A revision of the bee genus Ancyloscelis (Hymenoptera: Apidae) in Argentina.

A revision of the emphorine bee genus Ancyloscelis in Argentina is presented. The genus extends from the United States to the center of Argentina, but the maximum diversity of morphological structures is found among South American species. Its species form two distinctive groups regarding their mouthparts: one of them with hooked setae on the proboscis, and the other one with simple or plumose setae on the proboscis. To the first group belong in Argentina, A. bonariensis Brèthes, A. halictoides (Holmberg), A. mesopotamica (Holmberg), and the new species A. holmergi. To the second group belong in Argentina A. apiformis (Fabricius), A. romeroi (Holmberg), A. saltensis Rodríguez Roig-Alsina, and A. nigricornis Rodríguez Roig-Alsina. Lectotype designations are made for Leptergatis bonariensis Brèthes and Leptergatis mesopotamica Holmberg. Ancyloscelis turmalis Vachal is a junior new synonym of Ancyloscelis mesopotamica. The synonymy of Ancyloscelis gigas Friese as junior synonym of Ancyloscelis halictoides is confirmed. Descriptions, illustrations, and a key to the species are provided.

Efficacy and safety of secukinumab for the treatment of severe ABCA12 deficiency-related ichthyosis in a child.

Background: Patients with severe autosomal recessive congenital ichthyosis (ARCI) show a T helper 17/interleukin 17 (Th17/IL17) skewing in their skin and serum, resembling the inflammatory profile of psoriatic patients. Secukinumab, an IL-17A inhibitor, has shown clinical efficacy in patients with moderate-to-severe plaque psoriasis. Aims: To test the clinical efficacy and safety of secukinumab in a paediatric patient with ATP-binding cassette subfamily A member 12 deficiency-related severe erythrodermic ARCI. Materials & Methods: 6-months therapeutic trial. During the first 4-weeks induction period, the patient received weekly subcutaneous injections of 150 mg secukinumab (five injections in total). During the following 20-weeks maintenance period, the patient was given a subcutaneous injection of 150 mg secukinumab every 4 weeks. Result & Discussion: After the 6-months therapy period, there was a 48% reduction from the baseline Ichthyosis-Area-Severity-Index (-Erythema/-Scaling) score. The treatment was well tolerated. Moreover, cytokine analysis revealed a reduction of keratinocyte-derived proinflammatory cytokines and an abrogation of Th17-skewing during therapy. Conclusion: Further studies are needed to evaluate the effects of the use of IL-17A inhibition in ARCI patients.

Peptide signaling for drought-induced tomato flower drop.

The premature abscission of flowers and fruits limits crop yield under environmental stress. Drought-induced flower drop in tomato plants was found to be regulated by phytosulfokine (PSK), a peptide hormone previously known for its growth-promoting and immune-modulating activities. PSK formation in response to drought stress depends on phytaspase 2, a subtilisin-like protease of the phytaspase subtype that generates the peptide hormone by aspartate-specific processing of the PSK precursor in the tomato flower pedicel. The mature peptide acts in the abscission zone where it induces expression of cell wall hydrolases that execute the abscission process. Our results provide insight into the molecular control of abscission as regulated by proteolytic processing to generate a small plant peptide hormone.

A two-way molecular dialogue between embryo and endosperm is required for seed development.

The plant embryonic cuticle is a hydrophobic barrier deposited de novo by the embryo during seed development. At germination, it protects the seedling from water loss and is, thus, critical for survival. Embryonic cuticle formation is controlled by a signaling pathway involving the ABNORMAL LEAF SHAPE1 subtilase and the two GASSHO receptor-like kinases. We show that a sulfated peptide, TWISTED SEED1 (TWS1), acts as a GASSHO ligand. Cuticle surveillance depends on the action of the subtilase, which, unlike the TWS1 precursor and the GASSHO receptors, is not produced in the embryo but in the neighboring endosperm. Subtilase-mediated processing of the embryo-derived TWS1 precursor releases the active peptide, triggering GASSHO-dependent cuticle reinforcement in the embryo. Thus, a bidirectional molecular dialogue between embryo and endosperm safeguards cuticle integrity before germination.

[Allergic respiratory diseases related to mould in the home]. / Pathologies allergiques respiratoires liées aux moisissures de l'habitat.

