Neocerebellar Crus I Abnormalities Associated with a Speech and Language Disorder Due to a Mutation in FOXP2

Bilateral volume reduction in the caudate nucleus has been established as a prominent brain abnormality associated with a FOXP2 mutation in affected members of the ‘KE family’, who present with developmental orofacial and verbal dyspraxia in conjunction with pervasive language deficits. Despite the gene’s early and prominent expression in the cerebellum and the evidence for reciprocal cerebellum-basal ganglia connectivity, very little is known about cerebellar abnormalities in affected KE members. Using cerebellum-specific voxel-based morphometry (VBM) and volumetry, we provide converging evidence from subsets of affected KE members scanned at three time points for grey matter (GM) volume reduction bilaterally in neocerebellar lobule VIIa Crus I compared with unaffected members and unrelated controls. We also show that right Crus I volume correlates with left and total caudate nucleus volumes in affected KE members, and that right and total Crus I volumes predict the performance of affected members in non-word repetition and non-verbal orofacial praxis. Crus I also shows bilateral hypo-activation in functional MRI in the affected KE members relative to controls during non-word repetition. The association of Crus I with key aspects of the behavioural phenotype of this FOXP2 point mutation is consistent with recent evidence of cerebellar involvement in complex motor sequencing. For the first time, specific cerebello-basal ganglia loops are implicated in the execution of complex oromotor sequences needed for human speech

Highly wear-resistant and biocompatible carbon nanocomposite coatings for dental implants

Diamond-like carbon coatings are increasingly used as wear-protective coatings for dental implants, artificial joints, etc. Despite their advantages, they may have several weak points such as high internal stress, poor adhesive properties or high sensitivity to ambient conditions. These weak points could be overcome in the case of a new carbon nanocomposite coating (CNC) deposited by using a C60 ion beam on a Co/Cr alloy. The structure of the coatings was investigated by Raman and XPS spectroscopy. The wear resistance was assessed by using a reciprocating tribotester under the loads up to 0.4 N in both dry and wet sliding conditions. Biocompatibility of the dental implants was tested in vivo on rabbits. Biocompatibility, bioactivity and mechanical durability of the CNC deposited on a Co/Cr alloy were investigated and compared with those of bulk Co/Cr and Ti alloys. The wear resistance of the CNC was found to be 250e650 fold higher compared to the Co/Cr and Ti alloys. Also, the CNC demonstrated much better biological properties with respect to formation of new tissues and absence of negative morphological parameters such as necrosis and demineralization. Development of the CNC is expected to aid in significant improvement of lifetime and quality of implants for dental applications

DJELOVANJE FLAVOMICINA I PROTEKSINA NA RAST I POPULACIJU CRIJEVNE MIKROFLORE BROJLERA HRANJENIH OBROCIMA RAZLIČITE KOLIČINE SOJINOG ULJA

A study was conducted to determine the effects of supplementary flavomycin and protexin in diets containing different levels of soy oil on growth performance and intestinal microbial population of broiler chicks. Three hundred and sixty one-day old Ross broiler chicks were randomly allocated to 6 treatments, with 4 replicates and 15 birds per each replicate in a randomized complete block design. Treatments were: 3% soy oil + flavomycin (400g/t), 3% soy oil + protexin (500g/t), 3% soy oil without any growth promoter, 6% soy oil + flavomycin (400g/t), 6% soy oil + protexin (500g/t) and 6% soy oil without any growth promoter. The experimental period was 42 days and feed intake and body weight gain were recorded weekly. The ileal numbers of Lactobacilli and E. coli were counted at 21 and 42day of age. The results showed that addition of protexin to diets (containing 3 or 6% soy oil), reduced feed intake and weight gain significantly (P<0.05). Supplementation diets with flavomycin, resulted in significantly lower counts of Lactobacilli and E. coli. Lactobacilli counts in the ileum of birds receiving protexin were significantly higher (P < 0.05) than those of the other treatments. It could be concluded that supplementing diets containing fat with protexin have negative effects on broiler performance and high numbers of lactobacilli may play a role in growth depression related to impaired fat absorption due to bile acid deconjugationProvedeno je istraživanje radi određivanja djelovanja dodatka flavomicina i proteksina u obroke koji sadrže različite količine sojinog ulja na rast i crijevnu populaciju mikroorganizama u brojlerskih pilića. Tristo šezdeset jednodnevnih brojlerskih pilića Ross podijeljeno je slučajnim odabirom u 6 tretiranja s 4 ponavljanja i 15 pilića po svakom ponavljanju u slučajnom potpunom bloku. Tretiranja su bila: 3% sojino ulje + flavomicin (400g/t), 3% sojino ulje + proteksin (500g/t), 3% sojino ulje bez promotora rasta, 6% sojino ulje + flavomicin (400g/t), 6% sojino ulje + proteksin (500g/t) i 6% sojino ulje bez promotora rasta. Pokusno razdoblje trajalo je 42 dana i tjedno je bilježen unos hrane i porast tjelesne mase. Lactobacilli i R.coli prebrojavani su 21. i 42. dana starosti. Rezultati su pokazali da je dodavanje proteksina u obroke (uz 3 ili 6% sojinog ulja) značajno smanjilo (P<0.05) unos hrane i prirast tjelesne mase. Obroci s dodanim flavomicinom dali su značajno manji broj Lactobacilla i E. coli. Broj Lactobacilla u ileumu pilića koji su dobivali proteksin bio je značajno veći (P<0.05) od broja u drugim tretiranjima. Može se zaključiti da je dodavanje proteksina obrocima koji su sadržavali mast negativno djelovalo na rezultate brojlera a visoki broj lactobacilla možda igra ulogu u smanjenju rasta u vezi sa smanjenom apsorpcijom masti zbog razdvajanja/dekonjugacije žučne kiseline

