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The predominant narrative of covid-19 emphasizes its unpredictable origins, virulence, human targets, and spatial targets. Its international spread may be erratic, but at the regional level, diffus...

English cross beef calves (n=115; BW = 245 + 40 kg) were used in the first of a three-year project to examine the effects of three weaning systems on post weaning performance. Cattle were stratified by age of dam and assigned to: 1) Drylot (DRY), 2) Pasture (PAST) or 3) Fenceline (FEN) weaning system. Calves in DRY were physically separated from their dams and fed a mixed ration across 4 pens. Calves in PAST were physically separated from their dams and assigned to 2 pastures consisting of Bermudagrass and fed a supplement. Calves in FEN were separated from their dams in adjacent pastures (n = 2) but maintained nose contact with their dams and fed a supplement. Pasture analysis from PAST and FEN were used to calculate the amount of supplement, so that total NE would be similar to that fed to DRY. Cattle were weighed weekly, until d 28, then weighed on d 56. Pen/pasture were the experimental unit, animal within pen was the random effect, data were analyzed using PROC Mixed. No differences (P > 0.10) were noted with BW at d 0, 7 or 28; however, both FEN and PAST had greater BW at d 15 (P = 0.05) and tended to have greater BW at d 21 (P = 0.06); nevertheless, by d 56, DRY had greater BW compared with FEN and PAST (P=0.03). Similarly, ADG tended to be greater in FEN and PAST from d 0-14 (P= 0.06) and from d 0-21 (P = 0.07). Overall ADG from d 0-56 was greater for DRY compared with PAST and FEN (P = 0.03). By design, cattle in DRY had more measurable DMI compared with PAST and FEN at all points (P < 0.0004). Cost of gain was greater (P= 0.02) with more economical gain associated with FEN and PAST compared with DRY (P = 0.02).

Funding: This work was supported by Biotechnology and Biological Sciences Research Council (BBSRC) grants BB/L003988/1 and 1645891, and strategic funding to The Pirbright Institute, BBS/E/I/00007035, BBS/E/I/00007034, BBS/E/I/00007037 and BBS/E/I/00007039. Coronavirus sub-genomic mRNA (sgmRNA) synthesis occurs via a process of discontinuous transcription involving complementary transcription regulatory sequences (TRSs), one (TRS-L) encompassing the leader sequence of the 5' untranslated region (UTR), and the other upstream of each structural and accessory gene (TRS-B). Several coronaviruses have an ORF located between the N gene and the 3'-UTR, an area previously thought to be non-coding in the Gammacoronavirus infectious bronchitis virus (IBV) due to a lack of a canonical TRS-B. Here, we identify a non-canonical TRS-B allowing for a novel sgmRNA relating to this ORF to be produced in several strains of IBV: Beaudette, CR88, H120, D1466, Italy-02 and QX. Interestingly, the potential protein produced by this ORF is prematurely truncated in the Beaudette strain. A single nucleotide deletion was made in the Beaudette strain allowing for the generation of a recombinant IBV (rIBV) that had the potential to express a full-length protein. Assessment of this rIBV in vitro demonstrated that restoration of the full-length potential protein had no effect on viral replication. Further assessment of the Beaudette-derived RNA identified a second non-canonically transcribed sgmRNA located within gene 2. Deep sequencing analysis of allantoic fluid from Beaudette-infected embryonated eggs confirmed the presence of both the newly identified non-canonically transcribed sgmRNAs and highlighted the potential for further yet unidentified sgmRNAs. This HiSeq data, alongside the confirmation of non-canonically transcribed sgmRNAs, indicates the potential of the coronavirus genome to encode a larger repertoire of genes than has currently been identified. Publisher PDF

This study investigates the educational and economic attainment of Mexican Dreamers over the 4 years since DACA was implemented (2012–2016). A time-space stream of benefits and barriers is evaluated at the national, state, and individual levels. Based on assumptions linking the DACA-eligible to DACA recipients, I examine the annual American Community Survey (ACS) to glean insights not provided elsewhere. At national level, the results suggest that young Mexican Dreamers entered the workforce at higher rates, but college at lower rates, than a control group of Mexican Americans. At state level, in supportive states these Dreamers entered college at higher rates but the work force at slightly lower rates, than they did in restrictive states. At the individual level, it is revealed that DACA strongly promoted college over work for women, but just the reverse for men. These distinctions are bringing about new inequalities within the Mexican Dreamer community in the United States.

In this study, grounded in the literature on transnational migration, a theory of transnational social gravity is developed in which economic, social, and psychological dimensions of transn...

This exercise introduces students to the observation that warming is unequal at the level of regions and countries, helps them analyze why this is so, and encourages reflection on actions by specif...

