scholarly journals The inter-α-inhibitor family: from structure to regulation

1996 ◽  
Vol 315 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Jean-Philippe SALIER ◽  
Philippe ROUET ◽  
Gilda RAGUENEZ ◽  
Maryvonne DAVEAU
Keyword(s):  
Plasma Proteins ◽  
Recent Progress ◽  
Family Members ◽  
Protein Levels ◽  
The Family ◽  
Health And Disease ◽  
Structure Regulation ◽  
Uniform Nomenclature ◽  
Made In

Inter-α-inhibitor (IαI) and related molecules, collectively referred to as the IαI family, are a group of plasma protease inhibitors. They display attractive features such as precursor polypeptides that give rise to mature chains with quite distinct fates and functions, and inter-chain glycosaminoglycan bonds within the various molecules. The discovery of an ever growing number of such molecules has raised pertinent questions about their pathophysiological functions. The knowledge of this family has long been structure-oriented, whereas the structure/function and structure/regulation relationships of the family members and their genes have been largely ignored. These relationships are now being elucidated in events such as gene transcription, precursor processing, changes in plasma protein levels in health and disease and binding capacities that involve hyaluronan as well as other plasma proteins as ligands. This review presents some recent progress made in these fields that paves the way for an understanding of the functions of IαI family members in vivo. Finally, given the wealth of heterogeneous, complicated and sometimes contradictory nomenclatures and acronyms currently in use for this family, a new, uniform, nomenclature is proposed for IαI family genes, precursor polypeptides and assembled proteins.

Decisions Made by Family Members of Patients with Severe Head Injury

1991 ◽  
Vol 2 (2) ◽  
pp. 242-251 ◽  
Author(s):  
Michaelene P. Mirr
Keyword(s):  
Head Injury ◽  
Severe Head Injury ◽  
Family Members ◽  
Decision Makers ◽  
Acute Injury ◽  
Decision Making Process ◽  
The Family ◽  
The One ◽  
Family Nurses ◽  
Made In

An acute injury in which a family member requires critical care creates a period of intense stress for families. During such time, family members are often faced with decisions about the patient or the family. The ability of families to make decisions during this stressful period is not addressed in the literature. The purpose of this study was to determine what decisions families made in the one-month period after a patient’s admission. Families of patients with severe head injury were chosen because these families are often forced to make decisions quickly and to act as proxy decision-makers for the injured person. Nurses can make important contributions to assist family members in making decisions about the patient or the family. Nurses need to understand what decisions family members need to make and the circumstances surrounding the decision-making process to intervene appropriately

scholarly journals Recent Progress in Development of Polo-Like Kinase 1 Inhibitors: Efforts So Far

2021 ◽  
Author(s):  
Ramesh L. Sawant ◽  
Jyoti B. Wadekar ◽  
Rushikesh D. Ukirde ◽  
Ganesh D. Barkade
Keyword(s):  
Cell Proliferation ◽  
Protein Kinase ◽  
Cancer Therapy ◽  
Anticancer Agents ◽  
Clinical Studies ◽  
Recent Progress ◽  
Atp Binding Site ◽  
The Family ◽  
New Generation ◽  
Made In

Polo-like kinase 1(Plk1) plays an important role in the inhibition of cell proliferation and which is come under the family of serine/threonine-protein kinase. Which is a highly specific target for cancer therapy. In some clinical studies, Plk1 has been identified as a target for cancer. Currently, so many scientists are working on the development of the Plk1 inhibitors and so many scientists and researchers thinking about working on it. Recent strategy for Plk1 inhibition is the development of small molecule inhibitors which will inhibit the Plk1 through the ATP-binding site of the Plk. Now new generation Plk1 inhibitors being tested clinically which are targeting polo box domain. This review highlights the recent progress made in the development of Plk1 inhibitors as anticancer agents.

Murine Ifit3 restricts the replication of Rabies virus both in vitro and in vivo

2021 ◽  
Vol 102 (7) ◽  
Author(s):  
Benjie Chai ◽  
Dayong Tian ◽  
Ming Zhou ◽  
Bin Tian ◽  
Yueming Yuan ◽  
...  
Keyword(s):  
Rabies Virus ◽  
Cultured Cells ◽  
Immune Defence ◽  
Tetratricopeptide Repeats ◽  
Protein Levels ◽  
The Family ◽  
Deficient Mice ◽  
Insight Into

