Modulatory effects of estrous cycle on ingestive behaviors and energy balance in young adult C57BL/6J mice maintained on a phytoestrogen-free diet.

The estrous cycle is known to modify food, fluid, and electrolyte intake behaviors and energy homeostasis in various species, in part through fluctuations in estrogen levels. Simultaneously, commonly commercially available rodent dietary formulations greatly vary in soy protein content, and thereby the delivery of biologically active phytoestrogens. To explore the interactions among the estrous cycle, sodium, fluid, and caloric seeking behaviors, and energy homeostasis, young adult C57BL/6J female mice were maintained on a soy protein-free 2920x diet and provided water, or a choice between water and 0.15 mol/L NaCl drink solution. Comprehensive metabolic phenotyping was performed using a multiplexed Promethion (Sable Systems International) system, and estrous stages were determined via daily vaginal cytology. When provided food and water, estrous cycling had no major modulatory effects on intake behaviors or energy balance. When provided a saline solution drink choice, significant modulatory effects of the transition from diestrus to proestrus were observed upon fluid intake patterning, locomotion, and total energy expenditure. Access to saline increased total daily sodium consumption and aspects of energy expenditure, but these effects were not modified by the estrous stage. Collectively, these results indicate that when supplied a phytoestrogen-free diet, the estrous cycle has minor modulatory effects on ingestive behaviors and energy balance in C57BL/6J mice that are sensitive to sodium supply.NEW & NOTEWORTHY When provided a phytoestrogen-free diet, the estrous cycle had very little effect on food and water intake, physical activity, or energy expenditure in C57BL/6J mice. In contrast, when provided an NaCl drink in addition to food and water, the estrous cycle was associated with changes in intake behaviors and energy expenditure. These findings highlight the complex interactions among estrous cycling, dietary formulation, and nutrient presentation upon ingestive behaviors and energy homeostasis in mice.

Evaluation of the role of respiratory syncytial virus surface glycoproteins F and G on viral stability and replication: implications for future vaccine design.

Respiratory syncytial virus (RSV) remains a leading cause of infant mortality worldwide and exhaustive international efforts are underway to develop a vaccine. However, vaccine development has been hindered by a legacy of vaccine-enhanced disease, poor viral immunogenicity in infants, and genetic and physical instabilities. Natural infection with RSV does not prime for enhanced disease encouraging development of live-attenuated RSV vaccines for infants; however, physical instabilities of RSV may limit vaccine development. The role of RSV strain-specific differences on viral physical stability remains unclear. We have previously demonstrated that the RSV fusion (F) surface glycoprotein is responsible for mediating significant differences in thermostability between strains A2 and A2-line19F. In this study, we performed a more comprehensive analysis to characterize the replication and physical stability of recombinant RSV A and B strains that differed only in viral attachment (G) and/or F surface glycoprotein expression. We observed significant differences in thermal stability, syncytia size, pre-fusion F incorporation and viral growth kinetics in vitro, but limited variations to pH and freeze-thaw inactivation among several tested strains. Consistent with earlier studies, A2-line19F showed significantly enhanced thermal stability over A2, but also restricted growth kinetics in both HEp2 and Vero cells. As expected, no significant differences in susceptibility to UV inactivation were observed. These studies provide the first analysis of the physical stability of multiple strains of RSV, establish a key virus strain associated with enhanced thermal stability compared to conventional lab strain A2, and further support the pivotal role RSV F plays in virus stability.

The effect of chemotherapy on health-related quality of life in mesothelioma: results from the SWAMP trial.