Almost one-fifth of the “surge” of Central American migrants crossing the US border in early 2014 was unaccompanied children, mostly from the “Northern Triangle”—Honduras, Guatemala, and El Salvador. Although prior research identifies violence, economic factors, and US policies as probable causes, determining their relative importance is more challenging. In this article I examine time trends in child migration from the Northern Triangle in relation to trends in indicators for these causes for 2008 to 2014, and patterns of child migration and push factors over space for the 18 departments of Honduras at the peak of the surge in 2014. The findings are that increasingly immigrant-favorable bills introduced to Congress and an increasingly improving US economy were concordant with trends in child migration, each of which showed a visible upturn at the point of the initial migration surge in 2011. Although homicides and unemployment in the NT itself did not trend as child migration over time, homicides and migration were substantially related across Honduran departments at the height of the surge.

The biotrophic fungal pathogenBlumeria graminiscauses the powdery mildew disease of cereals and grasses. Proteins with a predicted ribonuclease (RNase)-like fold (termed RALPHs) comprise the largest set of secreted effector candidates within theB. graminisf. sp.hordeigenome. Their exceptional abundance suggests they play crucial functions during pathogenesis. We show that transgenic expression of RALPH CSEP0064/BEC1054 increases susceptibility to infection in monocotyledenous and dicotyledonous plants. CSEP0064/BEC1054 interactsin plantawith five host proteins: two translation elongation factors (eEF1α and eEF1γ), two pathogenesis-related proteins (PR5 and PR10) and a glutathione-S-transferase. We present the first crystal structure of a RALPH, CSEP0064/BEC1054, demonstrating it has an RNase-like fold. The protein interacts with total RNA and weakly with DNA. Methyl jasmonate levels modulate susceptibility to aniline-induced host RNA fragmentation.In plantaexpression of CSEP0064/BEC1054 reduces the formation of this RNA fragment. We propose that CSEP0064/BEC1054 is a pseudoenzyme that binds to host ribosomes, thereby inhibiting the action of plant ribosome-inactivating proteins that would otherwise lead to host cell death, an unviable interaction and demise of the fungus.

Current rhinometric and flow assessments measure nasal patency and are often poorly correlated with rhinitis symptoms. To evaluate magnetic resonance imaging (MRI) as a new method to measure inflammatory changes in nasal and sinus mucosa following nasal allergen challenge. A pilot study (n = 6) determined the optimal technical settings for MRI to measure inflammatory change which were then adopted for the main study. This study was a single blind, placebo-controlled, three-way crossover trial in 14 subjects with seasonal allergic rhinitis. Effects of cetirizine, cetirizine and pseudoephedrine (Cet+PE), or placebo on total nasal symptom scores (TNSS), peak nasal inspiratory flow (PNIF), nasal nitric oxide (nNO), acoustic rhinometry, and MRI end points following nasal intranasal allergen challenge were measured. There were significant changes in all parameters after allergen challenge (P 0.07; comparison of active versus placebo P > 0.09). MRI provides novel insights into the anatomical inflammatory changes post allergen challenge and provides a new method for assessment of nasal patency and objective measurement of inflammatory responses.

Objectives The question raised here is whether global labor migration has reached its high-water mark and will not in fact recover its prerecession magnitudes. This study examines this question, and the underlying causes of migration regression, reviewing studies at the international level and carrying out a case study of Jerez municipio, Zacatecas, Mexico. Methods Two surveys in Jerez—of 242 randomly selected households in six towns in 1995, and of 304 households in the same towns in 2009—provide a cross-section of conditions before and after U.S. economic setbacks beginning around 2000. Results The results point to a reduction in migration to the United States over the period. Furthermore, in the later period, lower fertility, higher educational attainment, and higher household income were all associated with lower levels of active U.S. migration, and income returns to local education were positive, whereas the income returns to U.S. migration were negative. Conclusions The results for Jerez are consistent with trends elsewhere in Mexico and those within leading sending nations globally, and they suggest a regression in future migration from these countries.

AIMS: To establish the dose-response for pharmacodynamics (bronchodilatation), safety and pharmacokinetics for a nebulised formulation of the long-acting muscarinic antagonist glycopyrrolate (EP-101) with a high efficiency nebuliser in patients with chronic obstructive pulmonary disease (COPD). METHODS: Patients with moderate to severe COPD (GOLD II/III), with reversible lung function were enrolled into this randomised, double-blind, placebo-controlled, 6-period cross-over study (n=42). Patients received single doses of EP-101 (12.5-400?g) and placebo via a high efficiency nebuliser (eFlow(�) PARI nebuliser), with washout between treatments. Plasma pharmacokinetics were assessed in a subset of patients (n=11). RESULTS: All treatments were well tolerated with similar adverse event rates reported with placebo and at all doses. There were no clinically relevant changes in heart rate, systolic and diastolic blood pressure or in ECG parameters including QTc interval. Following treatment with EP-101 at all doses there was a rapid bronchodilator response within 5?minutes. Significant improvements in mean change from baseline FEV1 at 24 hours were reported at doses >50?g compared with placebo, with a clear dose response relationship. Mean change in FEV1 were 0.10L (0.06-0.14 95%CI) and 0.12L (0.08-0.16) for 100?g and 200?g respectively. CONCLUSION: Single doses of EP-101 ranging from 12.5?g to 400?g were well tolerated. EP-101 delivered by high efficiency nebuliser device produced a rapid onset of bronchodilatation with clinically meaningful improvements in lung function maintained over a 24 hour period at all doses >50?g.

