Optimizing the vertebrate vestibular semicircular canal: could we balance any better?

The fluid-filled semicircular canals (SCCs) of the vestibular system are used by all vertebrates to sense angular rotation. Despite masses spanning seven decades, all mammalian SCCs are nearly the same size. We propose that the SCC represents a sensory organ that evolution has `optimally designed'. Four geometric parameters are used to characterize the SCC, and `building materials' of given physical properties are assumed. Identifying physical and physiological constraints on SCC operation, we find that the most sensitive SCC has dimensions consistent with available data.Comment: 4 pages, 3 figure

Row spacing and seed physiological quality of Crotalaria species.

Crotalaria crops have important uses, such as in green manuring, nematode control, biological nitrogen fixation and sugarcane reform in Savanna areas. Due to its strategic importance, knowledge about crotalaria seed production technology is a relevant factor to ensure the availability of high physiological quality seeds

Targeting of immunosuppressive myeloid cells from glioblastoma patients by modulation of size and surface charge of lipid nanocapsules

Background: Myeloid derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) are two of the major players involved in the inhibition of anti-tumor immune response in cancer patients, leading to poor prognosis. Selective targeting of myeloid cells has therefore become an attractive therapeutic strategy to relieve immunosuppression and, in this frame, we previously demonstrated that lipid nanocapsules (LNCs) loaded with lauroyl-modified gemcitabine efficiently target monocytic MDSCs in melanoma patients. In this study, we investigated the impact of the physico-chemical characteristics of LNCs, namely size and surface potential, towards immunosuppressive cell targeting. We exploited myeloid cells isolated from glioblastoma patients, which play a relevant role in the immunosuppression, to demonstrate that tailored nanosystems can target not only tumor cells but also tumor-promoting cells, thus constituting an efficient system that could be used to inhibit their function. Results: The incorporation of different LNC formulations with a size of 100 nm, carrying overall positive, neutral or negative charge, was evaluated on leukocytes and tumor-infiltrating cells freshly isolated from glioblastoma patients. We observed that the maximum LNC uptake was obtained in monocytes with neutral 100 nm LNCs, while positively charged 100 nm LNCs were more effective on macrophages and tumor cells, maintaining at low level the incorporation by T cells. The mechanism of uptake was elucidated, demonstrating that LNCs are incorporated mainly by caveolae-mediated endocytosis. Conclusions: We demonstrated that LNCs can be directed towards immunosuppressive cells by simply modulating their size and charge thus providing a novel approach to exploit nanosystems for anticancer treatment in the frame of immunotherapy.[Figure not available: see fulltext.

Myeloid Diagnostic and Prognostic Markers of Immune Suppression in the Blood of Glioma Patients.

Although gliomas are confined to the central nervous system, their negative influence over the immune system extends to peripheral circulation. The immune suppression exerted by myeloid cells can affect both response to therapy and disease outcome. We analyzed the expansion of several myeloid parameters in the blood of low- and high-grade gliomas and assessed their relevance as biomarkers of disease and clinical outcome. Methods: Peripheral blood was obtained from 134 low- and high-grade glioma patients. CD14+, CD14+/p-STAT3+, CD14+/PD-L1+, CD15+ cells and four myeloid-derived suppressor cell (MDSC) subsets, were evaluated by flow cytometry. Arginase-1 (ARG1) quantity and activity was determined in the plasma. Multivariable logistic regression model was used to obtain a diagnostic score to discriminate glioma patients from healthy controls and between each glioma grade. A glioblastoma prognostic model was determined by multiple Cox regression using clinical and myeloid parameters. Results: Changes in myeloid parameters associated with immune suppression allowed to define a diagnostic score calculating the risk of being a glioma patient. The same parameters, together with age, permit to calculate the risk score in differentiating each glioma grade. A prognostic model for glioblastoma patients stemmed out from a Cox multiple analysis, highlighting the role of MDSC, p-STAT3, and ARG1 activity together with clinical parameters in predicting patient's outcome. Conclusions: This work emphasizes the role of systemic immune suppression carried out by myeloid cells in gliomas. The identification of biomarkers associated with immune landscape, diagnosis, and outcome of glioblastoma patients lays the ground for their clinical use

Alterações da disponibilidade de nutrientes em um Latossolo Vermelho-Amarelo degradado e outro não-degradado fertilizados com biossólido e florestados com Eucalyptus grandis.