BACKGROUND: The effect of chemotherapy on health-related quality of life (HRQoL) in malignant pleural mesothelioma (MPM) is poorly understood. Patient-individualised prognostication and prediction of treatment response from chemotherapy is useful but little evidence exists to guide practice. METHOD: Consecutive patients with MPM who were fit for first-line chemotherapy with pemetrexed and cisplatin\carboplatin were recruited and followed up for a minimum of 12 months. This study focussed on the HRQoL outcomes of these patients using the EQ-5D, EORTC QLQ-C30 and LC13. RESULTS: Seventy-three patients were recruited of which 58 received chemotherapy and 15 opted for best supportive care (BSC). Compliance with HRQoL questionnaires was 98% at baseline. The chemotherapy group maintained HRQoL compared with the BSC group whose overall HRQoL fell (P=0.006) with worsening dyspnoea and pain. The impact of chemotherapy was irrespective of histological subtype although those with non-epithelioid disease had worse HRQoL at later time points (P=0.012). Additionally, those with a falling mesothelin or improvement on modified-RECIST CT at early follow-up had a better HRQoL at 16 weeks. CONCLUSIONS: HRQoL was maintained following chemotherapy compared with a self-selected BSC group. Once chemotherapy is initiated, a falling mesothelin or improved RECIST CT findings infer a quality-of-life advantage.

The South West Area Mesothelioma and Pemetrexed trial: a multicentre prospective observational study evaluating novel markers of chemotherapy response and prognostication.

BACKGROUND: Robust markers that predict prognosis and detect early treatment response in malignant pleural mesothelioma (MPM) would enhance patient care. METHODS: Consecutive patients with MPM who were considered fit for first-line chemotherapy were prospectively recruited. Patients of similar performance status opting for best supportive care were included as a comparator group. Baseline and interval CT, PET-CT and serum markers (mesothelin, fibulin-3 and neutrophil-lymphocyte ratio (NLR)) were obtained, and patients followed up for a minimum 12 months. FINDINGS: Seventy-three patients were recruited (58 chemotherapy/15 comparator arm). Baseline TGV (total glycolytic volume on PET-CT) was an independent predictor of worse overall survival (OS) (P=0.001). Change in interval TGV(baseline/after two cycles of chemotherapy) did not predict OS or chemotherapy response on CT. Baseline NLR<4 was an independent predictor of better OS (median survival 453 (IQR 272-576) days vs NLR⩾4, 257 (IQR 147-490), P=0.002). Although baseline serum mesothelin did not predict OS, a falling level at 8 weeks significantly predicted longer time to progression (TTP) (P<0.001). INTERPRETATION: Neutrophil-lymphocyte ratio and baseline TGV predict prognosis in malignant pleural mesothelioma (MPM), but PET-CT is unhelpful in monitoring chemotherapy response. Serum mesothelin is a useful early treatment response marker when measured serially during chemotherapy and may have a role in evaluating patients' treatment response.

Cellulose microfibril crystallinity is reduced by mutating C-terminal transmembrane region residues CESA1A903V and CESA3T942I of cellulose synthase.

The mechanisms underlying the biosynthesis of cellulose in plants are complex and still poorly understood. A central question concerns the mechanism of microfibril structure and how this is linked to the catalytic polymerization action of cellulose synthase (CESA). Furthermore, it remains unclear whether modification of cellulose microfibril structure can be achieved genetically, which could be transformative in a bio-based economy. To explore these processes in planta, we developed a chemical genetic toolbox of pharmacological inhibitors and corresponding resistance-conferring point mutations in the C-terminal transmembrane domain region of CESA1(A903V) and CESA3(T942I) in Arabidopsis thaliana. Using (13)C solid-state nuclear magnetic resonance spectroscopy and X-ray diffraction, we show that the cellulose microfibrils displayed reduced width and an additional cellulose C4 peak indicative of a degree of crystallinity that is intermediate between the surface and interior glucans of wild type, suggesting a difference in glucan chain association during microfibril formation. Consistent with measurements of lower microfibril crystallinity, cellulose extracts from mutated CESA1(A903V) and CESA3(T942I) displayed greater saccharification efficiency than wild type. Using live-cell imaging to track fluorescently labeled CESA, we found that these mutants show increased CESA velocities in the plasma membrane, an indication of increased polymerization rate. Collectively, these data suggest that CESA1(A903V) and CESA3(T942I) have modified microfibril structure in terms of crystallinity and suggest that in plants, as in bacteria, crystallization biophysically limits polymerization.

Learning leaves a memory trace in motor cortex.

