Hair cell maturation is differentially regulated along the tonotopic axis of the mammalian cochlea

Sound amplification within the mammalian cochlea depends upon specialized hair cells, the outer hair cells (OHCs), which possess both sensory and motile capabilities. In various altricial rodents, OHCs become functionally competent from around postnatal day 7 (P7), before the primary sensory inner hair cells (IHCs), which become competent at about the onset of hearing (P12). The mechanisms responsible for the maturation of OHCs and their synaptic specialization remain poorly understood. We report that spontaneous Ca2+ activity in the immature cochlea, which is generated by CaV1.3 Ca2+ channels, differentially regulates the maturation of hair cells along the cochlea. Under near‐physiological recording conditions we found that, similar to IHCs, immature OHCs elicited spontaneous Ca2+ action potentials (APs), but only during the first few postnatal days. Genetic ablation of these APs in vivo, using CaV1.3−/− mice, prevented the normal developmental acquisition of mature‐like basolateral membrane currents in low‐frequency (apical) hair cells, such as IK,n (carried by KCNQ4 channels), ISK2 and IACh (α9α10nAChRs) in OHCs and IK,n and IK,f (BK channels) in IHCs. Electromotility and prestin expression in OHCs were normal in CaV1.3−/− mice. The maturation of high‐frequency (basal) hair cells was also affected in CaV1.3−/− mice, but to a much lesser extent than apical cells. However, a characteristic feature in CaV1.3−/− mice was the reduced hair cell size irrespective of their cochlear location. We conclude that the development of low‐ and high‐frequency hair cells is differentially regulated during development, with apical cells being more strongly dependent on experience‐independent Ca2+ APs

Root seasonal pattern, spatial distribution, and C:N ratio of matgrasspasture (Nardus stricta L.) in the Lombardy Prealps

The aim of the present study was to investigate carbon and nutrient cycling and the role of root dynamics in terrestrial ecosystems such as large abandoned pastures and natural grasslands present in the Prealps, for which below-ground processes are currently enigmatic. In particular, we quantified root/leaf biomass and C:N ratio throughout two growing seasons. Additionally, root traits such as root length density (RLD), root mass density (RMD), and root diameter classes (RDC) were also investigated with the aim of understanding the spatial distribution of roots in the soil. In our samples, we found that the roots could be divided into three main diameter classes and hence quantified the presence of each class along the soil profile. With regard to total root biomass, we found the occurrence of two peaks of biomass accumulation during the growth season, and when biomass accumulation was compared with climatic data, it was impossible to obtain a clear indication of the root turnover rate. In fact, the strong influence of grazing on the above-ground biomass could have affected, in turn, root biomass. In future, this possible complication will be avoided by repeating the measurements within enclosures to avoid grazing interference. We found that C:N ratio remained constant, with a single peak, suggesting a lower root decomposition during the warmest period (August 2006). The concentration of nitrogen in roots decreased with depth as a result of a decrease in roots with smaller diameters. The reverse was found for carbon content, which increased with depth, probably due to an increase in roots with larger diameters. This study represents the first attempt to estimate root turnover rates in this prealpine ecosystem, which have been analysed to date only for the above-ground biomass

Bacteremic Pneumococcal Pneumonia: a Longitudinal Study in 279 Adult Patients from a Single Center

Background: Bacteremic pneumococcal pneumonia (BPP) is the most common clinical presentation of invasive pneumococcal disease (IPD). Although it has been extensively studied, there is little knowledge in our region in relation to burden of disease, demographic and outcome features. Methods: We conducted a prospective, longitudinal, observational study from 1989 to 2015 in adult patients with BPP, in order to deepen our knowledge of the characteristics of this disease in our community hospital in Tandil, Argentina. Results: 279 patients were included. The mean incidence was 2.8/1000 admissions with a sharp decrease in the last two years, reaching 0.8/1000 admissions. Mean patient age was 60 years. Comorbidities were found in 65% of the cases. Non-respiratory symptoms occurred in 50% of cases. Infiltrates on chest x ray were predominantly unilateral (75%) and lobar (57%). Regarding severity, a low PSI score I-II-II was found in 178 patients (64%), 60 (22%) were admitted to ICU, 40 (14%) required mechanical ventilation, and 21 (8%) developed empyema. Penicillin resistance was not found. Mortality was 18% (49/279), and by a multivariate analysis it was associated with confusion (OR= 5.44), age\u3e80 years (OR =5.72), leukopenia (OR =5.73) and dyspnea (OR=7.87). Conclusions: In this study of 279 bacteremic pneumococcal pneumonia we reinforce previous knowledge on this disease regarding incidence and clinical features and confirm a considerable an early mortality associated to age and severity of disease at onset. Recent changes in incidence of BPP in adults could be secondary to herd effect of PVC 13 a vaccine that is mandatory in children in our community since 2012

Inferring Foraging Areas of Nesting Loggerhead Turtles Using Satellite Telemetry and Stable Isotopes