A new migration pessimism argues that the economic benefits of international labour migration for migrant households may not justify the social costs. This article provides a test of this argument based on the author's survey of 304 households in Jerez municipio (municipality), Zacatecas, Mexico, in 2009. The results indicate that active households (those with at least one migrant abroad) perceived their economic situation to have improved more, but both their social cohesion and their happiness to be less than those of non-active households. Social cohesion (family unity and maintenance of values) is shown to be pivotal in the happiness differential enjoyed by the non-active households.

Since 2000, and especially since 2007, there has been a reduction in the importance of international migration and remittances in major global sending regions as a result of recession in receiving countries, anti-immigrant policies, and improvement in economic opportunities in origin countries. A household survey in five rural communities in Zacatecas, Mexico, in 1995 and again in 2009 exemplifies these trends. Among youthful adults likely to have first migrated in the decade prior to each of these years, there was a significant drop in the proportion of active migrants. Among the active migrants, stays abroad became longer and more permanent, and their households exhibited fewer remittances, less family business ownership, and fewer local purchases, in 2009 compared to 1995. Finally, non-migrant households greatly improved their economic status in relation to migrant households over the period, reaching approximate parity with their migrant counterparts. Remittances channeled into some of the most backward regions and countries of the third World are … likely to play a continuing role locally. [They] are safety nets for poor regions left behind by the agglomerative behavior of international capital, by the preoccupations of the international community with other matters, and by the indifference of their own governments (Jones, 1998).

Twenty-two flocks of turkeys affected by enteric problems, with ages between 10 and 104 days and located in the Southern region of Brazil, were surveyed for turkey by PCR for turkey astrovirus type 2 (TAstV-2), turkey coronavirus (TCoV), hemorrhagic enteritis virus (HEV), rotavirus, reovirus, Salmonella spp., and Lawsonia intracellularis (Li) infections. Eleven profiles of pathogen combination were observed. The most frequently encountered pathogen combinations were TCoV-Li, followed by TCoV-TAstV-2-Li, TCoV-TastV-2. Only TCoV was detected as the sole pathogen in three flocks. Eight and 19 flocks of the 22 were positive for TAstV-2 and TCoV, respectively. Six were positive for Salmonella spp. and L. intracellularis was detected in 12 turkey flocks. Reovirus and HEV were not detected in this survey. These results throw new light on the multiple etiology of enteritis in turkeys. The implications of these findings and their correlation with the clinical signs are comprehensively discussed, illustrating the complexity of the enteric diseases.

1. The possibility that infectious bronchitis virus (IBV) variants isolated from broilers with enteric and respiratory problems have a different tropism and pathological outcome from those IBV strains causing classical respiratory disease was investigated. 2. IBV variants were isolated from broiler flocks with enteric and respiratory problems in two regions of Brazil. The USP-10 isolate, of enteric origin, was inoculated via the oral oroculonasal routes into IBV-antibody-free broilers and specific pathogen-free (SPF) chickens to determine tissue tropism and pathogenicity and compared with an IBV variant (USP-50) isolated from chickens showing signs of respiratory disease only. 3. Both USP-10 and USP-50 strains caused similar pathological patterns by either route of inoculation. Both variants were detected in respiratory and non-respiratory tissues, including the kidney, intestine and testis. 4. Broilers were more susceptible to infection than SPF chickens, and seroconversion was detected in all of the chicks.

In cancer cells, the process of epithelial-mesenchymal transition (EMT) confers migratory and invasive capacity, resistance to apoptosis, drug resistance, evasion of host immune surveillance and tumor stem cell traits. Cells undergoing EMT may represent tumor cells with metastatic potential. Characterizing the EMT secretome may identify biomarkers to monitor EMT in tumor progression and provide a prognostic signature to predict patient survival. Utilizing a transforming growth factor-β-induced cell culture model of EMT, we quantitatively profiled differentially secreted proteins, by GeLC-tandem mass spectrometry. Integrating with the corresponding transcriptome, we derived an EMT-associated secretory phenotype (EASP) comprising of proteins that were differentially upregulated both at protein and mRNA levels. Four independent primary tumor-derived gene expression data sets of lung cancers were used for survival analysis by the random survival forests (RSF) method. Analysis of 97-gene EASP expression in human lung adenocarcinoma tumors revealed strong positive correlations with lymph node metastasis, advanced tumor stage and histological grade. RSF analysis built on a training set (n = 442), including age, sex and stage as variables, stratified three independent lung cancer data sets into low-, medium- and high-risk groups with significant differences in overall survival. We further refined EASP to a 20 gene signature (rEASP) based on variable importance scores from RSF analysis. Similar to EASP, rEASP predicted survival of both adenocarcinoma and squamous carcinoma patients. More importantly, it predicted survival in the early-stage cancers. These results demonstrate that integrative analysis of the critical biological process of EMT provides mechanism-based and clinically relevant biomarkers with significant prognostic value.

