Kinetic and dynamical properties of truncated hemoglobins of the Antarctic bacterium Pseudoalteromonas haloplanktis TAC125.

Due to the low temperature, the Antarctic marine environment is challenging for protein functioning. Cold-adapted organisms have evolved proteins endowed with higher flexibility and lower stability in comparison to their thermophilic homologs, resulting in enhanced reaction rates at low temperatures. The Antarctic bacterium Pseudoalteromonas haloplanktis TAC125 (PhTAC125) genome is one of the few examples of coexistence of multiple hemoglobin genes encoding, among others, two constitutively transcribed 2/2 hemoglobins (2/2Hbs), also named truncated Hbs (TrHbs), belonging to the Group II (or O), annotated as PSHAa0030 and PSHAa2217. In this work, we describe the ligand binding kinetics and their interrelationship with the dynamical properties of globin Ph-2/2HbO-2217 by combining experimental and computational approaches and implementing a new computational method to retrieve information from molecular dynamic trajectories. We show that our approach allows us to identify docking sites within the protein matrix that are potentially able to transiently accommodate ligands and migration pathways connecting them. Consistently with ligand rebinding studies, our modeling suggests that the distal heme pocket is connected to the solvent through a low energy barrier, while inner cavities play only a minor role in modulating rebinding kinetics.

Thalassemia, a human blood disorder / Talassemia, uma doença do sangue humano

A group of inherited blood defects is known as Thalassemia is among the world's most prevalent hemoglobinopathies. Thalassemias are of two types such as Alpha and Beta Thalassemia. The cause of these defects is gene mutations leading to low levels and/or malfunctioning α and β globin proteins, respectively. In some cases, one of these proteins may be completely absent. α and β globin chains form a globin fold or pocket for heme (Fe++) attachment to carry oxygen. Genes for alpha and beta-globin proteins are present in the form of a cluster on chromosome 16 and 11, respectively. Different globin genes are used at different stages in the life course. During embryonic and fetal developmental stages, γ globin proteins partner with α globin and are later replaced by β globin protein. Globin chain imbalances result in hemolysis and impede erythropoiesis. Individuals showing mild symptoms include carriers of alpha thalassemia or the people bearing alpha or beta-thalassemia trait. Alpha thalassemia causes conditions like hemolytic anemia or fatal hydrops fetalis depending upon the severity of the disease. Beta thalassemia major results in hemolytic anemia, growth retardation, and skeletal aberrations in early childhood. Children affected by this disorder need regular blood transfusions throughout their lives. Patients that depend on blood transfusion usually develop iron overload that causes other complications in the body systems like renal or hepatic impairment therefore, thalassemias are now categorized as a syndrome. The only cure for Thalassemias would be a bone marrow transplant, or gene therapy with currently no significant success rate. A thorough understanding of the molecular basis of this syndrome may provide novel insights and ideas for its treatment, as scientists have still been unable to find a permanent cure for this deadly disease after more than 87 years since it is first described in 1925.(AU)

Um grupo de defeitos sanguíneos hereditários é conhecido como talassemia e está entre as hemoglobinopatias mais prevalentes do mundo. As talassemias são de dois tipos, como talassemia alfa e beta. As causas desses defeitos são as mutações genéticas que levam a níveis baixos e/ou proteínas de globina com mau funcionamento, respectivamente. Em alguns casos, uma dessas proteínas pode estar completamente ausente. As cadeias de globina α e β formam uma dobra ou bolsa de globina para a fixação de heme (Fe ++) para transportar oxigênio. Os genes das proteínas alfa e beta globina estão presentes na forma de um cluster nos cromossomos 16 e 11, respectivamente. Diferentes genes de globina são usados em diferentes estágios do curso de vida. Durante os estágios de desenvolvimento embrionário e fetal, as proteínas γ globina se associam à α globina e, posteriormente, são substituídas pela proteína β globina. Os desequilíbrios da cadeia de globina resultam em hemólise e impedem a eritropoiese. Indivíduos que apresentam sintomas leves incluem portadores de talassemia alfa ou as pessoas com traços de talassemia alfa ou beta. A talassemia alfa causa condições como anemia hemolítica ou hidropsia fetal fatal, dependendo da gravidade da doença. A beta talassemia principal resulta em anemia hemolítica, retardo de crescimento e aberrações esqueléticas na primeira infância. As crianças afetadas por esse distúrbio precisam de transfusões de sangue regulares ao longo da vida. Os pacientes que dependem de transfusão de sangue geralmente desenvolvem sobrecarga de ferro que causa outras complicações nos sistemas do corpo, como insuficiência renal ou hepática, portanto as talassemias agora são classificadas como uma síndrome. A única cura para as talassemias seria um transplante de medula óssea ou terapia genética sem atualmente uma taxa de sucesso significativa. Uma compreensão completa da base molecular dessa síndrome pode fornecer novos insights e ideias para seu tratamento, [...].(AU)