Exposure to mould is a potential risk factor for asthma in both adults and children. In adult, the relation between exposure, sensitization and symptoms has been demonstrated in severe asthmatics sensitized to Alternaria. For children, exposure to mould in childhood is a risk factor for asthma in both atopic and non-atopic individuals. Exposure or sensitization to moulds are a risk factor for severe asthma and/or exacerbations in children. There appears to be a causal relationship between exposure and asthma. This link seems less significant in adults. However, in adults mould sensitive asthma seems to determine a phenotype of severe asthma associated with more marked obstructive lung disease. Moulds can stimulate either innate or the acquired immunity. They are responsible for a marked Th2 inflammation leading to more severe asthma. Besides the immunological mechanisms, toxic mechanisms can also intervene. It is therefore not correct to reduce the effect of moulds, particularly in respiratory symptoms, to only allergic mechanisms.

Regulation of plant peptide hormones and growth factors by post-translational modification.

The number, diversity and significance of peptides as regulators of cellular differentiation, growth, development and defence of plants has long been underestimated. Peptides have now emerged as an important class of signals for cell-to-cell communication over short distances, and also for long-range signalling. We refer to these signalling molecules as peptide growth factors and peptide hormones, respectively. As compared to remarkable progress with respect to the mechanisms of peptide perception and signal transduction, the biogenesis of signalling peptides is still in its infancy. This review focuses on the biogenesis and activity of small post-translationally modified peptides. These peptides are derived from inactive pre-pro-peptides of approximately 70-120 amino acids. Multiple post-translational modifications (PTMs) may be required for peptide maturation and activation, including proteolytic processing, tyrosine sulfation, proline hydroxylation and hydroxyproline glycosylation. While many of the enzymes responsible for these modifications have been identified, their impact on peptide activity and signalling is not fully understood. These PTMs may or may not be required for bioactivity, they may inactivate the peptide or modify its signalling specificity, they may affect peptide stability or targeting, or its binding affinity with the receptor. In the present review, we will first introduce the peptides that undergo PTMs and for which these PTMs were shown to be functionally relevant. We will then discuss the different types of PTMs and the impact they have on peptide activity and plant growth and development. We conclude with an outlook on the open questions that need to be addressed in future research.

[Is celecoxib a safe alternative for the Fernand Widal syndrome?] / Célécoxib, une alternative sûre pour les syndromes de Fernand Widal ?

The Fernand Widal syndrome is a set of associations between asthma, nasal polyposis and aspirin sensitivity. Selective cyclo-oxygenase 2 (COX 2) inhibitors are recognized as being a therapeutic alternative in cases needing analgesic or anti-inflammatory treatment. In a retrospective study, we have compiled data concerning oral provocation tests (OPT) undertaken with celecoxib, one of most the selective COX 2 inhibitors, in eight patients with the Fernand Widal syndrome. They were compared with twenty-seven control patients with sensitivity to aspirin or non-steroidal anti-inflammatories, manifesting as asthma, urticaria or rhino-conjunctivitis. Four patients with the Fernand Widal syndrome developed bronchospasm after taking the usually recommended daily dose of celecoxib while all the control patients tolerated it. The Fernand Widal patients who reacted during the OPT had a lower threshold of reactivity to aspirin, a more severe reaction with aspirin, and/or more severe asthma. In patients with the Fernand Widal syndrome, celecoxib is not always a possible alternative to non-steroidal anti-inflammatory drugs. Its introduction must be carried out in a hospital environment under medical supervision.

Multiple clinical profiles of families with the short QT syndrome.

Aims: Short QT syndrome (SQTS) is a rare cardiac channelopathy characterized by a shortened corrected QT (QTc)-interval that can lead to ventricular arrhythmias and sudden cardiac death. The aim of this study was to investigate the clinical phenotypes and long-term outcomes of three families harbouring genetic mutations associated with the SQTS. Methods and results: Clinical data included medical history, physical examination, 12-lead ECG, 24-h Holter-ECG, and transthoracic echocardiography from three index patients and their first-degree relatives. Next generation clinical exome sequencing and genetic cascade screening were performed in index patients and their relatives, respectively. Two index patients experienced malignant ventricular arrhythmias and one patient suffered from arrhythmogenic syncope during a median follow-up period of 8 years. They all had genetic mutations associated with the SQTS. Two mutations were found in the KCNH2 gene, and one in the CACNA2D gene. One patient had an additional SCN10A variant. Alive and mutation-positive family members had short QTc-intervals, but no further phenotypic manifestations. None of the mutation-negative family members had an abnormal ECG or any symptoms. In all patients with shortened QTc-intervals, the QTc-interval had a low long-term variability and QTc shortening always remained detectable by 12-lead ECG. Conclusion: This study shows the variety of phenotypic manifestations in different families with SQTS. It further emphasizes the importance of a 12-lead ECG for early diagnosis, and the utility of next generation sequencing for the identification of mutations associated with the SQTS.

