bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of choriodecidual cytokine production and inflammatory gene expression by selective I‐κB kinase (IKK) inhibitors
Authors: De Silva D , Mitchell MD , Keelan JA
Published: May 2010

BACKGROUND AND PURPOSE

Inflammation of the extraplacental membranes plays a key role in the pathogenesis of preterm labour. The aim of this study was to screen a number of commercially available small molecule nuclear factor‐kappa B inhibitors to identify candidates suitable for clinical evaluation as anti‐inflammatory agents for the prevention of preterm birth.

EXPERIMENTAL APPROACH

Nine inhibitors were evaluated across a range of concentrations for their ability to inhibit lipopolysaccharide (LPS)‐stimulated cytokine production in primary term choriodecidual cells in culture without affecting cell viability. Expression of 112 inflammation‐ and apoptosis‐related genes was evaluated using boutique oligonucleotide arrays.

KEY RESULTS

Two IKKβ inhibitors were found to be highly effective and non‐toxic inhibitors of choriodecidual cytokine production: parthenolide and [5‐(p‐fluorophenyl)‐2‐ureido] thiophene‐3‐carboxamide (TPCA‐1). Both compounds also inhibited LPS‐stimulated nuclear translocation of p65/RelA. Expression of 38 genes on the arrays (34%) was significantly (P < 0.05) inhibited by TPCA‐1 or parthenolide. Of the 14 genes significantly stimulated by LPS, all were inhibited by TPCA‐1 and 12 were inhibited by parthenolide. Overall, gene expression was more robustly inhibited by TPCA‐1 than parthenolide; however, expression of two genes was only inhibited by parthenolide. Neither compound significantly altered the expression profile of anti‐apoptosis genes on the arrays.

CONCLUSIONS AND IMPLICATIONS

These studies provide evidence that pharmacological inhibition of IKKβ activity holds promise as a potential strategy for the prevention and/or treatment of inflammation‐driven preterm birth. TPCA‐1 appeared the most promising compound among those tested in this study. Different inhibitors may have subtly different effect profiles despite having similar modes of action.
Investigation of the distribution and function of α‐adrenoceptors in the sheep isolated internal anal sphincter
Authors: Rayment SJ , Eames T , Simpson JAD , Dashwood MR , Henry Y , Gruss H , Acheson AG , Scholefield JH , Wilson VG
Published: May 2010

BACKGROUND AND PURPOSE

We have investigated the distribution of α‐adrenoceptors in sheep internal anal sphincter (IAS), as a model for the human tissue, and evaluated various imidazoline derivatives for potential treatment of faecal incontinence.

EXPERIMENTAL APPROACH

Saturation and competition binding with3H‐prazosin and3H‐RX821002 were used to confirm the presence and density of α‐adrenoceptors in sheep IAS, and the affinity of imidazoline compounds at these receptors. A combination ofin vitroreceptor autoradiography and immunohistochemistry was used to investigate the regional distribution of binding sites. Contractile activity of imidazoline‐based compounds on sheep IAS was assessed by isometric tension recording.

KEY RESULTS

Saturation binding confirmed the presence of both α1‐ and α2‐adrenoceptors, and subsequent characterization with sub‐type‐selective agents, identified them as α1A‐ and α2D‐adrenoceptor sub‐types. Autoradiographic studies with3H‐prazosin showed a positive association of α1‐adrenoceptors with immunohistochemically identified smooth muscle fibres. Anti‐α1‐adrenoceptor immunohistochemistry revealed similar distributions of the receptor in sheep and human IAS. The imidazoline compounds caused concentration‐dependent contractions of the anal sphincter, but the maximum responses were less than those elicited byl‐erythro‐methoxamine, a standard non‐imidazoline α1‐adrenoceptor agonist. Prazosin (selective α1‐adrenoceptor antagonist) significantly reduced the magnitude of contraction tol‐erythro‐methoxamine at the highest concentration used. Both prazosin and RX811059 (a selective α2‐adrenoceptor antagonist) reduced the potency (pEC50) of clonidine.

CONCLUSIONS AND IMPLICATIONS

This study shows that both α1‐ and α2‐adrenoceptors are expressed in the sheep IAS, and contribute (perhaps synergistically) to contractions elicited by various imidazoline derivatives. These agents may prove useful in the treatment of faecal incontinence.
Impacts of Marine Protected Areas on Fishing Communities
Authors: MASCIA MICHAEL B. , CLAUS C. ANNE , NAIDOO ROBIN
Published: May 2010

Abstract:  Marine protected areas (MPAs) are a popular conservation strategy, but their impacts on human welfare are poorly understood. To inform future research and policy decisions, we reviewed the scientific literature to assess MPA impacts on five indicators of human welfare: food security, resource rights, employment, community organization, and income. Following MPA establishment, food security generally remained stable or increased in older and smaller MPAs. The ability of most fishing groups to govern MPA resources changed. Increased resource rights were positively correlated with MPA zoning and compliance with MPA regulations. Small sample sizes precluded statistical tests of the impacts of MPAs on employment, community organization, and income. Our results demonstrate that MPAs shape the social well‐being and political power of fishing communities; impacts (positive and negative) vary within and among social groups; and social impacts are correlated with some—but not all—commonly hypothesized explanatory factors. Accordingly, MPAs may represent a viable strategy for enhancing food security and empowering local communities, but current practices negatively affect at least a minority of fishers. To inform policy making, further research must better document and explain variation in the positive and negative social impacts of MPAs.
Anti‐glycophorin C induces mitochondrial membrane depolarization and a loss of extracellular regulated kinase 1/2 protein kinase activity that is prevented by pretreatment with cytochalasin D: implications for hemolytic disease of the fetus and newborn caused by anti‐Ge3
Authors: Micieli Jonathan A. , Wang Duncheng , Denomme Gregory A.
Published: May 2010

BACKGROUND: Anti‐glycophorin C (GPC), blood group antibodies of which cause hemolytic disease of the fetus and newborn (HDFN), is a potent inhibitor of erythroid progenitor cell growth. The cellular mechanism for growth inhibition has not been characterized.

