To determine whether a model of transient mass-type brain damage (MTBD) in the rat produces early release of neurospecific enolase (NSE) and protein S100B in peripheral blood, as an expression of the ...induced brain injury.
An experimental study with a control group.
Experimental operating room of the Institute of Biomedicine (IBiS) of Virgen del Rocío University Hospital (Seville, Spain).
Fourteen adult Wistar rats.
Blood was sampled at baseline, followed by: MTBD group, a trephine perforation was used to insert and inflate the balloon of a catheter at a rate of 500 μl/20 sec, followed by 4 blood extractions every 20 min. Control group, the same procedure as before was carried out, though without trephine perforation.
Weight, early mortality, serum NSE and S100B concentration.
Differences in NSE and S100B concentration were observed over time within the MTBD group (P<.001), though not so in the control group. With the exception of the baseline determination, differences were observed between the two groups in terms of the mean NSE and S100B values. Following MTBD, NSE and S100B progressively increased at all measurement timepoints, with r=0.765; P=.001 and r=0.628; P=.001, respectively. In contrast, the control group showed no such correlation for either biomarker.
Serum NSE and S100B concentrations offer an early indication of brain injury affecting the gray and white matter in an experimental model of mass-type MTBD in the rat.
Severe spermatogenic failure (SPGF) represents one of the most relevant causes of male infertility. This pathological condition can lead to extreme abnormalities in the seminal sperm count, such as ...severe oligozoospermia (SO) or non-obstructive azoospermia (NOA). Most cases of SPGF have an unknown aetiology, and it is known that this idiopathic form of male infertility represents a complex condition. In this study, we aimed to evaluate whether common genetic variation in
, which encodes a key player in spermatogenesis, is involved in the susceptibility to idiopathic SPGF.
We designed a genetic association study comprising a total of 727 SPGF cases (including 527 NOA and 200 SO) and 1,058 unaffected men from the Iberian Peninsula. Following a tagging strategy, three tag single-nucleotide polymorphisms (SNPs) of
(rs1362912, rs323342, and rs323346) were selected for genotyping using TaqMan probes. Case-control association tests were then performed by logistic regression models.
analyses were also carried out to shed light into the putative functional implications of the studied variants.
A significant increase in
-rs1362912 minor allele frequency (MAF) was observed in the group of SO patients (MAF = 0.0842) compared to either the control cohort (MAF = 0.0468, OR = 1.90,
= 7.47E-03) or the NOA group (MAF = 0.0472, OR = 1.83,
= 1.23E-02). The genotype distribution of the SO population was also different from those of both control (
= 1.14E-02) and NOA groups (
= 4.33-02). The analysis of functional annotations of the human genome suggested that the effect of the SO-associated
variants is likely exerted by alteration of the binding affinity of crucial transcription factors for spermatogenesis.
Our results suggest that common variation in
is involved in the genetic predisposition to SO, thus supporting the notion of idiopathic SPGF as a complex trait.
It has been reported that phosphoinositide 3-kinase (PI 3-kinase) and its downstream target, protein kinase B (PKB), play a central role in the signaling of cell survival triggered by neurotrophins ...(NTs). In this report, we have analyzed the involvement of Ca2+and calmodulin (CaM) in the activation of the PKB induced by NTs. We have found that reduction of intracellular Ca2+concentration or functional blockade of CaM abolished NGF-induced activation of PKB in PC12 cells. Similar results were obtained in cultures of chicken spinal cord motoneurons treated with brain-derived neurotrophic factor (BDNF). Moreover, CaM inhibition prevented the cell survival triggered by NGF or BDNF. This effect was counteracted by the transient expression of constitutive active forms of the PKB, indicating that CaM regulates NT-induced cell survival through the activation of the PKB. We have investigated the mechanisms whereby CaM regulates the activation of the PKB, and we have found that CaM was necessary for the proper generation and/or accumulation of the products of the PI 3-kinase in intact cells.
A prospective four-year study on the infection rate of clean operative wounds is presented. From January 1982 to June 1985, a nurse epidemiologist and a medical team assessed 4,468 operative ...procedures, from the day of surgery to the patients' discharge from the hospital. The infection rate was 3.2%. A higher incidence of wound infection was detected in patients requiring emergency operations (5.1%), in drained wounds (5.4%), and in patients with conditions thought to predispose to infection, such as advanced cancer, hepatic cirrhosis, diabetes, nephrotic syndrome, previous splenectomy, and treatment with immunosuppressive drugs (7.8%). Age over 65 did not influence infection rates. There were up to tenfold differences in infection indices between surgeons performing the same clean procedures. The continued monitoring of clean wound infection rates allowed the early detection and control of infection outbreaks. Providing periodic information on infection rates to the different surgical services was associated with decreasing infection rates over time.
•The effect of the suckling period and energy intake in lactation on the duration of postpartum anestrus in Creole goats was determined.•Energy intake had no effect on the duration of postpartum ...anestrus.•Goats weaned at 30 days postpartum resumed estrus significantly earlier than those weaned at 60 days postpartum.
