The epidemiology of fasciolosis in the inter-Andean valley of Cajamarca, Peru

Fasciolosis is recognised as a major problem in dairy cattle in parts of Peru. A longitudinal study of dairy cattle in Cajamarca, Peru was used to determine the annual pattern of infection with Fasciola hepatica. After a gradual increase from January, peak egg production occurred in August/September and then dropped rapidly. Indirect indicators of infection, eosinophil counts and serum liver-enzyme activities, indicated that the major period of new infection in cattle occurred from December to May each year. Examination of snails demonstrated that, although there was no clear annual cycle in snail abundance, the majority of snails infected with cercariae were found between January and March. Climatological data indicated that there was sufficient moisture for development of the parasite during a limited period each year, coinciding with the period of maximum abundance of cercaria-infected snails, but that irrigation could substantially alter the amount of water available. Infections in tracer-calves decreased from December to September, with little or no infection occurring between June and August, but suggesting that there could be significant infection prior to December. Thus a defined annual cycle of infection was observed, where cattle acquired infection from December to May and this infection matured to produce peak egg counts in August/September which were then available to infect the intermediate host for the next cycle of infection.     

Praziquantel Treatment Decreases Schistosoma mansoni Genetic Diversity in Experimental Infections

Background

Schistosomiasis has a considerable impact on public health in many tropical and subtropical areas. In the new world, schistosomiasis is caused by the digenetic trematode Schistosoma mansoni. Chemotherapy is the main measure for controlling schistosomiasis, and the current drug of choice for treatment is praziquantel (PZQ). Although PZQ is efficient and safe, its repetitive large-scale use in endemic areas may lead to the selection of resistant strains. Isolates less susceptible to PZQ have been found in the field and selected for in the laboratory. The impact of selecting strains with a decreased susceptibility phenotype on disease dynamics and parasite population genetics is not fully understood. This study addresses the impact of PZQ pressure on the genetics of a laboratory population by analyzing frequency variations of polymorphic genetic markers.

Methodology

Infected mice were treated with increasing PZQ doses until the highest dose of 3×300 mg/Kg was reached. The effect of PZQ treatment on the parasite population was assessed using five polymorphic microsatellite markers. Parasitological and genetic data were compared with those of the untreated control. After six parasite generations submitted to treatment, it was possible to obtain a S. mansoni population with decreased susceptibility to PZQ. In our experiments we also observed that female worms were more susceptible to PZQ than male worms.

Conclusions

The selective pressure exerted by PZQ led to decreased genetic variability in S. mansoni and increased endogamy. The understanding of how S. mansoni populations respond to successive drug pressure has important implications on the appearance and maintenance of a PZQ resistance phenotype in endemic regions.     

Anticipatory Smooth Eye Movements in Autism Spectrum Disorder

Smooth pursuit eye movements are important for vision because they maintain the line of sight on targets that move smoothly within the visual field. Smooth pursuit is driven by neural representations of motion, including a surprisingly strong influence of high-level signals representing expected motion. We studied anticipatory smooth eye movements (defined as smooth eye movements in the direction of expected future motion) produced by salient visual cues in a group of high-functioning observers with Autism Spectrum Disorder (ASD), a condition that has been associated with difficulties in either generating predictions, or translating predictions into effective motor commands. Eye movements were recorded while participants pursued the motion of a disc that moved within an outline drawing of an inverted Y-shaped tube. The cue to the motion path was a visual barrier that blocked the untraveled branch (right or left) of the tube. ASD participants showed strong anticipatory smooth eye movements whose velocity was the same as that of a group of neurotypical participants. Anticipatory smooth eye movements appeared on the very first cued trial, indicating that trial-by-trial learning was not responsible for the responses. These results are significant because they show that anticipatory capacities are intact in high-functioning ASD in cases where the cue to the motion path is highly salient and unambiguous. Once the ability to generate anticipatory pursuit is demonstrated, the study of the anticipatory responses with a variety of types of cues provides a window into the perceptual or cognitive processes that underlie the interpretation of events in natural environments or social situations.     

Contributo alla sistematica degli attinomiceti: XVII actinomices scabies (Thaxter) Waksman

Riassunto Gli autori studiano un ceppo di attinomicete che essi identificano comeA. scabies. Con l'occasione essi precisano le caratteristiche diagnostiche di questa specie secondo quanto risulta da un esame critico della bibliografia in argomento, mettendo in evidenza che i ceppi collezionati sotto questo nome nelle varie micoteche hanno spesso caratteristiche differenti. La base di questo equivoco è, nelle considerazioni degli autori, da trovare nel riferimento patogenetico, cioè, in altri termini, nel voler considerare la malattia dei tuberi scabbiosi come provocata da un'unica specie.Dopo aver dato le caratteristiche delle specie presentano il seguente quadro tassonomico: Actinomyces scabies (Thaxter 1890)Gussov (1914) emendamentoWaksman (1919)=Oospora scabies Thaxter (1890)Diagnosi: vedi pag. 273.Habitat: frequente nel Nord America; isolato per la prima volta in Europa daSpalla eComaschi da tuberi scabbiosi provenienti dalla Germania. Actinomyces scabies varietàanglica Baldacci eBoncompagni =Actinomyces scabies Thaxter emendamentoMillard eBurr.Differisce dalla specie per il micelio vegetativo grigio, il micelio aereo spiccatamente grigio e per il pigmento giallo diffuso nel substrato.Habitat: isole inglesi.

