Haematology and serum biochemistry of West African Dwarf goats fed Pleurotus tuber-regium-treated cassava root sievate-based diets.

The study aimed at determining the effect of Pleurotus tuber-regium-treated cassava root sievate-based diets on haematology and serum biochemistry of West African Dwarf (WAD) goats. Thirty-two WAD goats between 6 and 8 months old were randomly divided into four groups of eight goats each. The four experimental diets were formulated to contain 0, 20, 40 and 60% dietary levels of inclusion of Pleurotus tuber-regium-treated cassava root sievate, respectively. The groups were randomly assigned to the four experiment diets (T1, T2, T3 and T4) for 90 days in a completely randomized design. At the start of the experiment, packed cell volume (PCV) ranged from 24.90 to 29.49% and red blood cell (RBC) 9.42-10.44 × 10 12/L while mean cell haemoglobin significantly (p < 0.05) ranged from 5.44 to 6.41 pg. At the end of the experiment, PCV and RBC showed significant differences (p < 0.05) and were better in T2. At the start of the experiment, cholesterol ranged from 2.15 to 2.29 mmol/l, creatinine from 75.72 to 80.32 µmol/l, urea from 16.39 to 16.72 mg/dl, total bilirubin from 0.25 to 0.28 µmol/l, total protein from 61.73 to 63.16 g/I, globulin from 29.08 to 29.59 g/I and aspartate aminotransferase (AST) from 68.62 to 71.06 U/L. At the end of the trial, cholesterol values were significantly (p < 0.05) higher in T1. Urea was significantly reduced (p < 0.05) with T1 showing significantly higher values than T3 and T4. Total protein, globulin and total bilirubin increased (p < 0.05) linearly from T1 to T4. AST was improved (p < 0.05) at the end of the study. The study revealed that the inclusion of Pleurotus tuber-regium-degraded cassava root sievate in the diets of West African Dwarf goats had no deleterious effects on the haematological and serum biochemical parameters of goats and could be included in goat diets up to 60%.

Alterations in the expression of a neurodevelopmental gene exert long-lasting effects on cognitive-emotional phenotypes and functional brain networks: translational evidence from the stress-resilient Ahi1 knockout mouse.

Many psychiatric disorders are highly heritable and may represent the clinical outcome of early aberrations in the formation of neural networks. The placement of brain connectivity as an 'intermediate phenotype' renders it an attractive target for exploring its interaction with genomics and behavior. Given the complexity of genetic make up and phenotypic heterogeneity in humans, translational studies are indicated. Recently, we demonstrated that a mouse model with heterozygous knockout of the key neurodevelopmental gene Ahi1 displays a consistent stress-resilient phenotype. Extending these data, the current research describes our multi-faceted effort to link early variations in Ahi1 expression with long-term consequences for functional brain networks and cognitive-emotional phenotypes. By combining behavioral paradigms with graph-based analysis of whole-brain functional networks, and then cross-validating the data with robust neuroinformatic data sets, our research suggests that physiological variation in gene expression during neurodevelopment is eventually translated into a continuum of global network metrics that serve as intermediate phenotypes. Within this framework, we suggest that organization of functional brain networks may result, in part, from an adaptive trade-off between efficiency and resilience, ultimately culminating in a phenotypic diversity that encompasses dimensions such as emotional regulation and cognitive function.

Apremilast, an oral phosphodiesterase 4 inhibitor, improves patient-reported outcomes in the treatment of moderate to severe psoriasis: results of two phase III randomized, controlled trials.