In recent years, the use of intrinsic markers such as stable isotopes to link breeding and foraging grounds of migratory species has increased. Nevertheless, several assumptions still must be tested to interpret isotopic patterns found in the marine realm. We used a combination of satellite telemetry and stable isotope analysis to (i) identify key foraging grounds used by female loggerheads nesting in Florida and (ii) examine the relationship between stable isotope ratios and post-nesting migration destinations. We collected tissue samples for stable isotope analysis from 14 females equipped with satellite tags and an additional 57 untracked nesting females. Telemetry identified three post-nesting migratory pathways and associated non-breeding foraging grounds: (1) a seasonal continental shelf-constrained migratory pattern along the northeast U. S. coastline, (2) a non-breeding residency in southern foraging areas and (3) a residency in the waters adjacent to the breeding area. Isotopic variability in both delta C-13 and delta N-15 among individuals allowed identification of three distinct foraging aggregations. We used discriminant function analysis to examine how well delta C-13 and delta N-15 predict female post-nesting migration destination. The discriminant analysis classified correctly the foraging ground used for all but one individual and was used to predict putative feeding areas of untracked turtles. We provide the first documentation that the continental shelf of the Mid-and South Atlantic Bights are prime foraging areas for a large number (61%) of adult female loggerheads from the largest loggerhead nesting population in the western hemisphere and the second largest in the world. Our findings offer insights for future management efforts and suggest that this technique can be used to infer foraging strategies and residence areas in lieu of more expensive satellite telemetry, enabling sample sizes that are more representative at the population level

Coordinated calcium signalling in cochlear sensory and non‐sensory cells refines afferent innervation of outer hair cells

Outer hair cells (OHCs) are highly specialized sensory cells conferring the fine‐tuning and high sensitivity of the mammalian cochlea to acoustic stimuli. Here, by genetically manipulating spontaneous Ca2+ signalling in mice in vivo, through a period of early postnatal development, we find that the refinement of OHC afferent innervation is regulated by complementary spontaneous Ca2+ signals originating in OHCs and non‐sensory cells. OHCs fire spontaneous Ca2+ action potentials during a narrow period of neonatal development. Simultaneously, waves of Ca2+ activity in the non‐sensory cells of the greater epithelial ridge cause, via ATP‐induced activation of P2X3 receptors, the increase and synchronization of the Ca2+ activity in nearby OHCs. This synchronization is required for the refinement of their immature afferent innervation. In the absence of connexin channels, Ca2+ waves are impaired, leading to a reduction in the number of ribbon synapses and afferent fibres on OHCs. We propose that the correct maturation of the afferent connectivity of OHCs requires experience‐independent Ca2+ signals from sensory and non‐sensory cells

DLGS97/SAP97 is developmentally upregulated and is required for complex adult behaviors and synapse morphology and function

The synaptic membrane-associated guanylate kinase (MAGUK) scaffolding protein family is thought to play key roles in synapse assembly and synaptic plasticity. Evidence supporting these roles in vivo is scarce, as a consequence of gene redundancy in mammals. The genome of Drosophila contains only one MAGUK gene, discs large (dlg), from which two major proteins originate: DLGA [PSD95 (postsynaptic density 95)-like] and DLGS97 [SAP97 (synapse-associated protein)-like]. These differ only by the inclusion in DLGS97 of an L27 domain, important for the formation of supramolecular assemblies. Known dlg mutations affect both forms and are lethal at larval stages attributable to tumoral overgrowth of epithelia. We generated independent null mutations for each, dlgA and dlgS97. These allowed unveiling of a shift in expression during the development of the nervous system: predominant expression of DLGA in the embryo, balanced expression of both during larval stages, and almost exclusive DLGS97 expression in the adult brain. Loss of embryonic DLGS97 does not alter the development of the nervous system. At larval stages, DLGA and DLGS97 fulfill both unique and partially redundant functions in the neuromuscular junction. Contrary to dlg and dlgA mutants, dlgS97 mutants are viable to adulthood, but they exhibit marked alterations in complex behaviors such as phototaxis, circadian activity, and courtship, whereas simpler behaviors like locomotion and odor and light perception are spared. We propose that the increased repertoire of associations of a synaptic scaffold protein given by an additional domain of protein-protein interaction underlies its ability to integrate molecular networks required for complex functions in adult synapses

High-Sensitivity C-Reactive Protein and Acute Kidney Injury in Patients with Acute Myocardial Infarction: A Prospective Observational Study