STUDY DESIGN AND METHODS: K562 cells were incubated in the presence of either anti‐GPC, an immunoglobulin G isotype control, an inhibitor of actin polymerization called cytochalasin D with anti‐GPC, or cytochalasin D alone. The JC‐1 cationic dye was used to detect mitochondrial depolarization and the activity of the mitogen‐activated protein kinases was assessed by Western blotting.

RESULTS: Anti‐GPC inhibits the activity of extracellular regulated kinase (ERK)1/2 within 10 minutes but does not alter the activity of p38 or c‐Jun N‐terminal kinase. After 24 hours there was a significant loss of mitochondrial membrane potential compared to isotype control–treated cells. Both the ERK1/2 inhibition and the loss of mitochondrial potential were prevented by pretreatment with cytochalasin D.

CONCLUSION: A cell surface antibody can cause anemia by altering the signaling pathways in erythroid cells by promoting depolarization of mitochondria via cytoskeletal rearrangement. The observation that neonates with anti‐GPC HDFN are unresponsive to erythropoietin can be explained by the antibody inhibiting a protein kinase through which this hematopoietic growth factor achieves its effects.
Physiological trade‐offs between flight muscle and reproductive development in the wing‐dimorphic cricket Velarifictorus ornatus
Authors: Zhao Lv‐Quan , Zhu Dao‐Hong , Zeng Yang
Published: May 2010

Morphology, flight muscles, and reproductive development were compared between long‐winged (LW) and short‐winged (SW) morphs of the cricket Velarifictorus ornatus (Shiraki) (Orthoptera: Gryllidae). There was no difference in body weight and pre‐oviposition between the two morphs, but LW individuals had better‐developed flight muscles than SW individuals during and after emergence of the adult. The flight muscles at adult emergence represented 11.9% of the total body weight in the LW female and 4.9% in the SW female. In addition, the weight of the flight muscle of LW females increased by 50% during the first 5 days, whereas the flight muscle of the SW variant increased only slightly after adult emergence. The process of oviposition in LW, SW, and de‐alated females varied: SW females produced more eggs at the early stage than LW females, but de‐alation could shorten the time until the peak of egg laying and caused histolysis of flight muscles of LW females. There was no significant difference in total egg production between the above three groups. In the male, unlike the female, the accessory glands of the two wing morphs enlarged continuously at the same rate. There was no difference between the two wing morphs in the mass of the testes during the first 7 days after adult emergence.
Stimuli associated with viburnum leaf beetle (Pyrrhalta viburni) aggregative oviposition behavior
Authors: Desurmont Gaylord A. , Weston Paul A.
Published: May 2010

Viburnum leaf beetle, Pyrrhalta viburni (Paykull) (Coleoptera: Chrysomelidae), oviposits in terminal twigs of Viburnum spp. shrubs (Caprifoliaceae). Twigs react to oviposition by producing neoplasm that overgrows the egg mass. Pyrrhalta viburni oviposition behavior is aggregative: females prefer to lay egg masses on twigs previously infested by other females and to position their egg masses adjacent to existing ones. Female oviposition preferences were studied in a series of choice tests under laboratory conditions. The three components of the egg mass (cavity, eggs, and egg cap) were not sufficient to elicit complete aggregation oviposition response when presented separately. Cavity and egg cap elicited positional preference, but not the artificial cavity, artificial egg cap, or frass, suggesting that stimulatory cues might be associated with insect saliva and egg cap secretion. Females preferred to lay eggs on twigs that had produced wound tissue in response to previous oviposition. We conclude that twig choice and positional preference for oviposition are likely to be dissociated, and that twig wound response might be used by P. viburni females to locate twigs already infested and possibly less defended against subsequent oviposition. Pyrrhalta viburni females preferred to lay egg masses on heavily infested twigs rather than on lightly infested twigs. Females did not show preference for twigs infested with their own egg masses, but laid more egg masses on twigs infested by multiple females than on twigs infested by single females. We conclude that both egg mass and conspecific density affect oviposition preferences of P. viburni and discuss the possible ecological implications of this behavior.
Larval crowding effects on the mosquito Culex quinquefasciatus: physical or chemical?
Authors: Roberts Derek , Kokkinn Michael
Published: May 2010

