Bacterial pili,with emphasis on Mycobacterium tuberculosis curli pili: potential biomarkers for point-of care tests and therapeutics

Context: Novel biomarkers are essential for developing rapid diagnostics and therapeutic interventions

Objective: This review aimed to highlight biomarker characterisation and assessment of unique bacterial pili.

Methods: A PubMed search for bacterial pili, diagnostics, vaccine and therapeutics was performed, with emphasis on the well characterised pili.

Results: In total, 46 papers were identified and reviewed.

Conclusion: Extensive analyses of pili enabled by advanced nanotechnology and whole genome sequencing provide evidence that they are strong biomarker candidates. Mycobacterium tuberculosis curli pili are emphasised as important epitopes for the development of much needed point-of-care diagnostics and therapeutics.     

Development of an in vitro tumor spheroid culture model amenable to high-throughput testing of potential anticancer nanotherapeutics

Context: Three-dimensional tumor spheroid cultures are a better representative of in vivo solid tumors than monolayer cultures and should be used for testing potential nanotherapeutics in vitro.

Objective: To develop techniques to test the disposition and efficacy of nanocarrier formulations in spheroids in a cost-effective manner amenable to high-throughput testing.

Methods: Spheroids were obtained using a modified liquid overlay technique in a 96-well plate. Several nanocarrier formulations were prepared and tested in the spheroid model. The disposition of the formulations in the spheroids was determined by confocal microscopy while the effect of the drug-loaded formulations was assessed in terms of the cell viability, loss of membrane integrity, induction of caspases and inhibition of growth of the spheroids.

Results: The surface charge of the formulations influenced the accumulation of the nanocarrier and drug in the spheroid, with the cationic formulation accumulating to the greatest extent. Also, the smallest particle size formulation, micelles, penetrated to the greatest extent in the spheroid. The iRGD tumor-penetrating peptide co-administered with unmodified liposomes exhibited both high accumulation and penetration. The effect studies revealed that the formulations that penetrated or accumulated to the highest extent in the spheroid exhibited better antitumor activity compared to the other formulations.

Conclusion: The 96-well plate format spheroid model developed in the study can be used toward the rational selection of nanocarrier therapeutics prior to their testing in in vivo models.     

A new species of Camaenidae (Gastropoda,Pulmonata) from Nusa Penida and Lombok Islands,Indonesia: novelty in a well-known fauna

A new species of camaenid land snail, Vulnus wallacei Páll-Gergely, Otani & Hosoda n. sp. is described from Nusa Penida and Lombok Islands, Indonesia. The new species is putatively classified into the genus Vulnus, which is only known so far from the Northern Maluku Islands. The genital anatomy, especially the presence of a well-developed penial sheath in V. wallacei, suggests a close relationship with Australian camaenids. However, the molecular phylogeny based on partial cytochrome c oxidase I, and 16S and 28S ribosomal RNA genes shows that the new species falls outside the cluster of all Australian Camaenidae.

http://www.zoobank.org/urn:lsid:zoobank.org:pub:D28554D0-3578-4E95-8849-09EAFB7D30F7     

Three new species of Crenitis Bedel, 1881 from South Africa,with a revised key to African species (Coleoptera: Hydrophilidae)

Three new species of Crenitis Bedel, 1881 are described from South Africa; C. castellus sp.n. and C. rupestris sp. n. from the KwaZulu-Natal Drakensberg, and C. quagga sp.n. from the Western Cape Province. All three new species were found in madicolous habitats, which appear to be characteristic for a number of species of the genus. A revised key to African species of Crenitis is included.

http://zoobank.org/urn:lsid:zoobank.org:pub:18BE876C-46CB-4AD5-9BB0-EA6F8D711F09     

JNK pathway in osteoarthritis: pathological and therapeutic aspects

Context: Osteoarthritis (OA) is a common chronic degenerative joint disease resulting in physical disability and reduced quality of life. Different biochemical signaling pathways are involved in the progression of OA, including the c-Jun NH2-terminal kinase (JNK) signal transduction pathway.

Objective: In this study, we have reviewed the recent updates on the association of JNK pathway with OA.