O presente trabalho teve como objetivos avaliar os efeitos da aplicação de biossólido sobre as modificações de fertilidade do solo e o crescimento de povoamentos de Eucalyptus grandis plantados em um Latossolo Vermelho-Amarelo Distrófico não-degradado e outro degradado

Techonolgy of Qualea grandiflora Mart. (Vochysiaceae) seeds

Qualea grandiflora Mart. (Vochysiaceae), commonly known as "pau-terra", is an arborous species native to the Brazilian savannah which possess commercial interests, as it can be used either as an ornamental or as a medicinal plant. "Pau-terra" can also be used in the heterogeneous reforestation of areas which are destined for restoration of permanent preservation degraded areas. Propagation studies with this species are scarce, being necessary then further clarification regarding the factors that influences the germination process. In this context, the objective of this work was to evaluate the influence of different temperatures, substrates and light conditions on seed germination. We selected light brown seeds which were subjected to different interactions between temperatures (15-25, 20-30, 25 and 30°C), substrate (paper, sand and vermiculite) and light (light and dark). All seeds were later dry-incubated at 32°C for 3, 6 and 12 hours. After treatments, seeds were kept in BOD at 58% RH and the following parameters were calculated: germination (%G) and germination speed index (GSI); the formation of normal and abnormal seedlings and the number dead seeds. Interaction was observed for all variables. In the optimum temperature range, the seeds behaved as photoblastic neutral or indifferent. Under alternating temperatures, darkness enhanced the germination, especially when combined with the lower temperatures. We noted that the sowing in sand, at 25°C, allowed the maintenance of suitable combinations of germination and seedling development. With respect to desiccation tolerance, "pau-terra" seeds presented an orthodox behavior, with a linear increase of the vigor as function of drying

Fine Tuning of Ca(V)1.3 Ca2+ Channel Properties in Adult Inner Hair Cells Positioned in the Most Sensitive Region of the Gerbil Cochlea

Hearing relies on faithful signal transmission by cochlear inner hair cells (IHCs) onto auditory fibres over a wide frequency and intensity range. Exocytosis at IHC ribbon synapses is triggered by Ca2+ inflow through CaV1.3 (L-type) Ca2+ channels. We investigated the macroscopic (whole-cell) and elementary (cell-attached) properties of Ca2+ currents in IHCs positioned at the middle turn (frequency ,2 kHz) of the adult gerbil cochlea, which is their most sensitive hearing region. Using near physiological recordings conditions (body temperature and a Na+ based extracellular solution), we found that the macroscopic Ca2+ current activates and deactivates very rapidly (time constant below 1 ms) and inactivates slowly and only partially. Single-channel recordings showed an elementary conductance of 15 pS, a sub-ms latency to first opening, and a very low steady-state open probability (Po: 0.024 in response to 500-ms depolarizing steps at ,218 mV). The value of Po was significantly larger (0.06) in the first 40 ms of membrane depolarization, which corresponds to the time when most Ca2+ channel openings occurred clustered in bursts (mean burst duration: 19 ms). Both the Po and the mean burst duration were smaller than those previously reported in high-frequency basal IHCs. Finally, we found that middle turn IHCs are likely to express about 4 times more Ca2+ channels per ribbon than basal cells. We propose that middle-turn IHCs finely-tune CaV1.3 Ca2+ channel gating in order to provide reliable information upon timing and intensity of lower-frequency sounds

Efferent Control of the Electrical and Mechanical Properties of Hair Cells in the Bullfrog's Sacculus

Background: Hair cells in the auditory, vestibular, and lateral-line systems respond to mechanical stimulation and transmit information to afferent nerve fibers. The sensitivity of mechanoelectrical transduction is modulated by the efferent pathway, whose activity usually reduces the responsiveness of hair cells. The basis of this effect remains unknown. Methodology and Principal Findings: We employed immunocytological, electrophysiological, and micromechanical approaches to characterize the anatomy of efferent innervation and the effect of efferent activity on the electrical and mechanical properties of hair cells in the bullfrog’s sacculus. We found that efferent fibers form extensive synaptic terminals on all macular and extramacular hair cells. Macular hair cells expressing the Ca 2+-buffering protein calretinin contain half as many synaptic ribbons and are innervated by twice as many efferent terminals as calretinin-negative hair cells. Efferent activity elicits inhibitory postsynaptic potentials in hair cells and thus inhibits their electrical resonance. In hair cells that exhibit spiking activity, efferent stimulation suppresses the generation of action potentials. Finally, efferent activity triggers a displacement of the hair bundle’s resting position. Conclusions and Significance: The hair cells of the bullfrog’s sacculus receive a rich efferent innervation with the heaviest projection to calretinin-containing cells. Stimulation of efferent axons desensitizes the hair cells and suppresses their spiking activity. Although efferent activation influences mechanoelectrical transduction, the mechanical effects on hair bundles ar