Background. Accumulating evidence suggests that inflammation plays a key role in acute kidney injury (AKI) pathogenesis. We explored the relationship between high-sensitivity C-reactive protein (hs-CRP) and AKI in acute myocardial infarction (AMI). Methods. We prospectively included 2,063 AMI patients in whom hs-CRP was measured at admission. AKI incidence and a clinical composite of in-hospital death, cardiogenic shock, and acute pulmonary edema were the study endpoints. Results. Two-hundred-thirty-four (11%) patients developed AKI. hs-CRP levels were higher in AKI patients (45 \ub1 87 vs. 16 \ub1 41 mg/L; p < 0.0001). The incidence and severity of AKI, as well as the rate of the composite endpoint, increased in parallel with hs-CRP quartiles (p for trend <0.0001 for all comparisons). A significant correlation was found between hs-CRP and the maximal increase of serum creatinine (R = 0.23; p < 0.0001). The AUC of hs-CRP for AKI prediction was 0.69 (p < 0.001). At reclassification analysis, addition of hs-CRP allowed to properly reclassify 14% of patients when added to creatinine and 8% of patients when added to a clinical model. Conclusions. In AMI, admission hs-CRP is closely associated with AKI development and severity, and with in-hospital outcomes. Future research should focus on whether prophylactic renal strategies in patients with high hs-CRP might prevent AKI and improve outcome

Metagenomic approach of associated fungi with Megaplatypus mutatus (Coleoptera: Platypodinae)

is a major forest pest in Argentina and an emerging pest in Europe. In this study the multitrophic interactions between and associated fungi were assessed with a metagenomics approach (454-pyrosequencing). A total of 270 collection points from insect galleries from three locations in Argentina were pooled for pyrosequencing analyses. Two hosts, and , were independently evaluated to characterize the fungal communities associated to ; compare the culture-independent approach with previous culturing studies, in terms of data recovery related to the fungal community composition, and test the specificity of the fungal communities amongst locations and hosts. A Generalized Linear Mixed Model was performed to compare the fungal richness in each dataset, which showed no significant differences between taxa richness amongst locations. Principal Coordinates Analyses showed a separation between fungal communities within the same host, suggesting that host identity would not be crucial to determine the specificity in fungal communities. and one species, present in all hosts and locations, achieved 37.6% of the total relative frequency per taxa. These results complement the data from culturing methods previously reported, thus improving the accuracy and understanding of the fungal assemblages associated to .Megaplatypus mutatusM. mutatusPopulus deltoidesCasuarina cunninghamianaM. mutatusCandida insectalensFusariumM. mutatu

Modeling and mapping isotopic patterns in the Northwest Atlantic derived from loggerhead sea turtles

Stable isotope analysis can be used to infer geospatial linkages of highly migratory species. Identifying foraging grounds of marine organisms from their isotopic signatures is becoming de rigueur as it has been with terrestrial organisms. Sea turtles are being increasingly studied using a combination of satellite telemetry and stable isotope analysis; these studies along with those from other charismatic, highly vagile, and widely distributed species (e.g., tuna, billfish, sharks, dolphins, whales) have the potential to yield large datasets to develop methodologies to decipher migratory pathways in the marine realm. We collected tissue samples (epidermis and red blood cells) for carbon (delta C-13) and nitrogen (delta N-15) stable isotope analysis from 214 individual loggerheads (Caretta caretta) in the Northwest Atlantic Ocean (NWA). We used discriminant function analysis (DFA) to examine how well delta C-13 and delta N-15 classify loggerhead foraging areas. The DFA model was derived from isotopic signatures of 58 loggerheads equipped with satellite tags to identify foraging locations. We assessed model accuracy with the remaining 156 untracked loggerheads that were captured at their foraging locations. The DFA model correctly identified the foraging ground of 93.0% of individuals with a probability greater than 66.7%. The results of the external validation (1) confirm that assignment models based on tracked loggerheads in the NWA are robust and (2) provide the first independent evidence supporting the use of these models for migratory marine organisms. Additionally, we used these data to generate loggerhead-specific delta C-13 and delta N-15 isoscapes, the first for a predator in the Atlantic Ocean. We found a latitudinal trend of delta C-13 values with higher values in the southern region (20-25 degrees N) and a more complex pattern with delta N-15, with intermediate latitudes (30-35 degrees N) near large coastal estuaries having higher delta N-15-enrichment. These results indicate that this method with further refinement may provide a viable, more spatially-explicit option for identifying loggerhead foraging grounds

Oxytocin in the Circadian Timing of Birth

BACKGROUND: The molecular components determining the timing for birth remain an incompletely characterized aspect of reproduction, with important conceptual and therapeutic ramifications for management of preterm, post-term and arrested labor. METHODOLOGY/PRINCIPAL FINDINGS: To test the hypothesis that oxytocin mediates circadian regulation of birth, we evaluated parturition timing following shifts in light cycles in oxytocin (OT)-deficient mice. We find that, in contrast to wild type mice that do not shift the timing of birth following a 6-h advance or delay in the light cycle, OT-deficient mice delivered at random times of day. Moreover, shifts in the light-dark cycle of gravid wild type mice have little impact on the pattern of circadian oxytocin release. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate oxytocin plays a critical role in minimizing labor disruption due to circadian clock resetting