scholarly journals Uridine Treatment of the First Known Case of SLC25A36 Deficiency

2021 ◽  
Vol 22 (18) ◽  
pp. 9929
Author(s):  
Luisa Jasper ◽  
Pasquale Scarcia ◽  
Stephan Rust ◽  
Janine Reunert ◽  
Ferdinando Palmieri ◽  
...  
Keyword(s):  
Embryonic Stem ◽  
Homozygous Mutation ◽  
Human Beings ◽  
Transport Activity ◽  
Pyrimidine Nucleotide ◽  
Developmental Progress ◽  
Whole Exome ◽  
Exome Analysis ◽  
Gene Functional Analysis

SLC25A36 is a pyrimidine nucleotide carrier playing an important role in maintaining mitochondrial biogenesis. Deficiencies in SLC25A36 in mouse embryonic stem cells have been associated with mtDNA depletion as well as mitochondrial dysfunction. In human beings, diseases triggered by SLC25A36 mutations have not been described yet. We report the first known case of SLC25A36 deficiency in a 12-year-old patient with hypothyroidism, hyperinsulinism, hyperammonemia, chronical obstipation, short stature, along with language and general developmental delay. Whole exome analysis identified the homozygous mutation c.803dupT, p.Ser269llefs*35 in the SLC25A36 gene. Functional analysis of mutant SLC25A36 protein in proteoliposomes showed a virtually abolished transport activity. Immunoblotting results suggest that the mutant SLC25A36 protein in the patient undergoes fast degradation. Supplementation with oral uridine led to an improvement of thyroid function and obstipation, increase of growth and developmental progress. Our findings suggest an important role of SLC25A36 in hormonal regulations and oral uridine as a safe and effective treatment.

scholarly journals Developmental regulation of yolk sac hematopoiesis by Krüppel-like factor 6

Blood ◽  
2006 ◽  
Vol 107 (4) ◽  
pp. 1357-1365 ◽  
Author(s):  
Nobuyuki Matsumoto ◽  
Atsushi Kubo ◽  
Huixian Liu ◽  
Kuniharu Akita ◽  
Friedrich Laub ◽  
...  
Keyword(s):  
Developmental Regulation ◽  
Es Cells ◽  
Embryonic Stem ◽  
Early Embryo ◽  
Yolk Sac ◽  
Homozygous Mutation ◽  
Mesoderm Induction ◽  
Mrna Levels ◽  
Mouse Development

Krüppel-like factor 6 (KLF6) is a member of a growing family of transcription factors that share a common 3 C2H2 zinc finger DNA binding domain and have broad activity in regulating proliferation and development. We have previously established that Klf6 is expressed in neuronal tissue, hindgut, heart, lung, kidney, and limb buds during midgestation. To explore the potential role of Klf6 in mouse development, we analyzed Klf6-/- mice and found that the homozygous mutation is embryonic lethal by embryonic day (E) 12.5 and associated with markedly reduced hematopoiesis and poorly organized yolk sac vascularization. Additionally, mRNA levels of Scl and Gata1 were reduced by approximately 80% in Klf6-/- yolk sacs. To further analyze this phenotype, we generated Klf6-/- embryonic stem (ES) cells by homologous recombination, and compared their capacity to differentiate into the hematopoietic lineage with that of either Klf6+/- or Klf6+/+ ES cells. Consistent with the phenotype in the early embryo, Klf6-/- ES cells displayed significant hematopoietic defects following differentiation into EBs. Prolongation of epiblast-like cells and delays in mesoderm induction were also observed in the Klf6-/- EBs, associated with delayed expression of Brachyury, Klf1, and Gata1. Forced expression of KLF6 using a tet-inducible system enhanced the hematopoietic potential of wild-type EBs. Collectively, these findings implicate Klf6 in ES-cell differentiation and hematopoiesis.