Methods: In this review, we have explored the databases like PubMed, Google Scholar, Medline, Scopus, etc., and collected the most relevant papers of JNK signaling pathway involved in the pathogenesis and therapeutics of OA

Results: JNK has been shown by scientific studies to be activated (phosphorylated) in OA that can play a key role in the cartilage destruction. Activation of JNK causes the phosphorylation of c-Jun that causes decreased proteoglycan synthesis and enhanced production of matrix metalloproteinase 13 (MMP-13). Overproduction of MMP-13 by chondrocytes plays a central role in cartilage degeneration in OA. Thus, targeting JNK pathway might be a promising therapeutic application for the prevention and treatment of OA. A number of JNK-inhibitors have been used in vitro and in vivo studies; however, not yet been translated into human use.

Conclusions: This review study indicates that JNK pathway plays an important role in development and progression of OA, and targeting the JNK pathway might be a potential approach for the treatment of OA in future.     

Pre-fledging survival in a Yellow-legged Gull Larus michahellis population in northern Iberia is mostly determined by hatching date

Capsule: Pre-fledging survival in a Yellow-legged Gull Larus michahellis population in northern Iberia is negatively correlated to hatching date.

Aims: To explore which factors have more importance in determining the pre-fledging daily survival rates in a Yellow-legged Gull population from northern Iberia. Specifically, we tested for the effect of hatching date and order, body size and condition and meteorological conditions on pre-fledging survival.

Methods: Cormack–Jolly–Seber models with mixtures were used to model daily survival rates.

Results: Daily survival rates were mostly negatively affected by hatching date.

Conclusions: Hatching date was the most important factor affecting survival of chicks during the pre-fledging period in a Yellow-legged Gull colony from northern Iberia.     

Diverse scaling relationships of tree height and diameter in five tree species

Background: Allometric scaling relationships are important in ecology and forestry. The metabolic scaling theory (MST) predicts a universal invariant scaling relationship for tree growth, relating height and diameter to each other.

Aims: Data on five tree species (Pinus taeda L., Pinus virginiana Mill., Liquidambar styraciflua L., Liriodendron tulipifera L., and Pinus palustris Mill.) were used to test the predictions from MST on the scaling of height–diameter and also diameter growth.

Methods: Data on tree height and diameter for five tree species from both natural forests and plantations were collected to study two types of scaling relationships: tree height–diameter and stem diameter growth. A reduced major axis of regression analysis model type II was used to determine scaling exponents from each species under different environmental conditions.

Results: No universal invariant scaling exponent was found in height–diameter and diameter growth for the five species. The scaling varied across natural forests, plantations and scales (e.g., time and number of measured trees). However, in some situations the scaling exponents failed to show significant difference with the predicted values (e.g., 2/3 or 1).

Conclusions: Diverse scaling exponents were observed for the five tree species with the scaling relationships varying with environmental settings.     

Predictors of leptin concentration and association with cardiovascular risk in patients with coronary artery disease: results from the AtheroGene study

Context: Leptin is produced in white adipose tissue, but also in human coronary atherosclerotic lesions.

Objective: The aim of this study is to assess the prognostic value of leptin in patients with proven coronary artery disease (CAD) (N?=?1907).

Methods: AtheroGene is a contemporary CAD cohort study (N?=?3229). Median follow-up time was 3.8 (Quartile 1/3 with 2.8/4.9) years.

Results: Leptin concentration was associated with a hazard ratio (HR) for the fully adjusted model of HR?=?1.32 in women but was not significant in men. The endpoint cardiovascular death and non-fatal myocardial infarction was observed in 167 patients.

Conclusion: In women with known CAD, increased leptin concentration is useful for predicting cardiovascular death and non-fatal myocardial infarction.     

Glutamate metabolism in HIV-1 infected macrophages: Role of HIV-1 Vpr

HIV-1 infected macrophages play a significant role in the neuropathogenesis of AIDS. HIV-1 viral protein R (Vpr) not only facilitates HIV-1 infection but also contribute to long-lived persistence in macrophages. Our previous studies using SILAC-based proteomic analysis showed that the expression of critical metabolic enzymes in the glycolytic pathway and tricarboxylic acid (TCA) cycle were altered in response to Vpr expression in macrophages. We hypothesized that Vpr-induced modulation of glycolysis and TCA cycle regulates glutamate metabolism and release in HIV-1 infected macrophages.

We assessed the amount of specific metabolites induced by Vpr and HIV-1 in macrophages at the intracellular and extracellular level in a time-dependent manner utilizing multiple reaction monitoring (MRM) targeted metabolomics. In addition, stable isotope-labeled glucose and an MRM targeted metabolomics assay were used to evaluate the de novo synthesis and release of glutamate in Vpr overexpressing macrophages and HIV-1 infected macrophages, throughout the metabolic flux of glycolytic pathway and TCA cycle activation.

