Early network activity propagates bidirectionally between hippocampus and cortex

Spontaneous activity in the developing brain helps refine neuronal connections before the arrival of sensory‐driven neuronal activity. In mouse neocortex during the first postnatal week, waves of spontaneous activity originating from pacemaker regions in the septal nucleus and piriform cortex propagate through the neocortex. Using high‐speed Ca²⁺ imaging to resolve the spatiotemporal dynamics of wave propagation in parasagittal mouse brain slices, we show that the hippocampus can act as an additional source of neocortical waves. Some waves that originate in the hippocampus remain restricted to that structure, while others pause at the hippocampus‐neocortex boundary and then propagate into the neocortex. Blocking GABAergic neurotransmission decreases the likelihood of wave propagation into neocortex, whereas blocking glutamatergic neurotransmission eliminates spontaneous and evoked hippocampal waves. A subset of hippocampal and cortical waves trigger Ca²⁺ waves in astrocytic networks after a brief delay. Hippocampal waves accompanied by Ca²⁺ elevation in astrocytes are more likely to propagate into the neocortex. Finally, we show that two structures in our preparation that initiate waves—the hippocampus and the piriform cortex—can be electrically stimulated to initiate propagating waves at lower thresholds than the neocortex, indicating that the intrinsic circuit properties of those regions are responsible for their pacemaker function. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 661–672, 2016     

Role of ultrasonography in diagnosing early rheumatoid arthritis and remission of rheumatoid arthritis - a systematic review of the literature

Introduction

Ultrasonography (US) might have an added value to clinical examination in diagnosing early rheumatoid arthritis (RA) and assessing remission of RA. We aimed to clarify the added value of US in RA in these situations performing a systematic review.

Methods

A systematic literature search was performed for RA, US, diagnosis and remission. Methodological quality was assessed; the wide variability in the design of studies prohibited pooling of results.

Results

Six papers on the added value of US diagnosing early RA were found, in which at least bilateral metacarpophalangeal (MCP), wrists and metatarsophalangeal (MTP) joints were scanned. Compared to clinical examination, US was superior with regard to detecting synovitis and predicting progression to persistent arthritis or RA. Eleven papers on assessing remission were identified, in which at least the wrist and the MCP joints of the dominant hand were scanned. Often US detected inflammation in patients clinically in remission, irrespective of the remission criteria used. Power Doppler signs of synovitis predicted X-ray progression and future flare in patients clinically in remission.

Conclusions

US appears to have added value to clinical examination for diagnosing of RA when scanning at least MCP, wrist and MTP joints, and, when evaluating remission of RA, scanning at least wrist and MCP joints of the dominant hand. For both purposes primarily power Doppler US might be used since its results are less equivocal than those of greyscale US.     

mtDNA haplotypes differ in their probability of being eliminated by a mass die-off in an abundant seabird

In this study, we take advantage of a natural experiment--a 2004 mass die-off of the Common Murre in Alaska to determine whether closely related mtDNA haplotypes differ in their probability of being eliminated during such a short term but a marked event removing hundreds of thousands of individuals. We sequenced complete mtDNA ND2 gene (1041 bp) for 168 Common Murres sampled from seven breeding colonies across Alaska before the 2004 die-off and 127 dead murres washed ashore during the die-off. We found little mtDNA variation and lack of geographical structuring among the seven Common Murre breeding colonies in Alaska. A comparison of the single-dominant mtDNA haplotype's frequency between live murres sampled on breeding colonies before the die-off (73.2%; 95% confidence interval 66.3-79.9%) and dead murres sampled during the die-off (59.1%; 95% confidence interval 50.4-67.4%; Fisher's exact P=0.01) showed that carriers of the dominant haplotype were significantly less likely to die than carriers of other haplotypes. At the same time, the ratio of non-synonymous to synonymous substitutions did not differ between live (10:35) and dead birds (18:34; Fisher's exact P=0.26), indicating that non-synonymous substitutions were as likely to be eliminated as synonymous substitutions. These results are consistent with the possibility of positive selection on the dominant mtDNA haplotype during the die-off.     

Mycobacterium bovis strain bacillus Calmette-Guérin-induced liver granulomas contain a diverse TCR repertoire, but a monoclonal T cell population is sufficient for protective granuloma formation

Granuloma formation is a form of delayed-type hypersensitivity requiring CD4(+) T cells. Granulomas control the growth and dissemination of pathogens, preventing host inflammation from harming surrounding tissues. Using a murine model of Mycobacterium bovis strain bacillus Calmette-Guérin (BCG) infection we studied the extent of T cell heterogeneity present in liver granulomas. We demonstrate that the TCR repertoire of granuloma-infiltrating T cells is very diverse even at the single-granuloma level, suggesting that before granuloma closure, a large number of different T cells are recruited to the lesion. At the same time, the TCR repertoire is selected, because AND TCR transgenic T cells (Valpha11/Vbeta3 anti-pigeon cytochrome c) are preferentially excluded from granulomas of BCG-infected AND mice, and cells expressing secondary endemic Vbeta-chains are enriched among AND cells homing to granulomas. Next, we addressed whether TCR heterogeneity is required for effective granuloma formation. We infected 5CC7/recombinase-activating gene 2(-/-) mice with recombinant BCG that express pigeon cytochrome c peptide in a mycobacterial 19-kDa bacterial surface lipoprotein. A CD4(+) T cell with a single specificity in the absence of CD8(+) T cells is sufficient to form granulomas and adequately control bacteria. Our study shows that expanded monoclonal T cell populations can be protective in mycobacterial infection.     