BACKGROUND: Apremilast, an oral phosphodiesterase 4 inhibitor, has an acceptable safety profile and is effective for treatment of plaque psoriasis and psoriatic arthritis. OBJECTIVES: To evaluate the impact of apremilast on health-related quality of life (HRQOL), general functioning and mental health using patient-reported outcome (PRO) assessments among patients with moderate to severe plaque psoriasis in the ESTEEM 1 and 2 trials. METHODS: A total of 1255 patients were randomized (2 : 1) to apremilast 30 mg BID or placebo for 16 weeks; all received apremilast through Week 32. PRO assessments included the Dermatology Life Quality Index (DLQI), 36-Item Short-Form Health Survey version 2 mental/physical component summary scores (SF-36v2 MCS/PCS), Patient Health Questionnaire-8 (PHQ-8), EuroQol-5D (EQ-5D) and Work Limitations Questionnaire-25 (WLQ-25). Post hoc analyses examined relationships between Psoriasis Area and Severity Index (PASI) scores and PHQ-8 in the apremilast-treated population at Week 16. RESULTS: Treatment with apremilast improved all HRQOL PROs at Week 16 (vs. placebo), except the SF-36v2 PCS, and improvements were sustained through Week 32. Mean DLQI and SF-36v2 MCS improvements exceeded minimal clinically important differences. Changes at Week 16 in PHQ-8 and PASI were weakly correlated, and only 35.8% of patients who achieved a ≥75% reduction from baseline in PASI score (PASI-75) with apremilast treatment also achieved PHQ-8 scores of 0-4. CONCLUSIONS: Apremilast led to improvements in HRQOL PROs vs. placebo in patients with moderate to severe plaque psoriasis.

Associations between markers of colorectal cancer stem cells, mutation, microRNA and the clinical features of ulcerative colitis.

AIM: Several factors have been implicated in the pathogenesis of colorectal cancer (CRC) associated with ulcerative colitis (UC). We investigated markers of cancer cell pluripotency, including CD44 and CD166, microRNA-21 (miR-21) and microRNA-215 (miR-215), and APC, K-ras and DCC mutations in biopsy specimens from patients with UC to evaluate any correlations with clinical risk factors. METHOD: We observed 18 patients with UC and collected two biopsy specimens from each patient at diagnosis and at a follow-up end-point. We examined the expression of CD44, CD166, miR-21 and miR-215, and APC, K-ras and DCC mutations. We compared these markers at the two time points and assessed their associations with clinical characteristics, including the duration of colitis, histological alterations and the age of the patient at the onset of UC. RESULTS: Most (16/18) patients had alleviation of mucosal inflammation or remained stable during follow-up; one patient developed dysplasia and one had severe aggravation of the lesion during follow-up. Enhanced expression of CD44, CD166 and miR-21 with miR-215 was found in the specimens obtained at follow-up, despite alleviation of mucosal lesions. Coherence of cancer stem cell markers and miRNAs was seen in patients who had significant worsening of inflammation, dysplasia and a long duration of colitis. APC mutation occurred in only one patient; this patient had the longest duration of UC (23 years). CONCLUSION: Enhanced markers of CRC in follow-up colonic mucosal samples support the conclusion that the duration of UC plays the most important role in UC-related carcinogenesis.

Reduction of large vessel traffic improves water quality and alters fish habitat-use throughout a large river.

Rivers are increasingly used as superhighways for the continental-scale transportation of freight goods, but the ecological impact of large vessel traffic on river ecosystems is difficult to study. Recently, the temporary maintenance closure of lock and dam systems on the Illinois Waterway (USA) brought commercial vessel traffic to a halt along the river's length, offering a rare opportunity to study the response of the ecosystem before, during, and after an extended pause of this persistent anthropogenic disturbance. We observed improvements in main- and side-channel water quality and a redistribution of fish habitat-use during a months-long, near-complete reduction of large vessel traffic. Over 3600 water quality and 1300 fish community samples indicate that large vessel traffic reduction coincided with a 33 % reduction in turbidity as well as increased use of sampling strata near vessel navigation corridors by sound-sensitive and rheophilic fishes. Gizzard shad (Dorosoma cepedianum), the most abundant species in the system, also expanded their use of these 'impact' areas. Though inland waterway transport is an economically- and climate-friendly alternative to trucking and rail for the shipment of freight, our data suggest that intense vessel traffic may have profound physical and biological impacts across a large river. Monitoring and mitigation of ecological impacts of the ongoing expansion of inland waterway transport around the world will be critical to balancing large rivers as both useful navigation corridors and functional ecosystems.