The metabolic flux studies demonstrated an increase in glucose uptake, glutamate release and accumulation of α-ketoglutarate (α-KG) and glutamine in the extracellular milieu in Vpr expressing and HIV-1 infected macrophages. Interestingly, glutamate pools and other intracellular intermediates (glucose-6-phosphate (G6P), fructose-6-phosphate (F6P), citrate, malate, α-KG, and glutamine) showed a decreased trend except for fumarate, in contrast to the glutamine accumulation observed in the extracellular space in Vpr overexpressing macrophages.

Our studies demonstrate that dysregulation of mitochondrial glutamate metabolism induced by Vpr in HIV-1 infected macrophages commonly seen, may contribute to neurodegeneration via excitotoxic mechanisms in the context of NeuroAIDS.     

Editorial Retraction

Upon a thorough investigation, it has been determined that the paper titled “Integrating Microbial Composting and Vermicomposting for Effective Utilization of By-Products of Sugar Cane-Processing Industries” by Shweta, Rahul Kumar, B.L. Singh, and Verma Deepshikha published in the Bioremediation Journal, 2010, Volume 14, pages 158–167, was simultaneously submitted and published in two journals. The same study with minor textual variations titled “Composting of sugar-cane waste by-products through treatment with microorganisms and subsequent vermicomposting” also written by Shweta, Rahul Kumar, B.L. Singh, and Verma Deepshikha published in the Elsevier publication, Bioresource Technology, 2010, 6707–6711, three months prior to publishing in Bioremedation Journal.

As a result the article published in Bioremediation Journal has been retracted and should not be cited in the electronic or print version of the journal.

Dr. Hanadi S. Rifai

Editor-in-Chief

Bioremediation Journal

Please click here to view the article to which this statement of retraction relates.     

Habitat associations of young Black Grouse Tetrao tetrix broods

Capsule: In the Scottish Highlands, Black Grouse Tetrao tetrix females with young broods selected areas rich in wet flushes, grasses and Sphagnum mosses.

Aims: To identify associations between young Black Grouse broods and habitat characteristics.

Methods: We located brood-rearing Black Grouse females in four areas of moorland-forest mosaic in the Scottish Highlands. Each brood was paired with a random reference location 100?m away. We recorded cover of different habitats and fine-scale vegetation and structure within squares of 1 and 0.25?ha, respectively. Associations between brood occurrence and habitat and vegetation variables were examined at the two scales.

Results: Black Grouse broods were positively associated with wet flushes (1?ha), and with Heather Calluna vulgaris, sedges Carex spp., grasses, Sphagnum mosses and taller vegetation with intermediate levels of height variability (0.25?ha).

Conclusions: This study highlights the importance of wet habitats for young Black Grouse chicks. In addition, relatively tall field-layer vegetation comprising Heather, sedges, grasses over a layer of Sphagnum mosses attracted brood-rearing Black Grouse females. Many management practices associated with peatland restoration, including drain-blocking, Sphagnum re-establishment and the avoidance of burning on deep peat soils, are therefore consistent with favourable habitat management for Black Grouse.     

The pharmacologic characterization of allosteric molecules: Gq protein activation

Context: Drugs such as positive allosteric modulators (PAMs) produce complex behaviors when acting on tissues in different physiological contexts in vivo.

Objective: This study describes the use of functional assays of varying receptor sensitivity to unveil the various behaviors of PAMs and thus quantify allosteric effect through system independent scales.

Materials and methods: Muscarinic receptor activation with acetylcholine (ACh) was used to the demonstrate activity of the PAM agonist 1–(4-methoxybenzyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid, Benzyl quinolone carboxylic acid (BQCA) in terms of direct agonism, potentiation of ACh affinity, and ACh efficacy. Concentration–response curves were fit to the functional allosteric model to yield indices of agonism (τ_B), effects on affinity (α cooperativity), and efficacy (β cooperativity).

Results: It is shown that a highly sensitive functional assay revealed the direct efficacy of BQCA as an agonist and relatively insensitive cells (produced by chemical alkylation of muscarinic receptor with phenoxybenzamine) revealed a positive allosteric effect of BQCA on ACh efficacy. A wide range of functional assay sensitivities produced a complex pattern of behavior for BQCA all of which was accurately quantified through the system-independent parameters of the functional allosteric model.