Pharmaceutical products that are contaminated with Burkholderia cepacia complex (BCC) bacteria may pose serious consequences to vulnerable patients. Benzyldimethylalkylammonium chloride (BZK) cationic surfactants are extensively used in medical applications and have been implicated in the coselection of antimicrobial resistance. The ability of BCC to degrade BZK, tetradecyldimethylbenzylammonium chloride (C14BDMA-Cl), dodecyldimethylbenzylammonium chloride (C12BDMA-Cl), decyldimethylbenzylammonium chloride (C10BDMA-Cl), hexyldimethylbenzylammonium chloride, and benzyltrimethylammonium chloride was determined by incubation in 1/10-diluted tryptic soy broth (TSB) to determine if BCC bacteria have the ability to survive and inactivate these disinfectants. With BZK, C14BDMA-Cl, and C12BDMA-Cl, inhibition of the growth of 20 BCC strains was observed in disinfectant solutions that ranged from 64 to 256 µg/ml. The efflux pump inhibitor carbonyl cyanide m-chlorophenylhydrazone increased the sensitivity of bacteria to 64 µg/ml BZK. The 20 BCC strains grew well in 1/10-diluted TSB medium with BZK, C12BDMA-Cl, and C10BDMA-Cl; they absorbed and degraded the compounds in 7 days. Formation of benzyldimethylamine and benzylmethylamine as the initial metabolites suggested that the cleavage of the C alkyl-N bond occurred as the first step of BZK degradation by BCC bacteria. Proteomic data confirmed the observed efflux activity and metabolic inactivation via biodegradation in terms of BZK resistance of BCC bacteria, which suggests that the two main resistance mechanisms are intrinsic and widespread., IMPORTANCE Benzyldimethylalkylammonium chloride is commonly used as an antiseptic in the United States. Several recent microbial outbreaks were linked to antiseptics that were found to contain strains of the Burkholderia cepacia complex. Burkholderia species survived in antiseptics, possibly because of the degradation of antiseptic molecules or regulation of relevant gene expression. In this study, we assessed the efflux pump and the potential of B. cepacia complex bacteria to degrade benzyldimethylalkylammonium chloride and improved our understanding of the resistance mechanisms, by using proteomic and metabolic information. To our knowledge, this is the first systematic report of the intrinsic mechanisms of B. cepacia complex strain resistance to benzyldimethylalkylammonium chloride, based on the metabolic and proteomic evidence for efflux pumps and the complete biodegradation of benzyldimethylalkylammonium chloride.

Immuno-oncology describes therapeutic approaches exploiting the body's immune system to fight cancer. One approach involves educating the immune-system to recognize and destroy tumor cells by targeting tumor-specific neoantigens. Neoantigens are antigens presented by tumors but not recognized by the immune-system. Identification of Neoantigens is therefore an active area of research and development. The major histocompatibility complex (MHC) plays a crucial role in antigen presentation. Peptides generated by protein degradation in the cytosol are presented, non-covalently bound to MHC Class I molecules, on the surface of cells for inspection by T-lymphocytes. Cytotoxic T lymphocytes (CTL) recognize peptides presented by MHC Class I. The recognition of peptide antigens presented by MHC Class I results in the destruction of the presenting cell by the CTL. Characterization of peptides associated with MHC Class I molecules requires a targeted protein complex enrichment, an unbiased peptide elution and finally a peptide analysis method. Here we present the latest results from our work optimizing and performing a workflow for the analysis of peptides associated with Class I MHC molecules. Citation Format: Michael J. Ford, Richard C. Jones, Ravi Amunugama, David Allen, Paul Del Rizzo, James Mobley, Michael Pisano. Optimization of methods for the analysis of class I MHC peptides by mass spectrometry [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 577.

Various authors have begun to address the social impacts of international migration on families left behind. Family disintegration results from two separate factors: family separation and the loss of traditional values. Findings from this research (based on a random survey of over 400 households in three municipios of the central part of the state of Cochabamba, Bolivia, in the autumn of 2007) indicate that economic well-being made possible by migration increases levels of professed family happiness. However, family disintegration resulting from migration decreases family happiness even more, with the net result that migrant households are considerably less happy than non-migrant households. It is suggested that this result can be traced to the dynamic conflict between the traditional, group-focused image of change prior to migration (engendering feelings of togetherness and security) and the modern, ego-focused image of change that is a major social remittance of migration (generating competition and role insecurity).