NK1 tachykinin receptor antagonist treatment reduces cerebral edema and intracranial pressure in an ovine model of ischemic stroke.

Following ischemic stroke, substance P (SP)-mediated neurogenic inflammation is associated with profound blood-brain barrier (BBB) dysfunction, cerebral edema, and elevated intracranial pressure (ICP). SP elicits its effects by binding the neurokinin 1 tachykinin receptor (NK1-R), with administration of an NK1-R antagonist shown to ameliorate BBB dysfunction and cerebral edema in rodent and permanent ovine stroke models. Given the importance of reperfusion in clinical stroke, this study examined the efficacy of NK1-R antagonist treatment in reducing cerebral edema and ICP in an ovine model of transient middle cerebral artery occlusion (tMCAo). Anesthetized sheep (n = 24) were subject to 2-hours tMCAo and randomized (n = 6/group) to receive early NK1-R treatment (days 1-3 post-stroke), delayed NK1-R treatment (day 5 post-stroke), or saline vehicle. At 6-days post-stroke animals were re-anaesthetized and ICP measured, followed by MRI to evaluate infarction, edema and BBB dysfunction. Following both early and delayed NK1-R antagonist administration, ICP was significantly reduced on day 6 compared to vehicle animals (p < 0.05), accompanied by a reduction in cerebral edema, midline shift and BBB dysfunction (p < 0.05). This study demonstrates that NK1-R antagonist treatment is an effective novel therapy for cerebral edema and elevated ICP following stroke in an ovine model, warranting future clinical evaluation.

Predation of invasive silver carp by native largemouth bass is size-selective in the Illinois River.

Silver carp (Hypophthalmichthys molitrix) are a nonnative, planktivorous, and highly invasive species of cyprinid located throughout the Mississippi River Basin. Although they co-occur with largemouth bass (Micropterus nigricans), an abundant native predatory fish, their predator-prey relationship is poorly understood. This potential relationship warrants investigation as largemouth bass are large-gaped predators capable of exhibiting top-down control on planktivorous fishes. The objectives of this study were to determine if largemouth bass consume juvenile silver carp, and if there was a relationship between length of largemouth bass and length of silver carp consumed. Largemouth bass were collected from the La Grange Pool of the Illinois River using 60 Hz-pulsed DC electrofishing and their diets were analyzed (n = 389, total length = 70-578 mm). Evidence of silver carp was present in 18% of diets of largemouth bass that consumed fish. Lengths of consumed silver carp were estimated from the dimensions of their recovered chewing pads or pharyngeal teeth in the stomachs of largemouth bass. A significant relationship between length of largemouth bass and length of silver carp consumed (p < 0.001, F = 34.63, r2 = 0.61) was observed. Estimated total lengths of silver carp were 34-101 mm and were recovered from diets of largemouth bass that were 94-262 mm total length. These results indicate enhancement of native largemouth bass populations is unlikely to substantially reduce silver carp populations in the Illinois River or in other waterways where these species co-occur.

Neurological scoring and gait kinematics to assess functional outcome in an ovine model of ischaemic stroke.

