Impact of Helminth Infection during Pregnancy on Cognitive and Motor Functions of One-Year-Old Children

ObjectiveTo determine the effect of helminth infection during pregnancy on the cognitive and motor functions of one-year-old children.MethodsSix hundred and thirty five singletons born to pregnant women enrolled before 29 weeks of gestation in a trial comparing two intermittent preventive treatments for malaria were assessed for cognitive and motor functions using the Mullen Scales of Early Learning, in the TOVI study, at twelve months of age in the district of Allada in Benin. Stool samples of pregnant women were collected at recruitment, second antenatal care (ANC) visit (at least one month after recruitment) and just before delivery, and were tested for helminths using the Kato-Katz technique. All pregnant women were administered a total of 600 mg of mebendazole (100 mg two times daily for 3 days) to be taken after the first ANC visit. The intake was not directly observed.ResultsPrevalence of helminth infection was 11.5%, 7.5% and 3.0% at first ANC visit, second ANC visit and at delivery, respectively. Children of mothers who were infected with hookworms at the first ANC visit had 4.9 (95% CI: 1.3–8.6) lower mean gross motor scores compared to those whose mothers were not infected with hookworms at the first ANC visit, in the adjusted model. Helminth infection at least once during pregnancy was associated with infant cognitive and gross motor functions after adjusting for maternal education, gravidity, child sex, family possessions, and quality of the home stimulation.ConclusionHelminth infection during pregnancy is associated with poor cognitive and gross motor outcomes in infants. Measures to prevent helminth infection during pregnancy should be reinforced.     

Genomic alterations in human umbilical cord–derived mesenchymal stromal cells call for stringent quality control before any possible therapeutic approach

Background aimsThe umbilical cord (UC) is a promising source of mesenchymal stromal cells (MSCs). UC-MSCs display very similar in vitro characteristics to bone marrow–MSCs and could represent a valuable alternative for cell-based therapies. However, it is still unclear whether UC-MSCs are prone or not to the acquisition of genomic imbalances during in vitro expansion.MethodsWith the use of array-comparative genomic hybridization, we compared copy number variations of early (P2–P3) and late (>P5) passages of in vitro–expanded UC-MSCs.ResultsIn two of 11 long-term UC-MSCs cultures, we observed the appearance of clones carrying genomic imbalances, which generated genetic mosaicism at intermediate passages. Although still able to reach the senescence phase, the cells carrying the genomic imbalance acquired a proliferative advantage, as demonstrated by the increase in frequency during long-term culture.ConclusionsAltogether, our results suggest that UC-MSC–based clinical protocols should be designed with caution; their clinical use should be preceded by array-comparative genomic hybridization screening for the acquisition of genomic imbalances during in vitro expansion.     

Calleida desenderi, new species from Ecuador (Coleoptera, Carabidae, Lebiinae)

Calleida desenderi Casale, sp. n., is described from Ecuador, Napo Province, surroundings of San Rafael. The new taxon is mostly characterized by the head and appendages rufous, the disc of elytra with marked metallic green reflection, the median lobe of aedeagus ring-like, and the endophallus with a long, twisted flagellum. A key for identification of the closer Neotropical species described so far is also provided.     

Two new Typhloreicheia species from Sardinia and their biogeographical significance (Coleoptera, Carabidae, Scaritinae)

Typhloreicheia monachasp. n. and Typhloreicheia ilianaesp. n. are described from two caves of Central-Eastern Sardinia (Nuoro province): the Bue Marino cave and the Nurra 'e Pradu cave, respectively. Both caves are located in the part of the island where many highly specialised subterranean carabid beetles are localised. Typhloreicheia monacha is apparently related to two other species of the same area, i.e. Typhloreicheia onnisi Casale & Magrini, 2004 and Typhloreicheia elegans (Dodero, 1916); Typhloreicheia ilianae is closely related to Typhloreicheia henroti Jeannel, 1957, known from a cave near Dorgali. Relationships and diagnostic features among these taxa are discussed and illustrated, and a key for identification of the specialised subterranean Typhloreicheia species of Sardinia is provided. The hypothesis of adaptive radiation of Reicheiina species in Sardinia, recently proposed by the senior author of this contribution, is further elaborated in light of new data.     

Kinome multigenic panel identified novel druggable EPHB4-V871I somatic variant in high-risk neuroblastoma

Neuroblastoma (NB) is the most common extracranial neoplasm in children. The overall outcome for high-risk NB patients is still unacceptable, therefore, it is critical to deeply understand molecular mechanisms associated with NB, which in turn can be utilized for developing drugs towards the treatment of NB. Protein kinases (TKs) play an essential role in the regulation of cell survival and proliferation. Different kinases, such as anaplastic lymphoma kinase (ALK), Aurora kinase, RET receptor tyrosine kinase, are potential therapeutic targets in various cancers, including NB. We analysed a cohort of 45 high-risk NB patients and 9 NB cell lines by a targeted—(t)NGS custom gene panel (genes codifying for the kinase domains of 90 TKs). We identified somatic variants in four TK genes (ALK, EPHB4, LMTK3 and EPHB6) in NB patients and we functionally characterized an interesting somatic variant, V871I, in EPHB4 gene. EPHB4 plays a crucial role in cardiovascular development and regulates vascularization in cancer-promoting angiogenesis, tumour growth and metastasis. Several EPHB4 mutations have previously been identified in solid and haematological tumour specimens but EPHB4 mutations were not described until now in NB. Interestingly, a re-analysis of public CGH-array showed that the EPHB4 gain is associated with advanced diseases in NB. We further demonstrated that higher EPHB4 expression is correlated to stage 4 of NB and with poor overall survival. Additionally, we also revealed that the EPHB4-V871I accounts for increased proliferation, migration and invasion properties in two NB cell lines by acting on VEGF, c-RAF and CDK4 target genes and by increasing the phosphorylation of ERK1-2 pathway. The use of two EPHB4 inhibitors, JI-101 and NVP-BHG712, was able to rescue the phenotype driven by the variant. Our study suggested that EPHB4 is a promising therapeutic target in high-risk NB.     