Conclusions: The study of complex allosteric molecules in a range of functional assays of varying sensitivity allows the measurement of the complete array of activities of these molecules on receptors and also better predicts which will be seen with these in vivo where a range of tissue sensitivities is encountered.     

The role of elevation and soil chemistry in the distribution and ion accumulation of floral morphs of Streptanthus polygaloides Gray (Brassicaceae), a Californian nickel hyperaccumulator

Background: The flora of serpentine/ultramafic soils provides an excellent model system for the study of natural selection in plant populations. Streptanthus polygaloides is a nickel hyperaccumulator that is endemic to serpentine soils in the Sierra Nevada of California, and has four floral morphs (yellow, purple, yellow-to-purple and undulate).

Aims: We investigate three hypotheses: (1) the purple morph occurs in colder, wetter climates than the yellow morph; (2) tissue–soil ionic relationships differ among morphs; and (3) morphs occur on soils with differing elemental concentrations.

Methods: We queried herbarium records to investigate patterns of occurrence among the yellow and purple floral morphs, and analysed soil and tissue samples from wild populations of all four morphs.

Results: The purple morph inhabited serpentine outcrops with colder temperatures and greater precipitation levels than the yellow morph. Concentrations of elements in leaf tissue and rhizosphere soil differed little among populations of the morphs, but showed substantial within-site variation.

Conclusions: Our results suggest that a climatic gradient may be responsible for divergence in floral colour among populations of S. polygaloides. Because of the large within-site variation in soil and tissue elemental concentrations, plants appear to have a varied physiological response to edaphic factors, regardless of morph membership.     

Mutation in the beta3 subunit of Guanine nucleotide-binding protein (GNB3) gene is not associated with Type II diabetes mellitus risk: a case–control study of a North Indian population

Context: Genetics play a major role in development and pathophysiology of Type 2 diabetes mellitus (T2DM).

Objective: To asses the association of Guanine nucleotide-binding protein (GNB3) (C825T) gene's polymorphism with T2DM.

Materials and methods: A case–control study including 400 North Indians was performed using Polymerase Chain Reaction–Restriction Fragment Length Polymorphism (PCR-RFLP) approach to analyze genetic polymorphism.

Results: No significant difference was observed in genotype and allele frequencies of GNB3 gene on comparing cases with controls.

Discussion: Our study is in agreement with studies on Polish, Japanese, Hispanic-American and Danish populations who observed no significant association between GNB3 (C825T) polymorphism and T2DM.

Conclusion: GNB3 (C825T) polymorphism is not associated with T2DM.     

Optimizing neuromuscular electrical stimulation for hand opening

Aim: To investigate the effect of introducing an interphase interval to a biphasic pulse on force production and muscle fatigue, during stimulation of the wrist and finger extensors and to determine whether the IPI effect on force is dependent on electrode position.

Methods: Electrically-induced contraction forces of the wrist and finger extensors were measured in 15 healthy subjects undergoing stimulation. These forces were assessed with interphase interval settings at 0, 100, and 200μs, with both electrodes located just distal to common extensor origin (proximal placement) or with the distal electrode placed over the extensor and abductor policies longus muscles (distal placement). The degree of discomfort related to stimulation sensation was evaluated using a numeric rating scale. Muscle fatigue was measured during proximal placement.

Results: Under both electrode locations, introduction of 100 or 200?μs interphase interval enhanced force production; yet, only the 100μs interphase interval increased force without increasing discomfort. Additionally, stimulation sensation was more comfortable with proximal placement. Introducing interphase interval significantly increased the muscle force output during a repetitive stimulation fatigue protocol.

Conclusions: When using neuromuscular electrical stimulation to activate the wrist and finger extensors, clinicians should consider locating both stimulating electrodes proximally over the extensor surface of the forearm and apply a 100?µs interphase interval to a biphasic pulse. Future research that should establish these findings in individuals with various pathologies, especially in patients with residual hand spasticity.     

Association between polymorphisms in IL21 gene and risk for sepsis

Context: Sepsis is now the leading cause of death in the noncardiovascular intensive care unit (ICU).

Objective: To investigate whether polymorphisms in IL21 gene contribute to sepsis susceptibility.

Materials and methods: Three single-nucleotide polymorphisms of IL21 (rs907715, rs2055979, rs12508721) were genotyped by TaqMan assay in patients with sepsis and control subjects.