Rabies virus (RABV) infection can initiate the host immune defence response and induce an antiviral state characterized by the expression of interferon (IFN)-stimulated genes (ISGs), among which the family of genes of IFN-induced protein with tetratricopeptide repeats (Ifits) are prominent representatives. Herein, we demonstrated that the mRNA and protein levels of Ifit1, Ifit2 and Ifit3 were highly increased in cultured cells and mouse brains after RABV infection. Recombinant RABV expressing Ifit3, designated rRABV-Ifit3, displayed a lower pathogenicity than the parent RABV in C57BL/6 mice after intramuscular administration, and Ifit3-deficient mice exhibited higher susceptibility to RABV infection and higher mortality during RABV infection. Moreover, compared with their individual expressions, co-expression of Ifit2 and Ifit3 could more effectively inhibit RABV replication in vitro. These results indicate that murine Ifit3 plays an essential role in restricting the replication and reducing the pathogenicity of RABV. Ifit3 acts synergistically with Ifit2 to inhibit RABV replication, providing further insight into the function and complexity of the Ifit family.

Mast cells in health and disease

2011 ◽  
Vol 120 (11) ◽  
pp. 473-484 ◽  
Author(s):  
Charlotte L. Weller ◽  
Sarah J. Collington ◽  
Tim Williams ◽  
Jonathan R. Lamb
Keyword(s):  
Wound Healing ◽  
Mast Cells ◽  
Allergic Disease ◽  
Effector Functions ◽  
Health And Disease ◽  
Developing Area ◽  
Deficient Mice ◽  
Made In

Although MCs (mast cells) were discovered over 100 years ago, for the majority of this time their function was linked almost exclusively to allergy and allergic disease with few other roles in health and disease. The engineering of MC-deficient mice and engraftment of these mice with MCs deficient in receptors or mediators has advanced our knowledge of the role of MCs in vivo. It is now known that MCs have very broad and varied roles in both physiology and disease which will be reviewed here with a focus on some of the most recent discoveries over the last year. MCs can aid in maintaining a healthy physiology by secreting mediators that promote wound healing and homoeostasis as well as interacting with neurons. Major developments have been made in understanding MC function in defence against pathogens, in recognition of pathogens as well as direct effector functions. Probably the most quickly developing area of understanding is the involvement and contribution MCs make in the progression of a variety of diseases from some of the most common diseases to the more obscure.

scholarly journals In vivo analysis of the evolutionary conserved BTD-box domain of Sp1 and Btd during Drosophila development

2020 ◽  
Author(s):  
David Blom-Dahl ◽  
Sergio Córdoba ◽  
Hugo Gabilondo ◽  
Pablo Carr-Baena ◽  
Fernando J. Díaz-Benjumea ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Unknown Function ◽  
Limb Development ◽  
Gene Editing ◽  
Target Genes ◽  
Zinc Fingers ◽  
Family Members ◽  
The Family ◽  
In Vivo Analysis

AbstractThe Sp family of transcription factors plays important functions during development and disease. An evolutionary conserved role for some Sp family members is the control of limb development. The family is characterized by the presence of three C2H2-type zinc fingers and an adjacent 10 aa region with an unknown function called the Buttonhead (BTD) box. The presence of this BTD-box in all Sp family members identified from arthropods to vertebrates, suggests that it plays an important role during development. However, despite its conservation, the in vivo function of the BTD-box has never been studied. In this work, we have generated specific BTD-box deletion alleles for the Drosophila Sp family members Sp1 and buttonhead (btd) using gene editing tools and analyzed its role during development. Unexpectedly, btd and Sp1 mutant alleles that lack the BTD-box are viable and have almost normal appendages. However, in a sensitized background the requirement of this domain to fully regulate some of Sp1 and Btd target genes is revealed. Furthermore, we have also identified a novel Sp1 role promoting leg vs antenna identity through the repression of spineless (ss) expression in the leg, a function that also depends on the Sp1 BTD-box.

Effects of neuronal drebrin on actin dynamics

2021 ◽  
Author(s):  
Elena E. Grintsevich
Keyword(s):  
Synaptic Plasticity ◽  
Posttranslational Modifications ◽  
Neurodegenerative Disorders ◽  
Neuronal Migration ◽  
Recent Progress ◽  
Actin Dynamics ◽  
Cytoskeletal Dynamics ◽  
Health And Disease ◽  
Made In

Drebrin is a key regulator of actin cytoskeleton in neuronal cells which is critical for synaptic plasticity, neuritogenesis, and neuronal migration. It is also known to orchestrate a cross-talk between actin and microtubules. Decreased level of drebrin is a hallmark of multiple neurodegenerative disorders such as Alzheimer's disease. Despite its established importance in health and disease, we still have a lot to learn about drebrin's interactome and its effects on cytoskeletal dynamics. This review aims to summarize the recently reported novel effects of drebrin on actin and its regulators. Here I will also reflect on the most recent progress made in understanding of the role of drebrin isoforms and posttranslational modifications on its functionality.