Poult enteritis complex has been associated with enteritis and reduction in growth rates in commercial turkeys worldwide. Intestinal samples from 76 turkey flocks from different Brazilian states affected or not with intestinal disorders were evaluated for the presence of adenovirus groups 1 and 2 (TAV), astrovirus types 1 and 2 (TAstV-1 and TAstV-2), turkey coronavirus (TCoV), reovirus, rotavirus, and avian nephritis virus (ANV) using PCR. The percentage of positive samples was categorized according to the geographic origin, age of the flocks, and presence of clinical signs of intestinal disease. The percentage of samples that were positive for at least one virus was 93.4%, whereas the percentage of samples that were positive for more than one virus was 69.7%. An average of 3.20 viruses per sample was detected in turkeys in the growing phase of the production cycle (1 to 4 wk of age). The TAstV-1 and TCoV were the most frequently observed viruses in growing phase turkeys and occurred simultaneously in 85% of these samples. In turkeys in the finishing phase of development (5 to 18 wk), a lower average number of viruses was observed (2.41), and the most frequent viruses isolated in these turkeys were TAstV-1 (57.1%) and rotavirus (51.8%). Overall, every virus was detected more frequently in growing phase turkeys than in finishing phase turkeys with the exception of TAV. Samples from flocks exhibiting clinical signs of intestinal disease showed a higher rate of positivity, and TAstV-1, TAstV-2, and TCoV were the most frequently occurring viruses in this cohort. Birds without clinical signs most frequently harbored TAstV-1 and rotavirus. Future studies should focus on the description and elucidation of the role of each virus, as well as the pathogenic and immunological implications of the different combinations of viruses in turkeys.

SummaryDNA unwinding at eukaryotic replication forks displaces parental histones, which must be redeposited onto nascent DNA in order to preserve chromatin structure. By screening systematically for replisome components that pick up histones released from chromatin into a yeast cell extract, we found that the Mcm2 helicase subunit binds histones cooperatively with the FACT (facilitiates chromatin transcription) complex, which helps to re-establish chromatin during transcription. FACT does not associate with the Mcm2-7 helicase at replication origins during G1 phase but is subsequently incorporated into the replisome progression complex independently of histone binding and uniquely among histone chaperones. The amino terminal tail of Mcm2 binds histones via a conserved motif that is dispensable for DNA synthesis per se but helps preserve subtelomeric chromatin, retain the 2 micron minichromosome, and support growth in the absence of Ctf18-RFC. Our data indicate that the eukaryotic replication and transcription machineries use analogous assemblies of multiple chaperones to preserve chromatin integrity.

A three-stage diffusion model of international migration and inequality posits that household income inequality first increases, then decreases, and finally increases again as a community's migration experience deepens. Analysis of data from a survey of 417 households in the Valle Alto region of Bolivia supports this model. Concomitant with the region's overall position in the middle stage, the results indicate that income inequality among active migrant households is less than that of non-migrant households, suggesting that migration reduces inequality. Furthermore, income inequality between urban and rural areas is diminished by migration. Individual towns in the region, however, illustrate all three stages of the diffusion model. The study supports other research showing that the middle stage of migration generates the most remittances, the highest commitment of resources to the home community, and the lowest inequalities among households.

In response to Giddens' structuration theory, this study attempts to unravel the linkages between migration and local economic growth by moving beyond the household to the community level of analysis, and by considering lagged relationships over several years. The case study -24 towns in central Zacatecas, Mexico-concludes that remittances from US migration play an ambiguous role, providing basic income but at the same time resulting in more expenditures outside the community, which results in a lower multiplier effect and lower growth rates (measured by population growth). The reason for the externalization of expenditures is not so much the migration experience itself, as the socio-economic structure of sending communities, including their small populations and poor employment structures, which put overwhelming constraints on their growth and development.

Pancreatic ductal adenocarcinoma (PDAC) is a major cause of cancer-related death, largely due to metastatic disease. To better understand PDAC metastatic spread and identify novel therapeutic targets, we analysed the proteome of primary tumours and matched lymph node (LN) metastases. As frozen specimens of metastatic lesions are scarce, we examined formalin-fixed paraffin-embedded (FFPE) tissues. This poses technical challenges because of the cross-linkages induced by fixation. Using laser capture microdissection (PALM system), we isolated malignant epithelia from seven FFPE primary PDAC tumours and matched LN metastases. Following dissection, samples were analysed in duplicate using Multidimensional Protein Identification Technology (MudPIT); this resulted in the identification of 1504 proteins, 854 of which were common to all samples analysed. Comparison of the obtained proteins with data from previous proteomics studies on pancreatic tissue, pancreatic juice, serum, and urine resulted in a less than 30% overlap, indicating that our study has substantially expanded the current database of proteins expressed in this malignancy. Statistical analysis further showed that 115/854 proteins (13.5%) were significantly differentially expressed (g-value ≥ 3.8). Two proteins, S100P and 14-3-3 sigma, with highly significant g-values were confirmed to be significantly differentially expressed (S100P: p = 0.05 and 14-3-3 sigma: p < 0.001) in a larger series of 55 cases of matched primary PDAC and LN metastases using immunohistochemistry. Thus, laser capture microdissection of FFPE tissue coupled with downstream proteomic analysis is a valid approach for the investigation of metastatic PDAC. This is the first study to establish and compare the protein composition of primary PDAC and matched LN metastases, and has resulted in the identification of several potential epithelial-specific therapeutic targets, including 14-3-3 sigma and S100P.