Thalassemia, a human blood disorder / Talassemia, uma doença do sangue humano

Abstract A group of inherited blood defects is known as Thalassemia is among the world's most prevalent hemoglobinopathies. Thalassemias are of two types such as Alpha and Beta Thalassemia. The cause of these defects is gene mutations leading to low levels and/or malfunctioning α and β globin proteins, respectively. In some cases, one of these proteins may be completely absent. α and β globin chains form a globin fold or pocket for heme (Fe++) attachment to carry oxygen. Genes for alpha and beta-globin proteins are present in the form of a cluster on chromosome 16 and 11, respectively. Different globin genes are used at different stages in the life course. During embryonic and fetal developmental stages, γ globin proteins partner with α globin and are later replaced by β globin protein. Globin chain imbalances result in hemolysis and impede erythropoiesis. Individuals showing mild symptoms include carriers of alpha thalassemia or the people bearing alpha or beta-thalassemia trait. Alpha thalassemia causes conditions like hemolytic anemia or fatal hydrops fetalis depending upon the severity of the disease. Beta thalassemia major results in hemolytic anemia, growth retardation, and skeletal aberrations in early childhood. Children affected by this disorder need regular blood transfusions throughout their lives. Patients that depend on blood transfusion usually develop iron overload that causes other complications in the body systems like renal or hepatic impairment therefore, thalassemias are now categorized as a syndrome. The only cure for Thalassemias would be a bone marrow transplant, or gene therapy with currently no significant success rate. A thorough understanding of the molecular basis of this syndrome may provide novel insights and ideas for its treatment, as scientists have still been unable to find a permanent cure for this deadly disease after more than 87 years since it is first described in 1925.

Resumo Um grupo de defeitos sanguíneos hereditários é conhecido como talassemia e está entre as hemoglobinopatias mais prevalentes do mundo. As talassemias são de dois tipos, como talassemia alfa e beta. As causas desses defeitos são as mutações genéticas que levam a níveis baixos e/ou proteínas de globina com mau funcionamento, respectivamente. Em alguns casos, uma dessas proteínas pode estar completamente ausente. As cadeias de globina α e β formam uma dobra ou bolsa de globina para a fixação de heme (Fe ++) para transportar oxigênio. Os genes das proteínas alfa e beta globina estão presentes na forma de um cluster nos cromossomos 16 e 11, respectivamente. Diferentes genes de globina são usados ​​em diferentes estágios do curso de vida. Durante os estágios de desenvolvimento embrionário e fetal, as proteínas γ globina se associam à α globina e, posteriormente, são substituídas pela proteína β globina. Os desequilíbrios da cadeia de globina resultam em hemólise e impedem a eritropoiese. Indivíduos que apresentam sintomas leves incluem portadores de talassemia alfa ou as pessoas com traços de talassemia alfa ou beta. A talassemia alfa causa condições como anemia hemolítica ou hidropsia fetal fatal, dependendo da gravidade da doença. A beta talassemia principal resulta em anemia hemolítica, retardo de crescimento e aberrações esqueléticas na primeira infância. As crianças afetadas por esse distúrbio precisam de transfusões de sangue regulares ao longo da vida. Os pacientes que dependem de transfusão de sangue geralmente desenvolvem sobrecarga de ferro que causa outras complicações nos sistemas do corpo, como insuficiência renal ou hepática, portanto as talassemias agora são classificadas como uma síndrome. A única cura para as talassemias seria um transplante de medula óssea ou terapia genética sem atualmente uma taxa de sucesso significativa. Uma compreensão completa da base molecular dessa síndrome pode fornecer novos insights e ideias para seu tratamento, já que os cientistas ainda não conseguiram encontrar uma cura permanente para essa doença mortal depois de mais de 87 anos desde que foi descrita pela primeira vez em 1925.

Thalassemia, a human blood disorder / Talassemia, uma doença do sangue humano

A group of inherited blood defects is known as Thalassemia is among the world's most prevalent hemoglobinopathies. Thalassemias are of two types such as Alpha and Beta Thalassemia. The cause of these defects is gene mutations leading to low levels and/or malfunctioning α and β globin proteins, respectively. In some cases, one of these proteins may be completely absent. α and β globin chains form a globin fold or pocket for heme (Fe++) attachment to carry oxygen. Genes for alpha and beta-globin proteins are present in the form of a cluster on chromosome 16 and 11, respectively. Different globin genes are used at different stages in the life course. During embryonic and fetal developmental stages, γ globin proteins partner with α globin and are later replaced by β globin protein. Globin chain imbalances result in hemolysis and impede erythropoiesis. Individuals showing mild symptoms include carriers of alpha thalassemia or the people bearing alpha or beta-thalassemia trait. Alpha thalassemia causes conditions like hemolytic anemia or fatal hydrops fetalis depending upon the severity of the disease. Beta thalassemia major results in hemolytic anemia, growth retardation, and skeletal aberrations in early childhood. Children affected by this disorder need regular blood transfusions throughout their lives. Patients that depend on blood transfusion usually develop iron overload that causes other complications in the body systems like renal or hepatic impairment therefore, thalassemias are now categorized as a syndrome. The only cure for Thalassemias would be a bone marrow transplant, or gene therapy with currently no significant success rate. A thorough understanding of the molecular basis of this syndrome may provide novel insights and ideas for its treatment, as scientists have still been unable to find a permanent cure for this deadly disease after more than 87 years since it is first described in 1925.

