Pattern of Tick Aggregation on Mice: Larger Than Expected Distribution Tail Enhances the Spread of Tick-Borne Pathogens

The spread of tick-borne pathogens represents an important threat to human and animal health in many parts of Eurasia. Here, we analysed a 9-year time series of Ixodes ricinus ticks feeding on Apodemus flavicollis mice (main reservoir-competent host for tick-borne encephalitis, TBE) sampled in Trentino (Northern Italy). The tail of the distribution of the number of ticks per host was fitted by three theoretical distributions: Negative Binomial (NB), Poisson-LogNormal (PoiLN), and Power-Law (PL). The fit with theoretical distributions indicated that the tail of the tick infestation pattern on mice is better described by the PL distribution. Moreover, we found that the tail of the distribution significantly changes with seasonal variations in host abundance. In order to investigate the effect of different tails of tick distribution on the invasion of a non-systemically transmitted pathogen, we simulated the transmission of a TBE-like virus between susceptible and infective ticks using a stochastic model. Model simulations indicated different outcomes of disease spreading when considering different distribution laws of ticks among hosts. Specifically, we found that the epidemic threshold and the prevalence equilibria obtained in epidemiological simulations with PL distribution are a good approximation of those observed in simulations feed by the empirical distribution. Moreover, we also found that the epidemic threshold for disease invasion was lower when considering the seasonal variation of tick aggregation.     

Mutation screening of melatonin-related genes in patients with autism spectrum disorders

Background

One consistent finding in autism spectrum disorders (ASD) is a decreased level of the pineal gland hormone melatonin and it has recently been demonstrated that this decrease to a large extent is due to low activity of the acetylserotonin O-methyltransferase (ASMT), the last enzyme in the melatonin synthesis pathway. Moreover, mutations in the ASMT gene have been identified, including a splice site mutation, that were associated with low ASMT activity and melatonin secretion, suggesting that the low ASMT activity observed in autism is, at least partly, due to variation within the ASMT gene.

Methods

In the present study, we have investigated all the genes involved in the melatonin pathway by mutation screening of AA-NAT (arylalkylamine N-acetyltransferase), ASMT, MTNR1A, MTNR1B (melatonin receptor 1A and 1B) and GPR50 (G protein-coupled receptor 50), encoding both synthesis enzymes and the three main receptors of melatonin, in 109 patients with autism spectrum disorders (ASD). A cohort of 188 subjects from the general population was used as a comparison group and was genotyped for the variants identified in the patient sample.

Results

Several rare variants were identified in patients with ASD, including the previously reported splice site mutation in ASMT (IVS5+2T>C). Of the variants affecting protein sequence, only the V124I in the MTNR1B gene was absent in our comparison group. However, mutations were found in upstream regulatory regions in three of the genes investigated, ASMT, MTNR1A, and MTNR1B.

Conclusions

Our report of another ASD patient carrying the splice site mutation IVS5+2T>C, in ASMT further supports an involvement of this gene in autism. Moreover, our results also suggest that other melatonin related genes might be interesting candidates for further investigation in the search for genes involved in autism spectrum disorders and related neurobehavioral phenotypes. However, further studies of the novel variants identified in this study are warranted to shed light on their potential role in the pathophysiology of these disorders.     

Semaphorin 4D regulates gonadotropin hormone-releasing hormone-1 neuronal migration through PlexinB1-Met complex

In mammals, reproduction is dependent on specific neurons secreting the neuropeptide gonadotropin hormone–releasing hormone-1 (GnRH-1). These cells originate during embryonic development in the olfactory placode and migrate into the forebrain, where they become integral members of the hypothalamic–pituitary–gonadal axis. This migratory process is regulated by a wide range of guidance cues, which allow GnRH-1 cells to travel over long distances to reach their appropriate destinations. The Semaphorin4D (Sema4D) receptor, PlexinB1, is highly expressed in the developing olfactory placode, but its function in this context is still unknown. Here, we demonstrate that PlexinB1-deficient mice exhibit a migratory defect of GnRH-1 neurons, resulting in reduction of this cell population in the adult brain. Moreover, Sema4D promotes directional migration in GnRH-1 cells by coupling PlexinB1 with activation of the Met tyrosine kinase (hepatocyte growth factor receptor). This work identifies a function for PlexinB1 during brain development and provides evidence that Sema4D controls migration of GnRH-1 neurons.     