Culex quinquefasciatus Say (Diptera: Culicidae) is an abundant urban mosquito that is the vector of filariasis. Breeding in septic tanks, where there are very high levels of bacterial food, it is likely to have a different reaction to crowding compared with other mosquitoes. To test for the presence and type of crowding effects, four larval densities of C. quinquefasciatus varying from 0.4 to 3.2 larvae ml−1 of water were reared in tubes. Mortality was found to greatly increase at densities above 0.8 larvae, whereas larval duration increased even above 0.4 larvae ml−1. Changing the water in the tubes daily gave a small (but significant) response in reducing mortality and larval duration. However, when larvae kept at a low density shared the same water with larvae at high density, there was no chemical influence on their growth rate and mortality. The effect of crowding was primarily due to physical disturbances between larvae. When larvae were kept at a high density in the same volume of water, but in shallow trays with a large surface area and therefore much less contact between them, mortality was the same as for the lowest density. There was still, however, a significant increase in larval duration from 8.6 days at 0.4 larvae ml−1 to 12.1 days at 3.2 larvae ml−1. It is therefore concluded that the larvae respond to physical rather than chemical factors by prolonging larval development and having some increase in mortality.
Mi‐mediated aphid resistance in tomato: tissue localization and impact on the feeding behavior of two potato aphid clones with differing levels of virulence
Authors: Pallipparambil Godshen R. , Reese John C. , Avila Carlos A. , Louis Joe M. , Goggin Fiona L.
Published: May 2010

The Mi‐1.2 gene in tomato, Solanum lycopersicum L. (Solanaceae), confers resistance against several herbivores, including the potato aphid, Macrosiphum euphorbiae (Thomas) (Hemiptera: Sternorrhyncha: Aphididae) and the sweetpotato whitefly, Bemisia tabaci (Gennadius) (Hemiptera: Sternorrhyncha: Aleyrodidae). Previous studies on the tissue localization of resistance have given varying results; whitefly resistance was attributed to factors localized in the mesophyll or epidermis, whereas aphid resistance was attributed to factors localized in the phloem. Our study utilizes the direct current electrical penetration graph (DC‐EPG) technique to compare aphid feeding behavior on resistant (Mi‐1.2+) and susceptible (Mi‐1.2−) tomato plants. This study also compares the impact of resistance on the feeding behavior of two aphid clones that vary in their virulence, or their ability to survive and reproduce on resistant plants. Previous work had shown that the avirulent WU11 clone is almost completely inhibited by resistance, whereas the semi‐virulent WU12 clone can colonize resistant hosts. Here, DC‐EPG analysis shows that both aphid clones take longer to initiate cell sampling and to establish a confirmed sieve element phase on resistant plants than on susceptible hosts, and have shorter ingestion periods on resistant plants. However, the magnitude of these deterrent effects is far less for the semi‐virulent clone than for the avirulent aphids. In particular, the WU12 clone is less sensitive to factors that limit sieve element ingestion, showing shorter non‐probe duration and rapidly establishing sustained phloem ingestion on resistant plants when compared to the WU11 clone. We conclude that, in addition to previously described factors in the phloem that inhibit ingestion, Mi‐mediated aphid resistance also involves factors (possibly in the mesophyll and/or epidermis) that delay initiation of phloem salivation, and that act in the intercellular spaces to deter the first cell sampling. Furthermore, the relative effectiveness of these components of resistance differs among insect populations.
Mechanism of resistance to the spotted stalk borer, Chilo sacchariphagus, in the sugarcane cultivar R570
Authors: Nibouche S. , Tibère R.
Published: May 2010

Resistance in sugarcane [Saccharum spec. (Poaceae)] to the spotted stalk borer, Chilo sacchariphagus (Bojer) (Lepidoptera: Pyralidae), was studied by comparing feeding behaviour on resistant cv. R570 and susceptible cv. R579. In a field survey, the feeding behaviour of C. sacchariphagus larvae was described to identify their feeding sites on the plant. In a greenhouse artificial infestation study, we compared the establishment of larvae on potted plants. In laboratory choice and no‐choice experiments, we studied the establishment of larvae on plant organs (stalk, sheath, leaf spindle). Study of the feeding behaviour showed that: (1) first to fourth instars are able to feed on stalk, sheath, and leaf spindle, (2) boring into the stalk occurs mostly in the four uppermost internodes, and (3) most young larvae bore through the abaxial surface of leaf sheaths to reach the stalk. In greenhouse experiments, we observed an early two‐fold reduction of the number of larvae on R570 plants within the first 48 h after infestation. In laboratory experiments, larval antixenosis was demonstrated at the abaxial surface of R570 leaf sheath, but was observed neither in the leaf spindle nor in the stalk. First, second, and third instars were susceptible to this antixenosis. We hypothesize that the main resistance mechanism in R570 is an early reduction of larval establishment on plants, due to antixenosis located at the abaxial surface of leaf sheaths.
Immediate provisional restoration of screw‐type implants in the posterior mandible: results after 5 years of clinical function
Authors: Payer Michael , Heschl Alexander , Wimmer Gernot , Wegscheider Walther , Kirmeier Robert , Lorenzoni Martin
Published: May 2010

Objective: The aim of this prospective study was to evaluate the outcome of immediately provisionally restored implants in the posterior mandible after a minimum of 60 months in function.

Material and methods: Twenty‐four patients were treated with 40 screw‐type implants replacing mandibular molars and premolars. Implants were provisionalized immediately after placement. Radiographic coronal bone levels, implant survival and success were evaluated 12, 24, 36, 48 and 60 months after the final restoration.

Results: Measurements of the mean marginal bone levels around immediately loaded implants after 12 months showed a significant bone loss (P<0.001) within the first year after the final restoration. Measurements of coronal bone levels after 24, 36, 48 and 60 months, respectively, showed no further significant increase of bone resorption. Two implants were lost within the first year after the final restoration, resulting in an overall survival rate of 95%; a total of three implants were recorded as failures (two implant losses and one excessive bone resorption above 50%), resulting in an overall success rate of 92.5 after an implant observation period of up to 8 years.

