A new species of Silvinichthys (Siluriformes,Trichomycteridae) lacking pelvic fins from mid‐elevation localities of the southern Andes,with comments on the genus

Silvinichthys huachi new species, is described from a stream along the lower slope of the Andean Cordillera in the Provincia de San Juan, Argentina. It shares the distinctive modifications characteristic of Silvinichthys, but is distinguished from the four previously described congeners by the combination of a lack of the pelvic fin and the pelvic girdle, details of pigmentation and various meristic and morphometric features. Silvinichthys huachi is apparently endemic to the type locality situated within an arid region of western central Argentina in the Andino Cuyana Province. Major gaps in the range of species of Silvinichthys may indicate that the origin of the genus predates the uplift events that subdivided drainages along the eastern slopes of the Andean Cordillera in west central Argentina. Silvinichthys huachi is hypothesized to be the sister species of Silvinichthys bortayro.     

Structural Dynamics of Glutamate Signaling Systems by smFRET

Single-molecule Förster resonance energy transfer (smFRET) is a powerful technique for investigating the structural dynamics of biological macromolecules. smFRET reveals the conformational landscape and dynamic changes of proteins by building on the static structures found using cryo-electron microscopy, x-ray crystallography, and other methods. Combining smFRET with static structures allows for a direct correlation between dynamic conformation and function. Here, we discuss the different experimental setups, fluorescence detection schemes, and data analysis strategies that enable the study of structural dynamics of glutamate signaling across various timescales. We illustrate the versatility of smFRET by highlighting studies of a wide range of questions, including the mechanism of activation and transport, the role of intrinsically disordered segments, and allostery and cooperativity between subunits in biological systems responsible for glutamate signaling.     

2-Hexadecynoic acid inhibits plasmodial FAS-II enzymes and arrests erythrocytic and liver stage Plasmodium infections

Acetylenic fatty acids are known to display several biological activities, but their antimalarial activity has remained unexplored. In this study, we synthesized the 2-, 5-, 6-, and 9-hexadecynoic acids (HDAs) and evaluated their in vitro activity against erythrocytic (blood) stages of Plasmodium falciparum and liver stages of Plasmodium yoelii infections. Since the type II fatty acid biosynthesis pathway (PfFAS-II) has recently been shown to be indispensable for liver stage malaria parasites, the inhibitory potential of the HDAs against multiple P. falciparum FAS-II (PfFAS-II) elongation enzymes was also evaluated. The highest antiplasmodial activity against blood stages of P. falciparum was displayed by 5-HDA (IC₅₀ value 6.6 μg/ml), whereas the 2-HDA was the only acid arresting the growth of liver stage P. yoelii infection, in both flow cytometric assay (IC₅₀ value 2-HDA 15.3 μg/ml, control drug atovaquone 2.5 ng/ml) and immunofluorescence analysis (IC₅₀ 2-HDA 4.88 μg/ml, control drug atovaquone 0.37 ng/ml). 2-HDA showed the best inhibitory activity against the PfFAS-II enzymes PfFabI and PfFabZ with IC₅₀ values of 0.38 and 0.58 μg/ml (IC₅₀ control drugs 14 and 30 ng/ml), respectively. Enzyme kinetics and molecular modeling studies revealed valuable insights into the binding mechanism of 2-HDA on the target enzymes. All HDAs showed in vitro activity against Trypanosoma brucei rhodesiense (IC₅₀ values 3.7–31.7 μg/ml), Trypanosoma cruzi (only 2-HDA, IC₅₀ 20.2 μg/ml), and Leishmania donovani (IC₅₀ values 4.1–13.4 μg/ml) with generally low or no significant toxicity on mammalian cells. This is the first study to indicate therapeutic potential of HDAs against various parasitic protozoa. It also points out that the malarial liver stage growth inhibitory effect of the 2-HDA may be promoted via PfFAS-II enzymes. The lack of cytotoxicity, lipophilic nature, and calculated pharmacokinetic properties suggests that 2-HDA could be a useful compound to study the interaction of fatty acids with these key P. falciparum enzymes.     