A novel mutation in BCS1L associated with deafness, tubulopathy, growth retardation and microcephaly.

UNLABELLED: We report a novel homozygous missense mutation in the ubiquinol-cytochrome c reductase synthesis-like (BCS1L) gene in two consanguineous Turkish families associated with deafness, Fanconi syndrome (tubulopathy), microcephaly, mental and growth retardation. All three patients presented with transitory metabolic acidosis in the neonatal period and development of persistent renal de Toni-Debré-Fanconi-type tubulopathy, with subsequent rachitis, short stature, microcephaly, sensorineural hearing impairment, mild mental retardation and liver dysfunction. The novel missense mutation c.142A>G (p.M48V) in BCS1L is located at a highly conserved region associated with sorting to the mitochondria. Biochemical analysis revealed an isolated complex III deficiency in skeletal muscle not detected in fibroblasts. Native polyacrylamide gel electrophoresis (PAGE) revealed normal super complex formation, but a shift in mobility of complex III most likely caused by the absence of the BCS1L-mediated insertion of Rieske Fe/S protein into complex III. These findings expand the phenotypic spectrum of BCS1L mutations, highlight the importance of biochemical analysis of different primary affected tissue and underline that neonatal lactic acidosis with multi-organ involvement may resolve after the newborn period with a relatively spared neurological outcome and survival into adulthood. CONCLUSION: Mutation screening for BCS1L should be considered in the differential diagnosis of severe (proximal) tubulopathy in the newborn period. WHAT IS KNOWN: • Mutations in BCS1L cause mitochondrial complex III deficiencies. • Phenotypic presentations of defective BCS1L range from Bjornstad to neonatal GRACILE syndrome. What is New: • Description of a novel homozygous mutation in BCS1L with transient neonatal acidosis and persistent de Toni-Debré-Fanconi-type tubulopathy. • The long survival of patients with phenotypic presentation of severe complex III deficiency is uncommon.

Selective growth of MFU-4l single crystals on microstructured plasma polymer coatings.

Single crystals of the metal-organic framework Ulm-4l(arge) (MFU-4l) can be grown site selectively on microtextured plasma polymer coatings comprising a pattern of alternating hydrophilic and hydrophobic domains. The crystals grow preferentially on the hydrophilic parts of the film surface. X-ray diffraction (XRD) shows that the cubic crystals have a high propensity to adhere with 〈1 0 0〉 orientation to the coating.

Heterologous expression from the human D-Loop in organello.

We report the expression of a linear reporter construct in isolated human mitochondria. The reporter construct contained the entire human D-Loop with adjacent tRNA (MTT) genes (mt.15956-647), the human ND1 gene with an in frame GFP gene and adjacent endogenous MTT genes and heterologous rat MTT genes. Natural competence of isolated human mitochondria of HepG2 cells was used to import reporter constructs. The import efficiency of various fluorescently labelled PCR-generated import substrates in the range of 250bp up to 3.5kb was assessed by quantitative PCR and evaluated by confocal microscopy. Heterologous expression of the imported construct was confirmed at RNA level by a circular RNA (cRNA)-RT-PCR assay for the expression of tRNAs and by in organello [α-(32)P]-UTP labelling and subsequent hybridisation to reporter-specific sequences for monitoring mRNA expression. Heterologous expression of rat mitochondrial tRNA(Leu(UUR)) (rMT-TL1) was confirmed by co-/post-transcriptional trinucleotide (CCA) addition. Interestingly, the rat-specific MT-TL1 was correctly processed in isolated human mitochondria at the 3' end, but showed an aberrant 5' end processing. Correct 3' end processing of the heterologous expressed mitochondrial rat tRNA(Ser2) (MT-TS2) was detected. These findings demonstrate the feasibility of genetic manipulation of human mitochondria, providing a tool for characterisation of cis-acting elements of the human mitochondrial genome and for the study of human mitochondrial tRNA processing in organello.