Um grupo de defeitos sanguíneos hereditários é conhecido como talassemia e está entre as hemoglobinopatias mais prevalentes do mundo. As talassemias são de dois tipos, como talassemia alfa e beta. As causas desses defeitos são as mutações genéticas que levam a níveis baixos e/ou proteínas de globina com mau funcionamento, respectivamente. Em alguns casos, uma dessas proteínas pode estar completamente ausente. As cadeias de globina α e β formam uma dobra ou bolsa de globina para a fixação de heme (Fe ++) para transportar oxigênio. Os genes das proteínas alfa e beta globina estão presentes na forma de um cluster nos cromossomos 16 e 11, respectivamente. Diferentes genes de globina são usados em diferentes estágios do curso de vida. Durante os estágios de desenvolvimento embrionário e fetal, as proteínas γ globina se associam à α globina e, posteriormente, são substituídas pela proteína β globina. Os desequilíbrios da cadeia de globina resultam em hemólise e impedem a eritropoiese. Indivíduos que apresentam sintomas leves incluem portadores de talassemia alfa ou as pessoas com traços de talassemia alfa ou beta. A talassemia alfa causa condições como anemia hemolítica ou hidropsia fetal fatal, dependendo da gravidade da doença. A beta talassemia principal resulta em anemia hemolítica, retardo de crescimento e aberrações esqueléticas na primeira infância. As crianças afetadas por esse distúrbio precisam de transfusões de sangue regulares ao longo da vida. Os pacientes que dependem de transfusão de sangue geralmente desenvolvem sobrecarga de ferro que causa outras complicações nos sistemas do corpo, como insuficiência renal ou hepática, portanto as talassemias agora são classificadas como uma síndrome. A única cura para as talassemias seria um transplante de medula óssea ou terapia genética sem atualmente uma taxa de sucesso significativa. Uma compreensão completa da base molecular dessa síndrome pode fornecer novos insights e ideias para seu tratamento, [...].

Thalassemia, a human blood disorder

Abstract A group of inherited blood defects is known as Thalassemia is among the worlds most prevalent hemoglobinopathies. Thalassemias are of two types such as Alpha and Beta Thalassemia. The cause of these defects is gene mutations leading to low levels and/or malfunctioning and globin proteins, respectively. In some cases, one of these proteins may be completely absent. and globin chains form a globin fold or pocket for heme (Fe++) attachment to carry oxygen. Genes for alpha and beta-globin proteins are present in the form of a cluster on chromosome 16 and 11, respectively. Different globin genes are used at different stages in the life course. During embryonic and fetal developmental stages, globin proteins partner with globin and are later replaced by globin protein. Globin chain imbalances result in hemolysis and impede erythropoiesis. Individuals showing mild symptoms include carriers of alpha thalassemia or the people bearing alpha or beta-thalassemia trait. Alpha thalassemia causes conditions like hemolytic anemia or fatal hydrops fetalis depending upon the severity of the disease. Beta thalassemia major results in hemolytic anemia, growth retardation, and skeletal aberrations in early childhood. Children affected by this disorder need regular blood transfusions throughout their lives. Patients that depend on blood transfusion usually develop iron overload that causes other complications in the body systems like renal or hepatic impairment therefore, thalassemias are now categorized as a syndrome. The only cure for Thalassemias would be a bone marrow transplant, or gene therapy with currently no significant success rate. A thorough understanding of the molecular basis of this syndrome may provide novel insights and ideas for its treatment, as scientists have still been unable to find a permanent cure for this deadly disease after more than 87 years since it is first described in 1925.

Resumo Um grupo de defeitos sanguíneos hereditários é conhecido como talassemia e está entre as hemoglobinopatias mais prevalentes do mundo. As talassemias são de dois tipos, como talassemia alfa e beta. As causas desses defeitos são as mutações genéticas que levam a níveis baixos e/ou proteínas de globina com mau funcionamento, respectivamente. Em alguns casos, uma dessas proteínas pode estar completamente ausente. As cadeias de globina e formam uma dobra ou bolsa de globina para a fixação de heme (Fe ++) para transportar oxigênio. Os genes das proteínas alfa e beta globina estão presentes na forma de um cluster nos cromossomos 16 e 11, respectivamente. Diferentes genes de globina são usados em diferentes estágios do curso de vida. Durante os estágios de desenvolvimento embrionário e fetal, as proteínas globina se associam à globina e, posteriormente, são substituídas pela proteína globina. Os desequilíbrios da cadeia de globina resultam em hemólise e impedem a eritropoiese. Indivíduos que apresentam sintomas leves incluem portadores de talassemia alfa ou as pessoas com traços de talassemia alfa ou beta. A talassemia alfa causa condições como anemia hemolítica ou hidropsia fetal fatal, dependendo da gravidade da doença. A beta talassemia principal resulta em anemia hemolítica, retardo de crescimento e aberrações esqueléticas na primeira infância. As crianças afetadas por esse distúrbio precisam de transfusões de sangue regulares ao longo da vida. Os pacientes que dependem de transfusão de sangue geralmente desenvolvem sobrecarga de ferro que causa outras complicações nos sistemas do corpo, como insuficiência renal ou hepática, portanto as talassemias agora são classificadas como uma síndrome. A única cura para as talassemias seria um transplante de medula óssea ou terapia genética sem atualmente uma taxa de sucesso significativa. Uma compreensão completa da base molecular dessa síndrome pode fornecer novos insights e ideias para seu tratamento, já que os cientistas ainda não conseguiram encontrar uma cura permanente para essa doença mortal depois de mais de 87 anos desde que foi descrita pela primeira vez em 1925.

Phenotypic variation in sickle cell disease: the role of beta globin haplotype, alpha thalassemia, and fetal hemoglobin in HbSS.

INTRODUCTION: The hematological and clinical features vary markedly between the different genotypes of sickle cell disease. Even within the single genotype of homozygous sickle cell disease (HbSS), there is marked variability that is presumed to result from interacting genetic and environmental factors. AREAS COVERED: The classification of the different genotypes of sickle cell disease with approximate prevalence at birth in different communities and some of the major clinical and hematological differences. This assessment includes three potential genetic factors influencing hematology and clinical outcome in HbSS, the beta globin haplotype, alpha thalassemia, and persistence of fetal hemoglobin (HbF). EXPERT OPINION: The author is a clinician with experience of sickle cell disease primarily in Jamaica but also in Greece, Uganda, Saudi Arabia, and India. It is therefore necessarily an account of clinical data and does not address current debates on molecular mechanisms. Most data derive from Jamaica where efforts have been made to reduce any symptomatic bias by long-term follow-up of patients all over the Island and further reduced by a cohort study based on newborn screening, which has been in operation for over 48 years.