Results: Polymorphisms rs2055979 and rs12508721 in IL21 were more frequent in sepsis patients compared to general population. But allele frequency of rs907715 was not significantly different between sepsis patients and control subjects.

Conclusion: Polymorphisms in IL21 may be associated with sepsis risk.     

Water-induced stress influences the relative investment in cleistogamous and chasmogamous flowers of an invasive grass,Microstegium vimineum (Poaceae)

Background: Global climate change has the potential to shape evolutionary trajectories of invasive species via many routes, including through changes in mating systems. Many cleistogamous (CL) plants adjust investment in CL (selfed) vs. chasmogamous (CH, potentially outcrossed) progeny across environmental gradients. However, the details of such adjustments are lacking for highly invasive plant species.

Aims: We used a highly invasive grass, Microstegium vimineum, as a model for understanding how changes in water-induced stress (including potential associated changes in soil nutrient availability) might affect mating systems and thus evolutionary change in invasive species. We predicted that plants would respond to increased water-induced stress through a relative reduction in investment in CL vs. CH reproduction (i.e., a decrease in the CL:CH ratio).

Methods: Under greenhouse conditions, we measured fecundity (number of inflorescences and florets per plant) as well as relative investment in CL vs. CH florets (CL:CH ratios for number of inflorescences, florets per inflorescence, overall florets) in response to three watering treatments approximating mesic (low) to inundated (high) conditions.

Results: Plant biomass was significantly lower in high-watering treatment relative to intermediate and low treatments, indicating that the high-water condition was stressful. Contrary to expectations, stressed plants significantly increased relative investment in CL reproduction, a pattern associated with decreased inflorescence number and increased numbers of CL florets per inflorescence.

Conclusions: We conclude that changes in water-induced stress could strongly influence realised rates of outcrossing in this invasive plant, leading to mating system evolution, and altered invasiveness.     

H19 non-coding RNA in urine cells detects urothelial carcinoma: a pilot study

Context: Urothelial carcinoma (UC) is common and highly recurrent. Diagnosis and follow-up involve invasive cystoscopies.

Objective: To evaluate H19 RNA in urine cells as diagnostic tool for UC.

Materials and methods: RT-PCR analysis of urine samples from healthy volunteers and UC patients.

Results: H19 RNA was unequivocally detected in the urine of 90.5% of patients and 25.9% of controls. H19 copies were three orders of magnitude higher in patients. Receiver operating characteristic analysis showed an area under the curve of 0.933.

Conclusions: This pilot study shows that urinary cell H19 is a highly sensitive test for UC and pending verification could transform patient management.     

Effect of liposome-treated red blood cells in an anemic rat model

Context: Liposomes have been shown to improve human red blood cell (RBC) in vitro quality by minimizing membrane damage occurring during 42-d hypothermic storage. Small animal models are necessary to evaluate novel blood products and guide future clinical studies.

Objectives: The aim of this study was to assess the effect of liposome treatments on rat RBC hypothermic storage lesion (HSL) and to examine in vivo outcomes of transfusing liposome treated RBCs in a rat model.

Materials and methods: Unilamellar liposomes were synthesized which contained saturated (DPPC:CHOL, 7:3?mol%), unsaturated (DOPC:CHOL, 7:3?mol%), saturated charged (DPPC:CHOL:PS, 6:3:1?mol%), and unsaturated charged (DOPC:CHOL:PS, 6:3:1?mol%) phospholipids. After liposome treatment, rat RBC quality was assessed by percent hemolysis, deformability, aggregation, hematological indices, microvesiculation, and cholesterol/phospholipid concentrations. An anemic rat model of myocardial ischemia and reperfusion (I/R) was used to evaluate the outcomes of transfusing liposome-treated RBCs.

Results: All four liposome treatments resulted in significant decreases in hemolysis, with the most prominent effect seen with DOPC-liposomes (DOPC: 1.6?±?0.1% versus control: 3.1?±?0.2%, p?=?0.015). RBCs treated with uncharged liposomes had lower hemolysis compared with charged liposomes (3.4?±?0.2% versus 3.9?±?0.4%, p?=?0.010). The in vivo study showed no significant difference in the hemoglobin levels and infarct size (53.3?±?13.1% versus 45.3?±?8.4%, p?=?0.223) between liposome and control groups.

Discussion and conclusion: Liposome treatment improved in vitro quality of stored rat RBCs. However, the changes observed in vitro were not sufficient to improve the in vivo outcomes of myocardial I/R in anemic rats transfused with liposome-treated RBCs.