Webb–Dattani Syndrome: Report of a Saudi Arabian Family with a Novel Homozygous Mutation in the ARNT2 Gene

2018 ◽  
Vol 17 (02) ◽  
pp. 071-076 ◽  
Author(s):  
Nouriya Abbas Al-Sannaa ◽  
Alexander Pepler ◽  
Hind Y. Al-Abdulwahed ◽  
Sami I. Al-Majed ◽  
Rifat F. Abdi ◽  
...  
Keyword(s):  
Saudi Arabian ◽  
Autosomal Recessive Disorder ◽  
Cortical Blindness ◽  
Hormone Deficiency ◽  
Pituitary Hormone ◽  
Homozygous Mutation ◽  
Loss Of Function ◽  
Whole Exome ◽  
Retinal Examination

AbstractWebb–Dattani syndrome (WEDAS) is an autosomal recessive disorder caused by mutation in the ARNT2 gene characterized by frontotemporal hypoplasia, globally delayed development, and pituitary and hypothalamic insufficiency. The condition is reported to be associated with consanguinity and with Saudi Arabian ancestry. Here we describe a family of three affected siblings born to healthy second cousin parents of Saudi Arabian ancestry. The children presented at 3 months of age with congenital central hypotonia and hypoventilation, central diabetes insipidus, multiple pituitary hormone deficiency, severe developmental delay, acquired microcephaly, cortical blindness with normal retinal examination, seizures, and gastroesophageal reflux. Whole exome sequencing detected a homozygous unclear variant (c.378C>T; p.G126G) in the ARNT2 gene in both the affected twins. According to splice prediction programs, this variant results in the creation of a cryptic donor splice site, possibly leading to a loss of function. These data support the role of the detected mutation in the ARNT2 gene in causing the described phenotype.

The role of Record of Rights (Khatian) in determining title or possession: An overview

IIUC Studies ◽  
2020 ◽  
Vol 15 ◽  
pp. 33-46
Author(s):  
Kalim Ullah
Keyword(s):  
Human Life ◽  
Vital Role ◽  
Critical Element ◽  
Human Beings ◽  
Supportive Evidence ◽  
Land Administration ◽  
Holy Quran ◽  
The Holy Quran ◽  
Religious Systems

Human beings are deeply related to land. Human beings take birth on land, live on land, die on land and mixes with land ultimately. As stated in the holy Quran: ‘We (Allah) created you (human beings) from the soil, we shall make you return to the soil and We shall call you back again from the soil’ (20:55). Human life is surrounded by soil i.e. land. So, land is a highly completed issue of human life involving economic, social, political, cultural and often religious systems. Land administration is thus a critical element and often a pre-condition for peaceful society and sustainable development. In administrating land, Khatian or record of rights plays a vital role to determine the rights and interests of the respective parties as supportive evidence. In this article, discussion is mainly made on the fact that Khatian or record of rights is not a document of title solely but it may be an evidence of title as well as possession. IIUC Studies Vol.15(0) December 2018: 33-46

Solidarity and Social Justice in the European Union Seventy Years after the Universal Declaration of Human Rights: The Role of European Judges

2019 ◽  
Vol 76 (3-4) ◽  
pp. 138-148
Author(s):  
Francesco Zammartino
Keyword(s):  
Human Rights ◽  
Universal Declaration ◽  
Social Progress ◽  
Economic Policies ◽  
International Level ◽  
The European Union ◽  
Human Beings ◽  
Government Programs ◽  
Binding Force

Seventy Years after its proclamation, the Universal Declaration of Human Rights, despite not having a binding force for the states, still provides at international level the fundamental text from which the principles and the values for the preservation of liberty and right of people are taken. In this article, the author particularly underlines the importance of Declaration’s article 1, which states: “All human beings are born free and equal in dignity and rights”. With these words the Declaration presses states to undertake economic policies aimed at achieving economic and social progress for all individuals. Unfortunately, we also have to underline the lack of effective social policies in government programs of the E.U. Member States. The author inquires whether it is left to European judges to affirm the importance of social welfare.