Evolutionary History of the Globin Gene Family in Annelids.

Animals depend on the sequential oxidation of organic molecules to survive; thus, oxygen-carrying/transporting proteins play a fundamental role in aerobic metabolism. Globins are the most common and widespread group of respiratory proteins. They can be divided into three types: circulating intracellular, noncirculating intracellular, and extracellular, all of which have been reported in annelids. The diversity of oxygen transport proteins has been underestimated across metazoans. We probed 250 annelid transcriptomes in search of globin diversity in order to elucidate the evolutionary history of this gene family within this phylum. We report two new globin types in annelids, namely androglobins and cytoglobins. Although cytoglobins and myoglobins from vertebrates and from invertebrates are referred to by the same name, our data show they are not genuine orthologs. Our phylogenetic analyses show that extracellular globins from annelids are more closely related to extracellular globins from other metazoans than to the intracellular globins of annelids. Broadly, our findings indicate that multiple gene duplication and neo-functionalization events shaped the evolutionary history of the globin family.

Synthesis and evaluation of resveratrol derivatives as fetal hemoglobin inducers.

Resveratrol (RVT) derivatives (10a-i) were designed, synthesized, and evaluated for their potential as gamma-globin inducers in treating Sickle Cell Disease (SCD) symptoms. All compounds were able to release NO at different levels ranging from 0 to 26.3%, while RVT did not demonstrate this effect. In vivo, the antinociceptive effect was characterized using an acetic acid-induced abdominal contortion model. All compounds exhibited different levels of protection, ranging from 5.9 to 37.3%; the compound 10a was the most potent among the series. At concentrations between 3.13 and 12.5 µM, the derivative 10a resulted in a reduction of 41.1-64.3% in the TNF-α levels in the supernatants of macrophages that were previously LPS-stimulated. This inhibitory effect was higher than that of RVT used as the control. In addition, the compound 10a and RVT induced double the production of the gamma-globin chains (γG + Î³A), compared to the vehicle, using CD34+ cells. Compound 10a also did not induce membrane perturbation and it was not mutagenic in the in vivo assay. Thus, compound 10a emerged as a new prototype of the gamma-globin-inducer group with additional analgesic and anti-inflammatory activities and proving to be a useful alternative to treat SCD symptoms.

Dioxygen Binding and Sensing Proteins.

Oxygen binding proteins (O2BIP) have been actively investigated for the past five decades due to their rich redox chemistry and function as O2 carriers in blood cells, as well as their function as gasotransmitters and sensors that modulate cellular signaling. A series of meetings on the periodic advances in the knowledge gained in the field of globin structure and function are conducted typically on a biannual basis. In the fall of 2018, the XXth International Conference was conducted, and very important articles with breakthrough discoveries were presented and very enthusiastically discussed. This was yet another highly successful meeting in the series. Select articles from this meeting were recently reviewed, updated, and published over several issues of Antioxidants and Redox Signaling, as Forum articles communicating the latest advances in this important area of redox biology. This Forum editorial introduces these articles and highlights their scientific significance in advancing the field. Each of these articles grew out of lectures presented in the meeting, and appears either as an original contribution or a comprehensive review in the journal. Overall, the articles published in the Forum provide in-depth details on the recent developments in the field as well as point the way to future directions. These Forum articles thus serve as an important summary of progress and the ongoing direction of this field, and serve to highlight recent advances in our understanding of O2BIP.

To boldly go: on invasive goblin spiders in Brazil (Araneae, Oonopidae)

Twelve non-native species of the spider family Oonopidae are recorded in Brazil: Brignolia dasysterna Platnick, Dupérré, Ott & Kranz-Baltensperger, 2011, B. parumpunctata (Simon, 1893), Triaeris stenaspis Simon, 1892, Ischnothyreus peltifer (Simon, 1892), I. velox Jackson, 1908, Opopaea concolor (Blackwall, 1859), O. deserticola Simon, 1892, Pelicinus marmoratus Simon, 1892, Heteroonops spinimanus (Simon, 1892), Gamasomorpha parmata (Thorell, 1890) (herein restored to its original combination in Xestaspis), Orchestina pavesiiformis Saaristo, 2007 and O. dentifera (Simon, 1893). Among these species, six new synonyms were detected: Hytanis oblonga Simon, 1893, Xestaspis bipeltis Thorell, 1895, Gamasomorpha insularis Simon, 1907 and Opopaea lutzi Petrunkevitch, 1929 with Xestaspis parmata Thorell, 1890; Gammasomorpha humilis Mello-Leitão, 1920 with Opopaea concolor (Blackwall, 1859) and Gamasomorpha rufa Banks, 1898 with Opopaea deserticola Simon, 1891. Since Hytanis oblonga is the type species of the genus, its synonymy with Xestaspis parmata imply in the synonymy of Hytanis Simon, 1893 with Xestaspis Simon, 1884. The partenogenetic species T. stenaspis is the most distributed synanthropic oonopid in Brazil, occurring all over the country, mainly in urban areas. Some species are reported here to occur in the interior of natural caves, a finding that should raise conservation concerns.

