Effects of microquantities of testosterone on the epididymis and accessory glands of the castrated rhesus monkey, Macaca mulatta

Release of testosterone from silastic implants over a period of 90 days resulted in variable stimulation of the epididymis and accessory glands of reproduction in the castrated rhesus monkey. While the weights of the seminal vesicles, prostate gland and bulbo-urethral glands were maintained at the same level as the intact control animals by four or eight implants of testosterone, those of the epididymis and ductus deferens were not affected by either dose of testosterone. Fructose in the seminal vesicles was stimulated significantly above intact control levels by eight implants of testosterone. There was no regional variation in the levels of sialic acid in the caput, corpus and cauda epididymides, but the concentrations of phospholipid and total lipid were significantly higher in the caput epididymidis. Our observations suggest there may be differential threshold requirements of androgens for the maintenance of the epididymis and accessory glands in the male rhesus monkey

Structural Ordering of Disordered Ligand-Binding Loops of Biotin Protein Ligase into Active Conformations as a Consequence of Dehydration

Mycobacterium tuberculosis (Mtb), a dreaded pathogen, has a unique cell envelope composed of high fatty acid content that plays a crucial role in its pathogenesis. Acetyl Coenzyme A Carboxylase (ACC), an important enzyme that catalyzes the first reaction of fatty acid biosynthesis, is biotinylated by biotin acetyl-CoA carboxylase ligase (BirA). The ligand-binding loops in all known apo BirAs to date are disordered and attain an ordered structure only after undergoing a conformational change upon ligand-binding. Here, we report that dehydration of Mtb-BirA crystals traps both the apo and active conformations in its asymmetric unit, and for the first time provides structural evidence of such transformation. Recombinant Mtb-BirA was crystallized at room temperature, and diffraction data was collected at 295 K as well as at 120 K. Transfer of crystals to paraffin and paratone-N oil (cryoprotectants) prior to flash-freezing induced lattice shrinkage and enhancement in the resolution of the X-ray diffraction data. Intriguingly, the crystal lattice rearrangement due to shrinkage in the dehydrated Mtb-BirA crystals ensued structural order of otherwise flexible ligand-binding loops L4 and L8 in apo BirA. In addition, crystal dehydration resulted in a shift of ∼3.5 Å in the flexible loop L6, a proline-rich loop unique to Mtb complex as well as around the L11 region. The shift in loop L11 in the C-terminal domain on dehydration emulates the action responsible for the complex formation with its protein ligand biotin carboxyl carrier protein (BCCP) domain of ACCA3. This is contrary to the involvement of loop L14 observed in Pyrococcus horikoshii BirA-BCCP complex. Another interesting feature that emerges from this dehydrated structure is that the two subunits A and B, though related by a noncrystallographic twofold symmetry, assemble into an asymmetric dimer representing the ligand-bound and ligand-free states of the protein, respectively. In-depth analyses of the sequence and the structure also provide answers to the reported lower affinities of Mtb-BirA toward ATP and biotin substrates. This dehydrated crystal structure not only provides key leads to the understanding of the structure/function relationships in the protein in the absence of any ligand-bound structure, but also demonstrates the merit of dehydration of crystals as an inimitable technique to have a glance at proteins in action

Sinteza, spazmolitsko i antidijaretsko djelovanje nekih 1-supstituiranih derivata imidazola

A series of 1-substituted imidazoles 1a-d and 2a-d were synthesized and screened for antispasmodic and antidiarrheal activities. Antispasmodic activity was tested at various concentrations on isolated tissue preparations; concentration-response curves were plotted and compared with atropine. All compounds were found to inhibit contraction of the guinea pig ileum. Castor oil-induced diarrhea model in rats was used for evaluation of antidiarrheal activity. Parameters such as intestinal transit and volume of intestinal fluid were measured for antidiarrheal activity at 40 mg kg-1 dose and compared with the standard drug loperamide at a 6 mg kg1 dose. Defecation frequency in the test group was found to be significantly lower (p < 0.01) compared to the control group and comparable with that of the standard. The present study reveals that the compounds exert antidiarrheal activity through possible inhibition of intestinal movement and reduction of capillary permeability in the abdominal cavity.U radu je opisana sinteza serije novih 1-supstituiranih imidazola 1a-d i 2a-d te evaluacija njihovog spazmolitskog i antidijaretskog djelovanja. Spazmolitsko djelovanje različith koncentracija ispitivanih spojeva (10, 50 i 100 µg mL1) ispitano je na izoliranim tkivnim preparatima; krivulje ovisnosti djelovanja o koncentraciji uspoređene su s djelovanjem atropina. Svi ispitivani spojevi inhibirali su kontrakcije ileuma zamorca. Dijarea inducirana ricinusovim uljem u štakora korištena je za vrednovanje antidijaretskog djelovanja. Intestinalni prijenos i volumen intestinalne tekućine mjereni su pri dozi od 40 mg kg1 i uspoređeni s učinkom standarda loperamida (doza 6 mg kg1). Učestalost defekacije u testiranoj skupini bila je značajno niža (p < 0,01) u usporedbi s kontrolnom skupinom i standardom. Provedena ispitivanja pokazuju da antidijaretsko djelovanje ispitivanih spojeva može biti posljedica inhibicije intestinalnih pokreta i redukcije kapilarne permeabilnosti u abdominalnoj šupljini