Transient finite element analysis of a traumatic fracture of the zygomatic bone caused by a head collision.

Midfacial fractures rank first concerning maxillofacial traumatology. Collisions of two heads or head to object are the main causes for these fractures. An investigation based on a transient simulation using the finite element method was performed. A biomechanical head model was created and tested. A transient collision of two heads was simulated. The results were compared to a typical real patient case. This comparison revealed an identical fracture pattern, which can be interpreted as a clinical match of the simulation. The results of this study show the validity of biomechanical investigations, which may serve as a method to better understand maxillofacial fracture patterns. These results will be used for the optimization of fracture therapy or trauma prevention in the future.

Contiguous ∼16 Mb 1p36 deletion: Dominant features of classical distal 1p36 monosomy with haplo-lethality.

Monosomy 1p36 results from heterozygous deletions of the terminal short chromosome 1 arm, the most common terminal deletion in humans. The microdeletion is split in two usually non-overlapping and clinically distinct classical distal and proximal 1p36 monosomy syndromes. Using comparative genome hybridization, MLPA and qPCR we identified the largest contiguous ∼16 Mb terminal 1p36 deletion reported to date. It covers both distal and proximal regions, causes a neonatally lethal variant with virtually exclusive features of distal 1p36 monosomy, highlighting the key importance of the gene-rich distal region for the "compound" 1p36 phenotype and a threshold deletion-size effect for haplo-lethality.

Impairment of mitochondrial tRNAIle processing by a novel mutation associated with chronic progressive external ophthalmoplegia.

We report a sporadic case of chronic progressive external ophthalmoplegia associated with ragged red fibers. The patient presented with enlarged mitochondria with deranged internal architecture and crystalline inclusions. Biochemical studies showed reduced activities of complex I, III and IV in skeletal muscle. Molecular genetic analysis of all mitochondrial tRNAs revealed a G to A transition at nt 4308; the G is a highly conserved nucleotide that participates in a GC base-pair in the T-stem of mammalian mitochondrial tRNA(Ile). The mutation was detected at a high level (approx. 50%) in muscle but not in blood. The mutation co-segregated with the phenotype, as the mutation was absent from blood and muscle in the patient's healthy mother. Functional characterization of the mutation revealed a six-fold reduced rate of tRNA(Ile) precursor 3' end maturation in vitro by tRNAse Z. Furthermore, the mutated tRNA(Ile) displays local structural differences from wild-type. These results suggest that structural perturbations reduce efficiency of tRNA(Ile) precursor 3' end processing and contribute to the molecular pathomechanism of this mutation.

Mitochondrial neurogastrointestinal encephalomyopathy in three siblings: clinical, genetic and neuroradiological features.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive disorder in which a nuclear mutation of the thymidine phosphorylase (TP) gene causes mitochondrial genomic dysfunction. Patients suffer from gastrointestinal dysmotility, cachexia, ptosis, external ophthalmoparesis, myopathy and polyneuropathy. Magnetic resonance imaging (MRI) shows leukoencephalopathy. We describe clinical, genetic and neuroradiological features of three brothers affected with MNGIE. Clinical examination, laboratory analyses, MRI and magnetic resonance spectroscopy (MRS) of the brain, and genetic analysis have been performed in all six members of the family with the three patients with MNGIE. Two of them are monozygous twins. They all suffered from gastrointestinal dysmotility, cachexia, ophthalmoplegia, muscular atrophies, and polyneuropathy. Urinary thymidine was elevated in the patients related to the severity of clinical disease, and urinary thymidine (normally not detectable) was also found in a heterozygous carrier. Brain MRI showed leukoencephalopathy in all patients; however, their cognitive functioning was normal. Brain MRS demonstrated reduced N-acetylaspartate and choline in severely affected areas. MRI of heterozygous carriers was normal. A new mutation (T92N) in the TP gene was identified. Urinary thymidine is for the first time reported to be detectable in a heterozygous carrier. MRS findings indicate loss of neurons, axons, and glial cells in patients with MNGIE, but not in heterozygous carriers.

Simultaneous quantitative detection of relevant biomarkers in breast cancer by quantitative real-time PCR.