Doze aranhas consideradas não-nativas da família Oonopidae são registradas em áreas urbanas no Brasil: Brignolia dasysterna Platnick, Dupérré, Ott & Kranz-Baltensperger, 2011, B. parumpunctata (Simon, 1893), Triaeris stenaspis Simon, 1892, Ischnothyreus peltifer (Simon, 1892), I. velox Jackson, 1908, Opopaea concolor (Blackwall, 1859), O. deserticola Simon, 1892, Pelicinus marmoratus Simon, 1892, Heteroonops spinimanus (Simon, 1892), Gamasomorpha parmata (Thorell, 1890) (aqui restaurada para sua combinação original em Xestaspis), Orchestina pavesiiformis Saaristo, 2007 and O. dentifera (Simon, 1893). Entre estas espécies, seis novos sinônimos foram detectados: Hytanis oblonga Simon, 1893, Xestaspis bipeltis Thorell, 1895, Gamasomorpha insularis Simon, 1907 e Opopaea lutzi Petrunkevitch, 1929 com Xestaspis parmata Thorell, 1890; Gammasomorpha humilis Mello-Leitão, 1920 com Opopaea concolor (Blackwall, 1859) e Gamasomorpha rufa Banks, 1898 with Opopaea deserticola Simon, 1891. Uma vez que Hytanis oblonga é a espécie-tipo do gênero, sua sinonímia com Xestaspis parmata implica na sinonímia de Hytanis Simon, 1893 com Xestaspis Simon, 1884. Triaeris stenaspis, uma espécie partenogenética, é o oonopídeo sinantrópico com distribuição mais ampla no Brasil, ocorrendo de norte a sul do país, principalmente em áreas urbanas. Algumas espécies relatadas aqui ocorrem no interior de cavernas naturais, uma descoberta que deve levantar preocupações em relação à conservação das espécies nativas de cavernas.

To boldly go: on invasive goblin spiders in Brazil (Araneae, Oonopidae)

ABSTRACT Twelve non-native species of the spider family Oonopidae are recorded in Brazil: Brignolia dasysterna Platnick, Dupérré, Ott & Kranz-Baltensperger, 2011, B. parumpunctata (Simon, 1893), Triaeris stenaspis Simon, 1892, Ischnothyreus peltifer (Simon, 1892), I. velox Jackson, 1908, Opopaea concolor (Blackwall, 1859), O. deserticola Simon, 1892, Pelicinus marmoratus Simon, 1892, Heteroonops spinimanus (Simon, 1892), Gamasomorpha parmata (Thorell, 1890) (herein restored to its original combination in Xestaspis), Orchestina pavesiiformis Saaristo, 2007 and O. dentifera (Simon, 1893). Among these species, six new synonyms were detected: Hytanis oblonga Simon, 1893, Xestaspis bipeltis Thorell, 1895, Gamasomorpha insularis Simon, 1907 and Opopaea lutzi Petrunkevitch, 1929 with Xestaspis parmata Thorell, 1890; Gammasomorpha humilis Mello-Leitão, 1920 with Opopaea concolor (Blackwall, 1859) and Gamasomorpha rufa Banks, 1898 with Opopaea deserticola Simon, 1891. Since Hytanis oblonga is the type species of the genus, its synonymy with Xestaspis parmata imply in the synonymy of Hytanis Simon, 1893 with Xestaspis Simon, 1884. The partenogenetic species T. stenaspis is the most distributed synanthropic oonopid in Brazil, occurring all over the country, mainly in urban areas. Some species are reported here to occur in the interior of natural caves, a finding that should raise conservation concerns.

RESUMO Doze aranhas consideradas não-nativas da família Oonopidae são registradas em áreas urbanas no Brasil: Brignolia dasysterna Platnick, Dupérré, Ott & Kranz-Baltensperger, 2011, B. parumpunctata (Simon, 1893), Triaeris stenaspis Simon, 1892, Ischnothyreus peltifer (Simon, 1892), I. velox Jackson, 1908, Opopaea concolor (Blackwall, 1859), O. deserticola Simon, 1892, Pelicinus marmoratus Simon, 1892, Heteroonops spinimanus (Simon, 1892), Gamasomorpha parmata (Thorell, 1890) (aqui restaurada para sua combinação original em Xestaspis), Orchestina pavesiiformis Saaristo, 2007 and O. dentifera (Simon, 1893). Entre estas espécies, seis novos sinônimos foram detectados: Hytanis oblonga Simon, 1893, Xestaspis bipeltis Thorell, 1895, Gamasomorpha insularis Simon, 1907 e Opopaea lutzi Petrunkevitch, 1929 com Xestaspis parmata Thorell, 1890; Gammasomorpha humilis Mello-Leitão, 1920 com Opopaea concolor (Blackwall, 1859) e Gamasomorpha rufa Banks, 1898 with Opopaea deserticola Simon, 1891. Uma vez que Hytanis oblonga é a espécie-tipo do gênero, sua sinonímia com Xestaspis parmata implica na sinonímia de Hytanis Simon, 1893 com Xestaspis Simon, 1884. Triaeris stenaspis, uma espécie partenogenética, é o oonopídeo sinantrópico com distribuição mais ampla no Brasil, ocorrendo de norte a sul do país, principalmente em áreas urbanas. Algumas espécies relatadas aqui ocorrem no interior de cavernas naturais, uma descoberta que deve levantar preocupações em relação à conservação das espécies nativas de cavernas.