The transmission of digenetic trematodes: style, elegance, complexity

Traditionally, the field of parasitology has dealt with eukaryoticanimals, to the exclusion of viruses, bacteria, fungi, etc.,which is the way it will be approached here. The focus of thepresent paper will be on certain ecological aspects of the lifecycles and life-history strategies employed by the Digenea,a diverse group of platyhelminths that includes some 25,000species. More specifically, the review will consider the natureof host/parasite interactions within molluscan intermediatehosts and the manner in which these interactions, or lack thereof,function in structuring trematode infracommunities within thesemolluscan intermediate hosts. Literature in this area suggeststhat predation/competition may be a significant structuringforce for infracommunities in certain marine prosobranchs, butnot others, and that temporal/spatial factors may be involvedas structuring mechanisms in at least some freshwater pulmonates.     

Plagioporus sinitsini (Digenea : Opecoelidae): a one-host life cycle

Adult Plagioporus sinitsini occur within daughter sporocysts voided with the feces of prosobranch snails Elimia symmetrica in Basin Creek, North Carolina. These worms produced eggs containing active miracidia while still in the snail. Adults in snails and adults in rosyside dace, Clinostomus funduloides, collected from the same stream were indistinguishable morphometrically. Adults in snails develop from cotylocercous cercariae sequestered in daughter sporocysts that pass through the metacercaria stage. These observations, and previous study in Michigan, suggest that the life cycle of P. sinitsini has 3 potential pathways, i.e., a 3-host life cycle involving molluscan, arthropod, and piscine hosts, a 2-host life cycle involving only molluscan and piscine hosts, and a 1-host life cycle involving only the snail host. The truncated life cycles do not appear to be the result of paedomorphosis.     

Genetic loss of D-amino acid oxidase activity reverses schizophrenia-like phenotypes in mice

Reduced function of the N -methyl- d -aspartate receptor (NMDAR) has been implicated in the pathophysiology of schizophrenia. The NMDAR contains a glycine binding site in its NR1 subunit that may be a useful target for the treatment of schizophrenia. In this study, we assessed the therapeutic potential of long-term increases in the brain levels of the endogenous NMDAR glycine site agonist D-serine, through the genetic inactivation of its catabolic enzyme D-amino acid oxidase (DAO) in mice. The effects of eliminating DAO function were investigated in mice that display schizophrenia-related behavioral deficits due to a mutation ( Grin 1 ^D481N ) in the NR1 subunit that results in a reduction in NMDAR glycine affinity. Grin 1 ^D481N mice show deficits in sociability, prolonged latent inhibition, enhanced startle reactivity and impaired spatial memory. The hypofunctional Dao 1 ^G181R mutation elevated brain levels of D-serine, but alone it did not affect performance in the behavioral measures. Compared to animals with only the Grin 1 ^D481N mutation, mice with both the Dao1 ^G181R and Grin 1 ^D481N mutations displayed an improvement in social approach and spatial memory retention, as well as a reversal of abnormally persistent latent inhibition and a partial normalization of startle responses. Thus, an increased level of D-serine resulting from decreased catalysis corrected the performance of mice with deficient NMDAR glycine site activation in behavioral tasks relevant to the negative and cognitive symptoms of schizophrenia. Diminished DAO activity and elevations in D-serine may serve as an effective therapeutic intervention for the treatment of psychiatric symptoms.     

Control of nematode parasites by grazing management—II. Decontamination of sheep and cattle pastures by varying periods of grazing with the alternate host

Commencing in December 1970, paddocks of a uniform series of sheep pastures were grazed for 6, 12 or 24 weeks by either yearling steers is or yearling ewes. Cattle pastures were treated similarly. All ewes and steers were pre-dosed with anthelmintic.At the conclusion of alternate grazing the effectiveness of the grazing treatments was evaluated by grazing each paddock for 1 month with either ten worm-free lambs (sheep pastures) or three wormfree calves (cattle pastures). The test animals were then slaughtered for total worm counts. The grazing of sheep pastures with cattle for 6, 12 or 24 weeks from December onwards resulted in reductions in numbers of Haemonchus contortus and Trichostrongylus colubriformis in test lambs. In comparison with continuous grazing by sheep, Nematodirus spp was only reduced after 24 weeks grazing by cattle. Cattle pastures grazed by sheep for 6 weeks showed no reduction in numbers of Ostertagia ostertagi or Cooperia oncophora in test calves. However after 12 weeks with sheep, numbers of O. ostertagi though not C. oncophora were reduced and after 24 weeks of alternate grazing both these species were reduced.Calves following the 6 week sheep treatments acquired both Haemonchus contortus and Trichostrongylus colubriformis and the calves from the 12 week sheep treatment paddock also carried H. contortus. For sheep the only evidence of cross-transmission was the occurrence of small numbers of Cooperia oncophora in test lambs from the 24 week cattle grazing treatment.The results provide evidence that sequential stocking with cattle and sheep in conjunction with anthelmintic treatment is an effective management strategy for preparing parasitologically safer pastures, but further information is required to determine the optimum timing of sequential stocking in farming situations.