AN ISOTOPIC MICROMETHOD FOR THE MEASUREMENT OF CHOLINESTERASE ACTIVITY IN INDIVIDUAL CELLS

—A microisotopic method for measuring acetylcholinesterase activity in isolated cells is described. The assay employs [¹⁴C]acetylcholine and can measure 7 × 10^-12 moles of acetylcholine hydrolysed/hr in 50-150 samples per experiment. The method described has been applied to the measurement of cholinesterase activity in individual sympathetic ganglion cells of the cat. It has been shown that under standard conditions the substrate has complete access to the enzymatic site.     

Accumulation and metabolism of pipecolic acid in the brain and other organs of the mouse

The long-term accumulation of pipecolic acid, as well as its disappearance following exogenous administration was studied in brain and other organs of the mouse. Mice were pulse-injected intraperitoneally or intravenously with 1Ci[³H]D,l-pipecolic acid (6.9 nmol/mouse=2.9 g/kg). The total radioactivity retained in tissues was measured in brain, liver, and kidney, as well as in plasma during the period 1 min to 24 hr. TLC separation of DNP-derivatives was performed. Three features of the pattern of retention of pipecolic acid are most salient; first the rapid accumulation in brain, second the rapid secretion of this compound in the urine, and third the long-lasting steady levels of radioactivity maintained in brain.Sixty minutes after i.v. injection, the brain/plasma ratio is approximately 0.2 and approaches unity only at 5 hr. Following intraperitoneal injection the percent recovered as pipecolic acid in brain is 78% at 30 min and 71% at 120 min, suggesting a slow metabolic activity. Liver shows a different trend than brain with a slower accumulation and a faster disappearance. Kidney shows a pattern similar to plasma with a rapid secretion of radioactivity into urine which correlates well with the exponential decrease in plasma and urine. The administration of probenecid significantly increases radioactivity due to pipecolic acid in brain, liver, and urine. Formation of -aminoadipic acid, a known metabolite of pipecolic acid, can be demonstrated in kidney 30 min after intraperitoneal injection. The present data together with results obtained previously with intracarotid injections suggest that pipecolic acid is taken up in the mouse brain from the circulation. Most of the pipecolic acid taken up is rapidly removed through the circulation and secreted in the urine; however, a small part is retained and probably metabolized by brain and kidney.     

The skull and vertebral column pathology of Ancient Egyptians. A study of the Marro Collection

The skull and vertebral column pathology of the Ancient Egyptian skeletal remains of the Marro Collection (1118 individuals) is mainly represented by “common” degenerative and inflammatory osteo-articular alterations. Apart from these, three cases of ankylosing spondylitis and two cases of probable multiple myeloma are described in detail. The frequency of these conditions seems to be almost the same as in modern times. Furthermore, a skull with larger osteolitic areas of probable metastatic origin is described.     

Modeling the spread of vector-borne diseases on bipartite networks

Background

Vector-borne diseases for which transmission occurs exclusively between vectors and hosts can be modeled as spreading on a bipartite network.

Methodology/Principal Findings

In such models the spreading of the disease strongly depends on the degree distribution of the two classes of nodes. It is sufficient for one of the classes to have a scale-free degree distribution with a slow enough decay for the network to have asymptotically vanishing epidemic threshold. Data on the distribution of Ixodes ricinus ticks on mice and lizards from two independent studies are well described by a scale-free distribution compatible with an asymptotically vanishing epidemic threshold. The commonly used negative binomial, instead, cannot describe the right tail of the empirical distribution.

Conclusions/Significance

The extreme aggregation of vectors on hosts, described by the power-law decay of the degree distribution, makes the epidemic threshold decrease with the size of the network and vanish asymptotically.