Introduction Embryo-derived PIF modulates systemic maternal immunity without suppression. Synthetic analog (sPIF) prevents juvenile diabetes, preserves islet function, reducing oxidative stress/protein misfolding. We investigate sPIF effectiveness in controlling neuroinflammation/MS. Methods Examine sPIF-induced protection against harsh, clinical-relevant murine EAE-PLP acute and chronic models. Evaluate clinical indices: circulating cytokines, spinal cord histology, genome, canonical global proteome, cultured PLP-activated splenocytes cytokines, and immunophenotype. Results Short-term, low-dose sPIF prevented paralysis development and lowered mortality (P 50%, by day 82. Prevention model: 12 days post-therapy, sPIF reduced circulating IL12 ten-fold and inflammatory cells access to spinal cord. Regression model: sPIF blocked PLP-induced IL17 and IL6 secretions. Long-term chronic model: sPIF reduced spinal cord pro-inflammatory cytokines/chemokines, (ALCAM, CF1, CCL8), apoptosis-promoters, inflammatory cells access (JAM3, OPA1), solute channels (ATPases), aberrant coagulation factors (Serpins), and pro-antigenic MOG. Canonical proteomic analysis demonstrated reduced oxidative phosphorylation, vesicle traffic, cytoskeleton remodeling involved in neuro-cytoskeleton breakdown (tubulins), associated with axon re-assembly by (MTAPs)/improved synaptic transmission. Conclusion sPIF – through coordinated central and systemic multi-targeted action – reverses neuroinflammation/MS and imparts significant neuroprotective effects up to total paralysis resolution. Clinical testing is warranted and planned.

Lactobacillus species are a predominant member of the vaginal microflora and are critical in maintaining an acidic vaginal environment thought to contribute to the prevention of a number of urogenital diseases. However, during menstruation the pH of the vaginal environment increases to neutrality, a pH conducive for Staphylococcus aureus proliferation and the production of toxic shock syndrome toxin 1 (TSST-1) in susceptible women. In order to generate Lactobacillus species capable of expressing lysostaphin (an endopeptidase that cleaves the cell wall of S. aureus ) in a modified genital tract secretion medium (mGTS) under neutral-pH conditions, six prominent proteins from Lactobacillus plantarum WCFS1 spent medium were identified by mass spectrometry. Sequences for promoters, signal peptides, and mature lysostaphin were used to construct plasmids that were subsequently transformed into L. plantarum WCFS1. The promoter and signal sequences of Lp_3014 (putatively identified as a transglycosylase) or the promoter sequence of Lp_0789 (putatively identified as glyceraldehyde 3-phosphate dehydrogenase) with the signal sequence of Lp_3014 exhibited lysostaphin activity on buffered medium containing heat-killed S. aureus . The cassettes were integrated into the chromosome of L. plantarum WCFS1, but only the cassette containing the promoter and signal sequence from Lp_3014 had integrated into the appropriate site. Coculture assays using buffered mGTS showed that lysostaphin expressed from L. plantarum WCFS1 reduced the growth of TSST-1-producing strains of S. aureus under neutral-pH conditions. This study provides the basis for determining whether lysostaphin-producing Lactobacillus strains could potentially be used as a means to inhibit the growth of S. aureus during menstruation.

In late mitosis and G1, Mcm2-7 are assembled onto replication origins to license them for initiation in the upcoming S phase. After initiation, Mcm2-7 provide helicase activity to unwind DNA at the replication fork. Here we examine the structure of Mcm2-7 on chromatin in Xenopus egg extracts. We show that prior to replication initiation, Mcm2-7 is present at licensed replication origins in a complex with a molecular mass close to double that of the Mcm2-7 hexamer. This complex has approximately stoichiometric quantities of the 6 Mcm2-7 proteins and we conclude that it consists of a double heterohexamer. This provides a configuration potentially capable of initiating a pair of bidirectional replication forks in S phase. We also show that after initiation, Mcm2-7 associate with Cdc45 and GINS to form a relatively stable CMG (Cdc45-MCM-GINS) complex. The CMG proteins also associate less strongly with other replication proteins, consistent with the idea that a single CMG complex forms the core of the replisome.