The assessment of ERa, PgR and HER2 status is routinely performed today to determine the endocrine responsiveness of breast cancer samples. Such determination is usually accomplished by means of immunohistochemistry and in case of HER2 amplification by means of fluorescent in situ hybridization (FISH). The analysis of these markers can be improved by simultaneous measurements using quantitative real-time PCR (Qrt-PCR). In this study we compared Qrt-PCR results for the assessment of mRNA levels of ERa, PgR, and the members of the human epidermal growth factor receptor family, HER1, HER2, HER3 and HER4. The results were obtained in two independent laboratories using two different methods, SYBR Green I and TaqMan probes, and different primers. By linear regression we demonstrated a good concordance for all six markers. The quantitative mRNA expression levels of ERa, PgR and HER2 also strongly correlated with the respective quantitative protein expression levels prospectively detected by EIA in both laboratories. In addition, HER2 mRNA expression levels correlated well with gene amplification detected by FISH in the same biopsies. Our results indicate that both Qrt-PCR methods were robust and sensitive tools for routine diagnostics and consistent with standard methodologies. The developed simultaneous assessment of several biomarkers is fast and labor effective and allows optimization of the clinical decision-making process in breast cancer tissue and/or core biopsies.

[Menkes' disease: heterozygosity testing by quantitative real-time PCR and the dilemma of therapeutic support]. / Quantitative Heterozygotentestung und das therapeutische Dilemma bei Menkes-Syndrom.

Menkes' disease is a rare X-linked multisystemic lethal disorder of copper transport metabolism. Failure of synthesis of several copper enzymes explains most of the clinical features, which were characterised by neurodegenerative symptoms and connective tissue manifestations. Most cases are still prone to rapidly progressive cerebral degeneration and early death in the first few years. Since CNS-dysfunction usually preceeds development of the pathognomonic "steely" hair, delay of clinical diagnosis and onset of therapeutic intervention precludes longlasting neurological benefit. This is particularly true for patients with large deletions or severe truncations of the responsible ATP7A gene. We report on our own experience with a patient, who was diagnosed to be affected by Menkes' syndrome at the age of one year, due to the specific hair texture and biochemical abnormalities. Molecular investigation revealed a total deletion of exon 15 of the ATP7A gene. Heterozygosity was confirmed by means of real-time PCR in the child's mother, but could be excluded in the grandmother and other female relatives at risk. Therapeutic support with subcutaneous injection of copper-histidinate normalised diminished copper and coeruloplasmin serum levels, but was unable to influence the clinical course and to prevent the fatal outcome at the age of two years. This observation is in line with the experience of the literature claiming that currently available medication will hardly be able to normalise brain copper levels. However, observations of clinical variants of Menkes' disease with quite a different outcome and, more importantly, emerging of alternative copper transport pathways might still justify this time-limited therapeutic intervention.

Use of recombinant ApxIV in serodiagnosis of Actinobacillus pleuropneumoniae infections, development and prevalidation of the ApxIV ELISA.

Actinobacillus pleuropneumoniae is the etiological agent of porcine pleuropneumonia, which causes worldwide severe losses in pig farming. The virulence of the 15 serotypes of A. pleuropneumoniae is mainly determined by the three major RTX toxins ApxI, ApxII and ApxIII, which are secreted by the different serotypes in various combinations. A fourth RTX toxin, ApxIV, is produced by all 15 serotypes only during infection of pigs, but not under in vitro conditions. Pigs infected with A. pleuropneumoniae show specific antibodies directed against ApxIV. In contrast, antibodies against the other three toxins ApxI, ApxII and ApxIII are also found in pigs free of A. pleuropneumoniae. The antibodies to the three latter might result from other, less pathogenic Actinobacillus species such as A. rossii and A. suis. We used a recombinant protein based on the N'-terminal part of ApxIV to serologically detect A. pleuropneumoniae infections in pigs by immunoblot analysis. The analysis of sera of experimentally infected pigs revealed that ApxIV-immunoblots detected A. pleuropneumoniae infections in the second to third week post infection. We developed an indirect ELISA based on the purified recombinant N'-terminal moiety of ApxIV. The analysis of sera from pigs that were experimentally or naturally infected by A. pleuropneumoniae, and of sera of pigs that were free of A. pleuropneumoniae, revealed that the ELISA had a specificity of 100% and a sensitivity of 93.8%. The pre-validation study of the ApxIV-ELISA revealed that the latter was able to detect A. pleuropneumoniae-positive herds, even when clinical and pathological signs of porcine pleuropneumonia were not evident. Pigs vaccinated with a subunit vaccine Porcilis App were serologically negative in the ApxIV-ELISA.