Conclusion: The present data revealed results comparable to conventionally loaded implants. Careful patient selection in combination with high primary stability seem to be key factors for immediately loaded implants. Larger long‐term randomized clinical trials are needed to confirm the final evidence of this protocol as the standard treatment concept for the partially edentulous mandible.

To cite this article:
 Payer M, Heschl A, Wimmer G, Wegscheider W, Kirmeier R, Lorenzoni M. Immediate provisional restoration of screw‐type implants in the posterior mandible: results after 5 years of clinical function. Clin. Oral Impl. Res. 21, 2010; 815–821. doi: 10.1111/j.1600‐0501.2010.01919.x
Early bone apposition and 1‐year performance of the electrodeposited calcium phosphate coatings: an experimental study in rabbit femora
Authors: Wang Jiawei , Sun Chen , Wang Yuchen , Wang Yining
Published: May 2010

Objectives: The aim of this study was to investigate the early bone apposition and 1‐year performance of the electrodeposited calcium phosphate coatings with or without chitosan.

Material and methods: Seventy‐two cylindrical implants with a length of 8 mm and a diameter of 3.3 mm were divided into three groups: electrodeposited calcium phosphate coated without chitosan, with chitosan, and an uncoated control. The implants adopted the special gap design and were inserted into the rabbit femora. After 2, 4, 26, and 52 weeks, the implants were retrieved and analyzed for bone formation, bone‐to‐implant contact, and coating degradation.

Results: It was found that the coatings without chitosan had the highest bone contact at early time (P<0.05). The coatings with chitosan had the least bone formation within gaps after 2, 4, and 26 weeks of implantation (P<0.05). However, no difference was found among the three groups after 52 weeks. Both coatings showed degradation as early as 2 weeks post‐implantation. And after 52 weeks, most of the coatings had been degraded. There were no inflammatory reactions and hardly any osteoclasts around the implants and the coatings. The confocal laser scanning microscopy observation further demonstrated the different bone deposition characteristics. With scanning electron microscopy, no coatings could be found on both the implant surface and the bone interface.

Conclusions: Bone apposition to both electrodeposited calcium phosphate coatings was different at early time but almost the same after 52 weeks. And both coatings showed early as well as a continued degradation in the rabbit femora.

To cite this article:
 Wang J, Sun C, Wang Y, Wang Y. Early bone apposition and 1‐year performance of the electrodeposited calcium phosphate coatings: an experimental study in rabbit femora. Clin. Oral Impl. Res. 21, 2010; 951–960. doi: 10.1111/j.1600‐0501.2010.01935.x
Serotonin transporter gene, childhood emotional abuse and cognitive vulnerability to depression
Authors: Antypa N. , Van der Does A. J. W.
Published: May 2010

Meta‐analyses evaluating the association between the serotonin transporter polymorphism (5‐HTTLPR) with neuroticism and depression diagnosis as phenotypes have been inconclusive. We examined a gene–environment interaction on a cognitive vulnerability marker of depression, cognitive reactivity (CR) to sad mood. A total of 250 university students of European ancestry were genotyped for the 5‐HTTLPR, including SNP rs25531, a polymorphism of the long allele. Association analysis was performed for neuroticism, CR and depression diagnosis (using a self‐report measure). As an environmental pathogen, self‐reported history of childhood emotional abuse was measured because of its strong relationship with depression. Participants with the homozygous low expressing genotype had high CR if they had experienced childhood emotional maltreatment but low CR if they did not have such experience. This interaction was strongest on the Rumination subscale of the CR measure. The interaction was not significant with neuroticism or depression diagnosis as outcome measures. Our results show that 5‐HTTLPR is related to cognitive vulnerability to depression. Our findings provide evidence for a differential susceptibility genotype rather than a vulnerability genotype, possibly because of the relatively low levels of abuse in our sample. The selection of phenotype and environmental contributor is pivotal in investigating gene–environment interactions in psychiatric disorders.
Neuroblastoma: What the nurse practitioner should know
Authors: Mazur Kate A.
Published: May 2010

Purpose: To provide a comprehensive review of the background, diagnosis, and primary care management of neuroblastoma (NBL) and to describe the pathophysiology, signs and symptoms, and diagnostic tests for the patient with NBL.

Data sources: Extensive review of the worldwide scientific literature on the condition, including primary care articles and studies performed.

Conclusions: NBL is one of the most common tumors of childhood and clinical presentation depends on the site of the primary tumor as well as the presence and location of any metastasis. Treatment includes a combination of surgery, chemotherapy, and radiation, as well as the newer immunotherapy.

Implications for practice: NBL is often identified in the primary care setting, and it is important to be able to recognize the presentation and correctly manage the disease. The clinical presentation of NBL, the vital facts needed to ensure that this diagnosis will not be overlooked, and follow‐up in a primary care setting will be reviewed.
The Genetic Information Nondiscrimination Act 2008: What clinicians should understand
Authors: Clifton Jennifer M. , VanBeuge Susan S. , Mladenka Christine , Wosnik Kelly K.
Published: May 2010

Purpose: To explain the Genetic Information Nondiscrimination Act (GINA), what it covers, and what it does not cover to aid primary care practitioners in advising their patients.

Data sources: Governmental agencies, congressional records, and various nongovernmental agencies, press releases, and journal articles.

Conclusions: The GINA will protect patients from employment and insurance information in multiple ways. However, loopholes exist which will need to be addressed at the next review of the Act in 6 years.