How are we able to learn new behaviors without disrupting previously learned ones? To understand how the brain achieves this, we used a brain-computer interface (BCI) learning paradigm, which enables us to detect the presence of a memory of one behavior while performing another. We found that learning to use a new BCI map altered the neural activity that monkeys produced when they returned to using a familiar BCI map in a way that was specific to the learning experience. That is, learning left a "memory trace" in the primary motor cortex. This memory trace coexisted with proficient performance under the familiar map, primarily by altering neural activity in dimensions that did not impact behavior. Forming memory traces might be how the brain is able to provide for the joint learning of multiple behaviors without interference.

Thoracic complications of rheumatoid disease.

Rheumatoid arthritis is a relatively common multisystem disease associated with significant mortality and morbidity. Thoracic disease, both pleural and pulmonary, is a frequent extra-articular manifestation of rheumatoid arthritis and responsible for approximately 20% of rheumatoid-associated mortality. Rheumatoid disease and its associated therapies can affect all compartments of the lung inciting a range of stereotyped pathological responses and it is not infrequent for multiple disease entities to co-exist. In some instances, development of pulmonary complications may precede typical rheumatological presentation of the disease and be the first indication of an underlying connective tissue disease. The spectrum of thoracic disease related to rheumatoid arthritis is reviewed.

Understanding Muslim patients: cross-cultural dental hygiene care.

BACKGROUND: Healthcare providers who understand the basic pillars of Islamic beliefs and common religious practices can apply these concepts, anticipate the needs of the Muslim patient and family, and attract Muslim patients to the practice. OBJECTIVE: Cross cultural knowledge can motivate dental hygienists to adopt culturally acceptable behaviors, strengthen patient-provider relationships and optimize therapeutic outcomes. Trends in Muslim population growth, Islamic history and beliefs, modesty practices, healthcare beliefs, contraception, childbearing, childrearing, pilgrimage, dietary practices, dental care considerations and communication are explained. MATERIALS AND METHODS: This paper reviews traditional Muslim beliefs and practices regarding lifestyle, customs, healthcare and religion as derived from the literature and study abroad experiences. RESULTS AND DISCUSSION: Recommendations are offered on how to blend western healthcare with Islamic practices when making introductions, appointments, eye contact, and selecting a practitioner. The significance of fasting and how dental hygiene care can invalidate the fast are also discussed. CONCLUSION: The ultimate goal is for practitioners to be culturally competent in providing care to Muslim patients, while keeping in mind that beliefs and practices can vary widely within a culture.

Double-crested cormorant (Phalacrocorax auritus) nesting effects on understory composition and diversity on island ecosystems in Lake Erie.

The context for this study is the management concerns over the severity and extent of the impact of cormorants on island flora in the recent past on Lake Erie islands. Accordingly, this study sought to quantify the nesting colonies' influence on coarse woody litter and how nest densities and litter depth may influence the herbaceous layer, the seed bank composition and viability across the extent of three Lake Erie islands. The data for this study were collected from 2004 to 2008 on East Sister Island and Middle Island using two main strategies. First, herbaceous layer surveys, cormorant nest counts, soil seed bank cores, and litter depth measurements were executed using a plotless-point quarter method to test island-wide impacts from nesting activities (data were also collected on a third island, West Sister Island as a reference for the other two islands). Secondly, a sub-sample of the entire plot set was examined in particularly high nesting density areas for two islands (Middle Island and East Sister Island). Kruskal-Wallis tests indicated that there are subtle changes in the herbaceous diversity (total, native and exotic) and seed bank composition across the islands. The sub sample set of the plots demonstrated that Phalacrocorax auritus nest density does influence litter depth, herbaceous species abundance and diversity. Cormorant nesting pressures are restricted to areas of high nesting pressures and competition. However, there remains a risk to the interior herbaceous layer of the island if the effects of nesting pressures at the edges advance inward from this perimeter.

Improving oral health in Pakistan using dental hygienists.

This paper reviews the healthcare system, available dental care, and oral health status of people in Pakistan. Considering the enormous unmet oral health needs, the insufficient supply of dental professionals and the current unstructured dental hygiene curriculum in Pakistan, a mission, vision, and goals for professional dental hygiene in Pakistan is recommended. The authors offer recommendations for competency-based dental hygiene education and practice, professional credentialing, a practice act, and a dental hygiene scope of practice to promote the health, welfare, and quality of life of the Pakistani people. Specifically, the authors recommend increasing the number of quality dental hygiene programs, establishing the dental hygienist as a primary care provider of oral health services, enhancing current dental hygiene curriculum, and establishing a dental hygiene council with responsibility for educational requirements and regulation of dental hygienists in Pakistan.