To boldly go: on invasive goblin spiders in Brazil (Araneae, Oonopidae)

Twelve non-native species of the spider family Oonopidae are recorded in Brazil: Brignolia dasysterna Platnick, Dupérré, Ott & Kranz-Baltensperger, 2011, B. parumpunctata (Simon, 1893), Triaeris stenaspis Simon, 1892, Ischnothyreus peltifer (Simon, 1892), I. velox Jackson, 1908, Opopaea concolor (Blackwall, 1859), O. deserticola Simon, 1892, Pelicinus marmoratus Simon, 1892, Heteroonops spinimanus (Simon, 1892), Gamasomorpha parmata (Thorell, 1890) (herein restored to its original combination in Xestaspis), Orchestina pavesiiformis Saaristo, 2007 and O. dentifera (Simon, 1893). Among these species, six new synonyms were detected: Hytanis oblonga Simon, 1893, Xestaspis bipeltis Thorell, 1895, Gamasomorpha insularis Simon, 1907 and Opopaea lutzi Petrunkevitch, 1929 with Xestaspis parmata Thorell, 1890; Gammasomorpha humilis Mello-Leitão, 1920 with Opopaea concolor (Blackwall, 1859) and Gamasomorpha rufa Banks, 1898 with Opopaea deserticola Simon, 1891. Since Hytanis oblonga is the type species of the genus, its synonymy with Xestaspis parmata imply in the synonymy of Hytanis Simon, 1893 with Xestaspis Simon, 1884. The partenogenetic species T. stenaspis is the most distributed synanthropic oonopid in Brazil, occurring all over the country, mainly in urban areas. Some species are reported here to occur in the interior of natural caves, a finding that should raise conservation concerns.(AU)

Doze aranhas consideradas não-nativas da família Oonopidae são registradas em áreas urbanas no Brasil: Brignolia dasysterna Platnick, Dupérré, Ott & Kranz-Baltensperger, 2011, B. parumpunctata (Simon, 1893), Triaeris stenaspis Simon, 1892, Ischnothyreus peltifer (Simon, 1892), I. velox Jackson, 1908, Opopaea concolor (Blackwall, 1859), O. deserticola Simon, 1892, Pelicinus marmoratus Simon, 1892, Heteroonops spinimanus (Simon, 1892), Gamasomorpha parmata (Thorell, 1890) (aqui restaurada para sua combinação original em Xestaspis), Orchestina pavesiiformis Saaristo, 2007 and O. dentifera (Simon, 1893). Entre estas espécies, seis novos sinônimos foram detectados: Hytanis oblonga Simon, 1893, Xestaspis bipeltis Thorell, 1895, Gamasomorpha insularis Simon, 1907 e Opopaea lutzi Petrunkevitch, 1929 com Xestaspis parmata Thorell, 1890; Gammasomorpha humilis Mello-Leitão, 1920 com Opopaea concolor (Blackwall, 1859) e Gamasomorpha rufa Banks, 1898 with Opopaea deserticola Simon, 1891. Uma vez que Hytanis oblonga é a espécie-tipo do gênero, sua sinonímia com Xestaspis parmata implica na sinonímia de Hytanis Simon, 1893 com Xestaspis Simon, 1884. Triaeris stenaspis, uma espécie partenogenética, é o oonopídeo sinantrópico com distribuição mais ampla no Brasil, ocorrendo de norte a sul do país, principalmente em áreas urbanas. Algumas espécies relatadas aqui ocorrem no interior de cavernas naturais, uma descoberta que deve levantar preocupações em relação à conservação das espécies nativas de cavernas.(AU)

To boldly go: on invasive goblin spiders in Brazil (Araneae, Oonopidae) / Audaciosamente indo: aranhas gnomo invasoras no Brasil (Araneae, Oonopidae)

Twelve non-native species of the spider family Oonopidae are recorded in Brazil: Brignolia dasysterna Platnick, Dupérré, Ott & Kranz-Baltensperger, 2011, B. parumpunctata (Simon, 1893), Triaeris stenaspis Simon, 1892, Ischnothyreus peltifer (Simon, 1892), I. velox Jackson, 1908, Opopaea concolor (Blackwall, 1859), O. deserticola Simon, 1892, Pelicinus marmoratus Simon, 1892, Heteroonops spinimanus (Simon, 1892), Gamasomorpha parmata (Thorell, 1890) (herein restored to its original combination in Xestaspis), Orchestina pavesiiformis Saaristo, 2007 and O. dentifera (Simon, 1893). Among these species, six new synonyms were detected: Hytanis oblonga Simon, 1893, Xestaspis bipeltis Thorell, 1895, Gamasomorpha insularis Simon, 1907 and Opopaea lutzi Petrunkevitch, 1929 with Xestaspis parmata Thorell, 1890; Gammasomorpha humilis Mello-Leitão, 1920 with Opopaea concolor (Blackwall, 1859) and Gamasomorpha rufa Banks, 1898 with Opopaea deserticola Simon, 1891. Since Hytanis oblonga is the type species of the genus, its synonymy with Xestaspis parmata imply in the synonymy of Hytanis Simon, 1893 with Xestaspis Simon, 1884. The partenogenetic species T. stenaspis is the most distributed synanthropic oonopid in Brazil, occurring all over the country, mainly in urban areas. Some species are reported here to occur in the interior of natural caves, a finding that should raise conservation concerns.