One-fifth of the Bolivian population lives abroad, and transnational behaviour strongly links their villages with destination communities. In this article we address whether the increasing difficulty of return migration (owing to legal and geographic barriers) results in diminished social and economic remittances to the country of origin. Results from a questionnaire survey of 417 households in the Valle Alto area of Cochabamba Department in 2007 reveal that monetary remittances account for one-half of the income of active migrant families (and one-quarter of income overall), and that transnational cultural ties remain strong. However, after ten years of cumulated time abroad the intention to return to Bolivia drops markedly along with economic and some social remittances. Closer analysis reveals that time abroad reduces these ties through the mediating forces of family members abroad, legal status, and home ownership abroad.

The Rho-like GTPase, Rac1, induces cytoskeletal rearrangements required for cell migration. Rac activation is regulated through a number of mechanisms, including control of nucleotide exchange and hydrolysis, regulation of subcellular localization or modulation of protein-expression levels. Here, we identify that the small ubiquitin-like modifier (SUMO) E3-ligase, PIAS3, interacts with Rac1 and is required for increased Rac activation and optimal cell migration in response to hepatocyte growth factor (HGF) signalling. We demonstrate that Rac1 can be conjugated to SUMO-1 in response to hepatocyte growth factor treatment and that SUMOylation is enhanced by PIAS3. Furthermore, we identify non-consensus sites within the polybasic region of Rac1 as the main location for SUMO conjugation. We demonstrate that PIAS3-mediated SUMOylation of Rac1 controls the levels of Rac1-GTP and the ability of Rac1 to stimulate lamellipodia, cell migration and invasion. The finding that a Ras superfamily member can be SUMOylated provides an insight into the regulation of these critical mediators of cell behaviour. Our data reveal a role for SUMO in the regulation of cell migration and invasion.

Until recently the role of international return migrants in local economic development has received little attention from researchers. Drawing upon Granovetter's notion of embeddedness and Levitt's concept of social remittances, I argue that return migrants are more locally embedded (in terms of local networks and cultural affinity) and better able to transfer social remittances (skills, social capital, and norms) from abroad, than active migrants. Therefore, I expect they will have a larger economic imprint (i.e., work, spend, and invest locally to a higher degree) than either non-migrants or active migrants. To test this expectation, I rely on my 2007 survey of over 400 households in the Valle Alto of Bolivia – a country where remittances from foreign labor migration have taken on great importance in recent years. I compare three types of households: (1) active migrant households, in which at least one member is working overseas; (2) return migrant households, in which at least one member has returned from overseas and there are no active migrants; and (3) non-migrant households, in which no one has ever worked abroad. The results suggest that return migrant households work and invest locally and contribute more to the economic base of their home communities than either of the other two types; and that this is made possible by the combination of their local embeddedness and their use of social remittances to further their economic success in Bolivia. Copyright © 2010 John Wiley & Sons, Ltd.

Existing multiple regression models of migration at the regional or interurban scales frequently (a) presuppose no particular causal patterns among the predictor variables and (b) presuppose that migrants possess equal needs and knowledge of opportunities at various destinations. Exceptions to (a) include several recent simultaneous-equation models that explicitly indicate causal loops by which currently endogenous variables "become" exogenous or lagged-endogenous at a subsequent point in time. Most recent regression analyses of interregional migration however employ single-equation models. Exceptions to (b) include several innovative attempts by economists to incorporate "behavioral" variables--operable at the level of the individual migrant. In particular expected future income streams weighted by such factors as employment probabilities access to information or expected life span have all been employed. Inspection of empirical studies of this genre reveal however that frequently the researcher has selected the potential benefits "for" the migrant. It is probably true that migrants act not upon objective characteristics of places but upon their perceptions of them. Many existing regression models tend therefore to generate inefficient or inconsistent regression coefficients. The magnitude and direction of these inconsistencies depend both upon the magnitude and direction of the unanalyzed associations among the predictor variables and upon the magnitude and direction of influence of intervening variables that reflect the needs contacts and perceptions of potential migrants. In this study a simple path-analytic model including both objective and subjective (perceptual) variables is developed with the purpose of addressing both problems. The major contention is that the reduced-form regression coefficients from this path-analytic "perceptual" model are more valid than those of a traditional single-equation model incorporating only objective variables. Their greater validity hinges upon the logical structure of the path-analytic model and upon its greater ability to interpret a given set of empirical data. (excerpt)