Do conhecimento objetivo ao problema corpo - mente

2018 ◽  
Vol 10 (2) ◽  
pp. 85-113
Author(s):  
Nathalia Gleyce dos Santos Salazar
Keyword(s):  
Third World ◽  
Sao Paulo ◽  
Karl Popper ◽  
São Paulo ◽  
Human Beings ◽  
The Third ◽  
Belo Horizonte ◽  
The Third World ◽  
The Mind

Resumo:  Apresenta-se uma discussão sobre o conhecimento e a tese dos três mundos no qual a interação entre estes nos aproxima da verdade do problema corpo-mente, tendo em vista, uma nova proposta de solução. O terceiro mundo é uma peça importante neste trabalho; sendo assim, analisaremos o que Popper designa como Mundo 3, em que ele consiste e o papel da linguagem como diferencial do ser humano. Apresentamos as críticas popperianas às correntes monistas e dualistas, ousando fazer uma crítica a Teoria do Conhecimento tradicional. Desta forma, a proposta apresentada por este filósofo da ciência diferencia-se de tudo que estava sendo feito até então, por isso, o interesse de apresentar essa abordagem pouco trabalhada de Popper. Palavras-chave: Conhecimento. Corpo-Mente. Mundo 3.Abstract: In this work, we present a discussion about knowledge and the theory of the three worlds in which the interaction between them approaches to the truth of the mind-body problem, in view of a proposed solution. The third world is an important piece in this work. Therefore, we will analyze what Popper describes as World 3, what it is and the role of language as a differential of human beings. We present Popper’s criticisms to the monistic and dualistic currents, daring to criticize the theory of traditional knowledge. Thus, the proposal of science presented by this philosopher differs from everything that was being done until then. This explains the interest in presenting this unusual approach to Popper.Keywords: Knowledge. Body-Mind.  World 3. REFERÊNCIASLEAL-TOLEDO, Gustavo . Popper e seu Cérebro. Revista da Faculdade de Letras. Série Filosofia, v. XXIII, p. 59-68, 2007.POPPER, Karl Raimund. A Lógica da Pesquisa Científica. Tradução de Leonidas Hegenberg e Octanny Silveira de Mota.  São Paulo: editora Cultrix. 2007.POPPER, Karl Raimund. Conhecimento Objetivo: uma abordagem evolucionária. Tradução de Milton Amado.  Belo Horizonte, Ed. Itatiaia Ilimitada. São Paulo, Ed. Da Universidade São Paulo, 1975._______.  O Conhecimento e o Problema Corpo –Mente. Tradução Joaquim Alberto Ferreira Gomes. Lisboa, Ed. 70. 1996.   _______. Conjecturas e Refutações: o desenvolvimento do conhecimento científico. Trad. Benedita Bettencourt. Ed. Livraria Almedina, 2006._______.  O Eu e Seu Cérebro. Karl Popper, Jonh C. Eccles;Tradução Silvio Meneses Garcia, Helena Cristina F. Arantes e Aurélio Osmar C. de Oliveira. – Campinas, SP: Papirus; Brasília, DF: Editora Universidade de Brasília. 1991.   _______. O Racionalismo Crítico na Política. Tradução de Maria da Conceição Côrte – Real. Brasília, Editora Universidade de Brasília, 2ª edição, 1994, 74p.SEARLE, John R. La construcción de la realidad social. Trad. Antoni Domènech. Barcelona: Paidós Ibérico, 1995.  

