliorhodopsin evolution is driven by photosensory promiscuity in monoderms

2021 ◽  
Author(s):  
Paul-Adrian Bulzu ◽  
Vinicius Silva Kavagutti ◽  
Maria-Cecilia Chiriac ◽  
Charlotte D. Vavourakis ◽  
Keiichi Inoue ◽  
...  
Keyword(s):  
High Energy ◽  
Protein Domain ◽  
History Of ◽  
Increased Sensitivity ◽  
Biological Complexes ◽  
And Function ◽  
Occurrence Patterns ◽  
Type 3

The ability to harness Sun’s electromagnetic radiation by channeling it into high-energy phosphate bonds empowered microorganisms to tap into a cheap and inexhaustible source of energy. Life’s billion-years history of metabolic innovations led to the emergence of only two biological complexes capable of harvesting light: one based on rhodopsins and the other on (bacterio)chlorophyll. Rhodopsins encompass the most diverse and abundant photoactive proteins on Earth and were until recently canonically split between type-1 (microbial rhodopsins) and type-2 (animal rhodopsins) families. Unexpectedly, the long-lived type-1/type-2 dichotomy was recently amended through the discovery of heliorhodopsins (HeRs) (Pushkarev et al. 2018), a novel and exotic family of rhodopsins (i.e. type-3) that evaded recognition in our current homology-driven scrutiny of life’s genomic milieu. Here, we bring to resolution the debated monoderm/diderm occurrence patterns by conclusively showing that HeR distribution is restricted to monoderms. Furthermore, through investigating protein domain fusions, contextual genomic information, and gene co-expression data we show that HeRs likely function as generalised light-dependent switches involved in the mitigation of light-induced oxidative stress and metabolic circuitry regulation. We reason that HeR’s ability to function as sensory rhodopsins is corroborated by their photocycle dynamics (Pushkarev et al. 2018) and that their presence and function in monoderms is likely connected to the increased sensitivity to light-induced damage of these organisms (Maclean et al. 2009).

THE EMERGENCE OF FRAILTY MAY LEAD TO A STATE OF BURNT OUT TYPE 2 DIABETES

2016 ◽  
pp. 1-6
Author(s):  
A.H. ABDELHAFIZ ◽  
L. KOAY ◽  
A.J. SINCLAIR
Keyword(s):  
Type 2 Diabetes ◽  
Β Cells ◽  
Risk Of Mortality ◽  
Vulnerable Patients ◽  
Increased Risk ◽  
History Of ◽  
The One ◽  
And Function ◽  
Glucose Dynamics

Ageing is associated with hyperglycaemic tendency due to the change in body composition leading to accumulation of visceral fat and increased insulin resistance on the one hand and reduced insulin secretion due to decreased number and function of the β-cells of the pancreas on the other. However, with the emergence of frailty there may be a tendency towards normoglycaemia or even hypoglycaemia due to malnutrition, weight loss and reduced physiologic reserve. This shift in glucose metabolism induced by frailty may change the natural history of type 2 diabetes from a progressive to a regressive course. Studies which showed increased risk of mortality with low HbA1c included frail patients in the lower HbA1c categories and healthier patients in the higher HbA1c categories suggesting that frailty is a possible confounding factor. Therefore, hypoglycemia may be a prognostic tool to identify vulnerable patients who may be at increased risk of mortality. The metabolic changes of insulin/glucose dynamics associated with frailty need further research.

scholarly journals Failed Dermal Allograft Procedures in Irreparable Rotator Cuff Tears Can Still Improve Pain and Function. The “Biologic Tuberoplasty Effect”

2018 ◽  
Vol 6 (7_suppl4) ◽  
pp. 2325967118S0009
Author(s):  
Raffy Mirzayan ◽  
Michael Allan Stone ◽  
Michael Batech ◽  
Daniel Acevedo ◽  
Anshu Singh
Keyword(s):  
Rotator Cuff ◽  
Average Length ◽  
Rotator Cuff Tears ◽  
Double Row ◽  
Significant Difference ◽  
Goutallier Classification ◽  
And Function ◽  
Type 3