scholarly journals Family health care decision making and self-efficacy with patients with ALS at the end of life

2008 ◽  
Vol 6 (3) ◽  
pp. 273-280 ◽  
Author(s):  
Marie T. Nolan ◽  
Joan Kub ◽  
Mark T. Hughes ◽  
Peter B. Terry ◽  
Alan B. Astrow ◽  
...  
Keyword(s):  
Health Care ◽  
Decision Making ◽  
End Of Life ◽  
Shared Decision Making ◽  
Family Members ◽  
Shared Decision ◽  
Health Care Decisions ◽  
The Family ◽  
Care Decision ◽  
Made In

ABSTRACTObjective:Persons with ALS differ from those with other terminal illnesses in that they commonly retain capacity for decision making close to death. The role patients would opt to have their families play in decision making at the end of life may therefore be unique. This study compared the preferences of patients with ALS for involving family in health care decisions at the end of life with the actual involvement reported by the family after death.Methods:A descriptive correlational design with 16 patient–family member dyads was used. Quantitative findings were enriched with in-depth interviews of a subset of five family members following the patient's death.Results:Eighty-seven percent of patients had issued an advance directive. Patients who would opt to make health care decisions independently (i.e., according to the patient's preferences alone) were most likely to have their families report that decisions were made in the style that the patient preferred. Those who preferred shared decision making with family or decision making that relied upon the family were more likely to have their families report that decisions were made in a style that was more independent than preferred. When interviewed in depth, some family members described shared decision making although they had reported on the survey that the patient made independent decisions.Significance of results:The structure of advance directives may suggest to families that independent decision making is the ideal, causing them to avoid or underreport shared decision making. Fear of family recriminations may also cause family members to avoid or underreport shared decision making. Findings from this study might be used to guide clinicians in their discussions of treatments and health care decision making with persons with ALS and their families.

Purification of the Antihemophilic Factor by Gel Filtration on Agarose

1969 ◽  
Vol 22 (03) ◽  
pp. 577-583 ◽  
Author(s):  
M.M.P Paulssen ◽  
A.C.M.G.B Wouterlood ◽  
H.L.M.A Scheffers
Keyword(s):  
Factor Viii ◽  
Plasma Proteins ◽  
Large Scale ◽  
Gel Filtration ◽  
Large Scale Preparation ◽  
Scale Preparation ◽  
Antihemophilic Factor

SummaryFactor VIII can be isolated from plasma proteins, including fibrinogen by chromatography on agarose. The best results were obtained with Sepharose 6B. Large scale preparation is also possible when cryoprecipitate is separated by chromatography. In most fractions containing factor VIII a turbidity is observed which may be due to the presence of chylomicrons.The purified factor VIII was active in vivo as well as in vitro.

The Development of Homologous (Canine/Anti-Canine) Antibodies in Dogs with Haemophilia A (Factor VIII Deficiency): A Ten-Year Longitudinal Study

1993 ◽  
Vol 69 (01) ◽  
pp. 021-024 ◽  
Author(s):  
Shawn Tinlin ◽  
Sandra Webster ◽  
Alan R Giles
Keyword(s):  
Factor Viii ◽  
Canine Model ◽  
Significant Inhibition ◽  
Human Condition ◽  
Haemophilia A ◽  
Variable Expression ◽  
The Family ◽  
Over Time

SummaryThe development of inhibitors to factor VIII in patients with haemophilia A remains as a serious complication of replacement therapy. An apparently analogous condition has been described in a canine model of haemophilia A (Giles et al., Blood 1984; 63:451). These animals and their relatives have now been followed for 10 years. The observation that the propensity for inhibitor development was not related to the ancestral factor VIII gene has been confirmed by the demonstration of vertical transmission through three generations of the segment of the family related to a normal (non-carrier) female that was introduced for breeding purposes. Haemophilic animals unrelated to this animal have not developed functionally significant factor VIII inhibitors despite intensive factor VIII replacement. Two animals have shown occasional laboratory evidence of factor VIII inhibition but this has not been translated into clinical significant inhibition in vivo as assessed by clinical response and F.VIII recovery and survival characteristics. Substantial heterogeneity of inhibitor expression both in vitro and in vivo has been observed between animals and in individual animals over time. Spontaneous loss of inhibitors has been observed without any therapies designed to induce tolerance, etc., being instituted. There is also phenotypic evidence of polyclonality of the immune response with variable expression over time in a given animal. These observations may have relevance to the human condition both in determining the pathogenetic factors involved in this condition and in highlighting the heterogeneity of its expression which suggests the need for caution in the interpretation of the outcome of interventions designed to modulate inhibitor activity.

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