Candida guilliermondii: biotechnological applications, perspectives for biological control, emerging clinical importance and recent advances in genetics

Candida guilliermondii (teleomorph Meyerozyma guilliermondii) is an ascomycetous species belonging to the Saccharomycotina CTG clade which has been studied over the last 40 years due to its biotechnological interest, biological control potential and clinical importance. Such a wide range of applications in various areas of fundamental and applied scientific research has progressively made C. guilliermondii an attractive model for exploring the potential of yeast metabolic engineering as well as for elucidating new molecular events supporting pathogenicity and antifungal resistance. All these research fields now take advantage of the establishment of a useful molecular toolbox specifically dedicated to C. guilliermondii genetics including the construction of recipient strains, the development of selectable markers and reporter genes and optimization of transformation protocols. This area of study is further supported by the availability of the complete genome sequence of the reference strain ATCC 6260 and the creation of numerous databases dedicated to gene ontology annotation (metabolic pathways, virulence, and morphogenesis). These genetic tools and genomic resources represent essential prerequisites for further successful development of C. guilliermondii research in medical mycology and in biological control by facilitating the identification of the multiple factors that contribute to its pathogenic potential. These genetic and genomic advances should also expedite future practical uses of C. guilliermondii strains of biotechnological interest by opening a window into a better understanding of the biosynthetic pathways of valuable metabolites.     

Do reading processes differ in transparent versus opaque orthographies? A study of acquired dyslexia in Welsh/English bilinguals

In English, the relationship between the written and spoken forms of words is relatively opaque, leading to proposals that skilled reading requires two procedures: (a) a sublexical grapheme/phoneme conversion process allowing the correct reading of regular words (CAT) and new or pseudowords (ZAT); (b) a lexical process necessary to read irregular words accurately (TWO) and assumed to be the dominant process for familiar words. However, it has been argued that the sublexical process may be sufficient in highly transparent languages such as Welsh. If this is the case, damage to the sublexical process may lead to more severe deficits in transparent languages due to the lack of an alternative lexical process. To test this hypothesis, we compared Welsh and English oral reading and written-word recognition and comprehension in seven bilingual stroke participants with comparably impaired pseudoword reading in English and Welsh. Performance was remarkably similar across languages. Irrespective of the language tested, words were read more accurately than pseudowords. Lexical decision and word comprehension were as accurate in Welsh and in English, and when imageability effects were present they were of a similar size in both languages. This study does not support the hypothesis that orthographic transparency determines the nature of cognitive reading processes, but rather suggests that readers develop a sight vocabulary through reading experience irrespective of orthographic transparency.     

Growth of children living in the outskirts of Ankara: Impact of low socio-economic status

Background:?Most studies of the growth of Turkish schoolchildren are limited to large cities and to subjects from high socio-economic background. Very little is known about growth and development of rural, suburban and low socio-economic children in Turkey.

Aim:?The purpose of this study is to compare height and weight of school-aged children of low socio-economic background with available growth data from high socio-economic strata, and to verify the possible influences of three socio-demographic parameters on their growth.

Subjects and methods:?The sample consisted of 1052 girls and 1223 boys, aged between 7–17 years, living in the outskirts of Ankara, a suburban area of poor socio-economic background. Centile distributions for height and weight were estimated by the LMS-method. ANOVA and Student's t-test were used to compare mean z-scores for height and weight among the various categories of the socio-demographic parameters.

Results:?Children living in the outskirts of Ankara have lower mean values for height and weight when compared with growth data of upper socio-economic strata children. The differences were most pronounced during adolescence. Skinfolds were higher in girls than in boys at all ages (largest p?≤?0.007). There was no clear relationship between growth and the number of siblings, the number of rooms in the house, the mother's and father's education, and the father's professional status (p>0.05), except for the height of girls (p?<?0.05).

Conclusion:?It is suggested that the lower growth status of children living in the outskirts of Ankara is attributable to the poor socio-economic status of this suburban population, which has not changed over the past decades. It is postulated that the growth impairment during adolescence might be due to a reduced tempo of growth in these children.

Résumé. Arrière plan: En Turquie, la plupart des études de croissance ont été limitées à des échantillons de grandes villes et de haut niveau socio-économique. On sait peu de choses sur les modalités de la croissance et du développement des enfants ruraux, périurbains et de niveau socio-économique modeste.

But: Cette étude compare les statures et les poids d’enfants turcs de milieu socioéconomique modeste avec les données des strates socioéconomiques favorisées et analyse les influences éventuelles de trois facteurs sociodémographiques sur leur croissance.