Background: Assessment of functional impairment following ischaemic stroke is essential to determine outcome and efficacy of intervention in both clinical patients and pre-clinical models. Although paradigms are well described for rodents, comparable methods for large animals, such as sheep, remain limited. This study aimed to develop methods to assess function in an ovine model of ischaemic stroke using composite neurological scoring and gait kinematics from motion capture. Methods: Merino sheep (n = 26) were anaesthetised and subjected to 2 hours middle cerebral artery occlusion. Animals underwent functional assessment at baseline (8-, 5-, and 1-day pre-stroke), and 3 days post-stroke. Neurological scoring was carried out to determine changes in neurological status. Ten infrared cameras measured the trajectories of 42 retro-reflective markers for calculation of gait kinematics. Magnetic resonance imaging (MRI) was performed at 3 days post-stroke to determine infarct volume. Intraclass Correlation Coefficients (ICC's) were used to assess the repeatability of neurological scoring and gait kinematics across baseline trials. The average of all baselines was used to compare changes in neurological scoring and kinematics at 3 days post-stroke. A principal component analysis (PCA) was performed to determine the relationship between neurological score, gait kinematics, and infarct volume post-stroke. Results: Neurological scoring was moderately repeatable across baseline trials (ICC > 0.50) and detected marked impairment post-stroke (p < 0.05). Baseline gait measures showed moderate to good repeatability for the majority of assessed variables (ICC > 0.50). Following stroke, kinematic measures indicative of stroke deficit were detected including an increase in stance and stride duration (p < 0.05). MRI demonstrated infarction involving the cortex and/or thalamus (median 2.7 cm3, IQR 1.4 to 11.9). PCA produced two components, although association between variables was inconclusive. Conclusion: This study developed repeatable methods to assess function in sheep using composite scoring and gait kinematics, allowing for the evaluation of deficit 3 days post-stroke. Despite utility of each method independently, there was poor association observed between gait kinematics, composite scoring, and infarct volume on PCA. This suggests that each of these measures has discreet utility for the assessment of stroke deficit, and that multimodal approaches are necessary to comprehensively characterise functional impairment.

Reduced O2 concentration during CAM development--its effect on physiological parameters of broiler embryos.

Embryo development is a dynamic process, determined by both the genetic background of the organism and the environment in which it develops. Environmental alterations during an organism's embryogenesis may induce changes in the development of some physiological regulatory systems, thereby causing permanent phenotypic changes in the embryo. The present study aimed to assess the effect of 17% O(2) concentration during chorioallantoic membrane (CAM) development on a) CAM development, b) cardiovascular parameters, and c) embryo development postexposure and up to hatch. Two replicated trials, each with 840 fertile Cobb eggs, were conducted. At embryonic d 5 (E5) eggs were divided into 2 treatments: 1) control, and 2) 17% O(2) concentration for 12 h/d from E5 through E12 (12H). The 12H embryos exhibited a clear and significant increase in the vascular area of the CAM, which grew to 6.8% larger than that of the control. Hematocrit and hemoglobin levels, as measured on E13 and E14, increased in response to the hypoxic treatments, but these differences were not maintained subsequently. Heart rate and relative heart weight were not affected by hypoxic exposure, but eggshell temperature in the 12H treatment was higher than that of the control, indicating higher heat production, which is consistent with the elevated plasma concentrations of triiodothyronine and thyroxin and with the enhanced oxygen consumption and residual yolk intake rate that followed exposure to hypoxic conditions. These findings indicate that embryos adapted to hypoxic condition enhance angiogenesis processes, which subsequently increase their blood oxygen-carrying capacity, enabling the increase of oxygen consumption, which positively affects their growth development and maturation compared with the control embryos. Such alterations may affect posthatch performance and the ability of broilers cardiovascular system to meet elevated oxygen demand.

The cysteine-rich regions of the regulatory domains of Raf and protein kinase C as retinoid receptors.

Vitamin A and its biologically active derivatives, the retinoids, are recognized as key regulators of vertebrate development, cell growth, and differentiation. Although nuclear receptors have held the attention since their discovery a decade ago, we report here on serine/threonine kinases as a new class of retinoid receptors. The conserved cysteine-rich domain of the NH(2)-terminal regulatory domains of cRaf-1, as well as several select domains of the mammalian protein kinase C (PKC) isoforms alpha, delta, zeta, and mu, the Drosophila and yeast PKCs, were found to bind retinol with nanomolar affinity. The biological significance was revealed in the alternate redox activation pathway of these kinases. Retinol served as a cofactor to augment the activation of both cRaf and PKC alpha by reactive oxygen, whereas the classical receptor-mediated pathway was unaffected by the presence or absence of retinol. We propose that bound retinol, owing to its electron transfer capacity, functions as a tag to enable the efficient and directed redox activation of the cRaf and PKC families of kinases.