Implications for practice: In order to provide accurate information regarding genetic testing, clinicians need to be familiar with key factors about GINA regarding law, practice, impact on patients and their rights in terms of genetic testing.
Evaluating the sleep/wake cycle in persons with asthma: Three case scenarios
Authors: Babcock Jenna , Krouse Helene J.
Published: May 2010

Purpose: To evaluate if wrist actigraphy, a measurement of movement, is an effective tool for assessing sleep/wake patterns and use in clinical practice in persons with asthma.

Data sources: Data from three individuals with asthma were utilized to develop three case scenarios. The case scenarios illustrated the use of actigraphy as the measurement tool for sleep patterns as they relate to individuals with varying degrees of asthma control.

Conclusions: The person with poorly controlled asthma had less total sleep time and lower sleep efficiency than the person with well‐controlled asthma. The actigraph provided useful information on sleep patterns such as daytime napping, nighttime sleep, and sleep efficiency in persons with varying degrees of asthma control.

Implications for practice: Nighttime asthma symptoms are often hard for the nurse practitioner (NP) to assess as they are often subjectively reported by patients. The use of actigraph in the clinical setting can provide useful, objective information on the sleep/wake cycles of persons with asthma to aid the NP in providing optimal management of the disease.
Preliminary Remarks on the Envisaged World Health Organization Pandemic Influenza Preparedness Framework for the Sharing of Viruses and Access to Vaccines and Other Benefits
Authors: Vezzani Simone
Published: May 2010

Over the last few decades, the World Health Organization (WHO) has played a significant role in the prevention and control of new strains of influenza virus in the human population. Beginning in the 1950s, it has coordinated a network of WHO‐linked laboratories, charged with monitoring the changes in influenza viruses and favouring the timely sharing of virus samples, which is necessary for the development and production of vaccines. In December 2006, the said system was brought into question by Indonesia, according to which it was unfair and in conflict with the principle of state sovereignty over biological and genetic resources. Although very controversial, the Indonesian decision to interrupt the supply of candidate influenza vaccine strains boosted intergovernmental negotiation, until then not achieved, aimed at establishing a new WHO framework. This article examines the outcome of such a negotiation, as well as the aspects of the framework still under discussion. It emphasizes the innovative nature of the proposed benefit‐sharing mechanism, which would promote access to vaccines mainly through the multilateralization of intellectual property rights governance. Similarities and differences between the envisaged framework and the benefit‐sharing mechanism established by the Food and Agricultural Organization International Treaty on Plant Genetic Resources for Food and Agriculture in the field of access to plant genetic resources are analysed.
Thymosin α 1 for treatment of hepatitis C virus: promise and proof
Authors: Sherman Kenneth E.
Published: May 2010

The hepatitis C virus (HCV) is a global public health problem, with chronic infection leading to development of cirrhosis, end‐stage liver disease and hepatocellular carcinoma (HCC). Treatment of HCV is suboptimal with overall response rates of slightly greater than 50% when patients are treated with pegylated interferon alfa and ribavirin. Thymosin alpha 1 (Tα1; TA‐1) is an immunomodulatory peptide with intrinsic activities that might improve treatment outcomes for HCV by incorporation of this agent in current treatment paradigms. An extensive body of literature supports a possible role for this agent in difficult to treat populations. However, clinical trials to date have failed to conclusively support the role of TA‐1 in combination interferon‐based therapies. Therefore, the promise of TA‐1 adjunctive therapy for HCV remains, but the proof will require investment in large randomized clinical trials of appropriate patient populations.
Prothymosin α as robustness molecule against ischemic stress to brain and retina
Authors: Ueda Hiroshi , Matsunaga Hayato , Uchida Hitoshi , Ueda Mutsumi
Published: May 2010

Following stroke or traumatic damage, neuronal death via both necrosis and apoptosis causes loss of functions, including memory, sensory perception, and motor skills. As necrosis has the nature to expand, while apoptosis stops the cell death cascade in the brain, necrosis is considered to be a promising target for rapid treatment for stroke. We identified the nuclear protein, prothymosin alpha (ProTα) from the conditioned medium of serum‐free culture of cortical neurons as a key protein‐inhibiting necrosis. In the culture of cortical neurons in the serum‐free condition without any supplements, ProTα inhibited the necrosis, but caused apoptosis. In the ischemic brain or retina, ProTα showed a potent inhibition of both necrosis and apoptosis. By use of anti‐brain‐derived neurotrophic factor or anti‐erythropoietin IgG, we found that ProTα inhibits necrosis, but causes apoptosis, which is in turn inhibited by ProTα‐induced neurotrophins under the condition of ischemia. From the experiment using anti‐ProTα IgG or antisense oligonucleotide for ProTα, it was revealed that ProTα has a pathophysiological role in protecting neurons in stroke.
Repolymerization of actin from actin:thymosin β4 complex induced by diaphanous related formins and gelsolin
Authors: Mannherz Hans Georg , Mazur Antonina Joanna , Jockusch Brigitte
Published: May 2010

The β‐thymosins are peptides of about 5 kDa molecular mass. Thymosin β4 (Tβ4) is the most ubiquitous member of this family and composed of 43 residues. Initially the β‐thymosins were supposed to be specifically produced and released by the thymic gland and to possess hormonal activities modulating the immune response. However, it was later noticed that β‐thymosins are present in the cytoplasm of almost all eukaryotic cells. Especially high concentrations of Tβ4 were detected in hematopoetic cells, like polymorpho‐nuclear leucocytes and in platelets. In these cells the main intracellular function of the β‐thymosins is to bind to monomeric actin and to inhibit its polymerization to filamentous actin. Thus Tβ4 allows resting eukaryotic cells to maintain a high concentration of monomeric actin, although the intracellular ionic conditions would favor its almost complete polymerization to F‐actin. Thereby monomeric actin is sequestered from the dynamic assembly and disassembly processes of the actin cytoskeleton that constantly occur intracellularly.
Thymosin β4 and cardiac repair
Authors: Shrivastava Santwana , Srivastava Deepak , Olson Eric N. , DiMaio J. Michael , Bock‐Marquette Ildiko
Published: May 2010

