Proline-Rich Antimicrobial Peptides in Medicinal Maggots of Lucilia sericata Interact With Bacterial DnaK But Do Not Inhibit Protein Synthesis

In the search for new antibiotics to combat multidrug-resistant microbes, insects offer a rich source of novel anti-infectives, including a remarkably diverse array of antimicrobial peptides (AMPs) with broad activity against a wide range of species. Larvae of the common green bottle fly Lucilia sericata are used for maggot debridement therapy, and their effectiveness in part reflects the large panel of AMPs they secrete into the wound. To investigate the activity of these peptides in more detail, we selected two structurally different proline rich peptides (Lser-PRP2 and Lser-PRP3) in addition to the a-helical peptide Lser-stomoxyn. We investigated the mechanism of anti-Escherichia coli action of the PRPs in vitro and found that neither of them interfered with protein synthesis but both were able to bind the bacterial chaperone DnaK and are therefore likely to inhibit protein folding. However, unlike Lser-stomoxyn that permeabilized the bacterial membrane by 1% at the low concentration (0.25 µM) neither of the PRPs alone was able to permeabilize E. coli membrane. In the presence of this Lser-stomoxyn concentration significant increase in anti-E. coli activity of Lser-PRP2 was observed, indicating that this peptide needs specific membrane permeabilizing agents to exert its antibacterial activity. We then examined the AMPs-treated bacterial surface and observed detrimental structural changes in the bacterial cell envelope in response to combined AMPs. The functional analysis of insect AMPs will help select optimal combinations for targeted antimicrobial therap

Evaluación de los riegos de la Comunidad de Regantes V del Canal de las Bardenas

14 Pag., 2 Tabl., 1 Fig.[ES] En este artículo se presentan los resultados de las evaluaciones de riego que se han llevado a cabo dentro de la segunda fase del trabajo denominado “Mejora de la Gestión Integral del Agua de Riego en la Comunidad de Regantes V del Canal de Bardenas”. El 80 % de la superficie de esta comunidad está ocupado por suelos de plataformas residuales, mientras que el resto son suelos de aluvial. Para caracterizar la capacidad de retención de agua de los suelos (CRA) se realizó un muestro en el que se describieron 50 perfiles. Para determinar la infiltración de los suelos y los índices de calidad del riego por superficie se realizaron 50 evaluaciones de riego. Un adecuado manejo del agua a nivel de parcela y unas texturas francas-franco arenosas permiten alcanzar niveles de eficiencia medios en las parcelas de las plataformas (53 % de media), cuyos suelos se caracterizan por una baja CRA (60 mm de media). En aluviales la eficiencia llega hasta un 80 % de media, gracias a las elevadas capacidades de retención de agua de estos suelos (182 mm de media). Actualmente se está realizado un reaprovechamiento de las aguas de desagüe que posiblemente provoque que la eficiencia a nivel de comunidad sea mayor que la obtenida a nivel de parcela. Estos resultados permiten pensar que la modernización de los regadíos, mediante el cambio a un sistema de riego presurizado, tendría un fuerte impacto sobre la eficiencia en parcela, aunque el impacto sobre la eficiencia en la comunidad sería menor. La modernización tendría resultados muy beneficiosos social y económicamente para los agricultores, además de mejorar la calidad de las aguas de los ríos que atraviesan la comunidad.[EN] Results of the irrigation evaluations performed in the second phase of the project “Improvement of the Water Irrigation Integral Management in the Comunidad de Regantes V del Canal de Bardenas” are presented in this paper. An 80 % of the area of the Irrigation District is occupied by soils of residual platforms, and the rest of the soils are alluvial. A soil survey was performed for characterising the water holding capacity (WHC) of the soils, using 50 soil profiles. A total of 50 irrigation evaluations was performed for determining soil infiltration and the performance indexes of surface irrigation in the study area. An adequate water management in border irrigation and loam-sandy loam textures permit to attain 53 % application efficiency in platforms, whose soils are characterized by a low WHC (with an average of 60 mm). In alluvial soils the application efficiency is higher, with an average of 80 %, due to the high water holding capacity of these soils (an average of 182 mm). Currently, The district is enforcing a program for irrigation return flows reuse. This program surely results in an irrigation district efficiency substantially higher that the average application efficiency. With these results is possible to think that an irrigation modernization, through a change to a pressurized irrigation system will severely improve the application efficiency, but the effect on the irrigation district efficiency will only be moderate. However, this modernisation would have great social and economical benefits for farmers, and also, the water quality of rivers crossing the irrigation district will be improved.Este proyecto de investigación ha sido cofinanciado por la CICYT, por Fondos FEDER, por el CONSI+D y por la Comunidad de Regantes V de Bardenas.Peer reviewe

MFN2 point mutations occur in 3.4% of Charcot-Marie-Tooth families. An investigation of 232 Norwegian CMT families