1. The use of vaccines is the main approach to control of the economically important poultry viral respiratory diseases infectious laryngotracheitis (ILT), avian metapneumovirus (aMPV) infections and infectious bronchitis (IB). This paper appraises the current methods of vaccine control in the light of the nature of each virus and epidemiological factors associated with each disease. 2. Infectious laryngotracheitis virus (ILTV) exists as a single type with a wide range of disease severity. It is a serious disease in certain regions of the world. Recent work has distinguished molecular differences between vaccine and field strains and vaccine virus can be a cause of disease. Vaccines have remained unaltered for many years but new ones are being developed to counter vaccine side effects and reversion and reactivation of latent virus. 3. Avian metapneumoviruses, the cause of turkey rhinotracheitis and respiratory disease in chickens exists as 4 subtypes, A, B, C and D. A and B are widespread and vaccines work well provided that accurate doses are given. Newer vaccine developments are designed to eliminate reversion and possibly counter the appearance of newer field strains which may break through established vaccine coverage. 4. IB presents the biggest problem of the three. Being an unstable RNA virus, part of the viral genome that codes for the S1 spike gene can undergo mutation and recombination so that important antigenic variants can appear irregularly which may evade existing vaccine protection. While conventional vaccines work well against homologous types, new strategies are needed to counter this instability. Molecular approaches involving tailoring viruses to suit field challenges are in progress. However, the simple use of two genetically different vaccines to protect against a wide range of heterologous types is now a widespread practice that is very effective. 5. None of the three diseases described can claim to be satisfactorily controlled and it remains to be seen whether the newer generations of vaccines will be more efficacious and cost effective. The importance of constant surveillance is emphasised and the testing of novel vaccines cannot be achieved without the use of vaccine-challenge experiments in poultry.

The fusion (F) protein of a subtype A AMPV was expressed in sections in Escherichia coli. Six genome sections were selected which encoded the majority of the protein. These were cloned then expressed from a His tag expression plasmid and, following purification on nickel columns, identities were confirmed by Western blot analysis. The interactions of each fragment with AMPV neutralizing antisera were determined. Purified fragments were mixed with AMPV sera raised against A-C subtypes by a natural route, in order to determine any reduction in their neutralizing capacities. Two fragments covering regions of the F ectodomain reduced neutralizing capacities of both subtype A and B antisera to a highly significant degree (p

The Rac-specific GEF (guanine-nucleotide exchange factor) Tiam1 has important functions in multiple cellular processes including proliferation, apoptosis and adherens junction maintenance. Here we describe a modified tandem affinity purification (TAP) technique that we have applied to specifically enrich Tiam1-containing protein complexes from mammalian cells. Using this technique in conjunction with LC-MS/MS mass spectrometry, we have identified additional Tiam1-interacting proteins not seen with the standard technique, and have identified multiple 14-3-3 family members as Tiam1 interactors. We confirm the Tiam1/14-3-3 protein interaction by GST-pulldown and coimmunoprecipitation experiments, show that it is phosphorylation-dependent, and that they colocalize in cells. The interaction is largely dependent on the N-terminal region of Tiam1; within this region, there are four putative phospho-serine-containing 14-3-3 binding motifs, and we confirm that two of them (Ser172 and Ser231) are phosphorylated in cells using mass spectrometry. Moreover, we show that phosphorylation at three of these motifs (containing Ser60, Ser172 and Ser231) is required for the binding of 14-3-3 proteins to this region of Tiam1. We show that phosphorylation of these sites does not affect Tiam1 activity; significantly however, we demonstrate that phosphorylation of the Ser60-containing motif is required for the degradation of Tiam1. Thus, we have established and proven methodology that allows the identification of additional protein-protein interactions in mammalian cells, resulting in the discovery of a novel mechanism of regulating Tiam1 stability.

Turkey coronavirus (TCoV) is a causative agent associated with poult enteritis and mortality syndrome (PEMS) in turkeys worldwide. The disease is an acute, highly contagious enteric disease that is characterized by depression, anorexia, diarrhea, and high mortality in commercial turkey flocks. The presence of TCoV in 12 intestinal-content samples, from turkey flocks aged between 10 and 104 days and exhibiting severe enteritis, was monitored during the period of 2004 to 2006. TCoV detection was accomplished by a reverse transcriptase-polymerase chain reaction (RT-PCR) through amplification of the 3' UTR region, followed by amplification of genes 3 and 5. Molecular characterization of the viruses was done through amplification of genes 3 and 5 and showed evidence of genetic similarity between them, although they differed from sequences of other TCoVs described in the literature. In relation to gene 3, samples showed a greater relationship with chicken infectious bronchitis virus (IBV), while gene 5 showed greater identity with pheasant coronavirus (PhCoV). Our results suggest that the strategy of amplification of the 3' UTR region, followed by sequencing of genes 3 and 5, has proven to be an effective means of detecting TCoV in intestinal contents.

At the same time that the Third World has become more dependent on international wage-labor migration, developed countries have become less hospitable to this migration. This inhospitality is beginning to have negative repercussions on rural sending regions such as north-central Mexico. This study is based on a survey of a stratified random sample of households in Villanueva municipio (county), Zacatecas, in 1988 and again in 2002, employing the same questions and methodology. The results suggest that restrictive U.S. border policies over this period have had a negative impact on village economies in the municipio. Although migrant families continued to hold a distinctive edge on nonmigrant families in terms of possessions and productive investments, there was a decline overall in levels of investment and remittances in the municipio. In the latter year, Villanueva had more nonmigrant families as well as more families with permanent migrants—both trends leading to less money remitted to rural families and...