How learning unfolds in the brain: toward an optimization view.

How do changes in the brain lead to learning? To answer this question, consider an artificial neural network (ANN), where learning proceeds by optimizing a given objective or cost function. This "optimization framework" may provide new insights into how the brain learns, as many idiosyncratic features of neural activity can be recapitulated by an ANN trained to perform the same task. Nevertheless, there are key features of how neural population activity changes throughout learning that cannot be readily explained in terms of optimization and are not typically features of ANNs. Here we detail three of these features: (1) the inflexibility of neural variability throughout learning, (2) the use of multiple learning processes even during simple tasks, and (3) the presence of large task-nonspecific activity changes. We propose that understanding the role of these features in the brain will be key to describing biological learning using an optimization framework.

Characterizing the Type 6 Secretion System (T6SS) and its role in the virulence of avian pathogenic Escherichia coli strain APECO18.

Avian pathogenic E. coli is the causative agent of extra-intestinal infections in birds known as colibacillosis, which can manifest as localized or systemic infections. The disease affects all stages of poultry production, resulting in economic losses that occur due to morbidity, carcass condemnation and increased mortality of the birds. APEC strains have a diverse virulence trait repertoire, which includes virulence factors involved in adherence to and invasion of the host cells, serum resistance factors, and toxins. However, the pathogenesis of APEC infections remains to be fully elucidated. The Type 6 secretion (T6SS) system has recently gained attention due to its role in the infection process and protection of bacteria from host defenses in human and animal pathogens. Previous work has shown that T6SS components are involved in the adherence to and invasion of host cells, as well as in the formation of biofilm, and intramacrophage bacterial replication. Here, we analyzed the frequency of T6SS genes hcp, impK, evpB, vasK and icmF in a collection of APEC strains and their potential role in virulence-associated phenotypes of APECO18. The T6SS genes were found to be significantly more prevalent in APEC than in fecal E. coli isolates from healthy birds. Expression of T6SS genes was analyzed in culture media and upon contact with host cells. Mutants were generated for hcp, impK, evpB, and icmF and characterized for their impact on virulence-associated phenotypes, including adherence to and invasion of host model cells, and resistance to predation by Dictyostelium discoideum. Deletion of the aforementioned genes did not significantly affect adherence and invasion capabilities of APECO18. Deletion of hcp reduced resistance of APECO18 to predation by D. discoideum, suggesting that T6SS is involved in the virulence of APECO18.

Characterizing avian pathogenic Escherichia coli (APEC) from colibacillosis cases, 2018.

Colibacillosis caused by avian pathogenic Escherichia coli (APEC) is a devastating disease of poultry that results in multi-million-dollar losses annually to the poultry industry. Disease syndromes associated with APEC includes colisepticemia, cellulitis, air sac disease, peritonitis, salpingitis, omphalitis, and osteomyelitis among others. A total of 61 APEC isolates collected during the Fall of 2018 (Aug-Dec) from submitted diagnostic cases of poultry diagnosed with colibacillosis were assessed for the presence of 44 virulence-associated genes, 24 antimicrobial resistance genes and 17 plasmid replicon types. Each isolate was also screened for its ability to form biofilm using the crystal violet assay and antimicrobial susceptibility to 14 antimicrobials using the NARMS panel. Overall, the prevalence of virulence genes ranged from 1.6% to >90% with almost all strains harboring genes that are associated with the ColV plasmid-the defining trait of the APEC pathotype. Overall, 58 strains were able to form biofilms and only three strains formed negligible biofilms. Forty isolates displayed resistance to antimicrobials of the NARMS panel ranging from one to nine agents. This study highlights that current APEC causing disease in poultry possess virulence and resistance traits and form biofilms which could potentially lead to challenges in colibacillosis control.

New discoveries and directions for medical, dental and dental hygiene research: low temperature atmospheric pressure plasma.