Objectives: Massive rotator cuff tears (MRCT) are a challenging problem. Dermal allografts have been used in “bridging” procedures and superior capsule reconstruction (SCR). Both have led to clinical improvement, but without correlation with post-operative imaging. The purpose of this study is to examine graft integrity on MRI in patients who underwent an SCR or bridging procedure to determine if graft integrity correlates with functional outcome. We also propose a new classification of dermal allograft re-tear on MRI. Methods: This study was approved by our IRB. Between 2006 and 2016, 11 patients (12 shoulders) underwent a bridging procedure and 10 patients underwent an SCR for MRCT with a dermal allograft by a single surgeon. The grafts were secured to the tuberosity in a double-row, trans-osseous equivalent (DR-TOE) fashion. Pre- and post-operative VAS, acromiohumeral distance (AHD), and ASES scores, and pre-operative Hamada grade and Goutallier classification were prospectively collected and retrospectively reviewed. An MRI was obtained on all patients post-operatively to assess graft integrity. The status of the graft was divided into three types based on MRI findings: Type 1- Graft intact medially (rim of cuff or glenoid) AND laterally (greater tuberosity); Type 2- Graft intact laterally but torn medially; Type 3- Graft torn laterally. The shoulders were then grouped based on these types for further analysis. Results: The average age was 61 (range: 49-73). Average follow-up was 21.6 months (range: 8-80). Average length from surgery to MRI was 13.9 months (range: 6-80). There was a significant improvement in VAS (pre-8.1 to post-1.3) and ASES (pre-26.3 to post-84.6) in Type 1 (P<0.01) and in VAS (pre-7.0 to post-0.7) and ASES (pre-32.6 to post-91.2) in Type 2 (P<0.01). There was no difference in post-operative VAS (1.3 vs 0.7) and ASES (84.6 vs 91.2) between Type 1 and Type 2 (P=0.8). There was no improvement in VAS (pre-7.3 vs post-5.7) and ASES (pre-30.6 vs post-37.2) in Type 3. There was a significant difference in post-operative VAS (5.7 vs 1) and ASES (37.2 vs 88.1) between Type 3 versus Types 1+2, respectively (P<0.01). The AHD decreased in type 3 (pre-7.8 mm to post-3.2 mm, P=0.02) but did not change in Types 1+2 (pre-7.8 mm to post-8.0 mm, P=0.7). Conclusion: In patients who have SCR or “bridging” procedures for MRCT with a dermal allograft, there is significant improvement in VAS and ASES scores if the graft heals to the tuberosity, regardless if it is still intact to the glenoid (in SCR) or the rim of rotator cuff tendon (“bridging”). Individuals whose graft is torn from the tuberosity did not have improvement in VAS or ASES scores versus baseline. There was no significant difference in AHD in all groups. We believe that the dermal graft acts as a “biologic (interpositional) tuberoplasty,” preventing bone-to-bone contact between the tuberosity and the acromion, thus eliminating pain and improving function. We still recommend performing an SCR when indicated because it has been shown to restore the normal kinematics of the shoulder in a laboratory setting. However, careful attention should be paid to the repair of the graft to the tuberosity, so that in case the primary procedure fails medially, the graft can still improve pain and function.

A Brief History of Prosthetics and Orthotics of the Lower Body and Their Types

2021 ◽  
pp. 365-380
Author(s):  
Dheeman Bhuyan ◽  
Kaushik Kumar
Keyword(s):  
Historical Perspective ◽  
State Of The Art ◽  
Lower Body ◽  
Form And Function ◽  
Current State ◽  
History Of ◽  
And Function ◽  
Shed Light

Prosthetics and orthotics are items taken for granted in today's day and age. However, this has not always been the case. The history of these everyday items is long and very colorful. In this chapter, the authors shed light on the history and development of prosthetics and orthotics of the lower body in order to better understand the current state of the art in the fields. A historical perspective is provided followed by enumeration of the types of devices and techniques available without going into the form and function of individual products.

scholarly journals DEVELOPMENT, PERSISTENCE, AND SIGNIFICANCE OF TYPE 2, POLIOMYELITIS COMPLEMENT-FIXING ANTIBODY IN MAN

1952 ◽  
Vol 96 (1) ◽  
pp. 35-53 ◽  
Author(s):  
Jordi Casals ◽  
Peter K. Olitsky ◽  
Albert B. Sabin
Keyword(s):  
Complement Fixation ◽  
Age Groups ◽  
Neutralizing Antibody ◽  
Paralytic Poliomyelitis ◽  
Newborn Mice ◽  
History Of ◽  
Almost All ◽  
Type 3