Doze aranhas consideradas não-nativas da família Oonopidae são registradas em áreas urbanas no Brasil: Brignolia dasysterna Platnick, Dupérré, Ott & Kranz-Baltensperger, 2011, B. parumpunctata (Simon, 1893), Triaeris stenaspis Simon, 1892, Ischnothyreus peltifer (Simon, 1892), I. velox Jackson, 1908, Opopaea concolor (Blackwall, 1859), O. deserticola Simon, 1892, Pelicinus marmoratus Simon, 1892, Heteroonops spinimanus (Simon, 1892), Gamasomorpha parmata (Thorell, 1890) (aqui restaurada para sua combinação original em Xestaspis), Orchestina pavesiiformis Saaristo, 2007 and O. dentifera (Simon, 1893). Entre estas espécies, seis novos sinônimos foram detectados: Hytanis oblonga Simon, 1893, Xestaspis bipeltis Thorell, 1895, Gamasomorpha insularis Simon, 1907 e Opopaea lutzi Petrunkevitch, 1929 com Xestaspis parmata Thorell, 1890; Gammasomorpha humilis Mello-Leitão, 1920 com Opopaea concolor (Blackwall, 1859) e Gamasomorpha rufa Banks, 1898 with Opopaea deserticola Simon, 1891. Uma vez que Hytanis oblonga é a espécie-tipo do gênero, sua sinonímia com Xestaspis parmata implica na sinonímia de Hytanis Simon, 1893 com Xestaspis Simon, 1884. Triaeris stenaspis, uma espécie partenogenética, é o oonopídeo sinantrópico com distribuição mais ampla no Brasil, ocorrendo de norte a sul do país, principalmente em áreas urbanas. Algumas espécies relatadas aqui ocorrem no interior de cavernas naturais, uma descoberta que deve levantar preocupações em relação à conservação das espécies nativas de cavernas.

The Chaperones Involved in Hemoglobin Synthesis Take the Spotlight: Analysis of AHSP in the Argentinean Population and Review of the Literature.

Hemoglobin (Hb) synthesis is a complex, well-coordinated process that requires molecular chaperones. These intervene in different steps: regulating epigenetic mechanisms necessary for the adequate expression of the α- and ß-globin clusters, binding the nascent peptides and helping them acquire their native structure, preventing oxidative damage by free globin chains and preventing the cleavage of essential erythroid transcription factors. This study analyzed the distribution of the single nucleotide polymorphism (SNP) rs4296276 in intron 1 of the α-globin chaperone α Hb-stabilizing protein (AHSP) in the Argentinean population. The risk allele was found in thalassemia patients who exhibited more severe phenotypes than expected. Future studies may help establish the role of these chaperones as modifiers in pathological states with globin chain imbalance, such as thalassemia.

Presence of Non-African Haplotypes Increase Genetic Diversity in Sickle Cell Anemia Patients in Colombia / Presencia de haplotipos no africanos incrementa la diversidad genética en pacientes con anemia falciforme en colombia

RESUMEN El objetivo de este estudio fue identificar la frecuencia de haplotipos dentro del cluster de Beta globina presente en pacientes con anemia falciforme en Colombia, establecer la presencia de haplotipos no africanos en esta población, así como verificar variaciones en el patrón de desequilibrio de ligamiento dentro del cluster de Beta globina. Se analizaron 83 individuos con anemia falciforme, los haplotipos se formaron utilizando cinco sitios de restricción dentro del cluster de Beta globina, se estableció la frecuencia de haplotipos, se calculó el grado de desequilibrio de ligamiento entre los sitios de restricción, así como la similitud genética de esta población con otra de afectados en América. Los haplotipos más frecuentes en la población fueron Benin (35,1 %) y Bantú (26, 5 %), ambos africanos. Sin embargo, haplotipos presentes en poblaciones indígenas americanas y europeas alcanzaron frecuencias entre el 2 - 10 %, así como haplotipos que no han sido reportados en otras poblaciones. Los sitios de restricción presentaron bajo o nulo desequilibrio de ligamiento entre ellos. Al compararse con otras poblaciones, la población colombiana presentó mayor similitud con la población de Venezuela en donde Benin y Bantú son también predominantes. Nuestros resultados muestran que el mestizaje ha facilitado el paso de la mutación para la anemia falciforme a un contexto genético no africano (amerindio y europeo). Además, el mestizaje también ha alterado el patrón de desequilibrio de ligamiento dentro del cluster de Beta globina generando modificaciones que pueden tener influencia en estudios de asociación dentro de esta población de afectados.

ABSTRACT The objective of this study was identify the frequency of Beta globin cluster's haplotypes present in sickle cell anemia patients in Colombia, to establish the presence of non-African haplotypes in this population, to verify variations in the pattern of linkage disequilibrium in the Beta globin cluster. It was analyzed 83 individuals affected with sickle cell anemia, the haplotypes were formed using five restriction sites into Beta globin cluster. The haplotype frequency was calculated, as well as the linkage disequilibrium among restriction sites, the genetic similarity among Colombian population and other affected American population was determined. The haplotypes most frequent were Benin (35.1 %) and Bantu (26.5 %), both African. However, haplotypes present in American indigenous and European populations got frequency between two to ten percent, as well as haplotypes not reported in others population were observed in our population. The restriction sites showed low or null linkage disequilibrium. When compare with other populations, the Colombian population showed higher similarity with Venezuelan population where Benin and Bantu are predominant too. Our results showed that admixture has facilitated the move of sickle cell mutation to a non-African genetic context (Amerindian and European). Further, the admixture has also modified the pattern of linkage disequilibrium into the Beta globin cluster generating modifications that could have influence in association studies in this affected population.

Evaluation of microbial globin promoters for oxygen-limited processes using Escherichia coli.