Hypoxic heart disease is a predominant cause of disability and death worldwide. As adult mammals are incapable of cardiac repair after infarction, the discovery of effective methods to achieve myocardial and vascular regeneration is crucial. Efforts to use stem cells to repopulate damaged tissue are currently limited by technical considerations and restricted cell potential. We discovered that the small, secreted peptide thymosin β4 (Tβ4) could be sufficiently used to inhibit myocardial cell death, stimulate vessel growth, and activate endogenous cardiac progenitors by reminding the adult heart on its embryonic program in vivo. The initiation of epicardial thickening accompanied by increase of myocardial and epicardial progenitors with or without infarction indicate that the reactivation process is independent of injury. Our results demonstrate Tβ4 to be the first known molecule able to initiate simultaneous myocardial and vascular regeneration after systemic administration in vivo. Given our findings, the utility of Tβ4 to heal cardiac injury may hold promise and warrant further investigation.
A randomized, placebo‐controlled, single and multiple dose study of intravenous thymosin β4 in healthy volunteers
Authors: Ruff Dennis , Crockford David , Girardi Gino , Zhang Yuxin
Published: May 2010

Synthetic thymosin beta 4 (Tβ4) may have a potential use in promoting myocardial cell survival during acute myocardial infarction. Four cohorts, with 10 healthy subjects each, were given a single intravenous dose of placebo or synthetic Tβ4. Cohorts received ascending doses of either 42, 140, 420, or 1260 mg. Following safety review, subjects were given the same dose regimen daily for 14 days. Safety evaluations, incidence of Treatment‐Emergent Adverse Events, and pharmacokinetic parameters were evaluated. Adverse events were infrequent, and mild or moderate in intensity. There were no dose limiting toxicities or serious adverse events. Pharmacokinetic profile for single dose showed a dose proportional response, and an increasing half‐life with increasing dose. Synthetic Tβ4 given intravenously as a single dose or in multiple daily doses for 14 days over a dose range of 42–1260 mg was well tolerated with no evidence of dose limiting toxicity. Further development for use in cardiac ischemia should be considered.
Transcription profile of human lymphocytes following in vitro treatment with thymosin alpha‐1
Authors: Matteucci Claudia , Minutolo Antonella , Sinibaldi‐Vallebona Paola , Palamara Anna Teresa , Rasi Guido , Mastino Antonio , Garaci Enrico
Published: May 2010

Thymosin alpha‐1 (Tα1) is a molecule retaining pleiotropic effects toward several pathological conditions, especially acting as a modulator of immune response and inflammation. However, molecular mechanisms underlying the peculiar, wide‐range activity of Tα1 have not been completely elucidated. To get information on the mechanism of action of Tα1 and to find new potential applications, we performed the analysis of the transcription profile of 8300 genes in human peripheral blood mononuclear cells in vitro treated with Tα1. Together with a variety of genes already known to be modulated by Tα1, our analysis revealed a remarkable number of genes not yet described before to be modulated by this thymic peptide, revealing a complex scenario that underlines the role of this peptide as a regulator of lymphocyte functions. Here, we report the list of the more representative modulated genes and discuss their implications on the modulation of the innate and adaptive responses. Our results open new perspectives on the use of Tα1 for the treatment of diseases associated with immune‐disregulation.
Thymosin β4and its posttranslational modifications
Authors: Hannappel E.
Published: May 2010

Thymosin β4as well as the other members of the β‐thymosin family are important G‐actin sequestering peptides. The chemical properties, the biosynthesis, and posttranslational modifications (PTMs) of these peptides are discussed. During biosynthesis of thymosin β4the initiator methionine is removed and the N‐terminus is acetylated. Research on proteomics revealed several acetylated lysine residues and two phosphorylated threonine residues. The enormous number of phosphorylable and acetylable sites in the human proteome raises the question about the biological significance of these PTMs in the context of β‐thymosins. Presently, this question cannot be answered because neither the concentration of these modified β‐thymosins in cells is known nor the consequences of the modifications on the biological function(s) of β‐thymosins have been studied yet. Thymosin β4is also posttranslationally modified by transglutaminase forming covalent bonds with other molecules. Prolyl oligopeptidase generates ac‐SDKP from thymosin β4. The concentration of C‐terminal peptide fragments of thymosin β4is elevated in the blood of patients with rheumatoid arthritis.
Preservation of Acidified Cucumbers with a Natural Preservative Combination of Fumaric Acid and Allyl Isothiocyanate that Target Lactic Acid Bacteria and Yeasts
Authors: Pérez‐Díaz I.M. , McFeeters R.F.
Published: May 2010