Joseph Ḥazzāyā. Book of the Chapters on Knowledge (Newfound Fragments)

2019 ◽  
pp. 15-51
Author(s):  
Максим Глебович Калинин
Keyword(s):  
Russian Translation ◽  
Mystical Experience ◽  
Original Text ◽  
Human Beings ◽  
Mystical Tradition

Продолжая публиковать оригинальный текст и русский перевод новонайденных фрагментов «Книги глав о ведении» Иосифа Хаззайи (VIII в.), одного из ярчайших представителей восточносирийской мистической традиции, предлагаем вниманию читателей главы 75-162 из фрагмента, представленного восточносирийской рукописью Paris. syr. 434. Эти главы включают в себя комментарий Иосифа Хаззайи на видение Иезекииля, другие экзегетические пассажи, изречения о смирении и любви, описания мистического опыта и пространное рассуждение о роли ангелов в жизни человечества. We proceed to publish the original text and Russian translation of the newly discovered fragments of «Book of the Chapters on Knowledge» of Joseph Ḥazzāyā (8th c.), one of the brightest representatives of the East Syriac mystical tradition. Now the readers are offered the original text and Russian translation of chapters 75-162 from the fragment of Joseph Ḥazzāyā’s work known from the East Syriac manuscript Paris. syr. 434. These chapters include the commentary of Joseph Ḥazzāyā on Ezekiel’s vision, another exegetical passages, sayings on humility and love, various descriptions of mystical experience, and a lengthy discourse on the role of angels in the life of human beings.

Virome and Inflammasomes, a Finely Tuned Balance with Important Consequences for the Host Health

2019 ◽  
Vol 26 (6) ◽  
pp. 1027-1044 ◽  
Author(s):  
Giulia Freer ◽  
Fabrizio Maggi ◽  
Mauro Pistello
Keyword(s):  
Immune System ◽  
Human Beings ◽  
Review Of The Literature ◽  
Adaptive Immune ◽  
Downstream Effects ◽  
Host Health ◽  
Inflammatory Processes ◽  
Human Immune ◽  
Immune Defences

Background:The virome is a network of viruses normally inhabiting humans. It forms a conspicuous portion of the so-called microbiome, once generically referred to as resident flora. Indeed, viruses infecting humans without leading to clinical disease are increasingly recognized as part of the microbiome and have an impact on the development of our immune system. In addition, they activate inflammasomes, multiprotein complexes that assemble in cells and that are responsible for the downstream effects of sensing pathogens.Objective:This review aims at summarizing the evidence on the role of the virome in modulating inflammation and emphasizes evidence for Anelloviruses as useful molecular markers to monitor inflammatory processes and immune system competence.Method:We carried out a review of the literature published in the last 5 years and summarized older literature to take into account ground-breaking discoveries concerning inflammasome assembly and virome.Results:A massive amount of data recently emerging demonstrate that the microbiome closely reflects what we eat, and many other unexpected variables. Composition, location, and amount of the microbiome have an impact on innate and adaptive immune defences. Viruses making up the virome contribute to shaping the immune system. Anelloviruses, the best known of such viruses, are present in most human beings, persistently without causing apparent disease. Depending on their interplay with such viruses, inflammasomes instruct host defences to tolerate or forfeit a specific microorganism.Conclusion:The virome plays an important role in shaping human immune defences and contributes to inflammatory processes by quenching or increasing them.

Moral Formation in Christ, the Beautiful Beloved

2017 ◽  
Author(s):  
Sarah Stewart-Kroeker
Keyword(s):  
Holy Spirit ◽  
Human Beings ◽  
Moral Formation ◽  
Way Of Life ◽  
The Holy Spirit ◽  
In Christ ◽  
Loving Relationship ◽  
Falling In Love

Christ’s healing of humanity consists, crucially, in forming human beings for loving relationship with himself and others. In this respect, Christ also takes the role of the beautiful beloved. Believers become pilgrims by falling in love with the beautiful Christ by the initiative of the Holy Spirit, who cleanses their eyes to see him as beautiful and enkindles desire in their hearts. By desiring and loving the beautiful Christ, the believer is conformed to him and learns to walk his path. Desiring the beautiful Christ forms a believing community shaped aesthetically and morally for a particular way of life: pilgrimage to the heavenly homeland. Formation is both earthly and eschatological, for so too is the journey and the activity of the pilgrim.

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