Sera from 81 patients with a diagnosis of paralytic or non-paralytic poliomyelitis, and from 159 individuals of similar age groups giving no history of the disease, were tested with a high titered, complement-fixing poliomyelitis antigen of Type 2 (Lansing-like). The antigen consisted of brain tissue from newborn mice injected with the MEF1 strain of virus as previously adapted to these animals. The presence or absence of Type 2 neutralizing antibody in the sera under test was found not to affect the complement fixation. Positive reactions were obtained with 57 per cent of the sera deriving from non-paralytic patients and in 70 per cent from paralytics, when the specimens were tested at a dilution of 1:16. The complement-fixing antibody was often present in highest titer as early as 24 hours after the onset of poliomyelitis, and in almost all instances within 7 days. In about half of the patients a 4-fold or greater drop in titer occurred within 3 months, with little or no change in the others. The incidence of titers of 1:16 or higher with the control sera varied with the season of the year at which they were procured, 3 per cent of the winter samples proving positive and 13 per cent of the summer. The tests of sera from the group of patients from whom poliomyelitis virus was recovered, disclosed no significant differences between those having the paralytic and those having the non-paralytic disease. Type 1 (Brunhilde-like) strains of virus were recovered from many of the patients yielding positive tests, although they presented no evidence of previous or concurrent infection with Type 2 virus. This finding shows that Type 1 virus can give rise in patients to Type 2 complement-fixing antibody. The application of these data to the serologic diagnosis of poliomyelitis infection in man will of necessity be limited until information is obtained on the development, persistence, and significance of complement-fixation reactions with antigens deriving from Type 1 and Type 3 poliomyelitis strains.

scholarly journals Single-cell transcriptional analysis reveals naïve helper ILC-like cells in zebrafish

2018 ◽  
Author(s):  
Pedro P. Hernández ◽  
Paulina M. Strzelecka ◽  
Emmanouil I. Athanasiadis ◽  
Ana F. Robalo ◽  
Catherine M. Collins ◽  
...  
Keyword(s):  
Single Cell ◽  
Lymphoid Cells ◽  
Transcriptional Analysis ◽  
Environmental Cues ◽  
Immune Challenge ◽  
Wild Type ◽  
And Function ◽  
Type 3 ◽  
Barrier Tissues

AbstractInnate lymphoid cells (ILCs) are important mediators of the immune response and homeostasis in barrier tissues of mammals. However, the existence and function of ILCs in other vertebrates is poorly understood. Here, we use single-cell RNA sequencing to generate a comprehensive atlas of zebrafish lymphocytes during tissue homeostasis and following immune challenge. We profiled 14,080 individual cells from the gut of wild-type zebrafish, as well as of rag1-deficient fish which lack T and B cells, and discovered diverse populations of helper ILC-like cells. Unexpectedly, fish displayed a rorc-positive, naïve subset that established a Type 3 or Type 2 response only upon immune challenge. Specifically, naïve ILC-like cells expressed il22 and tnfa following exposure to inactivated bacteria, or il13 following exposure to helminth extract. Cytokine-producing ILC-like cells express a specific repertoire of novel immune-type receptors, likely involved in recognition of environmental cues. We identified additional novel markers of zebrafish ILCs and generated a cloud repository for their in-depth exploration.

A Brief History of Prosthetics and Orthotics of the Lower Body and Their Types

2019 ◽  
pp. 36-56
Author(s):  
Dheeman Bhuyan ◽  
Kaushik Kumar
Keyword(s):  
Historical Perspective ◽  
State Of The Art ◽  
Lower Body ◽  
Form And Function ◽  
Current State ◽  
History Of ◽  
And Function ◽  
Shed Light

Prosthetics and orthotics are items taken for granted in today's day and age. However, this has not always been the case. The history of these everyday items is long and very colorful. In this chapter, the authors shed light on the history and development of prosthetics and orthotics of the lower body in order to better understand the current state of the art in the fields. A historical perspective is provided followed by enumeration of the types of devices and techniques available without going into the form and function of individual products.

scholarly journals Theory of language: a taxonomy

2021 ◽  
Vol 1 (3) ◽  
Author(s):  
Patrik Austin
Keyword(s):  
Intellectual History ◽  
School Type ◽  
Evolutionary Linguistics ◽  
History Of ◽  
Living Species ◽  
Theory Of Language ◽  
Type 3 ◽  
And Linguistics