Environmental shedding of toxigenic Clostridioides difficile by asymptomatic carriers: A prospective observational study.

OBJECTIVES: The aim was to compare the burden of environmental shedding of toxigenic Clostridioides difficile among asymptomatic carriers, C. difficile-infected (CDI) patients and non-carriers in an inpatient non-epidemic setting. METHODS: C. difficile carriage was determined by positive toxin-B PCR from rectal swabs of asymptomatic patients. Active CDI was defined as a positive two-step enzyme immunoassay/polymerase chain reaction (EIA/PCR) test in patients with more than three unformed stools/24 hr. C. difficile environmental contamination was assessed by obtaining specimens from ten sites in the patients' rooms. Toxigenic strains were identified by PCR. We created a contamination scale to define the overall level of room contamination that ranged from clean to heavy contamination. RESULTS: One hundred and seventeen rooms were screened: 70 rooms inhabited by C. difficile carriers, 30 rooms by active CDI patients and 17 rooms by non C. difficile -carriers (control). In the carrier rooms 29 (41%) had more than residual contamination, from which 17 (24%) were heavily contaminated. In the CDI rooms 12 (40%) had more than residual contamination from which three (10%) were heavily contaminated, while in the control rooms, one room (6%) had more than residual contamination and none were heavily contaminated. In a multivariate analysis, the contamination score of rooms inhabited by carriers did not differ from rooms of CDI patients, yet both were significantly more contaminated than those of non-carriers odd ratio 12.23 and 11.16 (95% confidence interval 1.5-99.96 p 0.0195, and 1.19-104.49 p 0.035), respectively. DISCUSSION: Here we show that the rooms of C. difficile carriers are as contaminated as those of patients with active CDI and significantly more than those of non-carriers.

Intracellular signaling by 14-hydroxy-4,14-retro-retinol.

In mammals, retinol is the precursor for retinoids, which affect various aspects of morphogenesis and development. However, B lymphocytes, although retinol-dependent, do not use retinoic acid as mediator. Retinol is metabolized by B lymphocytes and other cell lines to optically active 14-hydroxy-4,14-retro-retinol; it is this compound that mediates the growth control. Thus another second messenger molecule, in addition to retinoic acid and retinal, is derived from retinol.

Crystallography of Chevrel phases, MMo6T8 (M = Cd, Na, Mn, and Zn, T = S, Se) and their cation mobility.

Chevrel phases (CPs), M(x)Mo(6)T(8) (M = metal, T = S, Se) are unique materials, which allow for a fast and reversible insertion of various cations at room temperature. In spite of extensive studies of these materials, the origin of their high ionic mobility remained unclear. In a previous paper we presented for the first time a proper classification of the very complex transport behavior of different cations in the Mo(6)T(8) hosts: (i) apparent immobility of the large M cations such as Pb(2+), Sn(2+), Ag(+) in the ternary phases, MMo(6)T(8); (ii) coupled M+M' diffusion in the quaternary phases, M(x)M'(y)Mo(6)T(8), where both large and small cations can assist; (iii) cation trapping in the Mg-Mo(6)S(8), Cd-Mo(6)S(8), and Na-Mo(6)T(8) systems; (iv) a combination of low- and high-rate diffusion kinetics at the first and last intercalation stages, respectively, for the Cu-Mo(6)S(8), Mn-Mo(6)S(8), and Cd-Mo(6)Se(8) systems, and (v) a fast ionic transport for small cations such as Ni(2+), Zn(2+), and Li(+). It was shown that this behavior could be understood by a relatively simple crystallographic analysis (mapping of all the cation sites and estimations of their potential energy according to the distances of these sites from adjacent anions and cations) of the diffusion routes, which differ for different cations. For this analysis, it was necessary to complete our knowledge about the cation location in the crystal structure for several CPs with known ionic mobility. This article presents the results of a combined Rietveld analysis of powder X-ray and high-resolution neutron diffraction profiles for NaMo(6)T(8), ZnMo(6)T(8), CdMo(6)T(8), and MnMo(6)S(8). All seven compounds can be defined as classic CPs, where cation delocalization from the center of the largest cavity between the Mo(6)T(8) blocks decreases with the length of the ideal chemical bond, M-T. In addition, this work details the effect of the structural parameters on the ionic conductivity in CPs, namely, it shows how subtle changes in cation delocalization may be crucial for diffusion kinetics.