NIOX VERO: Individualized Asthma Management in Clinical Practice

As we move toward an era of precision medicine, novel biomarkers of disease will enable the identification and personalized treatment of new endotypes. In asthma, fractional exhaled nitric oxide (FeNO) serves as a surrogate marker of airway inflammation that often correlates with the presence of sputum eosinophils. The increase in FeNO is driven by an upregulation of inducible nitric oxide synthase (iNOS) by cytokines, which are released as a result of type-2 airway inflammation. Scientific evidence supports using FeNO in routine clinical practice. In steroid-naive patients and in patients with mild asthma, FeNO levels decrease within days after corticosteroid treatment in a dose-dependent fashion and increase after steroid withdrawal. In difficult asthma, FeNO testing correlates with anti-inflammatory therapy compliance. Assessing adherence by FeNO testing can remove the confrontational aspect of questioning a patient about compliance and change the conversation to one of goal setting and ways to improve disease management. However, the most important aspect of incorporating FeNO in asthma management is the reduction in the risk of exacerbations. In a recent primary care study, reduction of exacerbation rates and improved symptom control without increasing overall inhaled corticosteroid (ICS) use were demonstrated when a FeNO-guided anti-inflammatory treatment algorithm was assessed and compared to the standard care. A truly personalized asthma management approach—showing reduction of exacerbation rates, overall use of ICS and neonatal hospitalizations—was demonstrated when FeNO testing was applied as part of the treatment algorithm that managed asthma during pregnancy. The aim of this article is to describe how FeNO and the NIOX VERO® analyzer can help to optimize diagnosis and treatment choices and to aid in the monitoring and improvement of clinical asthma outcomes in children and adults

Quantifying Sources of Variability in Infancy Research Using the Infant-Directed-Speech Preference

Psychological scientists have become increasingly concerned with issues related to methodology and replicability, and infancy researchers in particular face specific challenges related to replicability: For example, high-powered studies are difficult to conduct, testing conditions vary across labs, and different labs have access to different infant populations. Addressing these concerns, we report on a large-scale, multisite study aimed at (a) assessing the overall replicability of a single theoretically important phenomenon and (b) examining methodological, cultural, and developmental moderators. We focus on infants’ preference for infant-directed speech (IDS) over adult-directed speech (ADS). Stimuli of mothers speaking to their infants and to an adult in North American English were created using seminaturalistic laboratory-based audio recordings. Infants’ relative preference for IDS and ADS was assessed across 67 laboratories in North America, Europe, Australia, and Asia using the three common methods for measuring infants’ discrimination (head-turn preference, central fixation, and eye tracking). The overall meta-analytic effect size (Cohen’s d) was 0.35, 95% confidence interval = [0.29, 0.42], which was reliably above zero but smaller than the meta-analytic mean computed from previous literature (0.67). The IDS preference was significantly stronger in older children, in those children for whom the stimuli matched their native language and dialect, and in data from labs using the head-turn preference procedure. Together, these findings replicate the IDS preference but suggest that its magnitude is modulated by development, native-language experience, and testing procedure

Viability of Bifidobacterium longum in cheddar cheese curd during manufacture and storage: effect of microencapsulation and point of inoculation

International audienceThe goal of this study was to assess the effect of methods of inoculation on the viability of probiotic bacteria during cheddar cheese manufacture as well as their stability during storage. Bifidobacterium longum ATCC 15708 was freeze-dried and microencapsulated by spray-coating. The effect of inoculation of free whole cell or microencapsulated cells at three points during manufacture (milk before renneting, at cheddaring or at salting) on the viable counts in cheese and whey was investigated. Microencapsulation had no effect on viable counts, chemical parameters (lactose, lactic acid, total nitrogen, nitrogen soluble in TCA, moisture) or sensory properties during manufacturing or storage of the fresh cheeses for 14 days. Inoculation of the bifidobacteria in milk before renneting resulted in higher viable counts in comparison to other points of inoculation. Bifidobacteria added at the salting step, which survived pressing, were subsequently more stable during storage than those inoculated in milk. The stability of B. longum 15708 during storage was greater in the pressed cheeses that in the free curds. The results of this study provides technological data for cheese makers on the optimum point of inoculation as well as the benefit of pressing the curds in order to ensure high levels of probiotics in fresh cheddar cheese