Sujets et méthodes: L’échantillon est formé de 1052 filles et de 1223 garçons âgés de 7 à 17 ans, vivant dans une zone périurbaine défavorisée de la banlieue d’Ankara. Les distributions de centiles pour la stature et pour le poids, ont été estimées par la méthode des moindres carrés et l’analyse de la variance et le test de Student ont été utilisés afin de comparer les z-scores moyens de la stature et du poids en fonction de diverses catégories de paramètres sociodémographiques.

Résultats: Les enfants de la banlieue d’Ankara ont des valeurs moyennes de stature et de poids plus basses que celles des enfants de milieu favorisés, les différences étant plus prononcées lors de l’adolescence. Les plis cutanés sont plus épais chez les filles que chez les garçons quelque soit l’âge (p?≤?0,007). Il n’y a pas d’association nette entre la croissance et le nombre de frères et s?urs, le nombre de pièces du foyer, l’éducation de la mère et du père et le statut professionnel du père (p>0,05), à l’exception de la stature des filles (p<0,05).

Conclusion: Il est vraisemblable que les modalités de croissance moins favorables qu’on observe chez les enfants de la banlieue d’Ankara, soient dues à leur mauvais statut socioéconomique qui n’a pas changé au cours des récentes décennies. On postule que leur déficit de croissance au cours de l’adolescence peut être le fait d’un tempo de croissance réduit.

Zusammenfassung. Hintergrund: Die meisten Wachstumsstudien an Türkischen Schulkindern sind auf große Städte und Probanden mit hohem sozioökonomischen Hintergrund beschränkt. In der Türkei ist sehr wenig über Wachstum und Entwicklung von Kindern aus ländlichen Regionen und Vorstädten und Kindern aus niedrigen sozioökonomischen Schichten bekannt.

Ziel: Sinn dieser Studie ist es, Körperhöhe und Gewicht von Kindern mit niedrigem sozioökonomischen Hintergrund im Schulalter mit verfügbaren Wachstumsdaten aus hohen sozioökonomischen Schichten zu vergleichen und mögliche Einflüsse von drei soziodemographischen Parametern auf ihr Wachstum nachzuweisen.

Probanden und Methoden: Die Stichprobe bestand aus 1052 Mädchen und 1223 Knaben im Alter zwischen 7 und 17 Jahren, die in den Vorstädten von Ankara wohnen, einem suburbanen Bezirk mit sozioökonomisch ärmlichem Hintergrund. Perzentilverteilungen für Körperhöhe und Gewicht wurden nach der LMS-Methode geschätzt. ANOVA und Student's t-Test wurden verwendet, um mittlere Z-Werte für Körperhöhe und Gewicht zwischen den verschiedenen Kategorien der soziodemographischen Parameter zu vergleichen.

Ergebnisse: Kinder, die in den Vorstädten von Ankara leben, haben, im Vergleich mit Wachstumsdaten aus der oberen sozioökonomischen Schicht, niedrigere Mittelwerte für Körperhöhe und Gewicht. Die Unterschiede waren während der Adoleszenz am stärksten ausgeprägt. In allen Altersgruppen waren Hautfettfalten bei Mädchen dicker als bei Knaben (maximal p<0,007). Es gab keine deutliche Korrelation zwischen Wachstum und Geschwisterzahl, Zimmerzahl im Hause, Bildungsgrad von Müttern und Vätern, und dem beruflichen Status des Vaters (p>0,05), mit Ausnahme der Körperhöhe von Mädchen (p<0,05).

Zusammenfassung: Es wird angenommen, dass das geringere Wachstum von Kindern, die in den Vorstädten von Ankara leben, auf den ärmlichen sozioökonomischen Status dieser suburbanen Bevölkerung, der sich in den vergangenen Jahrzehnten nicht geändert hat, zurückzuführen ist. Es wird postuliert, dass der Kleinwuchs in der Adoleszenz die Folge eines verringerten Wachstumstempos dieser Kinder ist.

Resumen. Antecedentes: la mayor parte de los estudios de crecimiento de los escolares turcos se limita a las grandes ciudades y a sujetos de nivel socioeconómico alto. Se sabe muy poco sobre el crecimiento y desarrollo de los niños rurales suburbanos de nivel socioeconómico bajo de Turquía.

Objetivo: el propósito de este estudio es comparar la estatura y el peso de los escolares de nivel socioeconómico bajo con datos disponibles sobre el crecimiento de los estratos de nivel socioeconómico alto, y verificar las posibles influencias de tres parámetros sociodemográficos sobre su crecimiento.