Longitudinal analysis of Voice Handicap Index in early glottic cancer patients treated with transoral laser microsurgery: age, gender, stage and time dependence.

OBJECTIVES: Transoral laser microsurgery is an increasingly common treatment modality for glottic carcinoma. This study aimed to determine the effect of age, gender, stage and time on voice-related quality of life using the Voice Handicap Index-10. METHODS: Primary early glottic carcinoma patients treated with transoral laser microsurgery were included in the study. Self-reported Voice Handicap Index testing was completed pre-operatively, three months post-operatively, and yearly at follow-up appointments. RESULTS: Voice Handicap Index improvement was found to be dependent on age and tumour stage, while no significant differences were found in Voice Handicap Index for gender. Voice Handicap Index score was significantly improved at 12 months and 24 months. Time versus Voice Handicap Index modelling revealed a preference for non-linear over linear regression. CONCLUSION: Age and stage are important factors, as younger patients with more advanced tumours show greater voice improvement post-operatively. Patient's Voice Handicap Index is predicted to have 95 per cent of maximal improvement by 5.5 months post-operatively.

Determining the Temporal Profile of Intracranial Pressure Changes Following Transient Stroke in an Ovine Model.

BACKGROUND AND PURPOSE: Cerebral edema and elevated intracranial pressure (ICP) are the leading cause of death in the first week following stroke. Despite this, current treatments are limited and fail to address the underlying mechanisms of swelling, highlighting the need for targeted treatments. When screening promising novel agents, it is essential to use clinically relevant large animal models to increase the likelihood of successful clinical translation. As such, we sought to develop a survival model of transient middle cerebral artery occlusion (tMCAO) in the sheep and subsequently characterize the temporal profile of cerebral edema and elevated ICP following stroke in this novel, clinically relevant model. METHODS: Merino-sheep (27M;31F) were anesthetized and subject to 2 h tMCAO with reperfusion or sham surgery. Following surgery, animals were allowed to recover and returned to their home pens. At preselected times points ranging from 1 to 7 days post-stroke, animals were re-anesthetized, ICP measured for 4 h, followed by imaging with MRI to determine cerebral edema, midline shift and infarct volume (FLAIR, T2 and DWI). Animals were subsequently euthanized and their brain removed for immunohistochemical analysis. Serum and cerebrospinal fluid samples were also collected and analyzed for substance P (SP) using ELISA. RESULTS: Intracranial pressure and MRI scans were normal in sham animals. Following stroke, ICP rose gradually over time and by 5 days was significantly (p < 0.0001) elevated above sham levels. Profound cerebral edema was observed as early as 2 days post-stroke and continued to evolve out to 6 days, resulting in significant midline shift which was most prominent at 5 days post-stroke (p < 0.01), in keeping with increasing ICP. Serum SP levels were significantly elevated (p < 0.01) by 7 days post-tMCAO. CONCLUSION: We have successfully developed a survival model of ovine tMCAO and characterized the temporal profile of ICP. Peak ICP elevation, cerebral edema and midline shift occurred at days 5-6 following stroke, accompanied by an elevation in serum SP. Our findings suggest that novel therapeutic agents screened in this model targeting cerebral edema and elevated ICP would most likely be effective when administered prior to 5 days, or as early as possible following stroke onset.