The study of plasma integrates physics, chemistry, biology, and engineering, and has recently engaged medicine and dental hygiene in research efforts. The study of plasma holds promise for a myriad of applications ranging from lasers and electronics, hazardous waste management, decontamination, sterilization and disinfection of foods, soil, water, instruments, to medical uses in wound healing and treating certain types of tumours and cancers. Plasma represents a new state-of-the-art sterilization and disinfection treatment for certain oral and enviornmental pathogens, heat-sensitive materials, contaminated medical waste, hard and soft surfaces, and ventilation systems may assist health care facilities in the management of various health concerns. The role that Low Temperature Atmospheric Pressure Plasma (LTAPP) could play in the inactivation of pathogenic microorganisms might prove to be a new, faster, noncorrosive, more economical alternative, as well as support green healthcare.

Characterization of Avian Pathogenic Escherichia coli (APEC) Associated With Turkey Cellulitis in Iowa.

Turkey cellulitis, also known as clostridial dermatitis is a significant cause of morbidity, mortality, and carcass condemnation at slaughter resulting in considerable losses for turkey producers. Here, we assessed the potential role of Avian Pathogenic Escherichia coli (APEC) in a cellulitis outbreak on a turkey farm in Iowa. Birds from one farm with a history of cellulitis and one farm with no history of disease (for comparison) were followed from the age of 10 weeks (before the outbreak) to 18 weeks (just prior to slaughter). E. coli recovered from the litter, from skin lesions of birds with cellulitis, and from systemic lesions of birds submitted for necropsy, were assessed. A total of 333 isolates were analyzed and screened for virulence-associated genes, antimicrobial resistance genes including heavy metal resistance, adhesins, invasins, and protectins, iron acquisition systems and their phylogenetic group through multiplex PCR. In addition, PCR was used to serogroup the isolates, and pulsed field gel electrophoresis (PFGE) was used to analyze a subset of strains from the farm environment (litter) and birds at 17 and 18 weeks of age when the cellulitis infection appeared to peak. Overall, E. coli isolates recovered from cellulitis lesions and systemic infection were identified as APEC, while a lower prevalence of E. coli recovered from the litter met the criteria of APEC-like. Direct comparison of E. coli isolates from the litter, lesions, and systemic strains using PFGE failed to find identical clones across all three sources reflecting the diversity of strains present in the poultry environment causing disease. This study highlights the role of APEC in turkey cellulitis and should not be overlooked as a significant contributor to the disease in turkeys.

A monoclonal antibody against the nuclear pore complex inhibits nucleocytoplasmic transport of protein and RNA in vivo.

A monoclonal antibody that reacts with proteins in the nuclear pore complex of rat liver (Snow, C. M., A. Senior, and L. Gerace. 1987. J. Cell Biol. 104:1143-1156) has been shown to cross react with similar components in Xenopus oocytes, as determined by immunofluorescence microscopy and immunoblotting. We have microinjected the antibody into oocytes to study the possible role of these polypeptides in nucleocytoplasmic transport. The antibody inhibits import of a large nuclear protein, nucleoplasmin, in a time- and concentration-dependent manner. It also inhibits export of 5S ribosomal RNA and mature tRNA, but has no effect on transcription or intranuclear tRNA processing. The antibody does not affect the rate of diffusion into the nucleus of two small proteins, myoglobin and ovalbumin, indicating that antibody binding does not result in occlusion of the channel for diffusion. This suggests that inhibition of protein and RNA transport occurs by binding of the antibody at or near components of the pore that participate in mediated transport.

CT appearances of pleural tumours.

Computed tomography (CT) is the imaging technique of choice for characterizing pleural masses with respect to their location, composition, and extent. CT also provides important information regarding invasion of the chest wall and surrounding structures. A spectrum of tumours can affect the pleura of which metastatic adenocarcinoma is the commonest cause of malignant pleural disease, while malignant mesothelioma is the most common primary pleural tumour. Certain CT features help differentiate benign from malignant processes. This pictorial review highlights the salient CT appearances of a range of tumours that may affect the pleura.

BrainNet: A Multi-Person Brain-to-Brain Interface for Direct Collaboration Between Brains.