Oxygen-responsive promoters can be useful for synthetic biology applications, however, information on their characteristics is still limited. Here, we characterized a group of heterologous microaerobic globin promoters in Escherichia coli. Globin promoters from Bacillus subtilis, Campylobacter jejuni, Deinococcus radiodurans, Streptomyces coelicolor, Salmonella typhi and Vitreoscilla stercoraria were used to express the FMN-binding fluorescent protein (FbFP), which is a non-oxygen dependent marker. FbFP fluorescence was monitored online in cultures at maximum oxygen transfer capacities (OTRmax) of 7 and 11 mmol L-1 h-1. Different FbFP fluorescence intensities were observed and the OTRmax affected the induction level and specific fluorescence emission rate (the product of the specific fluorescence intensity multiplied by the specific growth rate) of all promoters. The promoter from S. typhi displayed the highest fluorescence emission yields (the quotient of the fluorescence intensity divided by the scattered light intensity at every time-point) and rate, and together with the promoters from D. radiodurans and S. coelicolor, the highest induction ratios. These results show the potential of diverse heterologous globin promoters for oxygen-limited processes using E. coli.

[Regulation of the ß-globin gene family expression, useful in the search for new therapeutic targets for hemoglobinopathies]. / Regulación de expresión de genes de la familia de ß-globina humana, útil en la búsqueda de nuevos blancos terapéuticos para tratamiento de hemoglobinopatías.

Different hemoglobin isoforms are expressed during the embryonic, fetal and postnatal stages. They are formed by combination of polypeptide chains synthesized from the α- and ß-globin gene clusters. Based on the fact that the presence of high hemoglobin F levels is beneficial in both sickle cell disease and severe thalassemic syndromes, a revision of the regulation of the ß-globin cluster expression is proposed, especially regarding the genes encoding the y-globin chains (HBG1 and HBG2). In this review we describe the current knowledge about transcription factors and epigenetic regulators involved in the switches of the ß-globin cluster. It is expected that the consolidation of knowledge in this field will allow finding new therapeutic targets for the treatment of hemoglobinopathies.

Regulación de expresión de genes de la familia de ß-globina humana, útil en la búsqueda de nuevos blancos terapéuticos para tratamiento de hemoglobinopatías / Regulation of the ß-globin gene family expression, useful in the search for new therapeutic targets for hemoglobinopathies

Durante la etapa embrionaria, el desarrollo fetal y la vida posnatal se expresan isoformas funcionalmente distintas de hemoglobina, producto de la combinación de cadenas polipeptídicas sintetizadas a partir de los distintos genes que componen las familias de α- y β-globina. En función de que la presencia de altos niveles de hemoglobina fetal (Hb F) es beneficiosa en síndromes falciformes y talasémicos graves, se plantea revisar las bases de la regulación de la expresión de los genes de la familia de β-globina, en particular los genes que codifican las cadenas de γ-globina (HBG1 y HBG2). En este trabajo se revisan los conocimientos sobre factores de transcripción y reguladores epigenéticos que gobiernan los eventos de encendido y apagado de los genes de la familia de β-globina. Se espera que la consolidación de estos conocimientos permita hallar nuevos blancos terapéuticos para el tratamiento de hemoglobinopatías.

Different hemoglobin isoforms are expressed during the embryonic, fetal and postnatal stages. They are formed by combination of polypeptide chains synthesized from the α- and β- globin gene clusters. Based on the fact that the presence of high hemoglobin F levels is beneficial in both sickle cell disease and severe thalassemic syndromes, a revision of the regulation of the β-globin cluster expression is proposed, especially regarding the genes encoding the γ-globin chains (HBG1 and HBG2). In this review we describe the current knowledge about transcription factors and epigenetic regulators involved in the switches of the β-globin cluster. It is expected that the consolidation of knowledge in this field will allow finding new therapeutic targets for the treatment of hemoglobinopathies.

Molecular analysis of complex cases of alpha- and beta-thalassemia in Mexican mestizo patients with microcytosis and hypochromia reveals two novel alpha(0) -thalassemia deletions - -(Mex1) and - -(Mex2).

INTRODUCTION: Alpha-thalassemia (α-thal) is a common monogenic disorder worldwide. In mixed ethnic populations, α-thal and beta-thalassemia (ß-thal) can be expected, sometimes giving complex phenotypes, which without molecular analysis are not easily explained. We performed the molecular identification of α- and ß-thal alleles in 51 Mexican patients with microcytosis, hypochromia, and normal or low levels of HbA2 . METHODS: Common deletional alleles (-α(3.7) , -α(4.2) , - -(SEA) , - -(MED) , - -(FIL) , - -(THAI) , -α(20.5) ) and α-triplication were studied by gap-PCR and nondeletional alleles (α(IVSI) ((-5nt)) , α2 (NcoI) , α1 (NcoI) ) by ARMS. ß-thal alleles Cd39 (C>T), IVS1:1 (G>A), IVS1:110 (G>A), and Spanish δß-thal were also investigated. DNA sequencing was performed on HBA2, HBA1, and HBB genes. Negative samples were subjected to MLPA. RESULTS: In 35 subjects, we identified the mutations, -α(3.7) , - -(SEA) , - -(FIL) , α(IVSI) ((-5nt)) , and ααα(anti3.7) and two novel deletion alleles - -(Mex1) (6.8-8.9 kb) and - -(Mex2) (77.6-135.7 kb). Four individuals also had a ß-thal allele (Cd39/IVS1:110). No α-thal alleles were observed in 16 subjects, but three had a ß-thal mutation Cd39, IVS1:110, and Spanish δß-thal. CONCLUSION: α-thal is relatively common in Mexican patients, the combination with ß-thal is sometimes unexpected, and this underlines the importance of performing molecular analysis for both α- and ß-genes defects in patients showing microcytic hypochromic anemia.