Agrin/Lrp4 signal constrains MuSK-dependent neuromuscular synapse development in appendicular muscle.

The receptor tyrosine kinase MuSK, its co-receptor Lrp4 and the Agrin ligand constitute a signaling pathway that is crucial in axial muscle for neuromuscular synapse development, yet whether this pathway functions similarly in appendicular muscle is unclear. Here, using the larval zebrafish pectoral fin, equivalent to tetrapod forelimbs, we show that, similar to axial muscle, developing appendicular muscles form aneural acetylcholine receptor (AChR) clusters prior to innervation. As motor axons arrive, neural AChR clusters form, eventually leading to functional synapses in a MuSK-dependent manner. We find that loss of Agrin or Lrp4 function, which abolishes synaptic AChR clusters in axial muscle, results in enlarged presynaptic nerve regions and progressively expanding appendicular AChR clusters, mimicking the consequences of motoneuron ablation. Moreover, musk depletion in lrp4 mutants partially restores synaptic AChR patterning. Combined, our results provide compelling evidence that, in addition to the canonical pathway in which Agrin/Lrp4 stimulates MuSK activity, Agrin/Lrp4 signaling in appendicular muscle constrains MuSK-dependent neuromuscular synapse organization. Thus, we reveal a previously unappreciated role for Agrin/Lrp4 signaling, thereby highlighting distinct differences between axial and appendicular synapse development.

Forest phenoclusters for Argentina based on vegetation phenology and climate.

Forest biodiversity conservation and species distribution modeling greatly benefit from broad-scale forest maps depicting tree species or forest types rather than just presence and absence of forest, or coarse classifications. Ideally, such maps would stem from satellite image classification based on abundant field data for both model training and accuracy assessments, but such field data do not exist in many parts of the globe. However, different forest types and tree species differ in their vegetation phenology, offering an opportunity to map and characterize forests based on the seasonal dynamic of vegetation indices and auxiliary data. Our goal was to map and characterize forests based on both land surface phenology and climate patterns, defined here as forest phenoclusters. We applied our methodology in Argentina (2.8 million km2 ), which has a wide variety of forests, from rainforests to cold-temperate forests. We calculated phenology measures after fitting a harmonic curve of the enhanced vegetation index (EVI) time series derived from 30-m Sentinel 2 and Landsat 8 data from 2018-2019. For climate, we calculated land surface temperature (LST) from Band 10 of the thermal infrared sensor (TIRS) of Landsat 8, and precipitation from Worldclim (BIO12). We performed stratified X-means cluster classifications followed by hierarchical clustering. The resulting clusters separated well into 54 forest phenoclusters with unique combinations of vegetation phenology and climate characteristics. The EVI 90th percentile was more important than our climate and other phenology measures in providing separability among different forest phenoclusters. Our results highlight the potential of combining remotely sensed phenology measures and climate data to improve broad-scale forest mapping for different management and conservation goals, capturing functional rather than structural or compositional characteristics between and within tree species. Our approach results in classifications that go beyond simple forest-nonforest in areas where the lack of detailed ecological field data precludes tree species-level classifications, yet conservation needs are high. Our map of forest phenoclusters is a valuable tool for the assessment of natural resources, and the management of the environment at scales relevant for conservation actions.

Dynein promotes sustained axonal growth and Schwann cell remodeling early during peripheral nerve regeneration.

Following injury, axons of the peripheral nervous system have retained the capacity for regeneration. While it is well established that injury signals require molecular motors for their transport from the injury site to the nucleus, whether kinesin and dynein motors play additional roles in peripheral nerve regeneration is not well understood. Here we use genetic mutants of motor proteins in a zebrafish peripheral nerve regeneration model to visualize and define in vivo roles for kinesin and dynein. We find that both kinesin-1 and dynein are required for zebrafish peripheral nerve regeneration. While loss of kinesin-1 reduced the overall robustness of axonal regrowth, loss of dynein dramatically impaired axonal regeneration and also reduced injury-induced Schwann cell remodeling. Chimeras between wild type and dynein mutant embryos demonstrate that dynein function in neurons is sufficient to promote axonal regrowth. Finally, by simultaneously monitoring actin and microtubule dynamics in regenerating axons we find that dynein appears dispensable to initiate axonal regrowth, but is critical to stabilize microtubules, thereby sustaining axonal regeneration. These results reveal two previously unappreciated roles for dynein during peripheral nerve regeneration, initiating injury induced Schwann cell remodeling and stabilizing axonal microtubules to sustain axonal regrowth.

Celsr3 drives development and connectivity of the acoustic startle hindbrain circuit.