Sujetos y métodos: la muestra la componen 1.052 niñas y 1.223 niños, de 7 a 17 años de edad, residentes en los extrarradios de Ankara, un área suburbana de nivel socioeconómico pobre. Las distribuciones centilares de la estatura y el peso se estimaron mediante el método LMS. Se utilizaron un test ANOVA y la t de Student para comparar las puntuaciones z medias de la estatura y el peso entre las diferentes categorías según los parámetros sociodemográficos.

Resultados: los niños que residen en los extrarradios de Ankara tenían menores valores medios de estatura y peso cuando se les comparó con los niños de los estratos socioeconómicos más altos. Las diferencias fueron más marcadas durante la adolescencia. Los pliegues eran mayores en las chicas que en los chicos a todas las edades (la mayor p<0,007). No había una relación clara entre el crecimiento y el tamaño de la fratría, el número de habitaciones de la casa, el nivel educativo de la madre y del padre y la situación profesional del padre (p>0,05), excepto para la estatura de las chicas (p<0,05).

Conclusión: se sugiere que el menor nivel de crecimiento de los niños que viven en los extrarradios de Ankara es atribuible al bajo nivel socioeconómico de esta población suburbana, que no ha cambiado durante las últimas décadas. Se postula que las diferencias en el crecimiento durante la adolescencia podrían deberse a una reducción del ritmo de crecimiento en estos niños.     

Chromatin-to-nucleoprotamine transition is controlled by the histone H2B variant TH2B

The conversion of male germ cell chromatin to a nucleoprotamine structure is fundamental to the life cycle, yet the underlying molecular details remain obscure. Here we show that an essential step is the genome-wide incorporation of TH2B, a histone H2B variant of hitherto unknown function. Using mouse models in which TH2B is depleted or C-terminally modified, we show that TH2B directs the final transformation of dissociating nucleosomes into protamine-packed structures. Depletion of TH2B induces compensatory mechanisms that permit histone removal by up-regulating H2B and programming nucleosome instability through targeted histone modifications, including lysine crotonylation and arginine methylation. Furthermore, after fertilization, TH2B reassembles onto the male genome during protamine-to-histone exchange. Thus, TH2B is a unique histone variant that plays a key role in the histone-to-protamine packing of the male genome and guides genome-wide chromatin transitions that both precede and follow transmission of the male genome to the egg.     

VEGF-A165b Is an Endogenous Neuroprotective Splice Isoform of Vascular Endothelial Growth Factor A in?Vivo and in?Vitro