Background Point mutations in the mitofusin 2 (MFN2) gene has been identified exclusively in Charcot-Marie-Tooth type 2 (CMT2), and in a single family with intermediate CMT. MFN2 point mutations are probably the most common cause of CMT2. Methods Two-hundred and thirty-two consecutive unselected and unrelated CMT families with available DNA from all regions in Norway were included. We screened for point mutations in the MFN2 gene. Results We identified four known and three novel point mutations in 8 unrelated CMT families. The novel point mutations were not found in 100 healthy controls. This corresponds to 3.4% (8/232) of CMT families have point mutations in the MFN2 gene. The phenotypes were compatible with CMT1 in two families, CMT2 in four families, intermediate CMT in one family and distal Hereditary Motor Neuropathy (dHMN) in one family. This corresponds to 2.3% of CMT1, 5.5% of CMT2, 12.5% of intermediate CMT and 6.7% of dHMN families have a point mutation in the MFN2 gene. Point mutations in the MFN2 gene is likely to be the fourth most common cause to CMT after duplication of the peripheral myelin protein 22 (PMP22) gene, and point mutations in the Connexin32 (Cx32) and myelin protein zero (MPZ) genes. Conclusions The identified known and novel point mutations in the MFN2 gene expand the clinical spectrum from CMT2 and intermediate CMT to also include possibly CMT1 and the dHMN phenotypes. Thus, genetic analyses of the MFN2 gene should not be restricted to persons with CMT2

Spinocerebellar ataxia 27B: episodic symptoms and acetazolamide response in 34 patients

Ashton C et al report a retrospective multi-centre cohort of 34 patients from Canada, France, Austria and Australia with spinocerebellar ataxia 27B, describing the common feature of episodic ataxia and other episodic features, as well as the inefficacy of acetazolamide in these patients

Genetic and clinical characteristics of NEFL-related Charcot-Marie-Tooth disease

OBJECTIVES: To analyse and describe the clinical and genetic spectrum of Charcot-Marie-Tooth disease (CMT) caused by mutations in the neurofilament light polypeptide gene (NEFL). METHODS: Combined analysis of newly identified patients with NEFL-related CMT and all previously reported cases from the literature. RESULTS: Five new unrelated patients with CMT carrying the NEFL mutations P8R and N98S and the novel variant L311P were identified. Combined data from these cases and 62 kindreds from the literature revealed four common mutations (P8R, P22S, N98S and E396K) and three mutational hotspots accounting for 37 (55%) and 50 (75%) kindreds, respectively. Eight patients had de novo mutations. Loss of large-myelinated fibres was a uniform feature in a total of 21 sural nerve biopsies and 'onion bulb' formations and/or thin myelin sheaths were observed in 14 (67%) of them. The neurophysiological phenotype was broad but most patients with E90K and N98S had upper limb motor conduction velocities <38 m/s. Age of onset was ≤3 years in 25 cases. Pyramidal tract signs were described in 13 patients and 7 patients were initially diagnosed with or tested for inherited ataxia. Patients with E90K and N98S frequently presented before age 3 years and developed hearing loss or other neurological features including ataxia and/or cerebellar atrophy on brain MRI. CONCLUSIONS: NEFL-related CMT is clinically and genetically heterogeneous. Based on this study, however, we propose mutational hotspots and relevant clinical-genetic associations that may be helpful in the evaluation of NEFL sequence variants and the differential diagnosis with other forms of CMT

TIA1 Mutations in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia Promote Phase Separation and Alter Stress Granule Dynamics.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are age-related neurodegenerative disorders with shared genetic etiologies and overlapping clinical and pathological features. Here we studied a novel ALS/FTD family and identified the P362L mutation in the low-complexity domain (LCD) of T cell-restricted intracellular antigen-1 (TIA1). Subsequent genetic association analyses showed an increased burden of TIA1 LCD mutations in ALS patients compared to controls (p = 8.7 × 1

Complicated spastic paraplegia in patients with AP5Z1 mutations (SPG48)

Objective: Biallelic mutations in the AP5Z1 gene encoding the AP-5 ζ subunit have been described in a small number of patients with hereditary spastic paraplegia (HSP) (SPG48); we sought to define genotype–phenotype correlations in patients with homozygous or compound heterozygous sequence variants predicted to be deleterious. Methods: We performed clinical, radiologic, and pathologic studies in 6 patients with biallelic mutations in AP5Z1. Results: In 4 of the 6 patients, there was complete loss of AP-5 ζ protein. Clinical features encompassed not only prominent spastic paraparesis but also sensory and motor neuropathy, ataxia, dystonia, myoclonus, and parkinsonism. Skin fibroblasts from affected patients tested positive for periodic acid Schiff and autofluorescent storage material, while electron microscopic analysis demonstrated lamellar storage material consistent with abnormal storage of lysosomal material. Conclusions: Our findings expand the spectrum of AP5Z1-associated neurodegenerative disorders and point to clinical and pathophysiologic overlap between autosomal recessive forms of HSP and lysosomal storage disorders

Complicated spastic paraplegia in patients with AP5Z1 mutations (SPG48).

OBJECTIVE: Biallelic mutations in the AP5Z1 gene encoding the AP-5 ζ subunit have been described in a small number of patients with hereditary spastic paraplegia (HSP) (SPG48); we sought to define genotype-phenotype correlations in patients with homozygous or compound heterozygous sequence variants predicted to be deleterious. METHODS: We performed clinical, radiologic, and pathologic studies in 6 patients with biallelic mutations in AP5Z1. RESULTS: In 4 of the 6 patients, there was complete loss of AP-5 ζ protein. Clinical features encompassed not only prominent spastic paraparesis but also sensory and motor neuropathy, ataxia, dystonia, myoclonus, and parkinsonism. Skin fibroblasts from affected patients tested positive for periodic acid Schiff and autofluorescent storage material, while electron microscopic analysis demonstrated lamellar storage material consistent with abnormal storage of lysosomal material. CONCLUSIONS: Our findings expand the spectrum of AP5Z1-associated neurodegenerative disorders and point to clinical and pathophysiologic overlap between autosomal recessive forms of HSP and lysosomal storage disorders