M tuberculosis in the Adjuvant Modulates Time of Appearance of CNS-Specific Effector T Cells in the Spleen through a Polymorphic Site of TLR2

DC deliver information regulating trafficking of effector T cells along T-cell priming. However, the role of pathogen-derived motives in the regulation of movement of T cells has not been studied. We hereinafter report that amount of M tuberculosis in the adjuvant modulates relocation of PLP139-151 specific T cells. In the presence of a low dose of M tuberculosis in the adjuvant, T cells (detected by CDR3 BV-BJ spectratyping, the so-called “immunoscope”) mostly reach the spleen by day 28 after immunization (“late relocation”) in the SJL strain, whereas T cells reach the spleen by d 14 with a high dose of M tuberculosis (“early relocation”). The C57Bl/6 background confers a dominant “early relocation” phenotype to F1 (SJL×C57Bl/6) mice, allowing early relocation of T cells in the presence of low dose M tuberculosis. A single non-synonymous polymorphism of TLR2 is responsible for “early/late” relocation phenotype. Egress of T lymphocytes is regulated by TLR2 expressed on T cells. Thus, pathogens engaging TLR2 on T cells regulate directly T-cell trafficking, and polymorphisms of TLR2 condition T-cell trafficking upon a limiting concentration of ligand.     

Non-methane biogenic volatile organic compound emissions from boreal peatland microcosms under warming and water table drawdown

Boreal peatlands have significant emissions of non-methane biogenic volatile organic compounds (BVOCs). Climate warming is expected to affect these ecosystems both directly, with increasing temperature, and indirectly, through water table drawdown following increased evapotranspiration. We assessed the combined effect of warming and water table drawdown on the BVOC emissions from boreal peatland microcosms. We also assessed the treatment effects on the BVOC emissions from the peat soil after the 7-week long experiment. Emissions of isoprene, monoterpenes, sesquiterpenes, other reactive VOCs and other VOCs were sampled using a conventional chamber technique, collected on adsorbent and analyzed by GC–MS. Carbon emitted as BVOCs was less than 1% of the CO₂ uptake and up to 3% of CH₄ emission. Water table drawdown surpassed the direct warming effect and significantly decreased the emissions of all BVOC groups. Only isoprene emission was significantly increased by warming, parallel to the increased leaf number of the dominant sedge Eriophorum vaginatum. BVOC emissions from peat soil were higher under the control and warming treatments than water table drawdown, suggesting an increased activity of anaerobic microbial community. Our results suggest that boreal peatlands could have concomitant negative and positive radiative forcing effects on climate warming following the effect of water table drawdown. The observed decrease in CH₄ emission causes a negative radiative forcing while the increase in CO₂ emission and decrease in reactive BVOC emissions, which could reduce the cooling effect induced by the lower formation rate of secondary organic aerosols, both contribute to increased radiative forcing.     

Inflamm-Aging and Arachadonic Acid Metabolite Differences with Stage of Tendon Disease

The contribution of inflammation to the pathogenesis of tendinopathy and high prevalence of re-injury is not well established, although recent evidence suggests involvement of prostaglandins. We investigated the roles of prostaglandins and inflammation-resolving mediators in naturally occurring equine tendon injury with disease stage and age. Levels of prostaglandins E₂ (PGE₂), F_2α (PGF_2α), lipoxin A₄ (LXA₄) and its receptor FPR2/ALX were analysed in extracts of normal, sub-acute and chronic injured tendons. To assess whether potential changes were associated with altered PGE₂ metabolism, microsomal prostaglandin E synthase-1 (mPGES-1), prostaglandin dehydrogenase (PGDH), COX-2 and EP₄ receptor expression were investigated. The ability of tendons to resolve inflammation was determined by assessing FPR2/ALX expression in natural injury and IL-1β stimulated tendon explants.Alterations in the profile of lipid mediators during sub-acute injury included low PGE₂ and elevated LXA₄ levels compared to normal and chronic injuries. In contrast, PGF_2α levels remained unchanged and were three-fold lower than PGE₂. The synthetic capacity of PGE₂ as measured by the ratio of mPGES-1:PGDH was elevated in sub-acute injury, suggesting aberrations in tendon prostaglandin metabolism, whilst COX-2 and EP₄ receptor were unchanged. Paradoxically low tendon PGE₂ levels in early injury may be attributed to increased local clearance via PGDH or the class switching of lipid mediators from the prostaglandin to the lipoxin axis. PGE₂ is therefore implicated in the development of tendon inflammation and its ensuing resolution. Whilst there was no relationship between age and tendon LXA₄ levels, there was an age-associated decline in FPR2/ALX receptor expression with concurrent increased PGE₂ levels in injury. Furthermore, uninjured tendon explants from younger (<10 years) but not older horses (≥10 years) treated with IL-1β responded by increasing FPR2/ALX suggesting aged individuals exhibit a reduced capacity to resolve inflammation via FPR2/ALX, which may present a potential mechanism for development of chronic tendinopathy and re-injury.