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Zusammenfassung Die Verfasser studieren einen Stamm von Actinomyceten, den sie alsActinomyces Scabies identifizieren. In diesem Zusammenhang stellen sie die diagnostischen Merkmale dieser Art fest, bei kritischer Berücksichtigung der Literatur. Sie stellen fest, dass die unter diesem Namen gesammelten Stämme in den verschiedenen Mycoteken oft verschiedene Merkmale besitzen.Der Grund dieses Missverständnisses liegt, nach den Verfassern, in der pathogenischen Beziehung, i.c., dass man die in den vom Schorf befallenen Knollen die Krankheit als von einer einzigen Art verursacht annehmen will.Nachdem sie die Merkmale der Art festgelegt haben, geben sie die folgende Classification: Actinomyces scabies (Thaxter 1890)Gussov (1914), verbessert von Waksman (1919)=Oospora scabies Thaxter (1890).Diagnose: sieh Seite 273.Habitat: in Nord America ziemlich verbreitet und in Europa das erste Mal vonSpalla undComaschi aus schorfigen Knollen aus Deutschland isoliert. Actinomyces scabies Varietätanglica Baldacci eBoncompagni=Actinomyces scabies Thaxter verbessert vonMillard undBurr.Er unterscheidet sich von der Art durch ein graues vegetatives Mycel, durch ein sehr deutliches graues Luftmycel und durch ein gelbes im Substrat verbreitetes Pigment.Habitat: in England.

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I precedenti Contributi sono stati integralmente pubblicati sugli Atti dell'Istituto Botanico di Pavia e, in riassunto, su questa Rivista.     

GJB2 Gene Mutations in Syndromic Skin Diseases with Sensorineural Hearing Loss

The GJB2 gene is located on chromosome 13q12 and it encodes the connexin 26, a transmembrane protein involved in cell-cell attachment of almost all tissues. GJB2 mutations cause autosomal recessive (DFNB1) and sometimes dominant (DFNA3) non-syndromic sensorineural hearing loss. Moreover, it has been demonstrated that connexins are involved in regulation of growth and differentiation of epidermis and, in fact, GJB2 mutations have also been identified in syndromic disorders with hearing loss associated with various skin disease phenotypes. GJB2 mutations associated with skin disease are, in general, transmitted with a dominant inheritance pattern. Nonsyndromic deafness is caused prevalently by a loss-of-function, while literature evidences suggest for syndromic deafness a mechanism based on gain-of-function. The spectrum of skin manifestations associated with some mutations seems to have a very high phenotypic variability. Why some mutations can lead to widely varying cutaneous manifestations is poorly understood and in particular, the reason why the skin disease-deafness phenotypes differ from each other thus remains unclear. This review provides an overview of recent findings concerning pathogenesis of syndromic deafness imputable to GJB2 mutations with an emphasis on relevant clinical genotype-phenotype correlations. After describing connexin 26 fundamental characteristics, the most relevant and recent information about its known mutations involved in the syndromic forms causing hearing loss and skin problems are summarized. The possible effects of the mutations on channel expression and function are discussed.     

Localization, purification, and characterization of the rabbit sarcoplasmic reticulum associated calmodulin-dependent protein kinase

The Ca2+/calmodulin dependent protein kinase associated with the sarcoplasmic reticulum membranes (SR CaM kinase) plays a specific and important role in the modulation of both Ca2+ uptake and release functions of the sarcoplasmic reticulum itself. In this work we have localized a 60 kD SR CaM kinase in slow and fast twitch rabbit skeletal muscle fractions; the kinase was present in both the longitudinal and the junctional sarcoplasmic reticulum. We then developed a procedure for the purification of the active kinase from the longitudinal sarcoplasmic reticulum and performed biochemical and functional characterization of the enzyme. Differently from what was previously suggested, our analysis shows that the biochemical properties of the purified SR CaM kinase (Ca2+ sensitivity, K0.5 for calmodulin, Km for ATP, IC50 for the specific inhibitory peptide (290-309), autophosphorylation properties) are not significantly different from those of the soluble multifunctional CaM kinase II. Moreover, we show that the purified SR CaM kinase retains the ability to autophosphorylate in a Ca2+/calmodulin-dependent manner, becoming a Ca2+-independent enzyme. In the light of the knowledge of the rabbit SR CaM kinase biochemical properties, we propose and discuss the possibility that, under physiological conditions, the activity of the autophosphorylated kinase persists when the Ca2+ transient is over.     