Structural origins of fibrin clot rheology

The origins of clot rheological behavior associated with network morphology and factor XIIIa-induced cross-linking were studied in fibrin clots. Network morphology was manipulated by varying the concentrations of fibrinogen, thrombin, and calcium ion, and cross-linking was controlled by a synthetic, active-center inhibitor of FXIIIa. Quantitative measurements of network features (fiber lengths, fiber diameters, and fiber and branching densities) were made by analyzing computerized three-dimensional models constructed from stereo pairs of scanning electron micrographs. Large fiber diameters and lengths were established only when branching was minimal, and increases in fiber length were generally associated with increases in fiber diameter. Junctions at which three fibers joined were the dominant branchpoint type. Viscoelastic properties of the clots were measured with a rheometer and were correlated with structural features of the networks. At constant fibrinogen but varying thrombin and calcium concentrations, maximal rigidities were established in samples (both cross-linked and noncross-linked) which displayed a balance between large fiber sizes and great branching. Clot rigidity was also enhanced by increasing fiber and branchpoint densities at greater fibrinogen concentrations. Network morphology is only minimally altered by the FXIIIa-catalyzed cross-linking reaction, which seems to augment clot rigidity most likely by the stiffening of existing fibers.     

Identification of fused bicyclic heterocycles as potent and selective 5-HT(2A) receptor antagonists for the treatment of insomnia

A series of fused bicyclic heterocycles was identified as potent and selective 5-HT(2A) receptor antagonists. Optimization of the series resulted in compounds that had improved PK properties, favorable CNS partitioning, good pharmacokinetic properties, and significant improvements on deep sleep (delta power) and sleep consolidation.     

2-Alkynoic fatty acids inhibit topoisomerase IB from Leishmania donovani

2-Alkynoic fatty acids display antimycobacterial, antifungal, and pesticidal activities but their antiprotozoal activity has received little attention. In this work we synthesized the 2-octadecynoic acid (2-ODA), 2-hexadecynoic acid (2-HDA), and 2-tetradecynoic acid (2-TDA) and show that 2-ODA is the best inhibitor of the Leishmania donovani DNA topoisomerase IB enzyme (LdTopIB) with an EC(50)=5.3±0.7μM. The potency of LdTopIB inhibition follows the trend 2-ODA>2-HDA>2-TDA, indicating that the effectiveness of inhibition depends on the fatty acid carbon chain length. All of the studied 2-alkynoic fatty acids were less potent inhibitors of the human topoisomerase IB enzyme (hTopIB) as compared to LdTopIB. 2-ODA also displayed in vitro activity against Leishmania donovani (IC(50)=11.0μM), but it was less effective against other protozoa, Trypanosoma cruzi (IC(50)=48.1μM) and Trypanosoma brucei rhodesiense (IC(50)=64.5μM). The antiprotozoal activity of the 2-alkynoic fatty acids, in general, followed the trend 2-ODA>2-HDA>2-TDA. The experimental information gathered so far indicates that 2-ODA is a promising antileishmanial compound.     

Open field host selection and behavior by tamarisk beetles (Diorhabda spp.) (Coleoptera: Chrysomelidae) in biological control of exotic saltcedars (Tamarix spp.) and risks to non-target athel (T. aphylla) and native Frankenia spp.

Biological control of invasive saltcedars (Tamarix spp.) in the western U.S. by exotic tamarisk leaf beetles, Diorhabda spp., first released in 2001 after 15 years of development, has been successful. In Texas, beetles from Crete, Greece were first released in 2004 and are providing control. However, adults alight, feed and oviposit on athel (Tamarix aphylla), an evergreen tree used for shade and as a windbreak in the southwestern U.S. and México, and occasionally feed on native Frankenia spp. plants. The ability of tamarisk beetles to establish on these potential field hosts was investigated in the field. In no-choice tests in bagged branches, beetle species from Crete and Sfax, Tunisia produced 30–45% as many egg masses and 40–60% as many larvae on athel as on saltcedar. In uncaged choice tests in south Texas, adult, egg mass and larval densities were 10-fold higher on saltcedar than on adjacent athel trees after 2 weeks, and damage by the beetles was 2- to 10-fold greater on saltcedar. At a site near Big Spring, in west-central Texas, adults, egg masses and 1st and 2nd instar larvae were 2- to 8-fold more abundant on saltcedar than on athel planted within a mature saltcedar stand being defoliated by Crete beetles, and beetles were 200-fold or less abundant or not found at all on Frankenia. At a site near Lovelock, Nevada, damage by beetles of a species collected from Fukang, China was 12–78% higher on saltcedar than on athel planted among mature saltcedar trees undergoing defoliation. The results demonstrate that 50–90% reduced oviposition on athel and beetle dispersal patterns within resident saltcedar limit the ability of Diorhabda spp. to establish populations and have impact on athel in the field.     