In the developing brain, groups of neurons organize into functional circuits that direct diverse behaviors. One such behavior is the evolutionarily conserved acoustic startle response, which in zebrafish is mediated by a well-defined hindbrain circuit. While numerous molecular pathways that guide neurons to their synaptic partners have been identified, it is unclear if and to what extent distinct neuron populations in the startle circuit utilize shared molecular pathways to ensure coordinated development. Here, we show that the planar cell polarity (PCP)-associated atypical cadherins Celsr3 and Celsr2, as well as the Celsr binding partner Frizzled 3a/Fzd3a, are critical for axon guidance of two neuron types that form synapses with each other: the command-like neuron Mauthner cells that drive the acoustic startle escape response, and spiral fiber neurons which provide excitatory input to Mauthner cells. We find that Mauthner axon growth towards synaptic targets is vital for Mauthner survival. We also demonstrate that symmetric spiral fiber input to Mauthner cells is critical for escape direction, which is necessary to respond to directional threats. Moreover, we identify distinct roles for Celsr3 and Celsr2, as Celsr3 is required for startle circuit development while Celsr2 is dispensable, though Celsr2 can partially compensate for loss of Celsr3 in Mauthner cells. This contrasts with facial branchiomotor neuron migration in the hindbrain, which requires Celsr2 while we find that Celsr3 is dispensable. Combined, our data uncover critical and distinct roles for individual PCP components during assembly of the acoustic startle hindbrain circuit.

Six-year evaluation of the atraumatic restorative treatment approach in permanent-tooth Class III restorations.

PURPOSE: The aim of this study was to assess the 6-year performance of the ART (atraumatic restorative treatment) approach in Class III restorations in permanent teeth. MATERIALS AND METHODS: A total of 127 ART Class III restorations, using Ketac-Molar (3M ESPE) ionomer cement, was performed in 58 adult patients by one experienced operator in 1998. After a 6 years, 34 patients and 65 restorations were evaluated according to ART criteria. Two calibrated examiners carried out the evaluation. Data were analyzed by exact 95% Confidence Interval and Survival Analysis using the Jackknife method for standard error determination. RESULTS: Among assessed restorations, 73.8% (95% CI = 61.5% to 86.2%) were in good condition and classified as successful, with a 67.6% (95% CI = 54.4% to 80.7%) cumulative survival rate. Failed restorations included 13.9% completely or partially missing restorations, 9.2% restorations that had been replaced by other treatment, 1.5% restorations with a large defect at the margin, and 1.5% restorations that presented high wear on the surface. No caries was observed even in those teeth in which restorations were absent. CONCLUSION: The 6-year success rate of the ART approach in anterior permanent teeth (Class III) was considered high.

Evaluation of compatibility between different types of adhesives and dual-cured resin cement.

PURPOSE: The objective of this in vitro study was to evaluate the bonding compatibility between different adhesives and a dual-cured resin cement, using a conventional tensile bond test. MATERIALS AND METHODS: The adhesives used were: Prime & Bond (PB) (Dentsply) (PB), Scotchbond Multi Purpose (SB) (3M), and the activator Self Cure (SC) (Dentsply). The dual-curing resin cement used was Enforce (EF) (Dentsply). Six groups with five specimens in each were tested: G1: EF/PB/EF (light cured); G2: EF/SB/EF (light cured); G3: EF/PB+SC/EF (light cured); G4: EF/PB+SC/EF (only chemically cured); G5: EF/EF (light cured); G6: EF/EF (only chemically cured). The resin cement was applied in two stainless steel molds with a cone-shaped perforation measuring 4 mm in diameter and 1 mm in thickness, and the adhesive was applied between them. Ten minutes after specimens were cured, the tensile strength was measured in a universal testing machine at a crosshead speed of 0.5 mm/min. RESULTS: The mean values (MPa) +/- SD obtained in each experimental group were: G1: 1.4 +/- 0.2; G2: 1.3 +/- 0.2; G3: 1.2 +/- 0.4; G4: 0.8 +/- 0.2; G5: 1.2 +/- 0.1; G6: 0.7 +/- 0.1. The results were statistically evaluated using nonparametric Kruskal-Wallis and Dunn tests (p < or = 0.05). Statistically significant differences among groups were found only between G1 and G4, and G1 and G6. CONCLUSION: There was no incompatibility among the different adhesives used with dual-cured resin cement. The lowest tensile bond strength values occurred in the absence of photoactivation.

Clinical evaluation of three restorative materials applied in a minimal intervention caries treatment approach.