ABSTRACT:  Without the addition of preservative compounds cucumbers acidified with 150 mM acetic acid with pH adjusted to 3.5 typically undergo fermentation by lactic acid bacteria. Fumaric acid (20 mM) inhibited growth of Lactobacillus plantarum and the lactic acid bacteria present on fresh cucumbers, but spoilage then occurred due to growth of fermentative yeasts, which produced ethanol in the cucumbers. Allyl isothiocyanate (2 mM) prevented growth of Zygosaccharomyces globiformis, which has been responsible for commercial pickle spoilage, as well as the yeasts that were present on fresh cucumbers. However, allyl isothiocyanate did not prevent growth of Lactobacillus plantarum. When these compounds were added in combination to acidified cucumbers, the cucumbers were successfully preserved as indicated by the fact that neither yeasts or lactic acid bacteria increased in numbers nor were lactic acid or ethanol produced by microorganisms when cucumbers were stored at 30 °C for at least 2 mo. This combination of 2 naturally occurring preservative compounds may serve as an alternative approach to the use of sodium benzoate or sodium metabisulfite for preservation of acidified vegetables without a thermal process.
Biodegradable Poly(butylene adipate‐co‐terephthalate) Films Incorporated with Nisin: Characterization and Effectiveness against Listeria innocua
Authors: Bastarrachea Luis , Dhawan Sumeet , Sablani Shyam S. , Mah Jae‐Hyung , Kang Dong‐Hyun , Zhang Jinwen , Tang Juming
Published: May 2010

ABSTRACT:  Biodegradable poly(butylene adipate‐co‐terephthalate) (PBAT) films incorporated with nisin were prepared with concentrations of 0, 1000, 3000, and 5000 international units per cm2 (IU/cm2). All the films with nisin inhibited Listeria innocua, and generated inhibition zones with diameters ranging from 14 to 17 mm. The water vapor permeability and oxygen permeability after the addition of nisin ranged from 3.05 to 3.61 × 1011 g m m−2 s−1 Pa−1 and from 4.80 × 107 to 11.26 × 107 mL·m·m−2·d−1·Pa−1, respectively. The elongation at break (ɛb) was not altered by the incorporation of nisin (P > 0.05). Significant effect was found for the elastic modulus (E) and the tensile strength (σs) (P < 0.05). The glass transition and melting temperatures with the presence of nisin ranged from −36.3 to −36.6 °C and from 122.5 to 124.2 °C, respectively. The thermal transition parameters such as the crystallization and melting enthalpies and crystallization temperature were influenced significantly (P < 0.05) by incorporation of nisin into films. The X‐ray diffraction patterns exhibited decreasing levels of intensity (counts) as the concentration of nisin increased in a range of 2θ from 8° to 35°. Formation of holes and pores was observed from the environmental scanning electron microscopy images in the films containing nisin, suggesting interaction between PBAT and nisin.
Evaluation of Brining Ingredients and Antimicrobials for Effects on Thermal Destruction of Escherichia coli O157:H7 in a Meat Model System
Authors: Byelashov Oleksandr A. , Adler Jeremy M. , Geornaras Ifigenia , Ko Kyung Yuk , Belk Keith E. , Smith Gary C. , Sofos John N.
Published: May 2010

ABSTRACT:  Escherichia coli O157:H7 may become internalized during brine injection of meat. This study evaluated the effect of brining ingredients on E. coli O157:H7 in a meat model system after simulated brining, storage, and cooking. Fresh knuckles (5.3 ± 2.4% fat) or beef shoulder (15.3 ± 2.2% fat) were ground individually, mixed with an 8‐strain composite of rifampicin‐resistant E. coli O157:H7 (7 log CFU/g) and brining solutions. Treatments included no brining, distilled water, sodium chloride (NaCl, 0.5%), sodium tripolyphosphate (STP, 0.25%), sodium pyrophosphate (SPP, 0.25%), NaCl + STP, NaCl + SPP, NaCl + STP + potassium lactate (PL, 2%), NaCl + STP + sodium diacetate (SD, 0.15%), NaCl + STP + PL + SD, NaCl + STP + lactic acid (0.3%), NaCl + STP + acetic acid (0.3%), NaCl + STP + citric acid (0.3%), NaCl + STP + EDTA (20 mM) + nisin (0.0015%) or pediocin (1000 AU/g), NaCl + STP + sodium metasilicate (0.2%), NaCl + STP + cetylpyridinium chloride (CPC; 0.5%), and NaCl + STP + hops beta acids (0.00055%). Samples (30 g) were analyzed for pH, and total microbial and rifampicin‐resistant E. coli O157:H7 (inoculum) populations immediately after mixing, storage (24 h at 4 °C), and cooking to 65 °C. Fat and moisture contents and water activity were measured after storage and cooking only; cooking losses also were determined. The effect of beef type on microbial counts, pH, and water activity was negligible. No reductions in microbial counts were obtained by the brining solutions immediately or after storage, except for samples treated with CPC, which reduced (P < 0.05) pathogen counts after storage by approximately 1 log cycle. Cooking reduced pathogen counts by 1.5 to 2.5 logs, while CPC‐treated samples had the lowest (P < 0.05) counts compared to any other treatment. These data may be useful in developing/improving brining recipes for control of E. coli O157:H7 in moisture‐enhanced beef products.
Microbial Growth in Dry Grain Food (Sunsik) Beverages Prepared with Water, Milk, Soymilk, or Honey‐Water
Authors: Jung Jin‐Ho , Lee Sun‐Young
Published: May 2010