Systematic Review of Screening and Surveillance Programs to Protect Workers from Nanomaterials

BackgroundScreening and surveillance approaches for workers exposed to nanomaterials could aid in early detection of health effects, provide data for epidemiological studies and inform action to decrease exposure. The aim of this review is to identify such screening and surveillance approaches, in order to extract available data regarding (i) the studies that have successfully been implemented in present day, (ii) identification of the most common and/or toxic nano-related health hazards for workers and (iii) possible exposure surveillance markers. This review contributes to the current understanding of the risk associated with nanomaterials by determining the knowledge gap and making recommendations based on current findings.MethodsA systematic review was conducted. PubMed and Embase were searched to identify articles reporting on any surveillance-related study that described both exposure to nanomaterials and the health indicators that were measured. Four reviewers worked in pairs to independently assess the eligibility of studies and risk of bias before extraction of data. Studies were categorised according to the type of study and the medical surveillance performed, which included the type of nanomaterial, any exposure details provided, as well as health indicators and biomarkers tested.ResultsInitially 92 studies were identified, from which 84 full texts were assessed for eligibility. Seven studies met all the inclusion criteria, i.e. those performed in Taiwan, Korea, Czech Republic and the US. Of these, six compared health indicators between exposed and unexposed workers and one study described a surveillance program. All studies were at a high risk of bias. Workers were exposed to a mix of nanomaterials in three studies, carbon-based nanomaterials in two studies, nano-silver in one study and nano-titanium oxide in the other study. Two studies did not find a difference in biomarkers between exposed and unexposed workers. In addition, differences in early effects on pulmonary function or neurobehavioral tests were not observed. One study found an increased prevalence of allergic dermatitis and “sneezing” in the exposed group.ConclusionsThis review of recently published data on surveillance studies proves that there is a gap in the current knowledge, where most of the surveillance-related studies reported do not follow a set format that provides the required information on ENM characterisation, the type of exposure and the measured indicators/biomarkers. Hence, there is very low quality evidence that screening and surveillance might detect adverse health effects associated with workplace exposure. This systematic review is relevant because it proves that, although surveillance programs have been initiated and preliminary results are being published, the current studies are actually not answering the important questions or solving the overall problem regarding what the potential health hazards are among workers either handling or potentially exposed to ENMs. The recommendations, thus proposed, are based on an obvious need for (i) exposure registries, where longitudinal follow-up studies should inform surveillance, (ii) known exposure measurements or summary indices for ENMs as a reference (iii) validation of candidate biomarkers and (iv) studies that compare the effects of these surveillance approaches to usual care, e.g. those commonly followed for bulk-size hazardous materials.     

Cross-modal interactions between olfaction and touch

We report two experiments designed to investigate the nature of any cross-modal interactions between olfactory and tactile information processing. In Experiment 1, we assessed the influence of olfactory cues on the tactile perception of fabric softness using computer-controlled stimulus presentation. The results showed that participants rated fabric swatches as feeling significantly softer when presented with a lemon odor than when presented with an animal-like odor, demonstrating that olfactory cues can modulate tactile perception. In Experiment 2, we assessed whether this modulatory effect varied as a function of the particular odors being used and/or of the spatial coincidence between the olfactory and tactile stimuli. The results replicated those reported in Experiment 1 thus further supporting the claim that people's rating of tactile stimuli can be modulated by the presence of an odor. Taken together, the results of the two experiments reported here support the existence of a cross-modal interaction between olfaction and touch.     

Evaluation of adverse effects in tamoxifen exposed healthy female dogs

Background

Hypertension and proteinuria are medical complications associated with the multisystemic effects of long-term hypercortisolism in dogs with hyperadrenocorticism (HAC).

Methods

This study investigated the relationships among adrenocorticotropic hormone (ACTH)-stimulation test results, systemic blood pressure, and microalbuminuria in clinically-healthy dogs (n = 100), in dogs affected with naturally occurring pituitary-dependent (PDH; n = 40), or adrenal-dependent hyperadrenocorticism (ADH; n = 30).

Results

Mean systemic blood pressure was similar between clinically healthy dogs and dogs with HAC (p = 0.803). However the incidence of hypertension was highest in dogs with ADH (p = 0.017), followed by dogs with PDH, with the lowest levels in clinically healthy dogs (p = 0.019). Presence of microalbuminuria and albuminuria in clinically healthy dogs and dogs affected with HAC was significantly different (p < 0.001); incidences of albuminuria followed the same pattern of hypertension; highest incidence in dogs with ADH, and lowest level in clinically healthy dogs; but microalbuminuria showed a different pattern: clinically healthy dogs had highest incidences and dogs with ADH had lowest incidence. The presence of albuminuria was not associated with blood pressure values, regardless of whether dogs were clinically healthy or affected with ADH or PDH (p = 0.306).

Conclusions

Higher incidence of hypertension and albuminuria, not microalbuminuria was seen in dogs affected with HAC compared to clinically healthy dogs; incidence of hypertension and albuminuria was significantly higher in dogs affected with ADH compared to PDH. However, presence of albuminuria was not correlated with systemic blood pressure.