A terahertz-driven non-equilibrium phase transition in a room temperature atomic vapour.

There are few demonstrated examples of phase transitions that may be driven directly by terahertz frequency electric fields, and those that are known require field strengths exceeding 1 MV cm-1. Here we report a non-equilibrium phase transition driven by a weak (≪1 V cm-1), continuous-wave terahertz electric field. The system consists of room temperature caesium vapour under continuous optical excitation to a high-lying Rydberg state, which is resonantly coupled to a nearby level by the terahertz electric field. We use a simple model to understand the underlying physical behaviour, and we demonstrate two protocols to exploit the phase transition as a narrowband terahertz detector: the first with a fast (20 µs) non-linear response to nano-Watts of incident radiation, and the second with a linearised response and effective noise equivalent power ≤1 pW Hz-1/2. The work opens the door to a class of terahertz devices controlled with low-field intensities and operating in a room temperature environment.

Peptide Vaccines for Leishmaniasis.

Due to an increase in the incidence of leishmaniases worldwide, the development of new strategies such as prophylactic vaccines to prevent infection and decrease the disease have become a high priority. Classic vaccines against leishmaniases were based on live or attenuated parasites or their subunits. Nevertheless, the use of whole parasite or their subunits for vaccine production has numerous disadvantages. Therefore, the use of Leishmania peptides to design more specific vaccines against leishmaniases seems promising. Moreover, peptides have several benefits in comparison with other kinds of antigens, for instance, good stability, absence of potentially damaging materials, antigen low complexity, and low-cost to scale up. By contrast, peptides are poor immunogenic alone, and they need to be delivered correctly. In this context, several approaches described in this review are useful to solve these drawbacks. Approaches, such as, peptides in combination with potent adjuvants, cellular vaccinations, adenovirus, polyepitopes, or DNA vaccines have been used to develop peptide-based vaccines. Recent advancements in peptide vaccine design, chimeric, or polypeptide vaccines and nanovaccines based on particles attached or formulated with antigenic components or peptides have been increasingly employed to drive a specific immune response. In this review, we briefly summarize the old, current, and future stands on peptide-based vaccines, describing the disadvantages and benefits associated with them. We also propose possible approaches to overcome the related weaknesses of synthetic vaccines and suggest future guidelines for their development.

New cathode materials for rechargeable Mg batteries: fast Mg ion transport and reversible copper extrusion in CuyMo6S8 compounds.

We report on a discovery of fast cathode materials, ternary Chevrel phases (CPs), CuyMo6S8, for rechargeable magnesium batteries; the related electrochemical process displays a unique coupling between reversible Mg insertion, and Cu extrusion/ reinsertion; this coupling results in an entirely new intercalation mechanism which combines the total chemical reversibility of the electrochemical reaction of MgxCuyMo6S8 with irreversibility of its separate stages once Cu extrusion stage is reached (in MgxCuyMo6S8: 0.5x + y > 4).

Heparin is required for cell-free binding of basic fibroblast growth factor to a soluble receptor and for mitogenesis in whole cells.

Heparin is required for the binding of basic fibroblast growth factor (bFGF) to high-affinity receptors on cells deficient in cell surface heparan sulfate proteoglycan. So that this heparin requirement could be evaluated in the absence of other cell surface molecules, we designed a simple assay based on a genetically engineered soluble form of murine FGF receptor 1 (mFR1) tagged with placental alkaline phosphatase. Using this assay, we showed that FGF-receptor binding has an absolute requirement for heparin. By using a cytokine-dependent lymphoid cell line engineered to express mFR1, we also showed that FGF-induced mitogenic activity is heparin dependent. Furthermore, we tested a series of small heparin oligosaccharides of defined lengths for their abilities to support bFGF-receptor binding and biologic activity. We found that a heparin oligosaccharide with as few as eight sugar residues is sufficient to support these activities. We also demonstrated that heparin facilitates FGF dimerization, a property that may be important for receptor activation.