We present BrainNet which, to our knowledge, is the first multi-person non-invasive direct brain-to-brain interface for collaborative problem solving. The interface combines electroencephalography (EEG) to record brain signals and transcranial magnetic stimulation (TMS) to deliver information noninvasively to the brain. The interface allows three human subjects to collaborate and solve a task using direct brain-to-brain communication. Two of the three subjects are designated as "Senders" whose brain signals are decoded using real-time EEG data analysis. The decoding process extracts each Sender's decision about whether to rotate a block in a Tetris-like game before it is dropped to fill a line. The Senders' decisions are transmitted via the Internet to the brain of a third subject, the "Receiver," who cannot see the game screen. The Senders' decisions are delivered to the Receiver's brain via magnetic stimulation of the occipital cortex. The Receiver integrates the information received from the two Senders and uses an EEG interface to make a decision about either turning the block or keeping it in the same orientation. A second round of the game provides an additional chance for the Senders to evaluate the Receiver's decision and send feedback to the Receiver's brain, and for the Receiver to rectify a possible incorrect decision made in the first round. We evaluated the performance of BrainNet in terms of (1) Group-level performance during the game, (2) True/False positive rates of subjects' decisions, and (3) Mutual information between subjects. Five groups, each with three human subjects, successfully used BrainNet to perform the collaborative task, with an average accuracy of 81.25%. Furthermore, by varying the information reliability of the Senders by artificially injecting noise into one Sender's signal, we investigated how the Receiver learns to integrate noisy signals in order to make a correct decision. We found that like conventional social networks, BrainNet allows Receivers to learn to trust the Sender who is more reliable, in this case, based solely on the information transmitted directly to their brains. Our results point the way to future brain-to-brain interfaces that enable cooperative problem solving by humans using a "social network" of connected brains.

A position-dependent transcription-activating domain in TFIIIA.

Transcription of the Xenopus 5S RNA gene by RNA polymerase III requires the gene-specific factor TFIIIA. To identify domains within TFIIIA that are essential for transcriptional activation, we have expressed C-terminal deletion, substitution, and insertion mutants of TFIIIA in bacteria as fusions with maltose-binding protein (MBP). The MBP-TFIIIA fusion protein specifically binds to the 5S RNA gene internal control region and complements transcription in a TFIIIA-depleted oocyte nuclear extract. Random, cassette-mediated mutagenesis of the carboxyl region of TFIIIA, which is not required for promoter binding, has defined a 14-amino-acid region that is critical for transcriptional activation. In contrast to activators of RNA polymerase II, the activity of the TFIIIA activation domain is strikingly sensitive to its position relative to the DNA-binding domain. When the eight amino acids that separate the transcription-activating domain from the last zinc finger are deleted, transcriptional activity is lost. Surprisingly, diverse amino acids can replace these eight amino acids with restoration of full transcriptional activity, suggesting that the length and not the sequence of this region is important. Insertion of amino acids between the zinc finger region and the transcription-activating domain causes a reduction in transcription proportional to the number of amino acids introduced. We propose that to function, the transcription-activating domain of TFIIIA must be correctly positioned at a minimum distance from the DNA-binding domain.

Differential binding of zinc fingers from Xenopus TFIIIA and p43 to 5S RNA and the 5S RNA gene.

Zinc fingers are usually associated with proteins that interact with DNA. Yet in two oocyte-specific Xenopus proteins, TFIIA and p43, zinc fingers are used to bind 5S RNA. One of these, TFIIIA, also binds the 5S RNA gene. Both proteins have nine zinc fingers that are nearly identical with respect to size and spacing. We have determined the relative affinities of groups of zinc fingers from TFIIIA for both 5S RNA and the 5S RNA gene. We have also determined the relative affinities of groups of zinc fingers from p43 for 5S RNA. The primary protein regions for RNA and DNA interaction in TFIIIA are located at opposite ends of the molecule. All zinc fingers from TFIIIA participate in binding 5S RNA, but zinc fingers from the C terminus have the highest affinity. N-terminal zinc fingers are essential for binding the 5S RNA gene. In contrast, zinc fingers at the amino terminus of p43 are essential for binding 5S RNA.