AbstractThe study of language has been historically proposed as a model for human sciences. For the structuralists, it is because languages, like society, and cultural habits, are man-made rule-based systems. For the Darwinists, it is because cultures and societies are like living species, and can be studied with biological methodology. Sociology, biology and linguistics are considered analogous in different ways. To support work in theoretical and applied linguistics, this paper discusses the problem of the nature of language, investigating how the question “What is language?” has been approached from different angles. Textbook answers guide us in many different directions: language is a tool for communication—and for thinking. It is a collection of words and instructions how to use them. It is the characteristic which—arguably—separates humans from other animals. It is a social construction, a system of symbols, a system of systems, and so on. To classify perspectives, the intellectual history of schools of linguistic thought is examined, connecting linguistic theory with related disciplines. A taxonomy is proposed based on two axes: humanistic versus biological; and historical versus systemic. Main linguistics frameworks are identified and placed into a fourfold table based on these axes. They include the Bloomfieldian school (Type 1); Saussurean structuralism and its derivatives (Type 2); generative grammar and biolinguistics (Type 3); and cognitive‒evolutionary linguistics (Type 4).

scholarly journals The evolutionary history of topological variations in the CPA/AT superfamily

2020 ◽  
Author(s):  
Sudha Govindarajan ◽  
Claudio Bassot ◽  
John Lamb ◽  
Nanjiang Shu ◽  
Yan Huang ◽  
...  
Keyword(s):  
Evolutionary History ◽  
Repeat Unit ◽  
Evolutionary Relationship ◽  
Structure Topology ◽  
Repeat Units ◽  
Novel Structure ◽  
Other Information ◽  
History Of ◽  
The Difference ◽  
And Function

CPA/AT transporters consist of two structurally and evolutionarily related inverted repeat units, each of them with one core and one scaffold subdomain. During evolution, these families have undergone substantial changes in structure, topology and function. Central to the function of the transporters is the existence of two non-canonical helices that are involved in the transport process. In different families, two different types of these helices have been identified, reentrant and broken. Here, we use an integrated topology annotation method to identify novel topologies in the families. It combines topology prediction, similarity to families with known structure, and the difference in positively charged residues present in inside and outside loops in alternative topological models. We identified families with diverse topologies containing broken or reentrant helix. We classified all families based on 3 distinct evolutionary groups that each share a structurally similar C-terminal repeat unit newly termed as Fold-types. Using the evolutionary relationship between families we propose topological transitions including, a transition between broken and reentrant helices, complete change of orientation, changes in the number of scaffold helices and even in some rare cases, losses of core helices. The evolutionary history of the repeat units shows gene duplication and repeat shuffling events to result in these extensive topology variations. The novel structure-based classification, together with supporting structural models and other information, is presented in a searchable database, CPAfold (cpafold.bioinfo.se). Our comprehensive study of topology variations within the CPA superfamily provides better insight about their structure and evolution.

scholarly journals Periodic Severe Angioedema without Exogenous Hormone Exposure

2021 ◽  
Author(s):  
Mohammad Nabavi ◽  
Sima Bahrami ◽  
Saba Arshi ◽  
Afshin Rezaeifar ◽  
Mohammad Hassan Bemanian ◽  
...  
Keyword(s):  
Treatment Strategies ◽  
Underlying Mechanism ◽  
The Body ◽  
Factor Xii ◽  
Normal Amount ◽  
Rare Type ◽  
Hormonal Manipulation ◽  
History Of ◽  
And Function ◽  
Type 3

Hereditary angioedema (HAE) is characterized by recurrent attacks of skin and mucosal swelling in any part of the body including the digestive and respiratory tract which generally improve spontaneously within 12-72 hours. The underlying mechanism in HAE is related to bradykinin dysregulation which causes these attacks not to respond to common treatment strategies including epinephrine or corticosteroid. There are several types of HAE with different etiology but with the same clinical picture. Type 1 is due to the deficiency of C1 Inhibitor (C1- INH) protein and type 2 is related to dysfunctional C1-INH protein. The third type of HAE which comprises the minority of cases is associated with the normal amount and function of C1- INH protein. The presented case in this report was a 15-years old girl with a history of spontaneous angioedema attacks from the age of 14. The frequency of attacks was initially every two months but consequently increased to every two weeks after using some hormonal medications for ovarian cyst. Each episode has lasted around 10 days without any symptoms in between. Complement studies including C4, C1q, and C1-INH protein, both quantitative and qualitative, were reported as normal. A genetic assessment revealed a mutation in the exon 9 on the gene related to factor XII, hence the diagnosis of HAE type 3 was confirmed. This was a rare type of angioedema with normal amount and function of C1-INH protein which is predominantly seen in women during periods of imbalanced estrogen increments like pregnancy, lactation, and menopause, and hence it is responsive to hormonal manipulation strategies such as the use of progesterone containing medications.

Sign in / Sign up

Export Citation Format

Share Document