In‐depth protein profiling of the postsynaptic density from mouse hippocampus using data‐independent acquisition proteomics

Located at neuronal terminals, the postsynaptic density (PSD) is a highly complex network of cytoskeletal scaffolding and signaling proteins responsible for the transduction and modulation of glutamatergic signaling between neurons. Using ion‐mobility enhanced data‐independent label‐free LC‐MS/MS, we established a reference proteome of crude synaptosomes, synaptic junctions, and PSD derived from mouse hippocampus including TOP3‐based absolute quantification values for identified proteins. The final dataset across all fractions comprised 49 491 peptides corresponding to 4558 protein groups. Of these, 2102 protein groups were identified in highly purified PSD in at least two biological replicates. Identified proteins play pivotal roles in neurological and synaptic processes providing a rich resource for studies on hippocampal PSD function as well as on the pathogenesis of neuropsychiatric disorders. All MS data have been deposited in the ProteomeXchange with identifier PXD000590 ( http://proteomecentral.proteomexchange.org/dataset/PXD000590 ).     

Weight Loss Predicts Progression of Mild Cognitive Impairment to Alzheimer’s Disease

Background

Weight loss is common in people with Alzheimer’s disease (AD) and it could be a marker of impending AD in Mild Cognitive Impairment (MCI) and improve prognostic accuracy, if accelerated progression to AD would be shown.

Aims

To assess weight loss as a predictor of dementia and AD in MCI.

Methods

One hundred twenty-five subjects with MCI (age 73.8 ± 7.1 years) were followed for an average of 4 years. Two weight measurements were carried out at a minimum time interval of one year. Dementia was defined according to DSM-IV criteria and AD according to NINCDS-ADRDA criteria. Weight loss was defined as a ≥4% decrease in baseline weight.

Results

Fifty-three (42.4%) MCI progressed to dementia, which was of the AD-type in half of the cases. Weight loss was associated with a 3.4-fold increased risk of dementia (95% CI = 1.5–6.9) and a 3.2-fold increased risk of AD (95% CI = 1.4–8.3). In terms of years lived without disease, weight loss was associated to a 2.3 and 2.5 years earlier onset of dementia and AD.

Conclusions

Accelerated progression towards dementia and AD is expected when weight loss is observed in MCI patients. Weight should be closely monitored in elderly with mild cognitive impairment.     

Inhibition of elongation and H+ and K+ transport by the phosphodiesterase inhibitor aminophylline in plant tissue

Aminophylline, an inhibitor of cyclic nucleotide phosphodiesterase (EC 3.1.4.17), inhibits elongation and correlated H⁺ and K⁺ transport in embryos of Haplopappus gracilis and in pea internode segments. Moreover, the drug strongly inhibits the stimulation of these processes by fusicoccin and indole-3-acetic acid and reduces passive permeability of the membrane. The possible mechanisms of action of aminophylline are discussed.Abbreviations cAMP adenosine 3:5-cyclic monophosphate - FC fusicoccin - IAA indole-3-acetic acid - MES 2-N-morpholinoethanesulfonic acid - PDE cyclic nucleotide phosphodiesterase     

Extensive activation,tissue trafficking,turnover and functional impairment of NK cells in COVID-19 patients at disease onset associates with subsequent disease severity

The SARS-CoV-2 infection causes severe respiratory involvement (COVID-19) in 5–20% of patients through initial immune derangement, followed by intense cytokine production and vascular leakage. Evidence of immune involvement point to the participation of T, B, and NK cells in the lack of control of virus replication leading to COVID-19. NK cells contribute to early phases of virus control and to the regulation of adaptive responses. The precise mechanism of NK cell dysregulation is poorly understood, with little information on tissue margination or turnover. We investigated these aspects by multiparameter flow cytometry in a cohort of 28 patients hospitalized with early COVID-19.Relevant decreases in CD56^brightCD16+/- NK subsets were detected, with a shift of circulating NK cells toward more mature CD56^dimCD16+KIR+NKG2A+ and “memory” KIR+CD57+CD85j+ cells with increased inhibitory NKG2A and KIR molecules. Impaired cytotoxicity and IFN-γ production were associated with conserved expression of natural cytotoxicity receptors and perforin. Moreover, intense NK cell activation with increased HLA-DR and CD69 expression was associated with the circulation of CD69+CD103+ CXCR6+ tissue-resident NK cells and of CD34+DNAM-1^brightCXCR4+ inflammatory precursors to mature functional NK cells. Severe disease trajectories were directly associated with the proportion of CD34+DNAM-1^brightCXCR4+ precursors and inversely associated with the proportion of NKG2D+ and of CD103+ NK cells.Intense NK cell activation and trafficking to and from tissues occurs early in COVID-19, and is associated with subsequent disease progression, providing an insight into the mechanism of clinical deterioration. Strategies to positively manipulate tissue-resident NK cell responses may provide advantages to future therapeutic and vaccine approaches.