ABSTRACT:  This study was conducted to investigate the growth of microorganisms, including pathogenic bacteria such as Cronobacter sakazakii and Bacillus cereus, in Sunsik beverages made of water, milk, soymilk, or honey‐water during storage at room temperature. Prepared Sunsik beverages were stored at room temperature and the growth of total aerobic counts, Escherichia coli/coliforms, and yeast and mold were measured. Also, samples inoculated with a cocktail of C. sakazakii or B. cereus spores were stored at room temperature and their growths were determined during storage. Populations of total aerobic counts and coliforms significantly increased with increasing storage time at room temperature, which resulted in higher than 8 log and 7 log after 24 h in all samples except for the honey‐water sample, respectively. Levels of total aerobic counts and coliforms were significantly lower in the honey‐water sample than in the other samples after 6 and 9 h of storage, respectively. Initial populations of C. sakazakii and B. cereus ranged from 0 to 1 log CFU/mL, respectively, and these populations significantly increased with increasing storage time at room temperature. Therefore, populations of C. sakazakii and B. cereus were approximately 7 to 8 log CFU/mL after 24 h of storage. However, after 12 and 9 h of storage, there were significant differences in levels of C. sakazakii and B. cereus between the honey‐water sample and the other samples, respectively. Based on these results, the addition of honey can inhibit microbial growth in Sunsik beverages; however, the best way to avoid pathogen infection would be to consume Sunsik beverages as soon as possible after preparation.
Shelf‐Life Extension of Fresh Tuber aestivum and Tuber melanosporum Truffles by Modified Atmosphere Packaging with Microperforated Films
Authors: Rivera Carmen Susana , Blanco Domingo , Salvador María Luisa , Venturini María Eugenia
Published: May 2010

ABSTRACT:  The aim of this study was to design a modified atmosphere packaging suitable for Tuber melanosporum and Tuber aestivum truffles that extend their shelf life and their availability as a fresh product. Their respiration rates were determined by O2 depletion and CO2 formation in closed systems performed at different temperatures: 4, 10, and 23 °C. The results were fitted by exponential equations and derivatives of these equations were used to obtain the experimental respiration rates. Our results revealed high respiration rates in both species of truffles and respiratory quotients (RQ) higher than 1 in all the cases studied. A linear dependence of respiration rate, both RO2 and RCO2, on O2 concentration was revealed. A mathematical model was used to predict the evolution of the gaseous composition at 4 °C in the interior of polypropylene trays (250 mL) heat sealed with 4 microperforated films of different transmission rates. A microperforated film with 2 holes (90 × 50 μm) was selected to produce an internal atmosphere of 15%CO2/7%O2 at 4 °C. The predicted atmosphere composition was confirmed by the experimental results. The quality and microbiological characteristics of fresh truffles, packaged in these conditions, revealed that the microbial counts of pseudomonads and Enterobacteriaceae were decreased, the weight loss was reduced, the typical hard texture was maintained, and the development of mycelium growth was delayed, enabling good scores for aroma and flavor, and therefore prolonging the shelf life of T. melanosporum and T. aestivum truffles to 28 and 21 d, respectively.

Practical Application: This study describes the benefits of using MAP with microperforated films in the postharvest storage of Tuber melanosporum and Tuber aestivum fresh truffles. The shelf life of T. aestivum is prolonged to 21 d and of T. melanosporum to beyond 28 d increasing the possibilities for a foreign market.
Polyphenolic Acids from Mint (the Aerial of Mentha haplocalyx Briq.) with DPPH Radical Scavenging Activity
Authors: She G.‐M. , Xu C. , Liu B. , Shi R.‐B.
Published: May 2010

ABSTRACT:  Vegetables of mint (the aerial part of Mentha haplocalyx) contain a significant amount of polyphenols with many health benefits. The crude aqueous acetone extract exhibited high antioxidant activity (IC50= 45.67 μg/mL) in 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH) radical scavenging assay. The activity‐guided separation of chlorophyll removal fraction on column chromatography afforded 8 polyphenolic acids, including a new compound, cis‐salvianolic acid J (1), and 7 known compounds, salvianolic acid J (2), lithospermic acid (3), rosmarinic acid (4), lithospermic acid B (5), magnesium lithospermate B (6), sodium lithospermate B (7), and danshensu (8), respectively. Their structural elucidations of all the compounds were based on extensive spectroscopic methods, including HRESIMS and 2D NMR experiments (HSQC, HMBC, and ROESY) and by comparison with reference values. Compounds 2, 3, and 5 to 8 were isolated from Mentha genus for the 1st time. The DPPH radical scavenging activities of all the isolated compounds were evaluated.
Extraction and Removal of Caffeine from Green Tea by Ultrasonic‐Enhanced Supercritical Fluid
Authors: Tang Wei‐Qiang , Li Di‐Cai , Lv Yang‐Xiao , Jiang Jian‐Guo
Published: May 2010

ABSTRACT:  Low‐caffeine or caffeine‐removed tea and its products are widely welcomed on market in recent years. In the present study, we adopt ultrasonic‐enhanced supercritical fluid extraction process to remove caffeine from green tea. An orthogonal experiment (L16 (45)) was applied to optimize the best removal conditions. Extraction pressure, extraction time, power of ultrasound, moisture content, and temperature were the main factors to influence the removal rate of caffeine from green tea. The 5 factors chosen for the present investigation were based on the results of a single‐factor test. The optimum removal conditions were determined as follows: extraction pressure of 30 MPa, temperature at 55 °C, time of 4 h, 30% moisture content, and ultrasound power of 100 W. Chromatogram and ultraviolet analysis of raw material and decaffeinates suggests that under optimized conditions, the caffeine of green tea was effectively removed and minished without damaging the structure of active ingredients in green tea.