The objective of this study was to determine the effect of the length of the suckling period and the dietary energy level on the duration of postpartum anestrus in Creole goats. Twenty-eight multiparous pregnant goats (bodyweight BW 39.9±6.4kg; mean±SEM) each bearing a single fetus were used in a 2 suckling period (30 vs. 60 d)×2 levels of energy intake (low (L) vs. high (H)) factorial design. Kids were separated from their dams 3 d after birth and then suckled twice per day until weaned at 30 or 60 d postpartum. Dams weaned at 30 d postpartum were hand milked for the next 30 d. Goats were individually fed chopped alfalfa hay+balanced concentrates (45:55 DM basis) at 3% of BW in the last month of pregnancy and at the same level to the L goats in the postpartum period when the H goats were fed at 4% of BW. Energy balance was estimated by difference between energy intake and calculated energy requirements. Duration of postpartum anestrus was estimated by determining the occurrence of ovulation from changes in blood progesterone concentrations. There were no significant lengths of suckling x energy intake level interactions. Goats on all treatments lost weight until 45 d postpartum with more weight loss on the low than the high energy intake level (L 4.06±0.43 vs. H 1.99±0.64kg; P<0.05). The daily 4% FCM production was similar for all treatments (overall mean 1.10±0.01kg). The difference between the postpartum anestrus period between low (129 d) and high (128 d) dietary energy levels was not significant but no goat ovulated while in negative energy balance. The effect of suckling on the resumption of ovarian activity was highly significant (P<0.001) with goats weaned 30 d postpartum resuming ovulation 102 d after parturition compared to 155 d for those weaned 60 d postpartum. This study illustrates the importance of the bond between the doe and its kid in the prolongation of the anestrus period in goats.
Mathematical optimization is at the core of many problems in systems biology: (1) as the underlying hypothesis for model development, (2) in model identification, or (3) in the computation of optimal ...stimulation procedures to synthetically achieve a desired biological behavior. These problems are usually formulated as nonlinear programing problems (NLPs) with dynamic and algebraic constraints. However the nonlinear and highly constrained nature of systems biology models, together with the usually large number of decision variables, can make their solution a daunting task, therefore calling for efficient and robust optimization techniques. Here, we present novel global optimization methods and software tools such as cooperative enhanced scatter search (eSS), AMIGO, or DOTcvpSB, and illustrate their possibilities in the context of modeling including model identification and stimulation design in systems biology.
Simulations are currently an essential tool to develop and test wireless sensor networks (WSNs) protocols and to analyze future WSNs applications performance. Researchers often simulate their ...proposals rather than deploying high-cost test-beds or develop complex mathematical analysis. However, simulation results rely on physical layer assumptions, which are not usually accurate enough to capture the real behavior of a WSN. Such an issue can lead to mistaken or questionable results. Besides, most of the envisioned applications for WSNs consider the nodes to be at the ground level. However, there is a lack of radio propagation characterization and validation by measurements with nodes at ground level for actual sensor hardware. In this paper, we propose to use a low-computational cost, two slope, log-normal pathloss near ground outdoor channel model at 868 MHz in WSN simulations. The model is validated by extensive real hardware measurements obtained in different scenarios. In addition, accurate model parameters are provided. This model is compared with the well-known one slope path-loss model. We demonstrate that the two slope log-normal model provides more accurate WSN simulations at almost the same computational cost as the single slope one. It is also shown that the radio propagation characterization heavily depends on the adjusted model parameters for a target deployment scenario: The model parameters have a considerable impact on the average number of neighbors and on the network connectivity.
A putative partner of the already characterized CopZ from
Bacillus subtilis was found, both proteins being encoded by genes located in the same operon. This new protein is highly homologous to ...eukaryotic and prokaryotic P-type ATPases such as CopA, Ccc2 and Menkes proteins. The N-terminal region of this protein contains two soluble domains constituted by amino acid residues 1 to 72 and 73 to 147, respectively, which were expressed both separately and together. In both cases only the 73–147 domain is folded and is stable both in the copper(I)-free and in the copper(I)-bound forms. The folded and unfolded state is monitored through the chemical shift dispersion of
15N-HSQC spectra. In the absence of any structural characterization of CopA-type proteins, we determined the structure of the 73–147 domain in the 1–151 construct in the apo state through
1H,
15N and
13C NMR spectroscopies. The structure of the Cu(I)-loaded 73–147 domain has been also determined in the construct 73–151. About 1300 meaningful NOEs and 90 dihedral angles were used to obtain structures at high resolution both for the Cu(I)-bound and the Cu(I)-free states (backbone RMSD to the mean 0.35(±0.06) Å and 0.39(±0.07) Å, respectively). The structural assessment shows that the structures are accurate. The protein has the typical βαββαβ folding with a cysteine in the C-terminal part of helix α1 and the other cysteine in loop 1. The structures are similar to other proteins involved in copper homeostasis. Particularly, between BsCopA and BsCopZ, only the charges located around loop 1 are reversed for BsCopA and BsCopZ, thus suggesting that the two proteins could interact one with the other. The variability in conformation displayed by the N-terminal cysteine of the CXXC motif in a number of structures of copper transporting proteins suggests that this may be the cysteine which binds first to the copper(I) carried by the partner protein.
A new strategy to carry out the correction of analytical results affected by systematic errors due to the matrix effect is proposed. Two types of external calibrations must be established with the ...purpose to estimate the matrix effect: solvent calibration (SC) and matrix-matched calibration (MC). These calibration curves are statistically compared and a correction function (CF) is proposed with the aim to simplify the resolution to the problems associated with the incidence of matrix systematic error in the analytical results. Applying this correction function to the results obtained from the solvent calibration, it is possible to make a prediction of the values that would be obtained when the matrix-matched calibration is applied. On the other hand, a rigorous study of the associated uncertainty is developed and applied to the calculated correction function. Finally, this correction function is validated by means of obtained data of recovery studies carried out by a traditional methodology. The methodology has been satisfactorily applied to the quantification of the pesticide procymidone by HPLC for assessing dermal exposure.
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