Vascular endothelial growth factor (VEGF) A is generated as two isoform families by alternative RNA splicing, represented by VEGF-A₁₆₅a and VEGF-A₁₆₅b. These isoforms have opposing actions on vascular permeability, angiogenesis, and vasodilatation. The proangiogenic VEGF-A₁₆₅a isoform is neuroprotective in hippocampal, dorsal root ganglia, and retinal neurons, but its propermeability, vasodilatatory, and angiogenic properties limit its therapeutic usefulness. In contrast, a neuroprotective effect of endogenous VEGF-A₁₆₅b on neurons would be advantageous for neurodegenerative pathologies. Endogenous expression of human and rat VEGF-A₁₆₅b was detected in hippocampal and cortical neurons. VEGF-A₁₆₅b formed a significant proportion of total VEGF-A in rat brain. Recombinant human VEGF-A₁₆₅b exerted neuroprotective effects in response to multiple insults, including glutamatergic excitotoxicity in hippocampal neurons, chemotherapy-induced cytotoxicity of dorsal root ganglion neurons, and retinal ganglion cells (RGCs) in rat retinal ischemia-reperfusion injury in vivo. Neuroprotection was dependent on VEGFR2 and MEK1/2 activation but not on p38 or phosphatidylinositol 3–kinase activation. Recombinant human VEGF-A₁₆₅b is a neuroprotective agent that effectively protects both peripheral and central neurons in vivo and in vitro through VEGFR2, MEK1/2, and inhibition of caspase-3 induction. VEGF-A₁₆₅b may be therapeutically useful for pathologies that involve neuronal damage, including hippocampal neurodegeneration, glaucoma diabetic retinopathy, and peripheral neuropathy. The endogenous nature of VEGF-A₁₆₅b expression suggests that non–isoform-specific inhibition of VEGF-A (for antiangiogenic reasons) may be damaging to retinal and sensory neurons.Vascular endothelial growth factor (VEGF) A, originally described as a potent vascular permeability and growth factor for endothelial cells, is up-regulated in the brain during stroke and ischemic episodes¹ and has been linked with many neuronal diseases. The most widely studied isoform of VEGF-A, VEGF-A₁₆₅a, is up-regulated in hypoxia, induces increased vascular permeability in neuronal vasculature, and can stimulate angiogenesis after ischemic episodes. The resulting edema and hyperemia can be damaging, but VEGF-A₁₆₅a has also been found to have direct anticytotoxic effects on neurons, raising the possibility that it may act as an endogenous neuroprotective agent in neurodegenerative pathologies. VEGF-A exerts neurotrophic (survival) and neurotropic (neurogenesis and axon outgrowth) actions, which, although initially thought to be a function of increased angiogenesis and perfusion after neuronal injury,² are now appreciated as direct effects of VEGF-A on neurons.The vegfa gene encodes numerous products by differential splicing, but not all isoforms exert the same effects.³ Alternative splicing of exon 8 leads to two functionally distinct families: the proangiogenic VEGF-A_xxxa family and the counteracting VEGF-A_xxxb family.^4,5 VEGF-A₁₆₅b prevents the VEGF-A₁₆₅a effects on increased vascular permeability, blood vessel growth, and vasodilatation.^4–7The therapeutic potential of VEGF-A and anti–VEGF-A treatments are now widely recognized, and effective anti–VEGF-A treatments are available in ophthalmology⁸ and oncology.⁹ The finding that VEGF-A is implicated in neuronal disorders (eg, Alzheimer disease, Parkinson disease, Huntington disease, diabetic neuropathy, and amyotrophic lateral sclerosis¹⁰) provides a rationale for the use of VEGF-A as a therapeutic agent in neurodegenerative conditions. Although this rationale is supported by preclinical evidence,¹¹ the identification of the VEGF-A_xxxb family requires reexamination of VEGF-A isoforms in these contexts to allow for the clear evidence that VEGF-A splicing variants are not functionally equivalent³ and to determine whether augmentation of the proangiogenic isoform family (VEGF-A_xxxa) alone may have deleterious effects (eg, in occult malignancy and carcinoma in situ).The neuroprotective profile of the exon 8 alternatively spliced isoforms VEGF-A_xxxb remains unexplored. Interestingly, VEGF-A_xxxb isoforms do not exhibit the vascular effects seen with VEGF-A_xxxa isoforms, such as a sustained increase in capillary permeability or hypotension.^5,12 The lack of these potential adverse effects may make VEGF-A_xxxb isoforms more amenable as therapeutic agents in neurodegenerative diseases.We therefore tested the hypothesis that VEGF-A₁₆₅b is neuroprotective for central and peripheral neurons. We found that VEGF-A₁₆₅b is expressed in central neurons and is neuroprotective in vitro and in vivo. This finding indicates that VEGF-A₁₆₅b may prove to be a suitable therapeutic agent in neurodegenerative disorders, exhibiting fewer adverse effects than VEGF-A₁₆₅a.     

MR Imaging of the Perihepatic Space

The perihepatic space is frequently involved in a spectrum of diseases, including intrahepatic lesions extending to the liver capsule and disease conditions involving adjacent organs extending to the perihepatic space or spreading thanks to the communication from intraperitoneal or extraperitoneal sites through the hepatic ligaments. Lesions resulting from the dissemination of peritoneal processes may also affect the perihepatic space. Here we discuss how to assess the perihepatic origin of a lesion and describe the magnetic resonance imaging (MRI) features of normal structures and fluids that may be abnormally located in the perihepatic space. We then review and illustrate the MRI findings present in cases of perihepatic infectious, tumor-related, and miscellaneous conditions. Finally, we highlight the value of MRI over computed tomography.     

HPV genotype distribution according to severity of cervical neoplasia using the digene HPV genotyping LQ test

A new genotyping-based DNA assay (Digene LQ^®) was developed recently. The primary aim was to assess the distribution of HPV types using this new assay in atypical squamous cells of undeterminate significance (ASCUS). The secondary aim was to correlate the HPV types with the severity of the disease. The study population comprised 376 ASCUS women. The women were all Hybrid Capture II (HCII) positive and were admitted in three European referral gynecology clinics between 2007 and 2010. A colposcopy with histological examination was performed in all these patients. HPV 16 was typed in 40 % of patients, HPV 18 in 7 %, and HPV 31 in 17 %, and 18 % of patients had mixed genotypes. Patients aged over 30 more often had the HPV 16 genotype than patients aged under 30 (29 % vs. 11 %, chi-square test p < 0.001). The risk of cervical intra-epithelial neoplasia of grade 2 or more (CIN2 +) when HPV 18 positive is lower than the probability associated with HPV 16 or HPV 31: 28 % vs. 58 % and 52 %, respectively (chi-square test, p = 0.005 and p = 0.05, respectively). The Digene LQ^®, a new sequence-specific hybrid capture sample preparation, is fast and efficient and allows high-throughput genotyping of 18 HR HPV types by PCR compared to traditional non-sequence-specific sample preparation methods.