A rapid, hippocampus-dependent, item-memory signal that initiates context memory in humans.

The hippocampus, a structure located in the temporal lobes of the brain, is critical for the ability to recollect contextual details of past episodes. It is still debated whether the hippocampus also enables recognition memory for previously encountered context-free items. Brain imaging and neuropsychological patient studies have both individually provided conflicting answers to this question. We overcame the individual limitations of imaging and behavioral patient studies by combining them and observed a novel relationship between item memory and the hippocampus. We show that interindividual variability of hippocampal volumes in a large patient population with graded levels of hippocampal volume loss and controls correlates with context, but not item-memory performance. Nevertheless, concurrent measures of brain activity using magnetoencephalography reveal an early (350 ms) but sustained hippocampus-dependent signal that evolves from an item signal into a context memory signal. This is temporally distinct from an item-memory signal that is not hippocampus dependent. Thus, we provide evidence for a hippocampus-dependent item-memory process that initiates context retrieval without making a substantial contribution to item recognition performance. Our results reconcile contradictory evidence concerning hippocampal involvement in item memory and show that hippocampus-dependent mnemonic processes are more rapid than previously believed

Mutations in thyroid hormone receptor α1 cause premature neurogenesis and progenitor cell depletion in human cortical development

Mutations in the thyroid hormone receptor α 1 gene (THRA) have recently been identified as a cause of intellectual deficit in humans. Patients present with structural abnormalities including microencephaly, reduced cerebellar volume and decreased axonal density. Here, we show that directed differentiation of THRA mutant patient-derived induced pluripotent stem cells to forebrain neural progenitors is markedly reduced, but mutant progenitor cells can generate deep and upper cortical layer neurons and form functional neuronal networks. Quantitative lineage tracing shows that THRA mutation-containing progenitor cells exit the cell cycle prematurely, resulting in reduced clonal output. Using a micropatterned chip assay, we find that spatial self-organization of mutation-containing progenitor cells in vitro is impaired, consistent with down-regulated expression of cell–cell adhesion genes. These results reveal that thyroid hormone receptor α1 is required for normal neural progenitor cell proliferation in human cerebral cortical development. They also exemplify quantitative approaches for studying neurodevelopmental disorders using patient-derived cells in vitro

Overexpression of ubiquitin and amino acid permease genes in association with antimony resistance in Leishmania tropica field isolates

The mainstay therapy against leishmaniasis is still pentavalent antimonial drugs; however, the rate of antimony resistance is increasing in endemic regions such as Iran. Understanding the molecular basis of resistance to antimonials could be helpful to improve treatment strategies. This study aimed to recognize genes involved in antimony resistance of Leishmania tropica field isolates. Sensitive and resistant L. tropica parasites were isolated from anthroponotic cutaneous leishmaniasis patients and drug susceptibility of parasites to meglumine antimoniate (Glucantime®) was confirmed using in vitro assay. Then, complementary DNA-amplified fragment length polymorphism (cDNA-AFLP) and real-time reverse transcriptase-PCR (RT-PCR) approaches were utilized on mRNAs from resistant and sensitive L. tropica isolates. We identified 2 known genes, ubiquitin implicated in protein degradation and amino acid permease (AAP3) involved in arginine uptake. Also, we identified 1 gene encoding hypothetical protein. Real-time RT-PCR revealed a significant upregulation of ubiquitin (2.54-fold), and AAP3 (2.86-fold) (P<0.05) in a resistant isolate compared to a sensitive one. Our results suggest that overexpression of ubiquitin and AAP3 could potentially implicated in natural antimony resistance. © 2013, Korean Society for Parasitology and Tropical Medicine