OBJECTIVES: This paper reports on a longitudinal evaluation of three materials (glass ionomer, zinc oxide-eugenol cement, and composite) employed in a minimal restorative intervention approach of 81 high caries-active pregnant women selected for a preventive oral health program in Brazil. The aim of the study was to evaluate the clinical behavior of the glass ionomer cement, currently indicated in programs for control of carious lesions. METHODS: The patients were randomly divided into two groups. Both groups were engaged in an oral health promotion approach. In Group 1, 417 glass ionomer restorations were placed in 43 individuals, involving all types and sizes of cavities. In the second group, 213 posterior zinc oxide-eugenol (ZOE) restorations and 127 anterior composite restorations were placed in 38 patients. Minimal cavity preparations were made, in which only soft or infected dentin was removed, on the basis of clinical judgment. RESULTS: After two years, the restorations were clinically evaluated by two examiners for marginal integrity, amount of wear, presence of fracture, carious lesions, and lost restorations. Statistical analysis (chi-square test) identified statistically significant difference between glass ionomer and ZOE (90.6% vs 9.2%). Comparing glass ionomer and composite, similar survival rates were observed. The success rate observed for the glass ionomer cement ranged from 77.1 percent to 92.5 percent, depending on the type and size of cavity in which it was applied. Four teeth restored with glass ionomer cement and one tooth restored with composite showed caries signs. Regarding the ZOE restorations, caries was always associated with other causes of failure such as excessive wear, restoration loss, or marginal defects, with no possibility of separate evaluation. Despite the preventive and therapeutic measurements employed, a mean increase of 2.15 new surfaces with cavities was observed in Group 1, as well as 2.83 surfaces presenting the same status in Group 2. CONCLUSIONS: This study demonstrated that highly viscous glass ionomer cement applied in a minimal intervention approach provided high-quality preventive and restorative care after two years to a population at high risk for caries. The composite was employed in cavities exposed to lower stress, such as in the anterior teeth, and its behavior was comparable to that of the glass ionomer cement. The reinforced ZOE presented a high failure rate, thus contraindicating its use for such purpose.

[Solitary neurofibroma of the maxillary sinus]. / Neurofibroma solitario de seno maxilar.

Neurofibromas are benign tumours of peripheral nerve tissue, frequently associated with neurofibromatosis type I. Their isolated occurrence in the maxillary sinus is rare, with only 6 cases described in the literature. We present the case of a 70-year-old woman who consulted for left hemifacial paresthesias of 10 years' evolution. CT showed a heterogeneous lesion in the left maxillary sinus, eroding its lateral wall without signs of infiltration. Endoscopic surgery with nasalisation of the maxillary sinus was performed. The pathology was neurofibroma (positive for S-100 protein and vimentin). After 18 months, no tumour growth has been found.

Clinical evaluation of multiple-surface ART restorations: 12 month follow-up.

PURPOSE: The purpose of this study was to evaluate the performance of multiple-surface restorations employing 2 different glass ionomer cements (GICs) and the Atraumatic Restorative Treatment (ART) approach in permanent molar teeth. METHODS: This study examined 60 restorations--36 Class I restorations involving 2 or more tooth surfaces and 24 Class II restorations--that were placed in 46 schoolchildren (9-16 years of age) by 2 dentists using the ART approach. The restorations were randomly divided into 2 groups: (a) 30 cavities were filled with high strength GIC (Ketac Molar-3M ESPE), and (b) 30 cavities were filled with resin-modified GIC (Fuji VIII-GC Corp). Two independent calibrated examiners carried out the evaluations according to ART criteria. The interexaminer kappa was 0.92. Data were submitted to chi-square, McNemar, and Fisher's tests. A difference was statistically significant if P<.05. RESULTS: In a 12-month follow-up, 59 restorations were evaluated. The success rates of the restorations were 100% and 93% for Fuji VIII and Ketac Molar, respectively. There was no statistically significant difference between GICs, cavity types, or operators. CONCLUSIONS: Based on a 12-month follow-up evaluation, the clinical performance of the multiple-surface atraumatic restorative treatment restorations of both glass ionomer cements (high-strength and resin-modified) was considered satisfactory with a high success rate.

Neurofibroma solitario de seno maxilar / Solitary neurofibroma of the maxillary sinus

Los neurofibromas son tumores benignos del tejido neural periférico, más frecuentes asociados a neurofibromatosis tipo I. La aparición aislada en un seno maxilar es excepcional, estando descritos sólo 6 casos en la literatura. Presentamos una mujer de 70 años que consultó por parestesias hemifaciales izquierdas de 10 años de evolución. La TC mostró una lesión heterogénea en seno maxilar izquierdo que erosionaba la pared lateral del mismo sin signos de infiltración. Se intervino mediante endoscopia, nasalizando el seno maxilar. La anatomía patológica fue de neurofibroma (proteína S-100 y vimentina positivos). Tras 18 meses no hemos encontrado crecimiento tumoral (AU)

Neurofibromas are benign tumours of peripheral nerve tissue, frequently associated with neurofibromatosis type I. Their isolated occurrence in the maxillary sinus is rare, with only 6 cases described in the literature. We present the case of a 70-year-old woman who consulted for left hemifacial paresthesias of 10 years’ evolution. CT showed a heterogeneous lesion in the left maxillary sinus, eroding its lateral wall without signs of infiltration. Endoscopic surgery withnasalisation of the maxillary sinus was performed. The pathology was neurofibroma (positivefor S-100 protein and vimentin). After 18 months, no tumour growth has been found (AU)