Chimpanzees (Pan troglodytes) Fail a What-Where-When Task but Find Rewards by Using a Location-Based Association Strategy

Recollecting the what-where-when of an episode, or episodic-like memory, has been established in corvids and rodents. In humans, a linkage between remembering the past and imagining the future has been recognised. While chimpanzees can plan for the future, their episodic-like memory has hardly been investigated. We tested chimpanzees (Pan troglodytes) with an adapted food-caching paradigm. They observed the baiting of two locations amongst four and chose one after a given delay (15 min, 1 h or 5 h). We used two combinations of food types, a preferred and a less preferred food that disappeared at different rates. The subjects had to base their choices on the time elapsed since baiting, and on their memory of which food was where. They could recover either their preferred food or the one that remained present. All animals failed to obtain the preferred or present foods above chance levels. They were like-wise unsuccessful at choosing baited cups above chance levels. The subjects, thus, failed to use any feature of the baiting events to guide their choices. Nonetheless, their choices were not random, but the result of a developed location-based association strategy. Choices in the second half of the study correlated with the rewards obtained at each location in the first half of the study, independent from the choices made for each location in the first half of the study. This simple location-based strategy yielded a fair amount of food. The animals' failure to remember the what-where-when in the presented set-up may be due to the complexity of the task, rather than an inability to form episodic-like memories, as they even failed to remember what was where after 15 minutes

Genetic Variation of the Serotonin 2a Receptor Affects Hippocampal Novelty Processing in Humans

Serotonin (5-hydroxytryptamine, 5-HT) is an important neuromodulator in learning and memory processes. A functional genetic polymorphism of the 5-HT 2a receptor (5-HTR2a His452Tyr), which leads to blunted intracellular signaling, has previously been associated with explicit memory performance in several independent cohorts, but the underlying neural mechanisms are thus far unclear. The human hippocampus plays a critical role in memory, particularly in the detection and encoding of novel information. Here we investigated the relationship of 5-HTR2a His452Tyr and hippocampal novelty processing in 41 young, healthy subjects using functional magnetic resonance imaging (fMRI). Participants performed a novelty/familiarity task with complex scene stimuli, which was followed by a delayed recognition memory test 24 hours later. Compared to His homozygotes, Tyr carriers exhibited a diminished hippocampal response to novel stimuli and a higher tendency to judge novel stimuli as familiar during delayed recognition. Across the cohort, the false alarm rate during delayed recognition correlated negatively with the hippocampal novelty response. Our results suggest that previously reported effects of 5-HTR2a on explicit memory performance may, at least in part, be mediated by alterations of hippocampal novelty processing

How Emotion Strengthens the Recollective Experience: A Time-Dependent Hippocampal Process

Emotion significantly strengthens the subjective recollective experience even when objective accuracy of the memory is not improved. Here, we examine if this modulation is related to the effect of emotion on hippocampal-dependent memory consolidation. Two critical predictions follow from this hypothesis. First, since consolidation is assumed to take time, the enhancement in the recollective experience for emotional compared to neutral memories should become more apparent following a delay. Second, if the emotion advantage is critically dependent on the hippocampus, then the effects should be reduced in amnesic patients with hippocampal damage. To test these predictions we examined the recollective experience for emotional and neutral photos at two retention intervals (Experiment 1), and in amnesics and controls (Experiment 2). Emotional memories were associated with an enhancement in the recollective experience that was greatest after a delay, whereas familiarity was not influenced by emotion. In amnesics with hippocampal damage the emotion effect on recollective experience was reduced. Surprisingly, however, these patients still showed a general memory advantage for emotional compared to neutral items, but this effect was manifest primarily as a facilitation of familiarity. The results support the consolidation hypothesis of recollective experience, but suggest that the effects of emotion on episodic memory are not exclusively hippocampally mediated. Rather, emotion may enhance recognition by facilitating familiarity when recollection is impaired due to hippocampal damage

Separating content-specific retrieval from post-retrieval processing

According to cortical reinstatement accounts, neural processes engaged at the time of encoding are re-engaged at the time of memory retrieval. The temporal precision of event-related potentials (ERPs) has been exploited to assess this possibility, and in this study ERPs were acquired while people made memory judgments to visually presented words encoded in two different ways. There were reliable differences between the scalp distributions of the signatures of successful retrieval of different contents from 300 to 1100 ms after stimulus presentation. Moreover, the scalp distributions of these content-sensitive effects changed during this period. These findings are, to our knowledge, the first demonstration in one study that ERPs reflect content-specific processing in two separable ways: first, via reinstatement, and second, via downstream processes that operate on recovered information in the service of memory judgments